Gabriel Adrian (Sweden)

Lund University Clinical Sciences Lund, Division of Oncology & Pathology
I am a clinical oncologist with interest in translational radiobiology, including the use of ultrahigh dose rate irradiations.

Author Of 2 Presentations

FLASH SPARING OF MELANOMA CELLS IN VITRO AND IN VIVO

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Room 2.15
Lecture Time
10:40 - 10:50

Abstract

Background and Aims

We have previously found that FLASH-irradiation with a pulsed electron beam (average doserate ≥600Gy/s) was less efficient to sterilize cancer cells in-vitro compared with conventional doserate irradiation (CONV, 0.2Gy/s). In the current work we aimed at investigating the effect for a malignant cell line both in vitro and in vivo.

Methods

Radiation response of melanoma cell line B16_F10 was determined in-vitro by clonogenic assays for an absorbed dose in the range 0-9 Gy comparing FLASH to CONV. In-vivo-response was studied in a syngeneic mice model (C57BL/6J) with subcutaneously injected B16_F10-tumors, irradiated to an absorbed dose of 15, 20 or 25Gy (FLASH and CONV). The tumor growth was quantified by using the relative tumor volume, normalized to unity at the time of irradiation, TVrel.

Results

The in-vitro results showed a significantly increased survival after FLASH compared with CONV (F-test: p=0.02). Tumor growth curves in-vivo were similar for CONV and FLASH at 15 and 20Gy, but FLASH was relatively less efficient at 25Gy. Four weeks after irradiation with 25Gy, a relative tumor volume of TVrel<1 was seen in 2/9 mice in the CONV group but in 0/8 mice in the FLASH group. A relative tumor volume of TVrel<4 was seen in 5/9 mice in the CONV group but 0/8 mice in the FLASH group. Severe skin toxicity was observed in 5/9 vs 0/8.

Conclusions

FLASH may be less efficient than CONV to sterilize malignant cells in-vitro as well as in-vivo. Future work will address the differential response between normal tissue and tumors at higher doses.

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HYPOFRACTIONATED FLASH RADIOTHERAPY VERSUS CONVENTIONAL RADIOTHERAPY IN AN IMMUNOCOMPETENT RAT GLIOMA MODEL

Session Type
FLASH in the Clinic Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
14:50 - 15:50
Room
Room 2.31
Lecture Time
15:20 - 15:30

Abstract

Background and Aims

For a clinical translation of FLASH radiotherapy, evidence of an enhanced therapeutic index within the same biological system is needed. In this study we aim to simultaneously investigate the tumor response (TCP) and skin toxicity (NTCP) of hypofractionated FLASH compared to conventional radiotherapy (CONV) in a fully immunocompetent rat glioma model.

Methods

Fisher 344 rats with subcutaneously inoculated NS1 glioma cells were treated with FLASH (450-550 Gy/s) or CONV in three fractions of either 8 Gy, 12.5 Gy or 15 Gy (n=9-10) using a 10 MeV electron beam. Animals were followed for 100 days. The tumor control probability was determined as the ratio of animals with no tumor progression at the end of the study period. Local dermal side effects were evaluated weekly.

Results

There was a statistically significant difference in overall survival between controls and all treatment groups, but no significant difference between FLASH and CONV for any of the dose levels (log-rank test). The tumor control probability for 3x8 Gy, 3x12.5 Gy and 3x15 Gy, respectively, were 3/9, 5/10 and 9/10 for CONV and 3/10, 5/9 and 9/10 for FLASH. Local dermal side effects were generally mild, consisting of hair loss, erythema, and dry desquamation. The ratio of animals with erythema or more severe effects during the study period was 78%/60%/90% for CONV and 50%/78%/70% for FLASH.

Conclusions

In this study we demonstrate that hypofractionated FLASH is equally effective as CONV in terms of controlling glioma in rats. No difference in acute effects could be resolved. Late effects will be histologically evaluated.

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Presenter of 1 Presentation

FLASH SPARING OF MELANOMA CELLS IN VITRO AND IN VIVO

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Room 2.15
Lecture Time
10:40 - 10:50

Abstract

Background and Aims

We have previously found that FLASH-irradiation with a pulsed electron beam (average doserate ≥600Gy/s) was less efficient to sterilize cancer cells in-vitro compared with conventional doserate irradiation (CONV, 0.2Gy/s). In the current work we aimed at investigating the effect for a malignant cell line both in vitro and in vivo.

Methods

Radiation response of melanoma cell line B16_F10 was determined in-vitro by clonogenic assays for an absorbed dose in the range 0-9 Gy comparing FLASH to CONV. In-vivo-response was studied in a syngeneic mice model (C57BL/6J) with subcutaneously injected B16_F10-tumors, irradiated to an absorbed dose of 15, 20 or 25Gy (FLASH and CONV). The tumor growth was quantified by using the relative tumor volume, normalized to unity at the time of irradiation, TVrel.

Results

The in-vitro results showed a significantly increased survival after FLASH compared with CONV (F-test: p=0.02). Tumor growth curves in-vivo were similar for CONV and FLASH at 15 and 20Gy, but FLASH was relatively less efficient at 25Gy. Four weeks after irradiation with 25Gy, a relative tumor volume of TVrel<1 was seen in 2/9 mice in the CONV group but in 0/8 mice in the FLASH group. A relative tumor volume of TVrel<4 was seen in 5/9 mice in the CONV group but 0/8 mice in the FLASH group. Severe skin toxicity was observed in 5/9 vs 0/8.

Conclusions

FLASH may be less efficient than CONV to sterilize malignant cells in-vitro as well as in-vivo. Future work will address the differential response between normal tissue and tumors at higher doses.

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