- Email: [email protected]
Cancer-specific survival with or without adjuvant chemotherapy in high-risk stage I endometrial cancer
abstracts
Annals of Oncology Funding: National Natural Science Foundation of China (Youth fund project, no. 81602267). Disclosure: Y. Zhang: Full / Part-time employment: OrigiMed. S. Zhang: Full / Part-time employment: OrigiMed. S. Zhao: Full / Part-time employment: OrigiMed. F. Guo: Full / Part-time employment: OrigiMed. F. Pang: Full / Part-time employment: OrigiMed. L. Zhang: Full / Part-time employment: OrigiMed. X. Dong: Full / Part-time employment: OrigiMed. K. Wang: Full / Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.
1041P
Conclusions: WATi was present in nearly 50% of newly diagnosed EC patients regardless of stage. There was an association between the presence and severity of WATi and BMI among patients with EC. Specifically, WATi was associated with hyperglycemia, hypertension, and diabetes mellitus. Further investigation into the impact of WATi on the tumor microenvironment and patient outcomes is ongoing. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Clinical features and frequency of mismatch repair protein deficiency in ovarian clear cell and endometrioid carcinoma patients
Background: The rates of mismatch repair (MMR) protein deficiency and microsatellite instability (MSI) in ovarian clear cell (CC) and endometrioid (EM) cancer patients were investigated. The clinical features of CC and EM were also analyzed. Methods: Patients postoperatively diagnosed as CC or EM carcinoma from January 2006 to December 2015 were eligible. Diagnosis of all cases was confirmed by the Central Pathological Review Board. MMR protein was analyzed by IHC using a monoclonal antibody and MSI was examined by a multiplex PCR assay for five microsatellite markers, BAT25, BAT26, NR-21, NR-24, and MONO-27. MLH1 IHC-negative cases were examined for DNA hypermethylation of the MLH1 promoter. Results: We enrolled 339 cases consisting of 219 CC, 116 EM and 4 mixed type (MT) cases. One case could not be evaluated by IHC. MMR protein deficiency was confirmed in five CC (2.3%), 16 EM (13.9%) and 1 MT case (25%). Deficiency was observed in 4 cases for MLH1 and PMS2, in 13 cases for MSH2 and MSH6, in 1 case for MSH2 and PMS2, in 2 cases for MSH6, and in 1 case for PMS2. DNA hypermethylation of the MLH1 promoter was detected in one of the four MLH1 and PMS2 deficiency cases. Three of the 339 cases could not be evaluated by MSI. A high rate of MSI was confirmed in 13 cases (3.9%) and MMR deficiency was detected by IHC in these cases. However, MSI was not detected in the other nine cases where MMR deficiency was detected by IHC. The median age of all 339 cases was 54 (CC 54, EM 51) and that of CC and EM cases with MMR deficiency was 39 and 48 years, respectively. Conclusions: The rate of MMR deficiency in CC and EM was not high, whereas CC in young women was more frequent. IHC is a more successful screening method of MMR deficiency in ovarian CC and EM compared with MSI detection. The rate of MLH1 promoter hypermethylation (epigenetic MMR deficiency) in ovarian CC and EM was less than that of endometrial cancer. Legal entity responsible for the study: The author. Funding: National Hospital Organization of Japan. Disclosure: The author has declared no conflicts of interest.
1042P
Prospective study evaluating white adipose tissue inflammation and clinicopathologic features in endometrial cancer
L.A. Moukarzel1, A. Stylianou1, M. Wu1, S.P. Nobre1, N.R. Abu-Rustum1, V. Broach1, D.D. Giri2, N.M. Iyengar3, B. Weigelt2, V. Makker3 1 Surgery Department, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 2 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 3Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York City, NY, USA Background: Obesity is a chief mediator of endometrial cancer (EC) and is responsible for the increasing incidence and mortality of this malignancy. Obesity induced chronic inflammation, creates a pro-neoplastic environment via local and systemic processes. In other obesity-related cancers, white adipose tissue inflammation (WATi) is an independent predictor of shortened cancer-specific survival. A retrospective study in advanced EC revealed that WATi is associated with shorter progression-free survival. The aim of this prospective study was to investigate the presence of WATi in EC and to evaluate the relationship between WATi and clinicopathologic factors in women with EC. Methods: Patients who underwent primary surgical management of EC, regardless of stage or histology, had omental biopsies collected. WATi was detected by the presence of dead/dying adipocytes surrounded by CD68þ macrophages forming a crown-like structure (CLS). Clinicopathologic data were extracted from medical records. For association with WATi, Wilcoxon rank sum test was used for continuous variables, and the Fisher’s exact or v2 test for categorical variables. Results: A total of 101 EC patients who underwent primary surgical management between 2015 and 2019 were included. Of these, 46 (46%) had WATi. The presence of WATi was unaffected by race, histology, FIGO stage, smoking or menopausal state. In contrast, dyslipidemia (39% vs 13%, p ¼ 0.002), hypertension (70% vs 35%, p < 0.001) and diabetes mellitus (13% vs 9%, p ¼ 0.015) were significantly more frequent in EC patients with WATi. The median BMI was 35 kg/m2 and 29 kg/m2 in the WATi versus non WATi patients, respectively (p < 0.001). The median CLS based on BMI was 0.19 CLS/cm2 for those with a BMI of < 25kg/m2, 0.34 CLS/cm2 for those with a BMI of 2529kg/m2, and 1.01 CLS/cm2 for those with a BMI of > 30kg/m2.
Volume 30 | Supplement 5 | October 2019
Cancer-specific survival with or without adjuvant chemotherapy in high-risk stage I endometrial cancer
J. Ko1, B. Lester2, N. Le3, G. Bowering1, C. Rugayan2, A. Kumar4 Medical Oncology, BC Cancer - Abbotsford, Abbotsford, BC, Canada, 2Radiation Oncology, BC Cancer - Abbotsford, Abbotsford, BC, Canada, 3Biostatistics, BC Cancer Research Centre, Vancouver, BC, Canada, 4Medical Oncology, BC Cancer - Surrey, Surrey, BC, Canada
1
Background: Controversies exist for utility of adjuvant chemotherapy (AC) in early stage high risk endometrial cancer (EC). Our study sought to evaluate overall, relapsefree and cancer-specific survivals (OS, RFS, CSS) in patients with high risk FIGO stage I EC. Methods: Per provincial guideline, high risk stage I EC eligible for AC was defined as 1) endometrioid histology, stage IB and grade 3 or 2) non-endometrioid histology with any myometrial invasion. We identified all consecutive patients with stage I EC from 6 cancer centres in British Columbia, Canada diagnosed between 2000 and 2010. CSS was defined as time between diagnosis and death due to endometrial cancer. Descriptive statistics were used to evaluate patient, disease and treatment characteristics; Cox proportional hazard regression was used to evaluate differences in OS, RFS and CSS. Results: Among stage I EC (n ¼ 1426), 24 with endometrioid histology and 214 with non-endometrioid histology with high risk characteristics were identified (n ¼ 238). Median age was 66 (range 33-91); stage IA ¼ 196, IB ¼ 50; grade 1¼16, 2¼20, 3¼196; LVIþ 88. Among all high risk patients, OS (RR 0.37, 95% CI 0.20-0.71, p ¼ 0.002; median 6.3 vs 12.2 years) and RFS (RR 0.35, 95% CI 0.19-0.65, p ¼ 0.001; median 5.6 vs 12.2 years) were significantly better in patients who received AC, but CSS (RR 0.65, 95% CI 0.32-1.33, p ¼ 0.24; median not reached in both groups) was not statistically improved although numerically favoured AC. Similarly, among non-endometrioid histology, OS (RR 0.40, 95% CI 0.20-0.78, p ¼ 0.008; median 6.4 vs 12.2 years) and RFS (RR 0.38, 95% CI 0.20-0.72, p ¼ 0.03; median 5.9 vs 12.2 years) were significantly better in patients who received AC, but improvements in CSS with AC (RR 0.68, 95% CI 0.31.4, p ¼ 0.32; median not reached in both groups) were not statistically significant. Conclusions: Despite its use, there is insufficient evidence that AC reduces risk of death due to cancer in high risk stage I EC, although DSS is numerically improved in patients who received AC. Improvements in OS and RFS associated with chemotherapy may be largely attributed to other confounding factors. Future prospective studies are needed to clarify the role of contemporary AC in high risk stage I EC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1044P
Pembrolizumab in patients with MSI-H advanced endometrial cancer from the KEYNOTE-158 study
D. O’Malley1, A. Marabelle2, A. De Jesus-Acosta3, S.A. Piha-Paul4, A. Arkhipov5, F. Longo6, D. Motola-Kuba7, R. Shapira-Frommer8, R. Geva9, B.J. Rimel10, J.A. LopezMartin11, A.R. Hansen12, J.M. Mehnert13, X. Chen14, F. Jin14, K. Norwood14, P.A. Ott15 1 Ob/gyn, The Ohio State University James Cancer Hospital, Columbus, OH, USA, 2Drug Development Department, Institut Gustave Roussy, Villejuif, France, 3Medical Oncology, Johns Hopkins Hospital, Baltimore, MD, USA, 4Department of Investigational Cancer Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA, 5 Chemotherapy and Radiotherapy Department, Federal State Autonomous Institution “Treatment and Rehabilitation Center” of the Ministry of Health of Russian Federation, Moscow, Russian Federation, 6Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain, 7Clinical Investigation, COMOP A.C., Mexico City, Mexico, 8Oncology, Chaim Sheba Medical Centre, Ramat Gan, Israel, 9Division of Oncology, Tel Aviv Sourasky Medical Center-(Ichilov), Tel Aviv, Israel, 10Gynecology-Oncology, Cedars-Sinai Medical Centre, Los Angeles, CA, USA, 11Medical Oncology, 12 de Octubre University Hospital & Research Institute (i þ 12), Madrid, Spain, 12Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 13Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA, 14MRL, Merck & Co., Inc., Kenilworth, NJ, USA, 15Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA Background: Pembrolizumab (pembro) provides durable responses in patients (pts) with MSI-H cancers and is approved in the US/Japan for the treatment of MSI-H advanced solid tumors. MSI-H is expressed in 25% of endometrial cancers. An analysis of pts with MSI-H advanced endometrial cancer enrolled in cohorts D (advanced
doi:10.1093/annonc/mdz250 | v425
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz250.051/5577524 by guest on 26 October 2019
1043P K. Takehara Gynecologic Oncology, Shikoku Cancer Center, Matsuyama, Japan
Annals of Oncology Funding: National Natural Science Foundation of China (Youth fund project, no. 81602267). Disclosure: Y. Zhang: Full / Part-time employment: OrigiMed. S. Zhang: Full / Part-time employment: OrigiMed. S. Zhao: Full / Part-time employment: OrigiMed. F. Guo: Full / Part-time employment: OrigiMed. F. Pang: Full / Part-time employment: OrigiMed. L. Zhang: Full / Part-time employment: OrigiMed. X. Dong: Full / Part-time employment: OrigiMed. K. Wang: Full / Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.
1041P
Conclusions: WATi was present in nearly 50% of newly diagnosed EC patients regardless of stage. There was an association between the presence and severity of WATi and BMI among patients with EC. Specifically, WATi was associated with hyperglycemia, hypertension, and diabetes mellitus. Further investigation into the impact of WATi on the tumor microenvironment and patient outcomes is ongoing. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Clinical features and frequency of mismatch repair protein deficiency in ovarian clear cell and endometrioid carcinoma patients
Background: The rates of mismatch repair (MMR) protein deficiency and microsatellite instability (MSI) in ovarian clear cell (CC) and endometrioid (EM) cancer patients were investigated. The clinical features of CC and EM were also analyzed. Methods: Patients postoperatively diagnosed as CC or EM carcinoma from January 2006 to December 2015 were eligible. Diagnosis of all cases was confirmed by the Central Pathological Review Board. MMR protein was analyzed by IHC using a monoclonal antibody and MSI was examined by a multiplex PCR assay for five microsatellite markers, BAT25, BAT26, NR-21, NR-24, and MONO-27. MLH1 IHC-negative cases were examined for DNA hypermethylation of the MLH1 promoter. Results: We enrolled 339 cases consisting of 219 CC, 116 EM and 4 mixed type (MT) cases. One case could not be evaluated by IHC. MMR protein deficiency was confirmed in five CC (2.3%), 16 EM (13.9%) and 1 MT case (25%). Deficiency was observed in 4 cases for MLH1 and PMS2, in 13 cases for MSH2 and MSH6, in 1 case for MSH2 and PMS2, in 2 cases for MSH6, and in 1 case for PMS2. DNA hypermethylation of the MLH1 promoter was detected in one of the four MLH1 and PMS2 deficiency cases. Three of the 339 cases could not be evaluated by MSI. A high rate of MSI was confirmed in 13 cases (3.9%) and MMR deficiency was detected by IHC in these cases. However, MSI was not detected in the other nine cases where MMR deficiency was detected by IHC. The median age of all 339 cases was 54 (CC 54, EM 51) and that of CC and EM cases with MMR deficiency was 39 and 48 years, respectively. Conclusions: The rate of MMR deficiency in CC and EM was not high, whereas CC in young women was more frequent. IHC is a more successful screening method of MMR deficiency in ovarian CC and EM compared with MSI detection. The rate of MLH1 promoter hypermethylation (epigenetic MMR deficiency) in ovarian CC and EM was less than that of endometrial cancer. Legal entity responsible for the study: The author. Funding: National Hospital Organization of Japan. Disclosure: The author has declared no conflicts of interest.
1042P
Prospective study evaluating white adipose tissue inflammation and clinicopathologic features in endometrial cancer
L.A. Moukarzel1, A. Stylianou1, M. Wu1, S.P. Nobre1, N.R. Abu-Rustum1, V. Broach1, D.D. Giri2, N.M. Iyengar3, B. Weigelt2, V. Makker3 1 Surgery Department, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 2 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 3Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York City, NY, USA Background: Obesity is a chief mediator of endometrial cancer (EC) and is responsible for the increasing incidence and mortality of this malignancy. Obesity induced chronic inflammation, creates a pro-neoplastic environment via local and systemic processes. In other obesity-related cancers, white adipose tissue inflammation (WATi) is an independent predictor of shortened cancer-specific survival. A retrospective study in advanced EC revealed that WATi is associated with shorter progression-free survival. The aim of this prospective study was to investigate the presence of WATi in EC and to evaluate the relationship between WATi and clinicopathologic factors in women with EC. Methods: Patients who underwent primary surgical management of EC, regardless of stage or histology, had omental biopsies collected. WATi was detected by the presence of dead/dying adipocytes surrounded by CD68þ macrophages forming a crown-like structure (CLS). Clinicopathologic data were extracted from medical records. For association with WATi, Wilcoxon rank sum test was used for continuous variables, and the Fisher’s exact or v2 test for categorical variables. Results: A total of 101 EC patients who underwent primary surgical management between 2015 and 2019 were included. Of these, 46 (46%) had WATi. The presence of WATi was unaffected by race, histology, FIGO stage, smoking or menopausal state. In contrast, dyslipidemia (39% vs 13%, p ¼ 0.002), hypertension (70% vs 35%, p < 0.001) and diabetes mellitus (13% vs 9%, p ¼ 0.015) were significantly more frequent in EC patients with WATi. The median BMI was 35 kg/m2 and 29 kg/m2 in the WATi versus non WATi patients, respectively (p < 0.001). The median CLS based on BMI was 0.19 CLS/cm2 for those with a BMI of < 25kg/m2, 0.34 CLS/cm2 for those with a BMI of 2529kg/m2, and 1.01 CLS/cm2 for those with a BMI of > 30kg/m2.
Volume 30 | Supplement 5 | October 2019
Cancer-specific survival with or without adjuvant chemotherapy in high-risk stage I endometrial cancer
J. Ko1, B. Lester2, N. Le3, G. Bowering1, C. Rugayan2, A. Kumar4 Medical Oncology, BC Cancer - Abbotsford, Abbotsford, BC, Canada, 2Radiation Oncology, BC Cancer - Abbotsford, Abbotsford, BC, Canada, 3Biostatistics, BC Cancer Research Centre, Vancouver, BC, Canada, 4Medical Oncology, BC Cancer - Surrey, Surrey, BC, Canada
1
Background: Controversies exist for utility of adjuvant chemotherapy (AC) in early stage high risk endometrial cancer (EC). Our study sought to evaluate overall, relapsefree and cancer-specific survivals (OS, RFS, CSS) in patients with high risk FIGO stage I EC. Methods: Per provincial guideline, high risk stage I EC eligible for AC was defined as 1) endometrioid histology, stage IB and grade 3 or 2) non-endometrioid histology with any myometrial invasion. We identified all consecutive patients with stage I EC from 6 cancer centres in British Columbia, Canada diagnosed between 2000 and 2010. CSS was defined as time between diagnosis and death due to endometrial cancer. Descriptive statistics were used to evaluate patient, disease and treatment characteristics; Cox proportional hazard regression was used to evaluate differences in OS, RFS and CSS. Results: Among stage I EC (n ¼ 1426), 24 with endometrioid histology and 214 with non-endometrioid histology with high risk characteristics were identified (n ¼ 238). Median age was 66 (range 33-91); stage IA ¼ 196, IB ¼ 50; grade 1¼16, 2¼20, 3¼196; LVIþ 88. Among all high risk patients, OS (RR 0.37, 95% CI 0.20-0.71, p ¼ 0.002; median 6.3 vs 12.2 years) and RFS (RR 0.35, 95% CI 0.19-0.65, p ¼ 0.001; median 5.6 vs 12.2 years) were significantly better in patients who received AC, but CSS (RR 0.65, 95% CI 0.32-1.33, p ¼ 0.24; median not reached in both groups) was not statistically improved although numerically favoured AC. Similarly, among non-endometrioid histology, OS (RR 0.40, 95% CI 0.20-0.78, p ¼ 0.008; median 6.4 vs 12.2 years) and RFS (RR 0.38, 95% CI 0.20-0.72, p ¼ 0.03; median 5.9 vs 12.2 years) were significantly better in patients who received AC, but improvements in CSS with AC (RR 0.68, 95% CI 0.31.4, p ¼ 0.32; median not reached in both groups) were not statistically significant. Conclusions: Despite its use, there is insufficient evidence that AC reduces risk of death due to cancer in high risk stage I EC, although DSS is numerically improved in patients who received AC. Improvements in OS and RFS associated with chemotherapy may be largely attributed to other confounding factors. Future prospective studies are needed to clarify the role of contemporary AC in high risk stage I EC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1044P
Pembrolizumab in patients with MSI-H advanced endometrial cancer from the KEYNOTE-158 study
D. O’Malley1, A. Marabelle2, A. De Jesus-Acosta3, S.A. Piha-Paul4, A. Arkhipov5, F. Longo6, D. Motola-Kuba7, R. Shapira-Frommer8, R. Geva9, B.J. Rimel10, J.A. LopezMartin11, A.R. Hansen12, J.M. Mehnert13, X. Chen14, F. Jin14, K. Norwood14, P.A. Ott15 1 Ob/gyn, The Ohio State University James Cancer Hospital, Columbus, OH, USA, 2Drug Development Department, Institut Gustave Roussy, Villejuif, France, 3Medical Oncology, Johns Hopkins Hospital, Baltimore, MD, USA, 4Department of Investigational Cancer Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA, 5 Chemotherapy and Radiotherapy Department, Federal State Autonomous Institution “Treatment and Rehabilitation Center” of the Ministry of Health of Russian Federation, Moscow, Russian Federation, 6Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain, 7Clinical Investigation, COMOP A.C., Mexico City, Mexico, 8Oncology, Chaim Sheba Medical Centre, Ramat Gan, Israel, 9Division of Oncology, Tel Aviv Sourasky Medical Center-(Ichilov), Tel Aviv, Israel, 10Gynecology-Oncology, Cedars-Sinai Medical Centre, Los Angeles, CA, USA, 11Medical Oncology, 12 de Octubre University Hospital & Research Institute (i þ 12), Madrid, Spain, 12Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 13Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA, 14MRL, Merck & Co., Inc., Kenilworth, NJ, USA, 15Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA Background: Pembrolizumab (pembro) provides durable responses in patients (pts) with MSI-H cancers and is approved in the US/Japan for the treatment of MSI-H advanced solid tumors. MSI-H is expressed in 25% of endometrial cancers. An analysis of pts with MSI-H advanced endometrial cancer enrolled in cohorts D (advanced
doi:10.1093/annonc/mdz250 | v425
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz250.051/5577524 by guest on 26 October 2019
1043P K. Takehara Gynecologic Oncology, Shikoku Cancer Center, Matsuyama, Japan