Improved survival with combination chemotherapy and external beam radiation therapy in uterine carcinosarcoma.

OBJECTIVES: To evaluate differences in survival and recurrence patterns in stage I-IV uterine carcinosarcoma patients treated with surgery followed by adjuvant chemotherapy alone, radiation alone, or a combination of both chemotherapy and radiation therapy. METHODS: A multicenter retrospective analysis of patients with surgically staged carcinosarcoma receiving adjuvant therapy from January 2000 to December 2019 was conducted. Inclusion criteria were patients with carcinosarcoma who had received primary surgical treatment, followed by adjuvant therapy with chemotherapy alone, radiation therapy alone, or a combination of chemoradiation. Patients were excluded for incomplete surgical staging data, adjuvant brachytherapy alone, adjuvant chemotherapy and brachytherapy without external beam radiation therapy, receipt of neoadjuvant chemotherapy and/or pre-operative pelvic radiation, and death due to non-cancer causes. Sites of recurrence were analyzed by adjuvant treatment modality using Pearson's χ2 test. Progression-free and overall survival were calculated using Kaplan-Meier estimates. Multivariate analysis was performed using Cox proportional hazards model. RESULTS: Of 176 evaluable patients, 27% (n=47) had stage I, 14% (n=24) stage II, 37% (n=66) stage III, and 22% (n=39) stage IV disease. Among them, 33% (n=59) received chemotherapy alone, 17% (n=29) received radiation therapy alone, and 50% (n=88) received chemoradiation. Patients with stage I disease recurred less frequently (64%) versus stage II (83%), stage III (85%), and stage IV (90%) (p<0.001). Stage I disease demonstrated improved progression-free and overall survival relative to all other stages (p<0.01). Across all stages, patients receiving chemoradiation experienced superior progression-free (p=0.01) and overall survival (p=0.05) versus single modality therapy. However, when analyzed in a stage-specific manor, stage III disease derived the greatest survival benefit from chemoradiation versus all other stages (p<0.01). On multivariant analysis, only stage and receipt of chemoradiation were independent predictors of survival. CONCLUSION: Stage I disease demonstrated improved survival compared with other stages regardless of adjuvant treatment modality. Chemoradiation was associated with improved survival and better distant and local disease control for all stages of disease. Patients with stage III disease derived the most benefit from chemoradiation.

Multimodality adjuvant therapy and survival outcomes in stage I-IV uterine carcinosarcoma.

OBJECTIVES: Uterine carcinosarcoma is a rare, aggressive form of uterine cancer with a high recurrence rate and poor survival at all stages. We sought to evaluate the outcomes of patients treated with chemotherapy versus a combination of chemotherapy and radiation (chemoradiation) to determine survival. METHODS: A multicenter retrospective analysis of patients with stage I-IV carcinosarcoma was conducted from January 2000 to December 2017. Inclusion criteria were primary surgical management, defined as hysterectomy ± salpingo-oophorectomy, comprehensive surgical staging and/or tumor debulking, followed by adjuvant chemotherapy or chemoradiation. Differences in the frequencies of stage, cytoreduction status, treatment delays and sites of disease recurrence were identified using Pearson's χ2 test. Progression-free and overall survival rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 148 patients; 40.5% (n=60) chemotherapy and 59.5% (n=88) chemoradiation. The mean age was 67 years (range 39-89). Stage distribution included 24.3% stage I, 12.2% stage II, 37.2% stage III, and 26.3% stage IV. There was no difference in the frequency of stage (p=0.81), cytoreduction status (p=0.61), treatment delays (p=0.57), or location of recurrence (p=0.97) between cohorts. The most frequent location of recurrence was the abdomen (50.0%). The median progression-free survival favored chemoradiation over chemotherapy (15 vs 11 months, respectively), as did the median overall survival (26 vs 20 months, respectively). Chemoradiation was associated with a statistically significant improvement in 2 year progression-free survival (22.5% vs 13.6%; p=0.006) and 2 year overall survival (50.0% vs 35.6%; p=0.018) compared with chemotherapy alone. On subanalysis of patients receiving chemoradiation, 'sandwich sequencing' (chemotherapy-radiation-chemotherapy) was associated with superior overall survival compared with alternate therapy sequences (chemotherapy-radiation and radiation-chemotherapy) (34 months vs 14 months and 14 months, respectively) (p=0.038). CONCLUSIONS: Chemoradiation was associated with improvement in both progression-free and overall survival for all stages of carcinosarcoma compared with chemotherapy alone.

Cutaneous metastasis of PD-L1 positive ovarian carcinoma.

•Ovarian cancer (OC) metastasizes cutaneous in up to 6% of cases.•Cutaneous metastasis to the vulva is rare; with only one prior report in the literature.•Resection of cutaneous metastasis offers symptom relief as well as a potential survival benefit.•Molecular tumor profiling should be employed to expand therapy options.

A clinicopathologic study of endometrial cancer metastatic to bone: Identification of microsatellite instability improves treatment strategies.

Metastasis to bone (BM) is an uncommon manifestation of advanced endometrial cancer (EC). The present study will review the clinicopathologic features of a cohort of patients with EC and BM. We conducted a multi-center retrospective review of patients with EC and BM. Demographic and clinical information was extracted from the medical records. Survival outcomes were determined using Kaplan-Meier Curves. Final analysis included 10 patients. The median age was 65 years (range 31-71). 80% had FIGO stage III/IV disease. The most common site of BM was the spine (66%). All patients presented with extraosseous dissemination at the time of diagnosis of BM and 70% were found to have multiple sites of BM. 80% of patients were diagnosed with BM in the recurrent setting. The median time to diagnosis of bone recurrence was 14 months (range: 0-44). Median survival after diagnosis of BM was 11 months (range: 1-22 months). Patients with endometrioid histology and single site of bone metastasis experienced improved survival (p = 0.04 and p = 0.05, respectively). Eight patients had immunohistochemistry or molecular tumor profiles available for review. Seven of these patients (87.5%) were found to have microsatellite instability (MSI). The most common mutation was hypermethylation of MLH-1 (43%). To our knowledge, this is the first report demonstrating a correlation between MSI and metastasis to bone. The identification of BM in EC is uncommon, but will alter treatment strategies and dramatically impact prognosis. Molecular tumor profiling should be performed to identify targeted therapy options and optimize adjuvant treatment strategies.