Purpose An association between mutational burden and response to immune checkpoint therapy has been documented in several cancer types. The potential for such a mutational burden threshold to predict response to immune checkpoint therapy was evaluated in several clinical datasets, where mutational burden was measured either by whole-exome sequencing (WXS) or using commercially available sequencing panels. Methods WXS and RNA-seq data of 33 solid cancer types from TCGA were analyzed to determine whether a robust immune checkpoint activating mutation (iCAM) burden threshold associated with evidence of immune checkpoint activation exists in these cancers that may serve as a biomarker for response to immune checkpoint blockade therapy. Results We find that a robust iCAM threshold, associated with signatures of immune checkpoint activation, exists in 8 of 33 solid cancers: melanoma, lung adenocarcinoma, colon adenocarcinoma, endometrial cancer, stomach adenocarcinoma, cervical cancer, ER+HER2− breast cancer, and bladder-urothelial cancer. Tumors with mutational burden higher than the threshold (iCAM+) also had clear histologic evidence of lymphocytic infiltration. In published datasets of melanoma, lung adenocarcinoma and colon cancer, patients with iCAM+ tumors had significantly better response to immune checkpoint therapy compared to those with iCAM− tumors. ROC analysis using TCGA predictions as gold standard showed that iCAM+ tumors are accurately identifiable using clinical sequencing assays, such as FoundationOne or StrandAdvantage. Using the FoundationOne derived threshold, analysis of 113 melanoma tumors, showed that iCAM+ patients have significantly better response to immune checkpoint therapy. iCAM+ and iCAM− tumors have distinct mutation patterns and different immune microenvironments. Conclusion In 8 solid cancers, a mutational burden threshold exists that may predict response to immune checkpoint blockade. This threshold is identifiable using available clinical sequencing assays.

Gastrointestinal: Abdominal wall metastasis after percutaneous endoscopic gastrostomyA 53-year-old woman was referred for evaluation with recurrent carcinoma of the right piriform fossa. She had been previously treated by radiotherapy. Radical surgery was undertaken that included a total laryngopharyngectomy with reconstruction of the pharynx using a flap from the antero-lateral aspect of the left thigh. During the operation, percutaneous endoscopic gastrostomy was performed for post-operative feeding. The resected specimen revealed squamous cell carcinoma of moderate differentiation with infiltration of the tumor into the thyroid gland and into the esophageal wall. All surgical margins were free of tumor. After 5 months, she was noted to have a friable and bleeding mass at the gastrostomy site. The mass had raised margins and was approximately 5 cm in diameter (Fig. 1). Biopsies revealed squamous cell carcinoma of moderate differentiation (Fig. 2). Biopsies of a recurrent neck swelling also showed squamous cell carcinoma. She declined further therapy and is currently being treated symptomatically.Carcinomas of the head and neck are common neoplasms in many countries. Typical sites for metastases include lung, liver and bone. Surgical treatment for these neoplasms often involves prolonged avoidance of oral food and fluids and, because of this, feeding through a gastrostomy tube is widely used during the post-operative period. A metastasis in the abdominal wall at the site of the gastrostomy tube was first reported by Drs Preyer and Thul in 1989. Since that time, an additional 50 cases have been reported with an estimated frequency ranging from 0.5% to 1%. Clinically, metastases may present as non-healing peristomal ulceration, recurrent stomal bleeding, an exophytic peristomal mass or a deep abdominal wall mass. While direct spread of the neoplasm during the endoscopic procedure appears to be the most likely cause for abdominal wall metastases, other hypotheses have been suggested including hematogenous and lymphatic spread to the abdominal wall. The development of a gastrostomy metastasis with carcinoma of the head and neck is a poor prognostic feature. Such patients have a mean survival of 7 months and 1 year survival of <5%.

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Cardiac hydatid is a rare disease with varied presentation. We report a unique case of left ventricular epicardial hydatid cyst causing left circumflex artery compression. Cardiac hydatids have to be surgically treated on diagnosis because of the high risk of catastrophic rupture. We discuss the surgical principles and the other adjuncts to avoid recurrence.

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