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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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

To report the results of our prospective study on electronic patient-reported outcome (ePRO) monitoring-aided management of patients with breast cancer (BC) receiving hypofractionated adjuvant radiation therapy (RT). Between August 17, 2022, and October 4, 2023, 23 patients with localized BC were consented and enrolled. Patients received ePRO questionnaires across 6 domains (overall health, financial burden, education/communication of disease process, cosmesis, functional outcome, treatment-related toxicity) – a minimum of 12 questions if no adverse events (AEs) and a maximum of 31 questions if AEs were found in all domains. Suggested interventions were sent back to the patient and care team based on patient responses; questionnaires were sent pre-RT, at the end of treatment (EOT), and before 3-month (3m) follow-up. The primary analysis was conducted using a one-sided 1-sample proportion test with Yates continuity correction based on the 3m response rate of 50% as baseline. A correlation coefficient of 0.3-0.5 was considered low positive; 0.5-0.7 moderate positive; 0.7-0.9 high positive; > 0.9 very high positive. All patients were treated with 3D conformal image-guided radiation to a dose of 25 or 40 Gy in 5 or 15 fractions, respectively. All patients rated their well-being as good/excellent and reported being fully active or experiencing restrictions only in strenuous activities. Financial hardship of moderate or worse severity was not reported in any cases; 60% reported no hardship, while the remainder reported mild hardship but with expenses covered and maintaining daily living expenses unchanged. Patient-reported cosmesis was rated as good/excellent in 90% at baseline and 86% at 3m follow-up. Minimal radiation changes were reported by 8.3% pre-RT, 36% at EOT, and 19% at 3m of patients while Grade 1 skin dermatitis reported by physicians was found in 0% pre-RT, 90% at EOT, and 8% at 3m (correlation 0.41). Mild breast swelling was reported by 42% pre-RT, 57% at EOT, and 56% at 3m, while physician-reported Grade 1 breast lymphedema was observed in 5% pre-RT, 0% at EOT, and 17% at 3m (correlation 0.49). One case of breast infection was reported by both patients and physicians at 3m. Minimal breast pain was reported by 17% of patients pre-RT, 29% at EOT, and 63% at 3m, while physicians reported only breast pain in 12.5% at 3m (correlation 0.31). Mild functional impairment was observed in 1 patient at baseline and 2 patients at 3m. Electronic PROs monitoring increased patient response rates to 69% (p = 0.047), showing high discrimination for moderate/severe/very severe PROs and Grade 2 or higher AEs. However, PROs were more sensitive in reporting none to mild events. Grade 1 AE rates at baseline, at EOT, and at 3m were 21.7%, 47.8%, and 56.5%, respectively. Electronic PROs monitoring increased patient reporting and provided useful clinical information to aid management. Patients reported higher rates of mild AEs than physicians. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]