Tumor hypoxia is a predictive biomarker of treatment resistance in patients with head and neck squamous cell carcinoma (HNSCC). We previously reported the discovery of a tumor DNA methylation signature of hypoxia (Hypoxia-M), identifying HNSCC patients at risk for local recurrence (LR), all event progression, and death after primary radiochemotherapy (RCHT). We further validate Hypoxia-M in an independent cohort of HNSCC patients who underwent surgical resection followed by postoperative radiochemotherapy (PORT-C) METHODS: Hypoxia-M was validated in HPV-negative HNSCC patients (n = 134) homogeneously treated with PORT-C in the frame of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) multicenter biomarker trial. DNA methylation was profiled using Illumina450K technology. The performance of Hypoxia-M was integrated with previously reported biomarkers, including gene expression signatures (GES) of hypoxia, a methylome-based HPV-Independent Classifier of disease Recurrence (HICR), and immune cell score using immunohistochemistry (CD3/CD8/PD-L1/PD1). Hypoxia-M was independently prognostic for overall survival (OS, HR = 2.34, p = 0.03) and distant metastasis (DM, HR = 4.3, p = 0.001), but not for LR after PORT-C. Hypoxia-M remained significant after adjusting for patientś age, gender, smoking status, tumor stage, and high-risk features (ECE&/R1 resection). Hypoxia-M status was inversely associated with CD8 T-cell infiltration. Patient stratification improved by integrating previously reported biomarkers, with Hypoxia-M demonstrating independent prognostic performance. The prognostic utility of Hypoxia-M was validated in an independent cohort. Our results highlighted a difference in recurrence patterns of hypoxic tumors treated in the primary setting (local recurrence) versus postoperatively (distant metastasis) and the utility of Hypoxia-M for identifying the main pattern of recurrence.

BackgroundRadiological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemoradiation therapy (CRT) is challenging to assess.PurposeTo evaluate whether computed tomography (CT) and biological features can predict tumor regression grade (TRG), recurrence-free survival (RFS), and overall survival (OS) of patients who undergo surgery after CRT for PDAC.Material and MethodsThis retrospective study included 125 patients who underwent surgery after CRT for non-metastatic PDAC between January 2013 and March 2021. Two board-certified radiologists independently reviewed initial and post-CRT CT images and assessed the primary tumor extent and regional lymph node metastasis. Another board-certified radiologist quantitatively assessed the primary tumor on pre- and post-CRT diffusion-weighted and positron emission tomography images. Logistic regression and Cox regression analyses were performed to identify predictors of TRG 0/1, RFS, and OS.ResultsIn total, 44 (35.2%) patients had a TRG of 0/1. The normalized post-CRT carbohydrate antigen (CA) 19-9 level (<37 IU) (odds ratio [OR] = 3.69; P = 0.024) and adjacent organ invasion on post-CRT CT images (OR = 0.24; P = 0.042) were independent predictors of TRG 0/1. During follow-up (mean = 33.6 months), 68 (54.4%) patients experienced tumor recurrence and 65 (52.0%) died. The normalized post-CRT CA 19-9 level (<37 IU) (hazard ratio [HR] = 0.51; P = 0.028) was a significant predictor of RFS, and size change (%) after CRT (HR = 0.24; P = 0.044) was an independent predictor of OS.ConclusionThe normalized post-CRT CA 19-9 level and adjacent organ invasion on post-CRT CT images predicted TRG. The normalized post-CRT CA 19-9 level was associated with RFS, whereas size change was an independent predictor of OS.

Salvage laryngectomy is associated with significant reconstructive challenges related to pharyngocutaneous fistula (PCF) formation and need for secondary reconstruction. This retrospective study evaluates these surgical outcomes by comparing free flap onlay technique with pedicled muscle and fascial flap onlay technique. All patients underwent chemoradiation therapy with recommendations for salvage laryngectomy after being diagnosed with recurrent or persistent laryngeal malignant disease. Patients were excluded if the surgical defect required interposed flap tissue for pharyngeal closure. Subgroup analysis was performed to compare overall rates of fistula and need for secondary reconstructive surgery. A significant overall association (p = 0.014) between flap reconstruction type and presence of PCF was found. The odds of fistula formation was 55% lower in the pedicled pectoralis/latissimus muscle flap group and 70% lower for the free flap reconstruction group compared to the reference group that underwent only primary pharyngeal closure, without flap onlay (odds ratio = 0.3, p = 0.004). PCF rates and need for secondary reconstructive efforts are decreased when free tissue onlay is employed to reinforce the pharyngeal closure line compared to pedicled flaps.

Development of a Predictive Calculator for the Need for Abdominoperineal Resection after Chemoradiation Therapy in Anal Squamous Cell Carcinoma.

To develop and validate machine learning (ML) models for postoperative risk stratification in oral cavity squamous cell carcinoma (OCSCC) and to examine whether ML-derived risk groups modify the association between adjuvant therapy and overall survival (OS). Using the National Cancer Database, we identified adults with invasive OCSCC treated with primary surgery. The surgery-alone cohort (n = 18,543) was split 70/30 for training/testing to develop DeepSurv, Neural Multi-Task Logistic Regression (NMTLR), and Random Survival Forest (RSF) models. Risk scores were generated for the full cohort (n = 35,625) and converted to low, intermediate, and high groups. Within groups, treatment effects of adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) were estimated using multivariable Cox models. The best performance was achieved by DeepSurv (C-index 0.73), with similar discrimination for NMTLR/RSF (C-index 0.71-0.72). For DeepSurv, the full cohort was partitioned into low- (50.0%), intermediate- (32.0%), and high-risk (18.0%) groups with distinct 5-year OS rates: 77.6%, 53.0%, and 29.3%, respectively. In the low-risk group, adjuvant RT (adjusted hazard ratios [aHR], 0.94 [95% CI, 0.87 to 1.02]) and CRT (aHR, 1.03 [95% CI, 0.91 to 1.17]) did not improve OS. In the intermediate-risk group, OS improved with RT (aHR, 0.61 [95% CI, 0.57 to 0.65]) and CRT (aHR, 0.56 [95% CI, 0.52 to 0.61]). In the high-risk group, both adjuvant RT (aHR, 0.47 [95% CI, 0.43 to 0.51]) and CRT (aHR, 0.39 [95% CI, 0.36 to 0.41]) were associated with improved OS compared with surgery alone. CRT was associated with a modest benefit compared with RT. NMTLR and RSF yielded concordant patterns. Top features included pT4a stage, age ≥70 years, and extranodal extension. ML-derived risk stratification identifies patients with OCSCC most likely to benefit from adjuvant therapy, supporting intensification for intermediate-/high-risk patients and potential deintensification for low-risk patients. External prospective validation is warranted to enable clinical implementation.

Cumulative Incidence and Type-Specific Risk Factors of Pneumonitis After Definitive Chemoradiotherapy With or Without Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer.

A Phase 2 Exploratory Trial Evaluating Computed Tomography-Based Midtreatment Nodal Response to Select for De-escalated Chemoradiation Therapy in the Definitive Management of p16+ Oropharyngeal Cancer.

Immunotherapy (IO) has been associated with better outcomes in locally advanced non-small cell lung cancers (NSCLCs). In 2017, our center introduced compassionate use of immunotherapy for stage III NSCLC as follows: neoadjuvant chemotherapy combined to perioperative immunotherapy and surgery for resectable NSCLCs (PERIOPERATIVE) and chemo-radiation therapy followed by immunotherapy (PACIFIC) for non-resectable NSCLCs. We report the outcomes and complications of 78 patients. IWe reviewed all stage III NSCLC patients treated in the Center or Thoracic Surgery of Romandie (CURCT) between 2017 and 2023 with chemo-immunotherapy and surgery and radiation therapy using our prospectively collected database. We compared groups using Stata®. Intention to treat population consisted in 52 PERIOPERATIVE and 26 PACIFIC patients. PERIOPERATIVE patients were significantly younger (64 [60-71]vs73 [67-80], p=0.0001) and had better lung diffusion capacity compared to PACIFIC patients (%predicted DLCO: 74±18vs48±26, p=0.0008). Complications over the course of therapy occurred in more than 50% of patients but remained manageable in both groups. Forty-two of 52 PERIOPERATIVE (81%) and 18 of 26 (69%) PACIFIC patients completed the entire treatment plan. There was no 30-day mortality. Complete pathological response (pCR) occurred in 11 of the 50 operated PERIOPERATIVE patients (22%) and was associated with a 100% 5-year survival. Overall, 5-year survival was of 78% and 30% in the PERIOPERATIVE and PACIFIC groups respectively. The inclusion of immunotherapy in the management of stage III NSCLC has been associated with improved patient outcomes. Real life data suggests that patient complications are frequent but manageable and that patient dropout is low.

Low-Dose Fractionated Radiation Therapy as a Chemopotentiator of Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma: A Single-Arm Phase 1/2 Trial.

A pragmatic phase II trial evaluating treatment strategies using immune checkpoint inhibitors for metastatic esophageal cancer patients with severe dysphagia.

Is single implant and multiple fractions radio-biologically iso-effective for cervical cancer high-dose-rate brachytherapy: Observation from patient cohorts during COVID pandemic.

Manipulation of tumor microenvironment by induction of immunogenic cell death and immune check point inhibitors for enhancing the efficacy of cancer treatments.

Purpose To compare diffusion-weighted (DWI) MRI and PET/CT for diagnosing local-regional residual disease after curative-intent chemoradiation therapy (CRT) in oropharyngeal squamous cell carcinoma (OPSCC), including evaluation of DWI for clarifying equivocal PET/CT findings. Materials and Methods In this prospective study, consecutive participants with OPSCC treated with curative-intent CRT were enrolled between October 2018 and September 2021. DWI was added to the routine PET/CT protocol 3-3.5 months after treatment for local-regional residual disease detection. Reference standards were histopathologic confirmation or unequivocal progression or resolution at follow-up imaging. During qualitative evaluation, imaging findings were classified as negative, equivocal, or positive for residual disease; equivocal findings were considered positive for analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated, with differences between modalities assessed using the McNemar test. As a secondary analysis, a sequential imaging strategy using PET/CT and DWI was evaluated. Results A total of 95 participants (mean ± SD age, 61.3 years ± 9.3; 72 male, 85 p16-positive) were included, of whom eight (8.4%) had local-regional residual disease. Sensitivity and negative predictive value for local-regional residual disease detection were 100% for both PET/CT and DWI (eight of eight and 61 of 61 at PET/CT; eight of eight and 72 of 72 at DWI). DWI demonstrated higher specificity (83% [72 of 87] vs 70% [61 of 87]; P < .05) and positive predictive value (35% [eight of 23] vs 24% [eight of 34]; P < .05) than PET/CT. In the sequential imaging analysis, DWI resolved 14 of 34 positive or equivocal PET/CT findings, whereas PET/CT was negative in three of 23 positive or equivocal DWI cases. Conclusion Both PET/CT and DWI demonstrated excellent sensitivity for detecting local-regional residual disease after CRT in OPSCC, as no residual primary tumors or nodal metastases were missed by either modality. DWI showed higher specificity and positive predictive value than PET/CT and demonstrated potential to clarify equivocal PET/CT findings. Keywords: PET/CT, MR-Functional Imaging, MR-Diffusion Weighted Imaging, Head/Neck, Comparative Studies Supplemental material is available for this article. © RSNA, 2026.

Shorter time to initiation of adjuvant chemoradiation therapy as a risk factor for hydrocephalus following high-grade glioma resection: A case-control study

622 Background: Clinical stage I (CSI) testicular germ cell neoplasms (tGCN) represent the most frequent disease presentation and are highly curable. While active surveillance (AS) is increasingly favored as initial management, practice heterogeneity persists. The SWOG/CCTG S1823/GCC-001 trial is a prospective, non-interventional cohort study evaluating microRNA 371a-3p as a diagnostic biomarker in germ cell tumors. We hereby present a pre-planned secondary analysis of this dataset to characterize real-world treatment patterns and baseline characteristics of CSI tGCN across North America. Methods: We included patients from S1823 with pathologically confirmed CSI tGCN (seminoma or nonseminoma). Patients with metastatic disease, marker-positive status post-orchiectomy, or recurrent disease were excluded. Demographic, pathologic, and intended management data were extracted from case report forms and institutional source documents, as intended per pre-planned secondary use of data provisions. Results: Among 706 patients with CSI tGCN (428 seminoma, 278 nonseminoma), median age was higher in seminoma (38.7±10.7 years) than nonseminoma (32.4±9.4). There was a high prevalence of overweight or obese habitus (36.0% and 32.2%, respectively). AS was the most commonly selected management strategy: 92.1% in seminoma and 79.9% in nonseminoma. Adjuvant chemotherapy was used more often in nonseminoma (16.2%) than seminoma (6.3%), typically one cycle of BEP or carboplatin respectively. Radiation was nearly absent (&lt;1%). Across both histology groups, adjuvant chemotherapy was prescribed more frequently in U.S. centers than in Canada (seminoma: 8.4% vs 0.8%; nonseminoma: 19.2% vs 5.1%). Conclusions: AS is the predominant management strategy for CSI tGCN across North America, with limited use of adjuvant therapy. However, treatment patterns vary by histology and geography, with notably higher adjuvant chemotherapy use in the U.S. compared to Canada. These findings illustrate evolving practices and highlight the utility of large prospective registries to assess real-world care. Full S1823 trial analysis may further inform risk-adapted strategies in CSI tGCN. Clinical characteristics and management recommendations for CSI seminoma and nonseminoma patients enrolled on S1823. Clinical Characteristics Histology Race/Ethnicity White/Non-White/Hispanic pT stage pT1/pT2 Institution LAPS/NCOPR/Other Age (mean) BMI Sem 428 (60.6%)Non-sem 278 (39.4%) 79.2%/20.8%/16.1% 446 (63.2%)/ 250 (35.4%) 18%/38%/42% 36.2 Underwt. 1.1%Normal 30.4%Over Wt. 36.0%Obese 32.1% Planned Management Active surveillance Chemo Radiation Surgery Yes 616 (87.3%) BEP X1 41 (5.8%)Carbo X1 19 (2.7%)Carbo X2 6 (0.8%) Yes 2 (0.3%) Yes 18 (2.5%) Sem= seminoma; Non-sem= nonseminoma; BMI= body mass index; BEP= Bleomycin, Etoposide, Cisplatin; Carbo= Carboplatin.

Postsurgical immunotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) remains elusive. This study assesses the value and significance of postoperative immunotherapy in the treatment of locally advanced HNSCC. In total, 212 patients with locally advanced HNSCC who underwent radical surgery were stratified into three treatment groups: adjuvant radiotherapy alone, adjuvant chemoradiotherapy (CRT), and adjuvant chemoradiotherapy plus immunotherapy (PD-1 Ab). A comprehensive analysis was conducted to assess survival outcomes and prognostic factors across diverse patient cohorts. Four patients were lost to follow-up, with a follow-up rate of 98.1% and a median follow-up time of 41 months (IQR 24-68). A total of 64/212 individuals died, with cancer being the cause of 62 cases and noncancer causes accounting for the remaining two deaths; 62/212 (29.2%) patients experienced relapse and/or metastasis. The 3-year OS rates for the radiotherapy group, CRT group, and CRT plus PD-1 Ab group were 54.8%, 75.4%, and 82.2%, respectively. However, no statistically significant difference in OS or PFS was observed between the CRT and CRT + PD-1 Ab groups (pall > 0.05), although both were superior to radiotherapy alone (pall < 0.05). Multivariate analysis indicated that age, smoking history, TNM stage and treatment method were independent prognostic factors for OS (pall < 0.05). Smoking history and treatment methods were independent prognostic factors for PFS and DMFS (pall < 0.05). PD-1 Ab may contribute less to tumors with better treatment outcomes from concurrent chemoradiotherapy.

Radical cystectomy is the most commonly used definitive local treatment for muscle-invasive bladder cancer (MIBC), yet it carries substantial perioperative complication risk, alongside major changes in urinary and sexual function. Chemoradiotherapy (CRT) is used as a bladder-sparing alternative but is usually reserved for small, solitary tumors. Highly active systemic induction therapy could enable bladder preservation for patients with more advanced tumors and reduce recurrence risk. We previously demonstrated high activity of preoperative ipilimumab (3 mg kg-1) plus nivolumab in patients with stage III MIBC. Given this high activity, the single-arm, multicenter phase 2 INDIBLADE trial aimed to provide effective bladder-sparing treatment to patients with stage II/III (cT2-4aN0-2, n = 50) MIBC, using induction ipilimumab (3 mg kg-1) plus nivolumab followed by CRT. After a median follow-up of 28.7 months, the primary endpoint of estimated 2-year bladder-intact event-free survival (BI-EFS) was met at 78% (95% confidence interval (CI): 0.67-0.9, P < 0.001). Secondary endpoints included overall survival, safety and the predictive value of circulating tumor DNA (ctDNA). Two-year overall survival was 96% (95% CI: 0.91-1). Grade 3-4 immune-related adverse events occurred in 24% of patients; grade 3-4 CRT-related adverse events occurred in 7% of patients. Absence of detectable ctDNA after induction immunotherapy was associated with BI-EFS (hazard ratio 8.3, 95% CI: 1.38-50.36, P = 0.02). In conclusion, our results show that induction combination immunotherapy followed by CRT is an effective bladder-sparing treatment in MIBC, and response can be monitored by ctDNA. ClinicalTrials.gov identifier: NCT05200988 .

BackgroundStatins, widely prescribed for hypercholesterolemia, have demonstrated potential anti-neoplastic properties in preclinical studies. Despite growing interest in their oncologic effects, the role of statin therapy within curative treatment of esophageal cancer remains unexplored. This study aimed to evaluate the impact of statin use on pathologic complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) in patients undergoing neoadjuvant chemo(radio)therapy followed by esophagectomy.MethodsAll consecutive patients with esophageal or gastroesophageal junction cancer who underwent esophagectomy following neoadjuvant therapy between March 1994 and September 2013 were retrospectively analyzed using a prospectively maintained database. Baseline demographic and clinical variables were compared between statin users and non-users.ResultsA total of 463 patients were included, of whom 90 (19.4%) were statin users at diagnosis. Neoadjuvant chemotherapy (CT) was administered in 88 patients (19%) and chemoradiotherapy (CRT) in 375 patients (81%). pCR (ypT0N0M0) was achieved in 85 patients (18%), with no statistically significant difference between statin users and non-users (22.2% vs. 17.4%, P=0.29). Median DFS (45 vs. 40 months, P=0.25) and OS (44 vs. 42 months, P=0.28) were also not significantly different between the two groups. However, a non-significant trend toward improved DFS was identified in patients with esophageal adenocarcinoma receiving lipophilic statin therapy.ConclusionsIn this cohort, statin use was not associated with improved pathologic response or survival outcomes following neoadjuvant therapy for esophageal cancer. These findings do not support modification or discontinuation of statin therapy in this patient population.

The survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial. This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n = 121), group 2 (3 to 12 weeks, n = 113), group 3 (15 weeks, n = 30), and group 4 (≥ 18 weeks, n = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression. Group 4 achieved the highest 5-year OS (82.1%) and DFS (66.0%) rates. Compared with groups 1 and 2, group 4 demonstrated significantly improved OS (adj. P ≤ 0.001) and improved DFS versus group 1 (HR 0.621, 95% CI 0.443-0.870, adj. P = 0.017). In the TNT cohort, group 4 was associated with significantly improved OS and DFS compared with group 2 (adj. P < 0.01), but not with group 3. Additionally, group 4 showed a significantly lower risk of LRR than group 3. In the CRT cohort, group 4 was associated with improved OS compared with group 1 (adj. P = 0.005); however, this association was not retained in surgical patients. No significant differences in DFS, DM, or LRR were observed across groups in the CRT cohort. In TNT cohort, minimum 18 weeks of chemotherapy was associated with improved OS and DFS compared to 3 to 12 weeks. The observed OS benefit of minimum 18 weeks versus no chemotherapy in the CRT cohort was not retained among surgical patients. These findings suggest caution in shortening chemotherapy duration, particularly in high-risk patients treated with TNT, and warrant confirmation in prospective TNT-specific trials. The STELLAR trial was registered at ClinicalTrials.gov (identifier: NCT02533271); however, this post hoc analysis was retrospectively conducted.

Clinical Outcomes of Cervical Cancer Patients Treated with Surgery and Concurrent Chemoradiation Therapy in CMH, Dhaka