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The COVID-19 pandemic catalyzed the integration of a virtual education curriculum to support radiation oncologists in training. We report outcomes from Radiation Oncology Virtual Education Rotation (ROVER) 2.0, a supplementary virtual educational curriculum created for radiation oncology residents globally. A prospective cohort of residents completed surveys before and after the live virtual webinar sessions (pre- and post-surveys, respectively). Live sessions were structured as complex gray-zone cases across various core disease sites. Resident demographics and responses were summarized using means, standard deviations, and proportions. Nine ROVER sessions were held from October 2020 to June 2021. A total of 1487 registered residents completed the pre-survey, of which 786 attended the live case discussion and 223 completed post-surveys. A total of 479 unique radiation oncology residents (of which 95, n = 19.8%, were international attendees) from 147 institutions (national, n = 81, 55.1%; international, n = 66, 44.9%) participated in the sessions. There was similar participation across post-graduate year (PGY) 2 through 5 (range n = 86 to n = 105). Of the 122 unique resident post-surveys, nearly all reported learning through the virtual structure as "very easy" or "easy" (97.5%, n = 119). A majority rated the ROVER 2.0 educational sessions to be "valuable or "very valuable" (99.2%, n = 121), and the panelists-attendee interaction as "appropriate" (97.5%, n = 119). Virtual live didactics aimed at radiation oncology residents are feasible. These results suggest that the adoption of the ROVER 2.0 curricula may help improve radiation oncology resident education.

Background Glioblastoma (GBM) is a malignant brain tumor that is common and fatal among adults. The standard treatment for GBM involves chemoradiation per Stupp's protocol and additional chemotherapy regimens. However, Stereotactic Radiosurgery (SRS) is frequently used as a single-fraction treatment for punctate recurrent GBM to the contrast-enhancing target on T1 MRI scan without prior assessment of its efficacy. Objective This study aimed to evaluate the safety and efficacy of SRS for patients with distant punctate recurrent IDH-wild type (wt) GBM. Method This retrospective study analyzed the clinical and radiological outcomes of patients with distant punctate recurrent IDH-wt GBM who underwent CyberKnife SRS at the institute between 2013 and 2022. Results A total of five patients (median age of 53 years) with nine lesions were treated with a median margin dose of 20 Gy. The results indicated that SRS, delivered as a single fraction, did not provide good local tumor control. The 3-, 6-, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was 7 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was not associated with the T2-FLAIR hyperintense area surrounding the original tumor in the MRI. None of the patients presented adverse radiation effects. Conclusion SRS as a treatment for distant punctate recurrent IDH-wt GBM may lead to limited benefit in terms of local tumor control. Expanding the radiosurgical field to consider the T2-FLAIR hyperintense area may be necessary to improve local tumor control and survival outcomes. Further research is needed to improve SRS outcomes by developing new contouring and dosing strategies.

Introduction : Use of hypofractionated radiation (HFRT) and intensity-modulated radiation (IMRT) for organ preservation in bladder cancer is controversial and highly variable. We investigated practice patterns, trends, and predictors of HFRT and IMRT. Patients and Methods : The National Cancer Database was queried for patients with muscle-invasive, non-metastatic urothelial bladder cancer, treated with definitive (chemo)radiotherapy between 2004-2017. HFRT was defined as 50-60 Gy at >2 Gy/fraction. Multivariable logistic regression was used to identify predictors of receiving HFRT or IMRT. Multivariable Cox regression was used to model overall survival (OS), adjusting for potential confounders such as age, comorbidity, and chemotherapy. Results : Of 5132 patients identified, 490 (9.5%) received HFRT, and only 334 (6.5%) received ≥ 2.5 Gy/fraction. HFRT patients were significantly older, less fit, and less likely to receive chemotherapy relative to CFRT, even after controlling for age and comorbidity (adjusted odds ratio 0.36, 95% confidence interval [CI] 0.29-0.45, P Conclusion : HFRT is largely underutilized, being primarily reserved for older, frailer patients. Chemotherapy is significantly underused with HFRT relative to CFRT. IMRT is used frequently and was associated with equivalent or modestly increased overall survival. MICROABSTRACT : This National Cancer Database study of bladder cancer patients treated with definitive (chemo) radiotherapy uncovered significant under-utilization of hypofractionated RT (HFRT). Furthermore, chemotherapy was significantly underused with HFRT compared to patients receiving conventional fractionation. Use of both intensity-modulated RT (IMRT) and HFRT increased over time. IMRT was associated with similar or modestly increased survival, particularly in patients receiving HFRT.

Peri-RT mortality (death during or within 30 days of non-palliative radiotherapy) has been historically overlooked, and rates and risk factors are unclear.Patients with non-metastatic cancer, treated with non-palliative external beam radiation (RT) 2004-2016, were identified in the National Cancer Database for 11 cancer types: breast, prostate, non-prostate genitourinary, bone/soft tissue, gynecological, head/neck, lymphoma, gastrointestinal (GI), small cell lung, non-small cell lung, and central nervous system (CNS). Multivariable logistic regression was used to identify predictors of peri-RT mortality controlled for 17 covariates, including patient, tumor, and treatment factors.Approximately 1.53 million patients were identified. Peri-RT mortality was 2.46% overall, spanning two orders of magnitude from 0.14% for breast to 8.52% for CNS. Peri-RT mortality steadily improved from 3.13% in 2004 to 1.78% in 2016 (P .0001). Major predictors of peri-RT mortality included age, baseline comorbidity, male sex, and stage (P .0001). Conversely, higher patient volume at the treating facility and use of more conformal RT planning techniques were moderately protective (P .0001). Racial disparities varied based on disease site, as Black patients had increased peri-RT mortality for breast, lymphoma, and GI cancers, but not for other cancer types. Lack of private insurance was associated with substantially increased peri-RT mortality regardless of cancer type.Peri-RT mortality varied considerably according to multiple factors. Sociodemographic differences highlight areas of health disparities and opportunities for quality improvement. Early recognition of patients at increased risk may facilitate implementation of closer monitoring or other preventive measures.

Introduction Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases. Methods Data were retrospectively collected from three academic institutions. Two treatment groups (CNS-penetrant TKI alone versus TKI + CNS radiation therapy) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy. Results A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial progression (14.8 versus 20.5 mo, p = 0.51 [EGFR] and 18.1 versus 21.8 mo, p = 0.65 [ALK]), or time to treatment failure (13.8 versus 8.6 mo, p = 0.26 [EGFR] and 13.5 versus 23.2 mo, p = 0.95 [ALK]). Conclusions These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively affecting progression.

Purpose: Breast cancer is a heterogeneous disease and not all patients respond equally to adjuvant radiotherapy. Predictive biomarkers are needed to select patients who will benefit from the treatment and spare others the toxicity and burden of radiation.Experimental Design: We first trained and tested an intrinsic radiosensitivity gene signature to predict local recurrence after radiotherapy in three cohorts of 948 patients. Next, we developed an antigen processing and presentation-based immune signature by maximizing the treatment interaction effect in 129 patients. To test their predictive value, we matched patients treated with or without radiotherapy in an independent validation cohort for clinicopathologic factors including age, ER status, HER2 status, stage, hormone-therapy, chemotherapy, and surgery. Disease-specific survival (DSS) was the primary endpoint.Results: Our validation cohort consisted of 1,439 patients. After matching and stratification by the radiosensitivity signature, patients who received radiotherapy had better DSS than patients who did not in the radiation-sensitive group [hazard ratio (HR), 0.68; P = 0.059; n = 322], whereas a reverse trend was observed in the radiation-resistant group (HR, 1.53; P = 0.059; n = 202). Similarly, patients treated with radiotherapy had significantly better DSS in the immune-effective group (HR, 0.46; P = 0.0076; n = 180), with no difference in DSS in the immune-defective group (HR, 1.27; P = 0.16; n = 348). Both signatures were predictive of radiotherapy benefit (Pinteraction = 0.007 and 0.005). Integration of radiosensitivity and immune signatures further stratified patients into three groups with differential outcomes for those treated with or without radiotherapy (Pinteraction = 0.003).Conclusions: The proposed signatures have the potential to select patients who are most likely to benefit from radiotherapy. Clin Cancer Res; 24(19); 4754–62. ©2018 AACR.

Supplement Table 1. Genes and Cox regression coefficients in radiation-sensitivity signature Supplement Table 2. Univariate and multivariate Cox regression analysis of local recurrence-free survival using RSS and clinical variables in the prognostic biomarker training cohort (GSE30682). Supplement Table 3. Univariate and multivariate Cox regression analysis of the interaction effect with radiation treatment using IMS and clinical variables in the predictive biomarker training cohort (E-TABM-158). Supplement Table 4. Number of patients excluded in the METABRIC cohort during variable matching and the reason for exclusion. Supplement Table 5. Multivariate Cox regression analysis of the interaction effect with radiation treatment using RSS and clinical variables in the entire METABRIC cohort. Supplement Table 6. Multivariate Cox regression analysis of the interaction effect with radiation treatment using IMS and clinical variables in the entire METABRIC cohort. Supplement Table 7. Multivariate Cox regression analysis of the interaction effect with radiation treatment using the integrated signature (RSS+IMS) and clinical variables in the entire METABRIC cohort. Supplement Table 8. Multivariate Cox regression analysis of the interaction effect with radiation treatment using RSI and clinical variables on the entire METABRIC cohort. Supplement Table 9. Multivariate Cox regression analysis of the interaction effect with radiation treatment using OncotypeDX and clinical on the entire METABRIC cohort. Supplement Table 10. Multivariate Cox regression analysis of the interaction effect with radiation treatment using RSS, IMS, OncotypeDX, RSI, and clinical variables on the entire METABRIC cohort. Supplement Figure 1. Standardized log-rank test statistics at different cutoffs of RSS on GSE30682. Supplement Figure 2. Local recurrence-free survival stratified by RSS on the prognostic biomarker training cohort GSE30862. Supplement Figure 3. Standardized log-rank test statistics at different cutoffs of IMS on E-TABM-158. Supplement Figure 4. Disease-specific survival stratified by IMS on the predictive biomarker training cohort E-TABM-158. (A) immune-effective group; (B) immune-defective group; Pinteraction = 0.0007. Supplement Figure 5. Relapse-free survival stratified by IMS in the prognostic validation cohort: (A) NKI; (B) GSE2034. Supplement Figure 6. Kaplan-Meier plot of DSS for patients who had received radiation versus those who did not: (A) in the entire METABRIC cohort; (B) in the matched METABRIC cohort. Supplement Figure 7. Disease-specific survival stratified by RSS for patients with mastectomy on the METABRIC cohort. (A) Matched radiation-sensitive cohort; (B) matched radiation-resistant cohort; Pinteraction = 0.007. Disease-specific survival stratified by IMS for patients with mastectomy on the METABRIC cohort. (C) Matched immune-effective cohort; (D) matched immune-defective cohort; Pinteraction = 0.009. Supplement Figure 8. Disease-specific survival stratified by integrated RSS and IMS signature for patients with mastectomy on the METABRIC cohort. (A) Matched radiation-sensitive, immune-effective cohort; (B) matched radiation-resistant, immune-defective cohort; (C) matched radiation-resistant, immune-effective or radiation-sensitive, immune-defective; Pinteraction = 0.004. Supplement Figure 9. Disease-specific survival stratified by RSS for patients with BCS on the METABRIC cohort. (A) Matched radiation-sensitive cohort; (B) matched radiation-resistant cohort; Pinteraction = 0.54. Disease-specific survival stratified by IMS for patients with BCS on the METABRIC cohort. (C) Matched immune-effective cohort; (D) matched immune-defective cohort. Pinteraction = 0.15. Supplement Figure 10. Disease-specific survival stratified by integrated RSS and IMS signature for patients with BCS on the METABRIC cohort. (A) Matched radiation-sensitive, immune-effective cohort; (B) matched radiation-resistant, immune-defective cohort; (C) matched radiation-resistant, immune-effective or radiation-sensitive, immune-defective; Pinteraction = 0.36. Supplement Figure 11. Disease-specific survival stratified by RSI on the METABRIC cohort. (A) Matched low-RSI (< 25% quantile) cohort; (B) matched high-RSI (> 25% quantile) cohort; Pinteraction = 0.63. Supplement Figure 12. Disease-specific survival stratified by Oncotype DX on the METABRIC cohort. (A) Matched high-risk (> 30) cohort; (B) matched low-risk (< 30) cohort; Pinteraction = 0.52.

OBJECTIVE The CyberKnife (CK) has emerged as an effective frameless and noninvasive method for treating a myriad of neurosurgical conditions. Here, the authors conducted an extensive retrospective analysis and review of the literature to elucidate the trend for CK use in the management paradigm for common neurosurgical diseases at their institution. METHODS A literature review (January 1990–June 2019) and clinical review (January 1999–December 2018) were performed using, respectively, online research databases and the Stanford Research Repository of patients with intracranial and spinal lesions treated with CK at Stanford. For each disease considered, the coefficient of determination (r2) was estimated as a measure of CK utilization over time. A change in treatment modality was assessed using a t-test, with statistical significance assessed at the 0.05 alpha level. RESULTS In over 7000 patients treated with CK for various brain and spinal lesions over the past 20 years, a positive linear trend (r2 = 0.80) in the system's use was observed. CK gained prominence in the management of intracranial and spinal arteriovenous malformations (AVMs; r2 = 0.89 and 0.95, respectively); brain and spine metastases (r2 = 0.97 and 0.79, respectively); benign tumors such as meningioma (r2 = 0.85), vestibular schwannoma (r2 = 0.76), and glomus jugulare tumor (r2 = 0.89); glioblastoma (r2 = 0.54); and trigeminal neuralgia (r2 = 0.81). A statistically significant difference in the change in treatment modality to CK was observed in the management of intracranial and spinal AVMs (p < 0.05), and while the treatment of brain and spine metastases, meningioma, and glioblastoma trended toward the use of CK, the change in treatment modality for these lesions was not statistically significant. CONCLUSIONS Evidence suggests the robust use of CK for treating a wide range of neurological conditions.

Purpose We aimed to evaluate recent Instagram and Twitter posts to identify the primary disseminators of information related to radiation therapy on social media (health care professionals vs patients), to characterize their influencer status, and to characterize the content of this information. Methods and Materials Using 2 commercial hashtag analytics platforms, 1000 of the most recent eligible posts from each platform were evaluated for content, tone, and engagement, as well as user (poster) characteristics. Inclusion criteria were as follows: unique posts, written in English, relevant to human cancer treatment, and containing 1 of 11 predetermined hashtags (#radiation, #radiotherapy, #radiationtherapy, #radiationoncology, #radonc, #radiationtherapist #radiationtreatment, #medphys, #cyberknife, #radiosurgery, #protontherapy). Results Users of radiation oncology content on Instagram were primarily patients/caregivers (47%), specifically adult patients (94%) with breast cancer (53%). Patient/caregiver content was focused on patient experience (79%), with approximately half specific to radiation therapy (51%), and most patient/caregiver posts demonstrated a positive tone (86%). In contrast, Twitter content was dominated by health care professionals (53%), specifically within radiation oncology (90% of unique users). Health care professional content was focused on colleague education/research dissemination (53%), with a high proportion of posts specific to radiation therapy (95%). Conclusions Given the disproportionate number of patients versus radiation oncology professionals active on Instagram versus Twitter, and the lack of radiation therapy-specific content on Instagram, there may be an opportunity to improve patient outreach and education by promoting the presence of radiation oncologists on Instagram.

In the recent guideline statement from the American Society of Clinical Oncology, experts reviewed relevant literature and provided treatment recommendations for multimodality treatment approaches. The guidelines recommend either preoperative concurrent neoadjuvant chemoradiotherapy (CRT) or perioperative chemotherapy for locally advanced adenocarcinoma and either preoperative CRT followed by esophagectomy or definitive CRT for squamous cell carcinoma. Whether radiation can be omitted in patients with adenocarcinoma or whether surgery can be omitted in patients with squamous cell carcinoma is a subject of ongoing debate and clinical trials.

Brain metastases are a common occurrence in both non-small cell and small cell lung cancer with the potential to affect quality of life and prognosis. Due to concerns about the accessibility of the central nervous system by systemic chemotherapy agents, the management of brain metastases has historically relied on local therapies including surgery and radiation. However, novel targeted and immune therapies that improve overall outcomes in lung cancer have demonstrated effective intracranial activity. As a result, the management of brain metastases in lung cancer has evolved, with both local and systemic therapies now playing an important role. Factors such as tumor histology (non-small versus small cell), oncogenic driver mutations, and symptom burden from intracranial disease impact treatment decisions. Here, we review the current management of brain metastases in lung cancer, highlighting the roles of stereotactic radiosurgery and novel systemic therapies as well as the ongoing questions that remain under investigation.

OBJECTIVES We investigated differences in quality of life (QoL) in patients enrolled on a phase I/II dose-escalation study of 3-fraction resection cavity stereotactic radiosurgery (SRS) for large brain metastases. METHODS Eligible patients had 1 to 4 brain metastases, one of which was a resection cavity 4.2 to 33.5 cm3. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires core-30 (QLQ-30) and brain cancer specific module (QLQ-BN20) were obtained before SRS and at each follow-up. Nine scales were analyzed (global health status; physical, social, and emotional functioning; motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty). QoL was assessed with mixed effects models. Differences ≥10 points with q-value (adjusted P-value to account for multiplicity of testing)

BACKGROUND Financial toxicity includes distress and burden from cancer-related costs. Women are more likely to experience worse cancer-related financial outcomes than men. This study evaluated breast and gynecologic cancer patients' subjective experiences of financial toxicity and associations with distress and quality of life (QOL). METHODS A cross-sectional survey study included measures of financial toxicity (Comprehensive Score for Financial Toxicity [COST] Version 2), distress (Patient Health Questionnaire), and QOL (Functional Assessment of Cancer Therapy). Chi-square, t-tests, and ANOVAs examined bivariate relationships. Two regression models tested associations between financial toxicity and distress and QOL, controlling for covariates. Financial toxicity subgroups were compared based on a validated grading system. RESULTS Participants (N = 273; 74% breast cancer) averaged 54.65 years (SD = 12.08), were 3.42 years (SD = 4.20) post-diagnosis, and 33% reported cancer-related change in employment status. Financial toxicity was "mild" overall (COST M = 26.11, SD = 11.14); 32% worried about cancer-related financial problems (quite a bit/very much; item-level analysis). Worse financial toxicity related to younger age (p

Objective Financial toxicity associated with cancer treatment has a deleterious impact on patient outcomes but has not been well characterized among patients with metastatic cancers. We characterize the extent of financial toxicity among this population and identify factors associated with financial toxicity. Methods We prospectively surveyed adult patients with brain and spine metastases who received radiosurgery at a large academic medical center between January 2018 and December 2019. Financial toxicity was measured with the Personal Financial Wellness (PFW) scale. Results In total, 93 patients were included, with a median survival of 17.7 months. Most patients had private insurance (47%) or Medicare with supplementary insurance (42%), whereas 11% of patients were uninsured or insured by Medicaid/Medicare/Veterans Affairs. Of patients, 60% were primary income earners, of whom 52% had dependents. The median PFW score was 7.0 (interquartile range, 5.1–9.1), with financial toxicity reported in 23 patients (25%). After adjusting for age and education level, private insurance (odds ratio [OR], 0.28; P = 0.080) was associated with a lower likelihood of financial toxicity. Having ≥1 emergency department visit (OR, 3.87; P = 0.024) and a cancer-related change in employment status (OR, 3.63; P = 0.036) were associated with greater likelihood of reporting financial toxicity. Conclusions Most patients with cancer with brain and spine metastases with a poor prognosis treated at a tertiary center are primary income earners and experience financial toxicity. Further studies are warranted to assess the longitudinal impact of financial toxicity in patients with metastatic cancer, particularly those with ≥1 emergency department visit and a cancer-related change in employment status.

To quantify the survival impact of prolongation of definitive radiotherapy (RT) for head and neck cancer in a national, modern cohort, and to identify predictive factors for prolongation.The National Cancer Database was queried for adults with non-metastatic cancer of the nasopharynx, oropharynx, larynx, or hypopharynx diagnosed 2004-2015, treated with definitive RT to 66-70 Gy in 30-35 fractions at 2-2.2 Gy per fraction. Multivariable Cox regression and propensity score matching were used to model the survival impact of RT prolongation, adjusting for potential confounders such as age and comorbidity. Predictors of RT prolongation were identified using multivariable multinomial logistic regression.In total, 36,367 patients were identified. As a continuous variable, RT prolongation increased the relative hazard of death by 2% per day (P .0001). In the matched cohorts, patients with short (4-8 days) or long prolongation (8 days) had lower absolute 4-year overall survival by 4% and 12%, respectively (P .0001), while prolongation of 1-3 days was not significantly adverse. Major predictors of increased risk of prolongation were administration of systemic therapy, baseline comorbidity, lack of private insurance, and tumor/nodal stage. Conversely, higher facility volume was significantly protective, with a 55% lower risk of long prolongation within the topmost quartile (11.5 patients/year).RT prolongation, especially8 days, is significantly deleterious. Systemic therapy and facility volume were major predictors. Early identification of patients at increased risk of treatment interruptions may facilitate implementation of preventive measures.

Objectives To investigate the benefit of postoperative radiotherapy (PORT) for low-volume (pN1) nodal disease after resection of oral cavity squamous cell carcinoma. Materials and methods The National Cancer Database was queried for adults with nonmetastatic squamous cell carcinoma of the oral cavity treated by surgical resection with pathologic stage T1-2 N0-2 (American Joint Committee on Cancer 7th edition) and with the maximal exclusion of standard indications for PORT. Overall survival was compared within pN1 for observation versus PORT and then compared for pN1 versus pN0 and versus pN2 stratified by receipt of observation or PORT. Multivariable Cox regression was used to adjust for potential confounders between PORT and survival, including comorbidity and age. Results Overall 5017 pN0, 530 pN1, and 253 pN2 patients were identified, of whom 9%, 35%, and 64% received PORT, respectively. Within the pN1 cohort, PORT was associated with improved survival versus observation (adjusted hazard ratio, 0.66; 95% confidence interval, 0.46-0.97; P=0.03). Among observed patients, the prognosis of pN1 was equivalent to pN2 and inferior to pN0; in contrast, among patients treated with PORT, the prognosis of pN1 was equivalent to pN0 and superior to pN2. Without PORT, pN1 remained an adverse risk factor relative to pN0 regardless of the depth of invasion, lymph node size, lymph node location, and extent of lymph node dissection. Conclusions PORT was associated with a survival benefit compared with observation. Notably, pN1 was an adverse risk factor relative to pN0 if, and only if, patients did not receive PORT, suggesting pN1 by itself may be an indication for PORT.

Metabolic response assessment for oropharyngeal squamous cell carcinoma (OPSCC) aids in identifying locoregional persistence/recurrence (LRR). The Hopkins Criteria are a standardized qualitative response assessment system using posttreatment FDG-PET/CT.We conducted a retrospective cohort study of patients with node-positive OPSCC treated with definitive (chemo)radiotherapy. We assessed Hopkins Criteria performance for LRR, then developed and validated a competing-risks model.Between 2004 and 2018, 259 patients were included with median follow-up of 43 months. The Hopkins Criteria sensitivity, specificity, negative predictive value, and accuracy were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater with positive scores (45% vs. 5%, HR 12.60, p 0.001). PET/CTs performed ≤10 weeks after radiotherapy were associated with a four-fold increase in pathologically negative biopsies/surgeries (36% vs. 9%, p = 0.03). The AUC for LRR was 0.89 using a model integrating the Hopkins score.The Hopkins Criteria predict LRR with high accuracy for OPSCC response assessment.

Objective Being able to predict a patient’s life expectancy can help doctors and patients prioritize treatments and supportive care. For predicting life expectancy, physicians have been shown to outperform traditional models that use only a few predictor variables. It is possible that a machine learning model that uses many predictor variables and diverse data sources from the electronic medical record can improve on physicians’ performance. For patients with metastatic cancer, we compared accuracy of life expectancy predictions by the treating physician, a machine learning model, and a traditional model. Materials and Methods A machine learning model was trained using 14 600 metastatic cancer patients’ data to predict each patient’s distribution of survival time. Data sources included note text, laboratory values, and vital signs. From 2015–2016, 899 patients receiving radiotherapy for metastatic cancer were enrolled in a study in which their radiation oncologist estimated life expectancy. Survival predictions were also made by the machine learning model and a traditional model using only performance status. Performance was assessed with area under the curve for 1-year survival and calibration plots. Results The radiotherapy study included 1190 treatment courses in 899 patients. A total of 879 treatment courses in 685 patients were included in this analysis. Median overall survival was 11.7 months. Physicians, machine learning model, and traditional model had area under the curve for 1-year survival of 0.72 (95% CI 0.63–0.81), 0.77 (0.73–0.81), and 0.68 (0.65–0.71), respectively. Conclusions The machine learning model’s predictions were more accurate than those of the treating physician or a traditional model.

Objective Immunotherapy for patients with melanoma with brain metastasis has significantly improved outcomes; however, it has also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports have suggested that these reactions can precede improved treatment responses. For intracranial disease control, we sought to identify if such an association exists. Methods We conducted a retrospective chart review of patients with melanoma who underwent immunotherapy treatment after diagnosis of brain metastasis. The study cohort was then stratified into 2 groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analyses were used to evaluate survival and predictors of outcomes. Results Fifty-two patients met the inclusion criteria, 17 of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 versus 10.5 months (P = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival (mean, 33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (P = 0.013; hazard ratio, 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (P = 0.015; hazard ratio, 10.73). Conclusions Immune-related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to show promising outcomes as a first-line agent for melanoma with brain metastasis.

Management of symptomatic brain metastases often includes surgical resection with postoperative radiotherapy. Postoperative whole-brain radiotherapy (WBRT) improves intracranial control but detrimentally impacts quality of life and neurocognition. We sought to characterize the use in the United States of postoperative stereotactic radiosurgery (SRS), an evolving standard-of-care associated with reduced cognitive effects.With the MarketScan Commercial Claims and Encounters Database from 2007 to 2015, we identified patients aged 18-65 years treated with resection of a brain metastasis followed by SRS or WBRT within 60 days of surgery. Logistic regression estimated associations between co-variables (treatment year, age, sex, geographic region, place of service, insurance type, disease histology, comorbidity score, and median area household income and educational attainment) and SRS receipt.Of 4007 patients included, 1506 (37.6%) received SRS and 2501 (62.4%) received WBRT. Postoperative SRS increased from 16.5% (2007-2008) to 56.8% (2014-2015). Patients residing in areas with a median household income or an educational attainment below 50th percentile were significantly less likely to receive SRS after controlling for treatment year and other demographic characteristics (P0.01). Factors associated with greater odds of receiving SRS included younger age, female sex, melanoma histology, Western region location, hospital-based facility, and high-deductible health plan enrollment (P0.05 for each).Postoperative SRS for brain metastases has increased from 2007 to 2015, with the majority of patients now receiving SRS over WBRT. Patients in areas of lower socioeconomic class were less likely to receive SRS, warranting further investigation of barriers to SRS adoption.

The clinical and financial effects of mental disorders are largely unknown among gastrointestinal (GI) cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database, we identified patients whose first cancer was a primary colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer as well as those with coexisting depression, anxiety, psychotic, or bipolar disorder. Survival, chemotherapy use, total healthcare expenditures, and patient out‐of‐pocket expenditures were estimated and compared based on the presence of a mental disorder. We identified 112,283 patients, 23,726 (21%) of whom had a coexisting mental disorder. Median survival for patients without a mental disorder was 52 months (95% CI 50–53 months) and for patients with a mental disorder was 43 months (95% CI 42–44 months) (p, In this SEER‐Medicare study of GI cancers, the 21% of patients with a pre‐existing mental disorder had inferior overall survival outcomes (52 months vs 43 months, p

Purpose Although consensus guidelines for postresection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of postresection SRS for deep brain metastases based on whether or not the surgical corridor was targeted. Materials and Methods We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only “deep” tumors (defined as located ≥1.0 cm from the pial surface before resection). Results In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12 months for targeting versus not targeting the corridor, respectively, for overall local failure 2% (95% confidence interval [CI], 0%-11%) versus 9% (95% CI, 1%-25%; P = .25), corridor failure 0% (95% CI, 0%-0%) versus 9% (95% CI, 1%-25%; P = .06), cavity failure 2% (95% CI, 0%-11%) versus 0% (95% CI, 0%-0%; P = .91), and adverse radiation effect 5% (95% CI, 1%-15%) versus 13% (95% CI, 3%-30%; P = .22). Leptomeningeal disease (7%; 95% CI, 2%-18%) versus 26% (95% CI, 10%-45%; P = .03) was higher in those without the corridor targeted. Conclusions Omitting the surgical corridor in postoperative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of postresection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.

Purpose Our purpose was to report the outcome of stereotactic ablative radiation therapy (SABR) to the primary tumor for patients with metastatic pancreatic cancer. Methods and Materials We examined the records of patients with metastatic pancreatic cancer treated with SABR to the primary tumor between 2002 and 2018. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. Pain intensity pre- and post-SABR was scored according to the Stanford Pain Scale as reported by the patient. Time-to-events were calculated from the date of end of SABR delivery. Results In total, 27 patients were identified that met the inclusion criteria. Seventeen (63%) patients received single fraction SABR with a median dose of 25 Gy (range, 12.5-25), and 10 (37%) patients were treated in 5 fractions with a median dose of 33 Gy (range, 25-40). Before the start of SABR, 17 (63%) patients reported having abdominal pain, with a median intensity of 5 in the 0 to 10 pain scale (range, 1-9), 11 (41%) of them needing continuous opioid use. The median follow-up was 6 months (range, 0-18). Median overall survival was 7 months (95% confidence interval, 3-10), with a cumulative incidence of local failures at 1 year of 25% (95% confidence interval, 10-44). After SABR, there was a significant reduction in the mean intensity of pain (P = .01), and a 46% relative reduction in continuous opioid use. Only 2 patients (7%) presented a grade 3 toxicity that could be attributed to treatment. Conclusions In this small series, SABR was a safe and effective option for the local palliation of metastatic pancreatic cancer, with measurable improvements in abdominal pain and the need for opioids.

BACKGROUND The comparative risks of a second cancer diagnosis are uncertain after primary cancer treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam radiotherapy (PBRT). METHODS Pediatric and adult patients with a first cancer diagnosis between 2004 and 2015 who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database from 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The diagnosis of second cancer was modeled using multivariable logistic regression adjusting for age, follow-up duration, radiotherapy (RT) dose, chemotherapy, sociodemographic variables, and other factors. Propensity score matching also was used to balance baseline characteristics. RESULTS In total, 450,373 patients were identified (33.5% received 3DCRT, 65.2% received IMRT, and 1.3% received PBRT) with median follow-up of 5.1 years after RT completion and a cumulative follow-up period of 2.54 million person-years. Overall, the incidence of second cancer diagnosis was 1.55 per 100 patient-years. In a comparison between IMRT versus 3DCRT, there was no overall difference in the risk of second cancer (adjusted odds ratio [OR], 1.00; 95% CI, 0.97-1.02; P = .75). By comparison, PBRT had an overall lower risk of second cancer versus IMRT (adjusted OR, 0.31; 95% CI, 0.26-0.36; P

Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44–69 years). With a median clinical and radiological follow-up of 44 months (9–161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen’s correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = − 0.4, p = 0.001), right-sided tumor (r = − 0.3, p = 0.03), primary SRS (r = − 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = − 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12–30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

Background Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of ≥3 cm or tumor volume ≥14.2 cm3, are not candidates for stereotactic radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS. Methods With institutional review board approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007–2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage after past radiation treatment in 8.1%. A median tumor volume of 16.0 cm3 (range, 10.1–65.5 cm3) received a median dose of 24.0 Gy (range, 14.0–30.0 Gy) in a median of 3 fractions (range, 1–5), for a median single fraction equivalent dose (with alpha/beta of 3) of 14.8 Gy (range, 11.3–18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS. Results With a median clinical follow-up of 32.8 months (range, 0.6–125.9 months) and median radiologic follow-up of 28.5 months (range, 0.6–121.4 months), LC was 96.5% (95% confidence interval, 92.4%–100%) at 3 years and 91.7% (95% confidence interval, 87.6%–95.7%) at 5 years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (range, 7.8–34.5 months). ARE occurred in 9% of those with prior treatment compared with 5% who were radiation-naive (P = 0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen. Conclusions Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.

BackgroundNeoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer. There is interest in deescalating local therapy after a clinical complete response to CRT. We hypothesized that a watch-and-wait (WW) strategy offers comparable cancer-specific survival, superior quality-adjusted survival, and reduced cost compared with upfront TME.MethodsWe developed a decision-analytic model to compare WW, low anterior resection, and abdominoperineal resection for patients achieving a clinical complete response to CRT. Rates of local regrowth, pelvic recurrence, and distant metastasis were derived from series comparing WW with TME after pathologic complete response. Lifetime incremental costs and quality-adjusted life-years (QALY) were calculated between strategies, and sensitivity analyses were performed to study model uncertainty.ResultsThe base case 5-year cancer-specific survival was 93.5% (95% confidence interval [CI] = 91.5% to 94.9%) on a WW program compared with 95.9% (95% CI = 93.6% to 97.4%) after upfront TME. WW was dominant relative to low anterior resection, with cost savings of $28 500 (95% CI = $22 200 to $39 000) and incremental QALY of 0.527 (95% CI = 0.138 to 1.125). WW was also dominant relative to abdominoperineal resection, with a cost savings of $32 100 (95% CI = $21 800 to $49 200) and incremental QALY of 0.601 (95% CI = 0.213 to 1.208). WW remained dominant in sensitivity analysis unless the rate of surgical salvage fell to 73.0%.ConclusionsUsing current multi-institutional recurrence estimates, we observed comparable cancer-specific survival, superior quality-adjusted survival, and decreased costs with WW compared with upfront TME. Upfront TME was preferred when surgical salvage rates were low.

Trimodality therapy per the German Rectal Trial has led to excellent locoregional outcomes for locally advanced rectal cancer. Recent efforts have shifted toward improving distant control and health-related quality of life in this disease. To this end, total neoadjuvant therapy has become an increasingly used approach in which most, if not all, chemotherapy is delivered before surgery to improve compliance and to address micrometastases early. To avoid surgical morbidity, a "watch-and-wait" approach, in which total mesorectal excision is deferred, has also been studied for patients who achieve a clinical complete response after chemoradiation. These 2 concurrent treatment trends have raised many points of uncertainty in what used to be a relatively straightforward neoadjuvant treatment paradigm. We discuss here our approach to neoadjuvant therapy for locally advanced rectal cancer, based on the data we currently have and through shared decision-making with patients to help them select the treatment that best aligns with their preferences and values.

Stereotactic radiosurgery (SRS) to the surgical bed of resected brain metastases is now considered the standard of care due to its advantages over whole brain radiation therapy (WBRT). Despite the upward trend in SRS adoption since the 2000s, disparities have been reported suggesting that socio-economic factors can influence SRS utilization.To analyze recent trends in SRS use and identify factors that influence treatment.We conducted a retrospective cohort study with the Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who received SRS or WBRT within 60 days after resection of tumors metastatic to the brain.A total of 3495 patients met the inclusion and exclusion criteria. There were 1998 patients in the SRS group and 1497 patients in the WBRT group. SRS use now supersedes WBRT by a wide margin. Lung, breast and colon were the most common sites of primary tumor. Although we found no significant differences based on race among the treatment groups, patients with annual household income greater than $75,000 and those with some college or higher education are significantly more likely to receive SRS (OR 1.44 and 1.30; 95% CI 1.18-1.76 and 1.08-1.56; P = 0.001 and 0.005, respective). Patients with Elixhauser Comorbidity Index of three or more were significantly more likely to receive SRS treatment.The use of post-surgical SRS for brain metastasis has increased significantly over time, however education and income were associated with differential SRS utilization.

OBJECTIVE Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution’s experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both. METHODS Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS. RESULTS The median follow-up period was 24 (range 0.5–155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1–5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14–35) Gy, delivered in 1–5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3–60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was −1, 0 after SRS to tumor only, and −2 after SRS to both targets. CONCLUSIONS SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

PURPOSE The aim of this study was to report local failure (LF) outcomes and associated predictors in patients with oligometastatic colorectal cancer (CRC) treated with stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS We retrospectively reviewed patients with CRC metastases to the brain, liver, spine, or lung treated with SABR between 2001 and 2016. Time to LF was summarized using cumulative incidence of LF curves with death as a competing risk. RESULTS The analysis included a total of 130 patients and 256 lesions. Of the metastases treated, 129 (50%) were brain, 50 (20%) liver, 49 (19%) spine, and 28 (11%) lung. Median gross tumor volume was 24 mL for liver metastases, 2 mL for brain metastases, 4 mL for spine metastases, and 1 mL for lung metastases. The overall 1, 2, and 3-year cumulative incidence of LF rates were 21.6% (16.5, 27.1), 28.2% (22.3, 34.4), and 31.5% (25.2, 38.0), respectively. LF was highest among the liver metastases (1 y: 26.0%, 2 y: 38.5%), followed by spine (1 y: 25.1%, 2 y: 31.1%), brain (1 y: 20%, 2 y: 25.2%), and lung (1 y: 13.7%, 2 y: insufficient data). Metastases from right-sided primary CRC were significantly more likely to have LF (P=0.0146, HR=2.23). Biologically effective dose>70 Gy, defined using a standard linear quadratic model using α/β ratio of 10 on the individual lesion level, and pre-SABR chemotherapy were also significant predictors of LF (P= 0.0009 and 0.018, respectively). CONCLUSIONS CRC metastases treated with SABR had significantly higher rates of LF if they originated from right-sided primary CRC, compared with left-sided. Liver metastases had the highest rates of LF compared with other metastatic sites. Thus, CRC liver metastases and metastases from right-sided CRC may benefit from more aggressive radiotherapy.