Stereotactic Body Radiation Therapy (SBRT) for Pancreatic Cancer: A Radiosurgery Society Case-Based Practical Guidelines to Challenging Cases.

The use of radiation therapy (RT) for pancreatic cancer continues to be controversial despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control but currently no standardized approach exists. Advances in stereotactic body radiation therapy (SBRT), motion management, real time image guidance and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering SBRT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions.

Treatment Terminations During Radiation Therapy: A Ten-Year Experience.

PURPOSE: Patients undergoing radiation therapy may terminate treatment for any number of reasons. The incidence of treatment termination (TT) during radiation therapy has not been studied. Herein we present a cohort of TT at a large multi-center radiation oncology department over 10 years. METHODS AND MATERIALS: TTs between 1/2013 and 1/2023 were prospectively analyzed as part of an ongoing departmental quality and safety program. TT was defined as any premature discontinuation of therapy after initiating radiation planning. The rate of TT was calculated as a percentage of all patients starting radiation planning. All cases were presented at monthly morbidity and mortality (MM) conferences with a root cause reviewed (RCA). RESULTS: A total of 1,448 TTs were identified out of 31,199 planned courses of care (4.6%). Six hundred eighty-six (47.4%) involved patients treated with curative intent, while 753 (52.0%) with palliative intent, and 9 (0.6%) for benign disease. The rate of TT decreased from 8.49% in 2013 to 3.02% in 2022 with rates decreasing yearly. The most common disease sites for TT were CNS (21.7%), H&N (19.3%), Thorax (17.5%), and Bone (14.2%). The most common causes of TT were hospice and/or patient expiration (35.9%), patient choice unrelated to toxicity (35.2%), and clinician choice unrelated to toxicity (11.5%). CONCLUSION: This 10-year prospective review of TTs identified a year-over-year decrease in TTs as a percentage of planned patients. This decrease may be associated with the addition of RCA for TTs and discussion monthly at MM rounds, coupled with departmental upstream quality initiatives implemented over time. Understanding the reasons behind TTs may help to decrease preventable TTs. While some TTs may be unavoidable, open discourse and quality improvement changes effectively reduce TT incidents over time.

Effect of Immunotherapy and Stereotactic Body Radiation Therapy Sequencing on Local Control and Survival in Patients With Spine Metastases.

Purpose: Stereotactic body radiation therapy (SBRT) is commonly used to treat spinal metastases in combination with immunotherapy (IT). The optimal sequencing of these modalities is unclear. This study aimed to investigate whether sequencing of IT and SBRT was associated with differences in local control (LC), overall survival (OS), and toxicity when treating spine metastases. Methods and Materials: All patients at our institution who received spine SBRT from 2010 to 2019 with systemic therapy data available were reviewed retrospectively. The primary endpoint was LC. Secondary endpoints were toxicity (fracture and radiation myelitis) and OS. Kaplan-Meier analysis was used to determine whether IT sequencing (before versus after SBRT) and use of IT were associated with LC or OS. Results: A total of 191 lesions in 128 patients met inclusion criteria with 50 (26%) lesions in 33 (26%) patients who received IT. Fourteen (11%) patients with 24 (13%) lesions received the first IT dose before SBRT, whereas 19 (15%) patients with 26 (14%) lesions received the first dose after SBRT. LC did not differ between lesions treated with IT before SBRT versus after SBRT (1 year 73% versus 81%, log rank = 0.275, P = .600). Fracture risk was not associated with IT timing (χ2 = 0.137, P = .934) or receipt of IT (χ2 = 0.508, P = .476), and no radiation myelitis events occurred. Median OS was 31.8 versus 6.6 months for the IT after SBRT versus IT before SBRT cohorts, respectively (log rank = 13.193, P < .001). On Cox univariate analysis and multivariate analysis, receipt of IT before SBRT and Karnofsky performance status <80 were associated with worse OS. IT treatment versus none was not associated with any difference in LC (log rank = 1.063, P = .303) or OS (log rank = 1.736, P = .188). Conclusions: Sequencing of IT and SBRT was not associated with any difference in LC or toxicity, but delivering IT after SBRT versus before SBRT was associated with improved OS.

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

OBJECTIVE: Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS). METHODS: An institutional review board-approved database compiled outcomes of Koos grade 3-4 VS treated by GKRS from March 2014 to January 2021 with >6 months' follow-up. Baseline symptoms per Common Terminology Criteria for Adverse Events definitions were recorded. Control rates, toxicities, and post-treatment volumetric changes were analyzed. Aggregate impairment scores (AIs) were defined by the sum of relevant Common Terminology Criteria for Adverse Events grades to categorize symptomatic burdens. Baseline and post-treatment AIs were tested for association with definitive versus adjuvant strategies. RESULTS: In total, 34 patients with Koos grade 3-4 VS were identified, 19 treated with definitive GKRS (GKRS-D) and 15 with adjuvant GKRS (GKRS-A). Median follow-up was 34.2 months for GKRS-D and 48.8 months for GKRS-A. Patients who received GKRS-A had greater AIs at presentation (3.73 vs. 2.11, P = 0.017). Irrespective of treatment approach, tumor control rates were 100% without instances of brainstem necrosis or shunt placement. Six of 19 patients who received GKRS-D had improved post-treatment AI, and 63% of patients who received GKRS-D and 66% of patients who received GKRS-A had tumor shrinkage >20%. CONCLUSIONS: In well-selected patients with Koos grade 3-4 VS, definitive stereotactic radiosurgery may be an appropriate strategy with excellent control and minimal toxicity. Our data suggest that the need for surgical decompression should be considered based on pretreatment symptom burden rather than tumor size.

Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry and Correlation with Toxicity.

Purpose: Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation. Methods and Materials: Intensity modulated EBRT and 103Pd-based LDR treatment plans were combined for 138 patients using biological effective dose (BED) and deformable image registration. GU and gastrointestinal (GI) toxicity were compared with combined dosimetry for the urethra, bladder, and rectum. Differences between doses in each toxicity grade were assessed by analysis of variance (α = 0.05). Combined dosimetric constraints are proposed using the mean organ-at-risk dose, subtracting 1 standard deviation for a conservative recommendation. Results: The majority of our 138-patient cohort experienced grade 0 to 2 GU or GI toxicity. Six grade 3 toxicities were noted. Mean prostate BED D90 (± 1 standard deviation) was 165.5±11.1 Gy. Mean urethra BED D10 was 230.3±33.9 Gy. Mean bladder BED was 35.2±11.0 Gy. Mean rectum BED D2cc was 85.6±24.3 Gy. Significant dosimetric differences between toxicity grades were found for mean bladder BED, bladder D15, and rectum D50, but differences between individual means were not statistically significant. Given the low incidence of grade 3 GU and GI toxicity, we propose urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy as preliminary dose constraints for combined modality therapy. Conclusions: We successfully applied our dose integration technique to a sample of patients with intermediate- and high-risk prostate cancer. Incidence of grade 3 toxicity was low, suggesting that combined doses observed in this study were safe. We suggest preliminary dose constraints as a conservative starting point to investigate and escalate prospectively in a future study.

Four-Dimensional Computed Tomography-Based Correlation of Respiratory Motion of Lung Tumors With Implanted Fiducials and an External Surrogate.

PURPOSE: Our purpose was to assess the suitability of airway-implanted internal fiducial markers and an external surrogate of respiratory motion for motion management during radiation therapy of lung tumors. METHODS AND MATERIALS: We analyzed 4-dimensional computed tomography scans acquired during radiation therapy simulation for 28 patients with lung tumors who had anchored fiducial markers bronchoscopically implanted inside small airways in or near the tumor in a prospective trial. We used a linear mixed model to build population-based correlative models of tumor and surrogate motion. The first 24 of the 28 patients were used to build correlative models, and 4 of the 28 consecutive patients were excluded and used as an internal validation cohort. Of the 24 patients from the model building cohort, all were used for the models based on the internal fiducial. The external surrogate was completely visualized in 11 patients from the model building cohort, so only those were used for the models based on the external surrogate. Furthermore, we determined the predicted residual error sum of squares for our correlative models, which may serve as benchmarks for future research. RESULTS: The motion of the internal fiducials was significantly associated with the tumor motion in the anterior-posterior (P < .0001) and superior-inferior (SI) directions (P < .0001). We also observed a strong correlation of the external surrogate anterior-posterior motion to the tumor dominant SI motion (P < .0001). In the validation cohort, the internal fiducial SI motion was the only reliable predictor of lung tumor motion. CONCLUSIONS: The internal fiducials appear to be more reliable predictors of lung tumor motion than the external surrogate. The suitability of such airway-implanted internal fiducial markers for advanced motion management techniques should be further investigated. Although the external surrogate seems to be less reliable, its wide availability and noninvasive application support its clinical utility, albeit the greater uncertainty will need to be compensated for.

Biochemical Control and Toxicity Outcomes of Stereotactic Body Radiation Therapy Versus Low-Dose-Rate Brachytherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: Low-dose-rate (LDR) brachytherapy and stereotactic body radiation therapy (SBRT) have both shown acceptable outcomes in the treatment of low- and intermediate-risk prostate cancer. Minimal data have been published directly comparing rates of biochemical control and toxicity with these 2 modalities. We hypothesize that LDR and SBRT will provide similar rates of biochemical control. METHODS AND MATERIALS: All low- and intermediate-risk patients with prostate cancer treated definitively with SBRT or LDR between 2010 and 2018 were captured. Phoenix definition was used for biochemical failure. Independent t tests were used to compare baseline characteristics, and repeated measure analysis of variance test was used to compare American Urologic Association (AUA) and the Expanded Prostate Cancer Index Composite (EPIC) scores between treatment arms over time. Biochemical control was estimated using the Kaplan-Meier method. Differences in acute and late toxicity were assessed via Pearson χ2. RESULTS: In the study, 219 and 118 patients were treated with LDR and SBRT. Median follow-up was 4.3 years (interquartile range, 3.1-6.1). All patients treated with LDR received 125.0 Gy in a single fraction. SBRT consisted of 42.5 Gy in 5 fractions. Five-year biochemical control for LDR versus SBRT was 91.6% versus 97.6% (P = .108). LDR patients had a larger increase in mean AUA scores at 1 month (17.2 vs 10.3, P < .001) and 3 months posttreatment (14.0 vs 9.7, P < .001), and in mean EPIC scores at 1 month (15.7 vs 13.8, P < .001). There was no significant difference between LDR and SBRT in late grade 3 genitourinary toxicity (0.9% vs 2.5%, P = .238); however, LDR had lower rates of late grade 3 gastrointestinal toxicity (0.0% vs 2.5%, P = .018). CONCLUSIONS: Our data show similar biochemical control and genitourinary toxicity rates at 5 years for both SBRT and LDR, with slightly higher gastrointestinal toxicity with SBRT and higher AUA and EPIC scores with LDR.

Genomic Analyses for Predictors of Response to Chemoradiation in Stage III Non-Small Cell Lung Cancer.

BACKGROUND: Radiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy. METHODS: We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing. RESULTS: 110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between AKT2 mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7, P = .003 and P = .003, respectively). Analyses restricted to loss-of-function mutations identified KMT2C and KMT2D deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, P < .001 and P < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, P = .049). CONCLUSIONS: This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in AKT2, KMT2C, and KMT2D as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.

Patterns and Perceptions of "Away" Rotations Among Radiation Oncology Residency Applicants.

PURPOSE: Medical students often complete clinical rotations at other institutions (away rotations). This study assesses the number of away rotations undertaken by radiation oncology residency applicants and their value from the applicants' perspective. METHODS AND MATERIALS: A survey was sent to applicants to a single radiation oncology program from 2015 to 2017. Questions addressed away rotation frequency, funding, motivations, barriers, and match results. A χ2 test was used to assess the correlation between number of away rotations and matching to an away program. Binary logistic regression was used to assess factors associated with undertaking >2 away rotations. RESULTS: The response rate was 39% (n = 194); 89% of respondents completed ≥1 away rotation (median, 2; interquartile range, 2-3), of whom 39% (n = 67) matched to an away program. The number of away rotations completed did not differ between those who did and did not match (P = .29). Furthermore, the number of away rotations did not correlate with matching at an away program (P = .40). Factors associated with completing more away rotations included male sex and high loan burden (P < .05). Away rotations were perceived as extremely important (71%), with interest in a specific program (44%) and obtaining letters of recommendation (31%) the most common reasons to pursue away rotations. Only 9% (n = 15) of applicants did away rotations because they had no home program. Funding sources included personal savings (29%), family support (26%), and loans (22%). If costs were inconsequential, 67 applicants (35%) noted they would do more away rotations. CONCLUSIONS: Away rotations are common and often result in students matching to an away program, although benefits of ≥2 away rotations appear limited and have associated costs. Limiting the number of away rotations in radiation oncology may decrease costs without sacrificing one's chances of matching.

Analysis of pneumonitis and esophageal injury after stereotactic body radiation therapy for ultra-central lung tumors.

OBJECTIVES: SBRT has been associated with serious toxicity in ultra-central lung tumors, but little is known about the incidence and dosimetric correlates of pulmonary and esophageal complications in this setting. MATERIALS AND METHODS: We retrospectively reviewed SBRT patients whose lung tumor abutted proximal airways, or whose planning target volume overlapped esophagus. All patients received 5-15 fractions of high-dose, image-guided radiation. The primary endpoint was SBRT-related toxicity, with local control and survival as secondary endpoints. RESULTS: We included 88 patients. Nineteen patients (22 %) experienced grade ≥3 (G3+) toxicity, including 6 cases of G3+ radiation pneumonitis and 4 cases of G3+ esophageal injury. Two patients developed trachea-esophageal fistula. Overall incidence of radiation pneumonitis was 23 %. Ten patients (11.4 %) succumbed to SBRT-related complications. Multiple dosimetric parameters for lung (including mean lung dose and V20Gy) and esophagus (including maximum point dose) correlated with radiation pneumonitis and esophageal toxicity, respectively. No impact of fractionation on toxicity was seen. CONCLUSION: This analysis indicates that high rate and multiple manifestations of pulmonary and esophageal toxicity occur after SBRT for ultra-central tumors. In particular, severe radiation pneumonitis and tracheoesophageal fistula are possible. Dosimetric parameters such as mean lung dose and maximum esophageal dose are significantly correlated with toxicity. Further study is needed to optimize the safe delivery of SBRT in these patients.

Mind the Gap: An Analysis of "Gap Year" Prevalence, Productivity, and Perspectives Among Radiation Oncology Residency Applicants.

PURPOSE: Medical students may take a year off during medical school (a "gap year") to strengthen their applications for competitive specialties such as radiation oncology. This can incur significant financial and opportunity costs. We sought to understand the prevalence, nature, and funding of gap years undertaken by radiation oncology applicants. METHODS AND MATERIALS: An anonymous survey was emailed to all applicants to a single radiation oncology program from 2015 to 2017. Survey questions assessed gap year utilization, funding, motivations, and perceptions. Separately, all 2017 Electronic Residency Application Service (n = 176) applications to this program were reviewed for reference. RESULTS: The 2017 cohort had a response rate of 69% (n = 121), with an overall response rate of 39% (n = 194) for applicants between 2015 to 2017. Of non-MD/PhD respondents, 33% (n = 53) reported taking a gap year. The main reason for a gap year (68%) was to produce more publications, and 50% of all respondents viewed a gap year as "important" or "very important" for matching in radiation oncology. Twenty-eight students (53%) reported using personal loans, savings, or family support to cover gap year expenses. Most who took a gap year (83%) viewed funding as "difficult" or "extremely difficult" to obtain. Fewer publications before gap year and more dedicated research time were significant predictors of undertaking a gap year, whereas sex, marital status, dependent status, and financial aid were not significant. CONCLUSIONS: Research productivity is commonly perceived as important for matching in radiation oncology, leading many applicants to take gap years, which are usually supported by personal financial resources. We did not identify statistically significant socioeconomic disparities between applicants that took a gap year and those who did not. However, further study is warranted to determine whether pressure to take a gap year, particularly in the absence of readily available funding sources, deters some potential applicants from pursuing radiation oncology altogether.

Patterns of stereotactic radiotherapy utilization and fractionation for acoustic neuroma in the United States.

OBJECTIVE: Stereotactic radiosurgery is a commonly offered modality utilized for the treatment of acoustic neuromas. In this study we sought to analyze the national practice patterns and utilization of GK compared to LINAC based radiosurgery. METHODS: Patients diagnosed with an acoustic neuroma between 2004-2013 and treated with LINAC or GK radiosurgery in 1-5 fractions were identified in the National Cancer Database. RESULTS: There were 2,705 patients analyzed, of which 2,222 (82.1%) received GK and 483 (17.9%) received LINAC based radiosurgery. Single fraction treatment was observed in 98.8% of GK patients, versus 19.5% of LINAC patients. LINAC based radiosurgery use increased from 3.5-3.7% in 2004-2005 to 15-26% from 2007-2013. On multivariable logistic regression the use of 3-5 fractions was strongly associated with LINAC based radiosurgery (p<0.001). CONCLUSION: GK remains the predominant modality for delivering radiosurgery to acoustic neuroma. LINAC based radiosurgery is being cautiously adopted and often utilizes a hypofractionated approach.

Patterns of care and outcomes of postoperative radiation for intracranial hemangiopericytoma in United States hospitals.

OBJECTIVE: Several small (<100 patients) studies have been suggestive of a survival benefit associated with postoperative radiation for intracranial hemangiopericytoma. Given the rarity of this disease, we sought to examine the patterns of care and outcomes of this tumor in the National Cancer Database (NCDB). PATIENTS AND METHODS: We accessed the NCDB to identify patients with intracranial hemangiopericytoma between 2004-2012. Patients were categorized by surgical status, postoperative radiation usage, and location (meningeal or brain parenchyma). Multivariable Cox regression was used to identify covariables associated with differences in survival. RESULTS: There were 588 patients included in this study, of which 323 (54.9%) received postoperative radiation. The median age at diagnosis was 51 years and the median follow up was 55.1 months. There were no differences in overall survival between the two groups. The 5-year overall survival was 77.1% for those receiving postoperative radiation and 83.8% for those who did not (p = .14). On subgroup analysis by tumor location there remained no significant differences between groups. For those with tumors in the brain parenchyma, the 5-year overall survival was 77.6% for postoperative radiation compared to 85.8% for no postoperative radiation (p = .08). For those with tumors identified as being meningeal in origin, the 5-year overall survival was 75.7% for those who received postoperative radiation compared to 81.6% for those who did not receive postoperative radiation (p = .86). On multivariable analysis, postoperative radiation was not associated with any differences on survival (HR 1.35. 95% CI 0.90-2.02, p = .15). CONCLUSIONS: More than 50% of patients with hemangiopericytoma received postoperative radiation but there was no survival benefit associated with this treatment. This is a hypothesis-generating study and further studies are necessary to better determine how best to treat this rare disease.