654 results on '"Nadeem R. Abu-Rustum"'
Search Results
2. Uterine washings as a novel method for early detection of ovarian cancer: Trials and tribulations
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Tiffany Y. Sia, Zvi Yaari, Ron Feiner, Evan Smith, Arnaud Da Cruz Paula, Pier Selenica, Sital Doddi, Dennis S. Chi, Nadeem R. Abu-Rustum, Douglas A. Levine, Britta Weigelt, Martin Fleisher, Lakshmi V. Ramanathan, Daniel A. Heller, and Kara Long Roche
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Ovarian cancer ,Intrauterine lavage ,Early detection ,Gynecology and obstetrics ,RG1-991 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Given the tubal origin of high-grade serous ovarian cancer (HGSC), we sought to investigate intrauterine lavage (IUL) as a novel method of biomarker detection. IUL and serum samples were collected from patients with HGSC or benign pathology. Although CA-125 and HE4 concentrations were significantly higher in IUL samples compared to serum, they were similar between IUL samples from patients with HGSC vs benign conditions. In contrast, CA-125 and HE4 serum concentrations differed between HGSC and benign pathology (P =.002 for both). IUL and tumor samples from patients with HGSC were subjected to targeted panel sequencing and droplet digital PCR (ddPCR). Tumor mutations were found in 75 % of matched IUL samples. Serum CA-125 and HE4 biomarker levels allowed for better differentiation of HGSC and benign pathology compared to IUL samples. We believe using IUL for early detection of HGSC requires optimization, and current strategies should focus on prevention until early detection strategies improve.
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- 2024
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3. Recommendations for the prevention, screening, diagnosis, staging, and management of cervical cancer in areas with limited resources: Report from the International Gynecological Cancer Society consensus meeting
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Fernando Cotait Maluf, Graziela Zibetti Dal Molin, Andreia Cristina de Melo, Eduardo Paulino, Douglas Racy, Robson Ferrigno, Pedro Luiz Serrano Uson Junior, Reitan Ribeiro, Renato Moretti, Jose Carlos Sadalla, Angelica Nogueira-Rodrigues, Filomena Marino Carvalho, Glauco Baiocchi, Donato Callegaro-Filho, and Nadeem R. Abu-Rustum
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cervical cancer ,radiotherapy ,chemotherapeutics ,limited resource area ,limited resource countries ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionNearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical cancer in limited resources countries.MethodsThe expert panel, composed by invited specialists from 38 developing countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East, convened in Rio de Janeiro in September 2019, during the Global Meeting of the International Gynecological Cancer Society (IGCS). Panel members considered the published scientific evidence and their practical experience on the topics, as well as the perceived cost-effectiveness of, and access to, the available interventions. The focus of the recommendations was on geographic regions rather than entire countries because medical practice varies considerably in the countries represented. Resource limitation was qualified as limited access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or overall funding for provision of state-of-the-art care. Consensus was defined as at least 75% of the voting members selecting a particular answer of the multiple-choice questionnaire, whereas the majority vote was considered as 50% to 74.9%.ResultsConsensus was reached for 25 of the 121 (20.7%) questions, whereas for 54 (44.6%) questions there was one option garnering between 50% to 74.9% of votes (majority votes). For the remaining questions, considerable heterogeneity in responses was observed.DiscussionThe implementation of international guidelines is challenging in countries with resource limitations or unique health-care landscapes. The development of guidelines by the health care providers in those regions is more reflective of the reality on the ground and may improve medical practice and patient care. However, challenges remain toward achieving that goal at political, economic, social, and medical levels.
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- 2022
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4. The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas
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Lea A. Moukarzel, Lorenzo Ferrando, Arnaud Da Cruz Paula, David N. Brown, Felipe C. Geyer, Fresia Pareja, Salvatore Piscuoglio, Anastasios D. Papanastasiou, Nicola Fusco, Caterina Marchiò, Nadeem R. Abu‐Rustum, Rajmohan Murali, Edi Brogi, Hannah Y. Wen, Larry Norton, Robert A. Soslow, Anne Vincent‐Salomon, Jorge S. Reis‐Filho, and Britta Weigelt
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breast cancer ,carcinosarcoma ,homologous recombination DNA repair ,metaplastic ,uterine cancer ,whole‐exome sequencing ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Metaplastic breast carcinoma (MBC) and uterine carcinosarcoma (UCS) are rare aggressive cancers, characterized by an admixture of adenocarcinoma and areas displaying mesenchymal/sarcomatoid differentiation. We sought to define whether MBCs and UCSs harbor similar patterns of genetic alterations, and whether the different histologic components of MBCs and UCSs are clonally related. Whole‐exome sequencing (WES) data from MBCs (n = 35) and UCSs (n = 57, The Cancer Genome Atlas) were reanalyzed to define somatic genetic alterations, altered signaling pathways, mutational signatures, and genomic features of homologous recombination DNA repair deficiency (HRD). In addition, the carcinomatous and sarcomatous components of an additional cohort of MBCs (n = 11) and UCSs (n = 6) were microdissected separately and subjected to WES, and their clonal relatedness was assessed. MBCs and UCSs harbored recurrent genetic alterations affecting TP53, PIK3CA, and PTEN, similar patterns of gene copy number alterations, and an enrichment in alterations affecting the epithelial‐to‐mesenchymal transition (EMT)‐related Wnt and Notch signaling pathways. Differences were observed, however, including a significantly higher prevalence of FAT3 and FAT1 somatic mutations in MBCs compared to UCSs, and conversely, UCSs significantly more frequently harbored somatic mutations affecting FBXW7 and PPP2R1A as well as HER2 amplification than MBCs. Genomic features of HRD and biallelic alterations affecting bona fide HRD‐related genes were found to be more prevalent in MBCs than in UCSs. The distinct histologic components of MBCs and UCSs were clonally related in all cases, with the sarcoma component likely stemming from a minor subclone of the carcinoma component in the samples with interpretable chronology of clonal evolution. Despite the similar histologic features and pathways affected by genetic alterations, UCSs differ from MBCs on the basis of FBXW7 and PPP2R1A mutations, HER2 amplification, and lack of HRD, supporting the notion that these entities are more than mere phenocopies of the same tumor type in different anatomical sites.
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- 2021
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5. Assessment of wound perfusion with near-infrared angiography: A prospective feasibility study
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Beryl L. Manning-Geist, Renee A. Cowan, Brooke Schlappe, Kenya Braxton, Yukio Sonoda, Kara Long Roche, Mario M. Leitao Jr, Dennis S. Chi, Oliver Zivanovic, Nadeem R. Abu-Rustum, and Jennifer J. Mueller
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Indocyanine green ,Wound perfusion ,Near-infrared angiography ,Laparotomy ,Skin closure ,Gynecology and obstetrics ,RG1-991 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: To assess the feasibility of quantitatively measuring skin perfusion before and after suture or staple skin closure of vertical laparotomies using indocyanine green (ICG) uptake with near-infrared angiography. Methods: This was a prospective, non-randomized feasibility study of patients undergoing surgery with a gynecologic oncology service from 2/2018–8/2019. Feasibility was defined as the ability to quantitatively measure ICG uptake adjacent to the wound at the time of skin closure in ≥ 80% of patients. Patients were assigned suture or staple skin closure in a sequential, non-randomized fashion. Skin perfusion was recorded using a near-infrared imaging system after ICG injection and measured by video analysis at predefined points before and after skin closure. Clinicodemographic, pre- and intraoperative details, and surgical secondary events were recorded. Results: Of 20 participants, 10 were assigned staple closure and 10 suture closure. Two patients (10%) achieved objective quantification of ICG fluorescence before and after laparotomy closure, failing the predefined feasibility threshold of ≥ 80%. Reasons for failed quantification included overexposure (12), insufficient ICG signal uptake (6), and insufficient video quality (2). Near-infrared angiography wound perfusion was subjectively appreciated intraoperatively in 85% (17/20) of patients before and after wound closure. Conclusions: Objective assessment of laparotomy skin closure with near-infrared angiography–measured perfusion did not meet the pre-specified feasibility threshold. Adjustments to the protocol to minimize overexposure may be warranted. The ability to subjectively appreciate ICG perfusion with near-infrared angiography suggests a possible role for near-infrared angiography in the real-time intraoperative assessment of wound perfusion, particularly in high-risk patients.
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- 2022
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6. Machine learning-based prediction of microsatellite instability and high tumor mutation burden from contrast-enhanced computed tomography in endometrial cancers
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Harini Veeraraghavan, Claire F. Friedman, Deborah F. DeLair, Josip Ninčević, Yuki Himoto, Silvio G. Bruni, Giovanni Cappello, Iva Petkovska, Stephanie Nougaret, Ines Nikolovski, Ahmet Zehir, Nadeem R. Abu-Rustum, Carol Aghajanian, Dmitriy Zamarin, Karen A. Cadoo, Luis A. Diaz, Mario M. Leitao, Vicky Makker, Robert A. Soslow, Jennifer J. Mueller, Britta Weigelt, and Yulia Lakhman
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Medicine ,Science - Abstract
Abstract To evaluate whether radiomic features from contrast-enhanced computed tomography (CE-CT) can identify DNA mismatch repair deficient (MMR-D) and/or tumor mutational burden-high (TMB-H) endometrial cancers (ECs). Patients who underwent targeted massively parallel sequencing of primary ECs between 2014 and 2018 and preoperative CE-CT were included (n = 150). Molecular subtypes of EC were assigned using DNA polymerase epsilon (POLE) hotspot mutations and immunohistochemistry-based p53 and MMR protein expression. TMB was derived from sequencing, with > 15.5 mutations-per-megabase as a cut-point to define TMB-H tumors. After radiomic feature extraction and selection, radiomic features and clinical variables were processed with the recursive feature elimination random forest classifier. Classification models constructed using the training dataset (n = 105) were then validated on the holdout test dataset (n = 45). Integrated radiomic-clinical classification distinguished MMR-D from copy number (CN)-low-like and CN-high-like ECs with an area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI 0.58–0.91). The model further differentiated TMB-H from TMB-low (TMB-L) tumors with an AUROC of 0.87 (95% CI 0.73–0.95). Peritumoral-rim radiomic features were most relevant to both classifications (p ≤ 0.044). Radiomic analysis achieved moderate accuracy in identifying MMR-D and TMB-H ECs directly from CE-CT. Radiomics may provide an adjunct tool to molecular profiling, especially given its potential advantage in the setting of intratumor heterogeneity.
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- 2020
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7. Identification of recurrent FHL2-GLI2 oncogenic fusion in sclerosing stromal tumors of the ovary
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Sarah H. Kim, Arnaud Da Cruz Paula, Thais Basili, Higinio Dopeso, Rui Bi, Fresia Pareja, Edaise M. da Silva, Rodrigo Gularte-Mérida, Zhen Sun, Sho Fujisawa, Caitlin G. Smith, Lorenzo Ferrando, Ana Paula Martins Sebastião, Yonina Bykov, Anqi Li, Catarina Silveira, Charles W. Ashley, Anthe Stylianou, Pier Selenica, Wesley R. Samore, Achim A. Jungbluth, Dmitriy Zamarin, Nadeem R. Abu-Rustum, Kristian Helin, Robert A. Soslow, Jorge S. Reis-Filho, Esther Oliva, and Britta Weigelt
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Science - Abstract
Little is known about the genetics of sclerosing stromal tumor of the ovary, a rare type of sex cord-stromal tumor. Here, the authors use sequencing strategies to show that in a cohort of 26 tumor samples 65% carry a FHL2-GLI2 fusion gene and demonstrate in vitro that the fusion gene has oncogenic properties.
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- 2020
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8. Pattern of disease and response to pembrolizumab in recurrent cervical cancer
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Kathryn M. Miller, Olga T. Filippova, Sara A. Hayes, Nadeem R. Abu-Rustum, Carol Aghajanian, Vance Broach, Lora H. Ellenson, Pier Selenica, Elizabeth L. Jewell, Chrisann Kyi, Yuliya Lakhman, Jennifer J. Mueller, Roisin E. O'Cearbhaill, Kay J. Park, Yukio Sonoda, Dmitriy Zamarin, Britta Weigelt, Mario M. Leitao, Jr, and Claire F. Friedman
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Immune checkpoint blockade ,Cervical cancer ,PD-1 resistance ,Tumor microenvironment ,Gynecology and obstetrics ,RG1-991 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: Since the approval of pembrolizumab for advanced or recurrent PD-L1 positive (CPS > 1%) cervical cancer, the clinical characteristics associated with response have remained undefined. We sought to characterize the clinicopathologic features of patients with advanced cervical cancer at our institution who derived durable clinical benefit from treatment with pembrolizumab. Methods: We conducted a retrospective cohort study of 14 patients with recurrent or metastatic cervical cancer who received pembrolizumab monotherapy from August 2017 to November 2019 and were followed until November 1, 2020. Reviewed clinical data included age, histology, tumor molecular profiling results, stage at diagnosis, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 therapy, and outcomes. Treatment response was evaluated by computed tomography using RECIST v1.1 criteria. Results: The objective response rate was 21% (n = 3), including two partial responses and one complete response. Two patients (14%) had stable disease of six months or greater, for an observed durable clinical benefit rate of 36%. When stratified by those who derived clinical benefit, metastatic spread to lung and/or lymph node only at baseline was associated with improved response to pembrolizumab (n = 7, p = 0.02) and associated with significantly improved PFS and OS. Tumor mutational burden was higher in those with durable clinical benefit compared to non-responders (median 12.7 vs. 3.5 mutations/megabase, p = 0.03). Conclusions: Our findings highlight clinical features that may select for a population most likely to benefit from pembrolizumab monotherapy and underscores the need for identification of additional biomarkers of response.
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- 2021
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9. Quaternary and beyond cytoreduction: An updated and expanded analysis
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Beryl L. Manning-Geist, Dennis S. Chi, Kara Long Roche, Oliver Zivanovic, Yukio Sonoda, Ginger J. Gardner, Roisin E. O'Cearbhaill, Nadeem R. Abu-Rustum, and Mario M. Leitao, Jr.
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Ovarian cancer ,Cytoreduction ,Quaternary cytoreduction ,Quinary cytoreduction ,Senary cytoreduction ,Gynecology and obstetrics ,RG1-991 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: We sought to describe the clinicopathologic features and outcomes of patients undergoing quaternary, quinary, or senary cytoreductive surgery for ovarian cancer. Methods: We retrospectively identified patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who underwent quaternary or beyond cytoreduction at our institution between 1/1/1989 and 12/31/2020. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test. Cox-proportional hazards regression was used to detect variables associated with survival. Results: Twenty patients underwent 24 quaternary (n = 20), quinary (n = 3), or senary (n = 1) cytoreductive surgeries. Most patients had high-grade (89.5%) and serous (75.0%) tumors. At the time of quaternary cytoreduction, 44.7% of patients had single-site disease and 85.0% achieved a complete gross resection. After quaternary cytoreduction, 34.8% of patients developed a surgical complication, most of which were grade 1 or 2. Postoperatively, 80.0% of patients received additional medical treatment and 20.0% underwent observation alone. On univariate analysis, factors associated with progression-free survival included prolonged treatment-free interval (TFI), platinum sensitivity, and complete gross resection. Factors associated with disease-specific survival included platinum sensitivity and complete gross resection. Quinary and senary surgeries were associated with similar safety profiles, with no surgical complications reported. After quinary surgery, progression-free survival ranged from 5.0 to 216.0 months. Conclusions: In carefully selected patients, quaternary cytoreduction may be associated with acceptable morbidity and a relatively robust disease-specific survival. Patients who present to surgery with a prolonged TFI and achieve a complete gross resection likely derive the greatest benefit from quaternary surgery.
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- 2021
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10. Case report: Sentinel lymph node mapping of endometrial carcinoma occurring in uterine didelphys
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Dib Sassine, Sara Moufarrij, Anjelica Hodgson, Sarah Ehmann, Nadeem R. Abu-Rustum, Sarah Chiang, and Elizabeth L. Jewell
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Endometrial carcinoma ,Lymphadenectomy ,Uterine didelphys ,Sentinel lymph node mapping ,Gynecology and obstetrics ,RG1-991 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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11. Brain metastases in patients with low-grade endometrial carcinoma
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Paulina Cybulska, Marina Stasenko, Raanan Alter, Vicky Makker, Karen A. Cadoo, Yukio Sonoda, Nadeem R. Abu-Rustum, Jennifer J. Mueller, and Mario M. Leitao, Jr.
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Gynecology and obstetrics ,RG1-991 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: To report characteristics of patients with low-grade endometrioid endometrial carcinoma (EC) who develop brain metastases. Methods: We retrospectively identified all patients treated at our institution for FIGO grades 1/2 EC from 1/2000–12/2016, who developed brain metastases. Electronic medical records were reviewed, data abstracted. Overall survival (OS) was determined from time of brain metastases to death or last follow-up. Appropriate statistical tests were used. Results: Of 3052 patients, 23 (9, grade 1; 14, grade 2) developed brain metastases (incidence = 0.75%). Presentation at initial diagnosis: median age = 61.3 years (range, 41–81); median BMI = 29.8 kg/m2 (range, 20.3–42.6 kg/m2); distribution by stage: I, 15/23 (65%); II, 2/23 (8.7%); III, 3/23 (13.0%); IV, 3 (13.0%). None showed clinical evidence of brain metastases at presentation. Median time to diagnosis of brain metastases = 29.7 months (range, 6–145); median age = 64.6 years (range, 47.5–86.5). Brain metastases were the first, isolated site of recurrence in 2/23 (9%). All presented with neurological symptoms. Six (26%) had solitary brain lesions. Seventeen (74%) received treatment; 6 (28%), supportive care only. Median OS for patients receiving any treatment = 5.8 months (95% CI, 1.6–10.0), versus 2.4 months (95% CI, 1.5–3.3; p = .04) for best supportive care. Conclusion: Brain metastases in low-grade EC is rare, prognosis generally poor. Compared to supportive care only, any treatment results in more favorable outcomes. Keywords: Brain metastases, Endometrial carcinoma, Low-grade endometrial carcinoma
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- 2018
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12. Laparoscopy with or without robotic assistance does not negatively impact long-term oncologic outcomes in patients with uterine serous carcinoma
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Tiffany Y. Sia, Derman Basaran, Christian Dagher, Dib Sassine, Benny Brandt, Kendall Rosalik, Jennifer J. Mueller, Vance Broach, Vicky Makker, Robert A. Soslow, Nadeem R. Abu-Rustum, and Mario M. Leitao
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Oncology ,Obstetrics and Gynecology - Published
- 2023
13. Integration of clinical sequencing and immunohistochemistry for the molecular classification of endometrial carcinoma
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Eric Rios-Doria, Amir Momeni-Boroujeni, Claire F. Friedman, Pier Selenica, Qin Zhou, Michelle Wu, Antonio Marra, Mario M. Leitao, Alexia Iasonos, Kaled M. Alektiar, Yukio Sonoda, Vicky Makker, Elizabeth Jewell, Ying Liu, Dennis Chi, Dimitry Zamarin, Nadeem R. Abu-Rustum, Carol Aghajanian, Jennifer J. Mueller, Lora H. Ellenson, and Britta Weigelt
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Oncology ,Obstetrics and Gynecology - Published
- 2023
14. Germline drivers of gynecologic carcinosarcomas
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Tiffany Y. Sia, Sushmita B. Gordhandas, Ozge Birsoy, Yelena Kemel, Anna Maio, Erin Salo-Mullen, Margaret Sheehan, Martee L. Hensley, Maria Rubinstein, Vicky Makker, Rachel N. Grisham, Roisin E. O’Cearbhaill, Kara Long Roche, Jennifer J. Mueller, Mario M. Leitao, Yukio Sonoda, Dennis S. Chi, Nadeem R. Abu-Rustum, Michael F. Berger, Lora H. Ellenson, Alicia Latham, Zsofia Stadler, Kenneth Offit, Carol Aghajanian, Britta Weigelt, Diana Mandelker, and Ying L. Liu
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Oncology ,Obstetrics and Gynecology - Published
- 2023
15. Landscape of chromatin remodeling gene alterations in endometrial carcinoma
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Amir Momeni-Boroujeni, Chad Vanderbilt, Elham Yousefi, Nadeem R. Abu-Rustum, Carol Aghajanian, Robert A. Soslow, Lora H. Ellenson, Britta Weigelt, and Rajmohan Murali
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Oncology ,Obstetrics and Gynecology - Published
- 2023
16. Impact of immune infiltration signatures on prognosis in endometrial carcinoma is dependent on the underlying molecular subtype
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Kimberly Dessources, Lorenzo Ferrando, Qin C. Zhou, Alexia Iasonos, Nadeem R. Abu-Rustum, Jorge S. Reis-Filho, Nadeem Riaz, Dmitriy Zamarin, and Britta Weigelt
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Oncology ,Obstetrics and Gynecology - Published
- 2023
17. Predicting outcomes in female germ cell tumors using a modified International Germ Cell Cancer Collaborative Group classification system to guide management
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Ying L. Liu, Beryl L. Manning-Geist, Andrea Knezevic, Luxue Deng, Maria Bromberg, Samuel A. Funt, Jane L. Meisel, Oliver Zivanovic, Kara Long Roche, Yukio Sonoda, Ginger J. Gardner, Rachel N. Grisham, Roisin E. O'Cearbhaill, William P. Tew, Nadeem R. Abu-Rustum, Dennis S. Chi, Carol Aghajanian, and Darren R. Feldman
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Oncology ,Obstetrics and Gynecology - Published
- 2023
18. A modern-day experience with Brunschwig's operation: Outcomes associated with pelvic exenteration
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Eric, Rios-Doria, Olga T, Filippova, Alli M, Straubhar, Andrew, Chi, Ibraheem, Awowole, Jaspreet, Sandhu, Vance, Broach, Jennifer J, Mueller, Ginger J, Gardner, Elizabeth L, Jewell, Oliver, Zivanovic, Mario M, Leitao, Kara, Long Roche, Nadeem R, Abu-Rustum, and Yukio, Sonoda
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Oncology ,Obstetrics and Gynecology - Abstract
To evaluate postoperative and oncologic outcomes associated with pelvic exenteration for non-ovarian gynecologic malignancies.This was a retrospective review of patients who underwent pelvic exenteration for non-ovarian gynecologic malignancies at our institution from 1/1/2010-12/31/2019. Palliative exenteration cases were excluded from survival analysis. Postoperative complications were early (≤30 days) or late (31-180 days). Complications were graded using a validated institutional scale. Major complications were considered grade ≥ 3. Categorical variables were compared using the chi-square test, and the Kaplan-Meier method was used for survival analysis.Of 100 patients identified, 89 underwent pelvic exenteration for recurrent disease, 5 for palliation, 5 for primary disease, and 1 for persistent disease. Thirty percent had cervical, 27% vulvar, 24% uterine, and 19% vaginal cancer. Sixty-two percent underwent total, 30% anterior, and 8% posterior exenteration. No deaths occurred intraoperatively or within 30 days of surgery. Six patients died after 30 days. Ninety-seven experienced a perioperative complication-49 early, 1 late, and 47 both. Fifty experienced a major complication-22 (44%) early, 19 (38%) late, and 9 (18%) both. No variables were statistically associated with complication development. The 3-year progression-free survival rate was 61.0%; the 3-year overall survival rate was 61.6%. Of 58 surviving patients, 16 (28%) and 4 (7%) were alive after 5 and 10 years, respectively.The overall complication rate for pelvic exenteration remains high. No variables demonstrated association with complication development as the rate was nearly 100%. The low rate of perioperative mortality is likely due to improved perioperative care.
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- 2022
19. Progress in surgical oncology: Gynecology perspective
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Nadeem R, Abu-Rustum
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Gynecologic Surgical Procedures ,Surgical Oncology ,Oncology ,Genital Neoplasms, Female ,Gynecology ,Humans ,Female ,Surgery ,General Medicine ,Medical Oncology - Abstract
Since its founding in 1884, Memorial Sloan Kettering Cancer Center (MSK) has set standards of care in gynecologic oncology. Over time, the MSK treatment approach evolved into an effort of gynecologic oncology experts across disciplines. As the anatomic field of gynecologic oncology surgery expanded beyond the pelvis, experts in other fields of cancer care, including our hepatobiliary and thoracic colleagues, joined this interprofessional effort. Here, we describe recent, key contributions to surgical gynecologic oncology by the Gynecology Service at MSK.
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- 2022
20. Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system
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Simona Stolnicu, Lien Hoang, Noorah Almadani, Louise De Brot, Glauco Baiocchi, Graziele Bovolim, Maria Jose Brito, Georgia Karpathiou, Antonio Ieni, Esther Guerra, Takako Kiyokawa, Pavel Dundr, Carlos Parra-Herran, Sofia Lérias, Ana Felix, Andres Roma, Anna Pesci, Esther Oliva, Kay J. Park, Robert A. Soslow, and Nadeem R. Abu-Rustum
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Lymphatic Metastasis ,Carcinoma ,Humans ,Uterine Cervical Neoplasms ,Female ,Adenocarcinoma ,Prognosis ,Neoplasm Staging ,Retrospective Studies ,Pathology and Forensic Medicine - Abstract
Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.
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- 2022
21. Impact of obesity and white adipose tissue inflammation on the omental microenvironment in endometrial cancer
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Lea A. Moukarzel, Lorenzo Ferrando, Anthe Stylianou, Stephanie Lobaugh, Michelle Wu, Silvana Pedra Nobre, Alexia Iasonos, Gabriele Zoppoli, Dilip D. Giri, Nadeem R. Abu‐Rustum, Vance A. Broach, Neil M. Iyengar, Britta Weigelt, and Vicky Makker
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Inflammation ,Metabolic Syndrome ,Cancer Research ,Oncology ,Adipose Tissue, White ,Tumor Microenvironment ,Humans ,Female ,Obesity ,Biomarkers ,Endometrial Neoplasms - Abstract
A complex relationship between adipose tissue and malignancy, involving an inflammatory response, has been reported. The goal of this work was to assess the prevalence of white adipose tissue (WAT) inflammation in patients with endometrial cancer (EC), and the association with circulating inflammation markers. Furthermore, the aim was to characterize the pathways activated in and the cell type composition of adipose tissue in patients with EC.Adipose tissue and blood samples were prospectively collected from 101 patients with EC at initial surgery. WAT inflammation was determined based on adipocytes surrounded by macrophages forming crown-like structures. Circulating levels of metabolic syndrome-associated and inflammatory markers were quantified. RNA-sequencing was performed on adipose samples (n = 55); differential gene expression, pathway, and cellular decomposition analyses were performed using state-of-the-art bioinformatics methods.WAT inflammation was identified in 46 (45.5%) of 101 EC patients. Dyslipidemia, hypertension, and diabetes mellitus were significantly associated with WAT inflammation (p .05). WAT inflammation was associated with greater body mass index (p .001) and higher circulating levels of leptin, high-sensitivity C-reactive protein, and interleukin-6, as well as lower levels of adiponectin and sex hormone-binding globulin (p .05). Transcriptomic analysis demonstrated increased levels of proinflammatory and pro-neoplastic-related gene expression in inflamed omental adipose tissue.WAT inflammation is associated with metabolic syndrome, obesity, and inflammatory markers, as well as increased expression of proinflammatory and proneoplastic genes.
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- 2022
22. Supplementary Data from Microsatellite Instability–High Endometrial Cancers with MLH1 Promoter Hypermethylation Have Distinct Molecular and Clinical Profiles
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Britta Weigelt, Diana L. Mandelker, Yulia Lakhman, Lora H. Ellenson, Dmitriy Zamarin, Alexia Iasonos, Jorge S. Reis-Filho, Zsofia K. Stadler, Nadeem R. Abu-Rustum, Carol Aghajanian, Claire F. Friedman, Maria M. Rubinstein, Sushmita Gordhandas, Timothy Hoang, Lea A. Moukarzel, Ozge Ceyhan-Birsoy, Pier Selenica, Weining Ma, Qin C. Zhou, Arnaud Da Cruz Paula, Kelly A. Devereaux, Ying L. Liu, and Beryl L. Manning-Geist
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Supplementary Data from Microsatellite Instability–High Endometrial Cancers with MLH1 Promoter Hypermethylation Have Distinct Molecular and Clinical Profiles
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- 2023
23. Data from Microsatellite Instability–High Endometrial Cancers with MLH1 Promoter Hypermethylation Have Distinct Molecular and Clinical Profiles
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Britta Weigelt, Diana L. Mandelker, Yulia Lakhman, Lora H. Ellenson, Dmitriy Zamarin, Alexia Iasonos, Jorge S. Reis-Filho, Zsofia K. Stadler, Nadeem R. Abu-Rustum, Carol Aghajanian, Claire F. Friedman, Maria M. Rubinstein, Sushmita Gordhandas, Timothy Hoang, Lea A. Moukarzel, Ozge Ceyhan-Birsoy, Pier Selenica, Weining Ma, Qin C. Zhou, Arnaud Da Cruz Paula, Kelly A. Devereaux, Ying L. Liu, and Beryl L. Manning-Geist
- Abstract
Purpose:Microsatellite instability–high (MSI-H) endometrial carcinomas are underpinned by distinct mechanisms of DNA mismatch repair deficiency (MMR-D). We sought to characterize the clinical and genetic features of MSI-H endometrial cancers harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph).Experimental Design:Of > 1,100 patients with endometrial cancer that underwent clinical tumor-normal sequencing, 184 had MSI-H endometrial cancers due to somatic MMR mutations or MLH1ph, or harbored pathogenic germline MMR mutations. Clinicopathologic features, mutational landscape, and tumor-infiltrating lymphocyte (TIL) scores were compared among MMR-D groups using nonparametric tests. Log-rank tests were used for categorical associations; Kaplan–Meier method and Wald test based on Cox proportional hazards models were employed for continuous variables and survival analyses.Results:Compared with patients with germline (n = 25) and somatic (n = 39) mutations, patients with MLH1ph endometrial cancers (n = 120) were older (P < 0.001), more obese (P = 0.001) and had more advanced disease at diagnosis (P = 0.025). MLH1ph endometrial cancers were enriched for JAK1 somatic mutations as opposed to germline MMR-D endometrial cancers which showed enrichment for pathogenic ERBB2 mutations. MLH1ph endometrial cancers exhibited lower tumor mutational burden and TIL scores compared with endometrial cancers harboring germline or somatic MMR mutations (P < 0.01). MLH1ph endometrial cancer patients had shorter progression-free survival (PFS) on univariate analysis, but in multivariable models, stage at diagnosis remained the only predictor of survival. For stage I/II endometrial cancer, two-year PFS was inferior for patients with MLH1ph endometrial cancers compared with germline and somatic MMR groups (70% vs. 100%, respectively).Conclusions:MLH1ph endometrial cancers likely constitute a distinct clinicopathologic entity compared with germline and somatic MMR-D ECs with potential treatment implications.
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- 2023
24. Primary characteristics and outcomes of newly diagnosed low-grade endometrial stromal sarcoma
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Evan S Smith, Corinne Jansen, Kathryn M Miller, Sarah Chiang, Kaled M Alektiar, Martee L Hensley, Jennifer J Mueller, Nadeem R Abu-Rustum, and Mario M Leitao
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Adult ,Aged, 80 and over ,Sarcoma, Endometrial Stromal ,Lymphadenopathy ,Obstetrics and Gynecology ,Middle Aged ,Hysterectomy ,Article ,Endometrial Neoplasms ,Young Adult ,Oncology ,Lymphatic Metastasis ,Humans ,Lymph Node Excision ,Female ,Neoplasm Recurrence, Local ,Aged ,Neoplasm Staging ,Retrospective Studies - Abstract
ObjectiveTo assess potential predictive variables for nodal metastasis and survival outcomes in patients with newly diagnosed, low-grade endometrial stromal sarcoma.MethodsWe 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 ResultsWe 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 (pConclusionsLymph 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.
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- 2022
25. Sentinel lymph node biopsy alone compared to systematic lymphadenectomy in patients with uterine carcinosarcoma
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William A, Zammarrelli, Michelle, Greenman, Eric, Rios-Doria, Katie, Miller, Vance, Broach, Jennifer J, Mueller, Emeline, Aviki, Kaled M, Alektiar, Robert A, Soslow, Lora H, Ellenson, Vicky, Makker, Nadeem R, Abu-Rustum, and Mario M, Leitao
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Carcinosarcoma ,Oncology ,Sentinel Lymph Node Biopsy ,Transforming Growth Factor beta ,Humans ,Lymph Node Excision ,Obstetrics and Gynecology ,Medical Oncology ,Progression-Free Survival ,Article - 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 (
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- 2022
26. Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues
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Lea A. Moukarzel, Lorenzo Ferrando, Higinio Dopeso, Anthe Stylianou, Thais Basili, Fresia Pareja, Arnaud Da Cruz Paula, Gabriele Zoppoli, Nadeem R. Abu-Rustum, Jorge S. Reis-Filho, Kara Long Roche, William P. Tew, Dennis S. Chi, Yukio Sonoda, Dmitriy Zamarin, Carol Aghajanian, Roisin E. O'Cearbhaill, Oliver Zivanovic, and Britta Weigelt
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Ovarian Neoplasms ,Obstetrics and Gynecology ,Cytoreduction Surgical Procedures ,Hyperthermia, Induced ,Hyperthermic Intraperitoneal Chemotherapy ,Combined Modality Therapy ,Article ,Carboplatin ,Oncology ,Humans ,RNA ,Female ,Transcriptome ,Heat-Shock Proteins - Abstract
OBJECTIVE: To determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues. METHODS: Normal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting. RESULTS: RNA-sequencing revealed 4,231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value
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- 2022
27. Figure S1 from Clinical Utility of Prospective Molecular Characterization in Advanced Endometrial Cancer
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David M. Hyman, Barry S. Taylor, David B. Solit, Deborah F. DeLair, Carol Aghajanian, Nadeem R. Abu-Rustum, Michael F. Berger, Ahmet Zehir, Britta Weigelt, Jennifer Mueller, Bob T. Li, Marc Ladanyi, Robert A. Soslow, Kay J. Park, Sarah Chiang, Rajmohan Murali, Sumit Middha, Sarah J. Schweber, Mila Gorsky, Claire Friedman, Alexandra Snyder Charen, Tiffany A. Troso-Sandoval, David R. Spriggs, Paul Sabbatini, Vicky Makker, Martee L. Hensley, Jason A. Konner, William P. Tew, Roisin E. O'Cearbhaill, Rachel N. Grisham, Karen A. Cadoo, Dmitriy Zamarin, Matthew T. Chang, Preethi Srinivasan, Chaitanya Bandlamudi, Mark T.A. Donoghue, and Tara E. Soumerai
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Progression-free survival and hazard ratios by histology
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- 2023
28. Data from Clinical Utility of Prospective Molecular Characterization in Advanced Endometrial Cancer
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David M. Hyman, Barry S. Taylor, David B. Solit, Deborah F. DeLair, Carol Aghajanian, Nadeem R. Abu-Rustum, Michael F. Berger, Ahmet Zehir, Britta Weigelt, Jennifer Mueller, Bob T. Li, Marc Ladanyi, Robert A. Soslow, Kay J. Park, Sarah Chiang, Rajmohan Murali, Sumit Middha, Sarah J. Schweber, Mila Gorsky, Claire Friedman, Alexandra Snyder Charen, Tiffany A. Troso-Sandoval, David R. Spriggs, Paul Sabbatini, Vicky Makker, Martee L. Hensley, Jason A. Konner, William P. Tew, Roisin E. O'Cearbhaill, Rachel N. Grisham, Karen A. Cadoo, Dmitriy Zamarin, Matthew T. Chang, Preethi Srinivasan, Chaitanya Bandlamudi, Mark T.A. Donoghue, and Tara E. Soumerai
- Abstract
Purpose:Advanced-stage endometrial cancers have limited treatment options and poor prognosis, highlighting the need to understand genetic drivers of therapeutic vulnerabilities and/or prognostic predictors. We examined whether prospective molecular characterization of recurrent and metastatic disease can reveal grade and histology-specific differences, facilitating enrollment onto clinical trials.Experimental Design:We integrated prospective clinical sequencing and IHC data with detailed clinical and treatment histories for 197 tumors, profiled by MSK-IMPACT from 189 patients treated at Memorial Sloan Kettering Cancer Center.Results:Patients had advanced disease and high-grade histologies, with poor progression-free survival on first-line therapy (PFS1). When matched for histology and grade, the genomic landscape was similar to that of primary untreated disease profiled by TCGA. Using multiple complementary genomic and mutational signature-based methods, we identified patients with microsatellite instability (MSI), even when standard MMR protein IHC staining failed. Tumor and matched normal DNA sequencing identified rare pathogenic germline mutations in BRCA2 and MLH1. Clustering the pattern of DNA copy-number alterations revealed a novel subset characterized by heterozygous losses across the genome and significantly worse outcomes compared with other clusters (median PFS1 9.6 months vs. 17.0 and 17.4 months; P = 0.006). Of the 68% of patients harboring potentially actionable mutations, 27% were enrolled to matched clinical trials, of which 47% of these achieved clinical benefit.Conclusions:Prospective clinical sequencing of advanced endometrial cancer can help refine prognosis and aid treatment decision making by simultaneously detecting microsatellite status, germline predisposition syndromes, and potentially actionable mutations. A small overall proportion of all patients tested received investigational, genomically matched therapy as part of clinical trials.
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- 2023
29. Table S1 from Clinical Utility of Prospective Molecular Characterization in Advanced Endometrial Cancer
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David M. Hyman, Barry S. Taylor, David B. Solit, Deborah F. DeLair, Carol Aghajanian, Nadeem R. Abu-Rustum, Michael F. Berger, Ahmet Zehir, Britta Weigelt, Jennifer Mueller, Bob T. Li, Marc Ladanyi, Robert A. Soslow, Kay J. Park, Sarah Chiang, Rajmohan Murali, Sumit Middha, Sarah J. Schweber, Mila Gorsky, Claire Friedman, Alexandra Snyder Charen, Tiffany A. Troso-Sandoval, David R. Spriggs, Paul Sabbatini, Vicky Makker, Martee L. Hensley, Jason A. Konner, William P. Tew, Roisin E. O'Cearbhaill, Rachel N. Grisham, Karen A. Cadoo, Dmitriy Zamarin, Matthew T. Chang, Preethi Srinivasan, Chaitanya Bandlamudi, Mark T.A. Donoghue, and Tara E. Soumerai
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Additional clinical information for patients in MSKCC cohort
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- 2023
30. Data from Clinicopathologic and Genomic Analysis of TP53-Mutated Endometrial Carcinomas
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Robert A. Soslow, Britta Weigelt, Lora H. Ellenson, Marc Ladanyi, Nadeem R. Abu-Rustum, Carol Aghajanian, Kaled M. Alektiar, Eric V. Rios-Doria, Rajmohan Murali, Sarah Chiang, Chad M. Vanderbilt, Wissam Dahoud, and Amir Momeni-Boroujeni
- 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.
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- 2023
31. Supplementary Data from Clinicopathologic and Genomic Analysis of TP53-Mutated Endometrial Carcinomas
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Robert A. Soslow, Britta Weigelt, Lora H. Ellenson, Marc Ladanyi, Nadeem R. Abu-Rustum, Carol Aghajanian, Kaled M. Alektiar, Eric V. Rios-Doria, Rajmohan Murali, Sarah Chiang, Chad M. Vanderbilt, Wissam Dahoud, and Amir Momeni-Boroujeni
- Abstract
Supplementary Methods Supplementary Figures S1-S5 Supplementary Tables S1, S2
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- 2023
32. Supplementary Table and Figure Legends from Clinical Utility of Prospective Molecular Characterization in Advanced Endometrial Cancer
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David M. Hyman, Barry S. Taylor, David B. Solit, Deborah F. DeLair, Carol Aghajanian, Nadeem R. Abu-Rustum, Michael F. Berger, Ahmet Zehir, Britta Weigelt, Jennifer Mueller, Bob T. Li, Marc Ladanyi, Robert A. Soslow, Kay J. Park, Sarah Chiang, Rajmohan Murali, Sumit Middha, Sarah J. Schweber, Mila Gorsky, Claire Friedman, Alexandra Snyder Charen, Tiffany A. Troso-Sandoval, David R. Spriggs, Paul Sabbatini, Vicky Makker, Martee L. Hensley, Jason A. Konner, William P. Tew, Roisin E. O'Cearbhaill, Rachel N. Grisham, Karen A. Cadoo, Dmitriy Zamarin, Matthew T. Chang, Preethi Srinivasan, Chaitanya Bandlamudi, Mark T.A. Donoghue, and Tara E. Soumerai
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Supplementary Table and Figure Legends
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- 2023
33. Endometrial carcinosarcoma
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Giorgio Bogani, Isabelle Ray-Coquard, Nicole Concin, Natalie Yan Li Ngoi, Philippe Morice, Giuseppe Caruso, Takayuki Enomoto, Kazuhiro Takehara, Hannelore Denys, Domenica Lorusso, Robert Coleman, Michelle M Vaughan, Masashi Takano, Diane Michele Provencher, Satoru Sagae, Pauline Wimberger, Robert Póka, Yakir Segev, Se Ik Kim, Jae-Weon Kim, Francisco Jose Candido dos Reis, Pedro T Ramirez, Andrea Mariani, Mario Leitao, Vicky Makker, Nadeem R Abu-Rustum, Ignace Vergote, Gianfranco Zannoni, David Tan, Mary McCormack, Biagio Paolini, Marta Bini, Francesco Raspagliesi, Pierluigi Benedetti Panici, Violante Di Donato, Ludovico Muzii, Nicoletta Colombo, Sandro Pignata, Giovanni Scambia, Bradley J Monk, Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, and Monk, B
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female ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,Oncology ,genital neoplasms, female ,genital neoplasms ,Obstetrics and Gynecology ,carcinosarcoma ,uterine cancer - Abstract
Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion ofPOLEand microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.
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- 2023
34. Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes
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Kelsey Breen, Zsofia K. Stadler, Rachel N. Grisham, Kara Long Roche, Deborah J. Goldfrank, Melissa K. Frey, Alicia Latham, Ying L Liu, Carol Aghajanian, Amanda Catchings, Dennis S. Chi, Kenneth Offit, Megha Ranganathan, and Nadeem R. Abu-Rustum
- Subjects
Oncology ,medicine.medical_specialty ,Oncology (nursing) ,business.industry ,Health Policy ,medicine.disease ,Bilateral salpingo-oophorectomy ,Germline ,Internal medicine ,medicine ,Ovarian cancer ,business ,Gene - Abstract
Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/ 2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/ D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.
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- 2022
35. TSC2-mutant uterine sarcomas with JAZF1-SUZ12 fusions demonstrate hybrid features of endometrial stromal sarcoma and PEComa and are responsive to mTOR inhibition
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Rajmohan Murali, Amir Momeni-Boroujeni, Seth M. Cohen, Kay J. Park, Lora H. Ellenson, Matija Snuderl, Edaise M da Silva, Cheng-Han Lee, Ryma Benayed, Nadeem R. Abu-Rustum, Jason A. Konner, Varshini Vasudevaraja, Marc Ladanyi, Sarah Chiang, Achim A. Jungbluth, Jonathan Serrano, Mark A. Dickson, Britta Weigelt, Carol Aghajanian, Robert A. Soslow, Martee L. Hensley, Arnaud Da Cruz Paula, Esther Oliva, and Colin J.R. Stewart
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Pathology ,medicine.medical_specialty ,Somatic cell ,Biology ,Article ,Perivascular Epithelioid Cell ,Pathology and Forensic Medicine ,Cohort Studies ,Diagnosis, Differential ,medicine ,Humans ,Epigenetics ,In Situ Hybridization, Fluorescence ,PI3K/AKT/mTOR pathway ,Aged ,Endometrial stromal sarcoma ,Sarcoma ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Mutation ,Uterine Neoplasms ,Female ,Epithelioid cell - Abstract
Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2 mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12 gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n = 4), LGESS (n = 10), and HGESS (n = 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2 mutations. TSC2 mutations and JAZF1-SUZ12 fusion may help diagnose these tumors and possibly direct effective treatment.
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- 2022
36. Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines
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Sushmita B Gordhandas, Ryan Kahn, Dib Sassine, Emeline M Aviki, Becky Baltich Nelson, Amanda Catchings, Ying L Liu, Yuliya Lakhman, Nadeem R Abu-Rustum, Kay J Park, and Jennifer J Mueller
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Oncology ,Peutz-Jeghers Syndrome ,Humans ,Uterine Cervical Neoplasms ,Obstetrics and Gynecology ,Female ,Cervix Uteri ,Adenocarcinoma - Abstract
ObjectivesTo perform a systematic review of gastric-type adenocarcinoma of the cervix and lobular endocervical glandular hyperplasia (a possible precursor lesion) in Peutz-Jeghers syndrome, and to analyze data from the literature, along with our institutional experience, to determine recommendations for screening and detection.MethodsA comprehensive literature searc and retrospective search of pathology records at our institutio were conducted. Articles were screened by two independent reviewers. Case reports/series on lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma of the cervix in Peutz-Jeghers syndrome were included. Demographic, clinical, and radiologic information was collected.ResultsA total of 1564 publications were reviewed; 38 met the inclusion criteria. Forty-nine were included in the analysis (43 from the literature, 6 from our institution). Forty-three reported on gastric-type adenocarcinoma alone, 4 on lobular endocervical glandular hyperplasia alone, and 2 on concurrent lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma. Median age at diagnosis was 17 (range, 4–52) for patients with lobular endocervical glandular hyperplasia alone and 35 (range, 15–72) for those with gastric-type adenocarcinoma. The most common presenting symptoms were abdominal/pelvic pain and vaginal bleeding/discharge. Imaging was reported for 27 patients; 24 (89%) had abnormal cervical features. Papanicolaou (Pap) smear prior to diagnosis was reported for 12 patients; 6 (50%) had normal cytology, 4 (33%) atypical glandular cells, and 2 (17%) atypical cells not otherwise specified. Patients with gastric-type adenocarcinoma (n=45) were treated with surgery alone (n=16), surgery/chemotherapy/radiation (n=11), surgery/chemotherapy (n=9), surgery/radiation (n=5), or radiation/chemotherapy (n=4). Twelve (27%) of 45 patients recurred; median progression-free survival was 10 months (range, 1–148). Twenty patients (44%) died; median overall survival was 26 months (range, 2–156). Thirteen patients (27%) were alive with no evidence of disease.ConclusionsGastric-type adenocarcinoma in Peutz-Jeghers syndrome is associated with poor outcomes and short progression-free and overall survival. Screening recommendations, including pathognomonic symptom review and physical examination, with a low threshold for imaging and biopsy, may detect precursor lesions and early-stage gastric-type adenocarcinoma, leading to better outcomes in this high-risk population.PROSPERO registration numberCRD42019118151
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- 2021
37. Horizontal tumor extent (HZTE) has limited prognostic significance in 2018 FIGO stage I endocervical adenocarcinoma (ECA): a retrospective study of 416 cases
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Georgia Karpathiou, Esther Guerra Fernandez, Andres A. Roma, Simona Stolnicu, Graziele Bovolim, Anna Pesci, Robert A. Soslow, Louise De Brot, Esther Oliva, Lien Hoang, Pavel Dundr, Ana Félix, Glauco Baiocchi, Maria José Brito, Antonio Ieni, Kay J. Park, Sofia Lerias, Takako Kyiokawa, Nadeem R. Abu-Rustum, Carlos Parra-Herran, and Noorah Almadani
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Uterine Cervical Neoplasms ,Adenocarcinoma ,Hysterectomy ,Article ,Figo staging ,Recurrence free survival ,Internal medicine ,Humans ,Medicine ,Stage (cooking) ,Aged ,Retrospective Studies ,Univariate analysis ,business.industry ,Retrospective cohort study ,General Medicine ,Middle Aged ,Prognosis ,Cervical cancer staging ,Survival Rate ,Endocervical Adenocarcinoma ,Endocervical adenocarcinoma ,FIGO ,Horizontal tumor extent ,Management ,Prognostic significance ,Stage ,Female ,business ,Follow-Up Studies - Abstract
PURPOSE: The 2018 International Federation of Gynecology and Obstetrics (FIGO) update on cervical cancer staging eliminated horizontal tumor extent (HZTE) as a staging parameter in stage IA (microscopic) disease. We aimed to determine whether HZTE correlates with outcomes in early stage ECAs and FIGO should reinstate HZTE as a staging parameter in futures updates. METHODS: We retrospectively analyzed 416 FIGO 2009 stage I ECAs from 17 institutions and re-assigned stage using FIGO 2018. Correlation between HZTE, overall (OS) and recurrence free survival (RFS) was performed using univariable and multivariable analyses. RESULTS: Re-staging 416 cases resulted in 126 (30.3%) IA and 290 (69.7%) IB cases; 85 (67.5%) IA tumors had HZTE ≤7mm, while 41 (32.5%) were >7mm; 32 (11%) IB tumors had HZTE ≤7mm, while 258 (89%) were >7mm (p=0.0001). Four (3.2%) IA (1 IA1, 3 IA2) patients developed recurrence (3 ≤7mm, 1 >7mm) compared to 41 (14.1%) IB patients (p=0.002). Fourteen IB and no IA patients died of disease (8 IB1, 1 ≤7mm). Cox univariate analysis demonstrated that only RFS is significantly influenced by HZTE (p=0.01), while OS and RFS were not influenced by HZTE on multivariate analysis. CONCLUSION: HZTE has limited prognostic value in early stage ECAs and is only associated with RFS on univariate but not multivariate analysis. HZTE does not improve prognostication of patients with stage I ECAs as per 2018 FIGO staging. Consequently, the rationale to remove this variable from FIGO staging is justified for ECAs.
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- 2021
38. The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer
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Jaroslav Klat, Darwin Pari, Luc R.C.W. van Lonkhuijzen, Klára Benešová, Nicolò Bizzarri, Ignacio Zapardiel, Nadeem R. Abu-Rustum, Aldo Lopez, Jiří Sláma, Andreas Obermair, Fabio Landoni, Mehmet Mutlu Meydanli, Anna Fagotti, Diego Odetto, Veronika Javůrková, Sarah H. Kim, Vít Weinberger, Rosa A. Salcedo-Hernández, Jiri Jarkovsky, Henrik Falconer, Ali Ayhan, Jan Kosťun, David Cibula, L Dostalek, Constantijne H. Mom, Sahar Salehi, Juliana Rodriguez, Ranjit Manchanda, Martina Borčinová, Ricardo dos Reis, David Isla Ortiz, Rene Laky, Huseyin Akilli, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, Cibula, D, Dostalek, L, Jarkovsky, J, Mom, C, Lopez, A, Falconer, H, Fagotti, A, Ayhan, A, Kim, S, Isla Ortiz, D, Klat, J, Obermair, A, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, dos Reis, R, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Benesova, K, Borcinova, M, Pari, D, Salehi, S, Bizzarri, N, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Slama, J, van Lonkhuijzen, L, Amsterdam Reproduction & Development (AR&D), CCA - Cancer Treatment and quality of life, and Obstetrics and gynaecology
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Cancer Research ,medicine.medical_specialty ,Article ,Recurrence risk ,03 medical and health sciences ,0302 clinical medicine ,Risk groups ,Internal medicine ,Medicine ,In patient ,Cervical cancer ,030219 obstetrics & reproductive medicine ,Framingham Risk Score ,Surveillance ,business.industry ,Proportional hazards model ,medicine.disease ,3. Good health ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,Oncology ,030220 oncology & carcinogenesis ,Annual recurrence risk ,Cohort ,Prognostic model ,business - Abstract
Purpose Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Methods Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Results Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. Conclusion The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.
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- 2021
39. Intrathoracic surgery as part of primary cytoreduction for advanced ovarian cancer: Going to the next level - A Memorial Sloan Kettering Cancer Center study
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Ryan M. Kahn, Erin McMinn, Effi Yeoshoua, Thomas Boerner, Qin Zhou, Alexia Iasonos, Kara Long Roche, Oliver Zivanovic, Ginger J. Gardner, Yukio Sonoda, Roisin E. O'Cearbhaill, Rachel N. Grisham, William Tew, David Jones, James Huang, Bernard J. Park, Nadeem R. Abu-Rustum, and Dennis S. Chi
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Oncology ,Obstetrics and Gynecology - Abstract
We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer.We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006-9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded.Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7-61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%-56.2%). Median OS was 81.3 months (95% CI: 68.9-103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P.001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P = .003).Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS.
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- 2022
40. Management of patients with early-stage ovarian clear cell carcinoma: risk stratification and fertility conservation
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Beryl Manning-Geist, Sushmita Gordhandas, Anjelica Hodgson, Qin C Zhou, Alexia Iasonos, Dennis S Chi, Lora Ellenson, Carol A Aghajanian, Nadeem R Abu-Rustum, Mario Leitao, Kara Long, Maria M Rubinstein, Yukio Sonoda, Kaled Alektiar, Britta Weigelt, Oliver Zivanovic, and Rachel N Grisham
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Oncology ,Obstetrics and Gynecology ,Article - Abstract
ObjectiveWe sought to describe clinicopathologic and treatment factors associated with oncologic outcomes in patients with early-stage ovarian clear cell carcinoma undergoing complete staging and in a sub-set of these patients undergoing fertility-conserving surgery.MethodsWe retrospectively identified patients with ovarian clear cell carcinoma initially treated at our institution from January 1, 1996 to March 31, 2020. Survival was estimated using Kaplan–Meier curves and compared by log-rank test. Survival-associated variables were identified by Cox proportional hazards regression.ResultsOf 182 patients, mismatch repair and p53 protein expression were assessed by immunohistochemistry on 82 and 66 samples, respectively. There were no significant differences in progression-free survival or overall survival between mismatch repair-deficient (n=6, including 4 patients with Lynch syndrome; 7.3%) and mismatch repair-proficient patients, whereas aberrant p53 expression (n=3; 4.5%) was associated with worse progression-free (pConclusionsIn patients with completely staged ovarian clear cell carcinoma, those with stage IA/IC1 disease have an excellent prognosis, regardless of chemotherapy. Aberrant p53 expression may portend worse outcomes. Additional investigation is warranted on the safety of fertility conservation in patients with stage IA/IC1 disease.
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- 2022
41. Ten-year conditional probability of survival for patients with ovarian cancer: A new metric tailored to Long-term survivors
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Ryan Kahn, Olga Filippova, Sushmita Gordhandas, Anjile An, Alli M. Straubhar, Oliver Zivanovic, Ginger J. Gardner, Roisin E. O'Cearbhaill, William P. Tew, Rachel N. Grisham, Yukio Sonoda, Kara Long Roche, Nadeem R. Abu-Rustum, and Dennis S. Chi
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Oncology ,Obstetrics and Gynecology - Abstract
We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years.We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001-12/31/2009 and treated at our institution. Patients with3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S(x + y)/S(x). Confidence intervals were estimated using a variation of Greenwood's formula.Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25-95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%-32%)-75% (95% CI: 68%-82%) for stage I/II disease, 22% (95% CI: 19%-26%) for stage III, and 6.9% (95% CI: 3.9%-12%) for stage IV. For patients65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%-70%); for those ≥65 years, it was 48% (95% CI: 38%-57%). For patients65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%-94%); stage III, 58% (95% CI: 50%-66%); and stage IV, 26% (95% CI: 12%-42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%-91%), 42% (95% CI: 30%-53%), and 29% (95% CI: 7%-56%), respectively.For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods.
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- 2022
42. Microsatellite instability-high endometrial cancers with MLH1 promoter hypermethylation have distinct molecular and clinical profiles
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Beryl L. Manning-Geist, Ying L. Liu, Kelly A. Devereaux, Arnaud Da Cruz Paula, Qin C. Zhou, Weining Ma, Pier Selenica, Ozge Ceyhan-Birsoy, Lea A. Moukarzel, Timothy Hoang, Sushmita Gordhandas, Maria M. Rubinstein, Claire F. Friedman, Carol Aghajanian, Nadeem R. Abu-Rustum, Zsofia K. Stadler, Jorge S. Reis-Filho, Alexia Iasonos, Dmitriy Zamarin, Lora H. Ellenson, Yulia Lakhman, Diana L. Mandelker, and Britta Weigelt
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Cancer Research ,Brain Neoplasms ,DNA ,DNA Mismatch Repair ,Article ,Endometrial Neoplasms ,Oncology ,Neoplastic Syndromes, Hereditary ,Humans ,Female ,Microsatellite Instability ,Colorectal Neoplasms ,MutL Protein Homolog 1 ,Germ-Line Mutation - Abstract
Purpose: Microsatellite instability–high (MSI-H) endometrial carcinomas are underpinned by distinct mechanisms of DNA mismatch repair deficiency (MMR-D). We sought to characterize the clinical and genetic features of MSI-H endometrial cancers harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph). Experimental Design: Of > 1,100 patients with endometrial cancer that underwent clinical tumor-normal sequencing, 184 had MSI-H endometrial cancers due to somatic MMR mutations or MLH1ph, or harbored pathogenic germline MMR mutations. Clinicopathologic features, mutational landscape, and tumor-infiltrating lymphocyte (TIL) scores were compared among MMR-D groups using nonparametric tests. Log-rank tests were used for categorical associations; Kaplan–Meier method and Wald test based on Cox proportional hazards models were employed for continuous variables and survival analyses. Results: Compared with patients with germline (n = 25) and somatic (n = 39) mutations, patients with MLH1ph endometrial cancers (n = 120) were older (P < 0.001), more obese (P = 0.001) and had more advanced disease at diagnosis (P = 0.025). MLH1ph endometrial cancers were enriched for JAK1 somatic mutations as opposed to germline MMR-D endometrial cancers which showed enrichment for pathogenic ERBB2 mutations. MLH1ph endometrial cancers exhibited lower tumor mutational burden and TIL scores compared with endometrial cancers harboring germline or somatic MMR mutations (P < 0.01). MLH1ph endometrial cancer patients had shorter progression-free survival (PFS) on univariate analysis, but in multivariable models, stage at diagnosis remained the only predictor of survival. For stage I/II endometrial cancer, two-year PFS was inferior for patients with MLH1ph endometrial cancers compared with germline and somatic MMR groups (70% vs. 100%, respectively). Conclusions: MLH1ph endometrial cancers likely constitute a distinct clinicopathologic entity compared with germline and somatic MMR-D ECs with potential treatment implications.
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- 2022
43. Risk Stratification of Stage I Grade 3 Endometrioid Endometrial Carcinoma in the Era of Molecular Classification
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William A. Zammarrelli, Sarah H. Kim, Arnaud Da Cruz Paula, Eric V. Rios-Doria, Sarah Ehmann, Effi Yeoshoua, Etta J. Hanlon, Qin Zhou, Alexia Iasonos, Kaled M. Alektiar, Carol Aghajanian, Vicky Makker, Mario M. Leitao, Nadeem R. Abu-Rustum, Lora H. Ellenson, Britta Weigelt, and Jennifer J. Mueller
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Male ,Cancer Research ,Testicular Neoplasms ,Oncology ,Humans ,Female ,Prognosis ,Carcinoma, Endometrioid ,Lymphoma, Follicular ,Risk Assessment ,Endometrial Neoplasms - 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.
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- 2022
44. 2022-RA-1174-ESGO Role of adjuvant therapy in intermediate-risk cervical cancer patients – SCCAN study sub-analysis
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David Cibula, Huseyin Akilli, Luc RCW van Lonkhuijzen, Anna Fagotti, Lukáš Dostálek, David Isla Ortiz, Mehmet Mutlu Meydanli, Nadeem R Abu-Rustum, Diego Odetto, Fabio Landoni, Jiri Presl, Jaroslav Klat, Henrik Falconer, Aldo Lopez, Ricardo dos Reis, Ignacio Zapardiel, Rene Laky, Constantijne H Mom, Nicolò Bizzarri, and Ali Ayhan
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- 2022
45. 2022-RA-1301-ESGO The impact of hospital surgical volume on survival in early-stage cervical cancer treated with radical hysterectomy: a sub-analysis of the SCCAN study
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Nicolò Bizzarri, Lukáš Dostálek, Luc RCW Lonkhuijzen, Diana Giannarelli, Aldo Lopez, Henrik Falconer, Denis Querleu, Ali Ayhan, Sarah H Kim, David Isla Ortiz, Jaroslav Klat, Andreas Obermair, Fabio Landoni, Juliana Rodriguez, Ranjit Manchanda, Jan Kosťun, Pedro T Ramirez, Mehmet M Meydanli, Diego Odetto, Rene Laky, Ignacio Zapardiel, Vit Weinberger, Ricardo Dos Reis, Luigi Pedone Anchora, Karina Amaro, Sahar Salehi, Huseyin Akilli, Nadeem R Abu-Rustum, Rosa A Salcedo-Hernández, Veronika Javůrková, Constantijne H Mom, Giovanni Scambia, and David Cibula
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- 2022
46. Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm
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Mario M. Leitao, Nadeem R. Abu-Rustum, Anoushka M. Afonso, William A. Zammarrelli, Jennifer J. Mueller, Amelia Chan, Vance Broach, Oliver Zivanovic, and Yukio Sonoda
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Adult ,Indocyanine Green ,0301 basic medicine ,medicine.medical_specialty ,genetic structures ,Premedication ,Sentinel lymph node ,Contrast Media ,Article ,Drug Hypersensitivity ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Iodinated contrast ,Anti-Allergic Agents ,Biopsy ,Humans ,Medicine ,Prospective Studies ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,Sentinel Lymph Node Biopsy ,business.industry ,Incidence ,Endometrial cancer ,Diphenhydramine ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,eye diseases ,Endometrial Neoplasms ,body regions ,Administration, Intravaginal ,030104 developmental biology ,Oncology ,chemistry ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,Radiology ,Sentinel Lymph Node ,business ,Indocyanine green ,medicine.drug - Abstract
Objective To describe the incidence of adverse reactions to indocyanine green (ICG) administered during sentinel lymph node (SLN) biopsy for endometrial cancer, and to propose an ICG management algorithm for these patients. Methods All patients who underwent surgery for endometrial cancer with SLN biopsy using ICG from 1/2017 to 8/2020 were identified using a single-institution prospective database. Surgical adverse events (SAEs) related to the procedure were identified. A review of the literature was performed. Results In all, 1414 patients met inclusion criteria and were evaluated. Sixty-seven (4.7%) patients had a history of either an iodine or contrast allergy. No patients had a history of documented ICG allergy. Among patients with an iodine or contrast allergy, 65 (97%) received a corticosteroid with or without diphenhydramine prior to ICG administration. One hundred five patients (7.4%) experienced 116 SAEs. Among these patients, 3 experienced potentially allergic SAEs possibly related to ICG administration. After thorough chart review, however, the likelihood these SAEs were due to ICG appeared low. No patients experienced an anaphylactic response after ICG admission. Conclusion There were no anaphylactic reactions to ICG intracervical administration during 1414 consecutive SLN biopsies, including in patients with a documented iodine or contrast allergy. Intracervical injection of ICG is safe, and premedication using corticosteroids with or without diphenhydramine prior to SLN biopsy is a reasonable strategy in patients with iodinated contrast allergy.
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- 2021
47. NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021
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Steven W. Remmenga, Suzanne George, Stefanie Ueda, Angela D. Motter, Hye Sook Chon, Edward J. Tanner, Nadeem R. Abu-Rustum, Robert L. Giuntoli, Larissa Nekhlyudov, David K. Gaffney, Christine M. Fisher, Peter J. Frederick, Rachel C. Sisodia, Mirna B. Podoll, Jayanthi S. Lea, Brooke E. Howitt, Shari Damast, Kristin A. Bradley, Emily Wyse, David E. Cohn, Susana M. Campos, R. Kevin Reynolds, Christina Chu, Catheryn M. Yashar, Pamela T. Soliman, Warner K. Huh, Kristine M. Zanotti, Junzo Chino, Renata R. Urban, Stephanie L. Wethington, Marta A. Crispens, Andrea Mariani, Ritu Salani, Ernest S. Han, Nicole R. McMillian, Elisabeth Diver, and David G. Mutch
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Oncology ,medicine.medical_specialty ,Uterine sarcoma ,business.industry ,Endometrial cancer ,Internal medicine ,medicine ,MEDLINE ,Treatment options ,medicine.disease ,business ,Uterine Neoplasm - Abstract
The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.
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- 2021
48. Mesonephric and mesonephric-like carcinomas of the female genital tract: molecular characterization including cases with mixed histology and matched metastases
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Fresia Pareja, Pier Selenica, Edaise M da Silva, Jason A. Konner, Daniel J Fix, Jennifer J. Mueller, E. Smith, Britta Weigelt, Karen Cadoo, Nadeem R. Abu-Rustum, Jorge S. Reis-Filho, Kay J. Park, Anthe Stylianou, Ahmet Zehir, Sarah H. Kim, Lorenzo Ferrando, Arnaud Da Cruz Paula, and Ana Paula Martins Sebastiao
- Subjects
Adult ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Genital Neoplasms, Female ,Ovary ,Chromosome 9 ,medicine.disease_cause ,Article ,Pathology and Forensic Medicine ,Mesonephric duct ,03 medical and health sciences ,0302 clinical medicine ,Mesonephroma ,Carcinoma ,medicine ,Humans ,PTEN ,Chromosome 12 ,Aged ,biology ,Histology ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Female ,KRAS - Abstract
Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically similar, do not have obvious Wolffian derivation. Here, we sought to characterize the repertoire of genetic alterations in primary mesonephric and mesonephric-like carcinomas, in the distinct histologic components of mixed cases, as well as in matched primary tumors and metastases. DNA from microdissected tumor and normal tissue from mesonephric carcinomas (cervix, n = 8) and mesonephric-like carcinomas (ovarian n = 15, endometrial n = 13) were subjected to sequencing targeting 468 cancer-related genes. The histologically distinct components of four cases with mixed histology and four primary tumors and their matched metastases were microdissected and analyzed separately. Mesonephric-like carcinomas were underpinned by somatic KRAS mutations (25/28, 89%) akin to mesonephric carcinomas (8/8, 100%), but also harbored genetic alterations more frequently reported in Müllerian tumors. Mesonephric-like carcinomas that lacked KRAS mutations harbored NRAS (n = 2, ovary) or BRAF (n = 1, endometrium) hotspot mutations. PIK3CA mutations were identified in both mesonephric-like (8/28, 28%) and mesonephric carcinomas (2/8, 25%). Only mesonephric-like tumors harbored CTNNB1 hotspot (4/28, 14%) and PTEN (3/13, 23%) mutations. Copy number analysis revealed frequent gains of chromosomes 1q and 10 in both mesonephric (87% 1q; 50% chromosome 10) and mesonephric-like tumors (89% 1q; 43% chromosome 10). Chromosome 12 gains were more frequent in ovarian mesonephric-like carcinomas, and losses of chromosome 9 were more frequent in mesonephric than in mesonephric-like carcinomas (both p = 0.01, Fisher’s exact test). The histologically distinct components of four mixed cases were molecularly related and shared similar patterns of genetic alterations. The progression from primary to metastatic lesions involved the acquisition of additional mutations, and/or shifts from subclonal to clonal mutations. Our findings suggest that mesonephric-like carcinomas are derived from a Müllerian substrate with differentiation along Wolffian/mesonephric lines.
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- 2021
49. High-sensitivity mutation analysis of cell-free DNA for disease monitoring in endometrial cancer
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Charles W. Ashley, Pier Selenica, Juber Patel, Michelle Wu, Josip Nincevic, Yulia Lakhman, Qin Zhou, Ronak H. Shah, Michael F. Berger, Arnaud Da Cruz Paula, David N. Brown, Antonio Marra, Alexia Iasonos, Amir Momeni-Boroujeni, Kaled M. Alektiar, Kara Long Roche, Oliver Zivanovic, Jennifer J. Mueller, Dmitriy Zamarin, Vance A. Broach, Yukio Sonoda, Mario M. Leitao, Claire F. Friedman, Elizabeth Jewell, Jorge S. Reis-Filho, Lora H. Ellenson, Carol Aghajanian, Nadeem R. Abu-Rustum, Karen Cadoo, and Britta Weigelt
- Subjects
Cancer Research ,Oncology - 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
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- 2022
50. Sentinel lymph node mapping in patients with endometrial hyperplasia: A practice to preserve or abandon?
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Jennifer J. Mueller, Eric Rios-Doria, Kay J. Park, Vance A. Broach, Kaled M. Alektiar, Elizabeth L. Jewell, Oliver Zivanovic, Yukio Sonoda, Nadeem R. Abu-Rustum, Mario M. Leitao, and Ginger J. Gardner
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Oncology ,Obstetrics and Gynecology - Abstract
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.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.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.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.
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- 2022
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