Complete Remission Following Pembrolizumab in a Woman with Mismatch Repair-Deficient Endometrial Cancer and a Germline BRCA1 Mutation.

Endometrial cancer is the most common gynecologic malignancy in the U.S. and, although the majority of cases present at an early stage and can be treated with curative intent, those who present with advanced disease, or develop metastatic or recurrent disease, have a poorer prognosis. A subset of endometrial cancers exhibit mismatch repair (MMR) deficiency. It is now recognized that MMR-deficient cancers are particularly susceptible to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, and in a landmark judgement in 2017, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab for these tumors, the first tumor-agnostic approval of a drug. However, less is known about the sensitivity to PD-1 blockade among patients with known mutations in double-strand break DNA repair pathways involving homologous recombination, such as those in BRCA1 or BRCA2. Here we report a case of a patient with an aggressive somatic MMR-deficient endometrial cancer and a germline BRCA1 who experienced a rapid complete remission to pembrolizumab. KEY POINTS: Endometrial cancers, and in particular endometrioid carcinomas, should undergo immunohistochemical testing for mismatch repair proteins.Uterine cancers with documented mismatch repair deficiency are candidates for treatment with programmed cell death protein 1 inhibition.Genomic testing of recurrent, advanced, or metastatic tumors may be useful to determine whether patients are candidates for precision therapies.

Association of Hospital Volume With Racial and Ethnic Disparities in Locally Advanced Cervical Cancer Treatment.

OBJECTIVE: To evaluate racial-ethnic disparities in guideline-based care in locally advanced cervical cancer and their relationship to hospital case volume. METHODS: Using the National Cancer Database, we performed a retrospective cohort study of women diagnosed between 2004 and 2012 with locally advanced squamous or adenocarcinoma of the cervix undergoing definitive primary radiation therapy. The primary outcome was the race-ethnicity-based rates of adherence to the National Comprehensive Cancer Network guideline-based care. The secondary outcome was the effect of guideline-based care on overall survival. Multivariable models and propensity matching were used to compare the hospital risk-adjusted rates of guideline-based adherence and overall survival based on hospital case volume. RESULTS: The final cohort consisted of 16,195 patients. The rate of guideline-based care was 58.4% (95% confidence interval [CI] 57.4-59.4%) for non-Hispanic white, 53% (95% CI 51.4-54.9%) for non-Hispanic black, and 51.5% (95% CI 49.4-53.7%) for Hispanic women (P<.001). From 2004 to 2012, the rate of guideline-based care increased from 49.5% (95% CI 47.1-51.9%) to 59.1% (95% CI 56.9-61.2%) (Ptrend<.001). Based on a propensity score-matched analysis, patients receiving guideline-based care had a lower risk of mortality (adjusted hazard ratio 0.65, 95% CI 0.62-0.68). Compared with low-volume hospitals, the increase in adherence to guideline-based care in high-volume hospitals was 48-63% for non-Hispanic white, 47-53% for non-Hispanic black, and 41-54% for Hispanic women. CONCLUSION: Racial and ethnic disparities in the delivery of guideline-based care are the highest in high-volume hospitals. Guideline-based care in locally advanced cervical cancer is associated with improved survival.

Image-guided percutaneous thermal ablation of metastatic pelvic tumor from gynecologic malignancies.

BACKGROUND: Image-guided percutaneous thermal ablation is a commonly performed therapeutic procedure for various tumors. Thermal ablation is not frequently used in the pelvis as a result of anatomic concerns and the potential risk of nontarget tissue injury. TECHNIQUE: Percutaneous thermal ablation is a minimally invasive procedure involving special probes inserted through the skin to the target lesion under imaging guidance. Various delivery methods of thermal ablation exist, including radiofrequency ablation, which burns tissue, and cryoablation, which freezes tissue with an ultimate goal to destroy the target tumor while minimizing damage to adjacent structures. Protective measures can be used to provide access and safe treatment delivery such as pyeloperfusion to protect the ureter with the infusion of water using a ureteral stent or hydrodissection to protect adjacent structures by displacing them away with the infusion of water using percutaneously placed needles. EXPERIENCE: The authors' experience with the technique involves thermal ablation of recurrent pelvic tumor in three patients with various gynecologic malignancies who each had a single focus of pelvic recurrence after surgical resection and radiation treatment. No residual or recurrent disease was seen at the treatment site on follow-up imaging consistent with local tumor control. CONCLUSION: Thermal ablation of metastatic or recurrent pelvic tumor is technically feasible and should be considered in selected patients with no treatment alternative.