Exceptional response to combination ipilimumab and nivolumab in metastatic uveal melanoma: Insights from genomic analysis.

Uveal melanoma is the most common intraocular malignancy and has a poor prognosis compared to other melanoma subtypes with a median overall survival of 6-10 months. With immune checkpoint inhibitor therapy, either PD-1 inhibitor alone or combination ipilimumab/nivolumab (anti-CTLA-4/anti-PD-1), responses are rare and often not durable. We present a case report of a now 66-year-old woman with diffuse metastatic uveal melanoma previously treated with a combination of ipilimumab/nivolumab, followed by maintenance nivolumab. Almost complete resolution of all sites of metastatic disease was observed except for one liver metastasis which regressed partially on immunotherapy. Notably, the patient had a significantly elevated BMI and developed widespread vitiligo on treatment. Whole-genome and transcriptome analysis was performed on the residual liver biopsy and molecular markers that may have contributed to the exceptional response were investigated. Several alterations were observed in genes involved in T-cell responses. Estimates of tumour infiltrating immune cells indicated a high level of plasma cells compared to other uveal melanoma cases, a finding previously associated with indolent disease. The patient also carried several germline SNPs that may have contributed to her treatment response as well as widespread vitiligo. Whole-genome and transcriptome sequencing have provided insight into potential molecular underpinnings of an exceptional treatment response in a tumour type typically associated with poor prognosis. Immunological findings suggest a role for plasma cells in the tumour microenvironment. Elevated BMI and the development of vitiligo may be clinically relevant factors for predicting response to immune checkpoint inhibitor therapy, warranting further studies in patients with uveal melanoma.

Management of Malignant Rectal Pain and Tenesmus: A Systematic Review.

Background: Malignant rectal pain (MRP) and tenesmus cause significant morbidity for cancer patients at all stages of disease. There is little evidence to guide management of these symptoms. Objective: The objective of this review was to summarize the existing evidence base for palliative management of MRP and tenesmus outside of standard oncologic or surgical management. Design: A systematic review of PubMed and Embase was conducted according to PRISMA guidelines using preselected search terms for publications between 1980 and January 2017. Setting/Subjects: Studies that described management for patients with tenesmoid pain from malignant tumors of the rectum, anus, or perineum were identified. Measurements: The primary outcome was response of pain to treatment. Results: The search produced 1412 titles. Twenty articles met criteria for inclusion in the review, including 11 case series and 9 case reports. A variety of treatments were found with most patients receiving interventional procedures, but overall evidence to support any particular intervention is limited and of poor quality. Conclusions: This review highlights the limited current evidence base for medical and interventional treatments for MRP and tenesmus. Further study is needed to clarify the best approach to managing these challenging symptoms.