Regulatory Considerations in the Development of Radiation-Drug Combinations.

Radiation therapy remains a fundamental treatment for patients with cancer. Despite an increasing number of targeted molecular therapies that are US Food and Drug Administration (FDA)-approved for the treatment of patients with metastatic disease, there has been very little progress made in terms of drugs used concurrently with radiation. This article reviews the existing regulatory framework in which cancer drugs may be developed for use in combination with radiation therapy from the perspective of the FDA.

Expanding Our Impact in Cervical Cancer Treatment: Novel Immunotherapies, Radiation Innovations, and Consideration of Rare Histologies.

Cervical cancer is a socially and scientifically distinguishable disease. Its pathogenesis, sexual transmission of high-risk HPV to a metaplastic portion of the uterine cervix, makes cervical cancer preventable by safe and effective HPV vaccines commercially available since 2006. Despite this, cervical cancer remains the deadliest gynecologic cancer in the world.

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades.

Purpose: When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion.

Methods And Materials: This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades.

Lessons to Learn From a Successful Virtual Mock Oral Examination Pilot Experience.

oronavirus (COVID-19) has caused marked impact on graduate medical education for all medical specialties. Radiation Oncology and the American Board of Radiology have also had to rapidly adapt to converting education and examinations to virtual platforms. We describe our small pilot experience in transitioning our in-person mock oral examinations to a virtual platform.

Clinical Development of Novel Drug-Radiotherapy Combinations.

Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer.

On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial.

Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016.

A workshop entitled "Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate" (held in Rockville, MD, September 19, 2016) was organized by the Radiation Research Program and Radiation Oncology Branch of the Center for Cancer Research (CCR) of the National Cancer Institute (NCI), to identify critical research areas and directions that will advance the understanding of radiation-induced fibrosis (RIF) and accelerate the development of strategies to mitigate or treat it. Experts in radiation biology, radiation oncology and related fields met to identify and prioritize the key areas for future research and clinical translation. The consensus was that several known and newly identified targets can prevent or mitigate RIF in pre-clinical models.

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174).

Management of pediatric intracranial low-grade gliomas: long-term follow-up after radiation therapy.

Introduction: The treatment of pediatric intracranial low-grade gliomas (LGG) generally begins with maximal safe resection. Radiation therapy (RT) and chemotherapy are typically reserved for patients with incomplete resection and/or disease progression. We report long-term treatment outcomes and toxicities in a cohort of pediatric patients with LGG after RT.

Results of the 2013-2015 Association of Residents in Radiation Oncology Survey of Chief Residents in the United States.

Purpose: The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice.

Methods And Materials: During the academic years 2013 to 2014 and 2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported.

Use of standardized uptake value thresholding for target volume delineation in pediatric Hodgkin lymphoma.

Purpose: A limitation of [(18)F] 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDGPET) in radiation planning for Hodgkin lymphoma (HL) is significant variability in delineation of tumor volume. One approach to reduce variability is to apply automatic or semiautomatic segmentation methods such as thresholding based on a percent tumor maximum standardized uptake value (SUVmax). Here, we apply various tumor SUVmax thresholds and examine their effects in involved field radiation therapy (IFRT) and involved site radiation therapy (ISRT) target volumes.

Correlation of clinical stage and performance status with quality of life in patients seen in a pancreas multidisciplinary clinic.

Introduction: The objectives of this study were to evaluate quality of life (QoL) in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC), and to examine associations between disease status, performance status, and QoL in order to identify patient subgroups that are most at risk for reduced QoL.

Patients And Methods: Data from 77 patients were evaluated. At initial presentation, disease and performance status were assessed, as well as QoL, which was obtained with the European Organisation for Research and Treatment of Cancer QLQ-PAN26 questionnaire.

Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression?

A familiar challenge for neuroradiologists and neuro-oncologists is differentiating between radiation treatment effect and disease progression in the CNS. Both entities are characterized by an increase in contrast enhancement on MRI and present with similar clinical signs and symptoms that may occur either in close temporal proximity to the treatment or later in the disease course. When radiation-related imaging changes or clinical deterioration are mistaken for disease progression, patients may be subject to unnecessary surgery and/or a change from otherwise effective therapy.

Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer.

Knowledge of the basic mechanisms of the immune system as it relates to cancer has been increasing rapidly. These developments have accelerated the translation of these advancements into medical breakthroughs for many cancer patients. The immune system is designed to discriminate between self and non-self, and through genetic recombination there is virtually no limit to the number of antigens it can recognize.

Patterns of failure after involved field radiation therapy for pediatric and young adult Hodgkin lymphoma.

Background: Involved field radiation therapy (IFRT) is integral in curative therapy for Hodgkin lymphoma (HL), although primarily used in patients with intermediate/high-risk HL. We present failure patterns and clinical outcomes in a cohort of pediatric and young adult patients with HL treated with IFRT at the Johns Hopkins Hospital.

Procedure: Patients ≤40 years old with intermediate/high-risk HL who received chemotherapy and IFRT from 1997 to 2012 were included in this retrospective analysis.

Radiosensitizers in pancreatic cancer--preclinical and clinical exploits with molecularly targeted agents.

There has been an explosion in the number of molecularly targeted agents engineered to inhibit specific molecular pathways driving the tumorigenic phenotype in cancer cells. Some of these molecularly targeted agents have demonstrated robust clinical effects, but few result in meaningful durable responses. Therapeutic radiation is used to treat a majority of cancer patients with recent technologic and pharmacologic enhancements, leading to improvements in the therapeutic ratio for cancer care.

Intracranial germinoma in the pineal region arising after subtotal resection of epidermoid cyst: case report.

We present an unusual case of a germinoma of the pineal region arising adjacent to an epidermoid cyst in a 16-year-old male. Initial imaging findings were classic for epidermoid cyst. The patient underwent two partial resections at an outside institution, each specimen demonstrating pure epidermoid cyst.

Molecularly targeted agents as radiosensitizers in cancer therapy--focus on prostate cancer.

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control.

State-specific effects of sevoflurane anesthesia on sleep homeostasis: selective recovery of slow wave but not rapid eye movement sleep.

Background: Prolonged propofol administration does not result in signs of sleep deprivation, and propofol anesthesia appears to satisfy the homeostatic need for both rapid eye movement (REM) and non-REM (NREM) sleep. In the current study, the effects of sevoflurane on recovery from total sleep deprivation were investigated.

Methods: Ten male rats were instrumented for electrophysiologic recordings under three conditions: (1) 36-h ad libitum sleep; (2) 12-h sleep deprivation followed by 24-h ad libitum sleep; and (3) 12-h sleep deprivation, followed by 6-h sevoflurane exposure, followed by 18-h ad libitum sleep.

Isoflurane anesthesia does not satisfy the homeostatic need for rapid eye movement sleep.

Background: Sleep and general anesthesia are distinct states of consciousness that share many traits. Prior studies suggest that propofol anesthesia facilitates recovery from rapid eye movement (REM) and non-REM (NREM) sleep deprivation, but the effects of inhaled anesthetics have not yet been studied. We tested the hypothesis that isoflurane anesthesia would also facilitate recovery from REM sleep deprivation.

Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2.

Purpose: To evaluate clinical activity and target modulation of vandetanib in women with recurrent ovarian cancer.

Experimental Design: A phase II trial of orally administered vandetanib 300 mg daily was designed to include analyses of target inhibition through paired biopsies and dynamic imaging. Core 18-gauge needle biopsies and dynamic contrast-enhanced magnetic resonance imaging were obtained before initiation of therapy and 6 weeks into therapy.