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Michelle C. Nguyen, Manisha H. Shah, David A. Liebner, Floor J. Backes, John Phay and Lawrence A. Shirley

Therapeutic agents targeting the PD-1/PD-L1 axis have shown durable clinical responses in patients with various cancer types. Although objective responses are common, intrapatient heterogeneous responses have been described, and the mechanism for the different organ responses remains unknown. We present a series of patients in whom a lack of response was noted solely in the adrenal glands. This is the first case series describing 3 patients with heterogeneous patterns of response to pembrolizumab with progression of adrenal metastatic disease despite objective response (complete or partial response) in all other sites of metastatic disease. Two patients, one with melanoma and one with uterine carcinosarcoma, underwent robotic adrenalectomy for enlarging adrenal metastases. An additional patient with melanoma underwent laparotomy with attempted resection, but infiltration of the adrenal tumor into the inferior vena cava prohibited safe excision. This report provides additional insight into the heterogeneous patterns of disease response to anti–PD-1 therapy, highlighting the adrenal gland as a potential sanctuary site for this immunotherapy. These cases display the potential benefit of early surgical resection in this scenario and the pitfalls of delaying referral to a surgeon for assessment of operative intervention.

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David S. Ettinger, Mark Agulnik, Justin M. M. Cates, Mihaela Cristea, Crystal S. Denlinger, Keith D. Eaton, Panagiotis M. Fidias, David Gierada, Jon P. Gockerman, Charles R. Handorf, Renuka Iyer, Renato Lenzi, John Phay, Asif Rashid, Leonard Saltz, Lawrence N. Shulman, Jeffrey B. Smerage, Gauri R. Varadhachary, Jonathan S. Zager and Weining (Ken) Zhen

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David S. Ettinger, Charles R. Handorf, Mark Agulnik, Daniel W. Bowles, Justin M. Cates, Mihaela Cristea, Efrat Dotan, Keith D. Eaton, Panagiotis M. Fidias, David Gierada, G. Weldon Gilcrease, Kelly Godby, Renuka Iyer, Renato Lenzi, John Phay, Asif Rashid, Leonard Saltz, Richard B. Schwab, Lawrence N. Shulman, Jeffrey B. Smerage, Marvaretta M. Stevenson, Gauri R. Varadhachary, Jonathan S. Zager, Weining (Ken) Zhen, Mary Anne Bergman and Deborah A. Freedman-Cass

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation.