Sergi Benavente

AimTo evaluate real-world local control outcomes and identify clinical and dosimetric determinants of local progression following metastasis-directed stereotactic ablative radiotherapy (SABR) within the international OligoCare cohort.MethodsOligoCare is a prospective observational registry (EORTC-ESTRO E2-RADIatE) evaluating SABR for oligometastatic prostate, breast, colorectal, and non-small cell lung cancer (NSCLC). The secondary endpoint, local progression, was defined as recurrence within the planning target volume (PTV), with death treated as a competing risk. Multivariate analyses were performed at both the patient and lesions levels (restricted to single-lesion patients) to account for confounding factors.ResultsBetween July 2019 and July 2025, 2,805 eligible patients were enrolled. Of these, 2,447 from 57 institutions received the recommended protocol treatment and were included in the analysis (median follow-up 31 months). The distribution of primary tumors was prostate (41.7%), NSCLC (21.7%), colorectal (21.2%), and breast (15.4%).The 1- and 3-year local progression rates were 5.0% and 11.4%, respectively. Among single-lesion patients (n=1,714), a higher PTV minimum dose was the sole independent predictor of local control, with an 11% risk reduction per 10 Gy EQD2 increase (HR 0.89 [97.5% CI 0.82-0.98], p=0.005). Although de novo OMD showed better local control compared to repeat OMD in the patient-level analysis (HR 0.65 [97.5% CI 0.47-0.91], p=0.004), this effect was largely driven by higher dose delivery in de novo cases. Colorectal primaries faced a significantly higher risk of progression than prostate cancer (HR 2.63 [97.5% CI 1.71-4.05], p<0.001), despite receiving the highest dose per fraction.ConclusionSABR provides durable real-world local control in oligometastatic disease. Optimizing the minimum PTV dose appears the most critical technical factor for success. The inferior local control observed in colorectal metastases suggests a combination of treatment intensity challenges and intrinsic radioresistance, which could guide future trial design and dose-escalation strategies.

Current guidelines for elective nodal irradiation in oropharyngeal squamous cell carcinoma (OPSCC) recommend including large portions of the contralateral lymph system in the clinical target volume (CTV-N), even for lateralized tumors with no clinical lymph node involvement in the contralateral neck. This study introduces a probabilistic model of bilateral lymphatic tumor progression in OPSCC to estimate personalized risks of occult disease in specific lymph node levels (LNLs) based on clinical involvement, T-stage, and tumor lateralization. Building on a previously developed hidden Markov model for ipsilateral spread, we extend the approach to the contralateral neck. The model represents LNLs I, II, III, IV, V, and VII on both sides of the neck as binary hidden variables (healthy/involved), connected via arcs representing spread probabilities. These probabilities are learned using Markov chain Monte Carlo (MCMC) sampling from a dataset of 833 OPSCC patients, enabling the model to reflect the underlying lymphatic progression dynamics. The model accurately and precisely describes observed patterns of involvement with a compact set of interpretable parameters. Midline extension of the primary tumor is identified as the primary risk factor for contralateral involvement, with advanced T-stage and extensive ipsilateral involvement further increasing risk. Occult disease in contralateral LNL III is highly unlikely if upstream LNL II is clinically negative, and in contralateral LNL IV, occult disease is exceedingly rare without LNL III involvement. For lateralized tumors not crossing the midline, the model suggests the contralateral neck may safely be excluded from the CTV-N. For tumors extending across the midline but with a clinically negative contralateral neck, the CTV-N could be limited to LNL II, reducing unnecessary exposure of normal tissue while maintaining regional tumor control.

Purpose The increasing complexity of radiation treatments can hinder its clinical success. This study aimed to better understand evolving risks by re-evaluating a Failure Mode and Effects Analysis (FMEA) in lung SBRT. Methods An experienced multidisciplinary team conducted an FMEA and made a reassessment 3 years later. A process map was developed with potential failure modes (FMs) identified. High-risk FMs and their possible causes and corrective actions were determined. The initial FMEA analysis was compared to gain a deeper perspective. Results We identified 232 FMs. The high-risk processes were plan approval, target contouring, and patient evaluation. The corrective measures were based on stricter standardization of plan approval, pre-planning peer review, and a supporting pretreatment checklist, which substantially reduced the risk priority number in the revised FMEA. In the FMEA reassessment, we observed that the increased complexity and number of patients receiving lung SBRT conditioned a more substantial presence of human factors and communication errors as causal conditions and a potential wrong dose as a final effect. Conclusions Conducting a lung SBRT FMEA analysis has identified high-risk conditions that have been effectively mitigated in an FMEA reanalysis. Plan approval has shown to be a weak link in the process. The increasing complexity of treatments and patient numbers have shifted causal factors toward human failure and communication errors. The potential of a wrong dose as a final effect augments in this scenario. We propose that digital and artificial intelligence options are needed to mitigate potential errors in high-complexity and high-risk RT scenarios.

Despite intensive efforts and refined techniques, overall survival in HPV-negative head and neck cancer remains poor. Robust immune priming is required to elicit a strong and durable antitumor immune response in immunologically cold and excluded tumors like HPV-negative head and neck cancer. This review highlights how the tumor microenvironment could be affected by different immune and stromal cell types, weighs the need to integrate metabolic regulation of the tumor microenvironment into cancer treatment strategies and summarizes the emerging clinical applicability of personalized immunotherapeutic strategies in HPV-negative head and neck cancer.

To identify the novel genes involved in chemoresistance in head and neck squamous cell carcinoma (HNSCC), we explored the expression profiles of the following cisplatin (CDDP) resistant (R) versus parental (sensitive) cell lines by RNA-sequencing (RNA-seq): JHU029, HTB-43 and CCL-138. Using the parental condition as a control, 30 upregulated and 85 downregulated genes were identified for JHU029-R cells; 263 upregulated and 392 downregulated genes for HTB-43-R cells, and 154 upregulated and 68 downregulated genes for CCL-138-R cells. Moreover, we crossed-checked the RNA-seq results with the proteomic profiles of HTB-43-R (versus HTB-43) and CCL-138-R (versus CCL-138) cell lines. For the HTB-43-R cells, 21 upregulated and 72 downregulated targets overlapped between the proteomic and transcriptomic data; whereas in CCL-138-R cells, four upregulated and three downregulated targets matched. Following an extensive literature search, six genes from the RNA-seq (CLDN1, MAGEB2, CD24, CEACAM6, IL1B and ISG15) and six genes from the RNA-seq and proteomics crossover (AKR1C3, TNFAIP2, RAB7A, LGALS3BP, PSCA and SSRP1) were selected to be studied by qRT-PCR in 11 HNSCC patients: six resistant and five sensitive to conventional therapy. Interestingly, the high MAGEB2 expression was associated with resistant tumours and is revealed as a novel target to sensitise resistant cells to therapy in HNSCC patients.