Reirradiation presents a significant challenge despite recent advances in modern radiation therapy. Carbon ion radiotherapy has garnered increasing attention among radiation oncologists due to its potentially superior physical dosimetric distribution and radiobiological advantages. This systematic review comprehensively evaluated clinical outcomes from 27 original studies on the use of carbon ion reirradiation for locoregional recurrent malignancies, including those affecting the central nervous system, lung, head and neck, pancreas, liver, rectum, and gynecological sites. The findings suggest that carbon ion reirradiation for locoregional recurrent malignancies yields favorable clinical outcomes with a relatively low incidence of high-grade toxicities. For recurrent nasopharyngeal carcinoma, the reported 2-year overall survival, local control, regional control, and metastasis-free survival rates were 83.7%, 58.0%, 87.3%, and 94.7%, respectively. Grade ≥3 late nasopharyngeal necrosis occurred in 16% (33/206) of cases. In the case of recurrent glioblastoma, median overall survival and local control survival were reported at 13 and 7 months, respectively, with minimal high-grade complications
observed low-grade toxicities included acute involuntary movements, incomplete hemiparesis, and late-onset dysphasia. For recurrent lung cancer, 2-year local control and overall survival rates were reported as 54.0% and 61.9%, respectively. Grade ≥3 toxicities included two cases of radiation pneumonitis and one case of bronchopleural fistula. In recurrent pancreatic cancer, 1-year local control, progression-free survival, and overall survival rates were 53.5%, 24.5%, and 48.7%, respectively. A high-grade complication of Grade 3 acute duodenal stenosis was observed in one patient. Additionally, concurrent chemotherapy with carbon ion reirradiation was associated with minimal high-grade additive toxicities. Overall, carbon ion reirradiation appears to be a potentially safe and effective reirradiation modality for treating locoregional recurrent malignancies, though data remains limited.