Session Item

High grade glioma is the most common primary malignant brain tumor, and despite aggressive treatment, the tumor is highly resistant. The delivery of radiotherapy might be adjusted, in order to increase anti-tumor immune mediated effects. Our hypothesis is that increased dose/fraction and a small amount of fractions might result in a better immunological anti-tumor response.  

In the present study we explored if long-lasting anti-tumor response could be achieved using conventional radiotherapy (CONV) and FLASH radiotherapy in a fully immunocompetent rat glioblastoma model. A newly developed high grade glioma tumor cell line (NS1), generating tumors with an infiltrative growth pattern and perivascular dissemination, was used.

Fisher 344 rats with subcutaneously inoculated NS1 glioma cells were treated with FLASH in two fractions of either 8 Gy or 12.5 Gy (average dose rate 530 Gy/s and 410 Gy/s respectively) or CONV in two fractions of 8 Gy (n=8/group) using a 10 MeV electron beam, day 8 and 14 after inoculation of tumor cells. Animals were followed for 100 days. Animals with no sign of tumor at the end of this observation period were re-challenged with inoculation of glioma cells on the contralateral flank. 

Survival was significantly increased in all irradiated groups as compared to controls, with no between-group differences (post hoc Bonferroni adjusted tests - CONV-RT 8 Gy x 2 versus control p=0.004; FLASH 8 Gy x 2 versus control p=0.000; FLASH 12.5 Gy x 2 p=0.000) (Figure 1).

21 animals did not exhibit any sign of tumor growth at the end of the 100-day observation period; 8 treated with FLASH at 8 Gy x 2; 7 with FLASH at 12.5 Gy x 2 and 6 with CONV-RT at 8 Gy x 2. The cured animals were inoculated with NS1 cells on their contralateral flank in a re-challenge experiment. Another 10 animals were de novo inoculated control animals, not previously included in the study. All de novo inoculated control animals developed tumors. In the previously cured animals, however, no tumor growth could be detected during a 100-day observation period. 

Figure 1.  Survival during the 100-day observation period, with significant survival benefit in all groups compared to control animals. 

Both conventional radiotherapy and FLASH could generate long-term anti-tumor effects in fully immune competent animals with high grade glioma cells on the flank.