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Purpose: The objective of this study was to characterize the conditional risk of developing grade 2+ urinary or gastrointestinal (GI) toxicity for patients treated with external beam radiation therapy in Radiation Therapy Oncology Group 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and at later points of follow-up., Methods and Materials: One thousand five hundred thirty-two patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1499 were eligible and included in data analysis with a median follow-up of 8.4 years (range, 0.02-13 years). Patients were treated with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy according to institutional practice without the addition of androgen deprivation and randomized to receive either standard-dose radiation therapy of 70.2 Gy or dose-escalated radiation therapy of 79.2 Gy of radiation therapy to the prostate only with standard fractionation. Univariate and multivariate analyses were performed to determine whether initial factors were predictive of late toxicity at the time of treatment and at later time points., Results: As patients proceed further from completion of radiation therapy without the development of toxicity, the subsequent risk of both grade 2+ genitourinary (GU) and GI toxicity decreases with time. At the time of enrollment, the risk of developing grade 2+ toxicity over the next 5 years was 9.57% and 17.89%, respectively. After 5 years of toxicity-free survival, the risk of developing grade 2+ GU or GI toxicity in the subsequent 5 years was 3.02% and 1.54%, respectively. Baseline treatment and patient-related factors predicted late toxicity both at trial enrollment and after 2 years of toxicity-free survivorship. Baseline urinary dysfunction and dose-escalated radiation therapy were associated with increased late GU toxicity. Acute GI toxicity and dose-escalated radiation therapy were associated with increased risk of late GI toxicity. Treatment with intensity-modulated radiation therapy was associated with reduced risk of either toxicity., Conclusions: The conditional risk of grade 2+ toxicities decreases as patients proceed further from treatment, with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: A phase 2 study of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and SBRT in mNSCLC., Methods and Materials: STOMP is a single-arm, open-label phase 2 study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 10 11 vp) and SBRT (30 Gy in 5 fractions) followed by pembrolizumab 200 mg IV every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR) (complete response [CR] and partial response [PR]). Secondary endpoints included clinical benefit rate (CBR) (CR, PR and stable disease [SD]), progression-free survival (PFS), overall survival (OS), and safety., Results: 28 patients were enrolled, of whom 27 were evaluated for response. The ORR was 33.3%, including 2 CR (7.4%) and 7 PR (25.9%). CBR was 70.4%. Six of eight (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. The entire cohort had a median PFS of 7.4 months (95% CI, 5.1-9.6 months), and median OS of 18.1 months (95% CI, 15.4-20.9 months). The combination was well tolerated, with grade 3 or higher toxicity in 6 (21.4%) patients., Conclusions: The dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy-sparing strategy to enhance the antitumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury. Here, we compare the performance of FLA and FWAS and propose a novel method combining both approaches., Methods: We used breath-hold computed tomography (BHCT) and simulation 4-dimensional computed tomography (4DCT) from 12 lung stereotactic ablative radiation therapy patients. Four planning strategies were examined: (1) Conventional: no sparing other than clinical dose-volume constraints; (2) FLA: using a 4DCT-based ventilation map to delineate the HFL, plans were optimized to reduce mean dose and V 13.50 in HFL; (3) FWAS: we autosegemented 11 to 13 generations of individual airways from each patient's BHCT and assigned priorities based on the relative contribution of each airway to total ventilation. We used these priorities in the optimization along with airway dose constraints, estimated as a function of airway diameter and 5% probability of collapse; and (4) FLA + FWAS: we combined information from the 2 strategies. We prioritized clinical dose constraints for organs at risk and planning target volume in all plans. We performed the evaluation in terms of ventilation preservation accounting for radiation-induced damage to both lung parenchyma and airways., Results: We observed average ventilation preservation for FLA, FWAS, and FLA + FWAS as 3%, 8.5%, and 14.5% higher, respectively, than for Conventional plans for patients with ventilation preservation in Conventional plans <90%. Generalized estimated equations showed that all improvements were statistically significant (P ≤ .036). We observed no clinically relevant improvements in outcomes of the sparing techniques in patients with ventilation preservation in Conventional plans ≥90%., Conclusions: These initial results suggest that it is crucial to consider the parallel and the serial nature of the lung to improve post-radiation therapy lung function and, consequently, quality of life for patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To develop and validate a pretreatment computed tomography (CT)-based deep-learning (DL) model for predicting the treatment response to concurrent chemoradiation therapy (CCRT) among patients with locally advanced thoracic esophageal squamous cell carcinoma (TESCC)., Methods and Materials: We conducted a prospective, multicenter study on the therapeutic efficacy of CCRT among TESCC patients across 9 hospitals in China (ChiCTR2000039279). A total of 306 patients with locally advanced TESCC diagnosed by histopathology from August 2015 to May 2020 were included in this study. A 3-dimensional DL radiomics model (3D-DLRM) was developed and validated based on pretreatment CT images to predict the response to CCRT. Furthermore, the prediction performance of the newly developed 3D-DLRM was analyzed according to 3 categories: radiation therapy plan, radiation field, and prescription dose used., Results: The 3D-DLRM achieved good prediction performance, with areas under the receiver operating characteristic curve of 0.897 (95% confidence interval, 0.840-0.959) for the training cohort and 0.833 (95% confidence interval, 0.654-1.000) for the validation cohort. Specifically, the 3D-DLRM accurately predicted patients who would not respond to CCRT, with a positive predictive value (PPV) of 100% for the validation cohort. Moreover, the 3D-DLRM performed well in all 3 categories, each with areas under the receiver operating characteristic curve of >0.8 and positive predictive values of approximately 100%., Conclusion: The proposed pretreatment CT-based 3D-DLRM provides a potential tool for predicting the response to CCRT among patients with locally advanced TESCC. With the help of precise pretreatment prediction, we may guide the individualized treatment of patients and improve survival., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)