The impact of a positive COVID-19 test on timeliness of radiation in patients receiving brachytherapy.

Background: Delays in initiating and completing brachytherapy may have adverse oncologic outcomes for patients with cervical, uterine, and prostate cancer. The impact of the COVID-19 pandemic on brachytherapy in the United States has not been well-characterized.

Objectives: We aim to evaluate how a positive COVID-19 test affected timeliness of treatment for patients undergoing brachytherapy for cervical, uterine, and prostate cancer.

A Spontaneous Aggressive ERα+ Mammary Tumor Model Is Driven by Kras Activation.

The NRL-PRL murine model, defined by mammary-selective transgenic rat prolactin ligand rPrl expression, establishes spontaneous ER+ mammary tumors in nulliparous females, mimicking the association between elevated prolactin (PRL) and risk for development of ER+ breast cancer in postmenopausal women. Whole-genome and exome sequencing in a discovery cohort (n = 5) of end-stage tumors revealed canonical activating mutations and copy number amplifications of Kras. The frequent mutations in this pathway were validated in an extension cohort, identifying activating Ras alterations in 79% of tumors (23 of 29).

17-Estradiol and ICI182,780 Differentially Regulate STAT5 Isoforms in Female Mammary Epithelium, With Distinct Outcomes.

Prolactin (PRL) and estrogen cooperate in lobuloalveolar development of the mammary gland and jointly regulate gene expression in breast cancer cells . Canonical PRL signaling activates STAT5A/B, homologous proteins that have different target genes and functions. Although STAT5A/B are important for physiological mammary function and tumor pathophysiology, little is known about regulation of their expression, particularly of STAT5B, and the consequences for hormone action.

Management of GBM: a problem of local recurrence.

Forty years ago, adjuvant treatment of patients with GBM using fractionated radiotherapy following surgery was shown to substantially improve survival compared to surgery alone. However, even with the addition of temozolomide to radiotherapy, overall survival is quite limited and local failure remains a fundamental problem, despite multiple attempts to increase dose to the tumor target. This review presents the historical background and clinical rationale leading to the current standard of care consisting of 60 Gy total dose in 2 Gy fractions to the MRI-defined targets in younger, high performance status patients and more hypofractionated regimens in elderly and/or debilitated patients.

Debate: adjuvant whole brain radiotherapy or not? More data is the wiser choice.

Every year 170,000 patients are diagnosed with brain metastases (BMs) in the United States. Traditionally, adjuvant whole brain radiotherapy (AWBRT) has been offered following local therapy with neurosurgery (NSx) and/or stereotactic radiosurgery (SRS) to BMs. The aim is to increase intracranial control, thereby decreasing symptoms from intracranial progression and a neurological death.

Molecular Targeting of Growth Factor Receptor Signaling in Radiation Oncology.

Ionizing radiation has been shown to activate and interact with multiple growth factor receptor pathways that can influence tumor response to therapy. Among these receptor interactions, the epidermal growth factor receptor (EGFR) has been the most extensively studied with mature clinical applications during the last decade. The combination of radiation and EGFR-targeting agents using either monoclonal antibody (mAb) or small-molecule tyrosine kinase inhibitor (TKI) offers a promising approach to improve tumor control compared to radiation alone.

Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours.

Background: Mipsagargin (G-202; (8-O-(12-aminododecanoyl)-8-O-debutanoyl thapsigargin)-Asp-γ-Glu-γ-Glu-γ-GluGluOH)) is a novel thapsigargin-based targeted prodrug that is activated by PSMA-mediated cleavage of an inert masking peptide. The active moiety is an inhibitor of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. We evaluated the safety of mipsagargin in patients with advanced solid tumours and established a recommended phase II dosing (RP2D) regimen.

Pilot study of intravenous melphalan combined with continuous infusion L-S,R-buthionine sulfoximine for children with recurrent neuroblastoma.

Purpose: To evaluate BSO-mediated glutathione (GSH) depletion in combination with L-PAM for children with recurrent or refractory high-risk neuroblastoma (NB) as a means to enhance alkylator sensitivity.

Procedure: This pilot study (NCI #T95-0092) administered L-S,R-buthionine sulfoximine (BSO) as a bolus followed by 72 hr continuous infusion of either 0.75 g/m(2)/hr (level 1) or 1.

Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014.

Supportive care and palliative care are now recognised as critical components of global cancer control programmes. Many aspects of supportive and palliative care services are already available in some low-income and middle-income countries. Full integration of supportive and palliative care into breast cancer programmes requires a systematic, resource-stratified approach.

Results of the 2012-2013 Association of Residents in Radiation Oncology (ARRO) job search and career planning survey of graduating residents in the United States.

Purpose/objective(s): To determine the timeline used by postgraduate year (PGY)-5 radiation oncology residents during the job application process and the factors most important to them when deciding on a first job.

Methods And Materials: In 2012 and 2013, the Association of Residents in Radiation Oncology conducted a nationwide electronic survey of PGY-5 radiation oncology residents in the United States during the final 2 months of their training. Descriptive statistics are reported.

Sym004, a novel anti-EGFR antibody mixture, augments radiation response in human lung and head and neck cancers.

Sym004 represents a novel EGF receptor (EGFR)-targeting approach comprising a mixture of two anti-EGFR antibodies directed against distinct epitopes of EGFR. In contrast with single anti-EGFR antibodies, Sym004 induces rapid and highly efficient degradation of EGFR. In the current study, we examine the capacity of Sym004 to augment radiation response in lung cancer and head and neck cancer model systems.

Supportive and palliative care for metastatic breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement.

Many women diagnosed with breast cancer in low- and middle-income countries (LMICs) present with advanced-stage disease. While cure is not a realistic outcome, site-specific interventions, supportive care, and palliative care can achieve meaningful outcomes and improve quality of life. As part of the 5th Breast Health Global Initiative (BHGI) Global Summit, an expert international panel identified thirteen key resource recommendations for supportive and palliative care for metastatic breast cancer.

Enhanced radiation sensitivity in HPV-positive head and neck cancer.

Patients with human papillomavirus (HPV+)-associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques.

Severe late toxicities following concomitant chemoradiotherapy compared to radiotherapy alone in cervical cancer: an inter-era analysis.

Purpose: To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer.

Methods And Materials: Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade≥3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.

Results of the 2005 to 2008 Association of Residents in Radiation Oncology surveys of chief residents in the United States: didactics and research experience.

Objectives: To analyze the didactics and research experience reported by chief residents during their residency training.

Methods: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology (ARRO) conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistic was used to assess for changes in didactics and research experience over time.

The use of single-agent dasatinib in molecularly unselected non-small-cell lung cancer patients.

A Phase II study of the Src family kinase (SFK) inhibitor dasatinib was recently reported in molecularly unselected patients with metastatic NSCLC. SFK inhibition has a strong rationale as a clinical strategy in NSCLC. The reviewed study unfortunately showed disappointing activity as monotherapy in this molecularly unselected patient cohort and toxicity in terms of pleural effusion was problematic.

Randomized trial of adjuvant zoledronic acid in postmenopausal women with high-risk breast cancer.

Purpose: We present the results of a randomized multicenter clinical trial of adjuvant zoledronic acid (ZA) in postmenopausal women with high-risk breast cancer. The primary objective was change in bone mineral density (BMD) at the lumbar spine and femoral neck at 1 year. Secondary objectives included change in calcaneal BMD, disease-free survival (DFS), overall survival (OS), and toxicity.

Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model.

We recently demonstrated that Sirt1, a NAD(+) -dependent histone deacetylase, was overexpressed in prostate cancer (PCa) and its inhibition resulted in a significant antiproliferative response in human PCa cells. Studies have suggested a link between Sirt1 and circadian rhythms, the disruption of which has been linked to cancer. Interestingly, a decreased production of the pineal melatonin has been shown to deregulate the circadian rhythm machinery and increase cancer risk.

Why avoid the hippocampus? A comprehensive review.

In this review article, we provide a detailed and comprehensive discussion of the rationale for using modern IMRT techniques to spare the subgranular zone of the hippocampus during cranial irradiation. We review the literature on neurocognitive effects of cranial irradiation; discuss clinical and preclinical data associating damage to neural progrenitor cells located in subgranular zone of the hippocampus with radiation-induced neurocognitive decline, specifically in terms of short-term memory formation and recall; and present a review of our pilot investigations into the feasibility and risks of sparing the subgranular zone of the hippocampus during whole-brain radiotherapy for brain metastases. We also introduce our phase II cooperative group clinical trial (RTOG 0933) designed to prospectively evaluate the postulated neurocognitive benefit of hippocampal subgranular zone sparing and scheduled to open in 2010.

Results of the 2005-2008 Association of Residents in Radiation Oncology survey of chief residents in the United States: clinical training and resident working conditions.

Purpose: To document clinical training and resident working conditions reported by chief residents during their residency.

Methods And Materials: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistics were used to assess changes in clinical training and resident working conditions over time.

Novel insights into the management of brain metastases.

Purpose Of Review: This review provides available clinical evidence regarding current therapies, discusses ongoing controversies, and introduces investigational approaches in the management of brain metastases.

Recent Findings: Novel approaches to estimating prognosis of patients with brain metastases highlight the importance of tailoring treatment to each particular patient. In the setting of unfavorable prognosis, either hospice care, symptom management, or short-course whole-brain radiotherapy (WBRT) is a critical component of palliation.

Fractionated radiotherapy for intracranial meningiomas.

Fractionated external beam radiotherapy (EBRT) has multiple roles in the management of intracranial meningiomas. In multiple series post-operative EBRT has shown improved progression-free survival following subtotal resection and a reduction in long-term failures following an apparent gross total resection. In the definitive setting, the use of EBRT has increased as the growing utilization of neuro-imaging for various conditions identifies skull-based lesions which are not easily resectable.

Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy.

Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases.

Methods And Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed.

Understanding resistance to EGFR inhibitors-impact on future treatment strategies.

EGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. Following ligand binding, EGFR stimulates downstream cell signaling cascades that influence cell proliferation, apoptosis, migration, survival and complex processes, including angiogenesis and tumorigenesis. EGFR has been strongly implicated in the biology of human epithelial malignancies, with therapeutic applications in cancers of the colon, head and neck, lung, and pancreas.

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933.

Background And Purpose: RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5mm margin).

Materials/methods: Patients with < or = 10 brain metastases treated at two separate institutions were reviewed.