PErspective and current status of Radiotherapy Service in IRan (PERSIR)-1 study: assessment of current external beam radiotherapy facilities, staff and techniques compared to the international guidelines.

BACKGROUND AND PURPOSE: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. MATERIALS AND METHODS: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. RESULTS: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. CONCLUSION: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.

NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Omission of adjuvant radiotherapy in low-risk elderly males with breast cancer.

PURPOSE: Randomized clinical trials demonstrate that lumpectomy + hormone therapy (HT) without radiation therapy (RT) yields equivalent survival and acceptable local-regional outcomes in elderly women with early-stage, node-negative, hormone-receptor positive (HR +) breast cancer. Whether these data apply to men with the same inclusion criteria remains unknown. METHODS: The National Cancer Database was queried for male patients ≥ 65 years with pathologic T1-2N0 (≤ 3 cm) HR + breast cancer treated with breast-conserving surgery with negative margins from 2004 to 2019. Adjuvant treatment was classified as HT alone, RT alone, or HT + RT. Male patients were matched with female patients for OS comparison. Survival analysis was performed using Cox regression and Kaplan - Meier method. Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding. RESULTS: A total of 523 patients met the inclusion criteria, with 24.4% receiving HT, 16.3% receiving RT, and 59.2% receiving HT + RT. The median follow-up was 6.9 years (IQR: 5.0-9.4 years). IPTW-adjusted 5-yr OS rates in the HT, RT, and HT + RT cohorts were 84.0% (95% CI 77.1-91.5%), 81.1% (95% CI 71.1-92.5%), and 93.0% (95% CI 90.0-96.2%), respectively. On IPTW-adjusted MVA, relative to HT, receipt of HT + RT was associated with improvements in OS (HR: 0.641; p = 0.042). RT alone was not associated with improved OS (HR: 1.264; p = 0.420). CONCLUSION: Among men ≥ 65 years old with T1-2N0 HR + breast cancer, RT alone did not confer an OS benefit over HT alone. Combination of RT + HT demonstrated significant improvements in OS. De-escalation of treatment through omission of either RT or HT at this point should be done with caution.

Radiation Oncology Workforce: Supply and Demand.

Since 2017, the specialty of radiation oncology has experienced its fifth consecutive year of decline in residency applicants, resulting in a high number of unmatched positions. The cause of this precipitous decline is multifactorial. Factors cited include concerns about future job opportunities, the decreased pass rate in the ABR radiation biology and physics boards examinations in 2018, and the continued lack of formal exposure to radiation oncology during medical school training. We summarize the issues facing the field of radiation oncology and discuss how we could learn from similar experiences in diagnostic radiology and other specialties to address these concerns. We propose potential solutions to ensure an adequate and diverse number of residency applicants to serve the future workforce needs in radiation oncology.

Experience From an Early Exposure Education Program in Radiation Oncology for High School and Undergraduate Students.

Exposure to radiation oncology (RO), which is a small and highly subspecialized field of oncology, during undergraduate or medical education is often limited. Coupled with reduced elective exposures during the COVID-19 pandemic, unsubstantiated concerns regarding the RO job market have led to a noticeable decline in residency applications and medical students who express an interest in the field. Here, we describe a summer education program piloted in our RO department at a comprehensive cancer center to provide premedical school students (ranging from high school to postbaccalaureate) early exposure to the specialty through clinical shadowing, research opportunities, journal club, and formal didactic lectures. Pre- and postprogram surveys were administered to these students to evaluate the change in knowledge in RO. A total of 8 students participated in the program. We found an increase in understanding of the specialty, high levels of interest in considering RO as a career, and positive feedback regarding the program overall. This study supports the role of early exposure and education in stimulating interest in future medical students to pursue RO as a career. Future efforts are needed to further develop and evaluate these education programs as well as disseminate the program more broadly.

Perception and Utilization of Cannabinoids in Patients Undergoing Radiation Treatment: Our Patients Are Curious.

PURPOSE: Limited studies have described the utilization of cannabinoids among patients with cancer. This survey study aimed to characterize utilization patterns and perceptions of cannabinoid use for treatment-related side effects among patients receiving radiation treatment. METHODS AND MATERIALS: This was an anonymous survey study of patients who were undergoing or recently completed radiation treatment at a comprehensive cancer center. Data on cannabinoid use during cancer treatment, reasons for the use of cannabinoids, perceived effects of cannabinoids, and formulations of usage were collected and summarized using descriptive statistics. RESULTS: Of the 431 respondents, 111 (25.8%) patients reported cannabinoid use since their cancer diagnosis. Among the cannabinoid users, a majority (73.9%) experienced improvement in symptoms; 38.7% had better relief of cancer-treatment symptoms from cannabinoids in comparison to their prescription medications, and 16.2% lowered the amount of prescription pain medications needed after using cannabinoids. Cannabinoids appeared to be most effective in helping patients manage sleep (76.6%) and anxiety (72.1%). When asked about whether physicians should be discussing cannabinoid use, 45.1% of cannabinoid users wanted to speak with their doctors regarding its utilization. For patients who did not report cannabinoid use, a large majority (83.1%) never had discussions with their doctors regarding its utilization as part of their cancer care, and 34.8% wanted to learn more about cannabinoids from their doctors. CONCLUSIONS: About 1 in 4 patients with cancer reported cannabinoid use to assist in symptom control. A majority had subjective alleviation of treatment-related symptoms from cannabinoid use. Regardless of cannabinoid use, a sizable percentage of patients never had any discussions about cannabinoids with their oncologists, with some expressing interest in learning more. Guidelines are needed to assist radiation oncologists on how cannabinoids may play a role in caring for patients.

Explainable artificial intelligence analysis of brachytherapy boost receipt in cervical cancer during the COVID-19 era.

PURPOSE: Brachytherapy is a critical component of the standard-of-care curative radiotherapy regimen for women with locally advanced cervical cancer (LACC). However, existing literature suggests that many patients will not receive the brachytherapy boost. We used machine learning (ML) and explainable artificial intelligence to characterize this disparity. MATERIALS AND METHODS: Patients with LACC diagnosed from 2004 to 2020 who received definitive radiation were identified in the National Cancer Database. Five ML models were trained to predict if a patient received a brachytherapy boost. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To identify trends that may be attributable to the coronavirus disease 2019 (COVID-19) pandemic, the previous analysis was repeated and limited to 2019 to 2020. RESULTS: A total of 37,564 patients with LACC were identified; 5799 were diagnosed from 2019 to 2020 (COVID cohort). Of these patients, 59.3% received a brachytherapy boost, with 76.4% of patients diagnosed in 2019 to 2020 receiving a boost. The random forest model achieved the best performance for both the overall and COVID cohorts. In the overall cohort, the most important predictive features were the year of diagnosis, stage, age, and insurance status. In the COVID cohort, the most important predictive features were FIGO stage, age, insurance status, and hospital type. Of the 26 patients who tested positive for COVID-19 during their course of radiotherapy, 19 (73.1%) received a brachytherapy boost. CONCLUSIONS: A gradual increase in brachytherapy boost utilization has been noted, which did not seem to be significantly impacted by the onset of the COVID-19 pandemic. ML could be considered to identify patient populations where brachytherapy is underutilized, which can provide actionable feedback for improving access.

The impact of pretreatment symptom burden on long-term quality of life following head and neck radiation: A prospective longitudinal study.

BACKGROUND: This study characterized the impact of baseline symptom burden on long-term quality-of-life in patients receiving head and neck radiation therapy (RT). METHODS: The Vanderbilt Head and Neck Symptom Survey was collected prior to head and neck RT and at follow-up visits. Responses were divided into symptom clusters of toxicities and scored from 0 (asymptomatic) to 10 (severe). Patients with responses at baseline and 1-year or 2-year follow-up were stratified by scores ≤1 or >1 and compared using the Mann-Whitney U-test. RESULTS: At 1-year follow-up (n = 75), patients with higher baseline scores had greater symptom burden for every cluster except in taste/smell. At 2-year follow-up (n = 47), patients with higher baseline scores had greater symptom burden for every cluster except in nutrition, dry mouth, trismus, neck tightness, and hearing. CONCLUSION: The Vanderbilt Head and Neck Symptom Survey demonstrated a relationship between baseline symptom burden and long-term quality-of-life and might be useful as a screening tool.

Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma.

Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte-macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan-Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0-58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4-NR mos) and 2.8 mos (95% CI, 0.7-4.4 mos), respectively; p = 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6-NR mos) and 2.8 mos (95% CI, 0.7-4.4 mos), respectively (p = 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1-not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0-NR mos); p = 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4-26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7-NR mos) (p = 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly.

Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome.

We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68+ cells and FOXP3+ cells being associated with response or resistance to ICIs were also identified. In particular, CD68+ cells, CD33+ and FOXP3+ cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68dim cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.

American Radium Society Appropriate Use Criteria for Unresectable Locally Advanced Non-Small Cell Lung Cancer.

Importance: The treatment of locally advanced non-small cell lung cancer (LA-NSCLC) has been informed by more than 5 decades of clinical trials and other relevant literature. However, controversies remain regarding the application of various radiation and systemic therapies in commonly encountered clinical scenarios. Objective: To develop case-referenced consensus and evidence-based guidelines to inform clinical practice in unresectable LA-NSCLC. Evidence Review: The American Radium Society (ARS) Appropriate Use Criteria (AUC) Thoracic Committee guideline is an evidence-based consensus document assessing various clinical scenarios associated with LA-NSCLC. A systematic review of the literature with evidence ratings was conducted to inform the appropriateness of treatment recommendations by the ARS AUC Thoracic Committee for the management of unresectable LA-NSCLC. Findings: Treatment appropriateness of a variety of LA-NSCLC scenarios was assessed by a consensus-based modified Delphi approach using a range of 3 points to 9 points to denote consensus agreement. Committee recommendations were vetted by the ARS AUC Executive Committee and a 2-week public comment period before official approval and adoption. Standard of care management of good prognosis LA-NSCLC consists of combined concurrent radical (60-70 Gy) platinum-based chemoradiation followed by consolidation durvalumab immunotherapy (for patients without progression). Planning and delivery of locally advanced lung cancer radiotherapy usually should be performed using intensity-modulated radiotherapy techniques. A variety of palliative and radical fractionation schedules are available to treat patients with poor performance and/or pulmonary status. The salvage therapy for a local recurrence after successful primary management is complex and likely requires both multidisciplinary input and shared decision-making with the patient. Conclusions and Relevance: Evidence-based guidance on the management of various unresectable LA-NSCLC scenarios is provided by the ARS AUC to optimize multidisciplinary patient care for this challenging patient population.

Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies.

BACKGROUND: The study summarizes the potential use of immunotherapy for BRAF-mutated papillary thyroid cancer (PTC) by analyzing the immune profile of City of Hope PTC patient samples and comparing them to the thyroid dataset available in the TCGA database. MATERIALS AND METHODS: PTC cases with available formalin-fixed paraffin-embedded archived tumor tissue were identified. RNA was extracted from the tumor tissue and analyzed by NanoString to evaluate their immune gene expression profile. Immunohistochemistry was used to determine the expression of immune suppressive genes and lymphocytic infiltration into the tumor tissue. Thyroid cancer cell lines (MDA-T32, MDA-T68, MDA-T85, and MDA-T120) were used to determine the correlation between the BRAF inhibition and CD274 expression. RESULTS: The study found that PTC cases with BRAF mutations had higher expression of immune checkpoint markers CD274 and CTLA4, as well as higher tumor-infiltrating lymphocytes, particularly CD4+T cells. Additionally, the study identified immunosuppressive markers expressed by tumor cells like CD73, CD276, and CD200 that could be targeted for immunotherapy. Further experiments using PTC cell lines lead to the conclusion that CD274 expression correlates with BRAF activity and that inhibitors of BRAF could potentially be used in combination with immunotherapy to treat PTC. CONCLUSIONS: These findings suggest that PTC cases with BRAF mutations or high expression may be correlated with an immune hot signature and could benefit from immunotherapeutic strategies.

Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown. METHODS: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used. RESULTS: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR-NR) and was 5.5 (interquartile range: 2.4-10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3). CONCLUSIONS: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib.