Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab.

Merkel cell carcinoma has historically had dismal prognosis with limited cytotoxic chemotherapy options that provide durable control of metastatic disease. The advent of anti-programmed death protein (anti-PD1)/anti-programmed death-ligand 1 (anti-PD-L1) directed immunotherapy has shown initial promise in Merkel cell carcinoma and radiation might augment immune responses. We present a case report of a 70-year-old male who underwent resection of Merkel cell carcinoma of the right thigh with a close margin and positive right inguinal involvement. Due to high-risk features, the patient was treated with adjuvant radiation to the right groin and with systemic carboplatin/etoposide, but developed local failure requiring salvage surgical resection. The patient then developed metastatic disease with biopsy proven retroperitoneal involvement refractory to doxorubicin/cyclophosphamide chemotherapy. The patient was then transitioned to single-agent pembrolizumab with a partial response for 10 months until developing progressive disease involving the left inguinal and left external iliac nodal regions. The progressive left inguinal/pelvic disease was treated with conventionally fractionated intensity modulated radiation therapy to a dose of 45 Gy delivered in 25 fractions. Following radiation therapy, the patient had complete response of all sites of disease throughout the body on imaging by RECIST criteria including retroperitoneal and mediastinal disease outside the radiation field. At 20 months post-radiation, the patient remains on pembrolizumab without evidence of disease on imaging. Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy. Ongoing prospective trials evaluating the utility of radiation in conjunction with immunotherapy for Merkel cell carcinoma are anticipated to provide clarity on the frequency and durability of abscopal responses when radiation is combined with immune checkpoint inhibitors.

Prophylactic Cranial Irradiation Following Surgical Resection of Early-Stage Small-Cell Lung Cancer: A Review of the Literature.

With increasing use of low-dose screening CT scans, the diagnosis of early-stage small-cell lung cancer (SCLC) without evidence of mediastinal nodal or distant metastasis is likely to become more common, but the role of adjuvant therapies such as prophylactic cranial irradiation (PCI) are not well understood in this population. We performed a review of the literature pertaining to the impact of PCI in patients who underwent surgical resection of early-stage SCLC. Four studies were identified that were pertinent including three single-institution retrospective analyses and a National Cancer Database analysis. Based upon these studies, we estimate the rate of brain metastases to be 10-15% for Stage I and 15-25% for Stage II disease without PCI. However, the impact of PCI on the development of brain metastases and its ultimate impact on overall survival were not consistent across these studies. In summary, there is sparse evidence to guide recommendations for PCI following resection of early-stage SCLC. While it may be reasonable to offer PCI to maximize likelihood of cure, alternative strategies such as observation with close imaging follow-up can also be considered for the appropriate patient given the known neurocognitive side effects of PCI.