scholarly journals Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study

2016 ◽  
Vol 34 (25) ◽  
pp. 3062-3068 ◽  
Author(s):  
D. Scott McMeekin ◽  
David L. Tritchler ◽  
David E. Cohn ◽  
David G. Mutch ◽  
Heather A. Lankes ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Prognostic Indicators ◽  
Gynecologic Oncology Group ◽  
Free Survival ◽  
Gynecology And Obstetrics ◽  
Mlh1 Methylation ◽  
Lymphovascular Space Invasion

Purpose The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. Methods Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. Results A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. Conclusion MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors.

scholarly journals Pathologic and Treatment Outcomes Among a Geriatric Population of Endometrial Cancer Patients: An NRG Oncology/Gynecologic Oncology Group Ancillary Data Analysis of LAP2

2017 ◽  
Vol 27 (4) ◽  
pp. 730-737 ◽  
Author(s):  
Erin A. Bishop ◽  
James J. Java ◽  
Kathleen N. Moore ◽  
Joan L. Walker
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Early Stage ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Gynecologic Oncology Group ◽  
Free Survival ◽  
Early Stage Endometrial Cancer

ObjectivesElderly endometrial cancer patients have worse disease-specific survival than their younger counterparts, but the cause for this discrepancy is unknown. The goal of this analysis is to compare outcomes by age in a fully staged elderly endometrial cancer population.Methods/MaterialsThis is an analysis of patients on Gynecologic Oncology Group Study (GOG) LAP2, which included clinically early stage endometrial cancer patients randomized to laparotomy versus laparoscopy for surgical staging. Patients were divided into risk groups based on criteria defined by GOG protocol 99. Differences in outcomes and adjuvant therapy were assessed within these risk groups.ResultsLAP2 included 715 patients 70 years or older. With increasing age, worse tumor characteristics were seen. Older patients received similar rates of adjuvant therapy when stratified by stage. Patients 70 years or older had significantly worse progression-free survival and overall survival, and on multivariate analysis, older age and high-risk uterine factors were predictors of progression-free survival and overall survival, whereas stage and lymph node metastases were not. When patients were divided into GOG protocol 99 risk categories, most of those who met the high-intermediate risk criteria did so based on age above 70 years and grade 2 to 3 disease. These patients had low risk of recurrence (3.3%) compared with those who met the criteria by age above 70 years and all 3 uterine factors (20.9%).ConclusionsIn early stage endometrial cancer, patients 70 years or older who undergo similar surgical management and adjuvant therapy, age and tumor characteristics independently predict recurrence. Most patients older than 70 years meet the high-intermediate risk criteria for recurrence based on age and 1 other uterine risk factor, and our results suggest that these patients are at low risk for recurrence.

Endometrial cancer in young women: prognostic factors and treatment outcomes in women aged ≤40 years

2020 ◽  
Vol 30 (5) ◽  
pp. 631-639 ◽  
Author(s):  
Ji Son ◽  
Caitlin Carr ◽  
Meng Yao ◽  
Milena Radeva ◽  
Anju Priyadarshini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Myometrial Invasion ◽  
Progression Free Survival ◽  
Lymph Node Status ◽  
Free Survival ◽  
Fertility Sparing ◽  
Mlh1 Methylation ◽  
Lymphovascular Space Invasion

ObjectiveEndometrial cancer in pre-menopausal patients aged ≤40 years is rare and poses both diagnostic and management challenges. The goal of this study was to investigate the clinical and pathologic factors associated with endometrial cancer in this group and their impact on survival.MethodsPatients with endometrial cancer treated between January 2004 and August 2016 were retrospectively reviewed. Patients who underwent either primary surgical treatment or fertility-sparing therapy were included. Exclusion criteria were age >60 years and patients who received neoadjuvant chemotherapy or primary radiation. Age at diagnosis was used to classify patients into two groups: ≤40 and 41–60 years. Clinical and pathologic variables were compared between the groups. Progression-free survival and overall survival were estimated using Cox proportional hazards.ResultsA total of 551 patients were evaluated, of which 103 (18.7%) patients were ≤40 years and 448 (81.3%) were 41–60 years. Age ≤40 years was associated with higher body mass index (38.8 vs 35.8 kg/m2, p=0.008), non-invasive cancers (54.2% vs 32.6%, p<0.001), lower uterine segment involvement (27.2% vs 22.5%, p<0.001), and less lymphovascular space invasion (16.8% vs 29.1%, p=0.015). The rate of synchronous ovarian cancer was 9.2% vs 0.7% in age 41–60 years (p<0.001), and 19% of women with endometrial cancer aged ≤40 years underwent fertility-sparing therapy. Grade, stage, myometrial invasion, lymphovascular space invasion, and lymph node status were associated with survival, and fertility-sparing therapy adversely affected the recurrence rate of the age ≤40 years cohort. Among all patients aged ≤60 years, mismatch repair deficiency due to MLH1 methylation was associated with worse progression-free survival, 48.6% vs 83.3% (HR 1.98, 95% CI 1.06 to 3.17, p=0.032), and overall survival, 56.5% vs 90.0% (HR 2.58, 95% CI 1.13 to 5.90, p=0.025).ConclusionsPatients aged ≤40 years with endometrial cancer have more favorable prognostic factors and higher rates of synchronous tumors. Fertility-sparing therapy was associated with higher recurrence rates. The prognostic value of MLH1 methylation in this population warrants further investigation.

scholarly journals Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer

2020 ◽  
Vol 16 (7) ◽  
pp. 225-246 ◽  
Author(s):  
Carolyn E Haunschild ◽  
Krishnansu S Tewari
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Double Blind ◽  
Free Survival ◽  
Platinum Sensitive ◽  
The Us ◽  
Us Fda

On 13 June 2018, Genentech, Inc. issued a press release announcing that the US FDA had approved the antiangiogenesis drug, bevacizumab, in combination with chemotherapy for frontline and maintenance therapy for women with newly diagnosed ovarian cancer. Regulatory approval was based on the National Cancer Institute-sponsored Gynecologic Oncology Group (GOG) protocol 0218, the Phase III, randomized, placebo-controlled, double-blind, multi-center and multi-national clinical trial that met its primary end point, progression-free survival. Bevacizumab is now approved in the frontline, platinum-sensitive recurrent and platinum-resistant recurrent settings for epithelial ovarian cancer. This review will address the broad range of clinical trials addressing the efficacy of bevacizumab use in ovarian cancer.

scholarly journals Phase II Trial of Ixabepilone As Second-Line Treatment in Advanced Endometrial Cancer: Gynecologic Oncology Group Trial 129-P

2009 ◽  
Vol 27 (19) ◽  
pp. 3104-3108 ◽  
Author(s):  
Don S. Dizon ◽  
John A. Blessing ◽  
D. Scott McMeekin ◽  
Sudarshan K. Sharma ◽  
Paul DiSilvestro ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Gynecologic Oncology Group ◽  
Second Line ◽  
Chemotherapeutic Regimen ◽  
Recurrent Endometrial Cancer ◽  
Grade 3

Purpose A phase II study was conducted to determine the response rate of ixabepilone (BMS-247550, National Cancer Institute (NCI)–supplied agent investigational new drug No. 59,699) in patients with persistent or recurrent endometrial cancer who have progressed despite standard therapy. Patients and Methods Eligible patients had recurrent or persistent endometrial cancer and measurable disease. One prior chemotherapeutic regimen, which could have included either paclitaxel or docetaxel, was allowed. Patients received ixabepilone 40 mg/m2 as a 3-hour infusion on day 1 of a 21-day cycle. Treatment was continued until disease progression or until unacceptable toxicity occurred. Results Fifty-two patients were entered on the study, and 50 of these were eligible. The median age was 64 years (range, 40 to 83 years). Prior treatment included radiation in 21 patients (42%) and hormonal therapy in eight patients (16%). All patients had prior chemotherapy, and 47 (94%) received prior paclitaxel therapy. The overall response rate was 12%; one patient achieved a complete remission (2%), and five achieved partial remission (10%). Stable disease for at least 8 weeks was noted in 30 patients (60%). The median progression-free survival (PFS) was 2.9 months, and the 6-month PFS was 20%. Major grade 3 toxicities were neutropenia (52%), leukopenia (48%), gastrointestinal (24%), neurologic (18%), constitutional (20%), infection (16%), and anemia (14%). Conclusion In a cohort of women with advanced or recurrent endometrial cancer who were previously treated with paclitaxel, ixabepilone showed modest activity of limited duration as a second-line agent.

Multicenter Clinicopathological Study of High-Grade Serous Carcinoma Presenting as Primary Peritoneal Carcinoma

2018 ◽  
Vol 28 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Shinichi Komiyama ◽  
Yoshihiro Nishijima ◽  
Haruhiro Kondo ◽  
Hiroyuki Nomura ◽  
Satoshi Yamaguchi ◽  
...  
Keyword(s):  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Serous Carcinoma ◽  
Tumor Diameter ◽  
Gynecologic Oncology Group ◽  
High Grade ◽  
Debulking Surgery ◽  
Free Survival ◽  
Primary Debulking Surgery

ObjectiveWe conducted a multicenter clinicopathological study to characterize patients with high-grade serous carcinoma presenting as primary peritoneal carcinoma (clinical PPC).MethodsAt 9 sites in Japan, patients with clinical PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian involvement by high-grade serous carcinoma. There was no systematic detailed histopathological review of the fallopian tubes to determine whether they were involved by serous carcinoma.ResultsThere were 139 patients and 64% were aged 60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL. Pretreatment performance status was poor in more than 50%, endometrial cytology was positive in 40.3%, and the preoperative clinical diagnosis was correct in 72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64% underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). The main tumor sites were the upper abdomen (greater omentum), extrapelvic peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of patients undergoing systematic retroperitoneal node dissection. The optimal surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with postoperative chemotherapy. Median progression-free survival was 19.0 months and median overall survival was 41.0 months. Multivariate analysis showed that prognostic factors for progression-free survival were NAC and residual tumor diameter after debulking surgery, whereas the only prognostic factor for overall survival was the residual tumor diameter.ConclusionsThis study identified various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a reasonable treatment strategy, and complete debulking surgery is optimum.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study

2021 ◽  
Vol 31 (11) ◽  
pp. 1437-1442
Author(s):  
Ori Tal ◽  
Ram Eitan ◽  
Ofer Gemer ◽  
Limor Helpman ◽  
Zvi Vaknin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Platelet Count ◽  
Gynecologic Oncology ◽  
Myometrial Invasion ◽  
Gynecologic Oncology Group ◽  
Disease Specific Survival ◽  
Oncology Group ◽  
Disease Specific ◽  
Lymphovascular Space Invasion

ObjectiveEndometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients.MethodsThis is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II–IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate–high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon’s discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher’s exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations.ResultsOf the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival.ConclusionsPretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

scholarly journals Quality of Life of Patients With Endometrial Cancer Undergoing Laparoscopic International Federation of Gynecology and Obstetrics Staging Compared With Laparotomy: A Gynecologic Oncology Group Study

2009 ◽  
Vol 27 (32) ◽  
pp. 5337-5342 ◽  
Author(s):  
Alice B. Kornblith ◽  
Helen Q. Huang ◽  
Joan L. Walker ◽  
Nick M. Spirtos ◽  
Jacob Rotmensch ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Endometrial Cancer ◽  
Return To Work ◽  
Gynecologic Oncology ◽  
Surgical Techniques ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Gynecology And Obstetrics ◽  
The Difference

Purpose The study's objective was to compare the quality of life (QoL) of patients with endometrial cancer undergoing surgical staging via laparoscopy versus laparotomy. Patients and Methods The first 802 eligible patients (laparoscopy, n = 535; laparotomy, n = 267) participated in the QoL study in a Gynecologic Oncology Group (GOG) randomized trial of laparoscopy versus laparotomy (GOG 2222). Patients completed QoL assessments at baseline; at 1, 3, and 6 weeks; and at 6 months postsurgery. Results In an intent-to-treat analysis, laparoscopy patients reported significantly higher Functional Assessment of Cancer Therapy–General (FACT-G) scores (P = .001), better physical functioning (P = .006), better body image (BI; P < .001), less pain (P < .001) and its interference with QoL (P < .001), and an earlier resumption of normal activities (P = .003) and return to work (P = .04) over the 6-week postsurgery period, as compared with laparotomy patients. However, the differences in BI and return to work between groups were modest, and the adjusted FACT-G scores did not meet the minimally important difference (MID) between the two surgical arms over 6 weeks. By 6 months, except for better BI in laparoscopy patients (P < .001), the difference in QoL between the two surgical techniques was not statistically significant. Conclusion Although the FACT-G did not show a MID between the two surgical groups, and only modest differences in return to work and BI were found between the two groups, statistically significantly better QoL across many parameters in the laparoscopy arm at 6 weeks provides modest support for the QoL advantage of using laparoscopy to stage patients with early endometrial cancer.

scholarly journals Phase II Evaluation of Pemetrexed in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian or Primary Peritoneal Carcinoma: A Study of the Gynecologic Oncology Group

2009 ◽  
Vol 27 (16) ◽  
pp. 2686-2691 ◽  
Author(s):  
David S. Miller ◽  
John A. Blessing ◽  
Carolyn N. Krasner ◽  
Robert S. Mannel ◽  
Parviz Hanjani ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Free Survival ◽  
Peritoneal Cancer ◽  
Platinum Resistant ◽  
Grade 3 ◽  
Dose Delay

Purpose To estimate the antitumor activity of pemetrexed in patients with persistent or recurrent platinum-resistant epithelial ovarian or primary peritoneal cancer and to determine the nature and degree of toxicities. Patients and Methods A phase II trial was conducted by the Gynecologic Oncology Group. Patients must have had cancer that had progressed on platinum-based primary chemotherapy or recurred within 6 months. Pemetrexed at a dose of 900 mg/m2 was to be administered as an intravenous infusion over 10 minutes every 21 days. Dose delay and adjustment was permitted for toxicity. Treatment was continued until disease progression or unacceptable adverse effects. Results From July 6, 2004, to August 23, 2006, 51 patients were entered. A total of 259 cycles (median, four; range one to 19 cycles) of pemetrexed were administered, with 40% of patients receiving six or more cycles. Overall, the treatment was well tolerated. More serious toxicities (grade 3 and 4) included neutropenia in 42%, leukopenia in 25%, anemia in 15%, and constitutional in 15% of patients. No treatment-related deaths were reported. One patient (2%) had a complete and nine patients (19%) had partial responses, with a median duration response of 8.4 months. Seventeen patients (35%) had stable disease for a median of 4.1 months. Eighteen patients (38%) had increasing disease. Three patients (6%) were not assessable. Median progression-free survival was 2.9 months, and overall survival was 11.4 months. Conclusion Pemetrexed has sufficient activity in the treatment of recurrent platinum-resistant ovarian cancer at the dose and schedule tested to warrant further investigation.

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