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1,364 results on '"Santin, Alessandro"'

1. Preclinical evaluation of avutometinib and defactinib in high-grade endometrioid endometrial cancer.

Author

Hartwich, Tobias, Mansolf, Miranda, Demirkiran, Cem, Greenman, Michelle, Bellone, Stefania, McNamara, Blair, Nandi, Shuvro, Alexandrov, Ludmil, Yang-Hartwich, Yang, Coma, Silvia, Pachter, Jonathan, and Santin, Alessandro

Subjects
FAK inhibitor, MEK inhibitor, avutometinib, defactinib, endometrial cancer, Female, Humans, Animals, Mice, Endometrial Neoplasms, Xenograft Model Antitumor Assays, Cell Line, Tumor, Carcinoma, Endometrioid, Exome Sequencing, Antineoplastic Combined Chemotherapy Protocols, Cell Proliferation, Neoplasm Grading, Protein Kinase Inhibitors, Focal Adhesion Kinase 1, Oxazepines, Sulfonamides, Pyrazines, Benzamides, Imidazoles
Abstract

BACKGROUND: High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts. METHODS: Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage. RESULTS: WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (p

Published
2024

2. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2

Author

Mutlu, Levent, McNamara, Blair, Bellone, Stefania, Manavella, Diego D., Demirkiran, Cem, Greenman, Michelle, Verzosa, Miguel Skyler Z., Buza, Natalia, Hui, Pei, Hartwich, Tobias Max Philipp, Harold, Justin, Yang-Hartwich, Yang, Zipponi, Margherita, Altwerger, Gary, Ratner, Elena, Huang, Gloria S., Clark, Mitchell, Andikyan, Vaagn, Azodi, Masoud, Schwartz, Peter E., and Santin, Alessandro D.

Published
2024
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3. Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix.

Author

Bellone, Stefania, Jeong, Kyungjo, Halle, Mari, Krakstad, Camilla, McNamara, Blair, Greenman, Michelle, Mutlu, Levent, Demirkiran, Cem, Hartwich, Tobias, Yang-Hartwich, Yang, Zipponi, Margherita, Buza, Natalia, Hui, Pei, Raspagliesi, Francesco, Lopez, Salvatore, Paolini, Biagio, Milione, Massimo, Perrone, Emanuele, Scambia, Giovanni, Altwerger, Gary, Ravaggi, Antonella, Bignotti, Eliana, Huang, Gloria, Andikyan, Vaagn, Clark, Mitchell, Ratner, Elena, Azodi, Masoud, Schwartz, Peter, Quick, Charles, Angioli, Roberto, Terranova, Corrado, Zaidi, Samir, Nandi, Shuvro, Alexandrov, Ludmil, Siegel, Eric, Choi, Jungmin, Schlessinger, Joseph, and Santin, Alessandro

Subjects
cancer, genetic analysis, mutations, neuroendocrine, oncogene, Humans, Female, Uterine Cervical Neoplasms, Afatinib, Phylogeny, Phosphatidylinositol 3-Kinases, Neuroendocrine Tumors, Mutation, Class I Phosphatidylinositol 3-Kinases, Adenocarcinoma, Carcinoma, Neuroendocrine, DNA Mutational Analysis
Abstract

High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.6% (42/64) of the tumors. Recurrent mutations were identified in PIK3CA, KMT2D/MLL2, K-RAS, ARID1A, NOTCH2, and RPL10. The top mutated genes included RB1, ARID1A, PTEN, KMT2D/MLL2, and WDFY3, a gene not yet implicated in NETc. Somatic CNV analysis identified two copy number gains (3q27.1 and 19q13.12) and five copy number losses (1p36.21/5q31.3/6p22.2/9q21.11/11p15.5). Also, gene fusions affecting the ACLY-CRHR1 and PVT1-MYC genes were identified in one of the eight samples subjected to RNA sequencing. To resolve evolutionary history, multiregion WES in NETc admixed with adenocarcinoma cells was performed (i.e., mixed-NETc). Phylogenetic analysis of mixed-NETc demonstrated that adenocarcinoma and neuroendocrine elements derive from a common precursor with mutations typical of adenocarcinomas. Over one-third (22/64) of NETc demonstrated a mutator phenotype of C > T at CpG consistent with deficiencies in MBD4, a member of the base excision repair (BER) pathway. Mutations in the PI3K/AMPK pathways were identified in 49/64 samples. We used two patient-derived-xenografts (PDX) (i.e., NET19 and NET21) to evaluate the activity of pan-HER (afatinib), PIK3CA (copanlisib), and ATR (elimusertib) inhibitors, alone and in combination. PDXs harboring alterations in the ERBB2/PI3K/AKT/mTOR/ATR pathway were sensitive to afatinib, copanlisib, and elimusertib (P < 0.001 vs. controls). However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.

Published
2024

5. First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial

Author

Marth, Christian, Moore, Richard G., Bidziński, Mariusz, Pignata, Sandro, Ayhan, Ali, Rubio, M. Jesús, Beiner, Mario, Hall, Marcia, Vulsteke, Christof, Braicu, Elena Ioana, Sonoda, Kenzo, Wu, Xiaohua, Frentzas, Sophia, Mattar, André, Lheureux, Stephanie, Chen, Xiaojun, Hasegawa, Kosei, Magallanes-Maciel, Manuel, Choi, Chel Hun, Shalkova, Mariia, Kaen, Diego, Wang, Peng-Hui, Berger, Regina, Okpara, Chinyere E., McKenzie, Jodi, Yao, Lili, Orlowski, Robert, Khemka, Vivek, Gilbert, Lucy, Makker, Vicky, Kaen, Diego Lucas, Gomez Abuin, Gonzalo, Zamora, Liliana Beatriz, Alfie, Margarita Sonia, Casarini, Ignacio Alfredo, Harrison, Michelle, Ananda, Sumitra, Shannon, Catherine Margaret, Frentzas, Sophia, Friedlander, Michael, Meniawy, Tarek, Gao, Bo, Baron-Hay, Sally, Diakos, Connie, Marth, Christian, Polterauer, Stephan, Petru, Edgar, De Bock, Marlies, Vulsteke, Christof, Baurain, Jean-Francois, Van Gorp, Toon, Altintas, Sevilay, Lima, Joao Paulo da Silveira Nogueira, Mattar, Andre, de Freitas Junior, Ruffo, Santana, Rosane O., de Melo, Andreia Cristina, Franke, Fabio Andre, Zibetti Dal Molin, Graziela, Damian, Fernanda Bronzon, Guedes, João Daniel Cardoso, Ellard, Susan, Tinker, Anna, Samouëlian, Vanessa, Fortin, Suzanne, Bessette, Paul, Kolinsky, Michael, Kumar Tyagi, Nidhi, Ethier, Josee-Lyne, Gilbert, Lucy, Lheureux, Stephanie, MacKay, Helen, Lim, Charles, Wu, Xiaohua, Pan, Lingya, An, Ruifang, Chen, Xiaojun, Zheng, Hong, Wu, Yumei, Zhu, Jianqing, Yao, Shuzhong, Jia, Xuemei, Huang, Yi, Lv, Weiguo, Zhang, Yu, Zhou, Qi, Ma, Cailing, Chekerov, Radoslav, Mach, Pawel, Witteler, Ralf, Marmè, Frederik, Cadoo, Karen, Korach, Jacob, Levy, Talia, Beiner, Mario, Amnon, Amit, Scollo, Paolo, Naglieri, Emanuele, Pignata, Sandro, Zamagni, Claudio, Salutari, Vanda, Usami, Tomoka, Nakamura, Kazuto, Matsumoto, Koji, Yamagami, Wataru, Kobayashi, Yoichi, Takano, Masashi, Kato, Hidenori, Sonoda, Kenzo, Kikuchi, Akira, Katsumata, Noriyuki, Kamiura, Shoji, Horie, Koji, Hasegawa, Kosei, Tsunoda, Takuya, Suzuki, Nao, Yunokawa, Mayu, Nishio, Shin, Kudaka, Wataru, Guerrero Cabrera, Fernando Felix, Gonzalez Mendoza, Rene Lazaro, Magallanes Maciel, Manuel Ernesto, Villalobos Valencia, Ricardo, Escobar Penagos, Jose, Lopez Chuken, Yamil Alonso, Mackowiak-Matejczyk, Beata, Tarnawski, Rafal, Kalinka, Ewa, Bidzinski, Mariusz, Bednarek, Wieslawa, Danska-Bidzinska, Anna, Koralewski, Piotr, Roszak, Andrzej, Kedrova, Anna, Musaeva, Natalia, Urmancheeva, Adiliya Fettekhovna, Vasiliev, Aleksandr Gennadievich, Safina, Sufia Zievna, Lisyanskaya, Alla Sergeevna, Rykov, Ivan V., Rumyantsev, Alexey Alexandrovich, Belonogov, Aleksandr, Makarycheva, Yulia, Kim, Yong Man, Choi, Chel Hun, Kim, Yong Beom, Kim, Hee Seung, Kim, Sang Wun, Quindos Varela, Maria, Casado Herraez, Antonio, Diaz Redondo, Tamara, Rubio Perez, Maria Jesus, Romeo Marin, Margarita, Romero Noguera, Ignacio, Taus Garcia, Alvaro, Lin, Wu-Chou, Chou, Hung-Hsueh, Cheng, Wen-Fang, Lu, Chien-Hsing, Wang, Peng-Hui, Simsek, Tayup, Kose, Fatih, Ayhan, Ali, Vardar, Mehmet Ali, Ozerkan, Kemal, Hughes, Andrew, Stillie, Alison, Eminowicz, Gemma, Khalique, Saira, Shalkova, Mariia, Sukhina, Olena, Piatnytska, Tetiana, Averina, Hanna, Kulyaba, Yaroslav, Kryzhanivska, Anna, Bondarenko, Igor, Svintsitsky, Valentyn, Krasnohrud, Yuliia, Voitko, Nataliia, Buscema, Joseph, Ghamande, Sharad, Lewin, Sharyn, Graham, Deena M., Makker, Vicky, Bell, Maria, Santin, Alessandro, Lee, Christine, Blank, Stephanie, Konecny, Gottfried E., Corr, Bradley, Van Le, Linda, Moore, Richard G., Scalici, Jennifer, Anderson, Charles, Braly, Patricia, Fehniger, Julia, Westhoff, Gina, and Bollinger, Lauren

Published
2024
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6. Mismatch repair deficiency, next-generation sequencing-based microsatellite instability, and tumor mutational burden as predictive biomarkers for immune checkpoint inhibitor effectiveness in frontline treatment of advanced stage endometrial cancer

Author

Hill, Breana L, Graf, Ryon P, Shah, Kunal, Danziger, Natalie, Lin, Douglas I, Quintanilha, Julia, Li, Gerald, Haberberger, James, Ross, Jeffrey S, Santin, Alessandro D, Slomovitz, Brian, Elvin, Julia A, and Eskander, Ramez N

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Genetics, Digestive Diseases, Cancer, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Female, Humans, Biomarkers, Tumor, Colorectal Neoplasms, DNA Mismatch Repair, Endometrial Neoplasms, High-Throughput Nucleotide Sequencing, Immune Checkpoint Inhibitors, Microsatellite Instability, endometrium, uterine cancer, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

ObjectiveMolecular profiling is developing to inform treatment in endometrial cancer. Using real world evidence, we sought to evaluate frontline immune checkpoint inhibitor vs chemotherapy effectiveness in advanced endometrial cancer, stratified by Tumor Mutational Burden (TMB) ≥10 mut/MB and microsatellite instability (MSI).MethodsPatients with advanced endometrial cancer in the US-based de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database were included. Data originated from patients treated between January 2011- March 2022 at 280 US clinics. Next-generation sequencing assays were performed via FoundationOne or FoundationOneCDx. Longitudinal clinical data were derived from electronic health records. Immune checkpoint inhibitor treatment included pembrolizumab, dostarlimab, and nivolumab monotherapies. Time to next treatment, time to treatment discontinuation, and overall survival were assessed with the log-rank test and Cox proportional hazard models with adjusted hazard ratios (aHR) for known prognostic factors. We used the Likelihood ratio test to compare biomarker performance.ResultsA total of 343 patients received chemotherapy and 28 received immune checkpoint inhibitor monotherapy as frontline treatment. Patients who received monotherapy were more likely to be stage III at diagnosis (immune checkpoint inhibitor: 54.6% vs chemotherapy: 15.0%; p

Published
2023

10. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial

Author

Powell, Matthew A, Filiaci, Virginia L, Hensley, Martee L, Huang, Helen Q, Moore, Kathleen N, Tewari, Krishnansu S, Copeland, Larry J, Secord, Angeles A, Mutch, David G, Santin, Alessandro, Warshal, David P, Spirtos, Nick M, DiSilvestro, Paul A, Ioffe, Olga B, and Miller, David S

Subjects
Cancer, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Antineoplastic Combined Chemotherapy Protocols, Carboplatin, Carcinosarcoma, Disease-Free Survival, Female, Humans, Ifosfamide, Ovarian Neoplasms, Paclitaxel, Uterine Neoplasms, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeThis phase III randomized trial (NCT00954174) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS).Patients and methodsAdults with chemotherapy-naïve UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test.ResultsThe study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; P < .01 for noninferiority, P > .1 for superiority). The median progression-free survival was 16 versus 12 months (HR = 0.73; P = < 0.01 for noninferiority, P < .01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant.ConclusionPC was not inferior to the active regimen PI and should be standard treatment for UCS.

Published
2022

13. Quality of Life and Adverse Events: Prognostic Relationships in Long-Term Ovarian Cancer Survival

Author

Wenzel, Lari, Osann, Kathryn, McKinney, Chelsea, Cella, David, Fulci, Giulia, Scroggins, Mary J, Lankes, Heather A, Wang, Victoria, Nephew, Kenneth P, Maxwell, George L, Mok, Samuel C, Conrads, Thomas P, Miller, Austin, Mannel, Robert S, Gray, Heidi J, Hanjani, Parviz, Huh, Warner K, Spirtos, Nick, Leitao, Mario M, Glaser, Gretchen, Sharma, Sudarshan K, Santin, Alessandro D, Sperduto, Paul, Lele, Shashikant B, Burger, Robert A, Monk, Bradley J, and Birrer, Michael

Subjects
Cancer, Rehabilitation, Ovarian Cancer, Clinical Research, Rare Diseases, Management of diseases and conditions, 7.1 Individual care needs, Carcinoma, Ovarian Epithelial, Humans, Ovarian Neoplasms, Prognosis, Quality of Life, Survivors, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundThere is a critical need to identify patient characteristics associated with long-term ovarian cancer survival.MethodsQuality of life (QOL), measured by the Functional Assessment of Cancer Therapy-Ovarian-Trial Outcome Index (FACT-O-TOI), including physical, functional, and ovarian-specific subscales, was compared between long-term survivors (LTS) (8+ years) and short-term survivors (STS) (

Published
2021

15. Correction: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer

Author

Roque, Dana M., Siegel, Eric R., Buza, Natalia, Bellone, Stefania, Silasi, Dan-Arin, Huang, Gloria S., Andikyan, Vaagn, Clark, Mitchell, Azodi, Masoud, Schwartz, Peter E., Rao, Gautam G., Reader, Jocelyn C., Hui, Pei, Tymon-Rosario, Joan R., Harold, Justin, Mauricio, Dennis, Zeybek, Burak, Menderes, Gulden, Altwerger, Gary, Ratner, Elena, and Santin, Alessandro D.

Published
2024
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16. Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100

Author

Ledermann, Jonathan A., Shapira-Frommer, Ronnie, Santin, Alessandro D., Lisyanskaya, Alla S., Pignata, Sandro, Vergote, Ignace, Raspagliesi, Francesco, Sonke, Gabe S., Birrer, Michael, Provencher, Diane M., Sehouli, Jalid, Colombo, Nicoletta, González-Martín, Antonio, Oaknin, Ana, Ottevanger, P.B., Rudaitis, Vilius, Kobie, Julie, Nebozhyn, Michael, Edmondson, Mackenzie, Sun, Yuan, Cristescu, Razvan, Jelinic, Petar, Keefe, Stephen M., and Matulonis, Ursula A.

Published
2023
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17. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial

Author

Oaknin, Ana, Friedman, Claire F, Roman, Lynda D, D’Souza, Anishka, Brana, Irene, Bidard, François-Clement, Goldman, Jonathan, Alvarez, Edwin A, Boni, Valentina, ElNaggar, Adam C, Passalacqua, Rodolfo, T.M., Khanh, Santin, Alessandro D, Keyvanjah, Kiana, Xu, Feng, Eli, Lisa D, Lalani, Alshad S, Bryce, Richard P, Hyman, David M, Meric-Bernstam, Funda, Solit, David B, and Monk, Bradley J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Administration, Oral, Adult, Diarrhea, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Mutation, Nausea, Neoplasm Recurrence, Local, Progression-Free Survival, Protein Kinase Inhibitors, Quinolines, Receptor, ErbB-2, Response Evaluation Criteria in Solid Tumors, Severity of Illness Index, Uterine Cervical Neoplasms, Cervical cancer, HER2 mutant, Neratinib, Clinical trial, Tyrosine kinase inhibitor, Receptor, erbB-2, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis, Reproductive medicine
Abstract

ObjectiveSomatic HER2 mutations occur in ~5% of cervical cancers and are considered oncogenic and associated with poor prognosis. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, is active in multiple HER2-mutant cancers. SUMMIT is a phase II basket trial investigating the efficacy and safety of neratinib in solid tumors.MethodsPatients with HER2-mutant, persistent, metastatic/recurrent cervical cancer with disease progression after platinum-based treatment for advanced/recurrent disease received oral neratinib 240 mg/day with mandatory loperamide prophylaxis during cycle 1. The primary endpoint was confirmed objective response rate (ORR). Secondary endpoints included: response duration (DOR); clinical benefit rate (CBR); progression-free survival (PFS); overall survival (OS); safety.ResultsSixteen eligible patients were enrolled; 10 (62.5%) had endocervical adenocarcinoma. The most common HER2 mutation was S310F (63% of patients). Three of 12 RECIST-measurable patients had confirmed partial responses (ORR 25%; 95%CI 5.5-57.2%); 3 had stable disease ≥16 weeks (CBR 50%; 95%CI 21.1-78.9%). DOR for responders were 5.6, 5.9, and 12.3 months. Median PFS was 7.0 months (95%CI 0.7-18.3 months); median OS was 16.8 months (95%CI 4.1-NE months). Diarrhea (75%), nausea (44%), and decreased appetite (38%) were the most common adverse events. One patient (6%) reported grade 3 diarrhea. There were no grade 4 events, and no diarrhea-related treatment discontinuations.ConclusionsNeratinib monotherapy showed evidence of activity in heavily pretreated patients with HER2-mutant cervical cancer, with no new safety signals. Given the few effective options for cervical cancer after platinum-based therapy failure, neratinib warrants further investigation in this molecularly defined patient population.Trial registration numberNCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).

Published
2020

18. Stage III uterine serous carcinoma: modern trends in multimodality treatment

Author

Li, Jessie Y, Young, Melissa R, Huang, Gloria, Litkouhi, Babak, Santin, Alessandro, Schwartz, Peter E, and Damast, Shari

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Cancer, Adult, Aged, Aged, 80 and over, Brachytherapy, Endometrial Neoplasms, Female, Humans, Hysterectomy, Middle Aged, Neoplasm Staging, Radiotherapy, Adjuvant, Retrospective Studies, Endometrium, Carcinoma, Radiotherapy, Paediatrics and Reproductive Medicine, Oncology and carcinogenesis, Reproductive medicine
Abstract

ObjectiveTo examine outcomes in a modern treatment era for stage III uterine serous carcinoma (USC).MethodsFifty women were retrospectively identified as 2009 International Federation of Gynecology and Obstetrics stage III USC patients who received radiotherapy (RT) at our institution between 1/2003-5/2018. The patients were divided into 2 cohorts: 20 in the early era (2003-2010) and 30 in the modern era (2011-2018). Patient characteristics were compared using χ² tests for categorical variables and t-tests for continuous variables. Recurrence free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards.ResultsThe modern era differed from the early era in the increased use of volume-directed external beam RT (EBRT) as opposed to vaginal brachytherapy (VB) alone (33.3% vs 5.0%, p=0.048), minimally invasive surgery (56.7% vs. 25%, p=0.027), sentinel node sampling (26.7% vs. 0%, p=0.012), computed tomography imaging in the perioperative period (63.3% vs. 30%, p=0.044), and human epidermal growth factor receptor 2/neu testing (96.7% vs. 55%, p=0.001). Median follow-up for early and modern eras was 37.27 and 33.23 months, respectively. The early vs. modern 3-year RFS was 33% and 64% (p=0.039), respectively, while the 3-year OS was 55% and 90% (p=0.034). Regional nodal recurrence more common among the patients who received VB only (p=0.048).ConclusionModern era treatment was associated with improved RFS and OS in patients with stage III USC. Regional nodal recurrences were significantly reduced in patients who received EBRT.

Published
2020

19. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice

Author

Lorusso, Domenica, Colombo, Nicoletta, Herraez, Antonio Casado, Santin, Alessandro D., Colomba, Emeline, Miller, David Scott, Fujiwara, Keiichi, Pignata, Sandro, Baron-Hay, Sally E., Ray-Coquard, Isabelle Laure, Shapira-Frommer, Ronnie, Kim, Yong Man, McCormack, Mary, Massaad, Rachid, Nguyen, Allison Martin, Zhao, Qi, McKenzie, Jodi, Prabhu, Vimalanand S., and Makker, Vicky

Published
2023
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21. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor

Author

McNamara, Blair, Harold, Justin, Manavella, Diego, Bellone, Stefania, Mutlu, Levent, Hartwich, Tobias Max Philipp, Zipponi, Margherita, Yang-Hartwich, Yang, Demirkiran, Cem, Verzosa, Miguel Skyler Z., Yang, Kevin, Choi, Jungmin, Dong, Weilai, Buza, Natalia, Hui, Pei, Altwerger, Gary, Huang, Gloria S., Andikyan, Vaagn, Clark, Mitchell, Ratner, Elena, Azodi, Masoud, Schwartz, Peter E., Burton, Elizabeth A., Inagaki, Hiroaki, Albers, Aaron, Zhang, Chao, Bollag, Gideon, Schlessinger, Joseph, and Santin, Alessandro D.

Published
2023
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22. Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study

Author

Santin, Alessandro D, Vergote, Ignace, González-Martín, Antonio, Moore, Kathleen, Oaknin, Ana, Romero, Ignacio, Diab, Sami, Copeland, Larry J, Monk, Bradley J, Coleman, Robert L, Herzog, Thomas J, Siegel, Jonathan, Kasten, Linda, Schlicker, Andreas, Schulz, Anke, Köchert, Karl, Walter, Annette O, Childs, Barrett H, Elbi, Cem, and Bulat, Iurie

Published
2023
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23. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo

Author

Han, Chanhee, McNamara, Blair, Bellone, Stefania, Harold, Justin, Manara, Paola, Hartwich, Tobias Max Philipp, Mutlu, Levent, Yang-Hartwich, Yang, Zipponi, Margherita, Demirkiran, Cem, Verzosa, Miguel Skyler Z., Altwerger, Gary, Ratner, Elena, Huang, Gloria S., Clark, Mitchell, Andikyan, Vaagn, Azodi, Masoud, Dottino, Peter R., Schwartz, Peter E., and Santin, Alessandro D.

Published
2023
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24. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression

Author

Mauricio, Dennis, Bellone, Stefania, Mutlu, Levent, McNamara, Blair, Manavella, Diego D., Demirkiran, Cem, Verzosa, Miguel Skyler Z., Buza, Natalia, Hui, Pei, Hartwich, Tobias Max Philipp, Harold, Justin, Yang-Hartwich, Yang, Zipponi, Margherita, Altwerger, Gary, Ratner, Elena, Huang, Gloria S., Clark, Mitchell, Andikyan, Vaagn, Azodi, Masoud, Schwartz, Peter E., and Santin, Alessandro D.

Published
2023
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25. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor

Author

Manavella, Diego D., McNamara, Blair, Harold, Justin, Bellone, Stefania, Hartwich, Tobias Max Philipp, Yang-Hartwich, Yang, Mutlu, Levent, Zipponi, Margherita, Demirkiran, Cem, Verzosa, Miguel Skyler, Altwerger, Gary, Ratner, Elena, Huang, Gloria S., Clark, Mitchell, Andikyan, Vaagn, Azodi, Masoud, Schwartz, Peter E., Dottino, Peter R., Choi, Jungmin, Alexandrov, Ludmil B., Buza, Natalia, Hui, Pei, and Santin, Alessandro D.

Published
2023
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26. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma

Author

Harold, Justin, Bellone, Stefania, Manavella, Diego D., Mutlu, Levent, McNamara, Blair, Hartwich, Tobias Max Philipp, Zipponi, Margherita, Yang-Hartwich, Yang, Demirkiran, Cem, Verzosa, Miguel Skyler, Choi, Jungmin, Dong, Weilai, Buza, Natalia, Hui, Pei, Altwerger, Gary, Huang, Gloria S., Andikyan, Vaagn, Clark, Mitchell, Ratner, Elena, Azodi, Masoud, Schwartz, Peter E., and Santin, Alessandro D.

Published
2023
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27. Contributors

Author

Aviki, Emeline, primary, Berkowitz, Ross S., additional, Broach, Vance, additional, Cantrell, Leigh A., additional, Chui, M. Herman, additional, Cliby, William, additional, Elias, Kevin M., additional, Hedrick Ellenson, Lora, additional, Fader, Amanda N., additional, Filho, Donato Callegaro, additional, Fleming, Nicole D., additional, Frumovitz, Michael, additional, Gershenson, David M., additional, Gordhandas, Sushmita, additional, Grisham, Rachel N., additional, Herbst, Arthur, additional, Hillman, R. Tyler, additional, Hinchcliff, Emily, additional, Hodgson, Anjelica, additional, Horowitz, Neil S., additional, Kertowidjojo, Elizabeth, additional, Kim, Sarah H., additional, Knisely, Anne, additional, Kurnit, Katherine C., additional, Lawson, Barrett, additional, Leitao, Mario M., additional, Levine, Douglas A., additional, Liu, Ying, additional, Long, Beverly, additional, Manning-Geist, Beryl, additional, Miao, Diana, additional, Mueller, Jennifer J., additional, Nagarajan, Priyadharsini, additional, O’Cearbhaill, Roisin E., additional, Peng, Katherine, additional, Ramalingam, Preetha, additional, Ratan, Ravin, additional, Salvo, Gloria, additional, Santin, Alessandro D., additional, Shafer, Aaron, additional, Soliman, Pamela, additional, Somasegar, Sahana, additional, Tymon-Rosario, Joan R., additional, Wright, Jason D., additional, Yamada, S. Diane, additional, and Zivanovic, Oliver, additional

Published
2023
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29. GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study

Author

Brooks, Rebecca A, Tritchler, David S, Darcy, Kathleen M, Lankes, Heather A, Salani, Ritu, Sperduto, Paul, Guntupalli, Saketh, DiSilvestro, Paul, Kesterson, Joshua, Olawaiye, Alexander B, Moxley, Katherine, Waggoner, Steven, Santin, Alessandro, Rader, Janet S, Kizer, Nora T, Thaker, Premal H, Powell, Matthew A, Mutch, David G, Birrer, Michael J, and Goodfellow, Paul J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Cancer, Clinical Research, Genetics, Patient Safety, Uterine Cancer, 2.1 Biological and endogenous factors, Aetiology, Aged, Biomarkers, Tumor, Case-Control Studies, Disease Progression, Endometrial Neoplasms, Endometrium, ErbB Receptors, Female, Humans, Lymphatic Metastasis, Middle Aged, NM23 Nucleoside Diphosphate Kinases, Neoplasm Staging, Polymorphism, Single Nucleotide, Prognosis, Progression-Free Survival, Risk Assessment, Endometrial cancer, Risk stratification, SNP association, Node positivity, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis, Reproductive medicine
Abstract

ObjectivesThe ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients.MethodsSurgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated.Results361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables.ConclusionSNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

Published
2019

30. Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer

Author

Roque, Dana M., Siegel, Eric R., Buza, Natalia, Bellone, Stefania, Silasi, Dan-Arin, Huang, Gloria S., Andikyan, Vaagn, Clark, Mitchell, Azodi, Masoud, Schwartz, Peter E., Rao, Gautam G., Reader, Jocelyn C., Hui, Pei, Tymon-Rosario, Joan R., Harold, Justin, Mauricio, Dennis, Zeybek, Burak, Menderes, Gulden, Altwerger, Gary, Ratner, Elena, and Santin, Alessandro D.

Published
2022
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31. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu

Author

Yadav, Ghanshyam, Roque, Dana M., Bellone, Stefania, Manavella, Diego D., Hartwich, Tobias M.P., Zipponi, Margherita, Harold, Justin, Tymon-Rosario, Joan, Mutlu, Levent, Altwerger, Gary, Menderes, Gulden, Ratner, Elena, Buza, Natalia, Hui, Pei, Huang, Gloria S., Andikyan, Vaagn, Clark, Mitchell, Azodi, Masoud, Schwartz, Peter E., Alexandrov, Ludmil B., and Santin, Alessandro D.

Published
2022
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32. Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor

Author

Tymon-Rosario, Joan R., Manara, Paola, Manavella, Diego D., Bellone, Stefania, Hartwich, Tobias Max Philipp, Harold, Justin, Yang-Hartwich, Yang, Zipponi, Margherita, Choi, Jungmin, Jeong, Kyungjo, Mutlu, Levent, Yang, Kevin, Altwerger, Gary, Menderes, Gulden, Ratner, Elena, Huang, Gloria S., Clark, Mitchell, Andikyan, Vaagn, Azodi, Masoud, Schwartz, Peter E., Alexandrov, Ludmil B., and Santin, Alessandro D.

Published
2022
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33. Integrated mutational landscape analysis of uterine leiomyosarcomas

Author

Choi, Jungmin, Manzano, Aranzazu, Dong, Weilai, Bellone, Stefania, Bonazzoli, Elena, Zammataro, Luca, Yao, Xiaotong, Deshpande, Aditya, Zaidi, Samir, Guglielmi, Adele, Gnutti, Barbara, Nagarkatti, Nupur, Tymon-Rosario, Joan R., Harold, Justin, Mauricio, Dennis, Zeybek, Burak, Menderes, Gulden, Altwerger, Gary, Jeong, Kyungjo, Zhao, Siming, Buza, Natalia, Hui, Pei, Ravaggi, Antonella, Bignotti, Eliana, Romani, Chiara, Todeschini, Paola, Zanotti, Laura, Odicino, Franco, Pecorelli, Sergio, Ardighieri, Laura, Bilguvar, Kaya, Quick, Charles M., Silasi, Dan-Arin, Huang, Gloria S., Andikyan, Vaagn, Clark, Mitchell, Ratner, Elena, Azodi, Masoud, Imielinski, Marcin, Schwartz, Peter E., Alexandrov, Ludmil B., Lifton, Richard P., Schlessinger, Joseph, and Santin, Alessandro D.

Published
2021

36. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo

Author

Tymon-Rosario, Joan, Bonazzoli, Elena, Bellone, Stefania, Manzano, Aranzazu, Pelligra, Silvia, Guglielmi, Adele, Gnutti, Barbara, Nagarkatti, Nupur, Zeybek, Burak, Manara, Paola, Zammataro, Luca, Harold, Justin, Mauricio, Dennis, Buza, Natalia, Hui, Pei, Altwerger, Gary, Menderes, Gulden, Ratner, Elena, Clark, Mitchell, Andikyan, Vaagn, Huang, Gloria S., Silasi, Dan-Arin, Azodi, Masoud, Schwartz, Peter E., and Santin, Alessandro D.

Published
2021
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43. Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma

Author

Bonazzoli, Elena, Bellone, Stefania, Zammataro, Luca, Gnutti, Barbara, Guglielmi, Adele, Pelligra, Silvia, Nagarkatti, Nupur, Manara, Paola, Tymon-Rosario, Joan, Zeybek, Burak, Altwerger, Gary, Menderes, Gulden, Han, Chanhee, Ratner, Elena, Silasi, Dan-Arin, Huang, Gloria S., Andikyan, Vaagn, Azodi, Masoud, Schwartz, Peter E., and Santin, Alessandro D.

Published
2020
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45. Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum- resistant or refractory ovarian / fallopian tube / primary peritoneal cancer (NCT03093155): updated survival and subgroup analyses

Author

Roque, Dana M., primary, Siegel, Eric R., additional, Buza, Natalia, additional, Bellone, Stefania, additional, Huang, Gloria S., additional, Altwerger, Gary, additional, Andikyan, Vaagn, additional, Clark, Mitchell, additional, Azodi, Masoud, additional, Schwartz, Peter E., additional, Rao, Gautam G., additional, Ratner, Elena, additional, and Santin, Alessandro D., additional

Published
2024
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46. Supplementary Data S1 from Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)

Author

Sheth, Sangini S., primary, Oh, Ji Eun, primary, Bellone, Stefania, primary, Siegel, Eric R., primary, Greenman, Michelle, primary, Mutlu, Levent, primary, McNamara, Blair, primary, Pathy, Shefali, primary, Clark, Mitchell, primary, Azodi, Masoud, primary, Altwerger, Gary, primary, Andikyan, Vaagn, primary, Huang, Gloria, primary, Ratner, Elena, primary, Kim, Daniel J., primary, Iwasaki, Akiko, primary, Levi, Angelique W., primary, Buza, Natalia, primary, Hui, Pei, primary, Flaherty, Sean, primary, Schwartz, Peter E., primary, and Santin, Alessandro D., primary

Published
2024
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47. Supplementary Table S1 from Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)

Author

Sheth, Sangini S., primary, Oh, Ji Eun, primary, Bellone, Stefania, primary, Siegel, Eric R., primary, Greenman, Michelle, primary, Mutlu, Levent, primary, McNamara, Blair, primary, Pathy, Shefali, primary, Clark, Mitchell, primary, Azodi, Masoud, primary, Altwerger, Gary, primary, Andikyan, Vaagn, primary, Huang, Gloria, primary, Ratner, Elena, primary, Kim, Daniel J., primary, Iwasaki, Akiko, primary, Levi, Angelique W., primary, Buza, Natalia, primary, Hui, Pei, primary, Flaherty, Sean, primary, Schwartz, Peter E., primary, and Santin, Alessandro D., primary

Published
2024
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48. Supplementary Figure S1 from Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)

Author

Sheth, Sangini S., primary, Oh, Ji Eun, primary, Bellone, Stefania, primary, Siegel, Eric R., primary, Greenman, Michelle, primary, Mutlu, Levent, primary, McNamara, Blair, primary, Pathy, Shefali, primary, Clark, Mitchell, primary, Azodi, Masoud, primary, Altwerger, Gary, primary, Andikyan, Vaagn, primary, Huang, Gloria, primary, Ratner, Elena, primary, Kim, Daniel J., primary, Iwasaki, Akiko, primary, Levi, Angelique W., primary, Buza, Natalia, primary, Hui, Pei, primary, Flaherty, Sean, primary, Schwartz, Peter E., primary, and Santin, Alessandro D., primary

Published
2024
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49. Data from Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)

Author

Sheth, Sangini S., primary, Oh, Ji Eun, primary, Bellone, Stefania, primary, Siegel, Eric R., primary, Greenman, Michelle, primary, Mutlu, Levent, primary, McNamara, Blair, primary, Pathy, Shefali, primary, Clark, Mitchell, primary, Azodi, Masoud, primary, Altwerger, Gary, primary, Andikyan, Vaagn, primary, Huang, Gloria, primary, Ratner, Elena, primary, Kim, Daniel J., primary, Iwasaki, Akiko, primary, Levi, Angelique W., primary, Buza, Natalia, primary, Hui, Pei, primary, Flaherty, Sean, primary, Schwartz, Peter E., primary, and Santin, Alessandro D., primary

Published
2024
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50. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)

Author

Sheth, Sangini S., primary, Oh, Ji Eun, additional, Bellone, Stefania, additional, Siegel, Eric R., additional, Greenman, Michelle, additional, Mutlu, Levent, additional, McNamara, Blair, additional, Pathy, Shefali, additional, Clark, Mitchell, additional, Azodi, Masoud, additional, Altwerger, Gary, additional, Andikyan, Vaagn, additional, Huang, Gloria, additional, Ratner, Elena, additional, Kim, Daniel J., additional, Iwasaki, Akiko, additional, Levi, Angelique W., additional, Buza, Natalia, additional, Hui, Pei, additional, Flaherty, Sean, additional, Schwartz, Peter E., additional, and Santin, Alessandro D., additional

Published
2024
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