Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

Combining immunotherapy with radiation therapy in thoracic oncology.

Thoracic malignancies comprise some of the most common and deadly cancers. Immunotherapies have been proven to improve survival outcomes for patients with advanced non-small cell lung cancer (NSCLC) and show great potential for patients with other thoracic malignancies. Radiation therapy (RT), an established and effective treatment for thoracic cancers, has acted synergistically with immunotherapies in preclinical studies. Ongoing clinical trials are exploring the clinical benefits of combining RT with immunotherapies and the optimal manner in which to deliver these complementary treatments.

Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram.

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

The multidisciplinary approach to the treatment of rectal cancer: 2015 update.

The multidisciplinary approach to the management of rectal cancer continues to evolve with developments in surgery, radiation therapy as well as systemic chemotherapy. Refinement of surgical techniques to improve organ preservation, selective use of neoadjuvant (or adjuvant) therapies, improvements in staging modalities and emerging criteria for the selection of tailored therapies are some of the advancements made over the last three decades. In addition, neoadjuvant treatment alternatives, multimodality sequencing and adaptive therapies based on treatment response continue to be a subject of clinical investigation. The current article reviews the salient topics related to the multidisciplinary treatment of resectable rectal cancer.

Granulomatosis with polyangiitis presenting with pachymeningitis.

OBSERVATIONS: This case report describes a 75 year-old Caucasian male who initially presented with persistent daily headaches. Physical exam elicited multiple cranial nerve palsies. Gadolinium-enhanced brain MRI demonstrated pachymeningitis. Labs revealed elevated proteinase-3 antineutrophil cytoplasmic antibodies (PR3-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA), confirming a diagnosis of GPA. CONCLUSION: GPA should be considered in older patients presenting with persistent daily headaches and pachymeningitis. Contrast-enhanced brain MRI is an important diagnostic tool.