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PURPOSE/OBJECTIVE(S) Neoadjuvant chemoradiotherapy (CRT) serves to downstage and increase the rate of surgical resection for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). Although conventional staging provides prognostic information, it remains a challenge to predict which patients will proceed with resection. We hypothesize that the severity of vessel involvement and the trajectory of CA19-9 levels after neoadjuvant treatment would associate with proceeding to resection. MATERIALS/METHODS Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC and treated with neoadjuvant CRT between 1/2005 and 12/2020. Progress notes were evaluated to determine if a patient proceeded to surgery and the trajectory of CA 19-9 levels in response to treatment. Radiologist notes were evaluated to determine the extent of mesenteric vessel (superior mesenteric artery, celiac axis, portal vein, hepatic artery, and superior mesenteric vein) involvement. A vessel involvement score was calculated as the sum of all vessels in contact with tumor: 1 point for each vessel, with partial (< 180 degrees) encasement of artery counting as 2 points. Odds ratios (OR) of proceeding to resection were computed with 95% confidence intervals (CI) for CA19-9 response to treatment. Ordinal logistic regression models were fit to estimate the impact of greater vessel involvement on the odds of NOT proceeding with surgery. RESULTS Forty-two (n = 42) patients were included in the analysis. The median age was 65 years (IQR: 61 to 71). 73% of patients were treated with 3600 cGy in 15 fractions (fx), 24% of patients were treated with 4500-5040 cGy in 25-28 fx, and 3% of patients were treated with 3300 cGy in 5 fx. 55% of patients were treated with neoadjuvant FOLFIRINOX and 45% of patients were treated with other regimens. 88% of patients were considered borderline resectable and 12% were resectable at the time of diagnosis. Patients with any decrease in CA19-9 levels after CRT had higher odds of proceeding with resection (OR = 21.0, 95% CI: 3.2 to 139.2). However, decrease in CA19-9 levels after upfront chemotherapy was not significantly associated with proceeding with resection (P = 0.91). The odds of NOT proceeding with resection after neoadjuvant CRT were 1.81 times higher (95% CI: 0.97 to 3.39) for each increase in vessel involvement score, however these findings were not statistically significant (P = 0.062). CONCLUSION Patients diagnosed with (B)RPC proceeding with CRT have different odds of proceeding to surgery based on their response to CRT and extent of vessel involvement. Post-CRT CA19-9 can help predict which patients may proceed to resection. Future investigations will develop nomograms for estimating odds of proceeding to surgery in larger datasets to help aid in patient counseling and multidisciplinary discussion.

Purpose/Objective(s) Radiation therapy (RT) is a critical modality for the treatment of unresectable hepatocellular carcinoma (HCC). Little is known about how the etiology of HCC impacts overall and progression free survival (OS and PFS) in patients treated with definitive RT. We hypothesize that patients treated with definitive RT for HCC secondary to hepatitis B and hepatitis C viruses (viral group) would have favorable OS and PFS when compared to patients with HCC secondary to other etiologies (non-viral group). Materials/Methods Medical records were retrospectively reviewed at a single institution for patients diagnosed with unresectable HCC and treated with definitive RT between 1/2011 and 12/2020. Patients treated with prior surgery or radiofrequency ablation were excluded. Progress notes were reviewed to determine date of last follow-up, progression, and death. Notes were also assessed to determine the etiology of HCC, age at diagnosis, Child-Pugh classification (CPC), AJCC 8th edition T stage, RT strategy, and planning target volume (PTV). Descriptive statistics were quantified for baseline characteristics. Survival curves were estimated via Kaplan-Meier method; statistical difference was determined using the log-rank test. Multivariate (MVA) Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors. Results Forty-six patients were included in the analysis. 30 (65%) patients were in the viral group, while 16 (35%) patients were in the non-viral group. Median ages at diagnosis for the viral and non-viral groups were 64 (interquartile range (IQR): 60 to 69) and 71 years (IQR: 66.5 to 76.5), respectively (P = 0.014). Treatment with hypofractionated RT (P = 0.559), proton therapy (P = 0.686), performance status (P = 0.222), CPC (P = 0.270), T stage (P = 0.639), and PTV (P = 0.472) were not different between groups. There was a trend toward improved Median OS for the viral group compared to the non-viral group: 17.9 months (95% confidence interval (CI): 9.7 to not-reached (NR)) vs. 8.8 months (95% CI: 6.1 to NR) (P = 0.072). Similarly, PFS was not different between viral and non-viral groups: 9.3 (95% CI: 7.4 to 19.0) vs. 8.0 (95% CI: 4.0 to 10.3), P = 0.314. However, after controlling for confounding factors with MVA Cox proportional hazards models, the viral group had superior OS (HR = 4.20, 95% CI: 1.47 to 12.02, P = 0.008); the viral group also had superior PFS (HR = 2.48, 95% CI: 1.06 to 5.81, P = 0.037). Conclusion Our retrospective review of patients with unresectable HCC treated with definitive RT provides evidence that viral etiologies of HCC may fare better in OS and PFS when compared to non-viral etiologies. The etiology of HCC development for virally vs non-virally mediated tumors may have implications for treatment and response in the setting of radiation therapy.

Purpose Stereotactic body radiation therapy is increasingly used to treat a variety of oligometastatic histologies, but few data exist for ovarian cancer. Ablative stereotactic body radiation therapy dosing is challenging in sites like the abdomen, pelvis, and central thorax due to proximity and motion of organs at risk. A novel radiation delivery method, stereotactic magnetic-resonance–guided online-adaptive radiation therapy (SMART), may improve the therapeutic index of stereotactic body radiation therapy through enhanced soft-tissue visualization, real-time nonionizing imaging, and ability to adapt to the anatomy-of-the-day, with the goal of producing systemic-therapy–free intervals. This phase I trial assessed feasibility, safety, and dosimetric advantage of SMART to treat ovarian oligometastases. Methods and Materials Ten patients with recurrent oligometastatic ovarian cancer underwent SMART for oligometastasis ablation. Initial plans prescribed 35 Gy/5 fractions with goal 95% planning target volume coverage by 95% of prescription, with dose escalation permitted, subject to strict organ-at-risk dose constraints. Daily adaptive planning was used to protect organs-at-risk and/or increase target dose. Feasibility (successful delivery of >80% of fractions in the first on-table attempt) and safety of this approach was evaluated, in addition to efficacy, survival metrics, quality-of-life, prospective timing and dosimetric outcomes. Results Ten women with seventeen ovarian oligometastases were treated with SMART, and 100% of treatment fractions were successfully delivered. Online adaptive plans were selected at time of treatment for 58% of fractions, due to initial plan violation of organs-at-risk constraints (84% of adapted fractions) or observed opportunity for planning target volume dose escalation (16% of adapted fractions), with a median on-table time of 64 minutes. A single Grade ≥3 acute (within 6 months of SMART) treatment-related toxicity (duodenal ulcer) was observed. Local control at 3 months was 94%; median progression-free survival was 10.9 months. Median Kaplan-Meier estimated systemic-therapy–free survival after radiation completion was 11.5 months, with concomitant quality-of-life improvements. Conclusions SMART is feasible and safe for high-dose radiation therapy ablation of ovarian oligometastases of the abdomen, pelvis, and central thorax with minimal toxicity, high rates of local control, and prolonged systemic-therapy–free survival translating into improved quality-of-life.

Purpose To analyze the incidence of and risk factors for clinically significant radiation necrosis (cRN) in adult cranial oligodendrogliomas and astrocytomas treated with proton or photon therapy. Methods and Materials Between 2007 and 2015, 160 patients with grade 2 or 3 oligodendrogliomas (with 1p/19q codeletion, n = 53) or astrocytomas (without 1p/19q codeletion, n = 107) were treated with proton (n = 37) or photon (n = 123) therapy. Clinically significant radiation necrosis (RN) was defined as symptomatic RN or asymptomatic RN that resulted in surgery or bevacizumab administration. The cumulative incidence was calculated using competing risks. Risk factors were identified using Cox proportional hazards. Results After a median follow-up period of 28.5 months, cRN developed in 18 patients (proton, 6; photon, 12). The 2-year cumulative incidence of cRN for proton and photon therapy was 18.7% (95% confidence interval [CI], 7.5%-33.8%) and 9.7% (95% CI, 5.1%-16%), respectively (P = .16). On multivariate analysis, risk factors for cRN included oligodendroglioma (hazard ratio [HR], 3.57; 95% CI, 1.38-9.25; P = .009) and higher prescription dose (in gray relative biological equivalents [GyRBE]) (HR, 1.30; 95% CI, 1.05-1.61; P = .015). The 2-year cumulative incidence of cRN in oligodendrogliomas and astrocytomas was 24.2% and 6.2%, respectively (P = .01). The relative volume (percentage) of brain receiving 60 GyRBE was a significant dosimetric predictor of cRN in oligodendrogliomas (HR, 1.11; 95% CI, 1.03-1.20; P = .005). Conclusions The study showed that 1p/19q codeleted oligodendroglioma was a significant risk factor associated with cRN and the relative volume (percentage) of brain receiving 60 GyRBE was an important dosimetric predictor of cRN for oligodendroglioma patients. There is insufficient evidence at this time to conclude a significant difference in the incidence of cRN between proton and photon therapy.

PURPOSE/OBJECTIVE(S) Neoadjuvant chemoradiotherapy is a critical treatment for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). The PREOPANC trials employ a short course chemoradiation (SCCRT) regimen of 3600 cGy in 15 fractions with concurrent gemcitabine (GEM)-based chemotherapy, but little is known about the relative efficacy of capecitabine (CAPE)-based concurrent chemotherapy in this population. We hypothesize that patients treated with SCCRT with CAPE-based concurrent chemotherapy will have superior overall survival (OS) compared to GEM-based strategies. MATERIALS/METHODS Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC between 1/2005 and 12/2020. Patients treated with neoadjuvant SCCRT were included in the analysis. Descriptive statistics were quantified for baseline characteristics. OS was estimated using Kaplan-Meier estimates, statistical difference was determined using the log-rank test. Multivariate Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors. RESULTS Thirty-one (n = 31) patients were included in the analysis. 71% of patients (n = 22) were treated with CAPE-based concurrent chemotherapy, while 29% of patients (n = 9) were treated with GEM-based concurrent chemotherapy. Median age at diagnosis was 65 (interquartile range (IQR): 60 to 71) for the CAPE group, compared to 66 (IQR: 63 to 71) for the GEM group, P = 0.414. 100% of patients in the CAPE group were borderline resectable, compared to 82% of patients in the GEM group, P = 0.171. 44% of patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, compared to 14% in the GEM group, P = 0.016. Patients treated with concurrent 5-CAPE-based chemotherapy had a longer median OS than other concurrent chemotherapy approaches: Not reached (95% confidence interval (CI): 24 to not reached) vs. 17 months (95% CI: 6 to 22 months), P < 0.0001. Multivariate Cox proportional hazards models, controlling for borderline vs. resectable status, age at diagnosis, and use of neoadjuvant FOLFIRINOX, demonstrated that CAPE-based concurrent chemotherapy had a HR of death of 0.081 (95% CI: 0.018 to 0.369, P = 0.0012) compared to GEM-based concurrent chemotherapy. CONCLUSION Patients diagnosed with (B)RPC have many therapeutic options; this study suggests a benefit to CAPE-based concurrent chemotherapy when treating patients with SCCRT, even after controlling for significant confounding by greater use of neoadjuvant FOLFIRINOX with CAPE-based concurrent chemotherapy. SCCRT may be more effective with concurrent capecitabine instead of concurrent gemcitabine for (B)RPC.

Purpose/Objective(s) Radiation therapy (RT) remains a critical treatment modality for unresectable hepatocellular carcinoma (HCC), with proton beam therapy (PBT) being widely utilized due to its decreased exit dose compared to photon-based RT. We hypothesize that patients with HCC receiving definitive PBT would experience decreased acute toxicity when compared to those receiving photon-based RT. Materials/Methods Electronic medical records were retrospectively reviewed at a single institution for patients diagnosed with unresectable HCC and treated with definitive RT between 1/2011 and 12/2020. Patients treated with prior surgery or radiofrequency ablation were excluded. Progress notes and treatment summaries were reviewed to determine baseline characteristics including age at diagnosis, Child-Pugh classification (CPC), AJCC 8th edition T stage, performance status, and RT dose. Acute treatment toxicities were evaluated using Common Terminology Criteria for Adverse Events v5.0. Descriptive statistics were quantified for baseline characteristics. Odds ratios (OR) with 95% confidence intervals (CI) were generated to determine the association between PBT vs. photon therapy and acute radiation toxicities in bivariate and multivariate logistic regression models. Results Forty-six patients were included in the analysis. 24 (52%) patients received PBT while 22 (48%) received photon-based RT. Median age for the PBT and photon-based RT groups were 67 (interquartile range (IQR): 58.6 to 72.5) and 65.5 years (IQR: 61.0 to 73.0), respectively (P = 0.991). 50% of patients who received PBT had a T stage greater than T2, compared to 71% of patient in the photon group (P = 0.148). 42% of the PBT group had CPC B or worse, compared to 38% in the photon group (P = 0.813). Performance status and total dose did not significantly differ between groups (P = 0.351 and P = 0.773, respectively). PBT was associated with higher odds of any grade radiation dermatitis (RD) (OR = 6.00, 95% CI: 1.13 to 31.9) and lower odds of any grade anorexia (OR = 0.21, 95% CI 0.05 to 0.91). Odds of any grade diarrhea and fatigue, did not significantly differ between groups (P = 0.086 and P = 0.958, respectively). After controlling for performance status, total dose, T stage, CPC, and age at diagnosis, PBT was still associated with higher odds of RD (OR = 11.07, 95% CI: 1.14 to 107.71) and lower odds of anorexia (OR = 0.14, 95% CI: 0.02 to 0.93). Conclusion This study provides evidence that although PBT appears to have a superior safety profile in regard to acute anorexia, patients treated with PBT have higher odds of acute RD; these effects persist even after controlling for relevant confounding factors. PBT may result in fewer GI toxicities at the cost of greater skin toxicity.

SpaceOAR, a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years.Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds.The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02).The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

Purpose/objectives Multiparametric advanced MR and [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging may be important biomarkers for prognosis as well for distinguishing recurrent glioblastoma multiforme (GBM) from treatment-related changes. Methods/materials We retrospectively evaluated 30 patients treated with chemoradiation for GBM and underwent advanced MR and FDG-PET for confirmation of tumor progression. Multiparametric MRI and FDG-PET imaging metrics were evaluated for their association with 6-month overall (OS) and progression-free survival (PFS) based on pathological, radiographic, and clinical criteria. Results 17 males and 13 females were treated between 2001 and 2014, and later underwent FDG-PET at suspected recurrence. Baseline FDG-PET and MRI imaging was obtained at a median of 7.5 months [interquartile range (IQR) 3.7–12.4] following completion of chemoradiation. Median follow-up after FDG-PET imaging was 10 months (IQR 7.2–13.0). Receiver-operator characteristic curve analysis identified that lesions characterized by a ratio of the SUVmax to the normal contralateral brain (SUVmax/NB index) >1.5 and mean apparent diffusion coefficient (ADC) value of ≤1,400 × 10−6 mm2/s correlated with worse 6-month OS and PFS. We defined three patient groups that predicted the probability of tumor progression: SUVmax/NB index >1.5 and ADC ≤1,400 × 10−6 mm2/s defined high-risk patients (n = 7), SUVmax/NB index ≤1.5 and ADC >1,400 × 10−6 mm2/s defined low-risk patients (n = 11), and intermediate-risk (n = 12) defined the remainder of the patients. Median OS following the time of the FDG-PET scan for the low, intermediate, and high-risk groups were 23.5, 10.5, and 3.8 months (p