Use of PULSAR (personalized ultra-fractionated stereotactic adaptive radiotherapy) as consolidation with immune checkpoint inhibition in the treatment of pediatric metastatic melanoma.

We present a case of extensive and bulky pediatric metastatic melanoma originating in the head and neck which markedly responded to combination therapy with anti-programmed cell death (PD-1) inhibition and consolidative personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR). After surgical debulking with neck dissection, the patient was initially treated with anti-PD-1 and anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) dual checkpoint blockade immunotherapy, but quickly had disease progression. He was transitioned to a different anti-PD-1 immunotherapy in combination with tyrosine kinase inhibitors in conjunction with consolidative local therapy using PULSAR.

Modeling gamma knife radiosurgical toxicity for multiple brain metastases.

Background And Purpose: Radiation oncology protocols for single fraction radiosurgery recommend setting dosing criteria based on assumed risk of radionecrosis, which can be predicted by the 12 Gy normal brain volume (V12). In this study, we show that tumor surface area (SA) and a simple power-law model using only preplan variables can estimate and minimize radiosurgical toxicity.

Materials And Methods: A 245-patient cohort with 1217 brain metastases treated with single or distributed Gamma Knife sessions was reviewed retrospectively.

Socioeconomic and demographic determinants of radiation treatment and outcomes in glioblastoma patients.

Introduction: Poor outcomes in glioblastoma patients, despite advancing treatment paradigms, indicate a need to determine non-physiologic prognostic indicators of patient outcome. The impact of specific socioeconomic and demographic patient factors on outcomes is unclear. We sought to identify socioeconomic and demographic patient characteristics associated with patient survival and tumor progression, and to characterize treatment options and healthcare utilization.

Impact of CDKN2A/B, MTAP, and TERT Genetic Alterations on Survival in IDH Wild Type Glioblastomas.

Purpose: Poor outcomes in IDH wild-type (IDHwt) glioblastomas indicate the need to determine which genetic alterations can indicate poor survival and guidance of patient specific treatment options. We sought to identify the genetic alterations in these patients that predict for survival when adjusting particularly for treatments and other genetic alterations.

Methods: A cohort of 167 patients with pathologically confirmed IDHwt glioblastomas treated at our institution was retrospectively reviewed.

Neutrophilia and post-radiation thrombocytopenia predict for poor prognosis in radiation-treated glioma patients.

Introduction: Poor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival.

MicroRNA-21 is Required for Hematopoietic Cell Viability After Radiation Exposure.

Purpose: Radiation therapy is an essential intervention used in the treatment of more than half of cancer patients. With the increasing use of hypofractionated radiation regimens, concurrent use of radiation and chemotherapy, targeted agents and immunotherapy, the risk of radiation-induced toxicities is increased. However, much remains unknown about the molecular underpinnings responsible for radiation-induced toxicity.

Bevacizumab and re-irradiation for recurrent high grade gliomas: does sequence matter?

Purpose/objectives: We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG.

Materials/methods: After Institutional Review Board approval, patients with pathologically confirmed WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM) glioma who subsequently underwent re-irradiation at recurrence with FSRT were retrospectively reviewed.

Caloric restriction counteracts chemotherapy-induced inflammation and increases response to therapy in a triple negative breast cancer model.

Triple negative breast cancer (TNBC) is a heterogeneous disease that has no available targeted therapies. Previously, we have shown that caloric restriction (CR) can augment the effects of radiation therapy in a TNBC mouse model. To build upon this, we now present data regarding the combination of chemotherapy and CR in the same 4T1 model.

The Influence of Health Insurance Policy on Radiation Oncology Physician SBRT/SABR Use Practices: A North American Survey.

Purpose: European data suggest that 8-fraction stereotactic body radiation therapy (SBRT) regimens may be similar in efficacy with less toxicity than ≤5-fraction SBRT for central lung lesions. However, under current Centers for Medicare and Medicaid Services guidelines, SBRT in the United States (US) is reimbursed for only ≤5 fractions, whereas there are no such restrictions for reimbursement in Canada. We hypothesize that US-specific SBRT reimbursement policies influence the use of ≥5-fraction SBRT in US academic centers in comparison with comparable Canadian centers.

Radioisotopes in management of metastatic prostate cancer.

Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting.

Dosing, administration, and safety of radium-223: How I do it.

Radium-223 dichloride is a first-in-class bone-directed radiopharmaceutical that has been shown to prolong survival in men with metastatic castrate resistant prostate cancer (mCRPC). Unlike other radiopharmaceuticals, radium-223 uniquely uses alpha-emission to deliver high intensity, short range cytoxic treatments resulting in minimal myelosuppression. Following the results of the ALSYMPCA trial, radium-223 (Xofigo) was FDA approved in the United States in May 2013 and approved by Health Canada in December 2013 for the treatment of mCRPC with symptomatic bone metastases and no visceral disease.

Freedom from local and regional failure of contralateral neck with ipsilateral neck radiotherapy for node-positive tonsil cancer: updated results of an institutional clinical management approach.

Purpose: To update the outcomes of an institutional clinical management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion.

Methods And Materials: Between August 2003 and April 2014, 61 consecutive patients with ipsilateral node-positive squamous cell carcinoma of the tonsil without involvement of the base of the tongue or midline soft palate were treated at a community hospital-based cancer center with radiotherapy to the primary site and ipsilateral neck. Overall survival, disease-free survival and freedom from contralateral failure were calculated.

Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies.

Purpose/objectives: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer.

microRNA alterations driving acute and late stages of radiation-induced fibrosis in a murine skin model.

Purpose: Although ionizing radiation is critical in treating cancer, radiation-induced fibrosis (RIF) can have a devastating impact on patients' quality of life. The molecular changes leading to radiation-induced fibrosis must be elucidated so that novel treatments can be designed.

Methods And Materials: To determine whether microRNAs (miRs) could be responsible for RIF, the fibrotic process was induced in the right hind legs of 9-week old CH3 mice by a single-fraction dose of irradiation to 35 Gy, and the left leg served as an unirradiated control.

Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer.

Background And Purpose: Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN.

Materials And Methods: Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy.

Emerging drugs to replace current leaders in first-line therapy for breast cancer.

Increasing knowledge of drug resistance and side effects of currently approved agents, and of the biology of breast cancer, has given way to new treatment options that improve on previously available agents, or medications that target specific kinases and proteins associated with an oncogenic phenotype. This paper discusses new agents, including improved formulations of paclitaxel and epothilones, and molecularly targeted agents such as bevacizumab, sunitinib malate, pertuzumab, lapatinib, the mTOR inhibitors and farnesyl transferase inhibitors. Although endocrine therapy is a targeted therapy, it is not covered in this paper.