External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for palliative external beam radiation therapy (RT) in symptomatic bone metastases. METHODS: The American Society for Radiation Oncology (ASTRO) convened a task force to address 5 key questions regarding palliative RT in symptomatic bone metastases. Based on a systemic review by the Agency for Health Research and Quality, recommendations using predefined consensus-building methodology were established; evidence quality and recommendation strength were also assessed. RESULTS: For palliative RT for symptomatic bone metastases, RT is recommended for managing pain from bone metastases and spine metastases with or without spinal cord or cauda equina compression. Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone. Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression. Patients with non-spine bone metastases requiring surgery are recommended postoperative RT. Symptomatic bone metastases treated with conventional RT are recommended 800 cGy in 1 fraction (800 cGy/1fx), 2000 cGy/5fx, 2400 cGy/6fx, or 3000 cGy/10fx. Spinal cord or cauda equina compression in patients ineligible for surgery and receiving conventional RT are recommended 800 cGy/1fx, 1600 cGy/2fx, 2000 cGy/5fx, or 3000 cGy/10fx. Symptomatic bone metastases in selected patients with good performance status without surgery or neurological symptoms/signs are conditionally recommended SBRT over conventional palliative RT. Spine bone metastases re-irradiated with conventional RT are recommended 800 cGy/1fx, 2000 cGy/5fx, 2400 cGy/6fx, or 2000 cGy/8fx; non-spine bone metastases re-irradiated with conventional RT are recommended 800 cGy/1fx, 2000 cGy/5fx, or 2400 cGy/6fx. Determination of an optimal RT approach/regimen requires whole person assessment, including prognosis, previous RT dose if applicable, risks to normal tissues, quality of life, cost implications, and patient goals and values. Relatedly, for patient-centered optimization of treatment-related toxicities and quality of life, shared decision-making is recommended. CONCLUSIONS: Based on published data, the ASTRO task force's recommendations inform best clinical practices on palliative RT for symptomatic bone metastases.

Demographic Trends Among American Society for Radiation Oncology Clinical Practice Guideline Task Force Participants From 2010 to 2022.

PURPOSE: The American Society for Radiation Oncology (ASTRO) has produced evidence-based clinical practice guidelines since 2009. It is unknown whether task force members for these guidelines are representative of the diversity of the radiation oncology field, particularly in comparison to the ASTRO membership demographics. We sought to characterize the demographic composition of all task force members to date. METHODS: The author list for ASTRO-led published guidelines from 2010 to 2022 was assessed. Main practice location/institution was extracted from the guideline publication. Self-identified gender and race/ethnicity were obtained from the ASTRO membership database. Years of experience were measured as the number of years post-board certification at time of guideline development. For United States (US)-based physicians, gender was confirmed with the National Provider Identifier database. Proportions of task force members overall and by individual guideline were described by gender, underrepresented in medicine (URM) status, geography (US vs international), US region (if US based), years of experience (separated into ≤5 years including residents, 6-12 years, and >12 years), and type of practice. Proportions for gender, URM, and geography were compared with ASTRO membership demographics. RESULTS: Between 2010 and 2022, there were 25 guideline task forces, with a total of 366 participants: 233 men, 126 women, and 7 unknown gender. There were more men than women serving on most individual task force topics, with 28% of all task forces having >80% composition of men. Of those with self-identified race/ethnicity, 9/204 (4.4%) were URM, which was lower in proportion to URM self-identified ASTRO members (336/3277, 10.3%; P = .007). Most participants were based in the US (n = 323, 88.3%), had >12 years of experience (n = 141, 38.5%), and were from academic institutions (n = 302, 82.5%). Community practitioners were less likely to be women or URM. CONCLUSIONS: Improved data collection and more intentional efforts are needed to ensure that the diversity of guidelines task forces is representative of ASTRO membership and the specialty.

Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin: Executive Summary of an American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: This guideline reviews the evidence for the use of definitive and postoperative radiation therapy (RT) in patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on indications for RT in the definitive and postoperative setting for BCC and cSCC, as well as dose-fractionation schemes, target volumes, basic aspects of treatment planning, choice of radiation modality, and the role of systemic therapy in combination with radiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: The guideline recommends definitive RT as primary treatment for patients with BCC and cSCC who are not surgical candidates while conditionally recommending RT with an emphasis on shared decision-making in those situations in which adequate resection can lead to a less than satisfactory cosmetic or functional outcome. In the postoperative setting, a number of indications for RT after an adequate resection are provided while distinguishing the strength of the recommendations between BCC and cSCC. One key question is dedicated to defining indications for regional nodal irradiation. The task force suggests a range of appropriate dose-fractionation schemes for treatment of primary and nodal volumes in definitive and postoperative scenarios. The guideline also recommends against the use of carboplatin concurrently with adjuvant RT and conditionally recommends the use of systemic therapies for unresectable primaries where treatment may need escalation. CONCLUSIONS: Defining the role of RT in the management of BCC and cSCC has been hindered by a lack of high-quality evidence. This document synthesizes available evidence to define practice guidelines for the most common clinical situations. We encourage practitioners to enroll patients in prospective trials and to approach care in a multidisciplinary fashion whenever possible.

Palliative thoracic radiation therapy for non-small cell lung cancer: 2018 Update of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline.

PURPOSE: To revise the recommendation on the use of concurrent chemotherapy (CC) with palliative thoracic external beam radiation therapy (EBRT) made in the original 2011 American Society for Radiation Oncology guideline on palliative thoracic radiation for lung cancer. METHODS AND MATERIALS: Based on a systematic PubMed search showing new evidence for this key question, the task force felt an update was merited. Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength. RESULTS: Although few randomized clinical trials address the question of CC combined with palliative thoracic EBRT for non-small cell lung cancer (NSCLC), a strong consensus was reached among the task force on recommendations for incurable stage III and IV NSCLC. For patients with stage III NSCLC deemed unsuitable for curative therapy but who are (1) candidates for chemotherapy, (2) have an Eastern Cooperative Oncology Group PS of 0 to 2, and (3) have a life expectancy of at least 3 months, administration of a platinum-containing chemotherapy doublet concurrently with moderately hypofractionated palliative thoracic radiation therapy is recommended over treatment with either modality alone. For patients with stage IV NSCLC, routine use of concurrent thoracic chemoradiation is not recommended. CONCLUSIONS: Optimal palliation of patients with incurable NSCLC requires coordinated interdisciplinary care. Recent data establish a rationale for CC with palliative thoracic EBRT for a well-defined subset of patients with incurable stage III NSCLC. For all other patients with incurable NSCLC, data remain insufficient to support this treatment approach.

Silencing CDK4 radiosensitizes breast cancer cells by promoting apoptosis.

BACKGROUND: The discovery of molecular markers associated with various breast cancer subtypes has greatly improved the treatment and outcome of breast cancer patients. Unfortunately, breast cancer cells acquire resistance to various therapies. Mounting evidence suggests that resistance is rooted in the deregulation of the G1 phase regulatory machinery. METHODS: To address whether deregulation of the G1 phase regulatory machinery contributes to radiotherapy resistance, the MCF10A immortalized human mammary epithelial cell line, ER-PR-Her2+ and ER-PR-Her2- breast cancer cell lines were irradiated. Colony formation assays measured radioresistance, while immunocytochemistry, Western blots, and flow cytometry measured the cell cycle, DNA replication, mitosis, apoptosis, and DNA breaks. RESULTS: Molecular markers common to all cell lines were overexpressed, including cyclin A1 and cyclin D1, which impinge on CDK2 and CDK4 activities, respectively. We addressed their potential role in radioresistance by generating cell lines stably expressing small hairpin RNAs (shRNA) against CDK2 and CDK4. None of the cell lines knocked down for CDK2 displayed radiosensitization. In contrast, all cell lines knocked down for CDK4 were significantly radiosensitized, and a CDK4/CDK6 inhibitor sensitized MDA-MB-468 to radiation induced apoptosis. Our data showed that silencing CDK4 significantly increases radiation induced cell apoptosis in cell lines without significantly altering cell cycle progression, or DNA repair after irradiation. Our results indicate lower levels of phospho-Bad at ser136 upon CDK4 silencing and ionizing radiation, which has been shown to signal apoptosis. CONCLUSION: Based on our data we conclude that knockdown of CDK4 activity sensitizes breast cancer cells to radiation by activating apoptosis pathways.

The negative effect of triple-negative breast cancer on outcome after breast-conserving therapy.

PURPOSE: To evaluate disease failure patterns and overall survival (OS) of women with triple-negative (TN) breast cancer who underwent breast-conserving therapy (BCT) and to understand the relationship of TN tumors with other prognostic factors. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry identified 562 women diagnosed and/or treated with unilateral invasive breast cancer during 2003-2004 at three Emory hospitals. After medical record review, 193 eligible women, with all tumor types, received BCT. Primary endpoints (local, regional, and distant recurrences) and secondary endpoint (OS) were evaluated using chi-square tests and Cox proportional hazards models. RESULTS: Of the 193 women, 33 (17.1%) had TN tumors and 160 (82.9%) had non-TN tumors. Patient characteristics were similar between the two tumor types; however, tumor grade and use of chemotherapy and hormones differed between the two groups. Median follow-up was 3.4 years; 22 patients had recurrence (12.2%), and 12 died (6.2%). Patients with TN tumors had higher local (12% versus 4% for non-TN) and distant recurrences (15% versus 4% for non-TN) rates (p = 0.01). On multivariate survival analyses, TN status [hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.13-2.93] and African American (AA) race (HR 1.9, 95%CI 1.2-3.07) were independent predictors of inferior OS. CONCLUSIONS: Patients with TN breast cancer showed significant increases in local and distant metastatic recurrence rates after BCT, and TN status and AA race were independent negative predictors of survival. For the future, identification of these high risk features may bring personalized medicine closer to reality.