IB Grade Research Articles

Abstract CT302: Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors

Abstract Background: The immunomodulatory receptor TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers. In preclinical models, co-inhibition of the TIGIT and PD-L1/PD-1 pathways improved anti-tumor activity compared to either agent alone. Tiragolumab (tira or MTIG7192A) is a humanized IgG1/kappa monoclonal antibody (mAb) that binds TIGIT to prevent its interaction with its ligand PVR (CD155). In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of tira as a single agent and in combination with atezolizumab (atezo) in patients with advanced solid tumors. Methods: Enrolled patients, ECOG PS 0-1, had advanced tumors for whom standard therapy did not exist or was ineffective. Patients received escalating doses of tira alone IV Q3W alone (Phase Ia) or in combination with atezo 1200 mg IV Q3W (Phase Ib) to determine the maximum tolerated dose (MTD) and continued until disease progression, intolerable toxicity, or patient/investigator decision. Study objectives included evaluation of safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of tira alone or tira + atezo. Data cut-off date was April 2019. Results: 73 patients with multiple tumor types were treated in dose-escalation (24 in Phase Ia, 49 in Ib with tira + atezo). In Phase Ia and Phase Ib, median age was 60 and 54 years, ECOG 0 for 29% and 27% of patients, and those who received ≥ 3 prior therapies were 67% and 57%, respectively. No DLTs were observed. Across doses, treatment-related AEs occurred in 67% in Phase Ia and 59% in Phase Ib (Grade ≥ 3: 4% and 4%, respectively), and most common AEs were fatigue (38%) in Phase Ia and anemia (31%) in Phase Ib. Exposure of tira increased with increasing dose, and saturation of nonlinear PK occurred at tira doses ≥ 100 mg Q3W. Complete and sustained occupancy of peripheral TIGIT receptors was observed at tira doses ≥ 30 mg Q3W. In Phase Ia, there were no objective responses, but SD of > 4 months duration was observed (n=4). In Phase Ib, there were 3 responses, which all occurred in PD-L1 positive tumors (2 non-small cell lung cancer [NSCLC]: 1 CR, 1 PR; and 1 head/neck squamous cell carcinoma: PR) with two patients not receiving prior immunotherapy (CIT-naïve). Therefore, expansion cohorts were initiated in PD-L1-positive CIT-naïve indications in Phase Ib. In the metastatic NSCLC expansion cohort (n=14) ORR was 50%, with 1 CR and 6 PRs; DCR was 79%, and the safety profile was similar. Conclusions: Tira monotherapy or combined with atezo was well-tolerated and had an acceptable safety profile across all dose levels. Preliminary anti-tumor activity was observed in Phase Ib with tira + atezo in CIT-naïve PD-L1-positive tumors, including NSCLC, and enrollment is ongoing in these expansion cohorts. Citation Format: Johanna C. Bendell, Philippe Bedard, Yung-Jue Bang, Patricia LoRusso, Stephen Hodi, Michael Gordon, Sandra D'Angelo, Sandra D'Angelo, Jayesh Desai, Elena Garralda, Antoine Italiano, Myung-Ju Ahn, Andres Cervantes, Zev Wainberg, Emiliano Calvo, Marta Gil-Martin, Maria Martinez-Garcia, Rastilav Bahleda, Philippe Cassier, Jean-Pierre Delord, Amy Prawira, Ignacio Melero, Leisha Emens, Emanuela Romano, Karen Miller, Robert W. Hsieh, Cloris Xue, Kari Morrissey, Patrick Twomey, Kelly Gash, Namrata S. Patil, Jane Grogan, Raymond Meng, Byoung Cho, Tae Won Kim. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT302.

Survival benefit of radiation in high-risk, early-stage endometrioid carcinoma.

ObjectiveTo better delineate optimal management of high-risk, early-stage endometrial cancer, as national guidelines permit substantial practice variations.MethodsPatients with International Federation of Gynecology and Obstetrics (FIGO) stage IB grade 3 and stage II endometrioid carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant treatments were brachytherapy (BT), external beam radiation therapy (EBRT), and chemotherapy. Death from endometrial cancer (cancer-specific mortality [CSM]) and local recurrence were analyzed using Gray's test and Fine-Gray regression.ResultsIn total, 1,095 patients were identified: 52% received BT, 56% received EBRT, 16% received chemotherapy, and 29% received no adjuvant treatment. Survival outcomes were significantly worse for stage IB grade 3 and stage II grade 3 relative to stage II grades 1–2 (5-year CSM: 18% and 23% vs. 10%; p<0.001 and p=0.003, respectively), while there was no difference between stage IB grade 3 and stage II grade 3 (p=0.618). BT had a local control benefit across all patients (p<0.001) that translated into a survival benefit in stage IB grade 3 (adjusted hazard ratio [HR] for CSM=0.47, p=0.003). EBRT had a survival benefit in stage II grade 3 (adjusted HR for CSM=0.36; p=0.031), as did lymph node dissection (p=0.015). Chemotherapy was not significantly correlated with CSM.ConclusionsHigh-risk, early-stage endometrioid carcinoma is a heterogeneous population. BT was associated with a survival benefit in stage IB grade 3, whereas regional treatment with EBRT and lymphadenectomy was associated with a survival benefit in stage II grade 3.

Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy

IntroductionRisk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade...

Outcomes of FIGO 2009 stage IB grade 2 or 3 endometrioid endometrial adenocarcinoma treated with adjuvant vaginal brachytherapy following comprehensive surgical staging

Objective: Optimal adjuvant treatment of patients with FIGO 2009 stage IB grade 2 or 3 endometrioid endometrial cancer (EEC) is controversial. We sought to assess the outcomes of patients with FIGO 2009 stage IB grade 2 or 3 EEC treated with comprehensive surgical staging (CSS) and vaginal brachytherapy (VBT) as sole adjuvant treatment.

Survival Benefit of Radiation in High-Risk Early-Stage Endometrioid Carcinoma

Objective: To better delineate optimal management of high-risk, early-stage endometrial cancer, as national guidelines permit substantial practice variations. Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB grade 3 and stage II endometrioid carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant treatments were brachytherapy (BT), external beam radiation therapy (EBRT), and chemotherapy. Death from endometrial cancer (cancer-specific mortality [CSM]) and local recurrence were analyzed using Gray''s test and Fine-Gray regression. Results: In total, 1,095 patients were identified: 52% received BT, 56% received EBRT, 16% received chemotherapy, and 29% received no adjuvant treatment. Survival outcomes were significantly worse for stage IB grade 3 and stage II grade 3 relative to stage II grades 1-2 (5-year CSM: 18% and 23% vs. 10%; p<0.001 and p=0.003, respectively), while there was no difference between stage IB grade 3 and stage II grade 3 (p=0.618). BT had a local control benefit across all patients (p<0.001) that translated into a survival benefit in stage IB grade 3 (adjusted hazard ratio [HR] for CSM=0.47, p=0.003). EBRT had a survival benefit in stage II grade 3 (adjusted HR for CSM=0.36; p=0.031), as did lymph node dissection (p=0.015). Chemotherapy was not significantly correlated with CSM. Conclusions: High-risk, early-stage endometrioid carcinoma is a heterogeneous population. BT was associated with a survival benefit in stage IB grade 3, whereas regional treatment with EBRT and lymphadenectomy was associated with a survival benefit in stage II grade 3.

Management of Stage IB Grade III Endometrial Cancer: Single Institute Experience

Background and Objective: There is marked controversy regarding optimal management patients with stage IB grade III endometrial carcinoma. The present study analyzes the current practices regarding adjuvant radiation therapy for those patients in our institute and also assessed prognostic factor affecting overall survival outcome. Patients and Methods: A total 66 patients with postoperative FIGO stage 1B, grade III endometrial carcinoma were treated and evaluated between the years 2009 and 2014. Risk factors assessed age (4 cm), site of primary tumor (involvement of lower uterine segment versus no involvement), Lymphadenectomy (performed versus not performed), Lymph-vascular space invasion (positive or negative), type of surgery performed (less than total abdominal hysterectomy and bilateral salpingo-ophorectomy (TH/BSO) versus greater than or equal TH/BSO), radiation sequence with surgery (no radiation versus adjuvant radiation), and type of radiation (pelvic external beam radiotherapy versus vaginal brachytherapy versus both). Results: Adjuvant radiation therapy after surgery was associated with significantly better time to relapse (p = 0.001) in comparison to those patients who underwent surgery alone. There was statistically significant improvement of survival of patients who received adjuvant radiation therapy in comparison with those who underwent surgery alone. There was no statistically significant difference in relapse between external pelvic radiotherapy, brachytherapy and both (p = 0.161). There was no statistically significant difference in overall survival between different types of adjuvant radiation therapy (p = 0.318). Adjuvant radiation therapy (HR 0.173, 95% CI 0.049 - 0.609, p = 0.006) and tumor size (HR 4.065, 95% CI 1.120 - 14.761, p = 0.033) were the only statistically significant predictors for relapse in multivariate analysis. Adjuvant radiation therapy (HR 0.159, 95% CI 0.045 - 0.563, p = 0.004), age (HR 10.357, 95% CI 1.195 - 89.746, p = 0.034) and lymphadenectomy (HR 0.240, 95% CI 0.071 - 0.811, p = 0.022) were statistically significant predictors for overall survival. Conclusion: The current study suggested that adjuvant radiation therapy definitely improve survival of patients with stage IB, grade III endometrial cancer. There is a need for more randomized trials to define patients who require adjuvant radiation therapy and define what type of radiation should be received. Well defined guidelines are very important to standardize treatment and cut costs in clinical practice.

Predictors of Pelvic Recurrence in Stage IB Grade 2-3 Endometrioid Endometrial Adenocarcinoma Treated with Post-Operative Vaginal Brachytherapy

Optimal adjuvant management of surgically staged FIGO stage IB grade 2 (G2) and grade 3 (G3) endometrial endometrioid adenocarcinoma (EAC) is controversial. The objective of this study is to report outcomes utilizing adjuvant vaginal brachytherapy (VB) without pelvic radiotherapy (RT) for patients with surgically staged IB G2 and G3 EAC and to analyze rates and predictors of pelvic recurrence. Retrospective review of an institutional database identified patients diagnosed between 2005-2015 with 2009 FIGO stage IB G2 and G3 EAC. All patients underwent comprehensive surgical staging and VB as the sole adjuvant RT as per institutional guidelines during the study period. Disease free survival (DFS) was calculated from the date of primary surgery to date of last follow up or recurrence, and a minimum of 6 months follow-up was required for inclusion. Kaplan-Meier methods were used to estimate DFS. Pearson chi-squared test was used to determine association of pathologic variables and pelvic recurrence. A total of 78 patients were identified for inclusion. The median age at diagnosis was 67 (range, 42-93). Surgical staging included hysterectomy, bilateral salpingo-oopherectomy, pelvic washings, pelvic lymph node dissection (98.7%), and paraaortic node sampling (78.2%). Fifty-five patients (71%) had G2 EAC and 23 (29%) had G3 EAC. Lymphovascular invasion (LVI) was observed in 37 (47%), lower uterine segment involvement (LUSI) in 38 (49%), and outer 1/3rd myometrial invasion (MMI) (defined as ≥ 67% MMI) in 39 (50%). Median number of pelvic lymph nodes removed was 18. The majority (88.5%) received VB alone and 11.5% received VB in combination with chemotherapy. Median follow up was 45.5 months (range 6.3-151.8) and 3-year estimated DFS was 84.7% for the entire cohort. There were a total of 11 recurrences, of which 3 (27.3%) were distant only. The remainder (72.3%) had a pelvic component including 5 which were pelvic and distant and 3 which were isolated to the pelvis. Median time to recurrence was 27.8 months (range, 11.5 - 46.9). On univariate analysis, G3 versus G2 (p = 0.600), LVI present versus absent (p = 0.388), and ≥20 versus <20 pelvic nodes dissected (p = 0.051) were not associated with higher pelvic recurrence risk. Presence of LUSI (p = 0.03) and outer 1/3rd MMI (p = 0.03) were associated with increased risk of pelvic failure. Stage IB G2 and G3 patients treated with adjuvant VB following surgical staging overall fared well, and isolated pelvic recurrences were few in number. While grade and LVI were not associated with increased pelvic failure in this cohort, the association of LUSI and outer 1/3rd MMI is intriguing. Further investigation into risk factors for pelvic recurrence in stage I EAC would be valuable to identify subgroups which benefit the most from pelvic RT.

The impact of adjuvant therapy on survival in patients with FIGO Stage IB Grade 3 endometrial cancer

The impact of adjuvant therapy on survival in patients with FIGO Stage IB Grade 3 endometrial cancer

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Single-institutional outcomes of adjuvant brachytherapy for Stage I endometrial cancer—Are outcomes consistent with randomized studies?

PurposeVaginal brachytherapy (VBT) alone has been shown to be a viable adjuvant treatment strategy for most patients with Stage I endometrioid endometrial cancer. We sought to examine our institutional data following practice pattern changes resulting from the publications of GOG-99 and PORTEC-2. Methods and MaterialsWe retrospectively analyzed women who underwent adjuvant VBT after surgical staging for Stage 1 endometrioid endometrial cancer at our institution from 2007 to 2014. ResultsWe identified 297 women. Median time to last followup or death was 52.3 months (interquartile range: 32.3–72.3 months). By International Federation of Gynecology and Obstetrics 2009 staging, 162 patients (54.5%) had Stage IA and 128 (43.1%) had Stage IB disease. Ninety-nine (33.3%) patients had Grade 1, 153 (51.5%) had Grade 2, and 45 (15.2%) had Grade 3 disease. According to GOG-249 and PORTEC-2 criteria, 167 (56.2%) and 127 (42.7%) patients were with high–intermediate–risk disease. Two women had Stage IB Grade 3 disease. The most common high-dose-rate–VBT regimen was 2100 cGy/three fractions to a depth of 5 mm. Four (two acute and two late) (1.3%) Grade 3 genitourinary toxicities were reported: three episodes of vaginal dehiscence (after second course of VBT, 2 months after completion of VBT, and 1 year after completion of VBT) and one episode of radiation necrosis. Twenty-one (7%) women recurred: three recurred in the vagina, two recurred in the pelvic lymph nodes, and 16 recurred distantly. ConclusionsOutcomes appear consistent with published randomized data in women with high–intermediate–risk endometrial cancer who are treated with brachytherapy alone. Recurrence and complication rates were minimal.

Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort.

The role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity. From a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests. Median follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a "high-risk" group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001). In this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

Prognostic significance of peritoneal cytology in low-intermediate risk endometrial cancer

ObjectivesThere is uncertainty surrounding the prognostic value and clinical utility of peritoneal cytology in endometrial cancer. Our primary objective was to determine if positive cytology is associated with disease-free and overall survival in women treated surgically for endometrial cancer, specifically those with low or intermediate risk disease. MethodsThis was a retrospective population-based cohort study of British Columbia Cancer Registry patients who underwent surgery with peritoneal washings for endometrioid-type endometrial cancer from 2003 to 2009. Low risk was defined as Stage IA grade 1 or 2, and intermediate risk defined as Stage IA grade 3, or Stage IB grade 1 or 2 tumours. Five-year overall and disease free-survival were assessed using Kaplan-Meier estimation. Potential covariates including peritoneal cytology, grade, depth of myometrial invasion, LVSI, age, and adjuvant therapy were evaluated in a multivariable Cox proportional hazards model. ResultsThere were 849 patients, of whom 370 (43.6%) and 298 (35.1%) had low- and intermediate-risk disease, respectively. Overall, forty-nine (5.8%) patients had positive cytology, including 6 and 9 with low- and intermediate-risk respectively (2.2% within low and intermediate risk combined). Positive peritoneal cytology was not significantly associated with disease-free (HR 3.17, 95% CI 0.91–11.03) or overall survival (HR 1.33, 95% CI 0.47–3.76) in low and intermediate risk patients. Only age and extensive LVSI were associated with lower overall survival (HR 1.10, 95% CI 1.08–1.13, and HR 2.39, 95% CI 1.02–5.61, respectively). ConclusionsPositive peritoneal cytology was not associated with disease-free and overall survival in women with low and intermediate risk endometrial cancer.

Fluorescence-assisted sentinel (SND) and pelvic node dissections by single-port transvaginal laparoscopic surgery, for the management of an endometrial carcinoma (EC) in an elderly obese patient

ObjectiveTo explore the feasibility of an oncologically acceptable management for an intermediate-risk endometrial cancer (EC) in an elderly, using the combination of transvaginal single-port laparoscopy and sentinel node policy. MethodsFor this 85-years old patient, BMI 32kg/m2, with IB grade 2 endometrioid EC, a single vaginal approach was attempted [1] to perform a total hysterectomy, bilateral salpinago-oophorectomy and pelvic node assessment guided by SND [2].Injections of indocyanine green (ICG) were performed at 3 and 9 o'clock and 2 depths [3] into the uterine cervix A simple vaginal hysterectomy was first performed using a 5mm vessel sealer (LigaSure®-Medtronics) to limit ICG leakage. As poorly accessible, adnexas were divided close to cornuas; uterine corpus was delivered vaginally. Then, a single port device (Gelpoint®-Applied), equipped with 3 trocars for optique and instruments, was installed through vagina. After transvaginal pneumoperitoneum insufflation, bowel loops were cleared from the pelvis. Latero-pelvic peritoneum was incised between external iliac pedicles and ureters. Following the algorithm, node dissection was limited to sentinel node clearly identified on the right side under color-segmented fluorescence (Pinpoint®-Novadaq), but a full pelvic dissection completed an unsatisfactory SND on the left side. Procedure was terminated with salpingo-oophorectomies. After protected vaginal specimen delivery, the single-port device was removed and vagina was closed as usual. ResultsPatient was discharged on the 1st post-operative day. Final pathology confirmed the FIGO stageIB grade2 EC. ConclusionsA transvaginal laparoscopic pelvic SND after vaginal hysterectomy is feasible. This single-port “NOTES” strategy bridges the previous gaps of a pure vaginal approach and seems interesting in fragile EC patients.

Practices in Management of Stage IB Grade III Endometrioid Cancer in the United States

Practices in Management of Stage IB Grade III Endometrioid Cancer in the United States

Utilization and Outcomes of Chemotherapy in Women With Intermediate-Risk, Early-Stage Ovarian Cancer.

To examine utilization and efficacy of chemotherapy for stage I ovarian cancer. We conducted a retrospective cohort study using the National Cancer Data Base to identify women with stage I ovarian cancer treated from 1998 to 2012. Patients were classified into three groups based on grade and stage: stage IA or IB grade 1 (low risk); stage IA or IB grade 2 (intermediate risk); and stage IA or IB grade 3 or any stage IC (high risk). Multivariable models were developed to examine predictors of chemotherapy use and survival. We identified 21,758 patients including 4,196 (19.3%) low-risk, 3,777 (17.4%) intermediate-risk, and 13,785 (63.4%) high-risk women. The median follow-up of the cohort was 63.9 months. Use of chemotherapy within the groups was 15.5%, 39.5%, and 69.8%, respectively (P<.001). Among low-risk patients, chemotherapy was not associated with a change in survival (adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.85-1.42), whereas chemotherapy was associated with reduced mortality for high-risk patients (adjusted HR 0.78, 95% CI 0.71-0.85). For intermediate-risk patients (stage IA-IB grade 2), chemotherapy was associated with a 26% reduction in mortality (adjusted HR 0.74, 95% CI 0.62-0.89). The association between chemotherapy and improved survival among intermediate-risk patients remained significant when limited to patients who underwent staging lymphadenectomy (adjusted HR 0.77, 95% CI 0.62-0.97). There is widespread variation in the patterns of care for early-stage ovarian cancer. Chemotherapy was associated with improved survival for stage IA-IB grade 2 patients.

No survival benefit with adjuvant chemotherapy in nonserous stage IB grade 2 epithelial ovarian cancer

Objectives: Data on the utility of adjuvant chemotherapy in patients with stage IB grade 2 epithelial ovarian cancer (EOC) are scant. Because serous histology is now reported as low- or high-grade, without an intermediate grade, this study explored the use of adjuvant chemotherapy in mucinous or endometrioid ovarian cancer. Current National Comprehensive Cancer Network guidelines state that chemotherapy is optional. We sought to evaluate the efficacy of chemotherapy and to identify factors that may predict survival in this population. Methods: The National Cancer Data Base was queried for all stage IB grade 2 EOC patients from 1998 to 2012. Only patients with mucinous or endometrioid histology and nodal dissection were analyzed. Χ2 test, logistic regression analysis, log-rank test and multivariable Cox proportional regression were conducted to determine factors associated with utilization of chemotherapy and survival. Results: A total of 227,499 patients had EOC during this period. Of these patients, 541 had stage IB grade 2 disease, with 401 having a nodal dissection. There were 226 endometrioid histology and 42 mucinous cases, for a total of 268 patients who were included. Chemotherapy was given in 60% of cases, with the majority (97%) receiving multiagent chemotherapy. There were no factors associated with the utilization of chemotherapy including histology, tumor size, age, race, facility location, or type. No association with histology or tumor size was seen with survival. Age, Charlson-Deyo Comorbidity index, and urban/rural location of patients were associated with survival on univariate analysis, but only age and location remained significant on multivariable analysis. The 5-year overall survival rates were 90% and 78% for patients who did and did not receive chemotherapy, respectively (P = .12). Conclusions: Stage IB grade 2 nonserous EOC is exceedingly rare. Even in a very large dataset, there were very few patients with this stage, grade, and histology. Because chemotherapy does not demonstrate a survival benefit in this subgroup, we recommend against adjuvant administration, given unnecessary cost and potential side effects.

Adjuvant brachytherapy for Stage IB Grade 2 endometrial carcinoma: Multivariate analysis of a single institution experience.

Objective:The aim was to investigate the value of postoperative brachytherapy for patients with Stage IB, Grade 2 endometrial carcinoma.Patients and Methods:Forty-six patients with Stage IB, Grade 2 endometrial carcinoma, were treated with simple hysterectomy and bilateral oophorectomy in our institution. The mean age was 63 (range, 42-81). Surgical staging, defined as peritoneal washing and pelvic lymph node sampling was performed in 73% of patients. Twenty-two patients (47%) received a postoperative intravaginal brachytherapy (IVRT), and 24 patients (53%) were followed-up without additional treatment.Results:The median follow-up was 60 months. The 5-year overall survival for irradiated and nonirradiated patients, was 83.5 and 94.7%, respectively. Four patients (8.7%) developed relapse, two in the group of postoperative IVRT and 2 in the follow-up only group. Multivariate analysis demonstrated a borderline association (P = 0.06) between lower uterine segment involvement and poor pelvic-vaginal control. The presence of GOG #99 high-risk features did not affect the pelvic control rate.Conclusion:According to our experience and previously published data, most patients with FIGO Stage IB, Grade 2 endometrial carcinoma may be cured with surgery alone.

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer.

ObjectiveEvaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC).MethodsTwo hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study.ResultsStage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis.ConclusionSequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III.

Clinicopathologic characteristics of endometrial cancer in Lynch syndrome.

5098 Background: Poor data exist on clinico-pathological description of endometrial cancer (EC) in Lynch syndrome (LS) compared with sporadic ones. To evaluate the clinico-pathological findings of Lynch-related EC to establish histological criteria to discriminate familial and sporadic EC and to decide the optimal management of patients. Methods: Retrospective study of prospective cohort of patients with LS in our institution from 1999 to 2011. We identified and described all cases of endometrial cancers. Management and follow-up were detailed. Results: Of a cohort of 126 patients with LS, 10 women developed endometrial carcinoma. The median age at diagnosis was 51 years (41-58). Five patients had an identified mutation (2 hMLH1, 2 hMSH2 and 1 hMSH6). In 9 cases, EC was the first Lynch-related tumor to occur. No patient developed ovarian cancer. All, except 2 patients (1 serous carcinoma and 1 clear cell carcinoma), had endometrioid adenocarcinoma (80%). Tumor grade was grade 1 in 3 patients, grade 2 in 5 and grade 3 in 2 patients. Forty per cent of patients had lymphovascular space involvement (LVSI). The FIGO stages were as follows: stage IA (n=7), stage IB (n=2) and stage IIIC (n=1). Four in ten patients had tumor located in the lower uterine segment. With a median follow-up of 14 months (range 9 – 40 months), recurrence occurred in one patient with a stage IB grade 2 endometrioid adenocarcinoma with LVSI. Conclusions: EC in LS is characterized by early age at onset, localization in lower uterine segment, and high rate of LVSI. Other data on histology and survival do not differ from sporadic cancers. These results suggest that we can consider conservative treatment in patients with good prognosis tumors. Further studies are required.

Stratégie ganglionnaire et cancer de l’endomètre : résultats de senti-endo

Based on two randomized trials and a meta-analysis, the recommendations of the National Cancer Institute (INCa) have validated the absence of systematic pelvic lymphadenectomy for patients with endometrial cancer at low risk (type 1 histology stage IA grade 1-2) and intermediate (type 1 histology stage IA grade 3 and IB grade 1-2) but without taking into account the contribution of the sentinel node (SN) procedure. The senti-endo trial assessing the role of the SN procedure in patients with early stages endometrial cancer showed that the detection rate by hemi-pelvis right and left were 77 and 76%, respectively. The detection rate per patient was 89%. Among patients with at least a SN detected, the detection was unilateral in 34 cases (31%) and bilateral in 77 cases (69%). Of the 111 patients with at least a SN detected, 19 had lymph node metastases (17%). Considering the hemi-pelvis right and left as a unit, no false negative case was observed, hence the sensitivity and NPV was 100%. Considering the NPV per patient, three false negative cases were observed. Among the 57 patients at low risk, six (11%) had lymph node metastases on SN with negative non sentinel nodes. Of the 33 patients at intermediate risk, five (15%) had lymph node metastases on SN with negative non sentinel nodes. Senti-endo results emphasize the contribution of the SN procedure to assess the nodal status in patients with low or intermediate risk group raising the issue on new definition of the recommendations of INCa.