137 results on '"Alektiar KM"'
Search Results
2. Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity.
- Author
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Alektiar KM, Brennan MF, Healey JH, and Singer S
- Published
- 2008
3. Hypofractionated Preoperative Radiation Should Not Yet Be Used as Standard of Care for Extremity and Truncal Soft Tissue Sarcoma.
- Author
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Baldini EH, Guadagnolo BA, Salerno KE, Chung P, Bishop AJ, Kalbasi A, Miah A, Bedi M, Harris JP, Petersen I, Gillham C, Wiltink LM, Alektiar KM, Haas RL, and Kirsch DG
- Abstract
Hypofractionated radiation therapy regimens should not be used as standard of care for localized soft tissue sarcoma.
- Published
- 2024
- Full Text
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4. Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer.
- Author
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Rios-Doria E, Abu-Rustum NR, Alektiar KM, Makker V, Liu YL, Zamarin D, Friedman CF, Aghajanian C, Ellenson LH, Chiang S, Weigelt B, Mueller JJ, and Leitao MM
- Subjects
- Humans, Female, Middle Aged, Aged, Prognosis, Sentinel Lymph Node pathology, Retrospective Studies, Adult, Aged, 80 and over, Endometrial Neoplasms pathology, Endometrial Neoplasms therapy, Endometrial Neoplasms classification, Carcinoma, Endometrioid pathology, Carcinoma, Endometrioid therapy, Neoplasm Staging
- Abstract
Objective: We assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease., Methods: Patients diagnosed with stage IA, IB, or II endometrioid endometrial cancer and primary surgical management were identified from January 1, 2007 to December 31, 2019. All SLNs underwent ultrastaging according to the institutional protocol. Patients with cytokeratin positive cells, micrometastases, and macrometastases were excluded. Clinical, pathology, and molecular subtype data were reviewed., Results: Overall, 1214 patients with early stage endometrioid endometrial cancer met the inclusion criteria, of whom 1089 (90%) had node negative disease and 125 (10%) had isolated tumor cells. Compared with node negative disease, the presence of isolated tumor cells had a greater association with deep myometrial invasion, lymphovascular space invasion, receipt of adjuvant therapy, and adjuvant chemotherapy with or without radiation (p<0.01). There was no significant difference in survival rates between patients with isolated tumor cells and node negative disease (3 year progression free survival rate 94% vs 91%, respectively, p=0.21; 3 year overall survival rate 98% vs 96%, respectively, p=0.45). Progression free survival did not significantly differ among patients with isolated tumor cells who received no adjuvant therapy or chemotherapy with or without radiation (p=0.31). There was no difference in the distribution of molecular subtypes between patients with isolated tumor cells (n=28) and node negative disease (n=194; p=0.26). Three year overall survival rates differed significantly when stratifying the entire cohort by molecular subtype (p=0.04)., Conclusions: Patients with isolated tumor cells demonstrated less favorable uterine pathologic features and received more adjuvant treatment with similar survival compared with patients with nodenegative disease. Among the available data, molecular classification did not have a significant association with the presence of isolated tumor cells, although copy number-high status was a poor prognostic indicator in early stage endometrioid endometrial cancer., Competing Interests: Competing interests: BW reports research support by Repare Therapeutics, outside of the current work. CAA reports clinical trial funding paid to the institution from AstraZeneca; funding paid to the institution from BMS and SELLAS Life Sciences Group; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). DZ reports institutional grants from Genentech, AstraZeneca, BMS, SELLAS Life Sciences Group, and Plexxikon; personal fees from Genentech, AstraZeneca, Xencor, Memgen, Synthekine, Celldex, and Hookipa; and stock options from Immunos, Accurius, Mana Therapeutics, and Calidi Biotherapeutics, outside of the submitted work. DZ is also an inventor on a patent related to the use of oncolytic Newcastle disease virus for cancer therapy. YLL reports research funding from AstraZeneca, GSK, and Repare Therapeutics. NRA-R reports research funding paid to the institution from GRAIL. ML reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, and advisory board participation for JnJ/Ethicon and Takeda. VM reports advisory board participation (unpaid) for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. CFF reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. SC serves as a consultant for AstraZeneca., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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5. Isolated vaginal recurrence in women with stage I endometrial cancer.
- Author
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Rios-Doria E, Cun HT, Filippova OT, Mueller JJ, Alektiar KM, Ellenson LH, Makker V, Lakhman Y, Leitao MM Jr, Jhingran A, Soliman PT, and Abu-Rustum NR
- Subjects
- Humans, Female, Neoplasm Recurrence, Local pathology, Vagina surgery, Vagina pathology, Neoplasm Staging, Retrospective Studies, Endometrial Neoplasms surgery, Endometrial Neoplasms pathology, Brachytherapy
- Abstract
Objective: To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence., Methods: Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests., Results: Of 2815 women identified, 278 (10%) experienced a recurrence. Sixty-one patients (2%) had an isolated vaginal recurrence, including 42 (69%) at the vaginal apex; 217 (8%) had an extravaginal recurrence, including 18 with a vaginal component. Median time to recurrence was 11 months (range, 1-68) for isolated vaginal recurrence and 20 months (range, 1-98) for extravaginal recurrence (P < .004). Of 960 patients (34%) treated with adjuvant vaginal brachytherapy (VBT), 156 (16%) recurred; 19 (2%) had an isolated vaginal recurrence, including 16 (84%) at the vaginal apex. Three-year PFS rates for isolated vaginal recurrence were 97.6% (SE ± 0.4%) with minimally invasive surgery (MIS) versus 96.9% (SE ± 1.1%) with open (P = .8), and for extravaginal recurrence were 91.8% (SE ± 0.7%) with MIS versus 90.8% (SE ± 1.8%) with open (P = .8)., Conclusions: Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences. Surgical approach does not appear to impact recurrence. Adjuvant VBT after primary surgery carries a 1%-2% risk of isolated vaginal apex recurrence., Competing Interests: Declaration of Competing Interest Outside the submitted work, N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution. V. Makker reports meeting/travel support by Eisai and Merck; participation on a Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AstraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer, and Takeda. M.M. Leitao Jr. reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, Inc., and advisory board participation for JnJ/Ethicon and Takeda. Y. Lakhman serves as a consultant for Calyx Clinical Trial Solutions. A. Jhingran reports a consulting agreement and advisory board participation with Genentech, and a patent (adaptive intracavitary brachytherapy applicator for cervical cancer). The other authors do not have potential conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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6. Distinct genomic landscapes in radiation-associated angiosarcoma compared with other radiation-associated sarcoma histologies.
- Author
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Dermawan JK, Chi P, Tap WD, Rosenbaum E, D'Angelo S, Alektiar KM, and Antonescu CR
- Subjects
- Female, Humans, Male, Genomics, Bone Neoplasms, Hemangiosarcoma genetics, Neurofibrosarcoma, Sarcoma genetics, Sarcoma pathology
- Abstract
MYC amplifications have been frequently detected in radiation (RT)-associated angiosarcomas (ASs) by low-resolution molecular methods. However, large-scale next-generation sequencing (NGS) studies to investigate the genomic landscape of RT-AS are scarce, particularly compared with other RT-associated sarcomas. We performed a detailed comparative genomic investigation of RT-AS versus other RT-associated histotypes, as well as sporadic sarcomas with similar histologies. Our institutional targeted DNA-NGS assay database was searched for RT-associated sarcomas. Clinical outcome data, pathologic diagnosis, and the types and frequencies of genomic alterations, including single nucleotide variants (SNVs) and copy number alterations (CNAs), were analyzed. The cohort consisted of 82 patients, 68 (83%) females and 14 (17%) males, aged 37-88 (mean 64) years. Forty-four RT-ASs (38 from breast) and 38 RT sarcomas of other histologies, including 12 malignant peripheral nerve sheath tumors (RT-MPNSTs), 14 undifferentiated pleomorphic sarcomas (RT-UPSs), and 12 osteosarcomas (RT-OSs), were included. Median time intervals from radiation to initial diagnosis in RT-AS (8.0 years) were significantly lower than those in RT-MPNST and RT-UPS (12.5 and 18.5 years), respectively. Each RT-sarcoma histotype harbored distinct mutations and CNAs. RT-associated AS had more frequent MYC, FLT4, CRKL, HRAS, and KMT2D alterations than sporadic AS (enriched in TP53, KDR, ATM, ATRX), whereas the mutational landscapes of MPNST, UPS, and OS were similar in both RT and non-RT settings. CDKN2A/B deletions and TP53 alterations were infrequent in RT-AS compared with other RT sarcomas. Among RT sarcomas, RT-AS harbored the lowest fraction of genome altered (FGA), while RT-MPNST showed the highest FGA. RT-AS had the lowest insertion:SNV and deletion:SNV ratios, while RT-UPS had the highest. The predominant mutational signatures were associated with errors in DNA repair and replication. In conclusion, RT-AS has a distinct genomic landscape compared with other RT sarcomas and sporadic AS. Potential molecular targets for precision medicine may be histotype-dependent. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)
- Published
- 2023
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7. Integration of clinical sequencing and immunohistochemistry for the molecular classification of endometrial carcinoma.
- Author
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Rios-Doria E, Momeni-Boroujeni A, Friedman CF, Selenica P, Zhou Q, Wu M, Marra A, Leitao MM Jr, Iasonos A, Alektiar KM, Sonoda Y, Makker V, Jewell E, Liu Y, Chi D, Zamarin D, Abu-Rustum NR, Aghajanian C, Mueller JJ, Ellenson LH, and Weigelt B
- Subjects
- Female, Humans, Immunohistochemistry, Retrospective Studies, Prognosis, Mutation, Tumor Suppressor Protein p53 genetics, Endometrial Neoplasms genetics, Endometrial Neoplasms pathology
- Abstract
Purpose: Using next generation sequencing (NGS), The Cancer Genome Atlas (TCGA) found that endometrial carcinomas (ECs) fall under one of four molecular subtypes, and a POLE mutation status, mismatch repair (MMR) and p53 immunohistochemistry (IHC)-based surrogate has been developed. We sought to retrospectively classify and characterize a large series of unselected ECs that were prospectively subjected to clinical sequencing by utilizing clinical molecular and IHC data., Experimental Design: All patients with EC with clinical tumor-normal MSK-IMPACT NGS from 2014 to 2020 (n = 2115) were classified by integrating molecular data (i.e., POLE mutation, TP53 mutation, MSIsensor score) and MMR and p53 IHC results. Survival analysis was performed for primary EC patients with upfront surgery at our institution., Results: Utilizing our integrated approach, significantly more ECs were molecularly classified (1834/2115, 87%) as compared to the surrogate (1387/2115, 66%, p < 0.001), with an almost perfect agreement for classifiable cases (Kappa 0.962, 95% CI 0.949-0.975). Discrepancies were primarily due to TP53 mutations in p53-IHC-normal ECs. Of the 1834 ECs, most were of copy number (CN)-high molecular subtype (40%), followed by CN-low (32%), MSI-high (23%) and POLE (5%). Histologic and genomic variability was present amongst all molecular subtypes. Molecular classification was prognostic in early- and advanced-stage disease, including early-stage endometrioid EC., Conclusions: The integration of clinical NGS and IHC data allows for an algorithmic approach to molecularly classifying newly diagnosed EC, while overcoming issues of IHC-based genetic alteration detection. Such integrated approach will be important moving forward given the prognostic and potentially predictive information afforded by this classification., Competing Interests: Conflicts of interest N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution, outside the current study. C.F. Friedman reports institutional research support from Seagen, Merck, BMS, AstraZeneca, Mersana and Hotspot Therapeutics; consulting fees from BMS, Seagen and Aadi Biosciences; honoraria for lectures from Onclive; meeting/ travel support by Puma; participation on Data Safety Monitoring or Advisory Board of Merck, Genentech and Marengo (all uncompensated). D. Zamarin reports institutional research support from AstraZeneca, Merck, Plexxikon Synthekine and Genentech; consulting fees from AstraZeneca, Synthekine, Astellas, Tessa Therapeutics, Memgen, Celldex, Crown Biosciences, Hookipa Biotech, Kalivir, Xencor and GSK; royalties from Merck; and stock options from Accurius Therapeutics, ImmunOS Therapeutics and Calidi Biotherapeutics, all outside the submitted work. V. Makker reports meeting/travel support by Eisai and Merck; participation on Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AztraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer and Takeda. Y. Liu reports institutional research funding from Repare Therapeutics, AstraZeneca and GSK; honoraria from Total Health and Sarah Lawrence College; and travel/meeting support by AstraZeneca, outside the submitted work. B. Weigelt reports a research grant from REPARE Therapeutics paid to the institution, outside the submitted work. D.S. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. E.L. Jewell reports personal fees from Covidien/Medtronic. M. M. Leitao is an ad hoc speaker for Intuitive Surgical, Inc.; outside the submitted work, he is on the Advisory Board of Ethicon/Johnson & Johnson and Takeda; and reports grants paid to the institution by KCI/Acelity. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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8. High-Sensitivity Mutation Analysis of Cell-Free DNA for Disease Monitoring in Endometrial Cancer.
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Ashley CW, Selenica P, Patel J, Wu M, Nincevic J, Lakhman Y, Zhou Q, Shah RH, Berger MF, Da Cruz Paula A, Brown DN, Marra A, Iasonos A, Momeni-Boroujeni A, Alektiar KM, Long Roche K, Zivanovic O, Mueller JJ, Zamarin D, Broach VA, Sonoda Y, Leitao MM, Friedman CF, Jewell E, Reis-Filho JS, Ellenson LH, Aghajanian C, Abu-Rustum NR, Cadoo K, and Weigelt B
- Subjects
- Female, Humans, Prognosis, Mutation, High-Throughput Nucleotide Sequencing methods, Biomarkers, Tumor genetics, Cell-Free Nucleic Acids genetics, Circulating Tumor DNA genetics, Endometrial Neoplasms diagnosis, Endometrial Neoplasms genetics
- Abstract
Purpose: We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring., Experimental Design: Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods., Results: cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advanced-stage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and follow-up, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P < 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival., Conclusions: cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring. See related commentary by Grant et al., p. 305., (©2022 American Association for Cancer Research.)
- Published
- 2023
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9. Sentinel lymph node mapping in patients with endometrial hyperplasia: A practice to preserve or abandon?
- Author
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Mueller JJ, Rios-Doria E, Park KJ, Broach VA, Alektiar KM, Jewell EL, Zivanovic O, Sonoda Y, Abu-Rustum NR, Leitao MM Jr, and Gardner GJ
- Subjects
- Female, Humans, Sentinel Lymph Node Biopsy, Retrospective Studies, Lymph Nodes surgery, Lymph Nodes pathology, Lymph Node Excision, Neoplasm Staging, Sentinel Lymph Node surgery, Sentinel Lymph Node pathology, Endometrial Neoplasms genetics, Endometrial Neoplasms surgery, Endometrial Neoplasms diagnosis, Endometrial Hyperplasia surgery, Endometrial Hyperplasia pathology, Carcinoma, Endometrioid pathology
- Abstract
Objectives: To compare outcomes of patients with premalignant endometrial pathology undergoing hysterectomy with or without sentinel lymph node (SLN) removal. Outcomes of interest included surgical adverse events (AEs), cancer status on final pathology, postoperative treatment, and The Cancer Genome Atlas (TCGA) molecular risk profiles., Methods: We retrospectively identified patients with premalignant pathology on preoperative endometrial biopsy who underwent hysterectomy with or without SLN mapping/excision at our institution from 01/01/2017-12/31/2021. Clinical, pathologic, surgical, and TCGA profiling data were abstracted. Appropriate statistical tests were used., Results: Of 221 patients identified, 161 (73%) underwent hysterectomy with SLN excision and 60 (27%) underwent hysterectomy without SLN excision. Median age and body mass index were similar between groups. Median operative time was 130 min for those who underwent SLN mapping/excision versus 136 min for those who did not (p = 0.6). Thirty-day postoperative AE rates were 9% (n = 15/161) and 13% (n = 8/60), respectively (p = 0.9). Ninety-eight (44%) of 221 patients had grade 1-2 endometrioid endometrial cancer on final pathology (4 [4%] were stage IB or higher). Ten (10%) of 98 patients, all within the SLN group, received adjuvant treatment. Among all patients, of 33 (15%) with TCGA molecular classification data, 27 (82%) had copy number-low, 3 (9%) microsatellite instability-high, 2 (6%) POLE-ultramutated, and 1 (3%) copy number-high disease., Conclusions: SLN assessment appears safe, detects a small number of occult nodal metastases for those upstaged, and provides additional staging information that can guide adjuvant treatment. SLN mapping should be discussed in preoperative counseling and offered using a shared decision-making approach., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Jewell reports personal fee from Covidien/Medtronic; Dr. Abu-Rustum reports grant money from GRAIL paid to the institution; and Dr. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2023
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10. Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers.
- Author
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Ehmann S, Sassine D, Straubhar AM, Praiss AM, Aghajanian C, Alektiar KM, Broach V, Cadoo KA, Jewell EL, Boroujeni AM, Kyi C, Leitao MM, Mueller JJ, Murali R, Bhaloo SI, O'Cearbhaill RE, Park KJ, Sonoda Y, Weigelt B, Zamarin D, Abu-Rustum N, and Friedman CF
- Subjects
- Humans, Female, Retrospective Studies, Chemoradiotherapy, Neoplasm Staging, Uterine Cervical Neoplasms therapy, Uterine Cervical Neoplasms drug therapy, Adenocarcinoma therapy, Adenocarcinoma drug therapy, Stomach Neoplasms, Papillomavirus Infections therapy, Papillomavirus Infections drug therapy
- Abstract
Objectives: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center., Methods: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis., Results: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab., Conclusions: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype., Competing Interests: Declaration of Competing Interest Outside the submitted work, B. Weigelt reports ad hoc membership in the scientific advisory board of Repare Therapeutics, outside the scope of the study. C. Friedman reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. E. Jewell reports personal fee from Covidien/Medtronic. K. Cadoo reports grant funding from the Irish Cancer Society, MSD, and Immunogen; consulting fees from Nextcure, MJH Life Sciences, and GSK; payments/honoraria from GSK, AstraZeneca, and MSD; financial support to attend meetings from Roche, Pfizer, and MSD; advisory board participation at MSD, AstraZeneca, GSK, and Eisai; a voluntary advisory role at the National Cancer Control Programme Ireland; and a voluntary board member at ARC Cancer Support Centers. N. Abu-Rustum reports grant funding from GRAIL paid to the institution. S. issa Bhaloo reports stock or stock options in BioNTech, Moderna, Inc., Inovio, Relief Therapeutics Holding SA, Cansino Biologics, Inc., and Pfizer, Inc. M. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon. C. Aghajanian has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. R. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio. C. Kyi reports grant funding from Conquer Cancer Foundation; grant funding paid to the institution from Merus, Gritstone, and BMS; and consulting fees from Scenic Immunology B.V. and OncLive. D. Zamarin is an inventor on a patent related to the use of oncolytic Newcastle Disease Virus for cancer therapy, and reports grant funding paid to the institution from AstraZeneca, Roche, Plexxikon, and Synthekine; consulting fees from Memgen, Celldex, Agenus, Astellas, AstraZeneca, Crown Biosciences, Roche, GSK, Hookpia, ImmunOS, Kalvir, Synlogic Therapeutics, Synthekine, Takeda, Targovax, Tessa Therapeutics, and Xencor; stock options in Accurius Therapeutics, Immunos Therapeutics and Calidi Biotherapeutics; and a Merck licensed patent (with personal payments and payments to the institution). All other authors have no potential conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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11. Risk Stratification of Stage I Grade 3 Endometrioid Endometrial Carcinoma in the Era of Molecular Classification.
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Zammarrelli WA 3rd, Kim SH, Da Cruz Paula A, Rios-Doria EV, Ehmann S, Yeoshoua E, Hanlon EJ, Zhou Q, Iasonos A, Alektiar KM, Aghajanian C, Makker V, Leitao MM Jr, Abu-Rustum NR, Ellenson LH, Weigelt B, and Mueller JJ
- Subjects
- Female, Humans, Prognosis, Risk Assessment, Carcinoma, Endometrioid genetics, Endometrial Neoplasms genetics, Lymphoma, Follicular
- Abstract
Purpose: The role of adjuvant therapy in stage I grade 3 endometrioid endometrial carcinoma (EEC) is debatable. We sought to define the agreement between Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) high-intermediate risk (HIR) and Gynecologic Oncology Group (GOG)-99 HIR criteria, assess their concordance with The Cancer Genome Atlas molecular subtypes, and evaluate oncologic outcomes in this population., Methods: We identified patients with stage I grade 3 EECs who underwent surgical staging at our institution from January 2014 to January 2020. Patients were stratified into PORTEC-1 HIR, GOG-99 HIR, and The Cancer Genome Atlas molecular subtypes. Adjuvant treatment, and progression-free survival (PFS), and overall survival (OS) were analyzed., Results: Seventy-five patients were included. The agreement between PORTEC-1 and GOG-99 HIR classification was 68% (95% CI, 56.2 to 78.3), with a kappa of 0.36 ( P = .001). There was no agreement between PORTEC-1 or GOG-99 HIR classification and a dichotomized molecular classification (copy number-high [CN-H] v other subtypes), with a kappa of 0.03 ( P = .39) and -0.03 ( P = .601), respectively. There was no difference in PFS between PORTEC-1 HIR and non-HIR (HR, 10.9; 95% CI, 0.28 to 4.21) or between GOG-99 HIR and non-HIR (HR, 1.22; 95% CI, 0.32 to 4.6) stage I grade 3 EECs. Patients with CN-H compared with non-CN-H EEC had worse PFS (HR, 5.67; 95% CI, 1.73 to 18.63) and OS (HR, 5.05; 95% CI, 1.13 to 22.5)., Conclusion: In surgically staged patients with stage I grade 3 EEC, PORTEC-1 and GOG-99 HIR criteria were not prognostic and did not identify CN-H patients. Patients with CN-H EEC had worse PFS and OS compared with those with other molecular subtypes. The integration of the molecular classification with recognized clinicopathologic factors may identify patients with higher-risk stage I grade 3 EEC who benefit from additional therapy., Competing Interests: Alexia IasonosStock and Other Owner Interests: Bristol Myers Squibb/SanofiConsulting and Advisory Role: Intelligencia, Mirati Therapeutics Carol AghajanianConsulting and Advisory Role: AbbVie, Eisai, AstraZeneca/Merck, Roche/Genentech, Repare TherapeuticsResearch Funding: Genentech/Roche, AbbVie, Clovis Oncology, AstraZeneca Vicky MakkerConsulting and Advisory Role: Eisai, Merck, Karyopharm Therapeutics, Takeda, ArQuie, IBM, GlaxoSmithKline, Clovis Oncology, Faeth Therapeutics, Novartis, Duality, ITeos Therapeutics, Kartos Therapeutics, LillyResearch Funding: Lilly, AstraZeneca, Eisai, Merck, Bristol Myers Squibb, Karyopharm Therapeutics, Takeda, Clovis Oncology, Bayer, Zymeworks, Duality, Faeth TherapeuticsTravel, Accommodations, Expenses: Eisai, Merck, Karyopharm TherapeuticsOther Relationship: IBM Mario M. Leitao JrHonoraria: Intuitive SurgicalConsulting and Advisory Role: Intuitive Surgical, Ethicon/Johnson & Johnson, Medtronic, TakedaResearch Funding: KCITravel, Accommodations, Expenses: Intuitive Surgical Nadeem R. Abu-RustumHonoraria: Prime Oncology, NCCMResearch Funding: GRAILTravel, Accommodations, Expenses: Prime Oncology Britta WeigeltStock and Other Owner Interests: Repare Therapeutics (I)Consulting and Advisory Role: Ventana Medical Systems, VolitionRx, PAIGE, Goldman Sachs, Repare Therapeutics, Lilly (I)No other potential conflicts of interest were reported.
- Published
- 2022
- Full Text
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12. Histology-Specific Prognostication for Radiation-Associated Soft Tissue Sarcoma.
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Bartlett EK, Sharma A, Seier K, Antonescu CR, Agaram NP, Jadeja B, Rosenbaum E, Chi P, Brennan MF, Qin LX, Alektiar KM, and Singer S
- Subjects
- Adult, Humans, Fibrosarcoma, Histiocytoma, Malignant Fibrous pathology, Leiomyosarcoma pathology, Neurofibrosarcoma, Sarcoma pathology, Soft Tissue Neoplasms
- Abstract
Purpose: Radiation-associated sarcomas (RAS) are rare but aggressive malignancies. We sought to characterize the histology-specific presentation and behavior of soft tissue RAS to improve individualized prognostication., Methods: A single-institutional prospectively maintained database was queried for all patients with primary, nonmetastatic RAS treated with surgical resection from 1982 to 2019. Patients presenting with the five most common RAS histologies were propensity-matched to those with sporadic tumors of the same histology. Incidence of disease-specific death (DSD) was modeled using cumulative incidence analyses., Results: Among 259 patients with RAS, the five most common histologies were malignant peripheral nerve sheath tumor (MPNST; n = 19), myxofibrosarcoma (n = 20), leiomyosarcoma (n = 24), undifferentiated pleomorphic sarcoma (UPS; n = 55), and angiosarcoma (AS; n = 62). DSD varied significantly by histology ( P = .002), with RAS MPNST and UPS having the highest DSD. In unadjusted analysis, RAS MPNST was associated with increased DSD compared with sporadic MPNST (75% v 38% 5-year DSD, P = .002), as was RAS UPS compared with sporadic UPS (49% v 28% 5-year DSD, P = .004). Unadjusted DSD was similar among patients with RAS AS, leiomyosarcoma, or myxofibrosarcoma and sporadic sarcoma of the same histology. After matching RAS to sporadic patients within each histology, DSD only differed between RAS and sporadic MPNST (83% v 46% 5-year DSD, P = .013). Patients with RAS AS presented in such a distinct manner to those with sporadic AS that a successful match was not possible., Conclusion: The aggressive presentation of RAS is histology-specific, and DSD is driven by RAS MPNST and UPS histologies. Despite the aggressive presentation, standard prognostic factors can be used to estimate risk of DSD among most RAS. In MPNST, radiation association should be considered to independently associate with markedly higher risk of DSD.
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- 2022
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13. Small cell neuroendocrine carcinoma of the cervix: Analysis of prognostic factors and patterns of metastasis.
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Gordhandas S, Schlappe BA, Zhou Q, Iasonos A, Leitao MM Jr, Park KJ, de Brot L, Alektiar KM, Sabbatini PJ, Aghajanian CA, Friedman C, Zivanovic O, and O'Cearbhaill RE
- Abstract
Objectives: To describe characteristics and outcomes of patients with small cell neuroendocrine carcinoma of the cervix (SCNCC) and determine the staging system most predictive of outcome-the two-tier (limited-stage [LS] vs. extensive-stage [ES]) or International Federation of Gynecology and Obstetrics (FIGO) staging system., Methods: Patients with SCNCC evaluated at our institution from 1/1/1990-6/30/2021 were included. Medical records were reviewed for variables of interest. Appropriate statistical tests were performed to determine associations. Survival curves were created using the Kaplan-Meier method. Concordance probability estimates (CPEs) were calculated to evaluate the prediction probability of the staging systems., Results: Of 63 patients, 41 had LS and 22 ES SCNCC. Patients with ES disease were significantly older than those with LS disease (median, 54 and 37 years, respectively; p < 0.001). Smoking status, race, and history of HPV were not associated with stage or outcomes. Forty-eight patients had metastatic disease (24 [50%] at initial diagnosis). The most common first sites of metastasis were lung (n = 20/48, 42%), lymph nodes (n = 19/48, 40%), and liver (n = 13/48, 27%). Nine patients had brain metastasis (8 symptomatic at recurrence; 1 asymptomatic at initial diagnosis). Both staging systems were associated with progression-free and overall survival. Adjusted CPE found the FIGO staging system was more predictive of outcomes than the two-tier staging system., Conclusions: Providers should have a low threshold to obtain brain imaging for patients with SCNCC, especially in the presence of visceral metastases. FIGO staging should be used to classify SCNCC. Further research is necessary to understand prognostic factors of this rare disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
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- 2022
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14. Primary characteristics and outcomes of newly diagnosed low-grade endometrial stromal sarcoma.
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Smith ES, Jansen C, Miller KM, Chiang S, Alektiar KM, Hensley ML, Mueller JJ, Abu-Rustum NR, and Leitao MM Jr
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- Adult, Aged, Aged, 80 and over, Female, Humans, Hysterectomy, Lymph Node Excision, Lymphatic Metastasis, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Retrospective Studies, Young Adult, Endometrial Neoplasms surgery, Lymphadenopathy pathology, Sarcoma, Endometrial Stromal diagnosis, Sarcoma, Endometrial Stromal surgery
- Abstract
Objective: To assess potential predictive variables for nodal metastasis and survival outcomes in patients with newly diagnosed, low-grade endometrial stromal sarcoma., Methods: We performed a single-institution, retrospective analysis of consecutive patients with newly diagnosed, low-grade endometrial stromal sarcoma who presented between January 1, 1980 and December 31, 2019 and underwent hysterectomy at our institution or presented within 3 months of primary surgery elsewhere before recurrence. Patients who presented to our institution only at recurrence were excluded. Patients with <3 months of follow-up were excluded from survival analyses., Results: We identified 127 consecutive patients for analysis. Median age at diagnosis was 48 years (range 19-88 years); 91 (74.6%) of 127 were pre-menopausal; and 74 (58.3%) of 127 had uterine-confined, stage I tumors. Of 56 patients (44.1%) who underwent lymph node sampling, 10 (17.9%) had nodal metastasis. Of the 10 with nodal metastasis, 1 (10%) did not have lymphadenopathy or extra-uterine disease, 4 (40%) had lymphadenopathy only, 1 (10%) had extra-uterine disease only, and 4 (40%) had both. Among the 29 patients without apparent extra-uterine disease or gross lymphadenopathy, there was one occult lymph node metastasis (3.4%). Gross lymphadenopathy at time of surgery was predictive for lymph node metastasis (p<0.001). Median follow-up was 69 months (range 4-336) for the 95 patients included in the survival analyses. The 5-year progression-free survival and disease-specific survival rates were 79.8% and 90.8%, respectively. Patients with stage I tumors had longer progression-free survival than those with stage II-IV disease (p<0.001); there was no difference in disease-specific survival (p=0.63). Post-operative observation versus adjuvant therapy with hormone blockade or radiation therapy did not result in progression-free survival differences for stage I or completely resected stage II-IV disease (p=0.50 and p=0.81, respectively). Similarly, there was no disease-specific survival difference for completely resected stage II-IV disease (p=0.3)., Conclusions: Lymph node dissection in patients with low-grade endometrial stromal sarcoma should be reserved for those with clinically suspicious lymphadenopathy. Disease stage correlated with progression-free survival but not disease-specific survival. Post-operative therapy did not improve progression-free survival or disease-specific survival., Competing Interests: Competing interests: Outside the submitted work, ML reports personal fees from JnJ/Ethicon and Takeda, and grants from KCI/Acelity. He is also an ad hoc speaker for Intuitive Surgical, Inc. NRA-R reports grants from Stryker/Novadaq and GRAIL. SC reports personal fees from AstraZeneca. MLH reports “other” from Sanofi and UpToDate, as well as personal fees from GSK, Lilly, Thrive/Exact Sciences, and Research To Practice., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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15. Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets.
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Nacev BA, Sanchez-Vega F, Smith SA, Antonescu CR, Rosenbaum E, Shi H, Tang C, Socci ND, Rana S, Gularte-Mérida R, Zehir A, Gounder MM, Bowler TG, Luthra A, Jadeja B, Okada A, Strong JA, Stoller J, Chan JE, Chi P, D'Angelo SP, Dickson MA, Kelly CM, Keohan ML, Movva S, Thornton K, Meyers PA, Wexler LH, Slotkin EK, Glade Bender JL, Shukla NN, Hensley ML, Healey JH, La Quaglia MP, Alektiar KM, Crago AM, Yoon SS, Untch BR, Chiang S, Agaram NP, Hameed MR, Berger MF, Solit DB, Schultz N, Ladanyi M, Singer S, and Tap WD
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- Genomics, Humans, Bone Neoplasms, Osteosarcoma, Sarcoma drug therapy, Sarcoma therapy, Soft Tissue Neoplasms genetics
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The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analysis of 2,138 sarcomas representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations are in cell cycle control and TP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations include TERT amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varies between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response., (© 2022. The Author(s).)
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- 2022
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16. The ABR 2021 Radiation Oncology Remote Examinations: Development, Administration, and Implications for the Future.
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Wallner PE, Gerdeman AM, Warg L, Fussell MB, Segal S, Gudenkauf K, Laszakovits D, Bunting M, Davis BJ, Ng AK, Suh JH, Yashar CM, Alektiar KM, and Wagner BJ
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- Certification, Educational Measurement, Forecasting, Humans, Specialty Boards, United States, COVID-19, Internship and Residency, Radiation Oncology education
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With the onset of the global coronavirus disease 2019 pandemic in early 2020, it became apparent that routine administration of the ABR Qualifying and Certifying Exams would be disrupted. Initial intent for postponement was later altered to a recognition that replacement of the existing delivery methodologies was essential. Herein, the authors describe the conceptualization, development, administration, and future implications of the new remote examination delivery platforms., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)
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- 2022
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17. Sentinel lymph node biopsy alone compared to systematic lymphadenectomy in patients with uterine carcinosarcoma.
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Zammarrelli WA 3rd, Greenman M, Rios-Doria E, Miller K, Broach V, Mueller JJ, Aviki E, Alektiar KM, Soslow RA, Ellenson LH, Makker V, Abu-Rustum NR, and Leitao MM Jr
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- Humans, Lymph Node Excision, Medical Oncology, Progression-Free Survival, Transforming Growth Factor beta, Carcinosarcoma surgery, Sentinel Lymph Node Biopsy
- Abstract
Objective: To assess survival among patients diagnosed with uterine carcinosarcoma (CS) who underwent sentinel lymph node (SLN) biopsy alone vs. systematic lymph node dissection (LND)., Methods: We identified newly diagnosed CS patients who underwent primary surgical management from January 1996-December 2019. The SLN cohort underwent SLN biopsy alone with bilateral SLNs identified. The systematic LND cohort did not undergo SLN biopsy., Results: Ninety-nine patients underwent SLN biopsy, and 100 patients underwent systematic LND. There was no difference by age, stage, body mass index, myoinvasion (<50%, ≥50%), lymphovascular space invasion, or positive washings. Eighty-five SLN (85.9%) and 15 LND (15%) underwent minimally invasive surgery (P < 0.001). The median total node count was four (range, 1-13) for SLN and 19 (range, 2-50) for LND (P < 0.001). Nodal metastasis occurred in 23 (23.2%) SLN and in 22 (22%) LND (P = 0.4). Postoperative therapy was administered to 85 (85.9%) SLN and 71 (71%) LND (P = 0.02). Median follow-up was 33 months (range, 1-205) for SLN and 55.3 months (range, 1-269) for LND (P = 0.001). The three-year progression-free survival (PFS) was 62.9% (SE 5.2%) for SLN and 52.3% (SE 5.3%) for LND (P = 0.13). The three-year overall survival (OS) was 72.1% (SE 5.1%) for SLN and 71.6% (SE 4.6%) for LND (P = 0.68). An isolated nodal recurrence occurred in two (2%) SLN and four (4%) LND (P = 0.26)., Conclusions: There is no difference in PFS or OS among CS patients who undergo SLN biopsy vs. systematic LND. SLN biopsy detects nodal metastasis without compromising oncologic outcomes., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Makker reports industry support and unpaid consultant fees from Astra Zeneca, Eisai, Merck, Lilly, Karyopharm, Takeda, Genentech, Clovis, Novartis, Faeth, Zymeworks, GSK, and Moreo. Dr. Makker also discloses personal fees from IBM Watson. Dr. Abu-Rustum reports institutional grants from Stryker/Novadaq and GRAIL. Dr. Leitao reports grants from KCI/Acelity, personal fees from Takeda, J&J/Ethicon, and Intuitive Surgical. All other authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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18. In Regard to Dover et al.
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Ng AK, Yashar CM, Davis BJ, Suh JH, Alektiar KM, and Wallner PE
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- 2022
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19. Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline.
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Salerno KE, Alektiar KM, Baldini EH, Bedi M, Bishop AJ, Bradfield L, Chung P, DeLaney TF, Folpe A, Kane JM, Li XA, Petersen I, Powell J, Stolten M, Thorpe S, Trent JC, Voermans M, and Guadagnolo BA
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- Adult, Humans, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Quality of Life, Radiotherapy, Adjuvant, Radiation Oncology, Sarcoma radiotherapy
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Purpose: This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults., Methods: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength., Results: Multidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended., Conclusions: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life., (Copyright © 2021 American Society for Radiation Oncology. All rights reserved.)
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- 2021
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20. Non-exenterative surgical management of recurrent endometrial carcinoma.
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Moukarzel LA, Braxton KF, Zhou QC, Pedra Nobre S, Iasonos A, Alektiar KM, Tew WP, Abu-Rustum NR, Leitao MM Jr, Chi DS, and Mueller JJ
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- Adult, Aged, Aged, 80 and over, Clinical Decision-Making methods, Endometrial Neoplasms diagnosis, Endometrial Neoplasms mortality, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local mortality, Neoplasm Staging, Neoplasm, Residual, Patient Selection, Prognosis, Progression-Free Survival, Retrospective Studies, Survival Rate, Chemoradiotherapy, Adjuvant statistics & numerical data, Cytoreduction Surgical Procedures statistics & numerical data, Endometrial Neoplasms therapy, Neoplasm Recurrence, Local therapy
- Abstract
Objective: To examine the role of non-exenterative secondary cytoreductive surgery (SCS) compared with non-surgical treatments and identify predictors of improved survival for patients with recurrent endometrial cancer (EC)., Methods: All patients undergoing primary surgical management for EC 1/1/2009-12/31/2017 who subsequently developed recurrence were retrospectively identified. Survival was determined from date of diagnosis of first recurrence to last follow-up and estimated using Kaplan-Meier method. Differences in survival were analyzed using Log-rank and Wald tests, based on Cox Proportional Hazards model., Results: Among 376 patients with recurrent EC, median time to recurrence was 14.3 months (range, 0.2-102.2), post-recurrence median survival 29 months, median follow-up 29.2 months (range, 0-116). Sixty-one patients (16.2%) received SCS, 257 (68.4%) medical management (MM) (chemotherapy and/or radiation therapy), 32 (8.5%) hormonal therapy, 26 (6.9%) no further therapy. Patients selected for SCS were younger, had more endometrioid histology, more stage I disease at initial diagnosis, no residual disease after primary surgery, longer interval to first recurrence or progression, and the longest OS (57.6 months) (95% CI, 33.3-not reached). On multivariate analysis SCS was an independent predictor of improved survival. Among the 61 SCS patients, age < 70 at time of initial diagnosis, and endometrioid histology, were associated with improved post-relapse survival univariately (p = 0.008, 0.03, respectively)., Conclusions: While MM was the most common treatment for first recurrence of EC, patients selected for surgery demonstrated the greatest survival benefit even after controlling for tumor size, site, histology, stage, time to recurrence. Careful patient selection and favorable tumor factors likely play a major role in improved outcomes. Surgical management should be considered whenever feasible in medically eligible patients, with additional consideration given to our suggested criteria., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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21. Femoral Fracture in Primary Soft Tissue Sarcoma Treated with Intensity-Modulated Radiation Therapy with and Without Dose Constraints.
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Casey DL, Berry SL, Crago A, Fabbri N, Singer S, and Alektiar KM
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- Humans, Middle Aged, Radiotherapy Dosage, Femoral Fractures etiology, Radiotherapy, Intensity-Modulated adverse effects, Sarcoma radiotherapy, Soft Tissue Neoplasms
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Background: We previously reported that the cumulative risk of femoral fracture in patients treated with intensity-modulated radiation therapy (IMRT) for thigh and groin soft tissue sarcoma (STS) is low. In the current study, we sought to evaluate the effect of radiation dose constraints on the rate of femoral fracture in a more contemporary cohort., Methods: All patients treated with IMRT for STS of the thigh or groin from 2004 to 2016 were included (n = 145). Beginning in 2011, radiation dose was constrained to a mean dose of < 37 Gy, volume of bone receiving ≥ 40 Gy (V40Gy) < 64%, and maximum dose < 59 Gy to limit the dose to the femur., Results: Sixty-one patients were treated before dose constraints were implemented, and 84 patients were treated after. Median follow-up for patients treated before and after constraints were implemented was 6.1 and 5.7 years, respectively, and the two groups were demographically and clinically similar. On univariate analysis, the 5-year cumulative incidence of femoral fracture among patients treated with and without dose constraints was 1.8% (95% confidence interval [CI] 0.3-12.2%) versus 7.4% (95% CI 3.1-17.6%) [p = 0.11, p = non-significant, respectively]. On multivariable analysis, only age ≥ 60 years was significantly associated with increased risk of fracture., Conclusions: The risk of femoral fracture after IMRT for STS of the thigh/groin is low, and with the implementation of radiation dose constraints, the risk is < 2%. Although longer follow-up is needed, our results support the utilization of extremity sarcoma IMRT-specific dose constraints for fracture prevention.
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- 2021
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22. Socioeconomic inequality and omission of adjuvant radiation therapy in high-risk, early-stage endometrial cancer.
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Luo LY, Aviki EM, Lee A, Kollmeier MA, Abu-Rustum NR, Tsai CJ, and Alektiar KM
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- Black or African American statistics & numerical data, Aged, Cohort Studies, Endometrial Neoplasms mortality, Endometrial Neoplasms pathology, Female, Guideline Adherence, Humans, Logistic Models, Middle Aged, Neoplasm Staging, Proportional Hazards Models, Radiotherapy, Adjuvant economics, Radiotherapy, Adjuvant statistics & numerical data, Retrospective Studies, Risk Factors, Socioeconomic Factors, United States epidemiology, Endometrial Neoplasms economics, Endometrial Neoplasms radiotherapy, Healthcare Disparities statistics & numerical data
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Objective: Gaps in access to appropriate cancer care, and associated cancer mortality, have widened across socioeconomic groups. We examined whether demographic and socioeconomic factors influenced receipt of adjuvant radiation therapy (RT) in patients with high-risk, early-stage endometrial cancer., Methods: A retrospective study cohort was selected from 349,404 endometrial carcinoma patients from the National Cancer Database in whom adjuvant RT would be recommended per national guidelines. The study included surgically treated patients with endometrioid endometrial cancer with one of the following criteria: 1) FIGO 2009 stage IB, grade 1/2 disease, age ≥ 60 years; 2) stage IB, grade 3 disease; or 3) stage II disease. Logistic regression analysis was performed to identify factors associated with omission of adjuvant RT. Association between adjuvant RT, covariables, and overall survival (OS) was assessed with multivariable Cox proportional hazards models., Results: 19,594 patients were eligible for analysis; 47% did not receive adjuvant RT. Omission of adjuvant RT was more prevalent among African-American, Hispanic, and Asian compared to non-Hispanic white patients (OR 0.79, 95%CI: 0.69-0.91; OR 0.75, 95%CI: 0.64-0.87; OR 0.75, 95%CI: 0.60-0.94, respectively). Lower median household income of patient's area of residence, lack of health insurance, treatment at non-academic hospitals, farther distance to treatment facilities, and residence in metropolitan counties were associated with omission of adjuvant RT. Such omission was independently associated with worse OS (HR1.43, p < 0.001)., Conclusion: Adjuvant RT is omitted in 47% of patients with early-stage, high-risk endometrial cancer, which is associated with poor access to appropriate, high-quality care and worse outcome., Competing Interests: Declaration of Competing Interest C. Jillian Tsai reports consulting for Varian outside the submitted work. Dr. Abu-Rustum reports grants paid to his institution from Stryker/Novadaq, Olympus, and GRAIL outside the submitted work. The other authors have no conflict of interest to report., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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23. Clinicopathologic and Genomic Analysis of TP53 -Mutated Endometrial Carcinomas.
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Momeni-Boroujeni A, Dahoud W, Vanderbilt CM, Chiang S, Murali R, Rios-Doria EV, Alektiar KM, Aghajanian C, Abu-Rustum NR, Ladanyi M, Ellenson LH, Weigelt B, and Soslow RA
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- Combined Modality Therapy, DNA Copy Number Variations, Disease Management, Endometrial Neoplasms mortality, Endometrial Neoplasms therapy, Female, Gene Expression, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Tumor Suppressor Protein p53 metabolism, Biomarkers, Tumor, Endometrial Neoplasms diagnosis, Endometrial Neoplasms genetics, Mutation, Tumor Suppressor Protein p53 genetics
- Abstract
Purpose: Copy number-high endometrial carcinomas were described by The Cancer Genome Atlas as high-grade endometrioid and serous cancers showing frequent copy-number alterations (CNA), low mutational burden (i.e., non-hypermutant), near-universal TP53 mutation, and unfavorable clinical outcomes. We sought to investigate and compare the clinicopathologic and molecular characteristics of non-hypermutant TP53 -altered endometrial carcinomas of four histologic types., Experimental Design: TP53 -mutated endometrial carcinomas, defined as TP53 -mutant tumors lacking microsatellite instability or pathogenic POLE mutations, were identified ( n = 238) in a cohort of 1,239 endometrial carcinomas subjected to clinical massively parallel sequencing of 410-468 cancer-related genes. Somatic mutations and CNAs ( n = 238), and clinicopathologic features were determined ( n = 185, initial treatment planning at our institution)., Results: TP53 -mutated endometrial carcinomas encompassed uterine serous ( n = 102, 55.1%), high-grade endometrial carcinoma with ambiguous features/not otherwise specified (EC-NOS; n = 44, 23.8%), endometrioid carcinomas of all tumor grades ( n = 28, 15.1%), and clear cell carcinomas ( n = 11, 5.9%). PTEN mutations were significantly more frequent in endometrioid carcinomas, SPOP mutations in clear cell carcinomas, and CCNE1 amplification in serous carcinomas/EC-NOS; however, none of these genomic alterations were exclusive to any given histologic type. ERBB2 amplification was present at similar frequencies across TP53 -mutated histologic types (7.7%-18.6%). Although overall survival was similar across histologic types, serous carcinomas presented more frequently at stage IV, had more persistent and/or recurrent disease, and reduced disease-free survival., Conclusions: TP53 -mutated endometrial carcinomas display clinical and molecular similarities across histologic subtypes. Our data provide evidence to suggest performance of ERBB2 assessment in all TP53 -mutated endometrial carcinomas. Given the distinct clinical features of serous carcinomas, histologic classification continues to be relevant., (©2021 American Association for Cancer Research.)
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- 2021
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24. Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.
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Pitter KL, Casey DL, Lu YC, Hannum M, Zhang Z, Song X, Pecorari I, McMillan B, Ma J, Samstein RM, Pei IX, Khan AJ, Braunstein LZ, Morris LGT, Barker CA, Rimner A, Alektiar KM, Romesser PB, Crane CH, Yahalom J, Zelefsky MJ, Scher HI, Bernstein JL, Mandelker DL, Weigelt B, Reis-Filho JS, Lee NY, Powell SN, Chan TA, Riaz N, and Setton J
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- Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Child, Cohort Studies, Female, Gene Silencing, Humans, Male, Middle Aged, Radiation Tolerance genetics, Tumor Suppressor Protein p53 genetics, Young Adult, Ataxia Telangiectasia Mutated Proteins genetics, Mutation, Missense, Neoplasms genetics, Neoplasms radiotherapy
- Abstract
Background: Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure., Methods: We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided., Results: Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors., Conclusions: We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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25. A single-arm, prospective trial investigating the effectiveness of a non-hormonal vaginal moisturizer containing hyaluronic acid in postmenopausal cancer survivors.
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Carter J, Baser RE, Goldfrank DJ, Seidel B, Milli L, Stabile C, Canty J, Saban S, Goldfarb S, Dickler MN, Gardner GJ, Jewell EL, Sonoda Y, Kollmeier MA, and Alektiar KM
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- Adult, Aged, Atrophy, Breast Neoplasms pathology, Breast Neoplasms therapy, Endometrial Neoplasms pathology, Endometrial Neoplasms therapy, Female, Humans, Longitudinal Studies, Middle Aged, Postmenopause physiology, Prospective Studies, Vaginal Creams, Foams, and Jellies therapeutic use, Aromatase Inhibitors therapeutic use, Cancer Survivors, Hyaluronic Acid therapeutic use, Vagina pathology, Vaginal Diseases drug therapy, Vulva pathology
- Abstract
Purpose: To assess the feasibility and efficacy of a non-hormonal hyaluronic acid (HLA) vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in postmenopausal women with a history of hormone receptor-positive (HR+) cancer., Methods: For this single-arm, prospective longitudinal trial, we identified disease-free patients with a history of HR+ breast cancer treated with aromatase inhibitors or HR+ endometrial cancer treated with surgery and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1], 4-6 weeks [T2], 12-14 weeks [T3], 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL)., Results: Of 101 patients, mean age was 55 years (range, 31-78), 68% (n = 69) were partnered, and 60% (n = 61) were sexually active. In linear mixed models, VAS/VuAS scores significantly improved at all assessment points (all p < 0.001). MSCL scores similarly improved (all p < 0.001). FSFI scores significantly improved from T1 to T2 (p < 0.03), T3 (p < 0.001), and T4 (p < 0.001). Severe vaginal pH (> 6.5) decreased from 26% at T1 to 19% at T4 (p = 0.18)., Conclusions: HLA moisturization improved vulvovaginal health/sexual function of cancer survivors. While HLA administration 1-2×/week is recommended for women in natural menopause, a 3-5×/week schedule appears to be more effective for symptom relief in cancer survivors.
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- 2021
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26. Comparison of minimally invasive versus open surgery in the treatment of endometrial carcinosarcoma.
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Pedra Nobre S, Mueller JJ, Gardner GJ, Long Roche K, Brown CL, Soslow RA, Alektiar KM, Sonoda Y, Broach VA, Jewell EL, Zivanovic O, Chi DS, Abu-Rustum NR, and Leitao MM Jr
- Subjects
- Aged, Aged, 80 and over, Carcinosarcoma pathology, Conversion to Open Surgery, Endometrial Neoplasms pathology, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Laparoscopy adverse effects, Length of Stay, Middle Aged, Neoplasm Staging, Operative Time, Patient Readmission, Postoperative Complications etiology, Progression-Free Survival, Retrospective Studies, Robotic Surgical Procedures adverse effects, Survival Rate, Carcinosarcoma surgery, Endometrial Neoplasms surgery, Minimally Invasive Surgical Procedures adverse effects
- Abstract
Objective: The aim of this study was to compare perioperative and oncologic outcomes between minimally invasive and open surgery in the treatment of endometrial carcinosarcoma., Methods: We retrospectively identified all patients with newly diagnosed endometrial carcinosarcoma who underwent primary surgery via any approach at our institution from January 2009 to January 2018. Patients with known bulky disease identified on preoperative imaging were excluded. The χ
2 and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Kaplan-Meier curves were used to estimate survival, and compared using the log rank test., Results: We identified 147 eligible patients, of whom 37 (25%) underwent an open approach and 110 (75%) underwent minimally invasive surgery. Within the minimally invasive group, 92 (84%) of 110 patients underwent a robotic procedure and 14 (13%) underwent a laparoscopic procedure. Four minimally invasive cases (4%) were converted to open procedures. Median age, body mass index, operative time, stage, complication grade, and use of adjuvant treatment were clinically and statistically similar between groups. Median length of hospital stay in the open group was 4 days (range 3-21) compared with 1 day (range 0-6) in the minimally invasive group (p<0.001). The rates of any 30-day complication were 46% in the open and 8% in the minimally invasive group (p<0.001). The rates of grade 3 or higher complications were 5.4% and 1.8%, respectively (p=0.53). Median follow-up for the entire cohort was 30 months (range 0.4-121). Two-year progression-free survival rates were 52.8% (SE±8.4) in the open group and 58.5% (SE±5.1) in the minimally invasive group (p=0.7). Two-year disease-specific survival rates were 66.1% (SE±8.0) and 81.4% (SE±4.1), respectively (p=0.8)., Conclusions: In patients with clinical stage I endometrial carcinosarcoma, minimally invasive compared with open surgery was not associated with poor oncologic outcomes, but with a shorter length of hospital stay and a lower rate of overall complications., Competing Interests: Competing interests: ML is an ad hoc speaker for Intuitive Surgical, Inc. Outside the submitted work, ML reports personal fees from JNJ/Ethicon. EJ reports personal fees from Covidien/Medtronic. DSC reports personal fees from Bovie Medical Co, Verthermia Inc (now Apyx Medical Corp), C Surgeries, and Biom ‘Up. NRA-R reports grants from Stryker/Novadaq, Olympus, and GRAIL., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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27. A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors.
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Carter J, Goldfarb S, Baser RE, Goldfrank DJ, Seidel B, Milli L, Saban S, Stabile C, Canty J, Gardner GJ, Jewell EL, Sonoda Y, Kollmeier MA, and Alektiar KM
- Subjects
- Adult, Aged, Cancer Survivors, Cohort Studies, Endometrial Neoplasms physiopathology, Endometrial Neoplasms radiotherapy, Endometrial Neoplasms surgery, Female, Humans, Longitudinal Studies, Middle Aged, Prospective Studies, Vagina physiopathology, Vulva physiopathology, Endometrial Neoplasms rehabilitation, Hyaluronic Acid administration & dosage, Vagina drug effects, Vaginal Creams, Foams, and Jellies administration & dosage, Vulva drug effects
- Abstract
Objective: To assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer., Methods: For this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4-6 weeks [T2]; 12-14 weeks [T3]; 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL)., Results: Of 43 patients, mean age was 59 years (range, 38-78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41)., Conclusion: The HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1-2×/week is recommended for women in natural menopause; a 3-5×/week schedule appears more effective for symptom relief in cancer survivors., Competing Interests: Declaration of competing interest Outside the submitted work, Dr. Jewell reports personal fees from Covidien/Medtronic. All other authors have no conflicts of interest to report., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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28. Incidence of pelvic lymph node metastasis using modern FIGO staging and sentinel lymph node mapping with ultrastaging in surgically staged patients with endometrioid and serous endometrial carcinoma.
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Mueller JJ, Pedra Nobre S, Braxton K, Alektiar KM, Leitao MM Jr, Aghajanian C, Ellenson LH, and Abu-Rustum NR
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Endometrioid pathology, Endometrial Neoplasms pathology, Female, Humans, Incidence, Middle Aged, Neoplasm Staging, Young Adult, Carcinoma, Endometrioid surgery, Endometrial Neoplasms surgery, Lymphatic Metastasis pathology, Sentinel Lymph Node pathology, Sentinel Lymph Node Biopsy methods
- Abstract
Objective: We report the incidence of occult nodal metastasis in patients who underwent primary surgical staging for apparent early endometrioid or serous endometrial cancer with bilateral SLN mapping and enhanced pathology. Occult ovarian metastasis rates were also reported., Methods: Patients with clinical stage I serous or endometrioid endometrial cancer who underwent primary staging surgery with successful bilateral SLN mapping from 1/2005-12/2018 were retrospectively evaluated. Rates of isolated tumor cells (ITCs), micro- and macrometastatic nodal disease, and occult ovarian involvement were reported., Results: Of 1044 patients, 959 had endometrioid and 85 serous carcinoma. There were no positive SLNs among 510 patients with noninvasive FIGO grade 1/2 endometrioid carcinoma and < 1%ITCs. Grade 1: 4.5%(9/202) with inner-half and 10%(6/62) with outer-half myoinvasion had positive SLNs. Grade 2: rates were 4%(3/76) and 20%(8/41), respectively. Grade 3: 5%(1/20) with noninvasive, 3%(1/31) with inner-half, and 24%(4/17) with outer-half myoinvasion had positive SLNs. ITC incidence increased with depth of myoinvasion-25% of deeply invasive grade 1/2 and 18% of deeply invasive grade 3 tumors. Four (10%) of 41 patients with noninvasive serous endometrial carcinoma had ITCs or positive SLNs. There were no occult ovarian metastases with grades 1/2 disease, 2/68 (3%) with grade 3 disease, and 2/85 (2%) with serous endometrial carcinoma., Conclusion: Ultrastaging SLNs may be unwarranted in low-grade noninvasive endometrioid cancer but valuable in noninvasive serous carcinoma. Occult ovarian metastasis is uncommon in early endometrial carcinoma and occurs in 2-3% of high-risk histologies. Further research is needed to determine ITC significance, particularly with regard to adjuvant treatment., Competing Interests: Declaration of competing interest Outside the submitted work, the authors claim the following potential disclosures: Dr. Leitao is an ad-hoc speaker for Intuitive Surgical, Inc. and is on the advisory board of JNJ/Ethicon. Dr. Aghajanian reports personal fees from Tesaro, Immunogen, Eisai/Merck, Mersana Therapeutics, Roche, Clovis, and Mateon Therapeutics, as well as grants from Clovis, Genentech, AbbVie, and AstraZeneca. Dr. Abu-Rustum reports grants from Stryker/Novadaq, Olympus, and GRAIL., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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29. Sentinel lymph node mapping alone compared to more extensive lymphadenectomy in patients with uterine serous carcinoma.
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Basaran D, Bruce S, Aviki EM, Mueller JJ, Broach VA, Cadoo K, Soslow RA, Alektiar KM, Abu-Rustum NR, and Leitao MM Jr
- Subjects
- Adult, Aged, Aged, 80 and over, Cystadenocarcinoma, Serous mortality, Endometrial Neoplasms mortality, Female, Humans, Middle Aged, Retrospective Studies, Sentinel Lymph Node Biopsy methods, Survival Analysis, Cystadenocarcinoma, Serous pathology, Cystadenocarcinoma, Serous surgery, Endometrial Neoplasms pathology, Endometrial Neoplasms surgery, Lymph Nodes pathology, Lymph Nodes surgery, Sentinel Lymph Node pathology
- Abstract
Objectives: The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND)., Methods: We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test., Results: 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1-96) and 66 months (range, 4-265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8)., Conclusions: SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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30. Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer.
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Stasenko M, Tunnage I, Ashley CW, Rubinstein MM, Latham AJ, Da Cruz Paula A, Mueller JJ, Leitao MM Jr, Friedman CF, Makker V, Soslow RA, DeLair DF, Hyman DM, Zamarin D, Alektiar KM, Aghajanian CA, Abu-Rustum NR, Weigelt B, and Cadoo KA
- Subjects
- Adult, Aged, Carcinoma, Endometrioid enzymology, Carcinoma, Endometrioid pathology, Carcinoma, Endometrioid therapy, Cohort Studies, DNA Mismatch Repair, DNA Polymerase II metabolism, Endometrial Neoplasms enzymology, Endometrial Neoplasms pathology, Endometrial Neoplasms therapy, Female, Humans, Microsatellite Instability, Middle Aged, Mutation, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Poly-ADP-Ribose Binding Proteins metabolism, Prognosis, Prospective Studies, Carcinoma, Endometrioid genetics, DNA Polymerase II genetics, Endometrial Neoplasms genetics, Poly-ADP-Ribose Binding Proteins genetics
- Abstract
Objectives: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs)., Methods: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins., Results: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment., Conclusions: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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31. Secondary surgical resection for patients with recurrent uterine leiomyosarcoma.
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Cybulska P, Sioulas V, Orfanelli T, Zivanovic O, Mueller JJ, Broach VA, Long Roche KC, Sonoda Y, Hensley ML, O'Cearbhaill RE, Chi DS, Alektiar KM, Abu-Rustum NR, and Leitao MM Jr
- Subjects
- Adult, Aged, Disease-Free Survival, Female, Humans, Leiomyosarcoma mortality, Lung Neoplasms surgery, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm, Residual, Pelvic Neoplasms surgery, Retrospective Studies, Uterine Neoplasms mortality, Uterine Neoplasms surgery, Leiomyosarcoma secondary, Leiomyosarcoma surgery, Lung Neoplasms secondary, Neoplasm Recurrence, Local surgery, Pelvic Neoplasms secondary
- Abstract
Objectives: To assess outcomes after secondary surgical resection in patients with recurrent uterine leiomyosarcoma (uLMS)., Methods: We retrospectively identified all patients who had no evidence of disease after initial surgery for uLMS, who underwent surgery for a first recurrence at our institution between 1/1991 and 10/2013. We excluded patients who received any therapy for recurrence prior to secondary resection, and patients who underwent surgery soon after morcellation [of presumed benign fibroids] showed widespread disease. Overall survival (OS) was determined from time of first recurrence to death or last follow-up., Results: We identified 62 patients: 29 with abdominal/pelvic recurrence only, 30 with lung recurrence only, 3 with both. Median time to first recurrence was 18 months (95% CI: 13.3-23.3): 15.8 months (95% CI: 13.0-18.6) abdominal/pelvic recurrence; 24.1 months (95% CI: 14.5-33.7) lung-only recurrence (p = 0.03). Median OS was 37.7 months (95% CI: 25.9-49.6) abdominal/pelvic recurrence; 78.1 months (95% CI: 44.8-11.4) lung recurrence (p = 0.02). Complete gross resection (CGR) was achieved in 58 cases (93%), with gross residual ≤1 cm in 2 (3.5%) and >1 cm in 2 (3.5%). Median OS based on residual disease was 54.1 months (95% CI: 24.9-83.3), 38.7 months (95% CI: NE), 1.7 months (95% CI: NE), respectively (p < 0.001). In cases with CGR, neither adjuvant radiation (N = 9), chemotherapy (N = 8) nor hormonal therapy (N = 10) was associated with improved OS., Conclusions: Secondary surgical resection of recurrent uLMS is reasonable in patients with a high probability of achieving CGR. Lung-only recurrences were associated with more favorable outcome. Following CGR, additional therapy may not offer benefit., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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32. Brain metastasis in epithelial ovarian cancer by BRCA1/2 mutation status.
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Stasenko M, Cybulska P, Feit N, Makker V, Konner J, O'Cearbhaill RE, Alektiar KM, Beal K, Gardner GJ, Long Roche KC, Sonoda Y, Chi DS, Zivanovic O, Leitao MM Jr, Cadoo KA, and Tew WP
- Subjects
- Adult, Aged, Aged, 80 and over, BRCA1 Protein genetics, BRCA2 Protein genetics, Brain Neoplasms therapy, Carcinoma, Ovarian Epithelial therapy, Female, Genetic Predisposition to Disease, Humans, Middle Aged, Retrospective Studies, Brain Neoplasms genetics, Brain Neoplasms secondary, Carcinoma, Ovarian Epithelial genetics, Carcinoma, Ovarian Epithelial pathology, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation
- Abstract
Objective: To evaluate clinical outcomes of patients with BRCA-associated ovarian cancer who developed brain metastases (BM)., Methods: Patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and BM, treated at a single institution from 1/1/2008-7/1/2018, were identified from two institutional databases. Charts and medical records were retrospectively reviewed for clinical characteristics and germline BRCA mutation status. Appropriate statistics were used., Results: Of 3649 patients with EOC, 91 had BM (2.5%). Germline mutation status was available for 63 (69%) cases; 21 (35%) of these harbored a BRCA1/2 mutation (15 BRCA1, 6 BRCA2). Clinical characteristics were similar between groups. BM were diagnosed at a median of 31 months (95% CI, 22.6-39.4) in BRCA-mutated (mBRCA) and 32 months (95% CI, 23.7-40.3) in wild-type BRCA (wtBRCA) (p = 0.78) patients. Brain metastases were the only evidence of disease at time of BM diagnoses in 48% (n = 10) mBRCA and 19% (n = 8) wtBRCA (p = 0.02) patients. There was no difference in treatment of BM by mutation status (p = 0.84). Survival from time of BM diagnosis was 29 months (95%CI, 15.5-42.5) in mBRCA and 9 months (95% CI, 5.5-12.5) in wtBRCA patients, with an adjusted hazard ratio (HR) of 0.53, p = 0.09; 95% CI, 0.25-1.11. HR was adjusted for presence of systemic disease at time of BM diagnosis., Conclusion: This is the largest study to date comparing outcomes in patients with EOC and BM by mutation status. mBRCA patients were more likely to have isolated BM, which may be a factor in their long survival. This supports the pursuit of aggressive treatment for mBRCA EOC patients with BM. Additional studies examining the correlation of BRCA mutational status with BM are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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33. The American Board of Radiology Initial Certification in Radiation Oncology: Moving Forward Through Collaboration.
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Wallner PE, Kachnic LA, Alektiar KM, Davis BJ, Hardenbergh PH, and Ng AK
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- Certification, United States, Radiation Oncology, Radiology
- Published
- 2019
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34. Femoral Fracture in Primary Soft-Tissue Sarcoma of the Thigh and Groin Treated with Intensity-Modulated Radiation Therapy: Observed versus Expected Risk.
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Folkert MR, Casey DL, Berry SL, Crago A, Fabbri N, Singer S, and Alektiar KM
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Femoral Fractures etiology, Follow-Up Studies, Groin pathology, Humans, Male, Middle Aged, Nomograms, Prognosis, Prospective Studies, Radiation Injuries etiology, Sarcoma pathology, Survival Rate, Thigh pathology, Young Adult, Femoral Fractures diagnosis, Groin radiation effects, Radiation Injuries diagnosis, Radiotherapy, Intensity-Modulated adverse effects, Sarcoma radiotherapy, Thigh radiation effects
- Abstract
Purpose: This study was designed to compare the observed risk of femoral fracture in primary soft-tissue sarcoma (STS) of the thigh/groin treated with intensity-modulated radiation therapy (IMRT) to expected risk calculated using the Princess Margaret Hospital (PMH) nomogram., Methods: Expected femoral fracture risk was calculated by using the PMH nomogram. Cumulative risk of fracture was estimated by using Kaplan-Meier statistics. Prognostic factors were assessed with univariate and multivariate analysis using Cox's stepwise regression., Results: Between February 2002 and December 2010, 92 consecutive eligible patients were assessed. Median follow-up was 73 months (106 months in surviving patients). IMRT was delivered preoperatively (50 Gy) in 13 (14%) patients and postoperatively in 79 (86%) patients (median dose, 63 Gy; range, 59.4-66.6 Gy). The observed crude risk of fractures was 6.5% compared with 25.6% expected risk from the nomogram; the cumulative risk of fracture using IMRT at 5 years was 6.7% (95% CI 2.8-16.0%). The median time to fracture was 23 months (range, 6.9-88.6). Significant predictors of fracture on univariate analysis were age ≥ 60 years (p = 0.03), tumor location in the anterior thigh (p = 0.008), and periosteal stripping to > 20 cm (p < 0.0001). On multivariate analysis, age ≥ 60 years and periosteal stripping > 20 cm retained significance (p = 0.04 and p = 0.009, respectively)., Conclusions: In this study, the cumulative risk of femur fracture in patients treated with IMRT (6.7%) is less than the expected risk using the PMH nomogram (25.6%). Established predictors of femur fracture, such as gender, tumor size, and dose of RT, seem to have less impact on fracture risk when using IMRT.
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- 2019
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35. Snapshot of a Specialty: Results of the ABR 2016 Radiation Oncology Clinical Practice Analysis.
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Wallner PE, McGeagh AM, Gerdeman AM, Wilson LD, Shrieve DC, Alektiar KM, Hahn SM, Kachnic LA, and Jackson VP
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- Humans, Societies, Medical, Specialty Boards, Surveys and Questionnaires, United States, Radiation Oncology trends
- Abstract
Purpose: Beginning in 2010, the ABR has administered triennial clinical practice analysis surveys to inform examination development volunteers and staff about the actual state of radiation oncology practice., Methods and Materials: As reported here, the 2016 survey was designed to provide objective data regarding actual patient volumes of specific disease sites and subjective insight as to the importance and relevance of site-specific therapy to individual practices., Results: The survey instrument was circulated to 4,075 radiation oncologists listed in the membership database of the American Society for Radiation Oncology, and responses were received from 690 (16.9%); a total of 287 (41.5%) self-identified as being in academic practice. Even in the academic setting, a majority (216 of 287, or 75.3%) indicated that they spend most of their time in clinical practice., Conclusions: Data from the survey are informative regarding changes in the practice of radiation oncology over the past 6 years., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)
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- 2019
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36. The American Board of Radiology B. Leonard Holman Research Pathway to Initial Certification: Opportunities Lost for Diagnostic Radiology.
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Wallner PE, Alektiar KM, Donnelly LF, and Kaufman JA
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- Certification statistics & numerical data, Specialty Boards, United States, Certification methods, Radiation Oncology, Radiology
- Abstract
Objective: In 1998, the American Board of Radiology introduced the B. Leonard Holman Research Pathway (HRP) to initial certification for trainees in diagnostic radiology (DR) and radiation oncology (RO) motivated to pursue research-oriented careers in academic DR and RO., Conclusion: The HRP Committee anticipated that there would be a relatively even distribution between DR and RO participants, but with 18 years of experience that has not been the case. This article focuses on the HRP and DR.
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- 2019
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37. Comparison of outcomes in early-stage uterine clear cell carcinoma and serous carcinoma.
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Zhang M, Yang TJ, Desai NB, DeLair D, Kollmeier MA, Makker V, Leitao MM Jr, Abu-Rustum NR, and Alektiar KM
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- Adenocarcinoma, Clear Cell mortality, Adenocarcinoma, Clear Cell pathology, Adult, Aged, Aged, 80 and over, Brachytherapy, Chemotherapy, Adjuvant, Combined Modality Therapy, Cystadenocarcinoma, Serous mortality, Cystadenocarcinoma, Serous pathology, Disease-Free Survival, Female, Humans, Hysterectomy, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Ovariectomy, Radiotherapy, Adjuvant, Retrospective Studies, Salpingectomy, Uterine Neoplasms mortality, Uterine Neoplasms pathology, Adenocarcinoma, Clear Cell therapy, Cystadenocarcinoma, Serous therapy, Uterine Neoplasms therapy
- Abstract
Purpose: The treatment paradigm for uterine clear cell carcinoma is often linked to serous carcinoma. This study compares oncologic outcomes between women with uterine clear cell and serous carcinoma., Methods and Materials: We reviewed 114 women with stage I-II uterine clear cell carcinoma (n = 17, 15%) or serous carcinoma (n = 97, 85%) who underwent hysterectomy and salpingo-oophorectomy at our institution from April 1992 to December 2011; 86 (76%) had stage IA, 14 (12%) had stage IB, and 14 (12%) had stage II disease. Median followup was 57 months., Results: Patients with uterine clear cell and serous carcinoma did not differ significantly by age ≥60 years, stage, or rate of lymphovascular invasion. There was no difference in the number of patients with clear cell or serous histology who received adjuvant radiotherapy (71% vs. 84%, respectively; p = 0.31); however, significantly fewer patients with clear cell histology received adjuvant chemotherapy (35% vs. 67%, respectively; p = 0.02). At 5 years, there were no significant differences in disease-free survival (94% vs. 84%, respectively; p = 0.27), disease-specific survival (100% vs. 92%, respectively; p = 0.20), or overall survival (100% vs. 89%, respectively; p = 0.34). The differences in chemotherapy utilization did not impact pattern of relapse, specifically peritoneal spread (7% vs. 6%, respectively; p = 0.92) or other distant sites (0% vs. 9%, respectively; p = 0.17)., Conclusions: Oncologic outcomes and recurrence patterns of women with stage I-II uterine clear cell carcinoma compared favorably with those of women with serous carcinoma, despite significantly less adjuvant chemotherapy use. Potential reduction in adjuvant therapy in women with clear cell carcinoma should be studied prospectively., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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38. Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC nodal assessment.
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Aloisi A, Casanova JM, Tseng JH, Seader KA, Nguyen NT, Alektiar KM, Makker V, Chiang S, Soslow RA, Leitao MM Jr, and Abu-Rustum NR
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Neoplasm Staging, Retrospective Studies, Endometrial Neoplasms pathology, Lymph Nodes pathology, Neoplasm Recurrence, Local pathology
- Abstract
Objective: To assess the rates and distribution of first recurrence in patients with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic dissection at surgical staging., Methods: We retrospectively selected all (n = 207) stage IIIC1 patients treated at a single institution from 5/1993-1/2017. Sites of first recurrence were identified, disease-free (DFS) and overall survival (OS) calculated, multivariate logistic regression performed to identify factors associated with recurrence., Results: Three-year DFS and OS were 66.5% and 85.7%, respectively. The most common histology was endometroid (64.2%). Three-year DFS was 81% (SE±3.8%) endometrioid vs. 39.5% (SE±6.6%) non-endometrioid (P < 0.001). Three-year OS was 96.9% (SE±1.8%) endometrioid vs. 65.6% (SE±6.7%) non-endometrioid (P < 0.001). Sixty-two (30.1%) patients recurred. Patterns of recurrence were: 14 (8.3%) multiple sites, 17 (8.2%) abdominal, 14 (6.8%) extra-abdominal, 17 (8.3%) isolated nodal (8 of these (3.9%) paraaortic). Patients with isolated tumor cells (ITCs) in lymph nodes only had 12/71 (17%) recurrence rate vs. 50/135 (37%) for patients with micro-/macrometastasis. On univariate analysis, grade (HR 4.67 95%CI 1.5-14.5, P = 0.008), histology (HR 4.9 95%CI 2.6-9.3, P < 0.001), myometrial invasion (HR 1.9 95%CI 1.04-3.5, P = 0.04), pelvic washing (HR 2.2 95%CI 1.1-4.5, P = 0.03), tumor volume in pelvic LNs (ITC vs. micro-/macrometastasis; HR 0.3 95%CI 0.2-0.7, P = 0.003) were associated with recurrence. On multivariate analysis, only histology was associated with recurrence (HR 7.88 95%CI 3.43-18.13, P < 0.001)., Conclusions: Isolated paraaortic recurrence in stage IIIC1 EC is uncommon. Micro-/macrometastasis were associated with twice the recurrence rate compared to ITC. These data will help clinicians counsel patients with stage IIIC1 EC regarding paraaortic assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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39. Multicenter study comparing oncologic outcomes between two nodal assessment methods in patients with deeply invasive endometrioid endometrial carcinoma: A sentinel lymph node algorithm versus a comprehensive pelvic and paraaortic lymphadenectomy.
- Author
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Schlappe BA, Weaver AL, Ducie JA, Eriksson AGZ, Dowdy SC, Cliby WA, Glaser GE, Soslow RA, Alektiar KM, Makker V, Abu-Rustum NR, Mariani A, and Leitao MM Jr
- Subjects
- Aged, Aged, 80 and over, Algorithms, Carcinoma, Endometrioid mortality, Carcinoma, Endometrioid pathology, Endometrial Neoplasms mortality, Endometrial Neoplasms pathology, Female, Humans, Middle Aged, Neoplasm Invasiveness, Carcinoma, Endometrioid surgery, Endometrial Neoplasms surgery, Lymph Node Excision methods, Sentinel Lymph Node pathology
- Abstract
Objectives: To compare oncologic outcomes in the staging of deeply invasive endometrioid endometrial carcinoma (EEC) using a sentinel lymph node algorithm (SLN) versus pelvic and paraaortic lymphadenectomy to the renal veins (LND); to compare outcomes in node-negative cases., Methods: At two institutions, patients with deeply invasive (≥50% myometrial invasion) EEC were identified. One institution used LND (2004-2008), the other SLN (2005-2013). FIGO stage IV cases were excluded. Clinical characteristics and follow-up data were recorded., Results: 176 patients were identified (LND, 94; SLN, 82). SLN patients were younger (p = 0.003) and had more LVSI (p < 0.001). 9.8% in the SLN and 29.8% in the LND cohorts, respectively, received no adjuvant therapy (p < 0.001). There was no association between type of assessment and recurrence; adjusted hazard ratio (aHR; LND vs. SLN) 0.87 (95%CI 0.40, 1.89) PFS. After controlling for age and adjuvant therapy, there was no association between assessment method and OS (aHR 2.54; 95%CI 0.81, 7.91). The node-negative cohort demonstrated no association between survival and assessment method: aHR 0.69 (95%CI 0.23, 2.03) PFS, 0.81 (95%CI 0.16, 4.22) OS. In the node-negative cohort, neither adjuvant EBRT+/-IVRT (HR 1.63; 95%CI 0.18, 14.97) nor adjuvant chemotherapy+/-EBRT+/-IVRT (HR 0.49; 95%CI 0.11, 2.22) were associated with OS, compared to no adjuvant therapy or IVRT-only., Conclusion: Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2018
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40. Importance of wide re-resection in adult spermatic cord sarcomas: Report on oncologic outcomes at a single institution.
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Murray KS, Vertosick EA, Spaliviero M, Mashni JW Jr, Sjoberg DD, Alektiar KM, Herr HW, Russo P, and Coleman JA
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- Adult, Aged, Female, Follow-Up Studies, Humans, Male, Margins of Excision, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Prognosis, Retrospective Studies, Sarcoma pathology, Sarcoma surgery, Spermatic Cord pathology, Survival Rate, Neoplasm Recurrence, Local mortality, Sarcoma mortality, Spermatic Cord surgery
- Abstract
Background and Objectives: We evaluated the effect of re-resection with wide margins (undertaken because initial resection performed elsewhere was incomplete) on survival in patients with spermatic cord sarcoma (SCS)., Methods: After excluding those with metastatic disease and those not undergoing surgical intervention, the records of 72 consecutive patients treated for SCS between 1981 and 2011 at Memorial Sloan Kettering Cancer Center were reviewed. Recurrence-free survival (RFS) and cancer-specific survival were calculated using the Kaplan-Meier method for comparing between the 48 patients who underwent wide re-resection (WRR) within 5 months of diagnosis and the 24 who did not. The relationship of age, tumor size, tumor histology, adjuvant radiation, and wide re-resection with recurrence and death was assessed by univariate Cox regression., Results: WRR significantly improved RFS (hazard ratio [HR] 0.16, 95%CI 0.07-0.37; P < 0.0001), despite the fact that patients receiving WRR had higher-grade disease. Tumor-positive margins upon WRR were strongly associated with both disease recurrence (HR 5.56; 95%CI 1.14-27.11, P = 0.034) and death from cancer (HR 6.16, 95%CI 1.25-30.29; P = 0.025)., Conclusions: A WRR with negative margins is effective in the management of patients with SCS and leads to improved RFS., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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41. Survival of Patients with Serous Uterine Carcinoma Undergoing Sentinel Lymph Node Mapping.
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Schiavone MB, Scelzo C, Straight C, Zhou Q, Alektiar KM, Makker V, Soslow RA, Iasonos A, Leitao MM, and Abu-Rustum NR
- Subjects
- Aged, Aged, 80 and over, Cystadenocarcinoma, Serous pathology, Cystadenocarcinoma, Serous surgery, Female, Follow-Up Studies, Humans, Lymph Nodes pathology, Middle Aged, Neoplasm Staging, Retrospective Studies, Sentinel Lymph Node pathology, Survival Rate, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms surgery, Cystadenocarcinoma, Serous mortality, Lymph Node Excision mortality, Lymph Nodes surgery, Sentinel Lymph Node surgery, Sentinel Lymph Node Biopsy mortality, Uterine Cervical Neoplasms mortality
- Abstract
Objective: The aim of this study was to determine progression-free survival (PFS) in patients with serous uterine carcinoma undergoing sentinel lymph node (SLN) mapping compared with patients undergoing standard lymphadenectomy., Methods: We retrospectively reviewed all uterine cancer patients treated at our institution from 2005 to 2015. Patients were separated into two cohorts: those who underwent SLN mapping at the time of staging (SLN) and those who underwent routine lymphadenectomy (the non-SLN group). SLN mapping was performed according to institutional protocol, incorporating a surgical algorithm and pathologic ultrastaging., Results: Overall, 248 patients were identified-153 SLN mappings and 95 routine lymphadenectomies (pelvic and/or paraaortic lymph node dissection). No significant difference in age or body mass index was observed between the groups (p = 0.08 and p = 0.9, respectively). Minimally invasive surgery was utilized in 117/153 (77%) SLN patients and 30/95 (32%) non-SLN patients (p = <0.001). Stage distribution for the SLN and non-SLN cohorts demonstrated 106/153 (69%) and 59/95 (62%) patients with stage I/II disease, respectively, and 47/153 (31%) and 36/95 (38%) patients with stage III/IV disease, respectively (p = 0.3). The median number of nodes removed was 12 (range, 1-50) in the SLN cohort versus 21 (range, 1-75) in the non-SLN cohort (p = <0.001). Adjuvant chemotherapy alone or with radiation therapy was administered in 122/153 (80%) SLN patients and 79/95 (83%) non-SLN patients; radiotherapy alone was administered in 12/153 (8%) SLN patients and 7/95 (7%) non-SLN patients (p = 0.8). At a median follow-up of 40 months, the 2-year PFS rates were 77% (95% confidence interval [CI], 68-83%) in the SLN group and 71% (95% CI, 61-79%) in the non-SLN group (p = 0.3)., Conclusions: Incorporation of the SLN mapping algorithm into the staging of uterine serous cancer is feasible and does not appear to compromise prognosis. PFS in patients with uterine serous carcinoma undergoing SLN mapping, followed by adjuvant therapy, was similar to PFS in patients undergoing standard lymphadenectomy and adjuvant therapy.
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- 2017
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42. Intraoperative high-dose-rate brachytherapy: An American Brachytherapy Society consensus report.
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Lloyd S, Alektiar KM, Nag S, Huang YJ, Deufel CL, Mourtada F, and Gaffney DK
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- Child, Colorectal Neoplasms surgery, Consensus, Female, Genital Neoplasms, Female surgery, Head and Neck Neoplasms surgery, Humans, Intraoperative Care, Male, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Sarcoma surgery, United States, Brachytherapy methods, Colorectal Neoplasms radiotherapy, Genital Neoplasms, Female radiotherapy, Head and Neck Neoplasms radiotherapy, Sarcoma radiotherapy
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Purpose: This report presents recommendations from the American Brachytherapy Society for the use of intraoperative high-dose-rate (IOHDR) brachytherapy., Methods and Materials: Members of the American Brachytherapy Society with expertise in IOHDR formulated this document based on their clinical experience and a review of the literature. This report covers the use of IOHDR in colorectal cancer, soft tissue sarcoma, gynecologic cancers, head and neck cancers, and pediatric cancers. This report does not cover intraoperative brachytherapy for breast cancer. Details about treatment planning and delivery are emphasized so this document can serve as a guide to practices implementing this technique., Results: IOHDR brachytherapy is generally most beneficial for patients with either close or positive margins and/or recurrent disease in a previous resection bed or previously irradiated area. IOHDR brachytherapy requires a well-coordinated multidisciplinary team. IOHDR brachytherapy is recommended in the treatment of both recurrent and primary locally advanced disease for colorectal and gynecologic malignancies, soft tissue sarcoma, and selected head and neck and pediatric malignancies. Other techniques such as perioperative fractionated brachytherapy are also acceptable in many cases with some advantages and disadvantages compared to IOHDR., Conclusions: IOHDR brachytherapy is a specialized technique in radiation therapy with unique properties and advantages in cancer control. Special considerations for treatment planning and delivery are outlined herein., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)
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- 2017
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43. American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review.
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Harkenrider MM, Block AM, Alektiar KM, Gaffney DK, Jones E, Klopp A, Viswanathan AN, and Small W Jr
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- Adenocarcinoma, Clear Cell pathology, Advisory Committees, Carcinoma, Endometrioid pathology, Carcinosarcoma pathology, Combined Modality Therapy, Endometrial Neoplasms pathology, Female, Humans, Neoplasm Staging, Neoplasms, Cystic, Mucinous, and Serous pathology, Radiotherapy, Adjuvant methods, Societies, Medical, United States, Adenocarcinoma, Clear Cell radiotherapy, Brachytherapy methods, Carcinoma, Endometrioid radiotherapy, Carcinosarcoma radiotherapy, Endometrial Neoplasms radiotherapy, Hysterectomy, Neoplasm Recurrence, Local, Neoplasms, Cystic, Mucinous, and Serous radiotherapy, Vagina
- Abstract
This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the postoperative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early-stage endometrial cancer patients results in very low rates of vaginal recurrence (0-3.1%) with low rates of late toxicity which are primarily vaginal in nature. Post-Operative Radiation Therapy in Endometrial Cancer 2 (PORTEC-2) supports that VBT results in noninferior rates of vaginal recurrence compared to external beam radiotherapy for the treatment of high-intermediate risk patients. VBT as a boost after external beam radiotherapy, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians prefer joint decision making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multidisciplinary setting, and patients should be counseled properly regarding the risks and benefits of adjuvant therapy., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)
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- 2017
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44. Impact of postoperative intensity-modulated radiation therapy (IMRT) on the rate of bowel obstruction in gynecologic malignancy.
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Shih KK, Hajj C, Kollmeier M, Frey MK, Sonoda Y, Abu-Rustum NR, and Alektiar KM
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- Adult, Aged, Combined Modality Therapy, Female, Genital Neoplasms, Female surgery, Humans, Intestinal Obstruction etiology, Middle Aged, Retrospective Studies, Genital Neoplasms, Female radiotherapy, Intestinal Obstruction epidemiology, Radiotherapy, Intensity-Modulated adverse effects
- Abstract
Objective: The purpose was to determine the potential impact of IMRT on the rate of bowel obstruction (BO), in patients with gynecologic malignancies undergoing postoperative pelvic RT., Methods: We performed a retrospective review of all patients with endometrial or cervical cancer who received postoperative pelvic RT at our institution from 2000 to 2012. Patients who received definitive or palliative RT, or those with BO due to disease progression, were excluded. Standard two-sided statistical tests were used to evaluate for associated risk factors. Kaplan-Meier, Log rank and Cox proportional hazards regression analysis tests were performed for actuarial analysis., Results: A total of 224 patients were identified, 120 (54%) received postoperative pelvic IMRT and 104 (46%) 3-dimentional (3-D) RT. Median follow-up time was 67months. BO was grade 1 (asymptomatic) in 2/228 (0.9%), grade 2 (conservative management) in 4 (1.8%), and grade 3≥ in 4 (1.8%). Overall, the 5-year actuarial rate of BO was 4.8%. The 5-year rate of BO in the IMRT group was 0.9% compared to 9.3% for 3-D RT (p=0.006). Patients with BMI≥30kg/m(2) were less likely to develop BO (2.6% vs. 8.3; p=0.03). On multivariate analysis, only IMRT retained its significance as an independent predictor of less BO (p=0.022)., Conclusions: The use of postoperative IMRT for cervical and endometrial cancer was associated with significant reduction in the rate of bowel obstruction. This difference maintained its statistical significance on multivariate analysis. Such finding if confirmed by others will help further solidify the benefit of IMRT in gynecologic cancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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45. Stereotactic body radiotherapy for metastatic spinal sarcoma: a detailed patterns-of-failure study.
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Leeman JE, Bilsky M, Laufer I, Folkert MR, Taunk NK, Osborne JR, Arevalo-Perez J, Zatcky J, Alektiar KM, Yamada Y, and Spratt DE
- Subjects
- Adult, Aged, Aged, 80 and over, Disease Progression, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Radiotherapy Dosage, Sarcoma diagnostic imaging, Spinal Neoplasms diagnostic imaging, Spinal Neoplasms secondary, Treatment Outcome, Radiosurgery, Sarcoma surgery, Spinal Neoplasms surgery
- Abstract
OBJECTIVE The aim of this study was to report the first detailed analysis of patterns of failure within the spinal axis of patients treated with stereotactic body radiotherapy (SBRT) for sarcoma spine metastases. METHODS Between 2005 and 2012, 88 consecutive patients with metastatic sarcoma were treated with SBRT for 120 spinal lesions. Seventy-one percent of patients were enrolled on prospective institutional protocols. For patients who underwent routine posttreatment total-spine MRI (64 patients, 88 lesions), each site of progression within the entire spinal axis was mapped in relation to the treated lesion. Actuarial rates of local-, adjacent-, and distant-segment failure-free survival (FFS) were calculated using the Kaplan-Meier method. RESULTS The median follow-up for the cohort was 14.4 months, with 81.7% of patients followed up until death. The 12-month actuarial rate of local FFS was 85.9%; however, 83.3% of local failures occurred in conjunction with distant-segment failures. The 12-month actuarial rates of isolated local-, adjacent-, and distant-segment FFS were 98.0%, 97.8%, and 74.7%, respectively. Of patients with any spinal progression (n = 55), only 25.5% (n = 14) had progression at a single vertebral level, with 60.0% (n = 33) having progression at ≥ 3 sites within the spine simultaneously. Linear regression analysis revealed a relationship of decreasing risk of failure with increasing distance from the treated index lesion (R(2) = 0.87), and 54.1% of failures occurred ≥ 5 vertebral levels away. Treatment of the index lesion with a lower biological effective dose (OR 3.2, 95% CI 1.1-9.2) and presence of local failure (OR 18.0, 95% CI 2.1-152.9) independently predicted for distant spine failure. CONCLUSIONS Isolated local- and adjacent-segment failures are exceptionally rare for patients with metastatic sarcoma to the spine treated with SBRT, thereby affirming the treatment of the involved level only. The majority of progression within the spinal axis occurs ≥ 5 vertebral levels away. Thus, total-spine imaging is necessary for surveillance posttreatment.
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- 2016
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46. Low-Volume Lymph Node Metastasis Discovered During Sentinel Lymph Node Mapping for Endometrial Carcinoma.
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St Clair CM, Eriksson AG, Ducie JA, Jewell EL, Alektiar KM, Hensley ML, Soslow RA, Abu-Rustum NR, and Leitao MM Jr
- Subjects
- Adenocarcinoma, Clear Cell surgery, Adult, Aged, Aged, 80 and over, Cystadenocarcinoma, Serous surgery, Endometrial Neoplasms surgery, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Invasiveness, Neoplasm Micrometastasis, Neoplasm Recurrence, Local surgery, Neoplasm Staging, Prognosis, Sentinel Lymph Node surgery, Sentinel Lymph Node Biopsy, Survival Rate, Adenocarcinoma, Clear Cell secondary, Cystadenocarcinoma, Serous secondary, Endometrial Neoplasms pathology, Neoplasm Recurrence, Local pathology, Sentinel Lymph Node pathology
- Abstract
Purpose: The aim of this study was to characterize treatment patterns and oncologic outcomes in patients with low-volume lymph node metastasis (isolated tumor cells [ITCs] and micrometastasis [MM]) discovered during sentinel lymph node (SLN) mapping for endometrial carcinoma., Methods: We identified endometrial cancer cases treated surgically from September 2005 to April 2013 in which SLN mapping was performed. MM was defined as tumor within a lymph node measuring >0.2 mm but <2.0 mm, and ITCs were those measuring ≤0.2 mm., Results: Overall, 844 patients, with a median age of 61 years (range 30-90), met the inclusion criteria. Histology was as follows: endometrioid, 724 (85.8 %) patients; serous, 104 (12.3 %) patients; and clear cell, 16 (1.9 %) patients. The median number of lymph nodes resected was six (range 0-60), and the median number of SLNs was two (range 0-15). Overall, 753 (89.2 %) patients were node-negative, 23 (2.7 %) had ITCs only, 21 (2.5 %) had MM only, and 47 (5.6 %) had macrometastasis. Adjuvant chemotherapy was administered to 106 (14 %) of 753 node-negative patients, 19 (83 %) of 23 patients with ITCs, 17 (81 %) of 21 patients with MM, and 42 (89 %) of 47 with macrometastasis. Median follow-up was 26 months (range 0-108). Three-year recurrence-free survival was as follows: node-negative patients, 90 % (±1.5); ITCs only, 86 % (±9.4); MM only, 86 % (±9.7); and macrometastasis, 71 % (±7.2) [p < 0.001]., Conclusions: Patients with ITCs and MM frequently received adjuvant chemotherapy and had improved oncologic outcomes in comparison to those with macrometastasis to the lymph nodes. Further prospective study is needed to determine optimal post-resection management in patients with ITCs or MM alone.
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- 2016
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47. An Assessment of Prognostic Factors, Adjuvant Treatment, and Outcomes of Stage IA Polyp-Limited Versus Endometrium-Limited Type II Endometrial Carcinoma.
- Author
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Liang LW, Perez AR, Cangemi NA, Zhou Q, Iasonos A, Abu-Rustum N, Alektiar KM, and Makker V
- Subjects
- Adenocarcinoma, Clear Cell pathology, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Cystadenocarcinoma, Serous pathology, Endometrial Neoplasms pathology, Female, Follow-Up Studies, Humans, Hysterectomy, Middle Aged, Neoplasm Grading, Neoplasm Invasiveness, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Survival Rate, Adenocarcinoma, Clear Cell therapy, Chemotherapy, Adjuvant, Cystadenocarcinoma, Serous therapy, Endometrial Neoplasms therapy, Neoplasm Recurrence, Local therapy, Polyps, Radiotherapy, Adjuvant
- Abstract
Objective: To determine clinical outcomes in patients with stage IA polyp-limited versus endometrium-limited high-grade (type II) endometrial carcinoma (EC)., Methods: We identified all cases of stage IA polyp-limited or endometrium-limited high-grade EC (FIGO grade 3 endometrioid, serous, clear cell, or mixed) who underwent simple hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and para-aortic lymph node dissection and received adjuvant treatment at our institution from October 1995 to November 2012. Progression-free survival (PFS) and overall survival (OS) by histology, adjuvant therapy, and polyp-limited versus endometrium-limited disease status were determined using log-rank test. We analyzed 3 treatment groups: patients who received chemotherapy with or without radiation therapy (RT) (intravaginal or pelvic); patients who received RT (intravaginal RT or pelvic RT) alone; and patients who received no adjuvant treatment., Results: In all, 85 women underwent hysterectomy/salpingo-oophorectomy; all were surgically staged with lymph node assessment and had stage IA EC with no lymphovascular or myometrial invasion. Median follow-up for survivors was 46.5 months (range, 1.98-188.8 months). Forty-nine patients (57.6%) had polyp-limited disease, and 36 (42.4%) had endometrium-limited disease. There were no significant differences in clinicopathologic characteristics between patients within the 3 treatment groups with regard to age at diagnosis, mean body mass index, ECOG (Eastern Cooperative Oncology Group) performance status, polyp-limited or endometrium-limited disease, diabetes, or race. The 3-year PFS rate was 94.9% and the 3-year OS rate was 98.8%. Univariate PFS and OS analysis revealed that age was a relevant prognostic factor (PFS hazard ratio [95% confidence interval], 1.13 [1.02-1.25]; P = 0.022; OS hazard ratio [95% confidence interval], 1.19 [1.02-1.38]; P = 0.03). Adjuvant treatment did not impact outcomes., Conclusions: Clinical outcomes of surgical stage IA type II polyp- or endometrium-limited high-grade epithelial EC are equally favorable regardless of histologic subtype or adjuvant therapy received. The benefit of adjuvant therapy in this select group remains to be determined.
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- 2016
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48. High- and low-dose-rate intraoperative radiotherapy for thoracic malignancies resected with close or positive margins.
- Author
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Fleming C, Rimner A, Cohen GN, Woo KM, Zhang Z, Rosenzweig KE, Alektiar KM, Zelefsky MJ, Bains MS, and Wu AJ
- Subjects
- Adult, Aged, Humans, Intraoperative Care, Lung Neoplasms surgery, Middle Aged, Neoplasm, Residual, Radiotherapy Dosage, Retrospective Studies, Survival Rate, Young Adult, Brachytherapy adverse effects, Lung Neoplasms radiotherapy, Neoplasm Recurrence, Local prevention & control
- Abstract
Purpose: Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques., Methods and Materials: We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure., Results: Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy., Conclusions: IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)
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- 2016
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49. Early magnetic resonance imaging biomarkers to predict local control after high dose stereotactic body radiotherapy for patients with sarcoma spine metastases.
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Spratt DE, Arevalo-Perez J, Leeman JE, Gerber NK, Folkert M, Taunk NK, Alektiar KM, Karimi S, Lyo JK, Tap WD, Bilsky MH, Laufer I, Yamada Y, and Osborne JR
- Subjects
- Adult, Aged, Cohort Studies, Contrast Media, Disease Progression, Female, Fibrosarcoma diagnostic imaging, Fibrosarcoma secondary, Fibrosarcoma surgery, Hemangiopericytoma secondary, Hemangiopericytoma surgery, Humans, Leiomyosarcoma diagnostic imaging, Leiomyosarcoma secondary, Leiomyosarcoma surgery, Liposarcoma, Myxoid diagnostic imaging, Liposarcoma, Myxoid secondary, Liposarcoma, Myxoid surgery, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Reproducibility of Results, Retrospective Studies, Rhabdomyosarcoma diagnostic imaging, Rhabdomyosarcoma secondary, Rhabdomyosarcoma surgery, Sarcoma secondary, Sarcoma surgery, Spinal Neoplasms secondary, Spinal Neoplasms surgery, Hemangiopericytoma diagnostic imaging, Radiosurgery, Sarcoma diagnostic imaging, Spinal Neoplasms diagnostic imaging
- Abstract
Background Context: Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control., Purpose: This study aimed to identify early magnetic resonance imaging (MRI) biomarkers to predict local control after SBRT for patients with sarcoma spine metastases., Study Design/setting: This study used a retrospective case series at a large tertiary cancer center., Patient Sample: From 2011 to 2014, 9 consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) both pre- and post-SBRT., Outcome Measure: Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multiparametric magnetic resonance imaging (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control., Methods: All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t tests were used to compare groups. p<.05 was deemed statistically significant., Results: The median time from SBRT until posttreatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. The Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared with pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of "worsening," "no change," or "improvement," respectively, by both radiologists' graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2=0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared with the mpMRI score change post-SBRT (R2=0.026)., Conclusions: We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at 2 months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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50. Survival of Patients with Uterine Carcinosarcoma Undergoing Sentinel Lymph Node Mapping.
- Author
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Schiavone MB, Zivanovic O, Zhou Q, Leitao MM Jr, Levine DA, Soslow RA, Alektiar KM, Makker V, Iasonos A, and Abu-Rustum NR
- Subjects
- Aged, Aged, 80 and over, Carcinosarcoma pathology, Carcinosarcoma surgery, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prognosis, Prospective Studies, Survival Rate, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms surgery, Carcinosarcoma mortality, Lymph Node Excision mortality, Lymph Nodes pathology, Sentinel Lymph Node Biopsy mortality, Uterine Cervical Neoplasms mortality
- Abstract
Purpose: This study was designed to evaluate the outcome of patients with uterine carcinosarcoma undergoing sentinel lymph node (SLN) mapping., Methods: A prospectively maintained database was reviewed for all women with uterine cancer treated at our institution from January 1, 1998 to August 31, 2014. Patients were grouped based on whether they had undergone SLN mapping or routine lymphadenectomy at the time of staging. SLN evaluation was performed according to a standard institutional protocol that incorporates a surgical algorithm and pathologic ultrastaging., Results: We identified 136 patients with uterine carcinosarcoma who had undergone lymph node evaluation; 48 had surgical staging with SLN mapping and 88 had routine lymphadenectomy consisting of pelvic and/or para-aortic lymph node dissection. Stage distribution for the SLN group included: stage I, 31 (65 %); stage II, 1 (2 %); stage III, 11 (23 %); stage IV, 5 (10 %). Stage distribution for the non-SLN group included: stage I, 48 (55 %); stage II, 4 (4 %); stage III, 19 (22 %); stage IV, 17 (19 %) (p = 0.4). Median number of lymph nodes removed was 8 and 20, respectively (p ≤ 0.001). Median number of positive nodes was similar between the groups (p = 0.2). Of the 67 patients who had a documented recurrence, 14 of 20 (70 %) in the SLN and 34 of 47 (74 %) in the non-SLN group demonstrated a distant/multifocal pattern of recurrence. There was no difference in median progression-free survival between the groups (23 vs. 23.2 months, respectively; p = 0.7)., Conclusions: Progression-free survival in women with uterine carcinosarcoma undergoing SLN mapping with adjuvant therapy appears similar to that of patients treated before the incorporation of the SLN protocol. Additional prospective studies with longer follow-up are necessary to validate these early results.
- Published
- 2016
- Full Text
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