Re-irradiation is an increasingly utilized treatment for recurrent, metastatic or new malignancies after previous radiotherapy. It is unclear how re-irradiation is applied in clinical practice. We aimed to investigate the patterns of care of re-irradiation internationally. A cross-sectional survey conducted between March and September 2022. The survey was structured into six sections, each corresponding to a specific anatomical region. Participants were instructed to complete the sections of their clinical expertise. A total of 15 multiple-choice questions were included in each section, addressing various aspects of the re-irradiation process. The online survey targeted radiation and clinical oncologists and was endorsed by the European Society for Radiotherapy and Oncology (ESTRO) and the European Organisation for Research and Treatment of Cancer (EORTC). 371 physicians from 55 countries across six continents participated. Participants had a median professional experience of 16 years, and the majority (60%) were affiliated with an academic hospital. The brain region was the most common site for re-irradiation (77%), followed by the pelvis (65%) and head and neck (63%). Prolonging local control was the most common goal (90-96% across anatomical regions). The most common minimum interval between previous radiotherapy and re-irradiation was 6-12 months (45-55%). Persistent grade 3 or greater radiation-induced toxicity (77-80%) was the leading contraindication. Variability in organs at risk dose constraints for re-irradiation was observed. Advanced imaging modalities and conformal radiotherapy techniques were predominantly used. A scarcity of institutional guidelines for re-irradiation was reported (16-19%). Participants from European centers more frequently applied thoracic and abdominal re-irradiation. Indications did not differ between academic and non-academic hospitals. This study highlights the heterogeneity in re-irradiation practices across anatomical regions and emphasizes the need for high-quality evidence from prospective studies to guide treatment decisions and derive safe cumulative dose constraints.

Reirradiation (reRT), defined as administering a course of radiation therapy to a specific area previously irradiated, is an evolving treatment strategy for locoregionally recurrent cancer that offers significant potential and poses inherent challenges. Advances in such techniques as intensity‐modulated and stereotactic body radiation therapy have improved precision, making reRT a viable option for complex scenarios previously deemed high‐risk. Nevertheless, reRT remains associated with substantial risks—including life‐threatening side effects, functional impairments, and psychosocial effects—which must be carefully balanced against the patient's overall health and the likelihood of achieving cancer control or palliation. Patient selection is essential to optimize outcomes while mitigating risks. Decisions should account for tumor characteristics at the time of primary diagnosis and recurrence, elapsed time since prior treatment, the possibility of delivering meaningful doses to the tumor, and the cumulative irradiation tolerance of normal tissues. Advanced imaging modalities, such as functional magnetic resonance imaging and fluorine‐18–labeled fluorodeoxyglucose–positron emission tomography, are important for distinguishing recurrences from treatment‐induced changes, refining treatment targets, and minimizing exposure to healthy tissue. Combined treatment with systemic regimens—targeted therapies and immunotherapy in particular—offers promising opportunities but requires coordination to manage side effects. Standardized guidelines, such as those from the European Society of Therapeutic Radiology and Oncology‐European Society for Research and Treatment of Cancer, are essential for improving the consistency of reporting, guiding clinical decision making, and fostering patient‐centered care. Multidisciplinary collaboration and ongoing research, particularly through clinical trials, are central to fully exploiting reRT strategies. In addition, the development of innovative techniques, such as proton therapy, would likely enable safer treatments. These efforts aim to improve the therapeutic balance of reRT, enhancing outcomes and quality of life.

Reirradiation has gained increasing interest, as advances in systemic therapy increase the survival of patients with cancer, and modern radiation techniques allow more precise treatments. However, high-quality prospective evidence on the safety and efficacy of reirradiation to guide clinical practice remains scarce. This systematic review evaluates ongoing prospective studies on reirradiation to identify research gaps and priorities. A systematic review of ClinicalTrials.gov was conducted on July 11, 2024, using search terms related to reirradiation. Inclusion criteria were prospective studies that were "recruiting," "not yet recruiting," or "active, not recruiting." Studies with published results, retrospective, and in-silico studies were excluded. The review followed PRISMA 2020 guidelines and recommendations for systematic searches of clinical trial registries. Among 1026 identified studies, 307 were screened, 99 were included. Fourty (40%) focused on central nervous system (CNS), 23 (23%) head and neck, and 17 (17%) on pelvic reirradiation. Most studies (90%) were interventional, with 32 (32%) phase II and 4 (4%) phase III trials. Sixteen trials were randomized (RCTs), including the 4 phase III trials for recurrent glioblastoma, rectal and nasopharyngeal cancer. Ten dose escalation trials focus on recurrent prostate, rectal, and non-small cell lung cancer as well as glioma. Modern high-precision radiotherapy techniques were frequently used, with 21 (21%) studies using stereotactic radiotherapy and 17 (17%) using particle therapy. Combinations with systemic therapies were investigated in 41 (41%) studies. Ongoing studies most frequently focus on CNS, head and neck, and pelvic reirradiation. There remains a critical need for RCTs, in particular for lung, breast, and gynecological cancers. Dose escalation trials, application of precision radiation techniques and combinations with modern systemic therapy may help define the optimal multimodality treatment schedules.

Our purpose was to assess the suitability of airway-implanted internal fiducial markers and an external surrogate of respiratory motion for motion management during radiation therapy of lung tumors. We analyzed 4-dimensional computed tomography scans acquired during radiation therapy simulation for 28 patients with lung tumors who had anchored fiducial markers bronchoscopically implanted inside small airways in or near the tumor in a prospective trial. We used a linear mixed model to build population-based correlative models of tumor and surrogate motion. The first 24 of the 28 patients were used to build correlative models, and 4 of the 28 consecutive patients were excluded and used as an internal validation cohort. Of the 24 patients from the model building cohort, all were used for the models based on the internal fiducial. The external surrogate was completely visualized in 11 patients from the model building cohort, so only those were used for the models based on the external surrogate. Furthermore, we determined the predicted residual error sum of squares for our correlative models, which may serve as benchmarks for future research. The motion of the internal fiducials was significantly associated with the tumor motion in the anterior-posterior (P < .0001) and superior-inferior (SI) directions (P < .0001). We also observed a strong correlation of the external surrogate anterior-posterior motion to the tumor dominant SI motion (P < .0001). In the validation cohort, the internal fiducial SI motion was the only reliable predictor of lung tumor motion. The internal fiducials appear to be more reliable predictors of lung tumor motion than the external surrogate. The suitability of such airway-implanted internal fiducial markers for advanced motion management techniques should be further investigated. Although the external surrogate seems to be less reliable, its wide availability and noninvasive application support its clinical utility, albeit the greater uncertainty will need to be compensated for.