In a consecutive study of patients with grade III astrocytoma, glioblastoma or oligodendroglioma (according to previous WHO classification system), corticosteroids and radiotherapy (mean dose 59 Gy during 43 days) led to severe immunosuppression 10. However, delivery of radiotherapy with many fractions decreases lymphocyte count in circulating blood 9. Regarding experimental glioblastoma, delayed growth could be demonstrated in nude mice with xenotransplanted tumors with sparing of cognitive side effects after FLASH versus CONV-RT with some but not all of the irradiation protocols analyzed 5.Īccording to previous research by our research group 7 and others 8, radiotherapy delivered at optimal doses and fractions can induce an effective immune response, which seems to function in synergy with immunotherapy, also in the intracerebral setting. However, demonstrating that equal anti-tumor effects are actually achieved, has not been fully analyzed 3, and even less so in fully immunocompetent preclinical models 5, 6. Hopefully, FLASH radiotherapy could constitute a possible way of achieving equivalent anti-tumor effects, but with reduction of normal tissue damage 5. There is some evidence supporting that severe toxicities could be reduced with FLASH compared to CONV-RT 4, whereas there is less evidence supporting a maintained anti-tumor effect 3, 4. With FLASH radiotherapy, irradiation is delivered at an ultra-high dose rate, compared to conventional radiotherapy (CONV-RT) 3. A limiting factor concerning radiotherapy is the side effects, not least neuro-cognitive decline, in the setting of intracranial tumors. Radiotherapy is one of the cornerstones in oncological treatment of glioblastoma 1. According to guidelines it is recommended that patients with recurrent or progressing glioblastomas are included in clinical studies, but also adult patients with newly diagnosed glioblastomas should be considered 1. The majority of the patients would not even meet the inclusion criteria of recent clinical phase III trials 2. There are few effective treatment options for patients with glioblastoma, and the survival is poor, with median survival only around 12–15 months in well selected patients included in clinical trials with conventional therapy 1. Radiotherapy was highly efficient in the subcutaneous setting, leading to cure and long-term immunity in the majority of the animals. CONV-RT and FLASH were equally effective in fully immunocompetent animals with glioblastoma. Animals with intracranial tumors survived longer when treated with FLASH or CONV-RT at 12.5 Gy × 2, but cure was not reached. TIMP-1 in serum was reduced in animals treated with FLASH 8 Gy × 2 compared to control animals. Cured animals could reject tumor re-challenge. The majority of animals with subcutaneous tumors were cured when treated with FLASH or CONV-RT at 8 Gy × 2. Serum analytes and gene expression were explored. Cured animals were re-challenged in order to explore long-term anti-tumor immunity. Radiotherapy was delivered with FLASH or CONV-RT at 8 Gy × 2 (subcutaneous tumors) and 12.5 Gy × 2 (intracranial tumors). Fully immunocompetent Fischer 344 rats were inoculated with NS1 glioblastoma cells subcutaneously or intracranially. The efficacy of FLASH in relation to conventional radiotherapy (CONV-RT) has not been extensively explored in fully immunocompetent animals. Using FLASH radiotherapy, side effects could possibly be reduced. One limiting factor is side effects on normal tissue. Radiotherapy can induce an immunological response.
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