Considerations for shoot-through FLASH proton therapy

Purpose. To discuss several pertinent issues related to shoot-through FLASH proton therapy based on an illustrative case. Methods. We argue that with the advent of FLASH proton radiotherapy and due to the issues associated with conventional proton radiotherapy regarding the uncertainties of positioning of the Bragg peaks, the difficulties of in vivo verification of the dose distribution, the use of treatment margins and the uncertainties surrounding linear energy transfer (LET) and relative biological effectiveness (RBE), a special mode of shoot-through FLASH proton radiotherapy should be investigated. In shoot-through FLASH, the proton beams have sufficient energy to reach the distal exit side of the patient. Due to the FLASH sparing effect of normal tissues at both the proximal and distal side of tumors, radiotherapy plans can be developed that meet current planning constraints and issues regarding RBE can be avoided. Results. A preliminary proton plan for a neurological tumor in close proximity to various organs at risk (OAR) with strict dose constraints was studied. A plan with four beams mostly met the constraints for the OAR, using a treatment planning system that was not optimized for this novel treatment modality. When new treatment planning algorithms would be developed for shoot-through FLASH, constraints would be easier to meet. The shoot-through FLASH plan led to a significant effective dose reduction in large parts of the healthy tissue. The plan had no uncertainties associated to Bragg peak positioning, needed in principle no large proximal or distal margins and LET increases near the Bragg peak became irrelevant. Conclusion. Shoot-through FLASH proton radiotherapy may be an interesting treatment modality to explore further. It would remove some of the current sources of uncertainty in proton radiotherapy. An additional advantage could be that portal dosimetry may be possible with beams penetrating the patient and impinging on a distally placed imaging detector, potentially leading to a practical treatment verification method. With current proton accelerator technology, trials could be conducted for neurological, head&neck and thoracic cancers. For abdominal and pelvic cancer a higher proton energy would be required