Reirradiation With Proton Therapy for Recurrent Malignancies of the Esophagus and Gastroesophageal Junction: Results of the Proton Collaborative Group Multi-Institutional Prospective Registry Trial

Hotca, Alexandra; Sindhu, Kunal K.; Lehrer, Eric J.; Hartsell, William F.; Vargas, Carlos; Tsai, Henry K.; Chang, John H.; Apisarnthanarax, Smith; Nichols, Romaine C.; Chhabra, Arpit M.; Hasan, Shaakir; Press, Robert H.; Lazarev, Stanislav; Hajj, Carla; Kabarriti, Rafi; Rule, William G.; Simone, Charles B.; Choi, J. Isabelle

doi:10.1016/j.adro.2024.101459

Cited by 1 publication

(2 citation statements)

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“…Reirradiation with FLASH PRT after an initial scheme of Standard PRT is shown to mitigate RTinduced dermatitis, fibrosis, lymphedema, and bone damage. These acute and late toxicities are observed in the clinical setting after proton reirradiation, including in the treatment of sarcomas 27 , abdominal tumors 19,[28][29][30] , head and neck tumors 15,31 , esophageal cancer 17 , breast cancer 4,32 , and lung cancer 14,33,34 .…”

Section: Discussionmentioning

confidence: 99%

“…Proton radiotherapy (RT) is also used in reirradiation because of its physical characteristics, as protons deposit most of their energy within a narrow range (Bragg peak) with little exit dose. As a result, normal tissues may be exposed to less radiation, potentially enhancing the therapeutic ratio 1,[15][16][17][18][19][20] . Notwithstanding the benefits of these highly conformal modalities in the reirradiation setting, normal tissues will still likely receive high cumulative doses of radiation, leading to significant toxicity 1,7,8,19 .…”

Section: Introductionmentioning

confidence: 99%

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FLASH proton reirradiation, with or without hypofractionation, mitigates chronic toxicity in the normal murine intestine, skin, and bone

Verginadis,

Velalopoulou,

Kim

et al. 2024

Preprint

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Background and purposeThe normal tissue sparing afforded by FLASH radiotherapy (RT) is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton RT (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated.Materials and methodsIn studies of the intestine, single-dose irradiation was performed with 12 Gy of Standard proton RT (S-PRT), followed by a second dose of 12 Gy of F-PRT or S-PRT. Additionally, a hypofractionation scheme was applied in the reirradiation setting (3 x 6.4 Gy of F-PRT or S-PRT, given every 48 hrs). In studies of skin/bone of the murine leg, 15 Gy of S-PRT was followed by hypofractionated reirradiation with F-PRT or S-PRT (3 x 11 Gy).ResultsCompared to reirradiation with S-PRT, F-PRT reduced intestinal fibrosis and collagen deposition in the reirradiation setting and significantly increased survival rate, demonstrating its protective effects on intestinal tissues. In previously irradiated leg tissues, reirradiation with hypofractionated F-PRT created transient dermatitis that fully resolved in contrast to reirradiation with hypofractionated S-PRT. Lymphedema was also alleviated after a second course of radiation with F-PRT, along with significant reductions in the accumulation of fibrous connective tissue in the skin compared to mice reirradiated with S-PRT. The delivery of a second course of fractionated S-PRT induced tibial fractures in 83.3% of the mice, whereas only 20% of mice reirradiated with F-PRT presented with fractures.ConclusionThese studies provide the first evidence of the sparing effects of F-PRT, in the setting of hypofractionated reirradiation. The results support FLASH as highly relevant to the reirradiation regimen where it exhibits significant potential to minimize chronic complications for patients undergoing RT.

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