Radiation Therapy for IDH-Mutant Grade 2 and Grade 3 Diffuse Glioma: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for adults with isocitrate dehydrogenase (IDH)-mutant grade 2 and grade 3 diffuse glioma, as classified in the 2021 World Health Organization (WHO) Classification of Tumours. It includes indications for radiation therapy (RT), advanced RT techniques, and clinical management of adverse effects. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 4 key questions focused on the RT management of patients with IDH-mutant grade 2 and grade 3 diffuse glioma. 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: A strong recommendation for close surveillance alone was made for patients with oligodendroglioma, IDH-mutant, 1p/19q codeleted, WHO grade 2 after gross total resection without high-risk features. For oligodendroglioma, WHO grade 2 with any high-risk features, adjuvant RT was conditionally recommended. However, adjuvant RT was strongly recommended for oligodendroglioma, WHO grade 3. A conditional recommendation for close surveillance alone was made for astrocytoma, IDH-mutant, WHO grade 2 after gross total resection without high-risk features. Adjuvant RT was conditionally recommended for astrocytoma, WHO grade 2, with any high-risk features and strongly recommended for astrocytoma, WHO grade 3. Dose recommendations varied based on histology and grade. Given known adverse long-term effects of RT, consideration for advanced techniques such as intensity modulated radiation therapy/volumetric modulated arc therapy or proton therapy were given as strong and conditional recommendations, respectively. Finally, based on expert opinion, the guideline recommends assessment, surveillance, and management for toxicity management. CONCLUSIONS: Based on published data, the American Society for Radiation Oncology task force has proposed recommendations to inform the management of adults with IDH-mutant grade 2 and grade 3 diffuse glioma as defined by WHO 2021 classification, based on the highest quality published data, and best translated by our task force of subject matter experts.

Analysis of Internet-Based Search Patterns Utilized by Glioma Patients as Information Source.

The aim of this study is to assess the Internet usage pattern amongst glioma patients and to characterize its impact in their decision-making and clinical interactions. Glioma patients attending a tertiary cancer center between June and December 2019 were invited to participate in this study. A 26-item survey consisting of closed and open-ended questions was distributed with a unique identifier. Quantitative data were analyzed with descriptive statistics using SPSS Statistical package, and qualitative data with grounded theory approach. Thirty-two patients completed the survey. Demographics varied in age, time since diagnosis, glioma type, and level of education. Eighty-one percent were identified as "Internet users" who sought online glioma information. Google was the most popular search engine (96%), with "glioma" being the most frequent search term. The selection of websites often relied on perceived credibility and top search hits. The most searched topic was prognosis (73%). The majority of patients found that online information was easy to understand, and this did not vary significantly amongst age groups. Website quality was always assessed by 60% of patients. Only 62% patients found the Internet a useful resource, and 70% patients found it facilitated their understanding. Most patients discussed their Internet findings with a physician, largely regarding concerns about reliability. There is variable glioma information available online. Patients with glioma use the Internet as a resource, with variable impact on their interactions and decision-making. This information can be used by physicians, educators, and website developers to support glioma patients' needs.

Association Between Regional Nodal Irradiation and Breast Cancer Recurrence-Free Interval for Patients With Low-Risk, Node-Positive Breast Cancer.

PURPOSE: Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population. METHODS AND MATERIALS: Patients aged 40 to 79 years with pT1-2 pN1 (node-positive) breast cancer diagnosed between 2005 and 2014 were identified. The inclusion criteria were modeled off of the TAILOR RT study, which is a randomized noninferiority clinical trial designed to assess the value of RNI in patients with low-risk N1 disease. Eligible patients had breast-conserving surgery or mastectomy and axillary lymph node dissection with 1 to 3 positive nodes, breast-conserving surgery and sentinel lymph node biopsy with 1 to 2 positive nodes, or mastectomy and sentinel lymph node biopsy with 1 positive node. Additionally, patients had luminal A breast cancers, as approximated by estrogen receptor positive (Allred 6-8/8), progesterone receptor (PR) positive (Allred 6-8/8), human epidermal growth factor receptor 2-negative, and grade 1 to 2 immunohistochemical testing. All patients were prescribed hormonal treatment. The primary endpoint of BCRFI, the time to any breast cancer recurrence or breast cancer-related death, was analyzed using a multivariate competing risks analysis. RESULTS: The cohort included 1169 women with a median follow-up of 9.2 years. Radiation treatments were not performed in 151 women treated with mastectomy alone, were delivered to the breast only in 133 women, and were delivered locoregionally in 885 women. Patients undergoing RNI were younger (median age: 58 vs 62 years), more likely to have 2 to 3 macroscopic lymph nodes involved, and more often received chemotherapy (all P < .05). The 10-year estimate of BCRFI was 90% without RNI versus 90% with RNI (P = .5). On multivariable analysis, RNI was not a significant predictor of BCRFI (hazard ratio: 1.0; P = .9). CONCLUSIONS: In this retrospective analysis, RNI was not associated with improved BCRFI for women with biologically low-risk N1 breast cancer. We advocate accrual to the ongoing TAILOR RT study.

The Association Between Cardiac Mortality and Adjuvant Radiation Therapy Among Older Patients With Stage I Estrogen Positive Breast Cancer: A Surveillance, Epidemiology, and End Results (SEER)-Based Study on Cardiac Mortality and Radiation Therapy.

PURPOSE: We evaluated the risk of cardiac mortality in older patients who receive adjuvant radiation therapy (RT) for stage I breast cancer to determine whether this risk persists in the modern era. METHODS AND MATERIALS: Using the 2000 to 2015 Surveillance, Epidemiology, and End Results program data, we performed a population-based cohort study to evaluate the association between adjuvant breast RT, tumor laterality, and cardiac-specific survival (CSS) among patients 60 and older with stage I estrogen receptor positive breast cancer who received breast-conserving surgery and RT. RESULTS: At a median follow-up of 6 years (range, 0-15.9 years), patients receiving RT for left-sided breast cancer demonstrated no difference in 5- and 10-year CSS compared with those with right-sided breast cancer (5 year 98.3% vs 98.2%, 10 year 94.3% vs 93.9%; log-rank P = .56). Cox proportional hazards regression analysis confirmed the lack of association of tumor laterality on adjusted 5-year CSS (hazard ratio [HR] = 0.96; 95% confidence interval [CI] = 0.87-1.06), breast-cancer specific survival (HR = 0.96; 95% CI = 0.85-1.09), and overall survival (HR = 0.98; 95% CI = 0.94-1.03). There was also no association of inner versus outer quadrant location on adjusted 5-year CSS for right-sided (HR = 1.06; 95% CI = 0.89-1.12) and left-sided breast cancer (HR = 0.95; 95% CI = 0.79-1.15). CONCLUSIONS: With modern radiation therapy techniques, older patients who received left-sided RT for stage I estrogen-receptor positive breast cancer do not demonstrate an increased risk of cardiac mortality compared with patients with right-sided breast cancer. RT can be offered to older patients without concern for inducing cardiac-related death.

Breast Cancer Molecular Subtype as a Predictor of Radiation Therapy Fractionation Sensitivity.

PURPOSE: The predictive benefit of breast cancer molecular subtypes for systemic therapy approaches has been well established; yet, there is a paucity of data regarding their use as a predictor of radiation therapy fractionation sensitivity. The purpose of this study was to determine whether rates of local recurrence (LR) for patients treated with hypofractionated (HF) radiation therapy, in comparison to conventional fractionation, differ across breast cancer molecular subtypes in a large, prospectively collected cohort treated with modern systemic therapy. METHODS AND MATERIALS: Patients who received a diagnosis of stage I-III breast cancer between 2005 and 2009 were identified. Molecular subtype was determined using the American Joint Committee on Cancer classification system (luminal-A, luminal-B, HER2+, triple negative [TN]). Multivariable Cox regression modeling was used to identify predictors of LR. LR-free-survival (LRFS) was determined using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 5868 cases were identified with a median follow-up of 10.8 years. Patients with luminal-A subtype composed 45% of the cohort (n = 2628), compared with 30% luminal-B (n = 1734), 15% HER2+ (n = 903), and 10% TN (n = 603). A total of 76% (n = 4429) of patients were treated with HF. The 10-year LRFS was 97.1% (95% confidence interval [CI], 96.6-97.6) for the whole cohort. The 10-year LRFS based on molecular subtypes was 98.3% (95% CI, 97.6-98.7) luminal-A, 96.6% (95% CI, 95.5-97.4) luminal-B, 97.0% (95% CI, 95.5-98.0) HER2+, and 93.5% (95% CI, 91.1-95.3) TN (P < .001). There was no difference in the 10-year LRFS between patients treated with HF versus conventional fractionation among those with luminal-A (98.2% vs 98.4%; P = .42), luminal-B (96.6% vs 96.8%; P = .90), HER2+ (97.5% vs 95.8%; P = .12), or TN (93.9% vs 92.2%; P = .47). There was no significant interaction between subtype and fractionation regimen. CONCLUSIONS: These data support the routine use of hypofractionated radiation therapy regimens across all breast cancer subtypes.

Type and timing of systemic therapy use predict overall survival for patients with brain metastases treated with radiation therapy.

INTRODUCTION: This study aimed to investigate whether systemic therapy (ST) use surrounding radiation therapy (RT) predicts overall survival (OS) after RT for patients with brain metastases (BMs). METHODS: Provincial RT and pharmacy databases were used to review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016 (n = 3095). Multivariate analysis on a randomly selected subset was used to develop an OS nomogram. RESULTS: In comparison to the 2096 non-recipients of ST after RT, the median OS of the 999 recipients of ST after RT was 5.0 (95% Confidence interval (CI) 4.1-6.0) months longer (p < 0.0001). Some types of ST after RT were independently predictive of OS: targeted therapy (hazard ratio (HR) 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55), cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79), and immunotherapy (HR 0.64, CI 0.37-1.06). Patients who discontinued ST after RT had 0.9 (CI 0.3-1.4) months shorter median OS than patients who received no ST before or after RT (p < 0.0001). In the multivariate analysis of the 220-patient subset, established prognostic variables (extracranial disease, performance status, age, cancer diagnosis, and number of BMs), and the novel variables "ST before RT" and "Type of ST after RT" independently predicted OS. The nomogram predicted 6- and 12-month OS probability and median OS (bootstrap-corrected Harrell's Concordance Index = 0.70). CONCLUSIONS: The type and timing of ST use surrounding RT predict OS for patients with BMs.

Clinical features of head and neck cancer patients with brain metastases: A retrospective study of 88 cases.

OBJECTIVES: Brain metastases (BM) arising from head and neck cancer (HNC) are rare and not well characterized. This study aims to describe the clinicopathological features, treatments, prognostic factors, and survival in HNC patients with BM. MATERIALS AND METHODS: Non-thyroid HNC patients referred to BC Cancer from 1998 to 2016 were retrospectively reviewed for BM. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used to assess post-BM survival and prognostic factors. RESULTS: Out of 9432 HNC patients, 88 patients developed BM (0.9%, median follow-up 3.4 years). On average, the BM were diagnosed 18.5 months after the primary diagnosis and tended to arise after distant metastases to extracranial sites (85%) such as the lungs (78%). At BM presentation, 84% were symptomatic and two thirds had a poor performance status (ECOG ≥ 2, 68%). The median post-BM survival was 2.5 months (95% CI 2.1-3.3 months). On multivariable analysis, management of BM with radiotherapy (RT) alone (3.3 months, 95% CI 2.3-4.6, p = 0.005) and RT with surgery (4.4 months, 95% CI 2.8-6.9, p < 0.001) was associated with longer survival compared to best supportive care alone (1.4 months, 95% CI 1.0-2.0 months). Age, sex, performance status, sub-localization of the primary HNC, presence of extracranial metastases, and number of intracranial metastases were not associated with post-BM survival (all p ≥ 0.05). CONCLUSION: This is the largest study to date in BM from HNC. BM occur late in the course of HNC and carry a poor prognosis. Treatment with intracranial radiotherapy both with and without surgery was associated with improved survival.

Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy.

PURPOSE: To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. METHODS: A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1-10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. RESULTS: Forty-six patients survived ≥ 3 months after treatment. Age (OR 1.12 (1.04-1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06-1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7-24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. CONCLUSION: A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://clinicaltrials.gov/ct2/show/NCT01046123.

Radiation dose for thymic tumours.

Thymomas and thymic carcinomas are rare epithelial cell tumours arising from the thymus. Definitive surgical resection continues to be the primary approach for the management of thymomas and thymic carcinomas. However, complete resection is not always achievable due to the complexity of the mediastinal anatomy and in rare cases local recurrences may occur which are often incurable. Therefore, the use of Post-Operative Radiotherapy (PORT) may be considered with the intent of improving local control while being judicious of toxicity in the setting of prolonged clinical trajectories and proximity to critical structures. There continues to be a paucity of literature surrounding the use of PORT for thymomas and thymic carcinomas and the optimal dose has not yet been established. This review aims to summarize the current literature regarding radiotherapy indications and to explore issues surrounding radiotherapy dose-response-relationships for thymomas and thymic carcinoma. Long-term prospective studies using contemporary surgical and radiotherapy techniques are needed to further elucidate the optimal radiation approach in the management of thymic tumours.

Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT). METHODS: Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan-Meier method with differences compared by log-rank test. RESULTS: The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01-2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost. CONCLUSIONS: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.

Gender, Professional Experiences, and Personal Characteristics of Academic Radiation Oncology Chairs: Data to Inform the Pipeline for the 21st Century.

PURPOSE: Understanding the pathways and gateways to leadership and challenges faced by individuals in such roles can inform efforts to promote diversity and equity. We sought to describe the professional experiences and personal characteristics of academic radiation oncology (RO) chairs and to evaluate whether differences exist by gender. METHODS AND MATERIALS: Anonymous surveys were distributed to 95 chairs of RO departments during the 2016 annual meeting of the Society of Chairs of Academic Radiation Oncology Programs. The surveys included 28 closed-ended questions and the Leadership Practices Inventory. Results were analyzed by gender using χ2 tests, rank-sum, and t tests (significance P < .05). RESULTS: A total of 72 chairs responded (61 male, 10 female, 1 declined to identify gender) for a response rate of 76%. There were no significant gender differences in age, academic rank, publications, or prior leadership positions held at the time of the first chair appointment, but female respondents held significantly greater total direct funding from extramural grants than their male counterparts (median, $1.89 million [interquartile range, $0.5-$5 million] vs $0.25 million [interquartile range, $0-$1.0 million]; P = .006). Women were more likely to have spouses employed outside the home at time of their first chair appointment than men were, with a trend toward women experiencing greater difficulty relocating. Men and women identified budgeting and resource allocation as their greatest professional challenges. There were no gender differences in the Leadership Practices Inventory-identified leadership domains or professional goals. CONCLUSIONS: Female RO chairs are as equally qualified as men in terms of productivity or leadership skills, but they face distinct challenges in the context of a gender-structured society. The observation of higher grant funding among women at the time of chair appointment suggests a possible need for interventions such as unconscious bias training to ensure that selection processes do not unnecessarily hold women to a higher standard.

Salary and Resources Provided to Junior Faculty in Radiation Oncology.

PURPOSE: Given the importance of access to key resources to ensure future academic success, we seek to describe what is currently provided to junior faculty in radiation oncology. METHODS AND MATERIALS: We present descriptive analyses from a survey of academic radiation oncologists in the United States and Canada who were within 5 years of board certification. We used a pretested questionnaire evaluating time, space, staff, start-up funding, and compensation. RESULTS: We surveyed 347 faculty, with a response rate of 64% (n = 221). Respondents reported working an average of 56 hours per week. Most respondents (59.2%) reported that that their research time was "poorly" or "not at all" protected. Most perceived adequate access to space (75.7%) and equipment (73.6%). A substantial proportion perceived inadequate or no access to support from grant administrators (47.9%) or statisticians (55.5%). A third (33.6%) reported having a research assistant, and 22.2% received start-up research funding. CONCLUSIONS: These findings suggest perceived needs for protected time, grants administration, and statistical support among junior faculty in radiation oncology.

Mentorship Experiences of Early-Career Academic Radiation Oncologists in North America.

PURPOSE: Given concerns about attrition and career outcomes of academic radiation oncologists, we sought to gather empirical evidence regarding mentorship experiences. METHODS AND MATERIALS: We surveyed academic radiation oncologists in the United States and Canada who were within 5 years of board certification, using a pretested questionnaire that included 14 questions evaluating the following aspects of mentorship: relationship development, peer mentorship, satisfaction with mentorship, sponsorship, relationship nature, informal interactions, mentoring roles, presence of a primary mentor, and primary mentor characteristics. We described responses and evaluated associations with gender in separate multivariable regression models that adjusted for years in practice, nature of research, possession of higher degrees, and race. RESULTS: Of 347 faculty surveyed, 221 responded (64% response rate); 66% of respondents were men. Over half of respondents indicated difficulty in identifying role models (56%, n = 124); just under half reported ease in developing mentoring relationships (49%, n = 108). Peer-mentor use was commonly reported (62%, n = 138). Most respondents (66%, n = 145) spent ≤1 hour per month meeting with mentors. Only 51% (n = 112) reported having a primary mentor. Just under half of all respondents reported being very or somewhat satisfied with their mentorship experiences (49%, n = 108). CONCLUSIONS: These findings suggest a need for academic radiation oncology departments to facilitate mentorship of all junior faculty through deliberate, structured programs, with training of mentors and mentees alike. It is heartening that substantial rates of sponsorship and peer-mentorship use were reported, which may serve as the grounding for further initiatives.

Skull base or cervical vertebral osteomyelitis following chemoradiotherapy for pharyngeal carcinoma: A serious but treatable complication.

Osteomyelitis, infection of the bone and marrow, following high dose (chemo-)radiotherapy for head and neck cancer is uncommon and rarely seen in the cervical spine or temporal bone. Due to its proximity to critical structures, osteomyelitis in the latter regions could carry potentially important consequences. Furthermore, involvement near the skull base (e.g. temporal bone and high cervical vertebrae) presents unique challenges in diagnosis (especially in the differentiation from disease recurrence) and treatment, making early detection and timely intervention critical. In this report, we describe two cases of osteomyelitis, one involving the temporal bone and the other affecting the 2nd and 3rd cervical vertebrae, diagnosed and treated with good outcome in the setting of definitive chemoradiotherapy for locally advanced pharyngeal carcinomas. We suggest that for new or evolving post-radiotherapy osseous changes in regions that have received a high dose of radiotherapy, associated with unexpected and deteriorating spinal symptoms such as pain and spasm, radiation-related osteomyelitis should be considered in the differential diagnosis from tumor progression. Timely referral to a surgical oncologist and infectious diseases specialist is paramount in achieving satisfactory clinical outcomes.

Qualitative Assessment of Academic Radiation Oncology Department Chairs' Insights on Diversity, Equity, and Inclusion: Progress, Challenges, and Future Aspirations.

PURPOSE: A lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. We sought to gain a nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URMs) in these influential positions. METHODS AND MATERIALS: From March to June 2016, we conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was used to invite all chairs who were women (n = 13) or URMs (n = 3) and 11 male chairs who were not URMs. Multiple analysts coded the verbatim transcripts. RESULTS: Five themes were identified: (1) commitment to DEI promotes quality health care and innovation; (2) gaps remain despite some progress with promoting diversity in RO; (3) women and URM faculty continue to experience challenges in various career domains; (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race; and (5) expansion of the career pipeline is needed. CONCLUSIONS: The chairs' insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school.