Radiobiological analysis of the response of prostate cancer to different fractionations

Abstract

Purpose: To investigate the response of prostate cancer to different radiotherapy schedules, including hypofractionation, and to evaluate potential departures from the linear-quadratic (LQ) response. To obtain best-fitting parameters for low (LR), intermediate (IR), and high risk (HR) prostate cancer. Methods and Materials: We have constructed a dataset of dose-response containing 87 entries (35 LR, 32 IR, 20 HR), with doses per fraction ranging from 1.8 to 10 Gy. These data were fitted to tumor control probability models based on the LQ model, linear-quadratic-linear (LQL), and a modification of the LQ (LQmod) accounting for increasing radiosensitivity at large doses. Fits were performed with the maximum likelihood expectation methodology, and the Akaike-Information-Criterion (AIC) was used to compare models. Results: The AIC shows that the LQ model is superior to the LQL and LQmod for all risks, except for IR where the LQL outperforms the other models. The analysis shows a low α/β for all risks: 2.01 Gy for LR (95% confidence interval 1.74-2.26), 3.44 Gy for IR (2.99-4.02), and 2.78 Gy for HR (1.43-4.18). Best-fits do not show proliferation for LR, and only moderate proliferation for IR/HR. Conclusions: In general, the LQ model describes the response of prostate cancer better than the alternative models. Only for IR the LQL outperforms the LQ. This study confirms a low α/β for all risks, with doses per fraction ranging from <2 Gy up to 10 Gy.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This project has received funding from Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación and FEDER, UE (grant PID2021-128984OB-I00). This project has received funding from Xunta de Galicia, Axencia Galega de Innovación (grant IN607D 2022/02).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This was a retrospective analysis of open-access data, thus the analysis is exempt from IRB approval. Data of dose/response of prostate cancer radiotherapy were obtained from several publications presented in the supplementary materials: https://pubmed.ncbi.nlm.nih.gov/26798571/ https://pubmed.ncbi.nlm.nih.gov/22170628/ https://pubmed.ncbi.nlm.nih.gov/27035363/ https://pubmed.ncbi.nlm.nih.gov/17336216/ https://pubmed.ncbi.nlm.nih.gov/21324610/ https://pubmed.ncbi.nlm.nih.gov/29588072/ https://pubmed.ncbi.nlm.nih.gov/25452933/ https://pubmed.ncbi.nlm.nih.gov/25505732/ https://pubmed.ncbi.nlm.nih.gov/21300474/ https://pubmed.ncbi.nlm.nih.gov/21528663/ https://pubmed.ncbi.nlm.nih.gov/27458572/ https://pubmed.ncbi.nlm.nih.gov/25426447/ https://pubmed.ncbi.nlm.nih.gov/17544601/ https://pubmed.ncbi.nlm.nih.gov/16135479/ https://pubmed.ncbi.nlm.nih.gov/16965866/ https://pubmed.ncbi.nlm.nih.gov/12128109/ https://pubmed.ncbi.nlm.nih.gov/20493642/ https://pubmed.ncbi.nlm.nih.gov/27339115/ https://pubmed.ncbi.nlm.nih.gov/27044935/ https://pubmed.ncbi.nlm.nih.gov/33035622/ https://pubmed.ncbi.nlm.nih.gov/27339116/ https://pubmed.ncbi.nlm.nih.gov/28296582/ https://pubmed.ncbi.nlm.nih.gov/28355113/

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

All data produced in the present work are contained in the manuscript and supplementary materials.

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