Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current evidence on COVID-19 vaccination in patients undergoing radiotherapy (RT). Methods: PubMed, Livivo, Scopus, and Cochrane Library were systematically reviewed for relevant publications on COVID-19 vaccination in the context of radiation oncology, published by 19 April 2024. The treatment effects were calculated as the proportion of seroconverted individuals. Results: A total of 22 studies published between 2021 and 2024 were included, covering various aspects of vaccination, including safety, tolerability, qualitative and quantitative humoral responses, cellular responses, vaccination efficacy, and booster vaccinations. Notably, patients undergoing RT exhibited a high willingness to receive vaccination. Vaccination was overall well tolerated and safe, with a low incidence of side effects, which were primarily mild. The primary meta-analysis showed a seroconversion proportion of 91% [95% CI: 84–96%] overall, with a somewhat higher proportion of 93% in patients receiving RT alone, compared to 90% in patients receiving either RT or RT combined with chemotherapy. Furthermore, immunization during RT led to a sustained increase in antibody titers, with a notable long-term persistence of IgG. Conclusions: COVID-19 vaccines demonstrate excellent safety, immunogenicity, and efficacy in patients receiving RT, who also exhibit a high willingness to be vaccinated. The outcomes observed are comparable to those in healthy controls and superior to those seen in patients receiving other cancer treatments, such as chemotherapy. The vaccination of radiation oncology patients in future pandemics or epidemics is strongly advocated even during active treatment.

Advances in radiotherapy (RT) techniques have facilitated the increasing use of hypofractionated treatment schedules, which may be particularly advantageous for elderly patients by reducing treatment burden while maintaining acceptable toxicity. This study aimed to evaluate survival and symptom palliation and to investigate whether different fractionation approaches affected toxicity and clinical outcomes in nonagenarian patients. This single-center retrospective cohort included 199 nonagenarians treated with RT between 2005 and 2023. Fractionation was classified as normofractionated (NF-RT), hypofractionated (HF-RT: >2Gy) and ultra-hypofractionated (UHF-RT: ≥5Gy). Outcomes were symptom control, acute ≥ Grade 2 (G2) toxicity, and overall survival (OS). Median age at RT was 92 years (range 90-101); 42% received curative and 58% palliative RT. Median OS of all patients was 11 months (palliative treatment: 7 months), with 1- and 5-year OS rates of 47% and 11% respectively. Overall, symptom improvement was documented in 73% of patients, with particularly high frequencies of improvement in tumor-related bleeding (95%) and ulceration (80%), pain improved in 65%. Acute ≥ G2 toxicity occurred in 21% (G3, 5%). Generally, UHF-RT and HF-RT had lower odds of ≥ G2 toxicity than NF-RT, however they were treated with lower doses (EQD2) to smaller target volumes. After adjustment for confounding factors, the hazards for all-cause death were only slightly higher for HF-RT and UHF-RT compared to NF-RT. Oligometastatic patients had almost identical survival as those without metastases, patients with breast cancer had a better survival than those with other entities. RT in selected nonagenarians achieved high frequencies of palliation with low severe toxicity. Hypofractionation was well tolerated without clear impact on survival.