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1. A review of the biology and literature of the Gulf Coast Toad (Incilius nebulifer), native to Mexico and the United States

Author: Mendelson Iii, Joseph R., Kinsey, Se. T., and Murphy, Es. B.
Subjects: Amphibia, Animalia, Biodiversity, Anura, Chordata, Bufonidae, Taxonomy
Abstract: Mendelson Iii, Joseph R., Kinsey, Se. T., Murphy, Es. B. (2015): A review of the biology and literature of the Gulf Coast Toad (Incilius nebulifer), native to Mexico and the United States. Zootaxa 3974 (4): 517-537, DOI: http://dx.doi.org/10.11646/zootaxa.3974.4.4
Published: 2015

2. Incilius nebulifer Girard 1854

Author: Mendelson Iii, Joseph R., Kinsey, Se. T., and Murphy, Es. B.
Subjects: Amphibia, Incilius, Incilius nebulifer, Animalia, Biodiversity, Anura, Chordata, Bufonidae, Taxonomy
Abstract: Incilius nebulifer (Girard, 1854) Gulf Coast Toad Bufo granulosus Baird & Girard, 1852: 173. [Not of Spix, 1824]. Type-locality ��between Indianola and San Antonio, Texas�� [restricted to ��Indianola, Calhoun County, Texas�� by Schmidt, 1953: 66.]. Holotype (fide Kellogg, 1932), United States National Museum (USNM) 2595, age and sex unknown, collected by J. H. Clark in 1851, under the direction of survey leader J. D. Graham (not examined by authors) Fouquette & Dubois (2014) rejected the restriction of the type locality, claiming lack of published evidence. Bufo nebulifer Girard, 1854: 86, preoccupied by Bufo granulosus Spix, 1824 Bufo nebulifera Baird, 1859 a: 44. Chilophryne nebulifera Cope, 1862: 358. Incilius nebulifer Cope, 1863: 50. Bufo valliceps Peters, 1863: 81. Bufo nebulifer Mendelson & Mulcahy, 2000: 182 Cranopsis nebulifer Frost, Grant, Faivovich, Bain, Haas, Haddad, de S��, Channing, Wilkinson, Donnellan, Raxworthy, Campbell, Blotto, Moler, Drewes, Lynch, Green & Wheeler, 2006: 364. Ollotis nebulifer Frost, Grant & Mendelson, 2006: 558. Incilius nebulifer Frost, Mendelson & Pramuk, 2009: 418 ��419. Bufo (Incilius) nebulifer Fouquette & Dubois, 2014: 315. Nomenclatural history. This species was originally described as Bufo granulosus by Baird & Girard (1852) Girard (1854) provided the replacement name Bufo nebulifer, as the original name was preoccupied by Bufo granulosus Spix, 1824. Peters (1863) placed B. nebulifer in the synonymy of Mesoamerican species Bufo valliceps Wiegman, 1833, where it remained until Mulcahy & Mendelson (2000) showed that the two species were distinct. Frost et al. (2006 a) suggested multiple taxonomic changes among New World bufonids, and referred the taxon nebulifer into Cranopsis Cope, 1875, which was shown by Frost et al. (2006 b) to be preoccupied, so the taxon was referred to Ollotis Cope, 1875. Ollotis was found also to be unavailable, so nebulifer was finally referred to Incilius Cope, 1863, by Frost et al. (2009). Various English-language common names have been applied to this species, including Gulf Coast Toad, Coastal Plain Toad, Mexican Toad, Common Toad, and Nebulous Toad. Crother (2012) suggested the name Gulf Coast Toad, which is adopted here. Liner & Casas-Andreu (2008) suggested the standard Spanish name as Sapo nebuloso, but were consistent with Crother (2012) in suggesting the standard English name as Gulf Coast Toad. Definition. Incilius nebulifer is a large toad, with adult females up to 125 mm and males to 98 mm SVL. The head is broad, with a complete complement of low, robust cranial crests. The snout is pointed in dorsal view, and rounded in profile. The tympanum is large (about 50 % diameter of the eye). In males, the bilateral vocal slits are large and the m. interhyoideus forms a large, bilobed (anteroposteriorly), pigmented vocal sac that may be visible through the overlying gular skin. The skin is uniformly rough, with many evenly distributed sharply pointed tubercles. On the flanks a conspicuous lateral descending row of enlarged sharply pointed tubercles is evident. The ventral surfaces are granular, with unpointed tubercles. Ventral surfaces are usually uniform cream in color while dorsal surfaces are variable. In most individuals the dorsal pattern clearly shows a dark brown dorsal and dorsolateral background coloration, with a broad cream or yellow mid-dorsal stripe and paired dorsolateral stripes (usually ventral to the lateral row of tubercles) of a similar pale color. Variable pale brown or cream markings may be present, scattered across all dorsal surfaces. The tips of the digits are the same color as the remainder of the digit. The hands have short, robust fingers and lack webbing. The feet are long, with slender toes, being about halfwebbed. The larvae are small (attaining 20��25 mm total length) and appear, without magnification, to be nearly uniformly dark gray dorsally, with a series of conspicuous pale spots extending down the dorsal ridge of the tail. The caudal fins are tall and transparent, with some scattered melanophores and iridiophores. The ventrolateral surfaces and the ventral half of the caudal musculature are dark gray with densely distributed silvery iridiophores. The oral disc and the marginal papillae are small and the tooth row formula is 2 (2)/ 3; the A- 2 gap is broad, being about one third the length of the A- 2 row. The beak is small and shallowly notched. Advertisement call has a mean frequency of 1479��1785 and a mean pulse of 33.14��38.17 (corrected to 25 o C; Porter 1964 a). Diagnosis. A large species of Incilius (males to 98 mm SVL, females to 125 mm SVL) with the full complement of cranial crests (canthal, supraorbital, supratympanic, postorbital, parietal, preorbital, pretympanic, and suborbital), none of which are hypertrophied to any considerable degree. The tympanum is large (about 50 % diameter of the eye), and usually in contact with the pretympanic crest. The skin is rough, with many evenly distributed sharply pointed tubercles over all dorsal surfaces, and with a distinct lateral descending row of enlarged sharply pointed tubercles on the flanks. Tibial glands are absent. The vocal slits are large and bilateral. The parotoid glands are distinctly triangular or subtriangular in shape. The color pattern is remarkably invariable, with most individuals having dark brown dorsal and dorsolateral background coloration, with a broad cream or yellow mid-dorsal stripe and paired dorsolateral stripes (usually ventral to the lateral row of tubercles) of a similar pale color. No individuals show a distinctive ��dead leaf�� color pattern dorsally. The tips of the digits are of a similar color to the rest of the digit. Incilus nebulifer is similar in appearance to I. valliceps from which it most easily is distinguished by having the dorsal coloration described above (Fig. 2), which is virtually absent in the otherwise polymorphic I. valliceps. The two species are parapatric about a geographic line crossing the Gulf Versant of Veracruz, Mexico, near the town of Palma Sola (Mulcahy et al. 2006). The tadpoles of I. nebulifer (Fig. 3) and I. valliceps are essentially indistinguishable, fitting the characters presented in the keys presented by Altig (1970), Altig et al. (1998), and Mendelson et al. (1999)��all presented under the taxon Bufo valliceps. Hybridization between these two species has not been documented. Descriptions. The original description, as Bufo granulosus by Baird & Girard (1852) provided perfunctory details focusing on the cranial crests and coloration. The subsequent taxonomic note (Girard 1854), replacing the preoccupied name granulosus with Bufo nebulifer, provided no additional morphological descriptions. Baird (1859) also presented a brief description. Cope (1889, as B. valliceps) provided a description that is consistent with that of I. nebulifer (rather than I. valliceps) and indeed it appears to be based mostly on material that is geographically referable to I. nebulifer; references to specimens therein that geographically are referable to I. valliceps are limited to the ��Varieties�� section of the account. Kellogg��s (1932, as B. valliceps) description is a composite representing specimens referable to both I. nebulifer and I. valliceps. Descriptions referable to I. nebulifer may be found in the following publications: Wright & Wright (1938; 1949; both as B. valliceps); Blair et al. (1957, as B. valliceps), Conant (1958; 1975; both as B. valliceps); Dickerson (1969, as B. valliceps), Cochran & Goin (1979), Smith (1978, as B. valliceps); Behler & King (1979, as B. valliceps); Garrett & Barker (1987, as B. valliceps); Branson (1995, as B. valliceps), Dundee et al. (1989, as B. valliceps); Conant & Collins (1998, as B. valliceps); Trauth et al. (2004, as B. nebulifer), Lemos-Espinal & Smith (2007, as B. nebulifer), Dorcas & Gibbons (2008, as B. nebulifer); Elliott, Gerhardt, & Davidson (2009, as B. nebulifer / Ollotis nebulifer), Oliver-L��pez et al. (2009, as Ollotis nebulifer), Tipton et al. (2012), and Lemos-Epinal & Dixon (2013). Descriptions of metamorphic and juvenile individuals were provided by Greuter (2004). Descriptions of the tadpole (as B. valliceps) were presented by Wright (1929) and, in the form of dichotomous keys, were presented by Altig (1970), Altig et al. (1998), and Dodd (2013); Limbaugh & Volpe (1957) and Gosner (1960) described the tadpole through early development. Chromosomal information was presented by Cole et al. (1968), Bachman (1970), and Beck & Mahan (1979). Illustrations. Illustrations appear in all of the references cited in ��Descriptions�� above except that of Baird & Girard (1852). The illustration in Cope (1889) is referable to I. nebulifer. Others published illustrations include Cochran (1961, as B. valliceps), Clark (1971, as B. valliceps), Blair (1972, as B. valliceps), Mattison (2007, as B. nebulifer and Waddle (2011, as I. nebulifer). Illustrations of several osteological elements, based on un-vouchered specimens(s) from San Luis Potosi, Mexico, were presented by Holman (2003). The drawing presented by Powell et al. (1998:fig. 58; as B. valliceps) is intended to refer to populations in USA (i.e., I. nebulifer) but in fact represents the Neotropical species I. campbelli; Lemos-Espinal & Dixon (2013:fig. 6) reprinted the same image to represent I. nebulifer. Fossil Record. Holman (2003) reviewed published accounts of fossils referred to B. cf. valliceps and B. valliceps from Scurry County and Culberson County, Texas, USA, respectively. Both records are presumed to be referable to I. nebulifer, though both are extralimital with respect to the modern range of the species. The Scurry County record is from the Pliocene, and the Culberson County record is from the Pleistocene. Mulcahy & Mendelson (2000) posited a Miocene��Pliocene vicariant speciation event separating I. nebulifer and I. valliceps along the Caribbean Coast of modern-day Veracruz, Mexico, with subsequent Pleistocene dispersal of I. nebulifer northward into modern-day USA. This hypothesis is not entirely consistent with the fossil records from western Texas, USA. Holman (2003) in his review of North American anuran fossils states definitively the only fossil record of I. valliceps (= presumably I. nebulifer) is from Fowlkes Cave, Culberson County, Texas; thus he casts doubt on the validity of the Pliocene record from Scurry County, Texas. Remarks. The town of Indianola, referenced in the type locality, no longer is recognized after being decimated by a series of hurricanes in the 1800 s. It was located near the mouth of Matagorda Bay on the Gulf Coast of Calhoun County, Texas, USA, at approximately N 28 o 30 ��, W 96 o 29 ��. Despite the initial taxonomic misstep by Baird & Girard (1852) and the recent taxonomic changes of generic names for the clade of Mesoamerican bufonids (Frost et al. 2006 a; 2006 b; 2009), the species was referred consistently to as B. valliceps in all literature and taxonomic checklists (e.g., Gorham 1974) from the time of Cope (1863) until Mulcahy & Mendelson (2000) Consequently, the literature on this species is relatively simple to search and interpret, so long as the reader can determine the provenance of the material being discussed (i.e., USA and northern Mexico vs. southern Mexico and Central America) With this distinction in mind, the majority of the literature relating to ecology, behavior, and physiology that was published under the name Incilius (= Bufo) valliceps actually pertains to I. nebulifer. Note that Trauth et al. (2004) incorrectly listed Mulcahy & Mendelson as the authority for the taxon nebulifer when, in fact, it is Girard. Etymology. The name nebulifer is derived from nebula, meaning ��cloud�� and ��fer�� meaning ��bearing�� and is in reference to the generally clouded color pattern of this species. The etymology provided by Dodd (2013), for the taxon nebulifer, is incorrect. Distribution. We present a map of locality records in Fig. 4. Consideration of the distribution of I. nebulifer suggests that it is limited at its southern extent by the seemingly minimal eastern tail of the Trans-Mexican Volcanic Axis (Mulcay et al. 2006), whereas it appears to be capitalizing upon human habitat disturbance and actively expanding its distribution eastward in the United States (Vogel and Pechman 2010; Milko 2012). Presumably, the northern distributional limit is delimited by winter temperatures, although the species does occur in areas known to experience hard freezes. Similarly, it appears that the western distributional limits are contained by the cooler conditions on the uplift of the Sierra Madre Oriental in Mexico. In USA and extreme northern Mexico, the distributional pattern appears to follow permanent drainages in the Chihuahuan Desert, suggesting that aridity plays a factor in delimiting the range in this area. However, none of these hypotheses regarding physiological effects of low temperatures and dryness as factors limiting the distribution have been explicitly tested. MAP. The distribution of Incilius nebulifer. Dots indicate locality records. The approximate location of the type locality is indicated with a star. Question mark indicates a valid specimen record that likely does not represent a natural, nor established, population (see text). Distributional notes were presented by Hallowell (1856), Baird (1859), Garman (1887), Cope (1888), Strecker (1902), Stone (1903), Gadow (1905), Strecker (1908 a, b; 1909; 1926 a ��d), Sanders (1909), Strecker (1926 a �� c), Strecker & Williams (1927), Strecker (1928), Burt & Burt (1929), Strecker (1930), Burt (1935), Strecker & Johnson (1935), Schmidt & Owens (1944), Smith & Buechner (1947), Smith (1948), Blair (1950), Brown (1950), Milstead et al. (1950), Peterson (1950), Reese & Firschein (1950), Anderson et al. (1952), Smith & Sanders (1952), Raun (1959), Milstead (1960), Webb & Packer (1961), Lewis (1974), Conant (1977), Carl (1980), Rackowitz et al. (1983), Thornton & Smith (1993), Blair et al. (1995), McAllister & Ward (1986), Fleet & Aubrey (1997), Ram��rez-Bautista (1999), Dixon (2000), Dayton et al. (2001), Johnson (2002), Gifford & Fontenot (2003), Hibbitts et al. (2008), Price (2009), Lazcano et al. (2012), Dixon & Hibbitts (2013), Farr et al. (2013), and Maxwell (2013). Although this species is listed in most literature and field guides (e.g., Conant & Collins 1998; Dorcas & Gibbons 2008) as occurring in the state of Arkansas, USA, Trauth et al. (2004) reported that the occurrence in that state is based on but a single record (first reported by Smith & Langebartel (1949) near Calion, Union County, Arkansas; no additional records have been found. While Trauth et al. (2004) continued to list the species as part of the fauna of Arkansas, it seems unlikely that a viable population ever existed within the boundaries of Arkansas; that record is indicated on the map herein, but is not considered as part of the natural range of the species. A geographically proximal record, from Morehouse Parish, Louisiana, USA, is based on a specimen in the University of Louisiana at Monroe (ULM 16976) and does appear to be properly identified (J. L. Carr, pers. comm.); we have no information to discredit the validity of its locality data. However, we agree with J. Boundy (pers. comm.) that the natural northern boundary of I. nebulifer in Louisiana appears to lie in the lower Red River Valley, in Rapides Parish. The locality mapped by Dundee et al. (1989) for Richland Parish is not based on an extant voucher specimen (J. Boundy, pers. comm.); so, we do not include that record here. Given the proximity of Caddo Parish, in northwestern Louisiana, to known records in adjacent counties in northeastern Texas gives us a somewhat objective reason to predict the presence of the species in northeastern Texas, despite the apparent lack of records. Specimens mapped from Jones County, Mississippi, USA (Mendelson, in Lannoo 2005) are based on specimens at the University of Southern Mississippi that have highly suspect locality data (R. L. Jones, pers. comm.); based on this information, we discount records from that county. In the western extreme of its distribution, in the Chihuahuan Desert, I. nebulifer appears to be restricted to the primary watercourses draining into either basins or into the Rio Grande that forms the US ��Mexican border. In Mexico, Lemos-Espinal et al. (2004) do not list this species, under any taxonomic name from the State of Chihuahua; based on records of species in drainages into the Rio Grande in Texas, USA, we suspect this species will be found in similar drainages in Chihuahua, Mexico. Espino de Castillo et al. (2009) mention a toad they refer to Incilius valliceps from Los Riscos cave, in the State of Quer��taro, but with no mention of voucher specimens; we do not include this record on the map presented here. Biology of The Gulf Coast Toad. The catalogue account for Bufo valliceps (Porter, 1970), as well as Porter��s (1962; 1964 a��c) overall concept of the species, is a composite of I. nebulifer, I. valliceps, and additional species of Incilius (Mendelson 1998); however, those records and literature cited that pertain to specimens from the currently known range of I. nebulifer are valid for this latter species. Morphology. Morphological descriptions and analyses of morphological data were presented by Bauldauf (1958), McAlister (1961), W. Martin (1967; 1971), R. Martin (1972 a, b), Martin & Gans (1972), Gans (1973), Emerson (1982), Hutchinson & Savitzky (2004) R. Martin (1972 b). The analyses of sternal morphology and inguinal fat body organs by da Silva & Mendelson (1999) included specimens referable both to I. nebulifer and I. valliceps, however no differences in these structures are evident between the two species (Mendelson et al. 2011). The osteological review provided by Martin (1973) is problematic because it was based on specimens referable to I. nebulifer, but also included a skeletal specimen identified as Bufo valliceps (the specimen in Martin 1973:fig. 2 D is TNHC 41994; T. LaDuc, in lett.); this specimen bears the locality data �� Mexico: Sinaloa�� which is greatly extralimital for the either I. nebulifer or I. valliceps., Published as part of Mendelson Iii, Joseph R., Kinsey, Se. T. & Murphy, Es. B., 2015, A review of the biology and literature of the Gulf Coast Toad (Incilius nebulifer), native to Mexico and the United States, pp. 517-537 in Zootaxa 3974 (4) on pages 517-525, DOI: 10.11646/zootaxa.3974.4.4, http://zenodo.org/record/238380, {"references": ["Girard, C. (1854) A list of North American bufonids, with diagnoses of new species. Proceedings of the Academy of Natural Sciences Philadelphia, 7, 87.", "Baird, S. F. & Girard, C. (1852) Characteristics of some new reptiles in the Museum of the Smithsonian Institution. Third part. Proceedings of the Academy of Natural Sciences of Philadelphia, 6, 173.", "Spix, J. B. (1824) Animalia nove sive species novae Testudinum et Ranarum quas in itinere per Brasiliam annis MDCCCXVII - MCCCCXX jussu et auspiciis Maxmiliani Josephi I. Bavariae Regis. F. S. Hubschmann, Munchen, xxxix + 53 pp.", "Schmidt, K. P. (1953) A Check List of North American Amphibians and Reptiles, Sixth Edition. American Society of Ichthyologists and Herpetologists, University of Chicago Press, Chicago, Illinois, 280 pp.", "Kellogg, R. (1932) Mexican tailless amphibians in the United States National Museum. Bulletin of the United States National Museum, 160, 1 - 224. http: // dx. doi. org / 10.5479 / si. 03629236.160. i", "Fouquette, M. J. & Dubois, A. (2014) A Checklist of North American Amphibians and Reptiles, Seventh Edition. Vol. 1. Amphibians. Privately published via Xlibris. com Publishersa, 586 pp.", "Baird, S. F. (1859 a) Report upon the reptiles of the route. Reports of Explorations and Surveys to Ascertain the Most Practicable Route for a Railroad from the Mississippi River to the Pacific Ocean: Route Near the Thirty-fifth Parallel, Explored by Lieutenant A. W. Whipple, Assisted by J. C. Ives. Volume 10. Part 6 (Zoology: Reptilia), 4, 37 - 45. [Washington, District of Columbia.]", "Cope, E. D. (1863) On Trachycephalus, Scaphiopus and other Batrachia. Proceedings of the Academy of Natural Sciences of Philadelphia, 15, 43 - 54.", "Peters, W. C. H. 1863. Peters, W. C. H. 1863. Bemerkungen uber verschiedene Batrachier, namentlich uber die Originalexemplare der von Schneider und Wiegmann beschriebenen Arten des zoologischen Museums zu Berlin. Monatsberichte der Koniglichen Preussische Akademie des Wissenschaften zu Berlin 1863: 76 - 82", "Mulcahy, D. G. & Mendelson, J. R. III. (2000) Phylogeography and speciation of the morphologically variable, widespread species Bufo valliceps, based on molecular evidence from mtDNA. Molecular Phylogenetics and Evolution, 17, 173 - 189. http: // dx. doi. org / 10.1006 / mpev. 2000.0827", "Frost, D. R., Grant, T., Faivovich, J., Bain, R. H., Haas, A., Haddad, C. F. B., de Sa, R. O., Channing, A., Wilkinson, M., Donnellan, S. C., Raxworthy, C. J., Campbell, J. A., Blotto, B. L., Moler, P. E., Drewes, R. C., Nussbaum, R. A., Lynch, J. D., Green, D. M. & Wheeler, W. C. (2006 a) The amphibian tree of life. Bulletin of the American Museum of Natural History, 297, 1 - 370. http: // dx. doi. org / 10.1206 / 0003 - 0090 (2006) 297 [0001: TATOL] 2.0. CO; 2", "Frost, D. R., Grant, T. & Mendelson, J. R. III. (2006 b) Ollotis Cope, 1875 is the oldest name for the genus currently referred to as Cranopsis Cope, 1875. Copeia, 2006, 558. http: // dx. doi. org / 10.1643 / 0045 - 8511 (2006) 2006 [558: OCITON] 2.0. CO; 2", "Frost, D. R., Mendelson III, J. R., Pramuk, J. B. (2009) Further notes on the nomenclature of Middle American toads (Bufonidae). Copeia, 2009, 418. http: // dx. doi. org / 10.1643 / CH- 08 - 204", "Crother, B. I. (Ed.) (2012) Scientific and Standard English Names of Amphibians and Reptiles of North American North of Mexico, with Comments Regarding Confidence in our understanding, 7 th Edition. Society for the Study of Reptiles and Amphibians Herpetological Circular, 39, 1 - 92.", "Liner, E. A. & Casas-Andreu, G. (2008) Scientific, English and Scientific Names of the Amphibians and Reptiles of Mexico, Second Edition. Society for the Study of Amphibians and Reptiles Herpetological Circular, 38, 1 - 162.", "Porter, K. R. (1964 a) Morphological and mating call comparisons in the Bufo valliceps complex. The American Midland Naturalist, 71, 232 - 245. http: // dx. doi. org / 10.2307 / 2422697", "Mulcahy, D. G., Morrill, B. H. & Mendelson, J. R. III. (2006) Historical biogeography of lowland species of toads (Bufo) across the Trans-Mexican Neovolcanic Belt and the Isthmus of Tehuantepec. Journal of Biogeography, 33, 1889 - 1904. http: // dx. doi. org / 10.1111 / j. 1365 - 2699.2006.01546. x", "Altig, R. (1970) A key to the tadpoles of the continental United States and Canada. Herpetologica, 26, 180 - 207.", "Altig, R., McDiarmid, R. W., Nichols, K. A. & Ustach, P. C. (1998) A key to the anuran tadpoles of the United States and Canada. Contemporary Herpetology Information Series, 2, 1 - 53. Available from: http: // dataserver. calacademy. org / herpetology / herpdocs / chis / 1998 / 2 / index. htm (accessed 7 April 2014)", "Cope, E. D. (1889) The Batrachia of North America. United States National Museum Bulletin, 34, 1 - 525.", "Wright, A. H & Wright, A. A. (1938) Amphibians of Texas. Transactions of the Texas Academy of Science, 21, 1 - 36.", "Wright, A. H. & Wright, A. A. (1949) Handbook of Frogs and Toads of the United States and Canada, Third edition. Comstock Publishing Associates, Ithaca, New York, 640 pp.", "Blair, W. F., Blair, A. P., Brodkorb, P., Cagle, F. R. & Moore, G. A. (1957) Vertebrates of the United States. McGraw-Hill Book Company, New York, 819 pp.", "Conant, R. (1958) A Field Guide to Reptiles and Amphibians of the United States and Canada East of the 100 th Meridian. Houghton Mifflin Company, Boston, Massachusetts, xv + 366 pp.", "Conant, R. (1975) A Field Guide to Reptiles and Amphibians of Eastern and Central North America. Second edition. Houghton Mifflin Company, Boston, Massachusetts, 429 pp.", "Dickerson, M. C. (1969) The Frog Book: North American Toads and Frogs. Dover Publications, New York, 253 pp.", "Smith, H. M. (1978) A Guide to Field identification: Amphibians of North America. Golden Press, New York, 160 pp.", "Behler, J. L. & King, F. W. (1979) The Audubon Society Field Guide to North American Reptiles and Amphibians. Alfred A. Knopf Publishers, New York, 744 pp.", "Garrett, J. M. & Barker, D. G. (1987) A Field Guide to Reptiles and Amphibians of Texas. Texas Monthly Press, Austin, Texas, 225 pp.", "Branson, B. A. (1995) The Gulf Coast Toad: a distribution master. Reptiles and Amphibians Magazine, (Nov / Dec 1995), 59 - 63.", "Dundee, H. A., Rossman, D. A. & Beckham, E. C. (1989) The Amphibians and Reptiles of Louisiana. Louisiana State University Press, Baton Rouge, Louisiana, 316 pp.", "Conant, R. & Collins, J. T. (1998) A Field Guide to Amphibians and Reptiles: Eastern and Central North America. Third edition, expanded. Houghton Mifflin Company, Boston, Massachusetts, xviii + 616 pp.", "Trauth, S. E., Robinson, H. W. & Plummer, M. V. (2004) The Amphibians and Reptiles of Arkansas. University of Arkansas Press, Fayetteville, Arkansas, 421 pp.", "Lemos-Espinal, J. A. & Smith, H. M. (2007) Anfibios y Reptiles del Estado de Coahuila, Mexico. Universidad Nacional Autonoma de Mexico-Comision Nacional para el Conocimiento y Uso de la Biodiversidad, Mexico City, 550 pp.", "Dorcas, M. & Gibbons, W. (2008) Frogs and Toads of the Southeast. University of Georgia Press, Athens, Georgia, 264 pp.", "Elliott, L., Gerhardt, C. & Davidson, C. (2009) The Frogs and Toads of North America. Houghton Mifflin Harcourt Publishers, New York, 343 pp.", "Oliver-Lopez, L., Woolrich-Pina, G. A. & Lemos-Espinal, J. A. (2009) La Familia Bufonidae en Mexico. Universidad Nacional Autonoma de Mexico-Comision Nacional para el Conocimiento y Uso de la Biodiversidad, Mexico City, 139 pp.", "Tipton, B. L., Hibbitts, T. L., Hibbitts, T. D., Hibbitts, T. J. & LaDuc, T. J. (2012) Texas Amphibians: A Field Guide. University of Texas Press, Austin, Texas, 330 pp.", "Lemos-Espinal, J. A. & Dixon, J. R. (2013) Amphibians and Reptiles of San Luis Potosi. Eagle Mountain Publishing, Eagle Mountain, Utah, 300 pp.", "Greuter, K. L. (2004) Early juvenile ecology of the endangered Houston toad, Bufo houstonensis (Anura: Bufonidae). M. S. Thesis, Texas State University, San Marcos, Texas, 103 pp.", "Wright, A. H. (1929) Synopsis and description of North American tadpoles. Proceedings of the United States National Museum, 74, 1 - 70. http: // dx. doi. org / 10.5479 / si. 00963801.74 - 2756.1", "Dodd, C. K. (2013) Frogs of the United States and Canada. Johns Hopkins University Press, Baltimore, Maryland, 1032 pp.", "Limbaugh, B. A. & Volpe, E. P. (1957) Early development of the Gulf Coast Toad, Bufo valliceps Wiegmann. American Museum Novitates, 1842, 1 - 32.", "Gosner, K. L. (1960) A simplified table for staging anuran embyos and larvae with notes on identification. Herpetologica, 16, 183 - 190.", "Cole, C. J., Lowe, C. H. & Wright, J. W. (1968) Karyotypes of eight species of toads (genus Bufo) in North America. Copeia, 1968, 96 - 100. http: // dx. doi. org / 10.2307 / 1441555", "Bachman, K. (1970) Specific nuclear DNA amounts in toads of the genus Bufo. Chromosoma, 29, 365 - 374. http: // dx. doi. org / 10.1007 / BF 00325949", "Beck, M. L. & Mahan, J. T. (1979) Ammoniacal silver staining of nucleolar organizer regions in four species of Bufo. Copeia, 1979, 341 - 345. http: // dx. doi. org / 10.2307 / 1443422", "Cochran, D. M. (1961) Living Amphibians of the World. Doubleday and Company, Garden City, New York, 199 pp.", "Clark, D. R. Jr. (1971) Branding as a marking technique for amphibians and reptiles. Copeia, 1971, 148 - 151. http: // dx. doi. org / 10.2307 / 1441609", "Blair, W. F. (1972) Bufo of North and Central America. In: Blair, W. F. (Ed.), Evolution in the Genus Bufo. University of Texas Press, Austin, Texas, pp. 93 - 101.", "Mattison, C. (2007) 300 Frogs. A Visual Reference to Frogs and Toads from Around the World. Windmill Books, London, 528 pp.", "Holman, J. A. (2003) Fossil frogs and Toads of North America. Indiana University Press, Bloomington, Indiana, 246 pp.", "Powell, R., Collins, J. T. & Hooper, E. D. Jr. (1998) A key to amphibians and reptiles of the continental United States and Canada. University of Kansas Press, Lawrence, Kansas, 131 pp.", "Gorham, S. W. (1974) Checklist of World Amphibians. Liste des Amphibiens du Monde. The New Brunswick Museum, Saint John, New Brunswick, Canada, 172 pp.", "Vogel, L. S. & Pechmann, J. H. K. (2010) Response of Fowler's toads (Anaxyrus fowleri) to competition and hyproperiod in the presence of the invasive Coastal plain toad (Incilius nebulifer) Journal of Herpetology, 44, 382 - 389. http: // dx. doi. org / 10.1670 / 08 - 300.1", "Milko, L. V. (2012) Integrating museum and GIS data to identify changes in species distributions driven by a disturbanceinduced invasion. Copeia, 2012, 307 - 320. http: // dx. doi. org / 10.1643 / CE- 10 - 159", "Hallowell, E. (1856) Notes on the collection of reptiles from the neighborhood of San Antonio, Texas, recently presented to the Academy of Natural Sciences by Dr. A. Heermann. Proceedings of the Academy of Natural Sciences of Philadelphia, 8, 306 - 310.", "Garman, S. (1887) Reptiles and batrachians from Texas and Mexico. Bulletin of the Essex Institution, 19, 119 - 138.", "Cope, E. D. (1888) Catalogue of Batrachia and Reptilia brought by William Taylor from San Diego, Texas. Proceedings of the United States National Museum, 11, 395 - 398. http: // dx. doi. org / 10.5479 / si. 00963801.11 - 728.395", "Strecker, J. K. (1902) Reptiles and batrachians of McLennan County, Texas. Transactions of the Texas Academy of Sciences, 4, 95 - 101.", "Stone, W. (1903) A collection of reptiles and batrachians from Arkansas, Indian Territory, and western Texas. Proceedings of the Academy of Natural Sciences of Philadelphia, 55, 538 - 542.", "Gadow, H. (1905) The distribution of Mexican amphibians and reptiles. Proceedings of the Zoological Society of London, 1905, Part 2, 191 - 244. http: // dx. doi. org / 10.1111 / j. 1469 - 7998.1905. tb 08388. x", "Strecker, J. K. (1908 a) The reptiles and batrachians of Victoria and Refugio counties, Texas. Proceedings of the Biological Society of Washington, 21, 47 - 52.", "Strecker, J. K. (1908 b) A preliminary annotated list of the Batrachia of Texas. Proceedings of the Biological Society of Washington, 21, 53 - 62.", "Strecker, J. K. (1909) Notes on the herpetology of Burnet County, Texas. Baylor University Bulletin, 12, 1 - 9.", "Strecker, J. K. (1926 a) Notes on the herpetology of the east Texas timber belt. 1. Liberty County amphibians and reptiles. Contributions Baylor University Museum, 3, 1 - 3.", "Strecker, J. K. (1926 c) Notes on the herpetology of the east Texas timber belt. 2. Henderson County amphibians and reptiles. Contributions Baylor University Museum, 7, 3 - 7.", "Strecker, J. K. & Williams, W. J. (1927) Herpetologica l records from the vicinity of San Marcos, Texas, with distributional data on the amphibians and reptiles of the Edwards Plateau region and central Texas. Contributions Baylor University Museum, 12, 1 - 16.", "Strecker, J. K. (1928) Occurrence of the spotted night snake (Hypsiglena ochrorynchus Cope) in central Texas with other Bosque County herpetological notes. Contributions from Baylor University Museum, 15, 2 - 6.", "Burt, C. E. & Burt. M. D. (1929) A collection of amphibians and reptiles from the Mississippi Valley with field observations. American Museum Novitates, 381, 1 - 14.", "Strecker, J. K. (1930) A catalogue of the amphibians and reptiles of Travis County, Texas. Contributions from Baylor University Museum, 23, 1 - 16.", "Burt, C. E. (1935) Further records of the ecology and distribution of amphibians and reptiles in the Middle West. American Midland Naturalist, 16, 311 - 336. http: // dx. doi. org / 10.2307 / 2420031", "Strecker, J. K. & Johnson, J. E. Jr. (1935) Notes on the herpetology of Wilson County, Texas. Baylor University Bulletin, 38, 17 - 23.", "Schmidt, K. P. & Owens, D. W. (1944) Amphibians and reptiles of northern Coahuila, Mexico. Zoological Series of Field Museum of Natural History, 6, 97 - 115.", "Smith, H. M. & Buechner, H. K. (1947) The influence of the Balcones Escarpment on the distribution of amphibians and reptiles in Texas. Bulletin of the Chicago Academy of Sciences, 8, 1 - 16.", "Blair, W. F. (1950) The biotic provinces of Texas. Texas Journal of Science, 2, 93 - 117.", "Brown, B. C. (1950) An Annotated Checklist of the Reptiles and Amphibians of Texas. Baylor University Studies Publication Series, Waco, Texas, 257 pp.", "Milstead, W. W., Mecham, J. S. & McClintock, H. (1950. The amphibians and reptiles of the Stockton Plateau in northern Terrell County, Texas. Texas Journal of Science, 2, 543 - 562.", "Peterson, R. L. (1950) Amphibians and reptiles of Brazos County, Texas. American Midland Naturalist, 43, 157 - 164. http: // dx. doi. org / 10.2307 / 2421886", "Reese, R. W. & Firschein, I. L. (1950) Herpetological results of the University of Illinois field expedition, spring 1949. II. Amphibia. Transactions of the Kansas Academy of Sciences, 53, 44 - 54. http: // dx. doi. org / 10.2307 / 3625676", "Anderson, P. K., Liner, E. A. & Etheridge, R. E. (1952) Notes on amphibians and reptile populations in a Louisiana pineland areas. Ecology, 33, 274 - 278. http: // dx. doi. org / 10.2307 / 1930645", "Smith, H. M. & Sanders, O. (1952) Distributional data on Texas amphibians and reptiles. Texas Journal of Science, 4, 204 - 219.", "Raun, G. G. (1959) Terrestrial and aquatic vertebrates of a moist, relict area in central Texas. Texas Journal of Science, 11, 158 - 171.", "Milstead, W. W. (1960) Relict species of the Chihuahuan Desert. Southwestern Naturalist, 5, 75 - 88. http: // dx. doi. org / 10.2307 / 3669459", "Webb, R. G. & Packard, R. L. (1961) Notes of some amphibians and reptiles from eastern Texas. Southwestern Naturalist, 6, 105 - 107. http: // dx. doi. org / 10.2307 / 3669599", "Lewis, M. R. (1974) Recent county records and range extensions in south central Texas. Herpetological Review, 5, 21.", "Conant, R. (1977) Semiaquatic reptiles and amphibians of the Chihuahuan desert and their relationships to drainage patterns of the region. In: Wauer, R. H. & Riskind, D. H. (Eds.), Transactions of the Symposium on the Biological Resources of the Chihuhuan Desert Region: United States and Mexico. United States Department of the Interior National Park Transactions and Proceedings, Series 3, pp. 445 - 491.", "Carl, G. (1980) Distributional records for Johnson County, Texas. Herpetological Review, 11, 116 - 117.", "Thornton, O. W. & Smith, J. R. (1993) New county records for amphibians and reptiles from west-central Texas. Herpetological Review, 24, 35 - 36.", "Blair, K. B., Killebrew, F. C., Smith, H. M. & Chiszar, D. (1995) Geographic Distribution: Bufo valliceps. Herpetological Review, 26, 152.", "McAllister, C. T. & Ward, R. (1986) New distributional records of Texas herpetofauna. Texas Journal of Science, 38, 65 - 69.", "Fleet, R. R. & Aubrey, B. C. (1997) Geographic Distribution: Bufo valliceps. Herpetological Review, 28, 48.", "Ramirez-Bautista, A. (1999) Herpetofauna de la region El Huizache, San Luis Potosi. Informe Final del Proyecto R 045. Comision Nacional para el Conocimiento y Uso de la Biodiversidad, Mexico City, Mexico, 150 pp.", "Dixon, J. R. (2000) Amphibians and Reptiles of Texas. Texas A & M Press, College Station, Texas, 421 pp.", "Dayton, G. H., Fitzgerald, L. A. & Goldstein, M. I. (2001) Geographic Distribution: Bufo valliceps. Herpetological Review, 32, 112.", "Johnson, J. A. (2002) Bufo valliceps (Gulf Coast Toad): Geographic Distribution: Herpetological Review, 33, 219.", "Gifford, M. E. & Fontenot, B. E. (2003) Geographic Distribution: Bufo nebulifer Herpetological Review, 34, 257.", "Hibbitts, T. J., Saenz, D., Adams, C. & Pierce, J. (2008) Geographic Distribution: Ollotis (= Bufo) nebulifer (Gulf Coast Toad). Herpetological Review, 39, 480.", "Price, M. S. (2009) Geographic Distribution: Ollotis nebulifer (Gulf Coast Toad) Herpetological Review, 40, 109.", "Lazcano, D., Contreras-Lozano, J., Narvaez-Torrez, S. & Chavez-Cisneros, J. (2012) Notes on Mexican herpetofauna 18: herpetofauna of Cerro El Topo Chica Natural Protected Area, Nuevo Leon, Mexico. Bulletin of the Chicago Herpetological Society, 47, 149 - 155.", "Dixon, J. R. & Hibbitts, T. J. (2013) Amphibians and Reptiles of Texas: With Keys, Taxonomic Synopses, Bibliography, and Distribution Maps. W. L. Moody Natural History Series 45. Texas A & M University Press, College Station, Texas, 460 pp.", "Farr, W. L., Lazcano, D. & Lavin-Murcio, P. A. (2013) New distributional records for amphibians and reptiles from the State of Tamaulipas, Mexico III. Herpetological Review, 44, 631 - 645", "Maxwell, T. C. (2013) Wildlife of the Concho Valley. W. L. Moody Natural History Series 48. Texas A & M University Press, College Station, Texas, 292 pp.", "Smith, H. M. & Langebartel, D. A. (1949) The toad Bufo valliceps in Arkansas. Copeia, 1949, 230. http: // dx. doi. org / 10.2307 / 1439003", "Lemos-Espinal, J. A., Smith, H. M. & Chiszar, D. (2004) Anfibios y Reptiles del Estado de Chihuahua, Mexico. Universidad Nacional Autonoma de Mexico-Comision Nacional para el Conocimiento y Uso de la Biodiversidad, Mexico City, 128 pp.", "Espino de Castillo, A., Castano-Meneses, G., Davila-Montes, M. J., Miranda-Ayada, M., Morales-Malacara, J. B. & Paredes- Leon, R. (2009) Seasonal distribution and circadian activity in the troglophile long-footed robber frog Eleutherodactylus longipes (Anura: Brachycephalidae) at Los Riscos cave, Queretaro, Mexico: field and laboratory studies. Journal of Cave and Karst Studies, 71, 24 - 31.", "Porter, K. R. (1970) Chapter 94. Bufo valliceps. Catalogue of American Amphibians and Reptiles. Society for the Study of Amphibians and Reptiles, St. Louis, Missouri, 1 - 4.", "Mendelson, J. R., III (1998) Geographic variation in Bufo valliceps (Anura: Bufonidae), a widespread toad in the United States and Middle America. S cientific Papers of the Natural History Museum, University of Kansas, 9, 1 - 12.", "McAlister, W. H. (1961) Mechanics of sound productio
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3. EFFECT OF THE ANTIARRHYTHMIC AGENT MORICIZINE ON SURVIVAL AFTER MYOCARDIAL-INFARCTION

Author: ROGERS, WJ, EPSTEIN, AE, ARCINIEGAS, JG, CROSSLEY, GH, DAILEY, SM, KAY, GN, LITTLE, RE, MACLEAN, WAH, PAPAPIETRO, SE, PLUMB, VJ, SILBER, S, BAKER, AR, CARLISLE, K, COHEN, N, COX, M, THOMAS, C, LEVSON, L, VONHAGEL, D, WALTON, AE, PRATT, CM, MAHMARIAN, J, MORRIS, G, CAPONE, RJ, BERGER, EE, CHMIELEWSKI, C, GORKIN, L, KHAN, AH, KORR, K, HANDSHAW, K, CONNOLLY, E, FITZPATRICK, D, CAMERON, T, WYSE, DG, DUFF, HJ, MITCHELL, LB, GILLIS, AM, WARNICA, JW, SHELDON, RS, LESOWAY, NR, KELLEN, J, HALE, C, INKSTER, M, BRODSKY, M, WOLFF, L, ALLEN, B, ZELMAN, R, THOMAS, G, CAUDILLO, G, TAKEDA, D, SHERWOOD, C, RANAZZI, R, RAPAPORT, E, DOHRMANN, ML, RASKIN, S, DREW, DW, SOMELOFSKI, CA, DANFORTH, JW, HUI, PY, JOHNSON, MR, LABARCA, JR, WALDO, AL, CARLSON, MD, ADLER, DS, HOLLAND, JB, BUCHTER, CM, BAHLER, RC, PAMELIA, FX, JOSEPHSON, RA, HENTHORN, RW, ZUELGARAY, JG, WOOD, K, REDMON, P, VARGAS, MA, VARGO, L, SCHALLER, SE, KOBUS, CE, CHOBAN, NL, BIGGER, JT, GREENBERG, HM, GREGORY, JJ, HOCHMAN, JS, RADOSLOVICH, G, STEINBERG, JS, ROTHBART, ST, CASE, R, DWYER, EM, SQUATRITO, A, KELLY, M, CAMPION, JM, TORMEY, D, ANTHONY, R, CALLAGHAN, E, CHAPNICK, M, RIPLEY, B, FONTANA, C, SCHLANT, RC, ARENSBERG, D, CORSO, JA, HURST, JW, MORRIS, DC, SHERMAN, SW, SILVERMAN, BD, SILVERMAN, ME, ROBERTS, JS, BALLOU, SK, JEFFRIES, VD, BRACKNEY, BA, SEALS, AA, HARTLEY, J, BAKER, RM, GILMOUR, KE, BAKER, SB, HOWARD, J, KATZ, RJ, BESCH, GA, BRILL, D, DIBIANCO, R, DONOHUE, D, FISHER, G, FRANCIS, C, FRIEDMAN, D, GOLDBERG, D, GOLDBERG, S, KOSS, G, LARCA, L, LEONARD, R, LINDGREN, K, RONAN, J, ROSENBLATT, A, ROSING, D, ROSS, A, ROTSZTAIN, A, SHAWL, F, SINDERSON, T, STEVENSON, R, TINKER, B, VARGHESE, J, YACKEE, J, BIGHAM, H, FRANKLIN, W, GOLD, R, GRAHAM, G, GROSSBERG, D, HOARE, R, LEVY, W, MAHMOOD, T, TANNENBAUM, E, TULLNER, W, EISENHOWER, E, GERACI, T, WILHELMSEN, L, BERGSTRAND, R, FREDLUND, BO, SIGURDSSON, A, SIVERTSSON, R, SWEDBERG, K, HOULTZ, B, WIKLUND, I, SCHLYTER, G, HEDELIN, G, LEIJON, M, MORGANROTH, J, CARVER, J, HOROWITZ, L, KUTALEK, S, PAPA, L, SANDBERG, J, VICTOR, M, CESARE, S, VRABEL, C, TALARICO, K, LUHMANN, S, PALAZZO, D, GOLDSTEIN, S, GOLDBERG, AD, FRUMIN, H, WESTVEER, D, DEBUTLIER, M, SCHAIRER, J, STOMEL, R, FRANK, DM, JARANDILLA, R, DAVEY, D, HASSE, C, SHINNEY, S, MORLEDGE, JH, FARNHAM, DJ, HINDERACKER, PH, MUSSER, WE, DEVRIES, K, KUSHNER, JA, RAO, R, PETERSON, DT, MCCAULEY, CS, BERGEN, TS, BOWMAN, KO, GILLMAN, A, FULLER, L, OBRIEN, J, MORLEDGE, J, DEMARIA, AN, KUO, CS, KAMMERLING, JM, CORUM, J, THIEMANN, M, SCHRODT, R, PETERS, R, SUTTON, F, GOTTLIEB, S, PAPUCHIS, G, MATTIONI, T, TODD, L, CUSACK, C, SCHECK, J, HUANG, SKS, ALPERT, JS, GORE, JM, RYAN, M, COLLETTWILLEY, P, CHAHINE, RA, SEQUEIRA, RF, LOWERY, MH, DELGADO, LM, CORREA, JL, LASO, LJ, HODGES, M, SALERNO, D, ANDERSON, B, COLLINS, R, DENES, P, DUNBAR, D, GRANRUD, G, HAUGLAND, J, HESSION, W, MCBRIDE, J, GORNICK, C, SIMONSON, J, TOLINS, M, ETTINGER, A, PETERSON, S, SLIVKEN, R, GRIMALDI, L, ROY, D, THEROUX, P, LEMERY, R, MORISSETTE, D, BEAUDOIN, D, GIRARD, L, LAVALLEE, E, MCANULTY, JH, REINHART, SE, MAURICE, G, MURPHY, ES, KRON, J, MARCHANT, C, BOXER, J, PRINCEHOUSE, L, SINNER, K, BEANLANDS, D, DAVIES, R, GREEN, M, WILLIAMS, W, BAIRD, MJ, GARRARD, L, HEAL, S, HASPECT, A, BORTHWICK, J, MAROIS, L, WOODEND, K, AKIYAMA, T, HOOD, WB, EASLEY, R, RYAN, G, KENIEN, G, PATT, M, KAZIERAD, D, GOLDFARB, A, BUTLER, LL, KELLER, ML, STANLEY, P, PEEBLES, J, SYROCKI, D, LAVIN, D, SCHOENBERGER, JA, LIEBSON, PR, STAMATO, NJ, PETROPULOS, AT, BUCKINGHAM, TA, REMIJAS, T, KOCOUREK, J, JANKO, K, BARKER, AH, ANDERSON, JL, FOWLES, RE, KEITH, TB, WILLIAMS, CB, MORENO, FL, DORAN, EN, FOWLER, B, SUMMERS, K, WHITE, C, OHARA, G, ROULEAU, JL, PLANTE, S, VINCENT, C, BOUCHARD, D, ZOBLE, RG, OTERO, JE, BUGNI, WJ, SCHWARTZ, KM, SHETTIGAR, UR, BREWINGTON, JA, UMBERGER, J, COHEN, JD, BJERREGAARD, P, HAMILTON, WP, GARNER, M, ANDERSON, S, ELSHERIF, N, URSELL, SN, GABOR, GE, IBRAHIM, B, ASSADI, M, BREZSNYAK, ML, PORTER, AV, STANIORSKI, A, WOOSLEY, RL, RODEN, DM, CAMPBELL, WB, ECHT, DS, LEE, JT, MURRAY, KT, SPELL, JD, BONHOTAL, ST, JARED, LL, THOMAS, TI, GOLDNER, F, RICHARDSON, DW, ROMHILT, DW, ELLENBOGEN, KA, BANE, BB, FIELDS, J, SHRADER, S, POWELL, E, CHAFFIN, CF, WELLS, A, CONWAY, KT, PLATIA, EV, ODONOGHUE, S, TRACY, CM, ALI, N, BOWEN, P, BROOKS, KM, OETGEN, W, WESTON, LT, CARSON, P, OBIASMANNO, D, HARRISON, J, SAYLOR, A, POWELL, S, HAAKENSON, CM, SATHER, MR, MALONE, LA, HALLSTROM, AP, MCBRIDE, R, GREENE, HL, BROOKS, MM, LEDINGHAM, R, REYNOLDSHAERTLE, RA, HUTHER, M, SCHOLZ, M, MORRIS, M, FRIEDMAN, LM, SCHRON, E, VERTER, J, JENNINGS, C, PROSCHAN, M, BRISTOW, JD, DEMETS, DL, FISCH, C, NIES, AS, RUSKIN, J, STRAUSS, H, WALTERS, L, ROGERS, WJ, EPSTEIN, AE, ARCINIEGAS, JG, CROSSLEY, GH, DAILEY, SM, KAY, GN, LITTLE, RE, MACLEAN, WAH, PAPAPIETRO, SE, PLUMB, VJ, SILBER, S, BAKER, AR, CARLISLE, K, COHEN, N, COX, M, THOMAS, C, LEVSON, L, VONHAGEL, D, WALTON, AE, PRATT, CM, MAHMARIAN, J, MORRIS, G, CAPONE, RJ, BERGER, EE, CHMIELEWSKI, C, GORKIN, L, KHAN, AH, KORR, K, HANDSHAW, K, CONNOLLY, E, FITZPATRICK, D, CAMERON, T, WYSE, DG, DUFF, HJ, MITCHELL, LB, GILLIS, AM, WARNICA, JW, SHELDON, RS, LESOWAY, NR, KELLEN, J, HALE, C, INKSTER, M, BRODSKY, M, WOLFF, L, ALLEN, B, ZELMAN, R, THOMAS, G, CAUDILLO, G, TAKEDA, D, SHERWOOD, C, RANAZZI, R, RAPAPORT, E, DOHRMANN, ML, RASKIN, S, DREW, DW, SOMELOFSKI, CA, DANFORTH, JW, HUI, PY, JOHNSON, MR, LABARCA, JR, WALDO, AL, CARLSON, MD, ADLER, DS, HOLLAND, JB, BUCHTER, CM, BAHLER, RC, PAMELIA, FX, JOSEPHSON, RA, HENTHORN, RW, ZUELGARAY, JG, WOOD, K, REDMON, P, VARGAS, MA, VARGO, L, SCHALLER, SE, KOBUS, CE, CHOBAN, NL, BIGGER, JT, GREENBERG, HM, GREGORY, JJ, HOCHMAN, JS, RADOSLOVICH, G, STEINBERG, JS, ROTHBART, ST, CASE, R, DWYER, EM, SQUATRITO, A, KELLY, M, CAMPION, JM, TORMEY, D, ANTHONY, R, CALLAGHAN, E, CHAPNICK, M, RIPLEY, B, FONTANA, C, SCHLANT, RC, ARENSBERG, D, CORSO, JA, HURST, JW, MORRIS, DC, SHERMAN, SW, SILVERMAN, BD, SILVERMAN, ME, ROBERTS, JS, BALLOU, SK, JEFFRIES, VD, BRACKNEY, BA, SEALS, AA, HARTLEY, J, BAKER, RM, GILMOUR, KE, BAKER, SB, HOWARD, J, KATZ, RJ, BESCH, GA, BRILL, D, DIBIANCO, R, DONOHUE, D, FISHER, G, FRANCIS, C, FRIEDMAN, D, GOLDBERG, D, GOLDBERG, S, KOSS, G, LARCA, L, LEONARD, R, LINDGREN, K, RONAN, J, ROSENBLATT, A, ROSING, D, ROSS, A, ROTSZTAIN, A, SHAWL, F, SINDERSON, T, STEVENSON, R, TINKER, B, VARGHESE, J, YACKEE, J, BIGHAM, H, FRANKLIN, W, GOLD, R, GRAHAM, G, GROSSBERG, D, HOARE, R, LEVY, W, MAHMOOD, T, TANNENBAUM, E, TULLNER, W, EISENHOWER, E, GERACI, T, WILHELMSEN, L, BERGSTRAND, R, FREDLUND, BO, SIGURDSSON, A, SIVERTSSON, R, SWEDBERG, K, HOULTZ, B, WIKLUND, I, SCHLYTER, G, HEDELIN, G, LEIJON, M, MORGANROTH, J, CARVER, J, HOROWITZ, L, KUTALEK, S, PAPA, L, SANDBERG, J, VICTOR, M, CESARE, S, VRABEL, C, TALARICO, K, LUHMANN, S, PALAZZO, D, GOLDSTEIN, S, GOLDBERG, AD, FRUMIN, H, WESTVEER, D, DEBUTLIER, M, SCHAIRER, J, STOMEL, R, FRANK, DM, JARANDILLA, R, DAVEY, D, HASSE, C, SHINNEY, S, MORLEDGE, JH, FARNHAM, DJ, HINDERACKER, PH, MUSSER, WE, DEVRIES, K, KUSHNER, JA, RAO, R, PETERSON, DT, MCCAULEY, CS, BERGEN, TS, BOWMAN, KO, GILLMAN, A, FULLER, L, OBRIEN, J, MORLEDGE, J, DEMARIA, AN, KUO, CS, KAMMERLING, JM, CORUM, J, THIEMANN, M, SCHRODT, R, PETERS, R, SUTTON, F, GOTTLIEB, S, PAPUCHIS, G, MATTIONI, T, TODD, L, CUSACK, C, SCHECK, J, HUANG, SKS, ALPERT, JS, GORE, JM, RYAN, M, COLLETTWILLEY, P, CHAHINE, RA, SEQUEIRA, RF, LOWERY, MH, DELGADO, LM, CORREA, JL, LASO, LJ, HODGES, M, SALERNO, D, ANDERSON, B, COLLINS, R, DENES, P, DUNBAR, D, GRANRUD, G, HAUGLAND, J, HESSION, W, MCBRIDE, J, GORNICK, C, SIMONSON, J, TOLINS, M, ETTINGER, A, PETERSON, S, SLIVKEN, R, GRIMALDI, L, ROY, D, THEROUX, P, LEMERY, R, MORISSETTE, D, BEAUDOIN, D, GIRARD, L, LAVALLEE, E, MCANULTY, JH, REINHART, SE, MAURICE, G, MURPHY, ES, KRON, J, MARCHANT, C, BOXER, J, PRINCEHOUSE, L, SINNER, K, BEANLANDS, D, DAVIES, R, GREEN, M, WILLIAMS, W, BAIRD, MJ, GARRARD, L, HEAL, S, HASPECT, A, BORTHWICK, J, MAROIS, L, WOODEND, K, AKIYAMA, T, HOOD, WB, EASLEY, R, RYAN, G, KENIEN, G, PATT, M, KAZIERAD, D, GOLDFARB, A, BUTLER, LL, KELLER, ML, STANLEY, P, PEEBLES, J, SYROCKI, D, LAVIN, D, SCHOENBERGER, JA, LIEBSON, PR, STAMATO, NJ, PETROPULOS, AT, BUCKINGHAM, TA, REMIJAS, T, KOCOUREK, J, JANKO, K, BARKER, AH, ANDERSON, JL, FOWLES, RE, KEITH, TB, WILLIAMS, CB, MORENO, FL, DORAN, EN, FOWLER, B, SUMMERS, K, WHITE, C, OHARA, G, ROULEAU, JL, PLANTE, S, VINCENT, C, BOUCHARD, D, ZOBLE, RG, OTERO, JE, BUGNI, WJ, SCHWARTZ, KM, SHETTIGAR, UR, BREWINGTON, JA, UMBERGER, J, COHEN, JD, BJERREGAARD, P, HAMILTON, WP, GARNER, M, ANDERSON, S, ELSHERIF, N, URSELL, SN, GABOR, GE, IBRAHIM, B, ASSADI, M, BREZSNYAK, ML, PORTER, AV, STANIORSKI, A, WOOSLEY, RL, RODEN, DM, CAMPBELL, WB, ECHT, DS, LEE, JT, MURRAY, KT, SPELL, JD, BONHOTAL, ST, JARED, LL, THOMAS, TI, GOLDNER, F, RICHARDSON, DW, ROMHILT, DW, ELLENBOGEN, KA, BANE, BB, FIELDS, J, SHRADER, S, POWELL, E, CHAFFIN, CF, WELLS, A, CONWAY, KT, PLATIA, EV, ODONOGHUE, S, TRACY, CM, ALI, N, BOWEN, P, BROOKS, KM, OETGEN, W, WESTON, LT, CARSON, P, OBIASMANNO, D, HARRISON, J, SAYLOR, A, POWELL, S, HAAKENSON, CM, SATHER, MR, MALONE, LA, HALLSTROM, AP, MCBRIDE, R, GREENE, HL, BROOKS, MM, LEDINGHAM, R, REYNOLDSHAERTLE, RA, HUTHER, M, SCHOLZ, M, MORRIS, M, FRIEDMAN, LM, SCHRON, E, VERTER, J, JENNINGS, C, PROSCHAN, M, BRISTOW, JD, DEMETS, DL, FISCH, C, NIES, AS, RUSKIN, J, STRAUSS, H, and WALTERS, L

4. Memantine for Children With Brain Cancer: Are We there Yet?

Author: Li MP, Kahalley LS, and Murphy ES
Published: 2024
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5. Outcomes of adjuvant radiation treatment following subtotal resection of world health organization grade II meningiomas.

Author: Petitt JC, Murayi R, El-Abtah ME, Momin A, Halima A, Potter T, Ahorukomeye P, Jarmula J, Thapliyal M, Murphy ES, Chao ST, Suh JH, Recinos PF, and Kshettry VR
Abstract: Purpose: Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients., Methods: A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS)., Results: Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm 3 vs. 6.3 cm 3 , p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32)., Conclusion: Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS., Competing Interests: Declarations Conflict of interest Varun Kshettry is a consultant for Integra and Stryker. Pablo Recinos is a consultant for Stryker. Samuel Chao received honorariums from Varian Medical Systems and Blue Earth Diagnostics, as well as receives research support from Blue Earth Diagnostics. John Suh is consultant for Philips, Novocure, Neutron Therapeutics, and EmpNia. All other authors do not have any conflicts of interest to disclose. Ethical approval The study was approved by the Cleveland Clinic Foundation Institutional Review Board., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2024
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6. Metastatic-Site Radiation Therapy for Ewing Sarcoma and Rhabdomyosarcoma: Consensus Guidelines From the National Pediatric Cancer Foundation.

Author: Casey DL, Murphy ES, Shen CJ, Milgrom SA, Larrier NA, Bradley JA, Ladra MM, Indelicato DJ, Hill-Kayser CE, Borinstein SC, and Luo LY
Abstract: Purpose: Despite the urgent need for improved outcomes in patients with metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS), it is unknown how to best approach metastatic-site radiation therapy for these patients and whether such treatment provides a significant oncologic benefit that outweighs the toxicities., Methods and Materials: We gathered a panel of pediatric radiation oncologists from academic hospitals to identify and discuss current controversies regarding the role of radiation in the management of metastatic EWS and RMS. The panel reviewed existing clinical data and ongoing trials to address 5 key questions: (1) the role of whole lung irradiation (WLI) in treating lung metastases; (2) the number of metastatic sites warranting radiation therapy and the radicality of such an approach; (3) radiation techniques, including stereotactic body radiation therapy (SBRT); (4) the timing of metastatic-site radiation therapy; and (5) the utility of metastatic-site radiation therapy for relapsed metastatic disease., Results: After a review of existing data, consensus recommendations were developed to support the decision-making process in metastatic-site irradiation, aiming to improve long-term disease control. Patients with pulmonary metastases should receive WLI. In patients with limited (<8 sites) metastatic disease, a comprehensive approach should be taken to treat all sites of metastatic disease diagnosed at presentation. SBRT should be considered as a preferred treatment technique. The timing of metastatic-site treatment should coincide with the end of systemic therapy. However, if there is a dosimetric advantage or improved compliance, concurrent treatment with the primary site may be preferred., Conclusions: A consensus guideline was established to address several critical questions regarding the role of radiation in the treatment of metastatic EWS and RMS. The study highlights the existing controversies, provides a structured approach, and underscores the need for future studies to further evaluate the therapeutic ratio of metastatic-site directed therapy., Competing Interests: Disclosures Leo Y. Luo reports travel support from GT Medical Technologies. Julie A. Bradley reports a leadership role in PTCOG-NA. No other conflicts of interest to disclose., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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7. Pediatric Cranial Stereotactic Radiosurgery: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

Author: Murphy ES, Sahgal A, Regis J, Levivier M, Fariselli L, Gorgulho A, Ma L, Pollock B, Yomo S, Sheehan J, Paddick I, Suh JH, Saxena A, Ahmed MA, and Kotecha R
Abstract: Background: There are limited data on the use of stereotactic radiosurgery (SRS) for pediatric patients. The aim of this systematic review was to summarize indications and outcomes specific to pediatric cranial SRS to inform consensus guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS)., Methods: A systematic review, using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), analyzed English-language articles on SRS, published between 1989 and 2021, that included outcomes for at least 5 pediatric patients. MEDLINE database terms included tumor types and locations, and radiosurgical and age-specific terms. We excluded nonclinical reports, expert opinions, commentaries, and review articles. Meta-regressions for associations with local control were performed for medulloblastoma, craniopharyngioma, ependymoma, glioma, and arteriovenous malformation (AVM)., Results: Of the 113 articles identified for review, 68 met the inclusion criteria. These articles described approximately 400 pediatric patients with benign and malignant brain tumors and 5119 with AVMs who underwent cranial SRS. The rates of local control for benign tumors, malignant tumors, and AVMs were 89% (95% CI, 82%-95%), 71% (95% CI, 59%-82%), and 65% (95% CI, 60%-69%), respectively. No significant associations were identified for local control with patient-, tumor-, or treatment-related variables., Conclusions: This review is the first to summarize outcomes specific to SRS for pediatric brain tumors and AVMs. Although data reporting is limited for pediatric patients, SRS appears to provide acceptable rates of local control. We present ISRS consensus guidelines to inform the judicious use of cranial SRS for pediatric patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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8. Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

Author: Murphy ES, Yang K, Suh JH, Yu JS, Stevens G, Angelov L, Vogelbaum MA, Barnett GH, Ahluwalia MS, Neyman G, Mohammadi AM, and Chao ST
Subjects: Humans, Middle Aged, Male, Female, Aged, Adult, Maximum Tolerated Dose, Radiotherapy Dosage, Follow-Up Studies, Preoperative Care, Aged, 80 and over, Radiosurgery methods, Radiosurgery adverse effects, Brain Neoplasms secondary, Brain Neoplasms radiotherapy, Brain Neoplasms surgery
Abstract: Background: Single-session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2 cm) to determine the safety of preoperative SRS at escalating doses., Methods: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose-limiting toxicity was defined as grade III or greater acute toxicity., Results: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21 Gy. The maximum tolerated dose of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%., Conclusions: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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9. Single-Fraction Versus Fractionated Preoperative Radiosurgery for Resected Brain Metastases: A PROPS-BM International Multicenter Cohort Study.

Author: Prabhu RS, Akinyelu T, Vaslow ZK, Matsui JK, Haghighi N, Dan T, Mishra MV, Murphy ES, Boyles S, Perlow HK, Palmer JD, Udovicich C, Patel TR, Wardak Z, Woodworth GF, Ksendzovsky A, Yang K, Chao ST, Asher AL, and Burri SH
Subjects: Humans, Cohort Studies, Dose Fractionation, Radiation, Retrospective Studies, Treatment Outcome, Clinical Trials, Phase III as Topic, Randomized Controlled Trials as Topic, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Brain Neoplasms pathology, Radiation Injuries etiology, Radiosurgery adverse effects, Radiosurgery methods
Abstract: Purpose: Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS for resected brain metastases (BM). Most reported studies of preoperative SRS used single-fraction SRS (SF-SRS). The goal of this study was to compare outcomes and toxicity of preoperative SF-SRS with multifraction (3-5 fractions) SRS (MF-SRS) in a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM)., Methods and Materials: Patients with BM from solid cancers, of which at least 1 lesion was treated with preoperative SRS followed by planned resection, were included from 8 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included prior or planned whole brain radiation therapy. Intracranial outcomes were estimated using cumulative incidence with competing risk of death. Propensity score matched (PSM) analyses were performed., Results: The study cohort included 404 patients with 416 resected index lesions, of which SF-SRS and MF-SRS were used for 317 (78.5%) and 87 patients (21.5%), respectively. Median dose was 15 Gy in 1 fraction for SF-SRS and 24 Gy in 3 fractions for MF-SRS. Univariable analysis demonstrated that SF-SRS was associated with higher cavity local recurrence (LR) compared with MF-SRS (2-year: 16.3% vs 2.9%; P = .004), which was also demonstrated in multivariable analysis. PSM yielded 81 matched pairs (n = 162). PSM analysis also demonstrated significantly higher rate of cavity LR with SF-SRS (2-year: 19.8% vs 3.3%; P = .003). There was no difference in adverse radiation effect, meningeal disease, or overall survival between cohorts in either analysis., Conclusions: Preoperative MF-SRS was associated with significantly reduced risk of cavity LR in both the unmatched and PSM analyses. There was no difference in adverse radiation effect, meningeal disease, or overall survival based on fractionation. MF-SRS may be a preferred option for neoadjuvant radiation therapy of resected BMs. Additional confirmatory studies are needed. A phase 3 randomized trial of single-fraction preoperative versus postoperative SRS (NRG-BN012) is ongoing (NCT05438212)., (Copyright © 2023 Elsevier Inc. All rights reserved.)
Published: 2024
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10. Neutrophil to lymphocyte ratio (NTLR) predicts local control and overall survival after stereotactic body radiotherapy (SBRT) in metastatic sarcoma.

Author: Somasundaram E, Anderson PM, Smile TD, Halima A, Broughman JB, Reddy CA, Parsai S, Scott JG, Chan T, Campbell S, Angelov L, Zahler S, Trucco M, Thomas SM, Johnson S, Qi P, Magnelli A, and Murphy ES
Subjects: Humans, Treatment Outcome, Neutrophils, Retrospective Studies, Lymphocytes, Tumor Microenvironment, Radiosurgery, Sarcoma radiotherapy, Sarcoma surgery
Abstract: The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients with local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improve lymphocyte recovery should be investigated., (© 2023. The Author(s).)
Published: 2023
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11. Consensus recommendations in the management of Ewing sarcoma from the National Ewing Sarcoma Tumor Board.

Author: Gupta A, Riedel RF, Shah C, Borinstein SC, Isakoff MS, Chugh R, Rosenblum JM, Murphy ES, Campbell SR, Albert CM, Zahler S, Thomas SM, and Trucco M
Abstract: Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose-positron emission tomography, the role of interval compressed chemotherapy in patients aged 18 years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high-dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole-lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma. Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma., (© 2023 American Cancer Society.)
Published: 2023
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12. Salvage stereotactic body radiation therapy re-irradiation for unresectable locally recurrent nasopharyngeal rhabdomyosarcoma in a young adult: A case report.

Author: Buchberger DS, Cook SK, Anderson PM, Shepard DR, Ku JA, Fritz MA, Sindwani R, Recinos P, Murphy ES, and Koyfman SA
Subjects: Humans, Young Adult, Neoplasm Recurrence, Local radiotherapy, Salvage Therapy, Treatment Outcome, Re-Irradiation, Radiosurgery, Rhabdomyosarcoma radiotherapy, Nasopharyngeal Neoplasms radiotherapy
Published: 2023
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13. Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases.

Author: Prabhu RS, Akinyelu T, Vaslow ZK, Matsui JK, Haghighi N, Dan T, Mishra MV, Murphy ES, Boyles S, Perlow HK, Palmer JD, Udovicich C, Patel TR, Wardak Z, Woodworth GF, Ksendzovsky A, Yang K, Chao ST, Asher AL, and Burri SH
Subjects: Humans, Female, Middle Aged, Cohort Studies, Retrospective Studies, Risk Factors, Radiosurgery methods, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Brain Neoplasms secondary
Abstract: Importance: Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking., Objective: To evaluate preoperative SRS outcomes and prognostic factors from a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM)., Design, Setting, and Participants: This multicenter cohort study included patients with BMs from solid cancers, of which at least 1 lesion received preoperative SRS and a planned resection, from 8 institutions. Radiosurgery to synchronous intact BMs was allowed. Exclusion criteria included prior or planned whole-brain radiotherapy and no cranial imaging follow-up. Patients were treated between 2005 and 2021, with most treated between 2017 and 2021., Exposures: Preoperative SRS to a median dose to 15 Gy in 1 fraction or 24 Gy in 3 fractions delivered at a median (IQR) of 2 (1-4) days before resection., Main Outcomes and Measures: The primary end points were cavity local recurrence (LR), MD, ARE, overall survival (OS), and multivariable analysis of prognostic factors associated with these outcomes., Results: The study cohort included 404 patients (214 women [53%]; median [IQR] age, 60.6 [54.0-69.6] years) with 416 resected index lesions. The 2-year cavity LR rate was 13.7%. Systemic disease status, extent of resection, SRS fractionation, type of surgery (piecemeal vs en bloc), and primary tumor type were associated with cavity LR risk. The 2-year MD rate was 5.8%, with extent of resection, primary tumor type, and posterior fossa location being associated with MD risk. The 2-year any-grade ARE rate was 7.4%, with target margin expansion greater than 1 mm and melanoma primary being associated with ARE risk. Median OS was 17.2 months (95% CI, 14.1-21.3 months), with systemic disease status, extent of resection, and primary tumor type being the strongest prognostic factors associated with OS., Conclusions and Relevance: In this cohort study, the rates of cavity LR, ARE, and MD after preoperative SRS were found to be notably low. Several tumor and treatment factors were identified that are associated with risk of cavity LR, ARE, MD, and OS after treatment with preoperative SRS. A phase 3 randomized clinical trial of preoperative vs postoperative SRS (NRG BN012) has began enrolling (NCT05438212).
Published: 2023
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14. Low-Grade Glioma of the Spinal Cord: If Surgery is a No, Radiation is a Go.

Author: Mayo ZS and Murphy ES
Subjects: Humans, Spinal Cord, Glioma radiotherapy, Glioma surgery, Spinal Cord Neoplasms diagnostic imaging, Spinal Cord Neoplasms radiotherapy, Spinal Cord Neoplasms surgery
Published: 2023
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15. Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

Author: Olch AJ, Gopalakrishnan M, Murphy ES, MacDonald SM, and Hua CH
Subjects: Humans, Child, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Protons, Organs at Risk, Radiotherapy, Intensity-Modulated methods, Proton Therapy methods
Abstract: Purpose: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement., Methods and Materials: ACNS1123 stratum 1 patients (70) were evaluated. This included 50 photon and 20 proton plans. Digital Imaging and Communications in Medicine (DICOM) structure and dose data were obtained from the Children's Oncology Group. A commercially available plan quality scoring algorithm was used to create a scoring system we designed using the protocol dosimetric requirements. The whole ventricle and boost planning target volumes (PTVs) could earn a maximum of 70 points, whereas the organs at risk could earn 30 points (total maximum score of 100 points). The scoring algorithm adjusted scores based on the difficulty in achieving the structure dose requirements, which depended on the proximity of the PTVs and the dose gradients achieved relative to the organs at risk. The distribution of plan scores was used to determine the mean, median, and range of scores., Results: The median adjusted plan quality scores for the 20 proton and 50 photon plans were 83.3 and 86.9, respectively. The range of adjusted scores (maximum to minimum) was 50 points. The average score adjustment was 7.4 points. Photon and proton plans performed almost equally. Average plan quality by individual structure revealed that the brain stem, PTV boost, and cochlea lost the most points., Conclusions: This report is the first to systematically analyze overall radiation therapy plan quality scores for an entire cohort of patients treated in a cooperative group clinical trial. The methodology demonstrated a large variation in plan quality in this trial. Future clinical trials could potentially use this method to reduce plan quality variability, which may improve outcomes., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)
Published: 2023
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16. 18 F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

Author: Tom MC, DiFilippo FP, Jones SE, Suh JH, Obuchowski NA, Smile TD, Murphy ES, Yu JS, Barnett GH, Angelov L, Mohammadi AM, Huang SS, Wu G, Johnson S, Peereboom DM, Stevens GHJ, Ahluwalia MS, and Chao ST
Subjects: Adult, Humans, Positron Emission Tomography Computed Tomography methods, Pilot Projects, Prospective Studies, Necrosis diagnostic imaging, Necrosis etiology, Radiosurgery adverse effects, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Brain Neoplasms etiology
Abstract: Purpose: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18 F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions., Methods: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18 F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation., Results: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUV max statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUV mean (AUC = 0.875; p = 0.018), SUV peak (AUC = 0.813; p = 0.007), and SUV peak -to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUV max -to-normal-brain (p = 0.1) and SUV mean -to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2)., Conclusions: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18 F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2023
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17. Neutrophil to Lymphocyte Ratio (NTLR) Predicts Local Control Failure and Overall Survival after Stereotactic Body Radiotherapy (SBRT) In Metastatic Sarcoma.

Author: Somasundaram E, Smile TD, Halima A, Broughman JB, Reddy CA, Parsai S, Scott JG, Chan T, Campbell S, Angelov L, Zahler S, Trucco M, Thomas SM, Johnson S, Qi P, Magnelli A, Anderson PM, and Murphy ES
Abstract: The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improved lymphocyte recovery should be investigated., Competing Interests: CONFLICTS OF INTEREST STATEMENT The authors have no conflicts to disclose.
Published: 2023
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18. Combination of EGFR-Directed Tyrosine Kinase Inhibitors (EGFR-TKI) with Radiotherapy in Brain Metastases from Non-Small Cell Lung Cancer: A 2010-2019 Retrospective Cohort Study.

Author: Tatineni V, O'Shea PJ, Saxena S, Khosla AA, Ozair A, Kotecha RR, Jia X, Rauf Y, Murphy ES, Chao ST, Suh JH, Peereboom DM, and Ahluwalia MS
Abstract: Introduction: Traditionally, brain metastases have been treated with stereotactic radiosurgery (SRS), whole-brain radiation (WBRT), and/or surgical resection. Non-small cell lung cancers (NSCLC), over half of which carry EGFR mutations, are the leading cause of brain metastases. EGFR-directed tyrosine kinase inhibitors (TKI) have shown promise in NSCLC; but their utility in NSCLC brain metastases (NSCLCBM) remains unclear. This work sought to investigate whether combining EGFR-TKI with WBRT and/or SRS improves overall survival (OS) in NSCLCBM., Methods: A retrospective review of NSCLCBM patients diagnosed during 2010-2019 at a tertiary-care US center was performed and reported following the 'strengthening the reporting of observational studies in epidemiology' (STROBE) guidelines. Data regarding socio-demographic and histopathological characteristics, molecular attributes, treatment strategies, and clinical outcomes were collected. Concurrent therapy was defined as the combination of EGFR-TKI and radiotherapy given within 28 days of each other., Results: A total of 239 patients with EGFR mutations were included. Of these, 32 patients had been treated with WBRT only, 51 patients received SRS only, 36 patients received SRS and WBRT only, 18 were given EGFR-TKI and SRS, and 29 were given EGFR-TKI and WBRT. Median OS for the WBRT-only group was 3.23 months, for SRS + WBRT it was 3.17 months, for EGFR-TKI + WBRT 15.50 months, for SRS only 21.73 months, and for EGFR-TKI + SRS 23.63 months. Multivariable analysis demonstrated significantly higher OS in the SRS-only group (HR = 0.38, 95% CI 0.17-0.84, p = 0.017) compared to the WBRT reference group. There were no significant differences in overall survival for the SRS + WBRT combination cohort (HR = 1.30, 95% CI = 0.60, 2.82, p = 0.50), EGFR-TKIs and WBRT combination cohort (HR = 0.93, 95% CI = 0.41, 2.08, p = 0.85), or the EGFR-TKI + SRS cohort (HR = 0.46, 95% CI = 0.20, 1.09, p = 0.07)., Conclusions: NSCLCBM patients treated with SRS had a significantly higher OS compared to patients treated with WBRT-only. While sample-size limitations and investigator-associated selection bias may limit the generalizability of these results, phase II/III clinicals trials are warranted to investigate synergistic efficacy of EGFR-TKI and SRS.
Published: 2023
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19. First- versus Third-Generation EGFR Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases.

Author: Tatineni V, O'Shea PJ, Ozair A, Khosla AA, Saxena S, Rauf Y, Jia X, Murphy ES, Chao ST, Suh JH, Peereboom DM, and Ahluwalia MS
Abstract: Introduction: Up to 50% of non-small cell lung cancer (NSCLC) harbor EGFR alterations, the most common etiology behind brain metastases (BMs). First-generation EGFR-directed tyrosine kinase inhibitors (EGFR-TKI) are limited by blood-brain barrier penetration and T790M tumor mutations, wherein third-generation EGFR-TKIs, like Osimertinib, have shown greater activity. However, their efficacy has not been well-studied in later therapy lines in NSCLC patients with BMs (NSCLC-BM). We sought to compare outcomes of NSCLC-BM treated with either first- or third-generation EGFR-TKIs in first-line and 2nd-to-5th-line settings. Methods: A retrospective review of NSCLC-BM patients diagnosed during 2010-2019 at Cleveland Clinic, Ohio, US, a quaternary-care center, was performed and reported following 'strengthening the reporting of observational studies in epidemiology' (STROBE) guidelines. Data regarding socio-demographic, histopathological, molecular characteristics, and clinical outcomes were collected. Primary outcomes were median overall survival (mOS) and progression-free survival (mPFS). Multivariable Cox proportional hazards modeling and propensity score matching were utilized to adjust for confounders. Results: 239 NSCLC-BM patients with EGFR alterations were identified, of which 107 received EGFR-TKIs after diagnosis of BMs. 77.6% (83/107) received it as first-line treatment, and 30.8% (33/107) received it in later (2nd-5th) lines of therapy, with nine patients receiving it in both settings. 64 of 107 patients received first-generation (erlotinib/gefitinib) TKIs, with 53 receiving them in the first line setting and 13 receiving it in the 2nd-5th lines of therapy. 50 patients received Osimertinib as third-generation EGFR-TKI, 30 in first-line, and 20 in the 2nd-5th lines of therapy. Univariable analysis in first-line therapy demonstrated mOS of first- and third-generation EGFR-TKIs as 18.2 and 19.4 months, respectively ( p = 0.57), while unadjusted mPFS of first- and third-generation EGFR-TKIs was 9.3 and 13.8 months, respectively ( p = 0.14). In 2nd-5th line therapy, for first- and third-generation EGFR-TKIs, mOS was 17.3 and 11.9 months, ( p = 0.19), while mPFS was 10.4 and 6.08 months, respectively ( p = 0.41). After adjusting for age, performance status, presence of extracranial metastases, whole-brain radiotherapy, and presence of leptomeningeal metastases, hazard ratio (HR) for OS was 1.25 (95% CI 0.63-2.49, p = 0.52) for first-line therapy. Adjusted HR for mOS in 2nd-to-5th line therapy was 1.60 (95% CI 0.55-4.69, p = 0.39). Conclusions: No difference in survival was detected between first- and third-generation EGFR-TKIs in either first or 2nd-to-5th lines of therapy. Larger prospective studies are warranted reporting intracranial lesion size, EGFR alteration and expression levels in primary tumor and brain metastases, and response rates.
Published: 2023
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20. Area-level socioeconomic status is positively correlated with glioblastoma incidence and prognosis in the United States.

Author: Gorenflo MP, Shen A, Murphy ES, Cullen J, and Yu JS
Abstract: In the United States, an individual's access to resources, insurance status, and wealth are critical social determinants that affect both the risk and outcomes of many diseases. One disease for which the correlation with socioeconomic status (SES) is less well-characterized is glioblastoma (GBM), a devastating brain malignancy. The aim of this study was to review the current literature characterizing the relationship between area-level SES and both GBM incidence and prognosis in the United States. A query of multiple databases was performed to identify the existing data on SES and GBM incidence or prognosis. Papers were filtered by relevant terms and topics. A narrative review was then constructed to summarize the current body of knowledge on this topic. We obtained a total of three papers that analyze SES and GBM incidence, which all report a positive correlation between area-level SES and GBM incidence. In addition, we found 14 papers that focus on SES and GBM prognosis, either overall survival or GBM-specific survival. Those studies that analyze data from greater than 1,530 patients report a positive correlation between area-level SES and individual prognosis, while those with smaller study populations report no significant relationship. Our report underlines the strong association between SES and GBM incidence and highlights the need for large study populations to assess SES and GBM prognosis to ideally guide interventions that improve outcomes. Further studies are needed to determine underlying socio-economic stresses on GBM risk and outcomes to identify opportunities for intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gorenflo, Shen, Murphy, Cullen and Yu.)
Published: 2023
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21. Efficacy and Safety of Stereotactic Body Radiation Therapy for Pediatric Malignancies: The LITE-SABR Systematic Review and Meta-Analysis.

Author: Singh R, Valluri A, Didwania P, Lehrer EJ, Baliga S, Hiniker S, Braunstein SE, Murphy ES, Lazarev S, Tinkle C, Terezakis S, and Palmer JD
Abstract: Purpose: Limited data are currently available on clinical outcomes after stereotactic body radiation therapy (SBRT) for pediatric and adolescent and young adult (AYA) patients with cancer. We aimed to perform a systematic review and study-level meta-analysis to characterize associated local control (LC), progression-free survival (PFS), overall survival, and toxicity after SBRT., Methods and Materials: Relevant studies were queried using a Population, Intervention, Control, Outcomes, Study Design (PICOS)/Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)/Meta-analysis of Observational Studies in Epidemiology (MOOSE) selection criteria. Primary outcomes were 1-year and 2-year LC as well as incidence of acute and late grade 3 to 5 toxicities, with secondary outcomes of 1-year overall survival and 1-year PFS. Outcome effect sizes were estimated with weighted random effects meta-analyses. Mixed-effects weighted regression models were performed to examine potential correlations between biologically effective dose (BED 10 ), LC, and toxicity incidence., Results: Across 9 published studies, we identified 142 pediatric and AYA patients with 217 lesions that were treated with SBRT. Estimated 1-year and 2-year LC rates were 83.5% (95% confidence interval, 70.9%-96.2%) and 74.0% (95% CI, 64.6%-83.4%), respectively, with an estimated acute and late grade 3 to 5 toxicity rate of 2.9% (95% CI, 0.4%-5.4%; all grade 3). The estimated 1-year OS and PFS rates were 75.4% (95% CI, 54.5%-96.3%) and 27.1% (95% CI, 17.3%-37.0%), respectively. On meta-regression, higher BED 10 was correlated with improved 2-year LC with every 10 Gy 10 increase in BED 10 associated with a 5% improvement in 2-year LC ( P = .02) in sarcoma-predominant cohorts., Conclusions: SBRT provided durable LC for pediatric and AYA patients with cancer with minimal severe toxicities. Dose escalation may result in improved LC for sarcoma-predominant cohorts without a subsequent increase in toxicity. However, further investigations with patient-level data and prospective inquiries are indicated to better define the role of SBRT based on patient and tumor-specific characteristics., (© 2022 The Author(s).)
Published: 2023
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22. Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis.

Author: Mayo ZS, Halima A, Broughman JR, Smile TD, Tom MC, Murphy ES, Suh JH, Lo SS, Barnett GH, Wu G, Johnson S, and Chao ST
Subjects: Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, Neoplasm Recurrence, Local diagnosis, Diagnosis, Differential, Necrosis etiology, Radiosurgery methods, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Radiation Injuries diagnostic imaging
Abstract: Purpose: Cerebral radiation necrosis is a complication of radiation therapy that can be seen months to years following radiation treatment. Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis. The purpose of this article is to review the imaging modalities used in differentiating radiation necrosis from tumor progression following radiation therapy for brain metastases., Methods: We performed a review of the literature addressing the radiographic modalities used in the diagnosis of radiation necrosis., Results: Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis., Conclusion: Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2023
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23. Sex-Specific Differences in Low-Grade Glioma Presentation and Outcome.

Author: Tewari S, Tom MC, Park DYJ, Wei W, Chao ST, Yu JS, Suh JH, Kilic S, Peereboom DM, Stevens GHJ, Lathia JD, Prayson R, Barnett GH, Angelov L, Mohammadi AM, Ahluwalia MS, and Murphy ES
Subjects: Adolescent, Adult, Female, Humans, Male, Prognosis, Retrospective Studies, Sex Characteristics, Brain Neoplasms pathology, Glioma pathology
Abstract: Purpose: In addition to established prognostic factors in low-grade glioma (LGG), studies suggest a sexual dimorphism with male sex portending worse prognosis. Our objective was to identify the effect of sex on presentation and outcomes in LGG., Methods and Materials: We conducted a retrospective cohort study of adults (aged ≥18 years) diagnosed with LGG (World Health Organization 2016 grade 2 glioma). Patients with IDH wild-type tumors were excluded. Patients were matched between male and female sex by age, treatment, and surgery via propensity score matching. Patient, tumor, and treatment characteristics were analyzed by sex. Endpoints included overall survival (OS), next intervention-free survival (NIFS), progression-free survival, and malignant transformation-free survival. Kaplan-Meier analyses and Cox proportional hazards regression multivariable analysis with backward elimination were completed., Results: Of the 532 patients identified, 258 (48%) were men. Men were more likely to present with seizure (69.38% vs 56.57%, P = .002), but no other statistically significant differences between sexes at presentation were identified. Five-year OS was higher in women at 87% (95% confidence interval [CI], 83%-91%) versus 78% (95% CI, 73%-84%) in men (P = .0045). NIFS was significantly higher in female patients at 68% (95% CI, 62%-74%) versus 57% (95% CI, 51%-64%) in men (P = .009). On multivariable analysis, female sex was independently associated with improved OS (hazard ratio [HR], 1.54; 95% CI, 1.16-2.05; P = .002), NIFS (HR, 1.42; 95% CI, 1.42; P = .004), and malignant transformation-free survival (HR, 1.62; 95% CI, 1.24-2.12; P = .0004). In patients with molecularly defined LGG (IDH and 1p19q status; n = 291), female sex remained independently associated with improved OS (HR, 1.79; 95% CI, 1.16-2.77; P = .008) and NIFS (HR, 1.45; 95% CI, 1.07-1.96; P = .016)., Conclusions: In this study, female sex was independently associated with improved outcomes. These findings support intrinsic sex-specific differences in LGG behavior, justifying further studies to optimize management and therapeutics based on sex., (Copyright © 2022 Elsevier Inc. All rights reserved.)
Published: 2022
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24. Photon versus proton whole ventricular radiotherapy for non-germinomatous germ cell tumors: A report from the Children's Oncology Group.

Author: Mak DY, Siddiqui Z, Liu ZA, Dama H, MacDonald SM, Wu S, Murphy ES, Hall MD, Malkov V, Onar-Thomas A, Ahmed S, Dhall G, and Tsang DS
Subjects: Child, Humans, Male, Organs at Risk, Photons therapeutic use, Protons, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Testicular Neoplasms, Neoplasms, Germ Cell and Embryonal etiology, Neoplasms, Germ Cell and Embryonal radiotherapy, Proton Therapy methods, Radiotherapy, Intensity-Modulated adverse effects
Abstract: Purpose: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT)., Methods and Materials: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40)., Results: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs., Conclusions: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT., (© 2022 Wiley Periodicals LLC.)
Published: 2022
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25. Cognitive function after concurrent temozolomide-based chemoradiation therapy in low-grade gliomas.

Author: Park DY, Tom MC, Chen Y, Tewari S, Ahluwalia MS, Yu JS, Chao ST, Suh JH, Peereboom DM, Stevens GHJ, Barnett GH, Angelov L, Mohammadi A, Hogan T, Kissel C, Lapin B, Schuermeyer I, Parsons MW, Naugle R, and Murphy ES
Subjects: Adult, Antineoplastic Agents, Alkylating therapeutic use, Cognition, Female, Humans, Male, Temozolomide therapeutic use, Brain Neoplasms genetics, Glioma genetics
Abstract: Purpose: We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG)., Materials/methods: We included adult patients with LGG who were treated postoperatively with radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Patients were evaluated with comprehensive psychometric tests at baseline (prior to RT + TMZ) and at various time intervals following RT + TMZ. Baseline cognitive performance was analyzed by sex, age, education history, history of seizures, IDH mutation status, and 1p/19q codeletion status. Changes in neurocognitive performance were evaluated over time., Results: Thirty-seven LGG patients (mean age 43.6, 59.5% male) had baseline neurocognitive evaluation. Patients with an age > 40 years old at diagnosis and those with an education > 16 years demonstrated superior baseline verbal memory as assessed by HVLT. No other cognitive domains showed differences when stratified by the variables mentioned above. A total of 22 LGG patients had baseline and post RT + TMZ neurocognitive evaluation. Overall, patients showed no statistical difference between group mean test scores prior to and following RT + TMZ on all psychometric measures (with the exception of HVLT Discrimination)., Conclusion: Cognitive function remained stable following RT + TMZ in LGG patients evaluated prospectively up to 2 years. The anticipated analysis of RTOG 0424 will provide valuable neurocognitive outcomes specifically for high risk LGG patients treated with RT + TMZ., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2022
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26. Phase II trial of response-based radiation therapy for patients with localized germinoma: a Children's Oncology Group study.

Author: Bartels U, Onar-Thomas A, Patel SK, Shaw D, Fangusaro J, Dhall G, Souweidane M, Bhatia A, Embry L, Trask CL, Murphy ES, MacDonald S, Wu S, Boyett JM, Leary S, Fouladi M, Gajjar A, and Khatua S
Subjects: Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carboplatin therapeutic use, Child, Child, Preschool, Etoposide, Humans, Prospective Studies, Young Adult, Brain Neoplasms pathology, Germinoma drug therapy, Germinoma pathology, Germinoma radiotherapy, Pineal Gland pathology
Abstract: Background: The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate., Methods: Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim., Results: One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment., Conclusions: While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2022
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27. A Phase 2 Trial of Response-Based Radiation Therapy for Localized Central Nervous System Germ Cell Tumors: Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors.

Author: Murphy ES, Dhall G, Fangusaro J, Bartels U, Fouladi M, Shaw D, Khatua S, Hughes CW, Panigraphy A, Ioakeim-Ioannidou M, Souweidane M, Morris D, Gajjar A, Wu S, Onar-Thomas A, Haas-Kogan DA, and MacDonald SM
Subjects: Antineoplastic Combined Chemotherapy Protocols therapeutic use, Central Nervous System pathology, Child, Combined Modality Therapy, Female, Humans, Male, Neoplasm Recurrence, Local drug therapy, Prospective Studies, Radiation Dosage, Testicular Neoplasms, Central Nervous System Neoplasms pathology, Central Nervous System Neoplasms radiotherapy, Neoplasms, Germ Cell and Embryonal drug therapy, Neoplasms, Germ Cell and Embryonal radiotherapy
Abstract: Purpose: Children's Oncology Group study ACNS1123 tested the efficacy of reduced dose and field of radiation therapy (RT) for patients with localized nongerminomatous germ cell tumors (NGGCT) who achieved a complete (CR) or partial response (PR) to chemotherapy. Here, we evaluate the quality of RT and patterns of failure for patients eligible for reduced RT in this phase 2 trial., Methods and Materials: Patients with localized NGGCT with CR/PR after induction chemotherapy received reduced RT to 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed total dose. An atlas was provided to assist with complex RT volumes. Early interventional review was performed for the initial RT plan. Complete RT plans for all patients and images of relapsed patients were centrally reviewed at completion of therapy., Results: Between May 2012 and September 2016, 107 eligible patients were enrolled and 66 achieved a CR/PR after induction chemotherapy (± second-look surgery) and were eligible for reduced RT. Median follow-up was 4.4 years. Median age was 11.0 years (3.7-21.6), and 75% were male. Progression-free survival and overall survival at 4 years were 87.9% ± 4.0% and 92.4% ± 3.3% for 66 evaluable patients, respectively. Eight patients relapsed: 6 with isolated spinal relapse and 2 with disease in the brain and spine. After central review, 62 (94%) patients had RT targets contoured and dose delivered per protocol. None of the patients with deviations (n = 4) have progressed., Conclusions: Patterns of failure suggest the spine is at risk for recurrence for patients with localized NGGCT who receive reduced RT after a CR/PR to induction chemotherapy. Although survival data are encouraging, the pattern of failure has influenced the next prospective trial design. RT compliance was excellent despite complexity of radiation volumes, suggesting that providing visual guidance in the form of an online atlas contributes to higher quality RT plans., (Published by Elsevier Inc.)
Published: 2022
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28. Optimal management of brainstem metastases: a narrative review.

Author: Lee JY, Cunningham DA, Murphy ES, Chao ST, and Suh JH
Subjects: Brain Stem, Cranial Irradiation, Humans, Multicenter Studies as Topic, Prospective Studies, Quality of Life, Retrospective Studies, Brain Neoplasms secondary, Radiation Injuries etiology, Radiation Injuries surgery, Radiosurgery adverse effects
Abstract: Background and Objective: Brainstem metastases comprise fewer than 7% of all brain metastases. Nonetheless, they present clinicians with unique clinical challenges in symptom management and treatment. No comprehensive review summarizing the management of brainstem metastases exists. This review aims to summarize epidemiology, anatomy, clinical correlation, prognosis, options for management of symptoms, treatment, treatment toxicity, and dose and fractionation for brainstem stereotactic radiosurgery (SRS) as reported in the literature., Methods: In July 2021, we searched PubMed and Embase for retrospective studies of brainstem metastasis treatment, as well as case series and case reports describing diagnosis and clinical management of brainstem metastasis. Keywords and MeSH terms searched included "brainstem metastasis", "symptomatic brainstem metastasis", "brain metastasis", "stereotactic radiosurgery brainstem", "whole brain radiation brainstem", "brainstem metastasis resection", "brainstem radiation toxicity", "brainstem radiosurgery toxicity", "brainstem radiosurgery dose", and "radiosurgery dose tolerance". Titles and abstracts were screened for relevant articles and studies. References from full-text articles were screened for additional studies., Key Content and Findings: Single-institution studies and multicenter retrospective analyses from 1993 to 2021 reflect a shift from reliance on whole-brain radiation therapy (WBRT) to SRS for primary treatment of brainstem metastases. Recent multicenter retrospective analyses and single-institution case series support the safety and efficacy of SRS of brainstem metastases in symptom management and preservation of quality of life. Incidence of radiation-induced toxicity following SRS of brainstem metastases is comparable to that of SRS for other brain metastases. Complications following brainstem SRS are most strongly associated with prior WBRT., Conclusions: Radiation oncologists play a central role in the treatment of brainstem metastases due to reliance on SRS. Dose and fractionation of brainstem SRS remain largely institution-dependent. The field would benefit from inclusion of brainstem metastases in prospective trials of SRS and studies of adverse effects of salvage WBRT after prior SRS of brainstem metastases.
Published: 2022
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29. Quality of life following concurrent temozolomide-based chemoradiation therapy or observation in low-grade glioma.

Author: Park DY, Tom MC, Wei W, Tewari S, Ahluwalia MS, Yu JS, Chao ST, Suh JH, Peereboom D, Stevens GHJ, Barnett GH, Angelov L, Mohammadi AM, Hogan T, Kissel C, Lapin B, Schuermeyer I, Parsons MW, Naugle R, and Murphy ES
Subjects: Adult, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neoplasm Grading, Retrospective Studies, Treatment Outcome, Brain Neoplasms pathology, Brain Neoplasms therapy, Chemoradiotherapy, Glioma pathology, Glioma therapy, Quality of Life, Temozolomide therapeutic use, Watchful Waiting
Abstract: Purpose: Low-grade glioma (LGG) exhibits longer median survival than high-grade brain tumors, and thus impact of our therapies on patient quality of life remains a crucial consideration. This study evaluated the effects of concurrent temozolomide-based chemoradiation (RT + TMZ) or observation on quality of life (QOL) in patients with low-grade glioma., Methods: We completed a retrospective cross-sectional study of adults with LGG who underwent surgery with known molecular classification from 1980 to 2018. Postoperatively, patients were either observed or received adjuvant concurrent temozolomide-based chemoradiation. EQ-5D and PHQ-9 depression screen were completed before outpatient visits every 2-3 months. Baseline score was defined as ± 30 days within initial operation., Results: Of the 63 patients (mean age 44 ± 17 years, 51% female) with baseline EQ-5D or PHQ-9 depression screen data and at least one follow-up measure, 30 (48%) were observed and 33 (52%) received RT + TMZ. No significant decline was seen in EQ-5D or PHQ-9 scores at 3, 6, 9, 12, and 24 months compared to baseline scores for all patients. At each time point, there was no significant difference between those who were observed or received adjuvant therapy. The linear mixed model estimating PHQ-9 value or EQ-5D index demonstrated that there was no significant difference in PHQ-9 or EQ-5D index between treatment groups (p = 0.42 and p = 0.54, respectively) or time points (p = 0.24 and p = 0.99, respectively)., Conclusion: Our study found no significant decline in patient QOL or depression scores as assessed by patient- reported outcome measures for patients with low-grade glioma up to 2 years following surgery. We found no difference between RT + TMZ compared to observation during this time frame. Additional follow-up can help identify the longer-term impact of treatment strategy on patient experience., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2022
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30. Author Correction: Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases.

Author: Lauko A, Thapa B, Sharma M, Muhsen BA, Barnett A, Rauf Y, Borghei-Razavi H, Tatineni V, Patil P, Mohammadi A, Chao S, Murphy ES, Angelov L, Suh J, Barnett GH, Nowacki AS, Pennell N, and Ahluwalia MS
Published: 2022
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31. Author Correction: Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases.

Author: Lauko A, Kotecha R, Barnett A, Li H, Tatineni V, Ali A, Patil P, Mohammadi AM, Chao ST, Murphy ES, Angelov L, Suh JH, Barnett GH, Pennell NA, and Ahluwalia MS
Published: 2022
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32. Association between biologically effective dose and local control after stereotactic body radiotherapy for metastatic sarcoma.

Author: Somasundaram E, D Smile T, Halima A, Broughman JB, Reddy CA, Parsai S, Scott JG, Shah C, Chan T, Campbell S, Angelov L, Anderson PM, Zahler S, Trucco M, Thomas SM, Johnson S, Mesko N, Nystrom L, Shepard D, Budd GT, Qi P, Magnelli A, and Murphy ES
Abstract: Introduction: Stereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology., Methods: From our IRB-approved single-institution registry, all patients treated with SBRT for metastatic sarcoma between 2014 and 2020 were identified. Kaplan-Meier analysis was used to estimate local control and overall survival at 1 and 2 years. A receiver operating characteristic (ROC) curve was generated to determine optimal BED using an α/β ratio of 3. Local control was compared by SBRT dose using the BED cut point and evaluated by histology., Results: Forty-two patients with a total of 138 lesions met inclusion criteria. Median imaging follow up was 7.73 months (range 0.5-35.0). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 116.70 Gy BED (range 66.70-419.30). Desmoplastic small round cell tumor, Ewing sarcoma, rhabdomyosarcoma, and small round blue cell sarcomas were classified as radiosensitive ( n = 63), and all other histologies were classified as radioresistant ( n = 75). Local control for all lesions was 66.7% (95% CI, 56.6-78.5) at 1 year and 50.2% (95% CI, 38.2-66.1) at 2 years. Stratifying by histology, 1- and 2-year local control rates were 65.3% and 55.0%, respectively, for radiosensitive, and 68.6% and 44.5%, respectively, for radioresistant histologies ( p = 0.49). The ROC cut point for BED was 95 Gy. Local control rates at 1- and 2-years were 75% and 61.6%, respectively, for lesions receiving >95 Gy BED, and 46.2% and 0%, respectively, for lesions receiving <95 Gy BED ( p = 0.01). On subgroup analysis, local control by BED > 95 Gy was significant for radiosensitive histologies (p = 0.013), and trended toward significance for radioresistant histologies ( p = 0.25)., Conclusion: There is a significant local control benefit for sarcoma SBRT when a BED > 95 Gy is used. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index., Competing Interests: Authors’ declaration of potential conflicts of interest The authors have nothing to disclose., (© 2023 Old City Publishing, Inc.)
Published: 2022

33. A new conformity and dose gradient distance measure for stereotactic radiosurgery of brain metastasis.

Author: Cho YB, Murphy ES, Chao ST, Suh JH, Neyman G, and Xia P
Abstract: Purpose: Competing radiosurgery plans are compared based on their conformity and gradient of dose distribution to the target volume (TV). Most widely used quality metrics such as new conformity index (NCI) and gradient index (GI) are known to have strong volume dependency on the TV of interest. A simple quality measure without the volume dependency is presented for evaluating stereotactic radiosurgery plans, expressed in distance dimension compared to the unit-less volume ratio used in NCI and GI., Methods and Materials: The conformity distance measure (CDM) is defined as the effective radius of the union volume subtracted by that of the intersection volume, where volume operations are on TV and prescription isodose volume (PIV). Gradient distance measure (GDM) is defined as the effective radius of 50% PIV (low dose volume of the plan) subtracted by that of corresponding ideal low dose volume (iLDV). Volume independency and consistent sensitivity of CDM and GDM on PIV displacement and dose spillage are analyzed using a simple two-sphere model. 2429 cases of Gamma Knife and 76 cases of Linac based radiosurgery plans for brain metastasis were retrospectively studied to demonstrate volume independency of the new measures and their implication on target coverage., Results: The sensitivity of NCI on PIV displacement and dose spillage was inversely proportional to the effective radius of the target volume, while the sensitivity of CDM on target motion and dose spillage was constant regardless the target volume. The iLDV for 50% PIV was approximately 2.4 times of PIV based on previous Linac based radiosurgery/IMRT/VMAT plans and single shot analysis from Gamma Knife (GK), ICON. Although NCI ranged from 1 to 14.7 for GK plans and from 1.2 to 20.8 for VMAT plans showing strong volume dependency, CDM showed negligible volume dependency of less than 2.1 mm for more than 90% cases and peak frequency was at 0.8 mm. CDM was correlated well with target coverage as a function of PIV displacement regardless of target volume. Target coverage, V100, was larger than 95% when PIV displacement is less than CDM., Conclusions: The new conformity and gradient measure, CDM and GDM are proposed in this paper. The new measures are volume independent which is preferred for reliable evaluation of the radiosurgery plan quality over wide range of radiosurgery targets. As represented by distance dimension similar to PTV margin, the new measures may be more adequate for image guided radiosurgery applications., (© 2022 Old City Publishing, Inc.)
Published: 2022

34. Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study.

Author: Prabhu RS, Dhakal R, Vaslow ZK, Dan T, Mishra MV, Murphy ES, Patel TR, Asher AL, Yang K, Manning MA, Stern JD, Patel AR, Wardak Z, Woodworth GF, Chao ST, Mohammadi A, and Burri SH
Subjects: Cohort Studies, Humans, Neoplasm Recurrence, Local, Postoperative Complications, Retrospective Studies, Treatment Outcome, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Radiation Injuries, Radiosurgery adverse effects
Abstract: Purpose: Preoperative radiosurgery (SRS) is a feasible alternative to postoperative SRS, with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) relapse. However, previous studies are limited by small patient numbers and single-institution designs. Our aim was to evaluate preoperative SRS outcomes and prognostic factors from a large multicenter cohort (Preoperative Radiosurgery for Brain Metastases [PROPS-BM])., Methods and Materials: Patients with brain metastases (BM) from solid cancers who had at least 1 lesion treated with preoperative SRS and underwent a planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Radiographic meningeal disease (MD) was categorized as either nodular or classical "sugarcoating" (cLMD)., Results: The cohort included 242 patients with 253 index lesions. Most patients (62.4%) had a single BM, 93.7% underwent gross total resection, and 98.8% were treated with a single fraction to a median dose of 15 Gray to a median gross tumor volume of 9.9 cc. Cavity local recurrence (LR) rates at 1 and 2 years were 15% and 17.9%, respectively. Subtotal resection (STR) was a strong independent predictor of LR (hazard ratio, 9.1; P < .001). One and 2-year rates of MD were 6.1% and 7.6% and of any grade ARE were 4.7% and 6.8% , respectively. The median overall survival (OS) duration was 16.9 months and the 2-year OS rate was 38.4%. The majority of MD was cLMD (13 of 19 patients with MD; 68.4%). Of 242 patients, 10 (4.1%) experienced grade ≥3 postoperative surgical complications., Conclusions: To our knowledge, this multicenter study represents the largest cohort treated with preoperative SRS. The favorable outcomes previously demonstrated in single-institution studies, particularly the low rates of MD and ARE, are confirmed in this expanded multicenter analysis, without evidence of an excessive postoperative surgical complication risk. STR, though infrequent, is associated with significantly worse cavity LR. A randomized trial between preoperative and postoperative SRS is warranted and is currently being designed., (Copyright © 2021 Elsevier Inc. All rights reserved.)
Published: 2021
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35. Adjuvant radiation versus observation with salvage radiation after gross-total resection of WHO grade II meningiomas: a propensity score-adjusted analysis.

Author: Momin AA, Soni P, Shao J, Nowacki AS, Suh JH, Murphy ES, Chao ST, Angelov L, Mohammadi AM, Barnett GH, Recinos PF, and Kshettry VR
Abstract: Objective: After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary., Methods: The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed., Results: A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01)., Conclusions: In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.
Published: 2021
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36. Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases.

Author: Lauko A, Kotecha R, Barnett A, Li H, Tatineni V, Ali A, Patil P, Mohammadi AM, Chao ST, Murphy ES, Angelov L, Suh JH, Barnett GH, Pennell NA, and Ahluwalia MS
Subjects: Aged, Female, Humans, Immune Checkpoint Inhibitors therapeutic use, Male, Middle Aged, Multivariate Analysis, Brain Neoplasms secondary, Brain Neoplasms therapy, Immunotherapy, Lung Neoplasms pathology, Lung Neoplasms therapy, Mutation genetics, Proto-Oncogene Proteins p21(ras) genetics
Abstract: Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials., (© 2021. The Author(s).)
Published: 2021
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37. Author Correction: Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases.

Author: Lauko A, Thapa B, Sharma M, Muhsen BA, Barnett A, Rauf Y, Borghei-Razavi H, Tatineni V, Patil P, Mohammadi A, Chao S, Murphy ES, Angelov L, Suh J, Barnett GH, Nowacki AS, Pennell N, and Ahluwalia MS
Published: 2021
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38. Wilms Tumor (Nephroblastoma), Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

Author: Balis F, Green DM, Anderson C, Cook S, Dhillon J, Gow K, Hiniker S, Jasty-Rao R, Lin C, Lovvorn H, MacEwan I, Martinez-Agosto J, Mullen E, Murphy ES, Ranalli M, Rhee D, Rokitka D, Tracy EL, Vern-Gross T, Walsh MF, Walz A, Wickiser J, Zapala M, Berardi RA, and Hughes M
Subjects: Chemotherapy, Adjuvant, Child, Humans, Neoadjuvant Therapy, Neoplasm Staging, Kidney Neoplasms drug therapy, Kidney Neoplasms therapy, Wilms Tumor drug therapy, Wilms Tumor therapy
Abstract: The NCCN Guidelines for Wilms Tumor focus on the screening, diagnosis, staging, treatment, and management of Wilms tumor (WT, also known as nephroblastoma). WT is the most common primary renal tumor in children. Five-year survival is more than 90% for children with all stages of favorable histology WT who receive appropriate treatment. All patients with WT should be managed by a multidisciplinary team with experience in managing renal tumors; consulting a pediatric oncologist is strongly encouraged. Treatment of WT includes surgery, neoadjuvant or adjuvant chemotherapy, and radiation therapy (RT) if needed. Careful use of available therapies is necessary to maximize cure and minimize long-term toxicities. This article discusses the NCCN Guidelines recommendations for favorable histology WT.
Published: 2021
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39. Treatment paradigms for oligometastatic pediatric cancers: a narrative review with a focus on radiotherapy approaches.

Author: Smile TD, Parsai S, Pflederer TM, and Murphy ES
Subjects: Adult, Child, Humans, Prospective Studies, Retrospective Studies, Neoplasms radiotherapy, Radiosurgery
Abstract: There is a growing body of prospective evidence describing an oligometastatic phenotype in adults for whom local metastasis-directed therapy can improve outcomes in select patients. However, a relative paucity of data for pediatric patients with oligometastatic disease creates challenges in choosing optimal treatment. The purpose of this review is to evaluate the literature surrounding pediatric oligometastatic disease and treatment, specifically focusing on the role of radiotherapy. A review of studies ranging from 2008 to 2020 was performed. The radiotherapy techniques evaluated included conventionally fractionated radiotherapy, stereotactic body radiotherapy (SBRT), and stereotactic radiosurgery (SRS). Our search yielded 6 studies evaluating conventionally fractionated radiotherapy, 9 studies of SBRT, and 3 studies of spine SRS. Metastasis-directed therapy for treatment of pediatric oligometastasis is generally well-tolerated, is associated with favorable local control, and is shown to improve event-free survival and progression-free survival (PFS) outcomes in select pediatric patients. Pediatric patients with oligometastatic disease may benefit from aggressive local therapy to metastatic sites in conjunction with a comprehensive treatment paradigm. Retrospective data have led to promising prospective trials that will further clarify patient selection and management. Additional data are needed to elucidate long term oncologic and toxicity outcomes.
Published: 2021
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40. Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases.

Author: Lauko A, Thapa B, Sharma M, Muhsen B, Barnett A, Rauf Y, Borghei-Razavi H, Tatineni V, Patil P, Mohammadi A, Chao S, Murphy ES, Angelov L, Suh J, Barnett GH, Nowacki AS, Pennell N, and Ahluwalia MS
Subjects: Brain Neoplasms immunology, Female, Humans, Lung Neoplasms immunology, Male, Middle Aged, Multivariate Analysis, Progression-Free Survival, Survival Analysis, Treatment Outcome, Brain Neoplasms drug therapy, Brain Neoplasms secondary, Immune Checkpoint Inhibitors therapeutic use, Lung Neoplasms pathology, Lymphocytes pathology, Neutrophils pathology, Steroids therapeutic use
Abstract: Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient's NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.
Published: 2021
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41. Outcomes of salvage radiation for recurrent world health organization grade II meningiomas: a retrospective cohort study.

Author: Momin AA, Shao J, Soni P, Almeida JP, Suh JH, Murphy ES, Chao ST, Angelov L, Mohammadi AM, Barnett GH, Recinos PF, and Kshettry VR
Subjects: Adult, Aged, Cohort Studies, Female, Humans, Male, Middle Aged, Progression-Free Survival, Retrospective Studies, Treatment Outcome, Meningeal Neoplasms radiotherapy, Meningioma radiotherapy, Neoplasm Recurrence, Local radiotherapy, Salvage Therapy methods
Abstract: Purpose: The optimal modality of radiation-intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS)-in patients with recurrent WHO grade II meningiomas is not well-established. The purpose of this study was to compare progression-free survival (PFS) in patients undergoing salvage IMRT vs SRS. We compared PFS in those with and without history of prior radiation., Methods: Forty-two patients with 71 tumor recurrences treated with IMRT or SRS were retrospectively reviewed. Thirty-two salvage treatments were performed on recurrent tumors never treated with prior radiation ('radiation-naïve' cohort), whereas 39 salvage treatments were performed on recurrent tumors previously treated with radiation ('re-treatment cohort')., Results: In the 'radiation-naïve' cohort, 3-year PFS for IMRT and SRS was 68.8% and 60.7%, respectively (p = 0.61). The median tumor volume for patients treated with IMRT was significantly larger than for patients treated with SRS (5.7 vs 2.2 cm 3 ; p = 0.04). The 3-year PFS for salvage IMRT or SRS in the 're-treatment' cohort was 45.4% vs 65.8% in the 'radiation-naïve' cohort (p = 0.008). When analyzing the outcome of multiple re-treatments, median PFS was 47 months for 1 st or 2nd salvage radiation (IMRT or SRS) compared to 16 months for the 3rd or greater salvage radiation treatment (p = 0.003)., Conclusion: For salvage radiation of recurrent grade II tumors that are 'radiation-naïve', comparable 3-year PFS rates were found between IMRT and SRS, despite the IMRT group having significantly larger tumors. Salvage radiation overall was less successful in the 're-treatment' cohort compared with the 'radiation-naïve' cohort. Additionally, the effectiveness of radiation significantly declines with successive salvage radiation treatments.
Published: 2021
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42. Multiple Site SBRT in Pediatric, Adolescent, and Young Adult Patients With Recurrent and/or Metastatic Sarcoma.

Author: Parsai S, Sedor G, Smile TD, Scott J, Ochocki A, Vassil N, Zahler S, Angelov L, Chao ST, Qi P, Anderson P, and Murphy ES
Subjects: Adolescent, Adult, Child, Child, Preschool, Dose Fractionation, Radiation, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms pathology, Liver Neoplasms radiotherapy, Lung Neoplasms mortality, Lung Neoplasms pathology, Lung Neoplasms radiotherapy, Male, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local radiotherapy, Radiation Injuries etiology, Radiosurgery adverse effects, Re-Irradiation, Sarcoma mortality, Sarcoma pathology, Soft Tissue Neoplasms mortality, Soft Tissue Neoplasms pathology, Soft Tissue Neoplasms radiotherapy, Treatment Outcome, Young Adult, Radiosurgery methods, Sarcoma radiotherapy
Abstract: Background: Stereotactic body radiation therapy (SBRT) is increasingly used for patients with recurrent and or metastatic tumors. Sarcomas are generally considered not sensitive to radiotherapy and SBRT may allow for increased biological effectiveness. We report intermediate outcomes and toxicity for pediatric, adolescent, and young adult patients treated with SBRT to sites of recurrent and or metastatic sarcoma., Procedure: We queried an Institutional Review Board-approved registry of patients treated with SBRT for metastases from pediatric sarcomas. Patients age 29 and below were assessed for local control, survival, and toxicity., Results: Thirty-one patients with a total of 88 lesions met eligibility criteria. Median patient age was 17.9 years at treatment. Sixteen patients were treated with SBRT to >1 site of disease. The median dose was 30 Gy in 5 fractions. The median follow-up time was 7.4 months (range: 0.2 to 31.4 mo). Patients were heavily pretreated with systemic therapy. In 57 lesions with >3 months of radiographic follow-up, the 6-month and 12-month local control rates were 88.3%±4.5% and 83.4%±5.5%, respectively. Radiographic local failures were rare (6/57 in-field, 4/57 marginal). Only 1/88 treated lesions was associated with a radiation-related high-grade toxicity; late grade 3 intestinal obstruction in a re-irradiated field while on concurrent therapy (gemcitabine and docetaxel). No acute grade ≥3 toxicity was observed., Conclusions: SBRT was well tolerated in the majority of patients with favorable local control outcomes. Additional studies will be required to determine the optimal SBRT dose and fractionation, treatment volume, and appropriate concurrent therapies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2021
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43. Aggressive Local Control With Multisite Stereotactic Body Radiation in Metastatic Ewing Sarcoma: A Literature Review and Case Report.

Author: Karimi AM, Campbell SR, Parsai S, Angelov L, Scott J, Qi P, Anderson P, Chao ST, and Murphy ES
Subjects: Adult, Combined Modality Therapy, Humans, Magnetic Resonance Imaging, Male, Neoplasm Metastasis, Neoplasm Staging, Positron Emission Tomography Computed Tomography, Tomography, X-Ray Computed methods, Treatment Outcome, Radiosurgery adverse effects, Radiosurgery methods, Sarcoma, Ewing diagnosis, Sarcoma, Ewing radiotherapy
Abstract: Ewing sarcoma (ES) is an undifferentiated small round blue cell tumor most commonly originating in the bone of adolescents 10-20 years of age, although 30% are diagnosed in adults. The most important prognostic factor is the presence of metastatic disease. Results of the EURO-EWING 99 trial of ES patients showed that local treatment of not only the primary, but also of the sites of metastatic disease should be considered to improve event-free survival. The use of stereotactic body radiotherapy (SBRT) has been extensively reported for tumors of lung, liver, pancreas, and spine. The use of SBRT in these sites is well-accepted. Here, we report a detailed case of SBRT to multisite metastatic ES. We demonstrate the feasibility, safety, and efficacy of aggressive local control with multisite SBRT for the treatment of metastatic ES., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Published: 2020
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44. Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma.

Author: Tom MC, Park DYJ, Yang K, Leyrer CM, Wei W, Jia X, Varra V, Yu JS, Chao ST, Balagamwala EH, Suh JH, Vogelbaum MA, Barnett GH, Prayson RA, Stevens GHJ, Peereboom DM, Ahluwalia MS, and Murphy ES
Subjects: Adult, Aged, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms genetics, Brain Neoplasms mortality, Brain Neoplasms therapy, Cell Transformation, Neoplastic chemically induced, Cell Transformation, Neoplastic genetics, Chemoradiotherapy methods, Chemotherapy, Adjuvant, Female, Glioma genetics, Glioma mortality, Glioma therapy, Humans, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Mutation, Sex Factors, Temozolomide adverse effects, Temozolomide therapeutic use, Tumor Burden, Watchful Waiting, Brain Neoplasms pathology, Cell Transformation, Neoplastic pathology, Glioma pathology
Abstract: Purpose: Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG., Methods and Materials: We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus., Results: Among the included 486 adults with molecularly classified LGG, median age was 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDH mut 1p/19q codel in 169 (35%), IDH mut 1p/19q intact in 125 (26%), and IDH wt in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDH mut 1p/19q codel patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDH mut 1p/19q intact (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDH wt classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008)., Conclusions: MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG., (Copyright © 2019 Elsevier Inc. All rights reserved.)
Published: 2019
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45. Outcomes of stereotactic radiosurgery for pilocytic astrocytoma: an international multiinstitutional study.

Author: Murphy ES, Parsai S, Kano H, Sheehan JP, Martinez-Alvarez R, Martinez-Moreno N, Kondziolka D, Simonova G, Liscak R, Mathieu D, Lee CC, Yang HC, Lee JY, McShane BJ, Fang F, Trifiletti DM, Sharma M, and Barnett GH
Abstract: Objective: The current standard initial therapy for pilocytic astrocytoma is maximal safe resection. Radiation therapy is considered for residual, recurrent, or unresectable pilocytic astrocytomas. However, the optimal radiation strategy has not yet been established. Here, the authors describe the outcomes of stereotactic radiosurgery (SRS) for pilocytic astrocytoma in a large multiinstitutional cohort., Methods: An institutional review board-approved multiinstitutional database of patients treated with Gamma Knife radiosurgery (GKRS) between 1990 and 2016 was queried. Data were gathered from 9 participating International Radiosurgery Research Foundation (IRRF) centers. Patients with a histological diagnosis of pilocytic astrocytoma treated using a single session of GKRS and with at least 6 months of follow-up were included in the analysis., Results: A total of 141 patients were analyzed in the study. The median patient age was 14 years (range 2-84 years) at the time of GKRS. The median follow-up was 67.3 months. Thirty-nine percent of patients underwent SRS as the initial therapy, whereas 61% underwent SRS as salvage treatment. The median tumor volume was 3.45 cm3. The tumor location was the brainstem in 30% of cases, with a nonbrainstem location in the remainder. Five- and 10-year overall survival rates at the last follow-up were 95.7% and 92.5%, respectively. Five- and 10-year progression-free survival (PFS) rates were 74.0% and 69.7%, respectively. On univariate analysis, an age < 18 years, tumor volumes < 4.5 cm3, and no prior radiotherapy or chemotherapy were identified as positive prognostic factors for improved PFS. On multivariate analysis, only prior radiotherapy was significant for worse PFS., Conclusions: This represents the largest study of single-session GKRS for pilocytic astrocytoma to date. Favorable long-term PFS and overall survival were observed with GKRS. Further prospective studies should be performed to evaluate appropriate radiosurgery dosing, timing, and sequencing of treatment along with their impact on toxicity and the quality of life of patients with pilocytic astrocytoma.
Published: 2019
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46. Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

Author: Parsai S, Juloori A, Angelov L, Scott JG, Krishnaney AA, Udo-Inyang I, Zhuang T, Qi P, Kolar M, Anderson P, Zahler S, Chao ST, Suh JH, and Murphy ES
Abstract: Objective: There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation., Methods: An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported., Results: Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period., Conclusions: SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.
Published: 2019
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47. Mentors' perspectives on the successes and challenges of mentoring in the COG Young Investigator mentorship program: A report from the Children's Oncology Group.

Author: Esbenshade AJ, Kahalley LS, Baertschiger R, Dasgupta R, Goldsmith KC, Nathan PC, Harker-Murray P, Kitko CL, Kolb EA, Murphy ES, Muscal JA, Pierson CR, Reed D, Schore R, Unguru Y, Venkatramani R, Wistinghausen B, and Dhall G
Subjects: Female, Humans, Male, Program Evaluation, Medical Oncology, Mentoring, Mentors
Abstract: Background: Identification and development of young investigators (YI) is critical to the long-term success of research organizations. In 2004, the Children's Oncology Group (COG) created a mentorship program to foster the career development of YIs (faculty <10 years from initial appointment). This study sought to assess mentors' long-term assessment of this program., Procedure: In 2018, 101 past or current mentors in the COG YI mentorship program completed an online survey. Statistical comparisons were made with the Kruskal-Walis test., Results: The response rate was 74.2%. As some mentors had multiple mentees, we report on 138 total mentee-mentor pairs. Mentors were 57.4% male, and mentees were 39.1% male. Mentors rated being mentored as a YI as important with a median rating of 90 on a scale of 1-100, interquartile range (IQR) 80-100. Most mentors reported that being mentored themselves helped their own success within COG (78.2%) and with their overall career development (92.1%). Most mentors enjoyed serving in the program (72.3%) and the median success rating (on a scale of 1-100) across the mentor-mentee pairings was 75, IQR 39-90. Success ratings did not differ by mentor/mentee gender, but improved with increased frequency of mentor-mentee interactions (P < .001). Mentor-mentee pairs who set initial goals reported higher success ratings than those who did not (P < .001). Tangible successes included current mentee COG committee involvement (45.7%), ongoing mentor-mentee collaboration (53.6%), and co-authored manuscript publication (38.4%)., Conclusion: These data indicate that mentorship is important for successful professional development. Long-term mentoring success improves when mentors and mentees set goals upfront and meet frequently., (© 2019 Wiley Periodicals, Inc.)
Published: 2019
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48. The impact of sequencing PD-1/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis.

Author: Kotecha R, Kim JM, Miller JA, Juloori A, Chao ST, Murphy ES, Peereboom DM, Mohammadi AM, Barnett GH, Vogelbaum MA, Angelov L, Suh JH, and Ahluwalia MS
Subjects: B7-H1 Antigen antagonists & inhibitors, Humans, Immune Checkpoint Inhibitors, Programmed Cell Death 1 Receptor antagonists & inhibitors, Retrospective Studies, Brain Neoplasms therapy, Radiosurgery
Abstract: Background: The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest., Methods: Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS)., Results: One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: -100 vs -57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (-45%) compared with ICI naive lesions (-63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (-100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3-5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002)., Conclusions: Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2019
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49. Risk Factors for Progression Among Low-Grade Gliomas After Gross Total Resection and Initial Observation in the Molecular Era.

Author: Tom MC, Varra V, Leyrer CM, Park DY, Chao ST, Yu JS, Suh JH, Reddy CA, Balagamwala EH, Broughman JR, Kotagal KA, Vogelbaum MA, Barnett GH, Ahluwalia MS, Peereboom DM, Prayson RA, Stevens GHJ, and Murphy ES
Subjects: Adolescent, Adult, Age Factors, Brain Neoplasms diagnostic imaging, Brain Neoplasms genetics, Brain Neoplasms pathology, Disease Progression, Female, Glioma diagnostic imaging, Glioma genetics, Glioma pathology, Humans, Isocitrate Dehydrogenase genetics, Kaplan-Meier Estimate, Linear Models, Magnetic Resonance Imaging, Male, Progression-Free Survival, Proportional Hazards Models, Quality of Life, Risk Factors, Survival Analysis, Tumor Burden, Young Adult, Brain Neoplasms surgery, Glioma surgery
Abstract: Purpose: To identify risk factors for progression-free survival (PFS) in the molecular era among patients with low-grade glioma (LGG) who undergo gross total resection (GTR) followed by initial observation., Methods and Materials: We reviewed patients with World Health Organization grade 2 LGG treated at a single institution. We included only those who underwent magnetic resonance imaging (MRI)-confirmed GTR followed by initial observation. Molecular classification was obtained at either the time of diagnosis or pathology review. Cox proportional hazards regression, the Kaplan-Meier method, and the log-rank test were used. P values <.05 were considered statistically significant., Results: We included 144 patients who underwent MRI-confirmed GTR between 1994 and 2014 followed by initial observation. Median age was 29 years (interquartile range [IQR], 18-41), median tumor size was 2.7 cm (IQR, 1.8-4.0), and median follow-up was 81 months (IQR, 36-132). Molecular classification was 13% IDH-mutant 1p19q-codeleted; 21% IDH-mutant 1p19q-intact; 39% IDH1-R132H-wildtype; and 28% undetermined. For the entire cohort, 5- and 10-year PFS and overall survival were 71% and 53%, and 98% and 90%, respectively. On multivariate analysis, factors associated with worse PFS included increasing age at diagnosis (hazard ratio [HR], 1.05; 95% CI, 1.00-1.09; P = .03), increasing preoperative tumor size (HR, 1.07; 95% CI, 1.04-1.10; P < .0001), and IDH-mutant 1p19q-intact classification (HR, 3.18; 95% CI, 1.15-8.74, P = .025). Median PFS for patients with IDH-mutant 1p19q-codeleted, IDH-mutant 1p19q-intact, and IDH1-R132H-wildtype tumors were 113 months, 56 months, and not reached, respectively. Molecular classification was significantly associated with PFS (P < .0001) but not overall survival (P = .20)., Conclusions: Among patients with LGG who undergo MRI-confirmed GTR and initial observation in the molecular era, increasing age, increasing tumor size, and IDH-mutant 1p19q-intact classification are associated with worse PFS. Because tumor progression is associated with adverse health-related quality of life, these factors may aid clinicians and patients in the shared decision-making process regarding goals of surgery and timing of postoperative therapy. Further study is required to elucidate why IDH-mutant 1p19q-intact LGGs are at higher risk for early progression., (Copyright © 2019 Elsevier Inc. All rights reserved.)
Published: 2019
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50. Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis.

Author: Kim JM, Miller JA, Kotecha R, Chao ST, Ahluwalia MS, Peereboom DM, Mohammadi AM, Barnett GH, Murphy ES, Vogelbaum MA, Angelov L, Abraham J, Moore H, Budd GT, and Suh JH
Subjects: Adult, Aged, Aged, 80 and over, Brain Neoplasms secondary, Breast Neoplasms pathology, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Middle Aged, Prognosis, Retrospective Studies, Survival Rate, Antineoplastic Agents therapeutic use, Brain Neoplasms therapy, Breast Neoplasms therapy, Lapatinib therapeutic use, Radiosurgery mortality, Receptor, ErbB-2 antagonists & inhibitors
Abstract: Background: Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates., Methods: Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib. Outcome variables included the proportion of patients who achieved an intracranial complete response or progressive disease according to the RECIST 1.1 criteria, as well as individual lesion response rates, distant intracranial failure, and radiation necrosis., Results: Eighty-four patients with 487 brain metastases met inclusion criteria during the study period. Over 138 treatment sessions, 132 lesions (27%) were treated with SRS and concurrent lapatinib, while 355 (73%) were treated with SRS without lapatinib. Compared with patients treated with SRS alone, patients treated with concurrent lapatinib had higher rates of complete response (35% vs 11%, P = 0.008). On a per-lesion basis, best objective response was superior in the concurrent lapatinib group (median 100% vs 70% reduction, P < 0.001). Concurrent lapatinib was not associated with an increased risk of grade 2+ radiation necrosis (1.0% with concurrent lapatinib vs 3.5% without, P = 0.27). Lapatinib had no protective effect on distant intracranial failure rates (48% vs 49%, P = 0.91)., Conclusion: The addition of concurrent lapatinib to SRS was associated with improved complete response rates among patients with HER2-positive brain metastases., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2019
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