International Journal of Radiation Oncology Biology Physics最新文献

Purpose: Target volumes for irradiation remain ill-defined for head and neck squamous cell cancer of unknown primary (HNSCCUP). The aim of this study was to compare 2 commonly used radiation therapy strategies for patients diagnosed with HNSCCUP: ipsilateral or involved neck only (INO) versus bilateral neck and/or mucosal (MUC) radiation therapy, evaluating disease-related outcomes and enteral feeding rates.

Methods and materials: This was a retrospective, observational, multicenter cohort study. Patients diagnosed with unilateral HNSCCUP between 2015 and 2023 who underwent radical (chemo) radiation therapy were eligible for analysis. All patients underwent 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography - Computed Tomography (PET-CT). HNSCCUP was a diagnosis of exclusion made on the basis of negative investigations to detect a primary site. Patient and tumor characteristics, treatment details, toxicities, and disease control were recorded and compared between the 2 radiation therapy strategies.

Results: One hundred ninety-five patients were eligible for analysis, 66% had human papillomavirus-associated disease. Seventy-three patients received INO (37%) and 122 patients received MUC radiation therapy (63%). The median duration of follow-up was 58 months (IQR, 42-72 months). The rate of primary site emergence was 2.7% in the INO and 0.8% in the MUC cohorts, P = .56. Five-year overall survival was 80% (95% CI, 70%-90%) for INO and 82% (95% CI, 75%-90%) for MUC radiation therapy, P = .74. Those undergoing INO radiation therapy were more likely to die from HNSCCUP (17.8% vs 5.7%), and those receiving MUC were more likely to die from a non-HNSCCUP cause (15.6% vs 4.1%). The need for enteral feeding ≥12 months from radiation therapy was 5.7% for MUC versus 0% for INO (P = .046).

Conclusions: This is the largest series to date of patients with unilateral HNSCCUP treated radically with radiation therapy in the human papillomavirus and FDG PET-CT era. Acceptably low rates of primary site emergence, lower toxicity, and no difference in overall survival when compared with prophylactic MUC radiation therapy suggest that INO radiation therapy in HNSCCUP may be a feasible alternative in contemporary practice.

Purpose: The duodenum is a key organ at risk during sterotactic ablative radiotherapy (SABR). Understanding mechanisms of radiation-induced intestinal injury (RIII) could reveal novel strategies to reduce SABR toxicities. The gut microbiome contributes to RIII; however, existing preclinical models either require surgical manipulation or fail to recapitulate high-dose conformal treatment fields used during SABR, confounding microbiome studies. We developed a noninvasive focal bowel irradiation model to assess microbiome dynamics in both the duodenum and the stool after high-dose duodenal irradiation.

Methods and materials: C57BL/6J mice received sham treatment or focal irradiation (12 or 18 Gy) to the proximal duodenum using a small animal irradiator. Stool and duodenal tissue samples were collected at days 4, 14, and 91 after treatment and processed for bacterial 16S rRNA gene V4 region amplicon sequencing (Illumina MiSeq platform). Microbiome diversity metrics were calculated, and multivariable linear mixed modeling identified bacterial taxa associated with radiation therapy.

Results: Oral iodine contrast enabled duodenum visualization, and 100% of mice survived until euthanasia. Focal duodenal irradiation led to dose- and time-dependent changes in duodenal bacterial community composition that were not observed in stool. At days 4 and 14 after treatment, 18 duodenal taxonomic groups were significantly perturbed, whereas only 2 taxa were significantly altered in the stool.

Conclusions: Our focal duodenal irradiation model is safe, well tolerated, and easy to implement. It enables characterization of microbiome perturbations during both the acute and late phases of injury and serves as a platform for testing new RIII mitigation strategies. Our findings reveal that irradiation-induced changes in the duodenal microbiome are dose-, time-, and spatially dependent and are not reflected in stool samples. These results underscore the imperative of directly assessing tissue-associated microbiota, as relying solely on stool samples risks overlooking critical, localized microbial dynamics that may drive injury and repair.

Purpose: To determine albumin-bilirubin (ALBI) score change thresholds that indicate hepatotoxicity and predict poorer overall survival (OS) in hepatocellular carcinoma patients post-external beam radiation therapy (EBRT).

Methods and materials: The development cohort consisted of 329 hepatocellular carcinoma patients treated with liver-targeted EBRT across 2 centers from 2008 to 2023, with 71% classified as Child-Pugh (CP) A and 29% as CP-B/C. Recursive partitioning analysis identified thresholds associated with OS, which were evaluated using Cox regression, compared to a 2-point increase in CP score (CP2+) and externally validated using data from 2 independent centers (n = 248). The primary outcome was to establish ALBI score change thresholds associated with poorer OS. Secondary outcomes included comparing the prognostic accuracy of ALBI score change thresholds with the CP2+ criterion, analyzing the predictive value across different baseline liver functions, and examining the association between radiation dose to the normal liver and ALBI score changes.

Results: ALBI changes of >0.25 (ALBI change grade 1) and >0.5 (ALBI change grade 2) were identified as optimal thresholds. CP2+ showed superior discriminative performance in the overall cohort; however, when stratifying by baseline liver status, ALBI change grade 1 outperformed CP2+ in CP-B/C patients (hazard ratio, 4.4; 95% CI, 2.4-7.8). Overall, these findings were confirmed in the external validation cohort. Multivariable Cox models, including CP2+ or ALBI changes and baseline liver status, demonstrated higher or similar concordance for ALBI score changes across all data sets. Mean liver dose correlated more strongly with ALBI score changes (logistic regression odds ratio = 1.09/1.07 for grade 1/2) than with CP2+ (odds ratio = 1.04).

Conclusions: ALBI score changes of >0.25 and >0.5 are alternatives to CP2+ to evaluate radiation-induced hepatotoxicity, with the potential for more accurate assessment based on baseline liver function. Their objectivity and stronger correlation with normal liver dose make ALBI score changes more suitable for dose-response models aimed at minimizing the risk of liver complications following EBRT.

Purpose: The effective dose to immune cells-radiotherapy course-adjusted (EDRIC) is a dosimetry-based metric that estimates radiation exposure to circulating immune cells during radiotherapy. Elevated EDRIC is linked to lymphopenia, immune dysfunction, and poor tumor control in unresectable non-small cell lung cancer (NSCLC) after chemoradiation. However, it is unclear if EDRIC directly correlates with clinical outcomes and particularly with durvalumab consolidation, or if confounding factors drive this association. This study examined whether EDRIC independently correlates with progression-free survival (PFS).

Methods and materials: Data from 286 patients with unresectable stage III NSCLC treated with definitive-intent radiation therapy between 2017 and 2024 at 3 tertiary centers were collected. EDRIC was calculated using mean heart, lung, body doses, and the number of fractions. Maximally selected rank statistics identified the optimal EDRIC cutoff for PFS. Univariable and multivariable Cox regression models were used to assess the association between EDRIC and clinical outcomes.

Results: Following the exclusion of patients who did not meet the inclusion criteria, 251 patients remained in the final analysis dataset. Using a cutoff of 9.57 Gy, 53 patients were classified as having high EDRIC and 198 as low EDRIC. Patients with low EDRIC had significantly longer median PFS (23.7 vs 11.7 months; hazard ratios (HR) 0.56; 95% CI, 0.39-0.82; P = .003). In a multivariable analysis including EDRIC, PD-L1 (programmed death ligand-1) expression, N stage (N3 vs N0-2), and PTV (planning target volume), lower EDRIC remained directionally associated with longer PFS (low vs high HR = 0.67; 95% CI, 0.45-1.01; P = .053), PD-L1 positive status remained associated with longer PFS (vs PD-L1 negative: HR = 0.64; 95% CI, 0.44-0.94; P = .021), and N3 was directionally adverse (HR = 1.56; 95% CI, 0.99-2.46; P = .054).

Conclusions: In patients receiving durvalumab after chemoradiation for unresectable stage III NSCLC, lower EDRIC was associated with longer PFS. This effect was limited to patients with positive PD-L1 tumors.