Purpose: Head and neck (HN) radiotherapy contour quality directly impacts local control (LC) and survival; however, few departments peer review (PR) contours prior to radiotherapy planning (RTP). This study reports outcomes of a single institution's formal HN contour PR process.Methods: A formal HN contour PR process was implemented. Prior to RTP, HN radiation oncologists reviewed contours, provided feedback and assigned contour grades as follows: R0 (no change), R1 (minor revision, not high risk) or R2 (major revision; high risk). The PR task was completed and the contour grade was recorded. Cochran-Armitage trend test was performed.Results: Pilot PR process was performed over a 7-month period for 88 patients, followed by a maintenance phase. Contours were graded as follows: R0 (N = 51), R1 (N = 20) and R2 (N = 17). Over time, the number of R2 revisions decreased (p = 0.0001); month 1 (N = 7), month 2 (N = 3), month 3 (N = 5), month 4 (N = 2) and months 5-7 (N = 0). Conversely, the number of R0 revisions improved over time (p = 0.0203); month 1 (N = 5), months 2-3 (N = 9), month 4 (N = 5), month 5 (N = 8), month 6 (N = 12) and month 7 (N = 3). Each radiation oncologist demonstrated reduction in R2 revisions during the pilot. During maintenance, all 3 radiation oncologists demonstrated low rates of R2 revisions of less than 3 cases per year.Conclusion: Incorporation of HN contour PR into routine clinical workflow is feasible. The collective experience of multiple high-volume HN radiation oncologists led to improved contour quality in the pilot for each radiation oncologist and continued to ensure high quality in the maintenance phase.

Purpose/Objective(s) NRG 0617 established that the standard dose of photon RT for unresectable NSCLC is 60 Gy in 30 fractions. However, no dose-escalating trials have been reported for modern active-scanning PBT. A signal-seeking Phase II randomized study (MC1623) was designed and conducted to address this. Materials/Methods A single-institutional study was performed. Inclusion criteria included patient (pt)’s age ≥ 18 years; tissue confirmation of NSCLC; PFT’s FEV1 ≥ 1 L; unresectable or medically inoperable stage II-III; ECOG PS 0-1; acceptable labs for concurrent chemo; and curative intent. Exclusion criteria included weight loss ≥ 10%; M1 cancer; uncontrolled illnesses; active second malignancy; and prior RT that would overlap with planned PBT. A brain MRI was required. The original design was to randomize pts into 60 Gy/30 fractions (fx) vs. 66 Gy/33 fx vs. 72 Gy/36 fx arms in a 1:1:1 fashion. Contouring included generations of GTV, iGTV, and CTV’s. SFO/MFO optimization methods were used for PBT. The primary endpoint was progression-free survival (PFS) improvement, with secondary endpoints being overall survival (OS), adverse events, locoregional and distant failure rates. Results Accrual was slower than expected, and the 66-Gy arm was first closed, followed by the entire study. Between Aug 2017 and June 2021, 20 pts met inclusion criteria (originally planned for 48 pts). 1 pt was denied by insurance for PBT; 2 (11%) withdrew their consent after randomization. The final analysis consisted of 17 pts. 2 (12%) pts were randomized to the 66-Gy arm, and they were included with the other 8 pts (60 Gy) as standard-dose arm. 7 (41%) pts received 72 Gy (high-dose). The Mayo Prognostic scores for comorbidities were balanced (P = 0.89). The mean age was 76.4 (standard) vs. 74.2 years (P = 0.50); 8 (47%) were male. 13 (77%) smoked in the past. 8 (47%) pts had squamous cell carcinoma; 8 (50%) pts had T3/4 tumors, and 14 (82%) with N2 nodes. At the end of follow-up (median 1.86 years), 6 pts were alive, and 11 deaths had occurred. There was no difference in progression-free (2.04 vs. 0.94 years, P = 0.71) nor overall (3.05 vs. 2.36 years, P = 0.74) survivals, for standard vs high dose arms, respectively. Female gender appeared to favor PFS (P = 0.03), and no nodal involvement for improved OS (P = 0.08). There was 1 pt with grade 3 pneumonitis in standard-dose arm, and 1 pt each with grade 3 myocardial infraction and pulmonary fibrosis in high-dose arm. A competing risk analysis is being planned. Conclusion While the study was too small to statistically determine a benefit of one dose arm vs. the other, numerically, there appeared no clear advantage to 72-Gy dose escalation in terms of PFS and OS which could be verified in a larger randomized trial. NRG 1308 should clarify if PBT is superior to photon-based RT. With standard use of immunochemotherapy in addition to CRT for locally advanced NSCLC, the increased chance of cardiopulmonary toxicities may be lessened with better tissue-sparing PBT. This, too, will require further prospective studies.

Purpose/Objective(s) This study combines data from three multi-site phase II/III clinical trials focusing on HPV mediated oropharyngeal squamous cell cancer (OPSCC) to develop a predictive model for 12-month post radiotherapy treatment (RT) aspiration. The trials reported outcomes for standard of care (SOC) adjuvant concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), de-escalated adjuvant RT and chemotherapy (DART), and mucosal sparing proton beam therapy (MSPBT). We hypothesized that patient reported outcomes (PROs), clinical, and pathologic factors could identify patients with preserved swallow function 12 months post-RT. Materials/Methods Patients were assessed for swallowing dysfunction using Penetration-Aspiration Scale (PAS) at baseline and 12 months post-RT from a modified barium swallow study (MBSS). Aspiration was defined as PAS > = 6. Patient-reported outcomes (PROs) were measured using the EORTC QLQ HN35 instrument at baseline and 12-month post-RT. Age at RT, sex, ECOG performance status, tumor laterality/location, staging, treatment modality, fractions, dose, and disease recurrence were considered as potential predictors. A multivariate Bayesian logistic regression model with a lasso prior for feature selection was employed to predict 12-month post-RT aspiration. The model was validated using a 25% holdout test cohort, with training and test AUC serving as key performance metrics. An optimal predicted probability cut point calculated using Youden's J based on the training data was used to predict 12-month post-RT aspiration (PAS > = 6) on the test cohort. Results 12-month aspiration rates were similar for the training (8/238 = 3.4%) and test cohort (2/88 = 2.3%). Age at RT, baseline PAS, obesity (BMI > 31), pharyngeal constrictor V4Gy, and 12-month EORTC QLQ HN35 swallowing score were positively associated with the likelihood of aspiration based on 95% credible intervals. Model training AUC was 0.97 (95% CI = 0.97-1.0), and test AUC was 0.90 (0.70-1.0). Using the training-optimized predicted probability cut point to predict aspiration on the test cohort, prediction accuracy was 0.97 (0.90-0.99), specificity was 0.98 (0.92-1.0), sensitivity 0.5 (0.01-0.99), PPV 0.33 (0.01-0.91), and NPV 0.99 (0.92-1.0). Conclusion OPSCC 12-month post-RT aspiration can be reliably predicted using patient demographics, treatment characteristics, and PROs. The model's test NPV of 0.99, provides a novel tool to tailor the intensity of patient intervention during the surveillance phase. Using this validated model could have reduced the number of 12-month MBSS ordered from 88 to 3 (97% reduction) in the test cohort.

PURPOSE:The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. METHODS AND MATERIALS:A multicenter nonrandomized controlled trial with the primary outcome of adverse cosmesis at 3 years versus before PBI. Eligibility criteria were age ≥50 years treated with breast-conserving surgery for node-negative estrogen receptor-positive (ER+) invasive breast cancer or any ductal carcinoma in situ (DCIS) measuring ≤2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (relative biological effectiveness) and brachytherapy 21 Gy in 3 fractions. Radiation therapy technique and adjuvant endocrine therapy were selected at physician and patient discretion. RESULTS:Between June 17, 2015, and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. One hundred twenty-six (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). Fifty-four percent of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to the prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline and 2.3% at 3 years (difference, -12.2%; 95% CI, -100% to -6.4%). Adverse cosmesis at the last follow-up, with a median follow-up of 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient-reported outcomes, and just 2 grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. Five-year local recurrence-free survival and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences among 60 patients with invasive breast cancer and Ki67 ≤13.25%. CONCLUSIONS:Deintensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the prespecified criteria for acceptability. This approach is an attractive option for patients with small node-negative ER+ breast cancer and DCIS.

PURPOSE:This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM). METHODS AND MATERIALS:Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry. RESULTS:Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH- and NF1-mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors. CONCLUSIONS:The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation.

Purpose/Objective(s) Despite aggressive multimodality treatments, the median survival of glioblastoma (GBM) patients remains within the range of 12-15 months after diagnosis with standard-of-care; therefore, new therapeutic strategies are critically needed. Radiation is a common and effective therapeutic option for GBM. However, some GBMs are relatively radioresistant. Radiation-induced DNA damage repair requires a constant and balanced supply of dNTPs, which is catalyzed by ribonucleotide reductase (RNR). Therefore, we hypothesized that the inhibition of RRM2 by triapine sensitizes GBM to radiation. Materials/Methods We analyzed RRM2 expression in GBM at the mRNA level and assessed its correlation with clinical outcomes in GBM patients using different public datasets. We examined the effect of RRM2 inhibition, either by small interfering RNA (siRNA) or RRM2 inhibitor (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; triapine), on radiosensitization using clonogenic assays in both established and GBM patient-derived primary cells, as well as mouse GBM cells in vitro. Radiation-induced DNA damage was evaluated via γ-H2AX foci assays, and the underlying mechanism was studied using western blotting. To explore the radiosensitizing effect of triapine in vivo, we used both heterotopic and orthotopic syngeneic mouse models. Results RRM2 expression was significantly higher in GBM tissues than in non-tumor tissues, and higher RRM2 expression was significantly associated with higher tumor grade and worse overall survival. Interestingly, RRM2 inhibition sensitized GBM cells to radiation in vitro, led to reductions in tumor growth, and significantly increased mouse survival in vivo, with acceptable levels of toxicity. Mechanistically, RRM2 inhibition-mediated radiosensitization was associated with higher γ-H2AX foci counts and expression, indicating higher levels of unresolved DNA damage after radiation. Moreover, we confirmed that triapine leads to replication stress, which in turn upregulates RRM2 via a CHK1 mediated mechanism, as inhibition of CHK1 abrogated the triapine-induced induction of RRM2. Conclusion Our preclinical study suggests that RRM2 is a promising therapeutic target for GBM, and triapine inhibition of RRM2 sensitizes GBM cells to radiation treatment in vitro and in vivo. Our findings suggest that combining triapine with radiation may improve therapeutic outcomes in GBM, warranting additional preclinical studies and providing a justification for a phase I clinical trial potentially in the recurrent setting.

Purpose/Objective(s) Treatments for prostate cancer (PCa) can profoundly impact sexual health (SH). Previous studies have found that PCa patients (pts) are concerned about their SH as a consequence of treatment. Discussing and addressing these concerns upfront can help set appropriate expectations and impact treatment decisions. Limited studies have explored if SH concerns are adequately addressed by their oncologists. There is presently a lack of understanding of how to best address these concerns. Materials/Methods This was a survey study of pts with newly diagnosed, treatment-naïve, PCa to characterize their SH concerns and identify opportunities to facilitate discussions with oncologists. Anonymous surveys were administered to pts from a comprehensive cancer center and its network sites. Pts were approached by our study team or self-recruited via flyers posted in our clinics during follow-up or consultation related to PCa treatment. Demographics such as age, sexual orientation, and race/ethnicity were collected. Baseline sexual functions were assessed using International Index of Erectile Function. Pts were asked to rate statements about their SH concerns on a 6-point Likert scale ranging from “strongly disagree” to “strongly agree”. Respondents were also asked to evaluate their past discussions with their oncologists. Demographics and survey results were summarized using descriptive statistics. This study was approved by our institution's review board. Results From Dec 2023 to Feb 2024, a total of 36 pts participated in the study during this period, 25 (69%) pts met the screening criteria (i.e., excluded due to prior treatments) and proceeded to the actual survey. Of the 25 pts, the median age was 70 (range = 52 to 83) years. A majority identified as (non-Hispanic) White (44%), heterosexual (91%), married/living with a partner (92%), and college-educated or higher (68%). Sixteen (64%) reported that they were currently sexually active, with 44% reporting some degree of satisfaction with their overall sex life. Only four (16%) pts reported having had prior SH conversations with their oncologists, and among these, the majority (75%) were satisfied with their discussions. A sizeable number of pts reported some degree of concern about the cancer treatment's impact on their sexual performance (56%), libido (48%), erectile function (56%), and ability to satisfy their partner(s) (48%). The largest percentage (48%) of pts cited conversations with their oncologists as their preferred method of learning more about the impact of treatment on SH; others preferred educational brochures (32%) or referrals to SH specialists (20%). Conclusion In this survey study, we found that SH concerns are common among patients with newly diagnosed PCa. Only a small percentage of pts have had discussions about SH with their oncologists, but many would like to discuss SH with their oncologists, suggesting an unmet need in care.

Purpose: We report 5-year oncologic outcomes of a prospective series of patients with prostate cancer treated with spot-scanning proton therapy (SSPT). Methods and Materials: A prospective registry identified fi ed patients with prostate cancer treated with SSPT between January 2016 and December 2018. Five-year overall survival, local control, biochemical failure, regional and distant failures, and adverse events (AEs) were assessed. Biochemical failure was defined fi ned as rise in prostate-specific fi c antigen >= 2.0 ng/mL above nadir prostate-specific fi c antigen. Baseline-adjusted toxicities were assigned using the Common Terminology Criteria for Adverse Events version 5.0. Results: With a median follow-up of 4.4 years, 284 patients with prostate cancer were treated with SSPT. Median total radiation dose was 79.2 Gy over 44 fractions, 70 Gy over 28 fractions, and 38 Gy over 5 fractions for conventional fractionation (CF), hypofractionation (HF), and stereotactic body radiation therapy (SBRT), respectively. Biochemical failure rate for all patients was 6.7%. Five-year local control rates for CF, HF, and SBRT were 100%, 100%, and 97.3%, respectively (P P = .07). Regional recurrences occurred in 12 (4.2%) patients: 8 treated with CF, 2 with HF, and 2 with SBRT (P P = .62). Distant failures occurred in 12 patients (4.2%): 5 treated with CF, 7 with HF, and none with SBRT (P P = .05). Five-year overall survival for patients treated with CF, HF, and SBRT SSPT were 88.1%, 86.1%, and 97.2%, respectively (P P = .1). Acute and chronic grade 2+ gastrointestinal AEs occurred in 8 (2.8%) and 51 (18.0%) patients, respectively. Acute and chronic grade 3+ gastrointestinal AEs occurred in 3 (1.1%) and 4 (1.4%) patients, respectively. Acute and chronic grade 2+ genitourinary-related AEs were observed in 71 (25%) and 63 (22.2%) patients, respectively. Acute and chronic grade 3+ genitourinary toxicity were observed in 3 (1.1%) and 6 (2.1%) patients, respectively. Conclusions: SSPT provides high local control rates and excellent oncologic outcomes across different fractionation schedules with low long-term AE rates. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Purpose: To evaluate dose volume histogram (DVH) construction differences across 8 major commercial treatment planning systems (TPS) and dose reporting systems for clinically treated plans of various anatomic sites and target sizes. Methods and Materials: Dose f iles from 10 selected clinically treated plans with a hypofractionation, stereotactic radiation therapy prescription or sharp dose gradients such as head and neck plans ranging from prescription doses of 18 Gy in 1 fraction to 70 Gy in 35 fractions, each calculated at 0.25 and 0.125 cm grid size, were created and anonymized in Eclipse TPS, and exported to 7 other major TPS (Pinnacle, RayStation, and Elements) and dose reporting systems (MIM, Mobius, ProKnow, and Velocity) systems for comparison. Dose -volume constraint points of clinical importance for each plan were collected from each evaluated system (D0.03 cc [Gy], volume, and the mean dose were used for structures without speci fi ed constraints). Each reported constraint type and structure volume was normalized to the value from Eclipse for a pairwise comparison. A Wilcoxon rank -sum test was used for statistical signi fi cance and a multivariable regression model was evaluated adjusting for plan, grid size, and distance to target center. Results: For all DVH points relative to Eclipse, all systems reported median values within 1.0% difference of each other; however, they were all different from Eclipse. Considering mean values, Pinnacle, RayStation, and Elements averaged at 1.038, 1.046, and 1.024, respectively, while MIM, Mobius, ProKnow, and Velocity reported 1.026, 1.050, 1.033, and 1.022, respectively relative to Eclipse. Smaller dose grid size improved agreement between the systems marginally without statistical signi fi cance. For structure volumes relative to Eclipse, larger differences are seen across all systems with a range in median values up to 3.0% difference and mean up to 10.1% difference. Conclusions: Large variations were observed between all systems. Eclipse generally reported, at statistically signi fi cant levels, lower values than all other evaluated systems. The nonsigni fi cant change resulting from lowering the dose grid resolution indicates that this resolution may be less important than other aspects of calculating DVH curves, such as the 3 -dimensional modeling of the structure. (c) 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Background Minimal clinically important differences (MCIDs) quantify the clinical relevance of quality of life results at the individual patient and group level. The aim of this study was to estimate the MCID for the Brief Fatigue Inventory (BFI) and the Worst and Usual Fatigue items in patients with brain or CNS cancer undergoing curative radiotherapy.Methods Data from a multi-site prospective registry was used. The MCID was calculated using distribution-based and anchor-based approaches. For the anchor-based approach, the fatigue item from the PROMIS-10 served as the anchor to determine if a patient improved, deteriorated, or had no change from baseline to end of treatment (EOT). We compared the unadjusted means on the BFI for the 3 groups to calculate the MCID. For the distribution-based approaches, we calculated the MCID as 0.5 SD of the scores and as 1.96 times the standard error of measurement.Results Three-hundred and fifty nine patients with brain or CNS tumors undergoing curative radiotherapy filled out the 9-item BFI at baseline and EOT. The MCID for the BFI was 1.33 (ranging from 0.99 to 1.70 across the approaches), 1.51 (ranging from 1.16 to 2.02) and 1.76 (ranging from 1.38 to 2.14) for the usual and worst fatigue items, respectively.Conclusions This study provides the MCID ranges for the BFI and Worst and Usual fatigue items, which will allow clinically meaningful conclusions to be drawn from BFI scores. These results can be used to select optimal treatments for patients with brain or CNS cancer or to interpret BFI scores from clinical trials.

Purpose We aimed to determine if ultra-hypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. Materials and Methods This study was a multicenter, randomized, controlled, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 according to AJCC 7th ed. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Non-inferiority for FFF was determined based on one-sided confidence intervals. Toxicities were compared at different time points using Fisher's Exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. Results Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR 3.9–5.2). The 2-year FFF was 100% for both groups, with the one-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI: -1.70%–6.96%), favoring the SBRT arm, thus fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. Rates of gastrointestinal (GI) and genitourinary (GU) G2 and G3 toxicities did not differ significantly between groups but the the study was not powered to detect significant toxicity differences. Also, HRQoL metrics did not differ significantly between groups over the study median follow up. Conclusions SBPT is non-inferior to CFPT regarding FFF, with similar long-term GU and GI toxicity rates and minimal impact in patient reported HRQoL over time.

PURPOSE: We report 5-year oncologic outcomes of a prospective series of patients with prostate cancer treated with spot-scanning proton therapy (SSPT).METHODS AND MATERIALS: A prospective registry identified patients with prostate cancer treated with SSPT between January 2016 and December 2018. Five-year overall survival (OS), local control (LC), biochemical failure (BF), regional and distant failures, and adverse events (AEs) were assessed. Biochemical failure was defined as rise in PSA ≥ 2.0 ng/mL above nadir PSA. Baseline-adjusted toxicities were assigned using CTCAE v5.0.RESULTS: With a median follow up of 4.4 years, 284 prostate cancer patients were treated with SSPT. Median total radiation dose was 79.2 Gy over 44 fractions, 70 Gy over 28 fractions, and 38 Gy over 5 fractions for conventional fractionation (CF), hypofractionation (HF), and stereotactic body radiation therapy (SBRT), respectively. Biochemical failure rate for all patients was 6.7%. Five-year LC rates for CF, HF, and SBRT were 100%, 100%, and 97.3%, respectively (p = 0.07). Regional recurrences occurred in 12 (4.2%) patients: 8 treated with CF, 2 with HF, and 2 with SBRT (p = 0.62). Distant failures occurred in 12 patients (4.2%): 5 treated with CF, 7 with HF, and none with SBRT (p = 0.05). Five-year OS for patients treated with CF, HF, and SBRT SSPT were 88.1%, 86.1%, and 97.2%, respectively (p = 0.1). Acute and chronic grade 2+ GI AEs occurred in 8 (2.8%) and 51 (18.0%) patients, respectively. Acute and chronic grade 3+ GI AEs occurred in 3 (1.1%) and 4 (1.4%) patients, respectively. Acute and chronic grade 2+ GU-related AEs were observed in 71 (25%) and 63 (22.2%) patients, respectively. Acute and chronic grade 3+ GU toxicity were observed in 3 (1.1%) and 6 (2.1%) patients, respectively.CONCLUSIONS: SSPT provides high local control rates and excellent oncologic outcomes across different fractionation schedules with low long-term AE rates.

Purpose/Objective(s) Real-time cardiac side effects due to thoracic radiotherapy (RT) have never been previously characterized in patients (pts) with lung and esophageal cancers. We specifically designed and completed a prospective clinical trial to address this. Materials/Methods A planned cohort of 24 pts were accrued from Dec 2019 to Jan 2023. Two (8%) pts withdrew their consent prior to ICM insertion. All pts met eligibility criteria, which included ≥ 18 years; non-metastatic, de novo lung or esophageal cancer diagnosis; receiving standard-of-care curative RT or chemoRT with an anticipated heart dose V40 Gy ≥ 20 cc; and planned RT dose ≥ 40 Gy. Pts with any prior RT to the heart were excluded. The ICM provided continuous outpatient arrhythmia monitoring (24/7), and all cardiac rhythms were captured prior to RT, and 4 weeks, 3, 9, and 12 months after RT. The ICM was explanted at 12-month follow-up. The ICM automatically captured and alerted clinicians to the following cardiac events: bradycardia ≤ 40 bpm; asystole with pauses ≥ 3 seconds (s); high degree AV block ≤ 30 bpm lasting ≥ 8 seconds; symptomatic tachycardia ≥ 150 bpm for any duration; and atrial fibrillation. Clinical events such as heart failure were also recorded. The primary endpoint was pts’ 12-month cardiac event rate (both clinically and by ICM) after RT completion. Clopper-Pearson confidence intervals were used in the analysis. Results The final analysis included all 22 pts. Average age was 67 years; 13 pts were male. Eighteen pts finished 12-mo follow-up per protocol, 1 died during treatment, and 3 died during follow-up. At baseline, 4 (19%) reported arrhythmia, 2 (10%) had coronary artery disease, and 1 (5%) with prior myocardial infarction; 15 (68%) were past smokers. Seventeen (77%) received proton beam therapy, and 5 (23%) received photon therapy. The median RT dose was 50 Gy in 2 Gy/fraction. RT was interrupted in 2 (9%) pts, due to needing an ablation for atrial flutter and hospitalization. Cardiac changes as defined in the study were seen in 15 (68%) pts. ICMs detected events in 14 (64%) pts: 10 with atrial arrhythmias (fibrillation/flutter), 2 transient asystoles, 1 non-sustained ventricular tachycardia, and 1 paroxysmal 3rd degree AV block. These events led to 4 interventions including 2 atrial ablations, 1 pacemaker insertion, 1 aortic valve replacement (18% of pts, 95% CI = 5-40%). Conclusion With real-time cardiac monitoring, cardiac events were detected in 64% of pts within 12 months post-RT, leading to timely medical diagnoses and interventions, with potentially improved outcomes. This novel prospective data highlighted the possible benefits of close cardiac surveillance. Further prospective studies are warranted to study the broad impact of ICM-based cardiac evaluation in better characterizing the intricate effects of thoracic RT on the heart and the cardiac conduction system.

Number of patients in each of the patient cohorts used, and overlap between the cohorts.

Purpose/objectivesProton beam therapy (PBT) may provide a dosimetric advantage in sparing soft tissue and bone for selected patients with extremity soft sarcoma (eSTS). We compared PBT with photons plans generated using intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT).Materials/methodsSeventeen patients previously treated with pencil beam scanning PBT were included in this study. Of these patients, 14 treated with pre-operative 50 Gy in 25 fractions were analyzed. IMRT and 3D-CRT plans were created to compare against the original PBT plans. Dose-volume histogram (DVH) indices were evaluated amongst PBT, IMRT, and 3D plans. Kruskal-Wallis rank sum tests were used to get the statistical significance. A p value smaller than .05 was considered to be statistically significant.ResultsFor the clinical target volume (CTV), D2%, D95%, D98%, D-min, D-max,D- and V50Gy, were assessed. D-min, D1%, D-max, D-mean, V1Gy, V5Gy, and V50Gy were evaluated for the adjacent soft tissue. D1%, D-max, D-mean, and V35-50% were evaluated for bone. All plans met CTV target coverage. The PBT plans delivered less dose to soft tissue and bone. The mean dose to the soft tissue was 2 Gy, 11 Gy, and 13 Gy for PBT, IMRT, and 3D, respectively (p < .001). The mean dose to adjacent bone was 15 Gy, 26 Gy, and 28 Gy for PBT, IMRT, and 3D, respectively (p = .022).ConclusionPBT plans for selected patients with eSTS demonstrated improved sparing of circumferential soft tissue and adjacent bone compared to IMRT and 3D-CRT. Further evaluation will determine if this improved dosimetry correlates with reduced toxicity and improved quality of life.

Prognostic significance of SUVmax for local (cervix) recurrence (A) and any pelvic recurrence (B).

Ductal adenocarcinoma of the pancreas is the fourth leading cause of cancer deaths in the United States and accounts for approximately 3% of all cancers.1 Radiation therapy (RT) is a standard-of-care therapy for pancreatic cancer (PC). Although linked to a local control benefit and cancer-related symptom reduction, RT is also associated with fatigue and gastrointestinal side effects, including nausea, vomiting, anorexia, duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation.