Inhibition of the extracellular matrix protein fibulin-3 reduces immunosuppressive signaling in tumor stem cells and increases macrophage activation against glioblastoma.

Glioblastoma tumors remain a formidable challenge for immune-based treatments because of their molecular heterogeneity, poor immunogenicity, and growth in the largely isolated and immunosuppressive neural environment. As the tumor grows, GBM cells change the composition and architecture of the neural extracellular matrix (ECM), affecting the mobility, survival, and function of immune cells such as tumor-associated microglia and infiltrated macrophages (TAMs). We have previously described the unique expression of the ECM protein EFEMP1/fibulin-3 in GBM compared to normal brain and demonstrated that this secreted protein promotes the growth of the GBM stem cell (GSC) population.

Global Workforce and Access: Demand, Education, Quality.

There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-income countries (LMICs) widens, with a pronounced increase in cancer cases in LMICs. Even within HICs, iniquities within local communities may lead to a lack of access to care.

Stay on Track: A Pilot Randomized Control Trial on the Feasibility of a Diet and Exercise Intervention in Patients with Breast Cancer Receiving Radiotherapy.

Purpose: Among patients with breast cancer undergoing radiotherapy, posttreatment cardiovascular disease and worsened quality of life (QoL) are leading causes of morbidity and mortality. To overcome these negative radiotherapy effects, this prospective, randomized clinical trial pilots a 12-week Stay on Track exercise and diet intervention for overweight patients with nonmetastatic breast cancer undergoing whole-breast radiotherapy.

Experimental Design: The intervention group (n = 22) participated in three personal exercise and dietary counseling sessions, and received three text reminders/week to adhere to recommendations.

High-Grade Pneumonitis Events in Patients With Unresectable, Locally Advanced NSCLC Treated With Definitive Chemoradiation Followed by Adjuvant Durvalumab.

Background: The standard of care for unresectable locally advanced NSCLC is concurrent chemotherapy and radiation (CRT) followed by adjuvant durvalumab, established by the PACIFIC trial, which revealed acceptable although higher rates of pneumonitis with durvaluamb than placebo. We retrospectively reviewed patients with locally advanced NSCLC from 2018 to 2022 treated with definitive CRT (≥60 Gy) followed by at least one dose of adjuvant durvalumab.

Objective: To review the incidence of pneumonitis and contributing factors, and also to review grade 5 pneumonitis (G5) events.

Neighborhood Deprivation and Rurality Associated With Patient-Reported Outcomes and Survival in Men With Prostate Cancer in NRG Oncology RTOG 0415.

Purpose: Rurality and neighborhood deprivation can contribute to poor patient-reported outcomes, which have not been systematically evaluated in patients with specific cancers in national trials. Our objective was to examine the effect of rurality and neighborhood socioeconomic and environmental deprivation on patient-reported outcomes and survival in men with prostate cancer in NRG Oncology RTOG 0415.

Methods And Materials: Data from men with prostate cancer in trial NRG Oncology RTOG 0415 were analyzed; 1,092 men were randomized to receive conventional radiation therapy or hypofractionated radiation therapy.

The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited therapeutic options. The extracellular matrix protein fibulin-3/EFEMP1 accumulates in the pleural effusions of MPM patients and has been proposed as a prognostic biomarker of these tumors. However, it is entirely unknown whether fibulin-3 plays a functional role on MPM growth and progression.

Long term clinical outcomes and associated predictors of progression free survival in anal canal cancer.

Background: Reports of long term clinical outcomes for patients with squamous cell carcinoma (SCC) of the anal canal treated with chemotherapy and intensity modulated radiation therapy (IMRT) are limited. Pre-treatment hematologic variables associated with outcomes remain understudied. We sought to report the long-term clinical outcomes of a cohort of patients treated with definitive chemoradiation (CRT) utilizing helical tomotherapy (HT) IMRT at a single tertiary referral center.

The scaffolding protein DLG5 promotes glioblastoma growth by controlling Sonic Hedgehog signaling in tumor stem cells.

Background: Tumor invasion, a hallmark of malignant gliomas, involves reorganization of cell polarity and changes in the expression and distribution of scaffolding proteins associated with polarity complexes. The scaffolding proteins of the DLG family are usually downregulated in invasive tumors and regarded as tumor suppressors. Despite their important role in regulating neurodevelopmental signaling, the expression and functions of DLG proteins have remained almost entirely unexplored in malignant gliomas.

Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial.

Purpose: For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up.

Methods And Materials: From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT.

S100 Calcium-Binding Protein A9 Knockout Contributes to Neuroprotection and Functional Improvement after Traumatic Brain Injury.

S100 calcium-binding protein A9 (S100a9), a proinflammatory protein, has been shown to be involved in the development of neuroinflammatory disorders and neurodegenerative diseases. Upregulation of S100a9 in the brain during acute brain injury has been proposed to be associated with acute neuroinflammation. However, it remains unclear whether eliminating S100a9 expression will show beneficial outcomes after traumatic brain injury (TBI).

Stem cell factor and granulocyte colony-stimulating factor promote brain repair and improve cognitive function through VEGF-A in a mouse model of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia. To date, the pathogenesis of CADASIL remains poorly understood, and there is no treatment that can slow the progression of CADASIL. Using a transgenic mouse model of CADASIL (TgNotch3R90C), this study reveals novel findings for understanding CADASIL pathogenesis that decreased cerebral vascular endothelial growth factor (VEGF/VEGF-A) is linked to reduced cerebral blood vessel density.

Challenges and Prospects for Providing Radiation Oncology Services in Africa.

There are considerable challenges to meeting the demands of the impending cancer crisis in Africa. These include a rising incidence of cancer and cancer-related deaths, equipment and maintenance costs, and deficits in human resources and training. Addressing these issues would be crucial to tackling the increasing burden of cancer on the continent.

The Unique Issues With Brachytherapy in Low- and Middle-Income Countries.

Gynecologic carcinomas, including cervical cancer, present a significant burden on low- and middle-income countries (LMICs). Brachytherapy plays an integral role in the treatment of gynecologic carcinomas, as it is essential for both curative and palliative treatment. However, there are numerous geographic and economic barriers to providing brachytherapy to cancer patients in LMICs.

Global Health in Radiation Oncology: The Emergence of a New Career Pathway.

The massive global shortfall in radiotherapy equipment and human resources in developing countries is an enormous challenge for international efforts in cancer control. This lack of access to treatment has been long-standing, but there is now a growing consensus about the urgent need to prioritize solutions to this problem and that a global strategy is required for them to be successful. An essential element of making radiotherapy universally accessible is a coordinated approach to clinical training and practice.

Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck.

Background: The objective of this trial was to determine how a mucoadhesive hydrogel (MuGard), a marketed medical device, would fare when tested with the strictness of a conventional multi-institutional, double-blind, randomized, placebo-controlled study format.

Methods: A total of 120 subjects planned to receive chemoradiation therapy (CRT) for treatment of head and neck cancers were randomized to receive either MuGard or sham control rinse (SC) during CRT. Subjects completed the validated Oral Mucositis Daily Questionnaire.

Samarium-153-ethylene diamine tetramethylene phosphonate, a beta-emitting bone-targeted radiopharmaceutical, useful for patients with osteoblastic bone metastases.

Bone metastases are prevalent among cancer patients and frequently cause significant morbidity. Oncology providers must mitigate complications associated with bone metastases while limiting therapy-related adverse effects and their impact on quality of life. Multiple treatment modalities, including chemotherapy, surgery, external beam radiation therapy, and radioisotopes, among others, have been recommended and utilized for palliative treatment of bone metastases.