Radiotherapy (RT) has always been a mainstay for malignant tumors therapy, but it is also used for benign pathology. The application of low or intermediate doses of RT has been widely studied. This topic was presented and discussed in the last XX GOCO (Grup Oncològic Català-Occità) meeting. The aim of this article is to review the indications of low dose irradiation (LD-RT), total dose and different fractionations, the public to whom it can be directed, and to offer an analysis about secondary effects. We believe it can be useful not only for radiation oncologists, but for other physicians to consider this option for future patients.

Introduction: Radiotherapy is one of the standard treatments for brain metastases (BM). Over the past years, the introduction of immunotherapy as routine treatment for solid tumors has forced investigators to review and evaluate how it would interact with radiation. Radiation and Immunotherapy have shown a synergic effect activating the host’s immune system and enhancing treatment response. The combinatory effect on BM is currently under investigation.Methods: Data published on Pubmed to determine toxicity, survival, treatment characteristics and timing on the combination of radiotherapy and immunotherapy for the treatment of BM has been reviewed.Results: Mostly retrospective reviews report an improvement of intracranial progression free survival (iPFS) when combining radioimmunotherapy for BM patients. Two systematic reviews and meta-analysis and one phase II prospective trial also report a benefit on iPFS without an increase of toxicity. Among the published literature, the definition of concurrency is heterogeneous, being one month or even narrowed intervals correlated to better clinical outcomes. Toxicity due to concurrent radioimmunotherapy, specifically symptomatic radionecrosis, is also directly analyzed and reported to be low, similar to the toxicity rates secondary to stereotactic radiosurgery alone.Conclusion: Radiation combined with immunotherapy has shown in predominantly retrospective reviews a synergic effect on the treatment of BM. The concurrent combination of radioimmunotherapy is a feasible therapeutic strategy and seems to improve clinical outcomes, especially iPFS, when delivered within <30 days. Larger prospective and randomized studies are needed to establish reliable outcomes, best delivery strategies and toxicity profile.

Finding the perfect strategy to treat melanoma brain metastases (BMs) has become a real-world challenge. Despite the difference in response and survival from different primary tumors, multiple guidelines recommend a multidisciplinary approach to treating BM. Although these guidelines are not specific for melanoma BM, most subjects included in the studies on which the guidelines are based are patients with melanoma. One of the strategies for the treatment of melanoma BM that arouses the most interest is the concurrent use of stereotactic radiosurgery and immunotherapy. This strategy seems to be feasible and has shown to improve survival and local control in retrospective series and phase 1 and 2 prospective trials. Here, we present a review of the current recommendations for addressing melanoma BM and the evidence available about the strategy combining focal radiation and immune checkpoint inhibitors.

Background: Concurrent chemoradiotherapy (cCRT) followed by 1 year of consolidation durvalumab remains the standard of care for unresectable stage III non-small cell lung cancer (NSCLC), yet long-term survival is still limited and around 20% of patients present locoregional relapse. Hypofractionation may improve the therapeutic ratio by increasing the biologically effective dose (BED), shortening overall treatment time (OTT) and potentially mitigating radiation-induced lymphopenia. Objective: To identify which patients with unresectable stage II–III NSCLC may benefit most from radical-intent hypofractionated radiotherapy (HypoRT), with or without systemic therapy, and to define the technical aspects, contouring margins, and dosimetric requirements necessary for the safe use of hypofractionated schedule. Methods: A systematic search of PubMed, EMBASE, CENTRAL and Web of Science (January 2010–January 2024, English language) was performed following PRISMA principles. Eligible studies included unresectable NSCLC treated with a BED10 > 40 Gy, allowing induction systemic or targeted therapy; reviews were included for context. Records were screened by six independent reviewers. Studies were classified as non-photon vs. photon, and photon studies were further divided into non-concurrent and concurrent strategies. Clinical outcomes (dose, fractionation, biologically effective Dose for alpha/beta:10 (BED10), equivalent dose of 2 Gy/fraction (EQD2), overall treatment time (OTT), follow-up (FU), median progression-free survival (mPFS), median Overall Survival (mOS), local control (LC), grade ≥ 3 toxicity (G3) and technical variables (immobilization, simulation, GTV imaging, CTV/PTV margins, delivery, image-guided radiotherapy (IGRT), organ at risk (OAR) constraints) were extracted. Results: Of 340 records (170 duplicates), 26 studies including stage II–III disease were analyzed (1155 patients): 1 prospective cohort, 5 phase I, 12 phase II, 1 phase III and 2 phase I/II dose-escalation trials, 2 carbon-ion and 3 proton series. Of these, 13 were photon-based studies with contemporary simulation techniques. Two clinically distinct scenarios emerged. Group A (non-concurrent platinum-based strategies; 166 patients with modern 4DCT simulation) showed wide variability, ranging from a simultaneous-integrated-boost regimen to 75 Gy with 0% grade ≥ 3 toxicity and mPFS 40 months to a chemotherapy-driven schedule with 70% grade 4 chemo-related toxicity. Only one phase III trial was identified, reporting a 2-year local control of 85.8%. Group B (concurrent strategies; nine of the 14 platinum-based studies retrieved, namely those using modern simulation techniques) achieved a median BED of 89.7 Gy to the highest dose-volume, median of OS 20 months and toxicity GIII ≥ ranging 10–20%, with a median study-level grade 5 toxicity of 5.5% (range 0–17.8%; 34 fatal events among 431 evaluable patients, 7.9%), rising to 20.8% (11/53) in the most escalated randomized arm and 22.2% (2/9) in the highest dose-escalation cohort; adaptive SABR boost to 70 Gy/15 fr delivered high local control but clinically meaningful fatal toxicity. Fatal toxicity was confined to schedules exceeding BED10 100 Gy delivered to the whole tumor volume with concurrent platinum, whereas an equivalent BED restricted to a metabolically defined subvolume without concurrent chemotherapy produced no grade ≥3 events. Conclusions: Radical-intent hypofractionation is feasible across both unfit and fit unresectable stage II–III NSCLC populations, but the randomized evidence remains scarce and heterogeneous. Benefit appears most consistent when high BED is delivered with strict normal-tissue sparing in carefully selected patients using modern 4DCT-based simulation, IGRT and intensity-modulated delivery. The pattern of fatal toxicity with aggressive concurrent systemic treatments and dose escalation schedules argues for caution and for prospective trials with harmonized minimum technical standards.