300 results on '"David A. Shultz"'
Search Results
2. Origin of Ferromagnetic Exchange Coupling in Donor–Acceptor Biradical Analogues of Charge-Separated Excited States
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Ju Chen, Jing Yang, Munendra Yadav, David A. Shultz, and Martin L. Kirk
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Inorganic Chemistry ,Physical and Theoretical Chemistry - Abstract
A new donor-acceptor biradical complex, Tp
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- 2023
3. Dinuclear ligand-to-ligand charge transfer complexes
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David A. Shultz, Riley Stephenson, and Martin L. Kirk
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Inorganic Chemistry - Abstract
The synthesis and characterization of dinuclear ligand-to-ligand charge transfer complexes are described.
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- 2023
4. Review of 20 years of adult medulloblastoma treatment: Chemotherapy prescription trends and survival
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Marissa Sherwood, Seth Climans, Ronald Ramos, Normand J Laperriere, Andrew F Gao, Barbara-Ann Millar, David B Shultz, Derek S Tsang, and Warren P Mason
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Medicine (miscellaneous) - Abstract
Background The historic standard of care for adult medulloblastoma has been considered surgery and radiation, while chemotherapy is increasingly being prescribed. This study reviewed 20-year chemotherapy trends at a high-volume center, as well as overall and progression free-survival. Methods Adults with medulloblastoma treated at an academic center from January 1, 1999 to –December 31, 2020 were reviewed. Patient baseline data were summarized and Kaplan–Meier estimators were used for survival. Results Forty-nine patients were included; median age was 30 years and male: female ratio was 2:1. Desmoplastic and classical histologies were most common. Of all patients, 23 (47%) were high risk and 7 (14%) metastatic at diagnosis. Only 10 (20%) received initial chemotherapy, of which 70% were high risk and 30% metastatic, with most treated from 2010 to 2020. Forty percent of initial chemotherapy patients received salvage chemotherapy for recurrence or metastases (of all patients, 49% required salvage). Initial chemotherapy regimens were mainly cisplatin/lomustine/vincristine, and at recurrence cisplatin/etoposide. Median overall survival was 8.6 years (95% CI 7.5–∞), with 1-, 5-, and 10-year survival at 95.8%, 72%, and 46.7%. Median overall survival for those who did not receive initial chemotherapy was 12.4 years and 7.4 years for those who did (P-value .2). Conclusions Twenty years of adult medulloblastoma treatment was reviewed. Initial chemotherapy patients, most of whom were high risk, trended towards worse survival, but this was nonsignificant. The ideal timing and choice of chemotherapy for adult medulloblastoma is unknown—challenges of administering chemotherapy following photon craniospinal irradiation may have prevented it from becoming routine.
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- 2022
5. Survival after surgery for spinal metastases: a population-based study
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Kunal, Bhanot, Jessica, Widdifield, Anjie, Huang, J Michael, Paterson, David B, Shultz, and Joel, Finkelstein
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Cohort Studies ,Ontario ,Survival Rate ,Lung Neoplasms ,Spinal Neoplasms ,Humans ,Female ,Surgery ,Middle Aged ,Combined Modality Therapy ,Retrospective Studies - Abstract
There are limited published data on population estimates of survival after spinal surgery for metastatic disease. We performed a population-based study to evaluate survival and complications among patients with cancer who underwent surgery for spinal metastases in Ontario, Canada, between 2006 and 2016.We used health administrative databases to identify all patients who underwent surgery for spinal metastases in Ontario between Jan. 1, 2006, and Dec. 31, 2016. We assessed overall survival, mortality rates according to primary cancer lesion and complications after surgery. We contrast the results to those for a comparable cohort from 1991 to 1998.A total of 2646 patients (1194 women [45.1%]; mean age 62.5 yr [standard deviation 12.2 yr]) were identified. The median survival time was 236 (interquartile range 84-740) days. Mortality was highest for patients with melanoma, upper gastrointestinal cancer and lung cancer, with 50% dying within 90 days of surgery. The longest median survival times were observed for primary cancers of the thyroid (906 d) and breast (644 d), and myeloma (830 d). Overall 90-day and 1-year mortality rates were 29% and 59%, respectively.We identified differential survivorship based on primary tumour type and a shift in the distribution of operations performed for specific primary cancers over the past 2 decades in Ontario. Overall reductions in mortality associated with this shift in treatment may reflect the use of adjuvant therapies and more personalized treatment approaches.
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- 2022
6. Excited State Magneto-Structural Correlations Related to Photoinduced Electron Spin Polarization
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Martin L. Kirk, David A. Shultz, Patrick Hewitt, Ju Chen, and Art van der Est
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Colloid and Surface Chemistry ,General Chemistry ,Biochemistry ,Catalysis - Abstract
Photoinduced electron spin polarization (ESP) is reported in the ground state of a series of complexes consisting of an organic radical (nitronylnitroxide, NN) covalently attached to a donor-acceptor chromophore either directly or via
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- 2022
7. Bevacizumab for Cerebral Radionecrosis: A Single-Center Experience
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Seth A. Climans, Ronald C. Ramos, Paola A. Jablonska, David B. Shultz, and Warren P. Mason
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Neurology ,Neurology (clinical) ,General Medicine - Abstract
Background: Cerebral radionecrosis, a subacute or late effect of radiotherapy, can be debilitating and difficult to treat. Steroids can reduce symptoms, but have significant long-term side effects. Bevacizumab has been shown to reduce edema and other radiologic features associated with radionecrosis and improve patient symptoms. We report our experience using bevacizumab for cerebral radionecrosis. Methods: We retrospectively reviewed the charts of all patients treated at our institution with bevacizumab for non-glioma-associated cerebral radionecrosis. We recorded change in symptoms, change in steroids, change in performance status, time to tumor progression, and time to death. We delineated the volume of necrosis pre- and post-bevacizumab on T1-post-gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI scans. Results: We identified 15 patients, 8 with brain metastases, 6 with meningioma, and 1 with nasopharyngeal carcinoma. Most received four doses of bevacizumab, 7.5 mg/kg q 3 weeks × 4 doses. Neuroimaging demonstrated a reduced T1 gadolinium-enhancing volume and edema in 14/15 patients (the average reduction in T1-post-gadolinium volume was 3.0 cm3, and average reduction in FLAIR volume was 27.9 cm3). There was no appreciable change in patient performance status. Steroid doses decreased in five of nine patients. There was a high rate (26%) of adverse events, including pulmonary embolism, stroke, and wound dehiscence. The median progression-free survival was 6.5 months. Conclusion: Although bevacizumab is commonly prescribed for cerebral radionecrosis, in our retrospective cohort, the clinical benefits were modest and there was significant toxicity.
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- 2022
8. Supplementary Figure 1 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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A schematic of tumor/host combinations showing Gal-1 WT and null C57Bl6/mice subcutaneous injection with Wt and shGal-1 LLC1 cells, time line of cell injection, tumor irradiation and blood collection time points. The relative plasma Gal-1 levels for each treatment group is also shown.
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- 2023
9. Supplementary materials and methods and figure legends from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Supplementary materials and methods and figure legends from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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- 2023
10. Supplementary Figure 4 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Gal-1 inhibition increases tumor radiation response in vitro and in vivo.
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- 2023
11. Supplementary Tables 1-2 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Supplementary Table 1. Patient characteristics of 20 NSCLC patient receiving SABR. Supplementary Table 2. Patient characteristics of 24 HNSCC patients receiving radiation with cetuximab or cisplatin.
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- 2023
12. Supplementary Figure 2 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Tumor irradiation effect on T lymphocytes, common lymphoid progenitor cells (CLPs) and Gal-1 expression in bone marrow cells.
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- 2023
13. Supplementary Figure 5 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Radiation-related lymphopenia is associated with worse distant, local and regional progression free survival in NSCLC, in similar between radiation and cetuximab or cisplatin treated HNSCC and its severity trends with relapse in HNSCC. A higher rise in plasma Gal-1 was also seen with relapse.
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- 2023
14. Data from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
- Abstract
Purpose: Radiotherapy can result in lymphopenia, which has been linked to poorer survival. Here, we test the hypothesis that radiotherapy-induced lymphopenia is mediated by a tumor-secreted factor, Galectin-1 (Gal-1), which possesses T-cell proapoptotic activities.Experimental Design: Matched Gal-1 wild-type (WT) or null mice were implanted with Lewis lung carcinoma (LLC-1) that either expressed Gal-1 or had Gal-1 stably downregulated. Tumors were irradiated locally and circulating Gal-1 and T cells were measured. Tumor growth, lung metastasis, intratumoral T-cell apoptosis, and microvessel density count were quantified. Thiodigalactoside (TDG), a Gal-1 inhibitor, was used to inhibit Gal-1 function in another group of mice to validate the observations noted with Gal-1 downregulation. Lymphocyte counts, survival, and plasma Gal-1 were analyzed in cohorts of radiotherapy-treated lung [non–small cell lung cancer (NSCLC)] and head and neck cancer patients.Results: LLC irradiation increased Gal-1 secretion and decreased circulating T cells in mice, regardless of host Gal-1 expression. Inhibition of tumor Gal-1 with either shRNA or thiodigalactoside ablated radiotherapy-induced lymphopenia. Irradiated shGal-1 tumors showed significantly less intratumoral CD8+ T-cell apoptosis and microvessel density, which led to marked tumor growth delay and reduced lung metastasis compared with controls. Similar observations were made after thiodigalactoside treatment. Radiotherapy-induced lymphopenia was associated with poorer overall survival in patients with NSCLC treated with hypofractionated radiotherapy. Plasma Gal-1 increased whereas T-cell decreased after radiation in another group of patients.Conclusions: Radiotherapy-related systemic lymphopenia appeared to be mediated by radiotherapy-induced tumor Gal-1 secretion that could lead to tumor progression through intratumoral immune suppression and enhanced angiogenesis. Clin Cancer Res; 20(21); 5558–69. ©2014 AACR.
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- 2023
15. Supplementary Figure 6 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Increases in gal-1 secretion after tumor cell irradiation in vitro.
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- 2023
16. Supplementary Figure 3 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response
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Quynh-Thu Le, Maximilian Diehn, Albert C. Koong, Amato J. Giaccia, Bill W. Loo, Aparna Gupta, Carmen Say, Ziwei Wang, Cato Chan, Rie von Eyben, David B. Shultz, Scott V. Bratman, and Peiwen Kuo
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Lymphocytes from Gal-1 WT and null mice exhibiting similar sensitivity to ionizing radiation and recombinant Gal-1.
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- 2023
17. Factors correlating with survival following adjuvant or definitive radiosurgery for large brain metastases
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Enrique Gutiérrez-Valencia, Aristotelis Kalyvas, Conrad J Villafuerte, Barbara-Ann Millar, Normand Laperriere, Tatiana Conrad, Alejandro Berlin, Jessica Weiss, Gelareh Zadeh, Mark Bernstein, Paul Kongkham, and David B Shultz
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Cancer Research ,Oncology ,Brain Neoplasms ,Incidence ,Multivariate Analysis ,parasitic diseases ,Clinical Investigations ,Humans ,Neurology (clinical) ,Radiosurgery ,Retrospective Studies - Abstract
Background We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4 cc) brain metastases (BrM). Methods We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. Results We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P < .001), BrM quantity [HR 1.13 (1.06–1.22) (P < .001)]; performance status (PS) [HR 2.78 (1.73–4.46) (P < .001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P < .001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46–073) (P < .001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P < .0054)], SRS target volume [HR 1.03 (1.01,1.06) (P < .0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P < .015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20–2.19) (P = 0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89–4.69) (P = .091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. Conclusion SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM.
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- 2022
18. Excited State Exchange Control of Photoinduced Electron Spin Polarization in Electronic Ground States
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Martin L. Kirk, David A. Shultz, Patrick Hewitt, and Art van der Est
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General Materials Science ,Physical and Theoretical Chemistry - Abstract
Ground-state electron spin polarization (ESP) is generated in radical elaborated (bpy)Pt(CAT-NN) and (bpy)Pt(CAT
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- 2022
19. Conformational Exchange Modulation in Trimethylenemethane-Type Biradicals
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David A. Shultz
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- 2023
20. Single-Photon-Induced Electron Spin Polarization of Two Exchange-Coupled Stable Radicals
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Martin L. Kirk, David A. Shultz, Anil Reddy Marri, Patrick Hewitt, and Art van der Est
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Colloid and Surface Chemistry ,General Chemistry ,Biochemistry ,Catalysis - Abstract
Transient electron paramagnetic resonance spectroscopy has been used to probe photoinduced electron spin polarization of a stable exchange-coupled organic biradical in a Pt(II) complex comprising 4,4'-di
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- 2022
21. Magnetic Exchange Coupling through the Nonalternant Cyclopentadienyl π-System of Ferrocene
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David A. Shultz, Martin L. Kirk, and Patrick Hewitt
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Semiquinone ,Chemistry ,Ligand ,Organic Chemistry ,Molecular electronics ,Photochemistry ,Biochemistry ,Inductive coupling ,Magnetic exchange ,chemistry.chemical_compound ,Coupling (physics) ,Ferrocene ,Cyclopentadienyl complex ,Physical and Theoretical Chemistry - Abstract
Electronic and magnetic coupling through nonalternant π-systems is an area of intense interest in photonics and molecular electronics research, yet relatively little is known regarding coupling through nonalternant π-systems. Herein we present magnetic exchange coupling in two semiquinone-based biradicals: 1,3-SQ2Fc has two semiquinone radicals attached to the one- and three-positions of the same cyclopentadienyl ligand (a nonalternant π-system) of ferrocene, whereas 1,1'-SQ2Fc has one semiquinone radical attached to each of the two cyclopentadienyl ligands of ferrocene.
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- 2021
22. Multidisciplinary Intervention in Radiation-Associated Angiosarcoma of the Breast: Patterns of Recurrence and Response to Treatment
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Elizabeth G Demicco, Rebecca A. Gladdy, Abha A. Gupta, Andrea M Covelli, Sheena Guram, David B. Shultz, and Anne C. O'Neill
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medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,medicine.disease ,Malignancy ,Breast cancer ,Oncology ,Surgical oncology ,Internal medicine ,Cohort ,medicine ,Surgery ,Angiosarcoma ,Sarcoma ,business ,Radical mastectomy - Abstract
Radiation-associated angiosarcoma (RAAS) of the breast is an aggressive malignancy affecting 1 in 1000 breast cancer patients. This study aimed to determine differences in treatments and outcomes for RAAS initially managed through a sarcoma multi-disciplinary team (SMDT) compared with an outside center (OC) and to describe outcomes after recurrence. Patients with a diagnosis of breast RAAS between 2004 and 2019 were identified from our sarcoma database. Clinicopathologic characteristics, recurrence patterns, and factors predictive of survival were assessed. Differences in local recurrence-free survival (LRFS) and disease-specific survival (DSS) were estimated using Kaplan-Meier and compared using the log-rank test. Surgery was performed for 49 women with RAAS, who had a median age of 74 years (range 41–89 years). Primary management was performed by SMDT for 26 patients and by OC for 23 patients. Radical mastectomy and reconstruction were performed for 96% of the SMDT group versus 17% of the OC group (p = 0.00001). The proportion patients who received chemotherapy, radiation, or both was 42.3% in the SMDT group and 0% in the OC group. During a median follow-up period of 26 months, recurrence was experienced by 38% (10/26) of the SMDT cohort and 83% (19/23) of the OC cohort (p = 0.002). The 3-year LRFS was better in the SMDT cohort (59.3% vs 31.8%; p = 0.019). Of the 29 recurrences 16 received chemotherapy and 6 received radiation, surgery, or both. At the last follow-up visit, 20 patients were in first remission, 1 patient was in second remission, 8 patients were alive with disease, and 20 patients had died of disease. Initial treatment by SMDT was associated with more extensive surgery, multimodal treatments, and a better 3-year LRFS. Patients with breast RAAS likely benefit from early referral and treatment by an SMDT.
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- 2021
23. Metal Ion Control of Photoinduced Electron Spin Polarization in Electronic Ground States
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Patrick Hewitt, Art van der Est, Martin L. Kirk, Sangita Paudel, David A. Shultz, David R Daley, and Ju Chen
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Semiquinone ,Chemistry ,02 engineering and technology ,General Chemistry ,Chromophore ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,3. Good health ,Photoexcitation ,Bipyridine ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Excited state ,Singlet state ,0210 nano-technology ,Ground state ,Spin (physics) - Abstract
Both the sign and intensity of photoinduced electron spin polarization (ESP) in the electronic ground state doublet (2S0/D0) of chromophore-radical complexes can be controlled by changing the nature of the metal ion. The complexes consist of an organic radical (nitronyl nitroxide, NN) covalently attached to a donor-acceptor chromophore via a m-phenylene bridge, (bpy)M(CAT-m-Ph-NN) (1) (bpy = 4,4'-di-tert-butyl-2,2'-bipyridine, M = PdII (1-Pd) or PtII (1-Pt), CAT = 3-tert-butylcatecholate, m-Ph = meta-phenylene). In both complexes, photoexcitation with visible light produces an initial exchange-coupled, three-spin (bpy•-, CAT•+ = semiquinone (SQ), and NN•), charge-separated doublet 2S1 (S = chromophore excited spin singlet configuration) excited state that rapidly decays to the ground state via a 2T1 (T = chromophore excited spin triplet configuration) state. This process is not expected to be spin selective, and only very weak emissive ESP is found for 1-Pd. In contrast, strong absorptive ESP is generated in 1-Pt. It is postulated that zero-field-splitting-induced transitions between the chromophoric 2T1 and 4T1 states (1-Pd and 1-Pt) and spin-orbit-induced transitions between 2T1 and NN-based quartet states (1-Pt) account for the differences in polarization.
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- 2021
24. Special issue: advances in the multimodality management of brain metastases and ongoing approaches to further improve their treatment
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Priscilla K. Brastianos, Gelareh Zadeh, Jeffrey Zuccato, David B. Shultz, and Carey K. Anders
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medicine.medical_specialty ,business.industry ,medicine ,AcademicSubjects/MED00300 ,Supplement Articles ,AcademicSubjects/MED00310 ,Medical physics ,business ,Multimodality - Published
- 2021
25. Pattern of Recurrence of Glioblastoma Versus Grade 4 IDH-Mutant Astrocytoma Following Chemoradiation: A Retrospective Matched-Cohort Analysis
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James Stewart, Arjun Sahgal, Aimee K M Chan, Hany Soliman, Chia-Lin Tseng, Jay Detsky, Sten Myrehaug, Eshetu G Atenafu, Ali Helmi, James Perry, Julia Keith, Mary Jane Lim-Fat, David G Munoz, Gelareh Zadeh, David B Shultz, Sunit Das, Catherine Coolens, Paula Alcaide-Leon, and Pejman Jabehdar Maralani
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Cancer Research ,Oncology ,Brain Neoplasms ,Humans ,Chemoradiotherapy ,Prospective Studies ,Neoplasm Grading ,Glioblastoma ,Isocitrate Dehydrogenase ,Retrospective Studies - Abstract
Background and Purpose: To quantitatively compare the recurrence patterns of glioblastoma (isocitrate dehydrogenase-wild type) versus grade 4 isocitrate dehydrogenase-mutant astrocytoma (wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase, respectively) following primary chemoradiation. Materials and Methods: A retrospective matched cohort of 22 wild type isocitrate dehydrogenase and 22 mutant isocitrate dehydrogenase patients were matched by sex, extent of resection, and corpus callosum involvement. The recurrent gross tumor volume was compared to the original gross tumor volume and clinical target volume contours from radiotherapy planning. Failure patterns were quantified by the incidence and volume of the recurrent gross tumor volume outside the gross tumor volume and clinical target volume, and positional differences of the recurrent gross tumor volume centroid from the gross tumor volume and clinical target volume. Results: The gross tumor volume was smaller for wild type isocitrate dehydrogenase patients compared to the mutant isocitrate dehydrogenase cohort (mean ± SD: 46.5 ± 26.0 cm3 vs 72.2 ± 45.4 cm3, P = .026). The recurrent gross tumor volume was 10.7 ± 26.9 cm3 and 46.9 ± 55.0 cm3 smaller than the gross tumor volume for the same groups ( P = .018). The recurrent gross tumor volume extended outside the gross tumor volume in 22 (100%) and 15 (68%) ( P= .009) of wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase patients, respectively; however, the volume of recurrent gross tumor volume outside the gross tumor volume was not significantly different (12.4 ± 16.1 cm3 vs 8.4 ± 14.2 cm3, P = .443). The recurrent gross tumor volume centroid was within 5.7 mm of the closest gross tumor volume edge for 21 (95%) and 22 (100%) of wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase patients, respectively. Conclusion: The recurrent gross tumor volume extended beyond the gross tumor volume less often in mutant isocitrate dehydrogenase patients possibly implying a differential response to chemoradiotherapy and suggesting isocitrate dehydrogenase status might be used to personalize radiotherapy. The results require validation in prospective randomized trials.
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- 2022
26. MMAP-09 CHARACTERISTICS CORRELATING WITH SURVIVAL IN PATIENTS TREATED FOR LARGE BRAIN METASTASES
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Enrique Gutierrez-Valencia, Aristotelis Kalyvas, Barbara-Ann Millar, Normand Laperriere, Tatiana Conrad, Alejandro Berlin, Jessica Weiss, Gelareh Zadeh, Mark Bernstein, Paul Kongkham, and David B Shultz
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General Medicine - Abstract
BACKGROUND We aimed to identify factors predicting survival following treatment to large (>4cc) BrM. METHODS From a prospective registry database, we identified 364 adult patients treated for brain metastases (BrM) or surgical cavities larger than >4 cc: 127 and 237 treated with surgery plus stereotactic radiosurgery (S+SRS) and SRS alone, respectively. We compared the 2 treatment arms using propensity score-matched (PSMA) and multivariate analyses (MVA). P values RESULTS Median target volume was 6.6cc (4-36.9cc) for intact BrM and 15cc (4-54) for cavities. Median OS was 19 and 12 months for the S+SRS and SRS groups, respectively [HR 1.73 (1.35-2.22) (P CONCLUSION Reduced SRS target volume, treatment with systemic therapy following BrM treatment, and surgical resection prior to SRS correlate with survival in patients with large BrM. PMSA supports the hypothesis that surgery prior to SRS improves survival in patients with large BrM.
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- 2022
27. Dosimetric evaluation of adult and paediatric brain tumours planned using mask-based cobalt-60 fractionated stereotactic radiotherapy compared to linear accelerator-based volumetric modulated arc therapy
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Chin Heng Fong, Robert Heaton, Zhihui Amy Liu, Kecheng Li, Monique van Prooijen, Young‐Bin Cho, David B. Shultz, and Derek S. Tsang
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Radiological and Ultrasound Technology ,Radiology, Nuclear Medicine and imaging - Abstract
We conducted a study to evaluate the dosimetric feasibility of mask-based cobalt-60 fractionated stereotactic radiotherapy (mcfSRT) with the Leksell Gamma Knife® Icon™ device.Eleven patients with intracranial tumours were selected for this dosimetry study. These patients, previously treated with volumetric arc therapy (VMAT), were re-planned using mcfSRT. Target volume coverage, conformity/gradient indices, doses to organs at risk and treatment times were compared between the mcfSRT and VMAT plans. Two-sided paired Wilcoxon signed-rank test was used to compare differences between the two plans.The V95 for PTV was similar between fractionated mcfSRT and VMAT (P = 0.47). The conformity index and gradient indices were 0.9 and 3.3, respectively, for mcfSRT compared to 0.7 and 4.2, respectively, for VMAT (P 0.001 and 0.004, respectively). The radiation exposure to normal brain was lower for mcfSRT across V10, V25 and V50 compared with VMAT (P = 0.007,0.001 and0.001, respectively). The median D0.1cc for optic nerve and chiasm as well as the median D50 to the hippocampi were lower for mcfSRT compared to VMAT. Median beam-on time for mcfSRT was 9.7 min per fraction, compared to 0.9 min for VMAT (P = 0.002).mcfSRT plans achieve equivalent target volume coverage, improved conformity and gradient indices, and reduced radiation doses to organs at risk as compared with VMAT plans. These results suggest superior dosimetric parameters for mcfSRT plans and can form the basis for future prospective studies.
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- 2022
28. Radiological progression of extremity soft tissue sarcoma following pre-operative radiotherapy predicts for poor survival
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Peter C. Ferguson, Charles Catton, Christian Isaac, Peter Chung, Colleen Dickie, David B. Shultz, John Kavanagh, Anthony M. Griffin, Jay S. Wunder, and Rakesh Mohankumar
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Male ,medicine.medical_specialty ,Databases, Factual ,Preoperative radiotherapy ,medicine.medical_treatment ,Hemangiosarcoma ,Disease-Free Survival ,Stable Disease ,Preoperative Care ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Retrospective Studies ,Solid tumour ,Full Paper ,business.industry ,Soft tissue sarcoma ,Soft tissue ,Extremities ,Sarcoma ,General Medicine ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Liposarcoma, Myxoid ,Tumor Burden ,Radiation therapy ,Radiological weapon ,Disease Progression ,Female ,Radiology ,business ,Progressive disease - Abstract
Objectives: To determine if radiological response to pre-operative radiotherapy is related to oncologic outcome in patients with extremity soft tissue sarcomas (STSs). Methods: 309 patients with extremity STS who underwent pre-operative radiation and wide resection were identified from a prospective database. Pre- and post-radiation MRI scans were retrospectively reviewed. Radiological response was defined by the modified Response Evaluation Criteria in Solid Tumours. Local recurrence-free, metastasis-free (MFS) and overall survival (OS) were compared across response groups. Results: Tumour volume decreased in 106 patients (34.3%; PR - partial responders), remained stable in 97 (31.4%; SD - stable disease), increased in 106 (34.3%; PD - progressive disease). The PD group were older (p = 0.007), had more upper extremity (p = 0.03) and high-grade tumours (p < 0.001). 81% of myxoid liposarcomas showed substantial decrease in size. There was no difference in initial tumour diameter (p = 0.5), type of surgery (p = 0.5), margin status (p = 0.4), or complications (p = 0.8) between the three groups. There were 10 (3.2%) local recurrences with no differences between the three response groups (p = 0.06). 5-year MFS was 52.1% for the PD group vs 73.8 and 78.5% for the PR and SD groups, respectively (p < 0.001). OS was similar (p < 0.001). Following multivariable analysis, worse MFS and OS were associated with higher grade, larger tumour size at diagnosis and tumour growth following pre-operative radiation. Older age was also associated with worse OS. Conclusion: STS that enlarge according to Response Evaluation Criteria in Solid Tumour criteria following pre-operative radiotherapy identify a high risk group of patients with worse systemic outcomes but equivalent local control. Advances in knowledge: Post-radiation therapy, STS enlargement may identify patients with potential for worse systemic outcomes but equivalent local control. Therefore, adjunct therapeutic approaches could be considered in these patients.
- Published
- 2022
29. In Search of Stable, High-Spin Polymers
- Author
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Patrick Hewitt and David A. Shultz
- Subjects
Superconductivity ,Materials science ,Semiquinone ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,030218 nuclear medicine & medical imaging ,0104 chemical sciences ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,Crystallography ,0302 clinical medicine ,chemistry ,law ,Thiophene ,Polythiophene ,Spin (physics) ,Electron paramagnetic resonance ,Spectroscopy ,Cobalt - Abstract
Oligomers of poly(thiophene) and poly(ortho-phenyleneethynylene) having pendant S = 1/2 semiquinone radicals (as complexes of cobalt(III)) have been prepared and characterized by electron paramagnetic resonance (EPR) spectroscopy and magnetic measurements (superconducting quantum interferences device = SQUID magnetometry). Our results show that exchange coupling of semiquinone groups along a polythiophene backbone is greater than the corresponding coupling along a poly(ortho-phenyleneethynylene) backbone.
- Published
- 2020
30. Exploiting chemistry and molecular systems for quantum information science
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Jennifer P. Ogilvie, Karol Kowalski, K. Birgitta Whaley, Danna E. Freedman, Marc A. Baldo, Theodore Goodson, James K. McCusker, Randall H. Goldsmith, Natia L. Frank, Malcolm D. E. Forbes, David A. Shultz, Gregory D. Scholes, Martin L. Kirk, Michael R. Wasielewski, Joel Yuen-Zhou, and Stefan Stoll
- Subjects
General Chemical Engineering ,Supramolecular chemistry ,Complex system ,Societal impact of nanotechnology ,Nanotechnology ,General Chemistry ,Quantum information science ,Quantum ,Information science ,Coherence (physics) ,Quantum computer - Abstract
The power of chemistry to prepare new molecules and materials has driven the quest for new approaches to solve problems having global societal impact, such as in renewable energy, healthcare and information science. In the latter case, the intrinsic quantum nature of the electronic, nuclear and spin degrees of freedom in molecules offers intriguing new possibilities to advance the emerging field of quantum information science. In this Perspective, which resulted from discussions by the co-authors at a US Department of Energy workshop held in November 2018, we discuss how chemical systems and reactions can impact quantum computing, communication and sensing. Hierarchical molecular design and synthesis, from small molecules to supramolecular assemblies, combined with new spectroscopic probes of quantum coherence and theoretical modelling of complex systems, offer a broad range of possibilities to realize practical quantum information science applications. Molecular design and synthesis, from small molecules to supramolecular assemblies, combined with new spectroscopic probes of quantum coherence and theoretical modelling, offer a broad range of possibilities to realize practical quantum information science applications in computing, communications and sensing.
- Published
- 2020
31. Focal Leptomeningeal Disease with Perivascular Invasion in EGFR-Mutant Non-Small-Cell Lung Cancer
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David B. Shultz, Archya Dasgupta, S. Rawal, Fabio Y. Moraes, and Phedias Diamandis
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Pathology ,medicine.medical_specialty ,business.industry ,Leptomeninges ,medicine.medical_treatment ,Mutant ,medicine.disease ,030218 nuclear medicine & medical imaging ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Flip ,Epidermal growth factor ,medicine ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Perivascular space ,Lung cancer ,business ,Tyrosine kinase ,030217 neurology & neurosurgery - Abstract
SUMMARY: We report a previously undescribed pattern of brain metastases in patients with epidermal growth factor receptor–mutated non-small-cell lung cancer treated with tyrosine kinase inhibitors and radiation therapy. These highly distinct lesions appear to spread focally within the leptomeninges, with invasion along the perivascular spaces (FLIP). The survival of patients with FLIP was significantly better compared with patients with classic leptomeningeal disease (median survival, 21 versus 3 months; P = .003). It is unclear whether this pattern of growth is unique to epidermal growth factor receptor–mutated non-small-cell lung cancer.
- Published
- 2020
32. Epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusion: report of two cases
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Bret Wehrli, Samir Fasih, David B. Shultz, Elizabeth G Demicco, Brendan C. Dickson, Gelareh Zadeh, John S.A. Chrisinger, Angela C. Hirbe, and Abha A. Gupta
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,business.industry ,Cell ,Soft tissue ,Cell Biology ,General Medicine ,medicine.disease ,Cell morphology ,Pathology and Forensic Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Primary bone ,Frontal bone ,030220 oncology & carcinogenesis ,medicine ,Pelvic tumor ,business ,Rhabdomyosarcoma ,Spindle cell rhabdomyosarcoma ,Molecular Biology - Abstract
The WHO Classification of Tumors of Soft Tissue and Bone divides rhabdomyosarcoma (RMS) into alveolar, embryonal, pleomorphic, and spindle cell/sclerosing types. Advances in molecular diagnostics have allowed for further refinement of RMS classification including the identification of new subtypes. Very rare RMS with epithelioid and spindle cell morphology, female predominance, marked osseous predilection, ALK expression, EWSR1/FUS-TFCP2 gene fusions, and highly aggressive clinical behavior have recently been recognized with only 23 cases reported in the English language literature. Herein, we report two additional cases with detailed clinicopathologic description and molecular confirmation. In brief, two young women presented each with a primary bone tumor-one with a frontal bone tumor and another with an osseous pelvic tumor. Both tumors showed epithelioid to spindle cell morphology, ALK expression, and EWSR1/FUS-TFCP2 gene fusions. Both patients died of disease less than 17 months from diagnosis despite administration of multiple lines of aggressive treatment. In addition, we review the literature and discuss differential diagnostic and potential treatment considerations.
- Published
- 2020
33. Designing a Rational Follow-Up Schedule for Patients with Extremity Soft Tissue Sarcoma
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Anthony M. Griffin, Aaron Gazendam, Jay S. Wunder, Julia D. Visgauss, David A. Wilson, David L. Perrin, Charles Catton, Peter C. Ferguson, David B. Shultz, and Peter Chung
- Subjects
Adult ,Diagnostic Imaging ,Male ,medicine.medical_specialty ,Time Factors ,Kaplan-Meier Estimate ,Single Center ,Disease-Free Survival ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Surgical oncology ,medicine ,Humans ,Neoplasm Metastasis ,Aged ,Retrospective Studies ,Evidence-Based Medicine ,business.industry ,Incidence ,Soft tissue sarcoma ,Incidence (epidemiology) ,Extremities ,Sarcoma ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Predictive value of tests ,Cohort ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,Surgery ,Radiology ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
The risk of tumor recurrence after resection of soft tissue sarcoma (STS) necessitates surveillance in follow-up. The objective of this study was to determine the frequency/timing of metastasis and local recurrence following treatment for soft tissue sarcoma, and to use these data to justify an evidence-based follow-up schedule. Utilizing a prospective database, a retrospective single center review was performed of all patients with minimum 2-year follow-up after resection of a localized extremity STS. Kaplan–Meier estimates were used to calculate the incidence of local recurrence and metastases on an annual basis for 10 years. We identified a total of 230 low-grade, 626 intermediate-grade and 940 high-grade extremity STS and a total of 721 events, 150 local recurrences and 571 metastases. Based on tumor size and grade, follow-up cohorts were developed that had similar metastatic risk. Using pre-determined thresholds for metastatic event, a follow-up schedule was established for each cohort. Based on our results we recommend that patients with small low-grade tumors undergo annual follow-up for 5 years following definitive local treatment. Patients with large low-grade tumors, small intermediate-grade and small high-grade tumors should have follow-up every 6 months for the first 2 years, then yearly to 10 years. Only patients with large intermediate- or high-grade tumors require follow-up every 3 months for the first 2 years, then every 6 months for years 3–5, followed by annually until 10 years.
- Published
- 2020
34. Transferrable property relationships between magnetic exchange coupling and molecular conductance
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Diana Habel-Rodriguez, Jing Yang, David A. Shultz, Ranjana Dangi, Martin L. Kirk, and Jinyuan Zhang
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Coupling ,Physics ,Chemistry ,Molecular conductance ,Conductance ,Diamagnetism ,Valence bond theory ,General Chemistry ,Ground state ,Wave function ,Molecular physics ,Quantum tunnelling - Abstract
Calculated conductance through Aun–S–Bridge–S–Aun (Bridge = organic σ/π-system) constructs are compared to experimentally-determined magnetic exchange coupling parameters in a series of TpCum,MeZnSQ–Bridge–NN complexes, where TpCum,Me = hydro-tris(3-cumenyl-1-methylpyrazolyl)borate ancillary ligand, Zn = diamagnetic zinc(ii), SQ = semiquinone (S = 1/2), and NN = nitronylnitroxide radical (S = 1/2). We find that there is a nonlinear functional relationship between the biradical magnetic exchange coupling, JD→A, and the computed conductance, gmb. Although different bridge types (monomer vs. dimer) do not lie on the same JD→Avs. gmb, curve, there is a scale invariance between the monomeric and dimeric bridges which shows that the two data sets are related by a proportionate scaling of JD→A. For exchange and conductance mediated by a given bridge fragment, we find that the ratio of distance dependent decay constants for conductance (βg) and magnetic exchange coupling (βJ) does not equal unity, indicating that inherent differences in the tunneling energy gaps, Δε, and the bridge–bridge electronic coupling, HBB, are not directly transferrable properties as they relate to exchange and conductance. The results of these observations are described in valence bond terms, with resonance structure contributions to the ground state bridge wavefunction being different for SQ–Bridge–NN and Aun–S–Bridge–S–Aun systems., Calculated conductance through Aun–S–Bridge–S–Aun constructs are compared to experimental magnetic exchange coupling parameters in TpCum,MeZn(SQ–Bridge–NN) complexes, where SQ = semiquinone radical and NN = nitronylnitroxide radical.
- Published
- 2020
35. The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma
- Author
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Marilyn Heng, Abha Gupta, Peter W. Chung, John H. Healey, Max Vaynrub, Peter S. Rose, Matthew T. Houdek, Patrick P. Lin, Andrew J. Bishop, Francis J. Hornicek, Yen-Lin Chen, Santiago Lozano-Calderon, Ginger E. Holt, Ilkyu Han, David Biau, Xiaohui Niu, Nicholas M. Bernthal, Peter C. Ferguson, Jay S. Wunder, Takafumi Ueda, Shigeki Kakunaga, Akira Kawai, Hideshi Sugiura, Teruki Kidani, Toshiyuki Kunisasa, Toshifumi Ozaki, Keisuke Ae, Akihito Nagano, Takatoshi Ohno, Koji Hiraoka, Norio Yamamoto, Hiroyuki Tsuchiya, Yoshihiro Matsumoto, Takashi Yanagawa, Robart Nakayama, Hideo Morioka, Tadahiko Kubo, Shoji Simose, Yoshiki Yamagami, Tetsuji Yamamoto, Motohiro Kawasaki, Tomoaki Torigoe, Yasuo Yazawa, Toru Akiyama, Tabu Gokita, Jun Manabe, Mitsunori Kaya, Makoto Emori, Tomoki Nakamura, Akihiko Matsumine, Shinsuke Sugihara, Masahiro Yokouchi, Setsuro Komiya, Yoshiyuki Suehara, Tatsuya Takagi, Teruya Kawamoto, Junji Wasa, Tsukasa Yonemoto, Takeshi Ishii, Ichiro Baba, Manabu Hoshi, Kenichiro Hamada, Norifumi Naka, Tsukasa Sotobori, Nobuhito Araki, Tomotake Okuma, Takahiro Goto, Hiroshi Kobayashi, Hirotaka Kawano, Masami Hosaka, Hiroyuki Futani, Hiroaski Hiraga, Yoshihiro Nishida, Anthony Griffin, Albiruni R.Abdul Razak, David Benjamin Shultz, Charles Catton, Steven Robinson, Shreyaskumar R. Patel, Valerae O. Lewis, B. Ashleigh Guadagnolo, Thomas DeLaney, Haotong Wang, Kevin Raskin, Alexandra K. Callan, Robert Henshaw, Marc Isler, Sophie Mottard, Wei-Ming Chen, Frank Traub, Tom Wei-Wu Chen, Robert E. Turcotte, Darin Davidson, Per-Ulf Tunn, Herbert Loong, Michelle Ghert, Joel Werier, Paul Clarkson, and John A. Abraham
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,Extraskeletal Osteosarcoma ,medicine.medical_specialty ,medicine.medical_treatment ,Gastroenterology ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Humans ,Medicine ,In patient ,Cumulative incidence ,Aged ,Retrospective Studies ,Aged, 80 and over ,Osteosarcoma ,Chemotherapy ,business.industry ,Significant difference ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Radiation therapy ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,Sarcoma ,business ,Adjuvant - Abstract
Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.
- Published
- 2020
36. A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: Clinical Trial Protocol
- Author
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David B. Shultz, Normand Laperriere, Fabio Y. Moraes, Mark Bernstein, Hirokazu Takami, Barbara-Ann Millar, Alejandro Berlin, Tatiana Conrad, Paul Kongkham, Farshad Nassiri, and Gelareh Zadeh
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Phases of clinical research ,Radiosurgery ,Cohort Studies ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,0302 clinical medicine ,medicine ,Humans ,Multicenter Studies as Topic ,Radiation Injuries ,Prospective cohort study ,Neoadjuvant therapy ,Aged ,Brain Neoplasms ,business.industry ,Surrogate endpoint ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Clinical trial ,030220 oncology & carcinogenesis ,Toxicity ,Disease Progression ,Female ,Surgery ,Neurology (clinical) ,Radiology ,business ,030217 neurology & neurosurgery ,Brain metastasis - Abstract
Background Brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative cavity boost stereotactic radiosurgery (POCBS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (NaSRS) followed by resection was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation toxicity compared to a comparative cohort of patients treated with postoperative SRS. Objective To determine if the rate of symptomatic radiation toxicity at 1 yr in patients who receive NaSRS differs significantly from historical rates for patients treated with POCBS. Methods This is a multi-center, non-randomized, open phase II clinical trial. A total of 30 patients with up to 10 brain metastases, at least 1 of which is appropriate for surgical resection, will be enrolled for over 4 yr. All enrolled patients will be assigned to receive NaSRS followed by surgery. Expected outcome This study will clarify whether symptomatic radiation toxicity caused by NaSRS is significantly decreased compared to historical rates associated with POCBS. Secondary endpoints will include 1-yr local control (LC) of the treated lesion, 1-yr rates of LMD, median survival and 2-yr rates of progression-free and overall survival. Tertiary analyses will include correlation between LC and radiation toxicity with pretreatment clinical factors, serum markers, radiomic features, and molecular assessments of the resected tumors. Discussion This prospective study will determine the toxicity associated with NaSRS and provide additional quantitative metrics of efficacy for future comparative trials.
- Published
- 2019
37. Recommended first-line management of brain metastases from melanoma: A multicenter survey of clinical practice
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Paola Anna Jablonska, Chin Heng Fong, Timothy Kruser, Jessica Weiss, Zhihui Amy Liu, Hirokazu Takami, Yoshitaka Narita, Fabio Ynoe de Moraes, Archya Dasgupta, Choo Khoon Ong, James C.H. Yang, Jih Hsiang Lee, Nicholas Pavlakis, Paul Kongkham, Marcus Butler, and David B. Shultz
- Subjects
Proto-Oncogene Proteins B-raf ,Oncology ,Brain Neoplasms ,Surveys and Questionnaires ,Mutation ,Humans ,Radiology, Nuclear Medicine and imaging ,Hematology ,Melanoma ,Protein Kinase Inhibitors - Abstract
Radiotherapy (RT) and surgery (Sx) are effective in treating brain metastases. However, immune checkpoint inhibitors (ICI) have shown activity against asymptomatic melanoma brain metastases (MBM). BRAF/MEK inhibitors can be used to treat BRAF V600 mutation positive (BRAF+) MBM.We conducted an international survey among experts from medical oncology (MO), clinical oncology (CO), radiation oncology (RO), and neurosurgery (NS) about treatment recommendations for patients with asymptomatic BRAF+ or BRAF mutation negative (BRAF-) MBM. Eighteen specific clinical scenarios were presented and a total of 267 responses were collected. Answers were grouped and compared using Fisher's exact test.In most MBM scenarios, survey respondents, regardless of specialty, favored RT in addition to systemic therapy. However, for patients with BRAF+ MBM, MO and CO were significantly more likely than RO and NS to recommend BRAF/MEK inhibitors alone, without the addition of RT, including the majority of MO (51%) for patients with 1-3 MBM, all2 cm. Likewise, for BRAF- MBM, MO and CO more commonly recommended single or dual agent ICI only and dual agent ICI therapy alone was the most common recommendation from MO or CO for MBM2 cm. When at least 1 of 3 MBM (BRAF+ or BRAF-) was2 cm, upfront Sx was recommended by all groups with the exception that MO and RO recommended RT for BRAF- MBM.In most clinical settings involving asymptomatic MBM, experts recommended RT in addition to systemic therapy. However, recommendations varied significantly according to specialty, with MO and CO more commonly recommending dual systemic therapy alone for up to 9 BRAF- MBM2 cm.
- Published
- 2021
38. Pattern of Recurrence of Glioblastoma Versus Grade 4 IDH-Mutant Astrocytoma Following Chemoradiation
- Author
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David B. Shultz, Chia-Lin Tseng, Mary Jane Lim-Fat, David G. Munoz, Catherine Coolens, Sunit Das, Pejman Jabehdar Maralani, Hany Soliman, Ali Helmi, James Perry, Jay Detsky, Arjun Sahgal, Aimee K.M. Chan, Gelareh Zadeh, James Stewart, Eshetu G. Atenafu, Paula Alcaide-Leon, Sten Myrehaug, and Julia Keith
- Subjects
business.industry ,Mutant ,Cancer research ,Medicine ,Astrocytoma ,business ,medicine.disease ,Glioblastoma - Abstract
Purpose To quantitatively compare the recurrence pattern of glioblastoma (IDH-wild type) versus grade 4 IDH-mutant astrocytoma (herein referred to as wtIDH and mutIDH, respectively) following primary chemoradiation. Methods Twenty-two wtIDH and 22 mutIDH patients matched by sex, extent of resection, and corpus callosum involvement were enrolled. The recurrent gross tumor volume (rGTV) was compared with both the gross tumor volume (GTV) and clinical target volume (CTV) from radiotherapy planning. Failure patterns were quantified by the incidence and volume of the rGTV outside the GTV and CTV, and positional differences of the rGTV centroid from the GTV and CTV. Results The GTV was smaller in wtIDH compared to the mutIDH group (mean±SD: 46.5±26.0 cm3 v. 72.2±45.4 cm3, p=0.026). The rGTV was 10.7±26.9 cm3 and 46.9±55.0 cm3 smaller than the GTV for the same groups (p=0.018). The rGTV extended outside the GTV in 22 (100%) and 15 (68%) (p=0.009) of wtIDH and mutIDH patients, respectively; however, the volume of rGTV outside the GTV was not significantly different (12.4±16.1 cm3 vs. 8.4±14.2 cm3, p=0.443). The rGTV metrics extending outside the CTV was not different between the groups. The rGTV centroid was within 5.7 mm of the closest GTV edge for 21 (95%) and 22 (100%) of wtIDH and mutIDH patients, respectively. Conclusion The rGTV extended beyond the GTV less often in mutIDH patients, suggesting limited margin radiotherapy could be beneficial in this group. The results support the study of small margin adaptive radiotherapy per the ongoing UNITED MR-Linac 5 mm CTV trial (NCT04726397).
- Published
- 2021
39. Rules for Magnetic Exchange in Azulene-Bridged Biradicals
- Author
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Patrick, Hewitt, David A, Shultz, and Martin L, Kirk
- Abstract
Electronic coupling through organic bridges facilitates magnetic exchange interactions and controls electron transfer and single-molecule device electron transport. Electronic coupling through alternant π-systems (
- Published
- 2021
40. Radiation-induced Lumbosacral Plexopathy after Spine Stereotactic Body Radiotherapy – Should the Lumbosacral Plexi be Contoured?
- Author
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Michael C. Tjong, Yoshiya Yamada, Adam M. Schmitt, Ellen Yorke, Fabio Y. Moraes, S. Brar, G.Y. Cederquist, and David B. Shultz
- Subjects
Spine (zoology) ,medicine.medical_specialty ,Radiation-induced lumbosacral plexopathy ,Oncology ,business.industry ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Stereotactic body radiotherapy ,Lumbosacral joint - Published
- 2020
41. SPCR-04 EFFECTS OF BRAIN METASTASES ON NEUROCOGNITIVE FUNCTION: BASELINE RESULTS OF A LONGITUDINAL TRIAL
- Author
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Randa Higazy, Matthew Ramotar, Zhihui Amy Liu, Anna T Santiago, Natalya Kosyak, Geoffrey Liu, Rebecca Simpson, David B Shultz, and Kim Edelstein
- Subjects
General Medicine - Abstract
PURPOSE Neurocognitive dysfunction is common in patients with advanced metastatic cancer. The contribution of brain metastases (BrMets) to neurocognitive outcomes is uncertain. We examined the impact of BrMets on cognitive outcomes before CNS-directed treatment and compared findings to patients with advanced metastatic cancer without BrMets. Here we present results from an ongoing prospective, longitudinal study. METHODS English-speaking adults followed at the brain metastases and lung cancer clinics underwent neurocognitive testing using a standardized battery (prior to cranial radiotherapy, if applicable), with follow-up assessments 3, 6, 9, 12, 18, and 24 months later. We calculated z-scores and impairment rates for composite neurocognitive function and memory, attention/working memory, processing speed and executive function domains. Impairment was defined according to International Cancer and Cognition Task Force criteria. RESULTS 78 patients with BrMets (50% female; mean age (SD):61(11) years) and 28 patients with metastatic non-small cell lung cancer (mNSCLC) with no known BrMets (71% female; age 67(9) years) were included. Baseline neurocognitive composite scores were impaired in both groups (BrMets: 61.5%; nonBrMets: 60.7%). Impairment rates varied between groups and across domains (BrMets vs nonBrMets: memory: 35.9%vs25.0%; attention/working memory: 35.8%vs21.4%; processing speed: 10.3%vs7.1%; executive function: 44.0%vs35.7%). Subgroup comparisons between BrMets patients with mNSCLC (N=29) and mNSCLC patients without BrMets, none of whom had targetable mutations, revealed no differences in impairment rates, but BrMets patients had slower processing speed than nonBrMets patients (mean(SD): -0.6(1.4) vs -0.1(1.9); Wilcoxon signed-rank test, p = 0.043). CONCLUSION Neurocognitive impairment in patients with advanced cancers is common. Our preliminary findings demonstrate no clear difference in cognitive outcomes between patients with BrMets and those with advanced metastatic disease not involving the brain. Our work examining how neurocognitive outcomes evolve over time in patients with and without BrMets, and demographic, disease, and treatment variables associated with those outcomes, is ongoing.
- Published
- 2022
42. Resection and radiotherapy for intracranial ependymoma: a multiinstitutional 50-year experience
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Jeffrey A. Zuccato, Ozer Algan, Vimoj J. Nair, Tyler Gunter, Chad A. Glenn, Ian F. Dunn, Kar-Ming Fung, David B. Shultz, Gelareh Zadeh, Normand Laperriere, and Derek S. Tsang
- Subjects
General Medicine - Abstract
OBJECTIVE Maximal safe resection is the standard-of-care treatment for adults with intracranial ependymoma. The value of adjuvant radiotherapy remains unclear as these tumors are rare and current data are limited to a few retrospective cohort studies. In this study, the authors assembled a cohort of patients across multiple international institutions to assess the utility of adjuvant radiotherapy in this patient population. METHODS Adults with intracranial ependymoma managed surgically at the University Health Network in Toronto, Canada, the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, and The Ottawa Hospital in Ottawa, Canada, were included in this study. The primary end points were progression-free survival (PFS) and overall survival (OS). Clinicopathological variables were assessed in univariate and multivariate Cox proportional hazard models for prognostic significance of PFS and OS. RESULTS A total of 122 patients diagnosed between 1968 and 2019 were identified for inclusion. The majority of patients had grade II ependymomas on histopathology (78%) that were infratentorially located (71%), underwent gross-total (GTR) or near-total resection (NTR; 55%), and were treated with adjuvant radiotherapy (67%). A volumetric analysis of the extent of resection in 49 patients with available tumor volume data supported the accuracy of the categorical GTR, NTR, and subtotal resection (STR) groups utilized. Independent statistically significant predictors of poorer PFS in the multivariate analysis included STR or biopsy (vs GTR/NTR; HR 5.4, 95% confidence interval [CI] 2.4–11.0, p < 0.0001) and not receiving adjuvant radiotherapy; cranial (HR 0.5, 95% CI 0.2–1.1) and craniospinal (HR 0.2, 95% CI 0.04–0.5) adjuvant radiotherapy regimens improved PFS (p = 0.0147). Predictors of poorer OS in the multivariate analysis were grade III histopathology (vs grade II: HR 5.7, 95% CI 1.6–20.2, p = 0.0064) and undergoing a biopsy/STR (vs GTR/NTR: HR 9.8, 95% CI 3.2–30.1, p = 0.0001). CONCLUSIONS The results of this 50-year experience in treating adult intracranial ependymomas confirm an important role for maximal safe resection (ideally GTR or NTR) and demonstrate that adjuvant radiotherapy improves PFS. This work will guide future studies as testing for molecular ependymoma alterations become incorporated into routine clinical practice.
- Published
- 2021
43. Adult Head and Neck Rhabdomyosarcoma: Management, Outcomes, and the Impact of IMRT on Locoregional Control
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Normand Laperriere, David B. Shultz, Shao Hui Huang, John Waldron, Patrick J. Gullane, Ralph W. Gilbert, Brian O'Sullivan, Albiruni Ryan Abdul Razak, Ezra Hahn, J. Irish, David C. Hodgson, Abha A. Gupta, Ali Hosni, J de Almeida, Dale H. Brown, and S. Barot
- Subjects
Cancer Research ,Chemotherapy ,education.field_of_study ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.medical_treatment ,Population ,Disease ,medicine.disease ,Radiation therapy ,Exact test ,Paranasal sinuses ,medicine.anatomical_structure ,Oncology ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,Young adult ,Rhabdomyosarcoma ,business ,education - Abstract
Purpose/Objective(s) Only 9% of adult Rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS), often as a paranasal mass with proptosis, orbital and skull base invasion, and a prodigious risk of regional node involvement and distant metastatic dissemination to unusual locations in the young adult with the embryonal/alveolar (E/A) subtype. E/A-RMS respond rapidly to chemotherapy and radiotherapy (RT) and management is extrapolated from the pediatric experience where prognosis is better but treatment imperatives differ. We report on adults with HNRMS treated over 3 decades. Materials/Methods We reviewed adult patients treated from 1984 – 2017 via chart review and a prospectively maintained database from 1989 onward. RMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-RMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. Chemotherapy regimens included VAC and VAC/IE, with VC given concurrently with RT. P-RMS were treated with surgery +/- RT. IMRT was adopted from 2005 onward. Results Fifty-eight patients met inclusion criteria; median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were > 5cm. Of 45 patients with M0 disease treated with curative intent, 33 (73%) had E/A-RMS and 12 (27%) had P-RMS. All E/A-RMS patients received definitive RT with either 66 Gy or 70 Gy in 2 Gy per fraction, except 2 who had surgery for diagnostic purposes. Involved nodal regions were treated with radical dose RT and elective nodal RT was routinely delivered. In the IMRT-era, patients with primary disease in the nasopharynx or paranasal sinuses were treated with bilateral neck RT, while patients with well lateralized primary disease were generally treated with ipsilateral neck RT. Pre-IMRT, out of 23 patients with initial M0 E/A-RMS, 12 (52%) had a loco-regional recurrence. Post-IMRT, out of 10 patients with initial MO disease, only 1 (10%) had a local recurrence; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy due to local toxicity, but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was statistically superior in the IMRT era as compared to pre-IMRT (Fisher's exact test, P = 0.049). Overall, distant metastasis was the predominant mode of treatment failure (n = 17/33, 52%). Conclusion In our experience, the rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT is excellent. As such CRT should be considered the treatment of choice in this population to avoid extensive surgery including craniofacial resection and orbital exenteration, which would be needed for many of these patients but has functional and cosmetic consequence; it would also interrupt ongoing maintenance chemotherapy which has proven survival benefit. In contrast P-RMS is distinct and requires surgery +/- RT.
- Published
- 2021
44. Circulating tumor DNA (ctDNA) detection of molecular residual disease (MRD) as a potential biomarker in localized soft tissue sarcoma (STS)
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Abdulazeez Salawu, Elizabeth Demicco, Peter W. M. Chung, Jordan Feeney, Jasmine Lee, Eoghan Ruadh Malone, Charles Catton, Limore Arones, Madeline J. Phillips, Philip Wong, Jay Wunder, Peter Charles Ferguson, Stephen Willingham, David Benjamin Shultz, and Albiruni Ryan Abdul Razak
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Cancer Research ,Oncology - Abstract
11547 Background: Surgery and (neo)adjuvant radiotherapy are the mainstay curative treatments for localized STS. Despite treatment, approximately 50% of STS patients (pts) experience metastatic relapse and routine use of adjuvant systemic therapy (AST) remains controversial. The presence of ctDNA following curative treatment of STS is a potential biomarker for MRD and may identify patients who benefit from AST. Given the genomic heterogeneity of STS, a histology-agnostic approach to ctDNA detection in this population is desirable. Methods: Pts with localized, high risk (size ≥ 5cm, grade ≥ 2) disease were enrolled prior to (neo) adjuvant radiotherapy and surgery. Blood for ctDNA was collected at diagnosis; post-radiotherapy, post-surgery and every 3 months for up to 2 years. Whole exome sequencing (WES) of archival tumor- and matched buffy coat-DNA were carried out to identify somatic variants. Personalized and tumor-informed, multiplex PCR next generation sequencing-based ctDNA assay (Signatera™ assay) was performed on plasma obtained at the serial timepoints. A sample level positive call required ≥ 2 variants above a confidence calling threshold. Absolute ctDNA levels were expressed as mean tumor molecules per milliliter (MTM/ml) of plasma, based on variant allele frequencies and quantity of cell free DNA. Standard radiologic surveillance (every 3 months) was performed following surgery. The primary endpoint was a ctDNA detection rate of 70% at diagnosis. Secondary endpoints included MRD detection and correlation of ctDNA levels with disease relapse. Results: Seventy-six plasma samples from 10 pts [8 males and 2 females; median age 64 years (range 46–84)] were obtained prospectively. STS subtypes were undifferentiated pleomorphic sarcoma (n = 4), myxofibrosarcoma (n = 2), dedifferentiated liposarcoma (n = 2), myxoid liposarcoma (n = 1), and pleomorphic liposarcoma (n = 1). All tumors successfully underwent WES with adequate data quality for Signatera™ assay design. The personalized ctDNA assay was performed on a median of 7 plasma samples per patient (range: 5 – 10). ctDNA was detected in 7 pts (70%) at diagnosis, with median ctDNA level of 1.6 MTM/ml (range: 0.2 – 137.8), achieving the study primary endpoint. Immediate post-surgery samples were negative in all pts. However, ctDNA was detected in 2 out of 2 pts who developed metastatic disease during follow-up. Conclusions: Personalized tumor-informed ctDNA assays in localized high-risk STS at diagnosis are feasible. In this series, all patients had undetectable levels of ctDNA post-surgery and patients who experienced disease relapse demonstrated a detectable rise in ctDNA levels. Further interrogation of this approach for detection of post-treatment MRD as a possible biomarker of benefit from AST is ongoing.
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- 2022
45. 18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy
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Zheng Miao, Sandeep Apte, Amanda Simmons, Erqi L. Pollom, Maximilian Diehn, Yushen Qian, Nicolas D. Prionas, Yufei Liu, David B. Shultz, Billy W. Loo, Jeremy P. Harris, Albert C. Koong, Madelyn Kissel, Peter G. Maxim, Justin N. Carter, J. Martin Brown, Rie von Eyben, Edward E. Graves, Frederick T. Chin, and Michael S. Binkley
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Cancer Research ,medicine.medical_specialty ,Radiation ,Lung ,medicine.diagnostic_test ,Tumor hypoxia ,business.industry ,medicine.medical_treatment ,Tumor Oxygenation ,Hypoxia (medical) ,Imaging agent ,030218 nuclear medicine & medical imaging ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Medicine ,Radiology, Nuclear Medicine and imaging ,Carbogen Breathing ,Radiology ,medicine.symptom ,business - Abstract
Purpose Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. Methods and Materials Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. Results At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P Conclusions Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.
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- 2018
46. Radiation Dose Rate, Biologically Effective Dose, and Tumor Characteristics on Local Control and Toxicity After Radiosurgery for Acoustic Neuromas
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Normand Laperriere, Mark Bernstein, Alejandro Berlin, Julian Spears, Monique van Prooijen, Suneil K. Kalia, Fred Gentili, David Payne, David B. Shultz, Robert K. Heaton, Michael D. Cusimano, Gelareh Zadeh, Derek S. Tsang, Conrad Josef Villafuerte, Mojgan Hodaie, Michael L. Schwartz, and Justin Wang
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Adult ,Male ,medicine.medical_specialty ,Radiobiology ,Adolescent ,medicine.medical_treatment ,Acoustic neuroma ,Radiation Dosage ,Radiosurgery ,Effective dose (radiation) ,Lesion ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Postoperative Complications ,Edema ,medicine ,Humans ,Cranial Nerve Neoplasms ,Cobalt Radioisotopes ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Cysts ,Hazard ratio ,Retrospective cohort study ,Dose-Response Relationship, Radiation ,Neuroma, Acoustic ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Tumor Burden ,Treatment Outcome ,030220 oncology & carcinogenesis ,Calibration ,Surgery ,Female ,Neurology (clinical) ,Radiology ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Half-Life - Abstract
To evaluate the relationships between calibration dose rate, calculated biologically effective dose (BED), and clinical factors and tumor control after stereotactic radiosurgery (SRS) for acoustic neuroma.We performed a retrospective study of all patients with acoustic neuromas treated with frame-based cobalt-60 SRS at a single institution between 2005 and 2019. The calibration dose rate and cobalt-60 half-life were used to calculate the nominal dose rate during treatment. An SRS-specific monoexponential model accounting for treatment time per lesion was used to estimate BED.The study included 607 patients with 612 acoustic neuromas. Median follow-up was 5.0 years. There was no association between dose rate or BED with local failure (LF), radiologic edema, or symptomatic edema. Cystic tumors (adjusted hazard ratio 0.26, P = 0.028) were associated with lower LF, while use of SRS as salvage treatment for growing tumors (adjusted hazard ratio 4.9, P0.0001) was associated with higher LF. LF occurred more frequently in larger-diameter tumors, while radiologic or symptomatic edema occurred more frequently in larger-volume tumors.Radiosurgery dose rate and BED were not associated with tumor control or radiologic or symptomatic edema. Salvage SRS and larger tumors were associated with a higher LF rate, while cystic tumors were associated with a lower LF rate. Patients with larger tumors should be counseled appropriately about potential side effects and when to seek follow-up care.
- Published
- 2021
47. Durability of CNS disease control in NSCLC patients with brain metastases treated with immune checkpoint inhibitors plus cranial radiotherapy
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Adrian G. Sacher, Natasha B. Leighl, S. Lau, David B. Shultz, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Aline Fusco Fares, Penelope A. Bradbury, Lisa W. Le, Christopher Poletes, and Kate M. Mackay
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Lung Neoplasms ,Immune checkpoint inhibitors ,medicine.medical_treatment ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Cumulative incidence ,Immune Checkpoint Inhibitors ,Chemotherapy ,Cranial radiotherapy ,business.industry ,Brain Neoplasms ,First line treatment ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cns disease ,medicine.symptom ,Cranial Irradiation ,business - Abstract
Background Immune checkpoint inhibitors (ICIs) have excellent systemic activity and are standard first line treatment in EGFR/ALK wild type metastatic non-small cell lung cancer (NSCLC). However, their role in patients with brain metastases, which affects over 20% of patients and cause significant morbidity, is less clear. Methods We reviewed patients with EGFR/ALK wild-type mNSCLC with CNS metastases. Serial MRIs were reviewed to determine the time to intracranial progression (iPFS). Multivariate regression was performed to adjust for the disease-specific graded prognostic score (ds-GPA). Results We identified 36 ICI- and 33 chemotherapy-treated patients with baseline CNS metastases and available serial MRIs (average frequency:3.5 months). Baseline radiation was given except for 2 chemotherapy-treated patients with asymptomatic solitary metastasis. The CNS burden of disease was higher in the ICI-treated group (ICI:22% vs. chemotherapy:0% had >10 lesions; p = 0.02), but the utilization of WBRT was not (ICI:31% vs. chemotherapy:45%; p = 0.09). At the time of progression, CNS involvement was identified in 30 % of ICI-treated patients compared to 64 % of chemotherapy controls (p = 0.02). ICI-treated patients had superior iPFS (13.5 vs 8.4 months) that remained significant in multivariate analysis (HR 1.9; 95%CI 1.1-–3.4). Superior CNS outcomes in ICI-treated patients were driven by the PD-L1 high subgroup where the 12-month cumulative incidence rate of CNS progression was 19% in ICI-treated PD-L1 ≥ 50%, 50% in ICI-treated PD-L1 Conclusions Remarkable CNS disease control is seen with baseline RT plus ICIs in patients with PD-L1 ≥ 50%. Strategies for delaying WBRT should be investigated in this subgroup of patients.
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- 2021
48. P59.17 EGFR Mutation Status, Liver Metastasis, and Overall Survival in Advanced Lung Adenocarcinoma Patients
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P. Walia, L. Zhan, David B. Shultz, A. Sabouhanian, G. Liu, S. Cheng, Adrian G. Sacher, S. Schmid, M.C. Brown, Joseph M. Herman, E. Strom, P. A. Bradbury, M. Garcia, Natasha B. Leighl, Frances A. Shepherd, K. Khan, Devalben Patel, and M. T. A. Chowdhury
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Pulmonary and Respiratory Medicine ,Lung ,medicine.anatomical_structure ,Oncology ,Egfr mutation ,business.industry ,medicine ,Cancer research ,Overall survival ,Adenocarcinoma ,medicine.disease ,business ,Metastasis - Published
- 2021
49. FP12.07 Clinico-demographic Factors, EGFR status and their association with Stage at Diagnosis in Lung Adenocarcinoma Patients
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David B. Shultz, E. Strom, K. Khan, A. Sabouhanian, S. Schmid, L. Zhan, M. Garcia, M.C. Brown, Geoffrey Liu, Penelope A. Bradbury, J. Herman, Susanna Cheng, P. Walia, Adrian G. Sacher, Devalben Patel, Frances A. Shepherd, M. T. A. Chowdhury, and Natasha B. Leighl
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung ,medicine.anatomical_structure ,business.industry ,Internal medicine ,medicine ,Adenocarcinoma ,business ,medicine.disease ,Stage at diagnosis - Published
- 2021
50. 157: Preoperative Dural Contact Correlates with the Risk of Nodular Leptomeningeal Failure Following Adjuvant Stereotactic Radiosurgery
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Aristotelis V. Kalyvas, Enrique Gutierrez, Conrad Josef Villafuerte, David B. Shultz, Paul Kongkham, Jessica Weiss, Tatiana Conrad, Gelareh Zadeh, Normand Laperriere, Mark Bernstein, and Barbara-Ann Millar
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medicine.medical_specialty ,Oncology ,business.industry ,medicine.medical_treatment ,Medicine ,Radiology, Nuclear Medicine and imaging ,Hematology ,Radiology ,business ,Adjuvant ,Radiosurgery - Published
- 2021
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