Does time to retreatment matter? An NTCP model to predict radionecrosis after repeat SRS for recurrent brain metastases incorporating time-dependent discounted dose

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Autores principales: Sharma, Manju, Naqa, Issam El, Sneed, Penny K
Formato: Preprint
Publicado: 2024
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author Sharma, Manju
Naqa, Issam El
Sneed, Penny K
author_facet Sharma, Manju
Naqa, Issam El
Sneed, Penny K
contents Purpose: To develop and compare normal tissue complication probability (NTCP) models for recurrent brain metastases (BMs) treated with repeat single-fraction stereotactic radiosurgery (SRS), considering time-dependent discounted prior dose. Methods: We developed three NTCP models of BMs treated with GammaKnife-based SRS. The maximum dose to 0.2cc (D0.2cc) of each lesion-specific brain and one-year radionecrosis was fitted using a logistic model with equivalent-dose conversions in 2 Gy (EQD2). The M0 and M1-retreat modeled radionecrosis risk following SRS to 1029 non-recurrent lesions (patients=262) and 2nd SRS to 149 recurrent lesions (patients=87). The M1-combo model accounted for 2nd SRS and time-dependent discounted 1st SRS dose for recurrent lesions estimated by a modified Gompertzian function. Results: All three models fitted the data well (Chi-2 = 0.039-0.089 and p = 0.999-1.000). The fitted EQD250 was ~103 Gy for M0, ~88 Gy for M1-retreat, and ~165 Gy for M1-combo. The fitted EQD2_50 exhibited a progressively flatter dose-response curve across the three models, with values of 1.2 Gy for M0, 0.6 Gy for M1-retreat, and 0.4 Gy for M1-combo. For the brain D0.2cc of 29Gy and 19Gy, the steepest to shallowest dose-response or largest change in NTCP, i.e., NTCP29Gy - NTCP19Gy was observed in M1-retreat (0.16), M0 (0.14) and M1-combo (0.06). Conclusions: The model-fitted parameters predict that recurrent BMs have a lower threshold dose tolerance and a more gradual dose response for the 2nd SRS than non-recurrent BMs. This gradual dose-response becomes even more apparent when considering the time-dependent discounted 1st SRS as a cumulative 2nd SRS. Tailoring SRS retreatment protocols based on NTCP modeling can potentially enhance therapeutic efficacy.
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publishDate 2024
record_format arxiv
spellingShingle Does time to retreatment matter? An NTCP model to predict radionecrosis after repeat SRS for recurrent brain metastases incorporating time-dependent discounted dose
Sharma, Manju
Naqa, Issam El
Sneed, Penny K
Medical Physics
Biological Physics
Purpose: To develop and compare normal tissue complication probability (NTCP) models for recurrent brain metastases (BMs) treated with repeat single-fraction stereotactic radiosurgery (SRS), considering time-dependent discounted prior dose. Methods: We developed three NTCP models of BMs treated with GammaKnife-based SRS. The maximum dose to 0.2cc (D0.2cc) of each lesion-specific brain and one-year radionecrosis was fitted using a logistic model with equivalent-dose conversions in 2 Gy (EQD2). The M0 and M1-retreat modeled radionecrosis risk following SRS to 1029 non-recurrent lesions (patients=262) and 2nd SRS to 149 recurrent lesions (patients=87). The M1-combo model accounted for 2nd SRS and time-dependent discounted 1st SRS dose for recurrent lesions estimated by a modified Gompertzian function. Results: All three models fitted the data well (Chi-2 = 0.039-0.089 and p = 0.999-1.000). The fitted EQD250 was ~103 Gy for M0, ~88 Gy for M1-retreat, and ~165 Gy for M1-combo. The fitted EQD2_50 exhibited a progressively flatter dose-response curve across the three models, with values of 1.2 Gy for M0, 0.6 Gy for M1-retreat, and 0.4 Gy for M1-combo. For the brain D0.2cc of 29Gy and 19Gy, the steepest to shallowest dose-response or largest change in NTCP, i.e., NTCP29Gy - NTCP19Gy was observed in M1-retreat (0.16), M0 (0.14) and M1-combo (0.06). Conclusions: The model-fitted parameters predict that recurrent BMs have a lower threshold dose tolerance and a more gradual dose response for the 2nd SRS than non-recurrent BMs. This gradual dose-response becomes even more apparent when considering the time-dependent discounted 1st SRS as a cumulative 2nd SRS. Tailoring SRS retreatment protocols based on NTCP modeling can potentially enhance therapeutic efficacy.
title Does time to retreatment matter? An NTCP model to predict radionecrosis after repeat SRS for recurrent brain metastases incorporating time-dependent discounted dose
topic Medical Physics
Biological Physics
url https://arxiv.org/abs/2409.07647