Dramatic Response to Concurrent Anti-PD-1 Therapy and Radiation in Resistant Tumors with Sarcomatoid Differentiation.

A substantial fraction of patients demonstrate resistance to immune checkpoint inhibitors, which limits their use. Use of radiation concurrently with checkpoint inhibitors has been shown to boost immune responsiveness, resulting in significant tumor regression in patients with metastatic melanoma. However, it is unknown whether radiation could play a role in reversing the inherent resistance to checkpoint inhibition in certain tumor types. Most trials testing this concurrent approach exclude such modestly responsive tumors and pursue checkpoint inhibition using anti-cytotoxic T-lymphocyte-associated protein 4 antibody (anti-CTLA-4, ipilimumab). The efficacy of anti-programmed-death-1 (anti-PD-1) therapy when used concurrently with radiation is less known but remains an attractive option due to less autoimmune toxicity compared with CTLA-4 inhibition. In this first reported experience, we have safely and effectively combined anti-PD-1 therapy (nivolumab) concurrently with radiation to treat two patients with relapsed sarcomatoid renal carcinoma and heavily pretreated pleomorphic sarcoma. Both patients experienced a dramatic response that was durable.

Organ Preservation in Colon Cancer: An Illustrative Case Report.

The organ preservation strategy in non-metastatic rectal cancer is a rapidly evolving, novel treatment paradigm that is offered outside of a clinical trial in many advanced cancer centers. However, for non-metastatic colon cancer, upfront surgery followed by adjuvant chemotherapy in patients deemed at risk of cancer recurrence is the current standard of care. A significant proportion of patients with non-metastatic colon cancer harbor a deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) signature in tumors, which predicts a deep and durable response to immune checkpoint inhibitors (ICI) in a large proportion of such patients. This opens an opportunity for organ preservation in colon cancer in select circumstances. Herein, we describe a patient with locally advanced dMMR/MSI-H colon cancer who could not undergo standard colon surgery but achieved complete remission following treatment with ICI.