M.B. Spraker

T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas

Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited.

Emerging Targeted and Immune-Based Therapies in Sarcoma

Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials. Indeed, the spectrum of targeted drug development in sarcoma now spans many of the most active paradigms in cancer research and includes agents that target cancer-related vulnerabilities in receptor tyrosine kinases and intracellular signaling pathways, epigenetics, metabolism, nuclear-cytoplasmic transport, and many others. Our understanding of the sarcoma immune microenvironment and heterogeneous mechanisms of tumor immune evasion has also expanded. Although a subset of sarcomas appears inflamed and responsive to immune checkpoint blockade with programmed death 1 (PD-1) targeted agents, novel immunotherapies and combinations likely will be needed for most subtypes. A variety of approaches-including targeting immune checkpoints other than PD-1; modulating tumor-associated macrophage phenotype from tumor-promoting to tumor-suppressive status; using cellular-based therapies, such as chimeric antigen and high-affinity T-cell receptors to deepen the adaptive immune response; and reinvigorating older approaches, such as vaccines and oncolytic virus-based treatments-are being investigated. The goal of these new approaches is to harness subtype-specific insights into cancer and immune biology to bring more effective and less toxic treatments to the clinic for the benefit of patients with sarcoma.

A patient safety education program in a medical physics residency

Abstract Education in patient safety and quality of care is a requirement for radiation oncology residency programs according to accrediting agencies. However, recent surveys indicate that most programs lack a formal program to support this learning. The aim of this report was to address this gap and share experiences with a structured educational program on quality and safety designed specifically for medical physics therapy residencies. Five key topic areas were identified, drawn from published recommendations on safety and quality. A didactic component was developed, which includes an extensive reading list supported by a series of lectures. This was coupled with practice‐based learning which includes one project, for example, failure modes and effect analysis exercise, and also continued participation in the departmental incident learning system including a root‐cause analysis exercise. Performance was evaluated through quizzes, presentations, and reports. Over the period of 2014–2016, five medical physics residents successfully completed the program. Evaluations indicated that the residents had a positive experience. In addition to educating physics residents this program may be adapted for medical physics graduate programs or certificate programs, radiation oncology residencies, or as a self‐directed educational project for practicing physicists. Future directions might include a system that coordinates between medical training centers such as a resident exchange program.

Analysis of Gastrointestinal Toxicity in Patients Receiving Proton Beam Therapy for Prostate Cancer: A Single Institution Experience

Purpose We characterized both physician- and patient-reported rates of gastrointestinal (GI) toxicity in patients treated with proton beam therapy (PBT) at our institution for prostate adenocarcinoma and identified factors associated with toxicity. Methods and materials We treated 192 patients with PBT between July 2013 and July 2016. Included patients had ≥1 year of follow-up. Potential preexisting clinical and treatment-related risk factors for GI toxicity were recorded. Common Terminology Criteria for Adverse Events version 4.0 was used to score toxicity. Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires assessed patient-reported quality of life. Associations between grade (GR) 2+ toxicity and clinical, treatment, and dosimetric factors were assessed using Cox models and corresponding hazard ratios. Results The median follow-up was 1.7 years. Most of the observed GI toxicity (>90%) was in the form of rectal bleeding (RB). GR2+ GI toxicity and RB actuarial rates specifically at 2 years were 21.3% and 20.4%, respectively. GR3 toxicity was rare, with only 1 observed RB event. No GR4/5 toxicity was seen. The EPIC bowel domain median score was 96 (range, 61-100) pretreatment, 93 (range, 41-100) at 1 year, 89 (range, 57-100) at 1.5 years, and 89 (range, 50-100) at 2 years. Anticoagulation use was the only factor selected during multivariate analysis for predicting GR2+ RB, with a resulting concordance index of 0.59 (95% confidence interval, 0.48-0.68; P = .088). Type of proton technology (pencil beam scanning vs uniform scanning) and number of fields treated per day (1 vs 2) showed no significant difference in toxicity rate. Conclusions PBT was associated with acceptable rates of GR2+ transient GI toxicity, mostly in the form of RB, which correlated with anticoagulation use. High EPIC bowel domain quality of life was maintained in the 2 years after treatment.