Bagaria, Sanjay P.

We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

BACKGROUNDBiomarkers are routinely used to predict responses to systemic therapies, but their utility for predicting responses to local therapy for breast cancer is not known. This study determined whether biomarkers could predict responses to breast‐conserving therapy (BCT) and mastectomy.METHODSA review of the Surveillance, Epidemiology, and End Results database identified women diagnosed with early‐stage invasive ductal breast cancer and treated with BCT or mastectomy from 1998 to 2008. The estrogen receptor (ER) status and the histologic grade were used to construct 3 biomarker profiles: low risk (ER‐positive, low/intermediate grade), intermediate risk (ER‐positive, high grade), and high risk (ER‐negative, any grade). The primary measured outcome was disease‐specific survival (DSS).RESULTSBCT and mastectomy were performed in 114,486 patients (59.2%) and 79,035 patients (40.8%), respectively. There were 122,420 low‐risk patients (63.3%), 34,341 intermediate‐risk patients (17.7%), and 36,760 high‐risk patients (19.0%). Multivariate analyses were performed separately for patients with low‐, intermediate‐, and high‐risk tumors. The adjusted hazard ratios for DSS for patients who underwent mastectomy versus BCT for low‐, intermediate‐, and high‐risk tumors were 1.66 (95% confidence interval [CI], 1.54‐1.79; P < .001), 1.40 (95% CI, 1.29‐1.53; P < .001), and 1.27 (95% CI, 1.19‐1.35; P < .001), respectively.CONCLUSIONSPatients with ER‐positive, low‐grade breast cancers who underwent mastectomy had a 66% increase in disease‐specific mortality versus those who underwent BCT. Biomarker profiles defined by the ER status and grade may improve the selection of local therapy for breast cancer. Cancer 2015;121:2705‐2712. © 2015 American Cancer Society

Abstract Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti–PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti–PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti–PD-1) that were characterized with marked T-cell infiltrates with few PD-1–positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. Cancer Immunol Res; 3(1); 18–22. ©2014 AACR.

BackgroundWe sought to examine adherence to National Comprehensive Cancer Network guidelines for use of radiation therapy (RT) in patients with soft tissue sarcoma (STS) in the United States.MethodsThe surveillance, epidemiology, and end results cancer registry was queried to identify patients undergoing surgery for truncal and extremity STS from 2004 to 2009.ResultsOf 5,075 patients, 50% received RT. Although routine RT is not recommended for Stage I patients, 25% still underwent RT. Even though routine RT is recommended for Stage II and III tumors, only 60% underwent RT. On multivariate analysis predictors of RT included age <50 years (OR 1.57, 95% CI 1.28–1.91), malignant fibrous histiocytoma histology (OR 1.47, 95% CI 1.3–1.92), T2 classification (OR 1.88, 95% CI 1.60–2.20), and G3 (OR 6.27, 95% CI 5.10–7.72). Patients with Stage III STS who received RT showed improved disease specific survival at 5 years compared to those who did not, 68% versus 46%, P <0.001.ConclusionsUnderuse of RT is seen for a significant proportion of patients undergoing treatment for STS in the United States. More effort needs to be directed towards compliance with appropriate treatment recommendations, perhaps by regionalizing sarcoma care or remote multidisciplinary tumor boards. J. Surg. Oncol 2014; 109:633–638. © 2014 Wiley Periodicals, Inc.