Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer.
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ABSTRACT:
SUBMITTER: Chapman BV
PROVIDER: S-EPMC7523189 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer.
Chapman Bhavana V BV Swanick Cameron W CW Ning Matthew S MS Allen Pamela K PK Soliman Pamela T PT Westin Shannon N SN Pardeshi Vishakha V Broaddus Russell R RR Lu Karen H KH Jhingran Anuja A Eifel Patricia J PJ Klopp Ann H AH
Gynecologic oncology 20190517 1
<h4>Objective</h4>To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer.<h4>Methods</h4>We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method.<h4>Results</h4>The 5-y ...[more]
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Project description:BackgroundThis study aimed to develop a nomogram to predict the survival for stage IIIC endometrial cancer (EC) patients with adjuvant radiotherapy (ART) alone and personalize recommendations for the following adjuvant chemotherapy (ACT).MethodsIn total, 746 stage IIIC EC patients with ART alone were selected from the Surveillance, Epidemiology, and End Results (SEER) registry. Cox regression analysis was performed to identify independent risk factors. A nomogram was developed accordingly, and the area under the receiver operating characteristic curve (AUC) and C-index were implemented to assess the predictive power. The patients were divided into different risk strata based on the total points derived from the nomogram, and survival probability was compared between each risk stratus and another SEER-based cohort of stage IIIC EC patients receiving ART+ACT (cohort ART+ACT).ResultsFive independent predictors were included in the model, which had favorable discriminative power both in the training (C-index: 0.732; 95% CI: 0.704-0.760) and validation cohorts (C-index: 0.731; 95% CI: 0.709-0.753). The patients were divided into three risk strata (low risk <135, 135 ≤ middle risk ≤205, and high risk >205), where low-risk patients had survival advantages over patients from cohort ART+ACT (HR: 0.45, 95% CI: 0.33-0.61, P < 0.001). However, the middle- and high-risk patients were inferior to patients from cohort ART+ACT in survival (P < 0.001).ConclusionA nomogram was developed to exclusively predict the survival for stage IIIC EC patients with ART alone, based on which the low-risk patients might be perfect candidates to omit the following ACT. However, the middle- and high-risk patients would benefit from the following ACT.
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Project description:ObjectiveTo examine the survival of women with stage I non-endometrioid endometrial cancer with malignant peritoneal cytology.MethodsA retrospective observational cohort study was conducted to examine the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I serous, clear cell, carcinosarcoma, undifferentiated, and mixed endometrial cancer with known peritoneal cytology results at hysterectomy were examined (N = 4506). Propensity score inverse probability of treatment weighting was used to balance the measured covariates, and survival outcomes were assessed according to peritoneal cytology results.ResultsMalignant peritoneal cytology was reported in 401 (8.9%) women. In multivariable analysis, older age, serous histology, and large tumors were associated with an increased likelihood of malignant peritoneal cytology (all, P < 0.05). In a propensity score weighted model, malignant peritoneal cytology was associated with a nearly two-fold increase in all-cause mortality risk compared to negative peritoneal cytology (5-year rates, 63.4% versus 80.2%, hazard ratio 2.18, 95% confidence interval 1.78-2.66). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in old and young age groups, serous, clear cell, carcinosarcoma, and mixed histology groups, stage T1a disease, and staged and unstaged cases, but not for stage T1b disease. Difference in 5-year overall survival rates between the malignant and negative peritoneal cytology groups was particularly large among those with clear cell histology (24.0%), stage T1a disease (19.4%), aged >78 years (18.2%), and serous tumors (17.6%).ConclusionMalignant peritoneal cytology can be prevalent in stage I non-endometrioid endometrial cancer. Our study suggests that malignant peritoneal cytology is a prognostic factor for decreased survival in stage I non-endometrioid endometrial cancer.
| S-EPMC7751572 | biostudies-literature
Project description:ImportanceCombined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small cell lung cancer (SCLC), but there may be barriers to utilization in the United States.ObjectiveTo estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database.Design, setting, and participantsAnalysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database.Main outcomes and measuresUtilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival.ResultsA total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P < .001) and radiation therapy (OR, 0.75; 95% CI, 0.67-0.85; P < .001) administration on multivariable analysis. Medicare/Medicaid insurance had no impact on chemotherapy use, whereas Medicaid (OR, 0.79; 95% CI, 0.72-0.87; P < .001) and Medicare (OR, 0.86; 95% CI, 0.82-0.91; P < .001) were independently associated with a lower likelihood of radiation therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P < .001), Medicaid (HR, 1.27; 95% CI, 1.21-1.32; P < .001), and Medicare (HR, 1.12; 95% CI, 1.09-1.15; P < .001) coverage were independently associated with shorter survival on adjusted analysis, while chemotherapy (HR, 0.55; 95% CI, 0.54-0.57; P < .001) and radiation therapy (HR, 0.62; 95% CI, 0.60-0.63; P < .001) were associated with a survival benefit.Conclusions and relevanceSubstantial proportions of patients documented in a major US cancer registry did not receive radiation therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.
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Project description:PURPOSE:Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathologic characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. EXPERIMENTAL DESIGN:We used two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. RESULTS:The Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test, P = 0.565 for disease stage, 0.567 for tumor grade, and 1.3 × 10(-4) for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. CONCLUSIONS:Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies.
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Project description:Objective: The prognostic value of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IIIC staging in endometrioid carcinoma patients remains debatable. The current study aimed to compare the prognosis between IIIC1 and IIIC2 patients with endometrioid carcinoma and attempt to conduct a new subdivision. Methods: By using the Surveillance, Epidemiology, and End Results (SEER) database, patients with endometrioid-type endometrial cancer diagnosed from 2004 to 2015 were identified and randomly divided into training and validation sets. We developed a Fine-Gray competing risk model to compare the cancer-specific mortality (CSM). The IIIC subdivision system was built based on the independent prognostic factors. The cumulative incidence curves were compared using Gray's test or log-rank test. Nomogram for predicting 3- or 5-years CSM was constructed and subsequently validated internally and externally. Results: The IIIC subdivision defined by FIGO staging, including IIIC1 and IIIC2, exhibited no association with CSM in multivariate analysis [subdistribution hazard ratio [SHR] = 1.03, 95% CI [0.85-1.26], P = 0.760]. The IIIC category was subdivided into three subcategories based on the tumor (T) and nodes (N) stage, including IIICa (T1N1 and T1N2), IIICb (T2N1 and T2N2), and IIICc (T2N1 and T2N2). The prognosis across new IIIC subcategories with CSM remained significant [IIICb vs. IIICa: SHR = 1.53, 95% CI [1.18-1.98], P = 0.001; IIICc vs. IIICa: SHR = 2.64, 95% CI [2.13-3.28], P < 0.001]. Postoperative adjuvant chemotherapy or radiotherapy alone did not improve survival for patients categorized as IIICa or IIICb, and all IIIC patients benefited most from combination of postoperative chemotherapy and radiotherapy [IIICa: SHR = 0.59, 95% CI [0.43-0.82], P = 0.001; IIICb: SHR = 0.66, 95% CI [0.45-0.97], P = 0.036; IIICc: SHR = 0.44, 95% CI [0.34-0.58], P < 0.001]. A nomogram based on competing risk model was built to predict the long-term survival of IIIC patients, with a concordance index above 0.70 both in training and validation set. Conclusion: There was no prognostic difference between FIGO IIIC1 and IIIC2 patients with endometrioid-type endometrial cancer. A new subdivision of IIIC category facilitates prognosis prediction and treatment modalities. A combination of postoperative chemotherapy and radiotherapy exerted as the optimal choice for endometrioid cancer patients with IIIC stage.
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Project description:Study designRetrospective cohort study.IntroductionDebates remain regarding the role of lymphadenectomy in patients with apparent stage IA endometrial cancer, especially subtypes with a favorable prognosis. This study aimed to explore the prognostic value of staging surgeries in apparent stage IA endometrial endometrioid cancer patients in a retrospective cohort study.MethodsCases from June 1, 2010 to June 1, 2017 were reviewed in patients with pathologically confirmed endometrial endometrioid carcinoma limited to <1/2 of the myometrium, without extrauterine metastasis on preoperative evaluation and during surgical inspection. Survival outcomes were compared between patients with and without lymphadenectomy and between patients with and without metastasis to lymph nodes.ResultsIn total, 1,312 eligible patients were included, among which 836 underwent staging surgeries and 476 underwent simple hysterectomy. Twenty-eight patients were found with metastasis to retroperitoneal lymph nodes. After a median follow-up of 57.4 months, lost to follow-up, recurrence, death, and cancer-specific death occurred in 28, 39, 24, and 16 patients, respectively. In a univariate analysis, lymphadenectomy of the pelvis with or without para-aortic lymph nodes had no significant impact on disease-free survival, overall survival or cancer-specific overall survival (p values >0.05). However, after adjusting for important baseline risk factors [menopausal status, tumor differentiation, maximum diameter and location, lymph-vascular space invasion (LVSI) status, and postoperative adjuvant therapy), lymphadenectomy resulted in significantly improved survival outcomes (p values <0.05). Menopause (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.3-16.4, p=0.015), tumor diameter larger than 2 cm (OR 4.6, 95% CI 1.3-16.0, p=0.016), grade 3 tumors (OR 3.0, 95% CI 1.0-8.5, p=0.042), positive LVSI (OR 8.7, 95% CI 3.7-20.4, p<0.001) and lower uterine segment involvement (OR 3.1, 95% CI 1.4-7.2, p=0.007) had more extrauterine metastases.ConclusionIn cases of apparent stage IA endometrioid endometrial carcinoma, staging surgeries should be considered in patients with larger, higher grade tumors, positive LVSI, or lower uterine segment involvement.
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Project description:ObjectiveGaps in access to appropriate cancer care, and associated cancer mortality, have widened across socioeconomic groups. We examined whether demographic and socioeconomic factors influenced receipt of adjuvant radiation therapy (RT) in patients with high-risk, early-stage endometrial cancer.MethodsA retrospective study cohort was selected from 349,404 endometrial carcinoma patients from the National Cancer Database in whom adjuvant RT would be recommended per national guidelines. The study included surgically treated patients with endometrioid endometrial cancer with one of the following criteria: 1) FIGO 2009 stage IB, grade 1/2 disease, age ≥ 60 years; 2) stage IB, grade 3 disease; or 3) stage II disease. Logistic regression analysis was performed to identify factors associated with omission of adjuvant RT. Association between adjuvant RT, covariables, and overall survival (OS) was assessed with multivariable Cox proportional hazards models.Results19,594 patients were eligible for analysis; 47% did not receive adjuvant RT. Omission of adjuvant RT was more prevalent among African-American, Hispanic, and Asian compared to non-Hispanic white patients (OR 0.79, 95%CI: 0.69-0.91; OR 0.75, 95%CI: 0.64-0.87; OR 0.75, 95%CI: 0.60-0.94, respectively). Lower median household income of patient's area of residence, lack of health insurance, treatment at non-academic hospitals, farther distance to treatment facilities, and residence in metropolitan counties were associated with omission of adjuvant RT. Such omission was independently associated with worse OS (HR1.43, p < 0.001).ConclusionAdjuvant RT is omitted in 47% of patients with early-stage, high-risk endometrial cancer, which is associated with poor access to appropriate, high-quality care and worse outcome.
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Project description:Stage III NSCLC comprises of a heterogeneous group of patients with regard to stage, extent of disease and prognosis. Disease presentation can often be complex in clinical practice, and the challenges are not well-defined in clinical trials or practice guidelines. In order to improve the therapeutic ratio of treatment, one needs to either increase the benefit of treatment or reduce toxicities, or both. Priorities in radiation therapy include dose escalation, imaging advances, improved target delineation, reduced planning target volume margin, intensity-modulated radiotherapy, image-guided radiotherapy, motion management and the use of cytoprotectants. Priorities in systemic therapy include the incorporation of molecularly targeted and immune-modulatory agents.
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Project description:There are many studies assessing the importance of myometrial invasion using a cut-off limit as 50% of myometrial invasion for endometrial cancer, and there are a limited number of studies evaluating tumor-free distance to the serosa. To evaluate the prognostic performance of tumor-free distance and percentage of myometrial invasion in patients with stage IB endometrioid endometrial cancer, we retrospectively evaluated 133 patients diagnosed and treated as stage IB endometrioid endometrial cancer. Tumor-free distance was assessed, and recurrence and recurrence-free survival were analyzed. Nine patients had recurrent disease (6.8%). Recurrence-free survival was 200 months. Two patients died because of malignancy. In the Cox regression model according to tumor-free distance, depth of invasion, and percentage of myometrial invasion, it was seen that none of these parameters were significant to predict the recurrence (p > 0.05). In conclusion, tumor-free distance is not an independent prognostic factor for patients with stage IB endometrioid endometrial cancer.
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