“Primer shot” fractionation with an early treatment break is theoretically superior to consecutive weekday fractionation schemes for early-stage non-small cell lung cancer Journal Article
| Authors: | Gouw, Z. A. R.; Jeong, J.; Rimner, A.; Lee, N. Y.; Jackson, A.; Fu, A.; Sonke, J. J.; Deasy, J. O. |
| Article Title: | “Primer shot” fractionation with an early treatment break is theoretically superior to consecutive weekday fractionation schemes for early-stage non-small cell lung cancer |
| Abstract: | Purpose: Radiotherapy is traditionally given in equally spaced weekday fractions. We hypothesize that heterogeneous interfraction intervals can increase radiosensitivity via reoxygenation. Through modeling, we investigate whether this minimizes local failures and toxicity for early-stage non-small cell lung cancer (NSCLC). Methods: Previously, a tumor dose-response model based on resource competition and cell-cycle-dependent radiosensitivity accurately predicted local failure rates for early-stage NSCLC cohorts. Here, the model mathematically determined non-uniform inter-fraction intervals minimizing local failures at similar normal tissue toxicity risk, i.e., iso-BED3 (iso-NTCP) for fractionation schemes 18Gyx3, 12Gyx4, 10Gyx5, 7.5Gyx8, 5Gyx12, 4Gyx15. Next, we used these optimized schedules to reduce toxicity risk (BED3) while maintaining stable local failures (TCP). Results: Optimal schedules consistently favored a “primer shot” fraction followed by a 2-week break, allowing tumor reoxygenation. Increasing or decreasing the assumed baseline hypoxia extended or shortened this optimal break by up to one week. Fraction sizes of 7.5 Gy and up required a single primer shot, while smaller fractions needed one or two extra fractions for full reoxygenation. The optimized schedules, versus consecutive weekday fractionation, predicted absolute LF reductions of 4.6%-7.4%, except for the already optimal LF rate seen for 18Gyx3. Primer shot schedules could also reduce BED3 at iso-TCP with the biggest improvements for the shortest schedules (94.6Gy reduction for 18Gyx3). Conclusion: A validated simulation model clearly supports non-standard “primer shot” fractionation, reducing the impact of hypoxia-induced radioresistance. A limitation of this study is that primer-shot fractionation is outside prior clinical experience and therefore will require clinical studies for definitive testing. © 2023 Elsevier B.V. |
| Keywords: | cancer radiotherapy; cell survival; cell cycle; radiotherapy dosage; radiotherapy; cohort analysis; lung cancer; mathematical modeling; simulation; radiation oncology; radiation dose fractionation; early cancer; radiosensitivity; risk reduction; radiation sickness; tumor hypoxia; reoxygenation; non small cell lung cancer; radiation resistance; article; radiation dose response; modification of radiation sensitivity |
| Journal Title: | Radiotherapy and Oncology |
| Volume: | 190 |
| ISSN: | 0167-8140 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-01-01 |
| Start Page: | 110006 |
| Language: | English |
| DOI: | 10.1016/j.radonc.2023.110006 |
| PUBMED: | 37972733 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Z.A.R. Gouw -- Source: Scopus |
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