Purpose:Following initial stereotactic radiosurgery (SRS), risk factors for high-burden intracranial progression (ICP) necessitating whole brain radiation remain poorly characterized. We hypothesize that specific clinical parameters at initial SRS are associated with high-burden ICP-defined as either ≥5 brain metastases (BMs) (ICP5) or ≥11 BMs (ICP11). Materials and Methods:Across 2 institutions, we retrospectively identified all patients completing an initial SRS course from January 2015 to December 2020. ICP was defined as any radiographic concern for distant and/or in-field progression. Overall survival (OS) and freedom from ICP were estimated via the Kaplan-Meier method. Cox models assessed the association between clinical parameters and freedom from ICP5 and ICP11. Results:We identified 1383 patients completing SRS. Post-SRS ICP was identified for 555 (40.1%) patients: 72.6% had 1 to 4 progressive BMs, 11.5% had 5 to 10 BMs, and 15.9% had ≥11 new BMs. Among these groups, 12-month OS was 56.8% (95% CI: 52.1%-61.9%), 46.0% (95% CI: 35.1%-60.1%), and 38.7% (95% CI: 29.4%-50.9%), respectively (P < .001). Neurologic symptoms at ICP were observed in 21.1%, 28.1%, and 50.0% of cases, respectively (P < .001). Oligometastatic disease at the time of SRS [ICP5: hazard ratio (HR) 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97], no pre-SRS immunotherapy (ICP11: HR 1.74, 95% CI: 1.03-2.97), receipt of post-SRS immunotherapy (ICP5: HR 0.60, 95% CI: 0.402-0.906; ICP11: HR 0.57, 95% CI: 0.332-0.988), and a single BM at initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84) were negative predictive factors of high-burden ICP. Conclusions:High-burden ICP was associated with decreased OS and neurologic decline. Patients who had oligometastatic disease, who received post-SRS immunotherapy, who did not receive pre-SRS immunotherapy, and who had a single BM had improved freedom from high-burden ICP. These findings may justify consideration of upfront whole brain radiation for those at risk for high-burden ICP and prospective analysis of short-interval post-SRS surveillance in this population.

Purpose:To compare outcomes between gastrointestinal and nongastrointestinal patients with brain metastases after radiosurgery. Methods and Materials:Retrospective cohort study identifying patients completing an initial course of radiosurgery between January 2015 and December 2020, with follow-up data collected through November 2022. Multi-institutional, academic referral centers. The primary outcomes were overall survival and intracranial progression-free survival, calculated by the Kaplan-Meier method. Progression was defined as concern on postradiosurgery imaging for recurrence determined by clinical multidisciplinary consensus. Cox proportional hazard models were used to assess associations between outcomes and covariates. Results:This study included 1281 nongastrointestinal patients and 102 gastrointestinal patients, of which 45.1% were colorectal, 33.3% esophageal, and the remaining 21.6% comprising other sites. Gastrointestinal patients were more likely to be younger (mean 59.1 vs 63.5 years, P = .001), male (56.9% vs 44.3%, P = 0.014), have received systemic therapy (73.5% vs 63.9%, P = .049), and have resection of brain metastases (45.1% vs 25.0%, P < .001) prior to radiosurgery. Median overall survival was lower for gastrointestinal patients at 5.4 months (95% CI, 3.8-7.7) versus nongastrointestinal patients at 10.6 months (95% CI, 9.3-11.6, P < 0.0001). In a multivariate model, gastrointestinal patients had worse overall survival compared to nongastrointestinal patients (hazard ratio, 1.92; P < .0001; 95% CI, 1.53-2.41). Median intracranial progression-free survival was lower for gastrointestinal patients at 6.2 months (95% CI, 4.0-9.6) versus nongastrointestinal patients at 12.3 months (95% CI, 10.8-13.9; P = 0.0002). In a multivariate model, gastrointestinal patients had worse intracranial progression-free survival compared to nongastrointestinal patients (hazard ratio, 1.60; 95% CI, 1.20-2.14; P = 0.0013). There were no significant differences between colorectal primary patient or esophageal primary patient outcomes compared to all other gastrointestinal primary patients. Conclusions:Across a multi-institutional stereotactic radiosurgery cohort, brain metastases of gastrointestinal origin demonstrated inferior overall survival and intracranial progression-free survival to those of nongastrointestinal origin. These data may help inform treatment decisions and postradiosurgery surveillance.

Purpose/Objective(s) The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-like 2 (NFE2L2) pathway is important for cellular processing of reactive oxygen species that contribute to indirect cell killing from radiotherapy. KEAP1/NFE2L2 mutations have been shown to be promising molecular markers of clinical radioresistance in localized non-small cell lung cancer (NSCLC). However, it is unknown if these mutations similarly impact the response of brain metastases to radiation therapy. In this study, we tested whether KEAP1/NFE2L2 mutations associate with outcomes in patients with brain metastases from NSCLC undergoing stereotactic radiosurgery (SRS). The objective of this study is to determine the impact of KEAP1/NFE2L2 mutations on overall and intracranial progression free survival (OS, ICP), radionecrosis (RN), and intracranial local control (LC) in this population receiving SRS. We hypothesize that KEAP1/NFE2L2 mutations are associated with decreased local control. Materials/Methods Patients undergoing SRS for brain metastases secondary to NSCLC at a single institution were retrospectively identified. A subset of these patients also underwent molecular profiling with next generation sequencing (NGS). Kaplan-Meier survival analyses were calculated based on KEAP1/NFE2L2 mutation status using the log-rank test. Comparisons were performed for mutation versus no mutation, and also by mutational variant (pathogenic variant (PV); variant of unknown significance (VUS)). Results 541 patients with brain metastases from NSCLC who received SRS were included in the study. Of these, 269 underwent molecular profiling. KEAP1 variants were identified in 24.5% of patients. At 12 months, among patients with mutations, LC was 87.8% (95% CI, 74.2-96.1%), compared to 90.6% (84.4-94.4%) in patients without mutations. No significant difference was observed up to 24 months. The incidence of RN was similar between patients harboring KEAP1/NFE2L2 mutations and those without (9.3 ± 4.5% and 6.7 ± 2.1% at 12 months, respectively). There was no significant difference in median OS between patients with mutations (12.5 months; 95% CI, 9.5-21.7 months) compared to those without (14.9 months; 95% CI, 11.7-20.5 months). Similarly, there was no significant difference in median ICP between patients with mutations (5.1 months; 95% CI, 3.3-9.5 months) compared to those without (7.2 months; 95% CI, 5.7-9.5 months). Analyses by variant subtype also showed no significant differences. Conclusion While numeric differences were noted, KEAP1/NFE2L2 mutation status did not demonstrate a statistically significant difference in LC, RN, OC, and ICP after SRS for brain metastases from NSCLC in this cohort. Interestingly KEAP1/NFE2L2 PV and VUS diverged when analyzed separately for PFS, LC, and RN. Further analyses combining domain mapping of variants and co-mutated genes in larger patient cohorts may further clarify this observation and these data.

MRI-based BT for MIEC patients results in high rates of local control and favorable rates of late grade ≥3 morbidity. Older age, higher grade, and larger GTV at BT predicted for poorer PFS. Sigmoid colon was the predominant organ at risk for grade ≥3 toxicity with a dose -volume relationship observed. Attention to the location of the sigmoid throughout the treatment course may add insight into its predilection for risk. Future work will include additional institutions and dose-volume relationships of target volumes and normal tissues for further disease control and toxicity analysis.

ChatGPT failed to consistently generate accurate and comprehensive responses to the majority of radiation oncology patient centered questions, particularly across less common cancers and with "negative control" questions that included incorrect assumptions. This raises concern for the possible ChatGPT mediated reinforcement of patient misperceptions regarding radiotherapy.

ChatGPT's responses consistently included a large proportion of non-existent and incorrectly summarized studies. Furthermore, our secondary analysis suggests variability in the content and accuracy of ChatGPT responses to identical questions, raising further concerns regarding reliability. Overall, our findings argue against the use of ChatGPT as a tool for reviewing literature related to radiation oncology.

In this modern, multi-institutional cohort of SRS patients, melanoma BM patients had worse FFICP compared to non-melanoma BM patients, and BRAFmut patients had worse FFICP than BRAFwt patients. RN was associated with mutational status and receipt of TT pre-SRS. OS did not vary significantly across groups. This analysis may help inform systemic therapy decisions and future genomic studies for patients with BMs from melanoma.

While this single-site pilot project is limited by small sample size, it highlights the need for a formalized curriculum, scope of practice, and credentialing for RO nurses. These data can help to target education needs while guiding curriculum development.

Abstract PURPOSE While stereotactic radiosurgery (SRS) is often an efficacious treatment for brain metastases, it carries a significant risk of radionecrosis (RN). Single and dual immune checkpoint inhibition (ICPI) have emerged as common treatment options for many patients, particularly those with melanoma and non-small cell lung cancer (NSCLC). While data suggest a cancer control benefit of combining SRS and ICPI, we hypothesized that concurrent receipt of dual ICPI with SRS increases the risk for RN. METHODS We performed a retrospective review of serial patients with metastatic melanoma or NSCLC treated with SRS for intact brain metastases from 2014-2020 at our single institution. Patients were stratified by receipt of dual vs. single ICPI vs. SRS alone. RN was biopsy confirmed or determined radiographically, in combination with clinical assessment and steroid use. Kaplan-Meier estimates were used to compare rates of RN between cohorts. RESULTS 673 brain lesions from 93 patients met inclusion criteria [median (Q1, Q3): 5.0 (2.0-10.0) lesions per patient]. Median follow-up of lesions was 8.1 months (95% CI: 7.3, 8.7). Most (82.8%) lesions were supratentorial and histologies included melanoma (53.5%), adenocarcinoma NSCLC (27.3%), squamous cell NSCLC (6.1%), and NSCLC NOS (6.1%). In the entire cohort, 88 lesions from 25 patients (27%) developed RN. 77 (87%) lesions were diagnosed clinico-radiographically and 11 (13%) were biopsy-proven. ICPI use was highly enriched among lesions that developed RN (85.2%) versus those that did not (19.8%). Freedom from RN at 6 months was 80% for dual ICPI, 82% for single ICPI, and 97% for SRS alone; 12 month rates were 78% in each of the ICPI cohorts and 95% with SRS alone (P=0.0002). CONCLUSIONS In a large cohort of SRS-treated brain metastases, we observed an increased risk of RN among patients who received either dual or single ICPI concurrently with SRS.

Purpose/Objective(s) To develop a radiomics-integrated deep learning (RIDL) model for identifying radionecrosis in brain metastasis patients with post-SRS radiographic progression. Such a novel model is hypothesized to outperform classic radiomics and deep learning approaches in radionecrosis/recurrence differentiation. Materials/Methods The model was developed based on a 51-patient cohort at our institution with post-SRS radiographic progression and known biopsy outcome (37 radionecrosis, 14 recurrence) from Laser Interstitial Thermal Therapy (LITT). Utilizing the 3-month post-SRS high resolution T1+c volume, the RIDL model comprises three key steps: 1) 184 radiomics features (RFs) are extracted from within the SRS planning target volume (PTV) and 60% isodose volume (V60) followed with Z-score normalization; 2) a deep neural network (DNN) mimicking the encoding path of U-net is trained for radionecrosis/recurrence prediction using the 3D volume. Prior to the binary prediction output, latent variables in the DNN are extracted as 512 deep features (DFs); and 3) all extracted features are synthesized as an input of support vector machine (SVM) execution. Key features with higher linear kernel weighting factor values are identified by clustering analysis, and these key features are utilized by SVM to generate the final radionecrosis/recurrence prediction result. During the model training, a 7:3 training/test data sample ratio was adopted, and 50 model versions were acquired with random validation sample assignments. Sensitivity, specificity, accuracy, and ROC of the model were evaluated, and these results were compared with 1) classic radiomics-based prediction (i.e., radiomics features-only for SVM input) and 2) DNN prediction results. Potential associations between the identified key radiomics/deep features and patients' genetic profiles were studied. Results As seen in the table, while radiomics-based prediction achieved acceptable accuracy but very low sensitivity, DNN prediction achieved similar accuracy with an improved sensitivity; in contrast, the RIDL achieved the best prediction accuracy and sensitivity results with 32 identified key features (3 RFs+29 DFs), and it also demonstrated superior ROC results. For patients with NSCLC primary disease, 2 RFs extracted in SRS V60 exhibited significant correlation with ALK mutation (R>0.6), and 1 DF exhibited significant correlation with EGFR mutation (R>0.7). Conclusion The developed RIDL can accurately differentiate brain metastasis radionecrosis/recurrence using a single post-SRS MR scan. Future work that investigates its integration with genomics as a comprehensive radiogenomic tool is indicated.

Purpose/Objective(s) While Ataxia Telangectasia Mutated gene (ATM) variants have been associated with improved local control after radiation, adverse radiation events have been reported following conventional radiotherapy for extracranial tumors. It remains unknown whether ATM variants affect rates of radiation necrosis (RN) and local intracranial progression (LIP) following stereotactic radiosurgery (SRS) for brain metastases. We questioned whether pathologic ATM variants increase rates of RN and/or decrease rates of LIP following SRS for brain metastasis in non-small cell lung cancer (NSCLC) patients. Materials/Methods Patients undergoing an initial course of SRS for NSCLC brain metastases between 1/2015 and 12/2020 were retrospectively identified at our institution. RN and LIP were determined by either biopsy or multi-disciplinary serial MRI review. Cumulative incidence of RN and LIP were estimated via the Kaplan Meier method. Cox proportional hazards testing was performed for variant classification (not detected [ND] vs variant of unknown significance [VUS] or pathogenic variant [PV]). A power analysis estimated that 34 events would need to be observed to detect a >4-fold hazard ratio for event. Results 541 patients completed SRS for brain metastasis secondary to NSCLC, of which 260 completed molecular profiling. Comprehensive Genomic Profiling (CGP) was performed on cell free circulating tumor DNA (61%), primary tumor (17%), extracranial metastasis (17%), and brain tumor (18%), including ≥2 sites for 33 (13%) patients. Availability of CGP data was significantly associated with more recent year of SRS completion (2018-20, 64% vs 2015-17, 25%; p<0.001), younger age at brain metastasis diagnosis (64.8 years [IQR 57.1-72.8] vs 67.8 years [IQR 59.6-72.8]; p=0.036), no prior tobacco use (22% vs 10%; p<0.001), adenocarcinoma histology (84% vs 73%; p=0.002), and metastatic disease at initial diagnosis (73% vs 63%; p=0.017). ATM variants were identified in 36 cases (13.8%; 13 PV, 23 VUS). For all patients with CPG, RN incidence was 4.9% (95% CI 1.6 – 8.2%) at 6 months and 9.9% (95% CI 4.8 - 15.0%) at 12 months and LIP was 5.4% (95% CI 2.4 – 8.4%) at 6 months and 9.8% (5.5 – 14.1%) at 12 months. For patients with ATM variants, RN incidence was 5.3% (0.0 - 15.3%) at both 6 and 12 months, with 2 total RN events at 5.7 months and 13.9 months following SRS, respectively; LIP was 3.1% (0.0 - 9.1%) at both 6 and 12 months, with one total LIP event at 2.0 months following SRS (P=0.46 and P=0.26 for RN and LIP, respectively). Conclusion We did not detect significant differences in RN or LIP risk following SRS for NSCLC brain metastases associated with ATM variants. These results suggest that at this time, ATM status should not inform SRS use when otherwise indicated for NSCLC brain metastases. This dataset additionally allowed us to estimate the number of patients needed to detect a given magnitude of relative risk for RN or LIP associated with a given variant. These data can inform future studies as CGP data accumulate.

In this multi-institutional analysis of 1139 early-stage PC patients treated with moderately hypofractionated IMRT or PBT, risk of serious late GU and GI complications was low for both treatment groups. Analysis of the dosimetric variables identified an association of Grade 3+ GU toxicity with low-dose radiation exposure of the bladder. Grade 3+ GI toxicity was unrelated to dosimetric variables. PBT plans yielded less exposure of non-target organs to lower-dose radiation while IMRT plans yielded less exposure of non-target organs to higher-dose radiation.

Moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer; however, there are limited data addressing the use of MHRT in unfavorable high-risk prostate cancer (HRPC) and/or African American patients. We report the clinical outcomes and toxicity profiles for men with HRPC treated in an equal access system comparing endpoints across race. Men with HRPC treated with MHRT at a Veterans' Affairs referral center were identified. Exclusion criteria included <12 months of follow up and elective nodal irradiation. MHRT included 70Gy at 2.5Gy/fx or 60Gy at 3Gy/fx. Demographics, clinical endpoints, and toxicity data were retrospectively obtained. Acute and late (defined as ≥3 months following completion of MHRT) gastrointestinal (GI) and genitourinary (GU) toxicities were graded using CTCAE, version 5.0. Clinical endpoints including biochemical recurrence-free survival (BRFS; per Phoenix criteria), distant metastases-free survival (DMFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated via the Kaplan Meier method. Clinical outcomes, acute toxicity, and late toxicity-free survival were compared between African American (AA) and Caucasian (C) men with logistic regression and log rank testing. 100 HRPC patients were treated with MHRT between 11/2008-8/2018. Mean age was 65.7 years (range, 36-80 years). Median follow up was 64.2 months (IQR 37.2 – 86.3 months). 53 patients were African American (AA), 46 Caucasian (C), and 1 of unknown race. 84 men had unfavorable high-risk disease. T stages included T1c (52), T2 (33), and T3 (15). Median PSA was 16.48 (IQR 8.45 – 35.25). 97 men received concurrent ADT typically starting 6-8 weeks before MHRT, for a median duration of 24 months (IQR 23.3 – 32.8). 97 men received 70Gy at 2.5Gy/fx and 3 men received 60Gy at 3Gy/fx. Clinical outcomes are shown below, with no significant differences between AA and C men. Acute toxicity included GU grade 0 (32), grade 1 (20) and grade 2 (48) and GI grade 0 (89), grade 1 (9), and grade 2 (2). There were no grade 3+ GU or GI acute toxicities. Late toxicities included GU grade 0 (31), grade 1 (10), grade 2 (54), and grade 3 (5), and GI grade 0 (74), grade 1 (13), grade 2 (11), grade 3 (1), and grade 4 (1). Men with HRPC treated with MHRT in an equal access setting demonstrated favorable clinical outcomes with acceptable rates of acute and late toxicities. Clinical outcomes were not significantly different between African American and Caucasian men.Tabled 1Abstract 2940; TableBRFSDMFSOSPCSS5-year median (95% CI)78.7 (69.5 - 87.9)87.0 (79.3 - 94.7)77.2 (68.1 – 86.3)93.1 (87.2 – 99.0)8-year median (95% CI)65.0 (51.0 - 79.0)78.7 (68.1 - 89.3)54.3 (40.0 - 68.6)80.4 (68.3 – 92.5)Race, African American (HR; 95% CI)0.99 (0.65 – 1.52)0.80 (0.46 – 1.35)0.91 (0.64 – 1.28)0.92 (0.48 – 1.74) Open table in a new tab

Moderately hypofractionated radiation therapy (MHRT) is an accepted standard of care for patients with intact low and intermediate risk prostate cancer. Proton beam therapy for prostate cancer offers certain dosimetric advantages, but data directly comparing MHRT modalities are lacking. We aim to compare late toxicity profiles of localized prostate cancer patients treated with proton and photon MHRT. Prospectively-collected institutional databases from 7 tertiary referral centers were queried for patients with intact low or intermediate risk prostate cancer treated from 1998 to 2018 with MHRT, defined as 2.4 – 4.0 Gy per daily fraction given over 4-6 weeks. Patients were stratified based on receipt of proton or photon MHRT. Primary outcomes were late Grade 3+ GU and late Grade 2+ GI toxicity, per CTCAE v4.0, scored by treating institution. Late toxicity was defined as occurring >3 months after treatment completion. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, NCCN risk group, age, pretreatment IPSS (GU only) and anti-coagulant use (GI only). Odds ratios and significance were assessed using generalized linear mixed effects models, with random effects by site. A total of 1850 patients (1282 photon and 568 proton) were included with 1 year minimum follow up. The cohorts were similar in risk group and T stage. However, the photon group had significantly higher baseline IPSS (median 10 vs 7), anti-coagulant use (32.6% vs 15.3%), performance status (28% vs 6% ECOG 1+), PSA (7.6 vs 6.1), and percentage of patients with Gleason 6 disease (66% vs 57%). Late toxicity rates and odds ratios are described in the table below. The most common late toxicities were urinary frequency and rectal bleeding in the proton group and cystitis and rectal bleeding in the photon group. On adjusted analysis for late toxicity, no factors were significantly predictive of GU toxicity and only anti-coagulant use was significantly predictive of GI toxicity (OR 1.88, 95% CI 1.19-2.99). In this large, multi-institutional dataset analysis, rates of late GU and GI toxicity were low with both proton and photon MHRT. No statistically significant difference was seen in late GU toxicity rates. Higher rates of late GI toxicity were found with proton MHRT, but this difference lost statistical significance when adjusted for covariates. Overall, both proton and photon MHRT appear to be safe treatment approaches for low and intermediate risk prostate cancer patients.Abstracts 4058; TableLate Toxicity TypeProton MHRT Toxicity RatePhoton MHRT Toxicity RateOdds Ratio (Confidence Interval)G3+ GUUnadjusted1.6%3.7%0.45 (0.16-1.28)Adjusted2.0%3.9%0.47 (0.17-1.28)G2+ GIUnadjusted11.1%4.8%2.71 (1.17-6.26)Adjusted14.6%4.7%2.69 (0.80-9.05) Open table in a new tab

Moderately hypofractionated radiation therapy (mHFRT) is an accepted standard for treating localized prostate cancer. The toxicity of mHFRT is unknown in men with large prostate volume (LPV), questioning the utility of mHFRT in this scenario. We report efficacy and acute genitourinary (GU) and gastrointestinal (GI) toxicity in men treated with mHFRT according to PV. Localized prostate cancer patients treated with mHFRT at a single Veteran’s Affairs Medical Center from 8/20/08-1/31/18 were identified. Patient, tumor, treatment, and dosimetric variables were recorded. Patients were placed into an LPV cohort if their simulation PV was in the highest quartile. Acute GU and GI toxicities were defined according to the CTCAE v 5.0. Biochemical recurrence free survival (BRFS) (defined as nadir + 2 ng/ml or initiation of salvage ADT) and overall survival (OS) were estimated using the Kaplan Meier method. Univariate logistic regression and Cox proportional hazards modeling estimated the effects of PV on clinical endpoints. 392 men with low (11%), intermediate (63%), and high risk (26%) prostate cancer were treated with mHFRT. Median age was 64 (range 36-80). Median follow up was 68 months (IQR 45.7 – 89.9). Most men (n = 388) received 70 Gy in 2.5 Gy fractions, and 73% received ADT. Median PV was 45.0 cc (IQR 35.1 cc - 60.0 cc). The LPV cohort was defined as > 60 cc (n = 98). The overall rates of 5-year BRFS and OS were 86.8% (95% CI 83.1%– 90.5%) and 83.0% (95% CI 78.9% – 87.1%), respectively. The rates of 5-year BRFS and OS for the LPV cohort were 86.8% (95% CI 83.0%– 90.6%) and 83.3% (95% CI 79.2% – 87.3%). 44% had acute G2+ GU toxicity and 3.8% had acute G2+ GI toxicity. Only 6 experienced acute G3 GU toxicity and 1 acute G3 GI toxicity. Men with PV > 60 cc had similar rates of acute G2+ GU toxicity (OR 0.90 (95% CI 0.57-1.42), p = 0.65) and G2+ GI toxicity (OR 0.73 (95% CI 0.20-2.65), p = 0.63) compared to those with PV < 60 cc. 52% and 7.9% of men had late G2+ GU and late G2+ GI toxicity, respectively. 14 and 6 experienced late G3 GU and G3+ GI toxicity, respectively. Men with PV > 60 cc had similar time to development of late G2+ GU toxicity (HR 1.13 (95% CI 0.96 – 1.31), p = 0.13) and G2+ GI toxicity (HR 0.75 (95% CI 0.43 – 1.15, p = 0.20) compared to those with PV < 60 cc. mHFRT for prostate cancer was well-tolerated among men with PV > 60 cc with high rates of BRFS and OS. Despite higher volumes of bladder and rectal irradiation, men with PV > 60 cc did not have increased rates of acute or late GI/GU toxicity.Abstract 4081; TableVolume, Mean (95% CI)2-sided t-testPV > 60 ccPV < 60 ccp valueBladder V70 (cc)5.19 (4.49 - 5.90)3.21 (2.92 - 3.49)<0.0001Bladder V50 (cc)42.49 (39.31 - 45.66)31.64 (30.08 - 33.20)<0.0001Rectum V50 (cc)18.5 (17.16 - 19.92)14.30 (13.60 – 15.00)<0.0001Rectum V31 (cc)50.67 (47.19 - 54.15)40.56 (38.88 - 42.24)<0.0001 Open table in a new tab

Objectives: Head and neck radiotherapy (RT) is a risk factor for cerebrovascular disease. We performed a retrospective cohort study to evaluate carotid artery stenosis (CAS) incidence in head and neck cancer (HNC) patients undergoing RT, characterizing associated risk factors. Materials and methods: Records were retrospectively reviewed for HNC patients undergoing carotid ultrasound screening after definitive or adjuvant RT between January 2000 and May 2016. CAS was defined as >= 50% stenosis on imaging, stroke, or transient ischemic attack. Actuarial CAS rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses predicted CAS risk based on carotid dosimetric and clinical parameters. Results: 366 patients met inclusion criteria. Median time from RT completion to last follow-up was 4.1 yr. Actuarial risk for CAS was 29% (95% CI 22-36%) at 8 years. Univariate analysis showed that smoking (HR 1.7; 95% CI 1.1-2.7), hyperlipidemia (HR 1.6; 95% CI 1.03-2.6), diabetes (HR 2.8; 95% CI 1.6-4.8), coronary artery disease (HR 2.4; 95% CI 1.4-4.2), and peripheral artery disease (HR 3.6; 95% CI 1.1-11.6) were significantly associated with increased CAS. In multivariate analysis, diabetes was predictive of time to CAS (HR 1.9; 95% CI 1.1-3.4). Carotid dose parameters were not significantly associated with CAS. Conclusions: CAS incidence is high after head and neck radiotherapy, gradually rising over time. No clear dose-response effect between carotid dose and CAS was identified for HNC patients. Carotid artery screening and preventative strategies should be employed in this high-risk patient population.

To assess whether radiographic/metabolic changes on mid-chemoradiation (CRT) FDG-PET/CT for cervical cancer predict outcome. Thirty women with FIGO stage IB1-IVB cervical cancer treated with concurrent cisplatin-based CRT and brachytherapy (BT) were prospectively enrolled between Feb 2012 and Jun 2016. FDG-PET/CT was obtained pre-CRT and ∼3 weeks intra-CRT. Max and mean standard uptake values (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor and clinically involved lymph nodes (LN+) from the pre-CRT and intra-CRT FDG-PET/CT were recorded. Clinical endpoints analyzed include overall survival (OS), disease-free survival (DFS), and rates of cervical recurrence (CR), nodal recurrence (NR), and distant metastasis (DM). FDG-PET/CT variables and other prognostic factors associated with clinical endpoints were identified via univariate Cox proportional hazards modeling, with multivariate modeling performed for PET-derived variables where p<0.1. Median patient age was 41 (interquartile range 37-51), most common FIGO stage was IIB (40%), 24 (80%) women had pelvic LN+, 8 (27%) women had para-aortic LN+, and 2 (7%) had IVB disease due to supraclavicular LN+. Median dose to the elective volume, pelvic sidewall, and LN+ were 45 Gy, 55 Gy, and 65 Gy, respectively. Median BT dose was 27.5 Gy in 5 fractions. All received concurrent cisplatin and 3 women with small cell histology also received etoposide. After a median follow up of 22 months for living patients, 2 year rates of CR, NR, DM, DFS, and OS were 11% (95% confidence interval [CI] 0-22%), 21% (95% CI 4-38%), 45% (95% CI 25-65%), 44% (95% CI 26-63%), and 72% (95% CI 55-89%), respectively. While several PET metrics were associated with individual clinical endpoints, TLG was more consistently associated across endpoints on univariate analysis. Intra-CRT TLG was associated with NR (HR 1.40, 95% CI 1.09-1.76; p=0.016), DFS (HR 1.19, 95% CI 1.03-1.34; p=0.018), and OS (HR 1.33, 95% CI 1.13-1.54; p=0.002), with a trend for DM (HR 1.20, 95% CI 0.99-1.40; p=0.053). Relative change in TLG was associated with CR (p=0.021) and NR (p=0.035). Pre-CRT TLG was significantly associated with DM (HR 1.06, 95% CI 1.001-1.12; p=0.031), with a trend for DFS (HR 1.05, 95% CI 0.999-1.10; p=0.059) and OS (HR 1.06, 95% CI 0.98-1.12; p=0.057). On multivariate analysis, DFS was significantly associated with the difference in pre- to intra-CRT SUVmean (HR 3.00, 95% CI 1.09-12.7; p=0.031) with a trend for intra-CRT SUVmean (HR 2.11, 95% CI 0.90-4.92; p=0.064), while controlling for age, FIGO, grade, and LN+. In this group of high-risk cervical cancer patients treated with CRT+BT, TLG on mid-treatment FDG-PET/CT was associated with recurrence and OS, while the difference in SUVmean between pre- and mid-CRT scans was independently associated with DFS. These metrics may provide an early signal for selective treatment intensification, with either dose escalation or adjuvant chemotherapy.

A prior analysis quantified anomalous data within the National Cancer Database (NCDB) that was internally inconsistent or outside accepted norms of adjuvant radiation therapy (RT) using node positive uterine cancer as a test clinical scenario. This project seeks to determine the effect of anomalous data on overall survival (OS). All NCDB subjects with FIGO stage IIIC1-IIIC2 uterine cancer treated with hysterectomy and adjuvant RT between 1998-2012 were identified. Variables reviewed to identify anomalous data included RT site, modality, dose, fractions, timing, duration and stage. Log rank test was used to calculate OS for subjects with and without anomalous data. Univariate and multivariate (MVA) cox regression analyses of anomalous data with respect to OS were performed with and without insufficient, anomalous, or unknown RT dose, with both models controlling for the following factors: facility type, facility location, race, median income, educational status, Charlson-Deyo score, and diagnosis year. A total of 2,288 (16.0%) of the 14,298 analyzed subjects had ≥1 anomalous datum; 538 (3.8%) subjects had anomalies limited to insufficient dose or fractions which could be from an incomplete RT course. 5 year OS in those with ≥1 anomalous datum was 51.32% (95% CI 48.89-53.71%) versus 57.97% (95% CI 57.89-58.07%) for those without anomalous data (p<0.0001). MVA showed that facility location (HR 1.212, 95% CI 1.062-1.383; p=0.0008), age at diagnosis (HR 1.043, 95% CI 1.040-1.047; p<0.0001), race (HR 1.263, 95% CI 1.110-1.438; p<0.0001), Charlson-Deyo score (HR 1.149, 95% CI 1.053-1.253; p=0.0001), diagnosis year (HR 0.972, 95% CI 0.958-0.987; p=0.0002), RT dose per Gy, (HR 0.998, 95% CI 0.997-0.999; p=0.0007), and any anomalous data (HR 1.133, 95% CI 1.086-1.183; p<0.0001) were significantly associated with OS. After excluding subjects with an insufficient, anomalous, or unknown total RT dose (unknown, n=5022; <40 Gy, n=671; >90 Gy, n=172), the 814 (9.7%) of 8,433 subjects with ≥1 anomalous datum had overlapping 5 year OS (57.19%, 95% CI 53.27-61.11%) versus those without anomalous data (61.46%, 95% CI 60.15-62.77%). MVA of this subset showed OS correlated significantly with facility location (HR 1.187, 95% CI 1.012-1.392; p=0.0014), age at diagnosis (HR 1.044, 95% CI 1.040-1.048; p<0.0001), race (HR 1.248, 95% CI 1.068-1.458; p<0.0001), Charlson-Deyo score (HR 1.141, 95% CI 1.027-1.267; p=0.0132), diagnosis year (HR 0.973, 95% CI 0.955-0.991; p=0.032), and RT dose (HR 1.012, 95% CI 1.005-1.019; p=0.0008); however, there was no longer an association with anomalous data (HR 1.000, 95% CI 0.929-1.077; p=0.996). Unaccounted-for anomalous data within the NCDB in this test clinical scenario, particularly insufficient RT dose, was significantly associated with worse OS. Careful accounting for inconsistently recorded entries and anomalous data is critical for future investigations using the NCDB, particularly when radiation details are examined.