Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer

Giorgio Arcangeli, Stefano Arcangeli, Valentina Pinzi, Michaela Benassi, Marcello Benassi, Lidia Strigari

Research output: Contribution to journalArticle

Abstract

Purpose: We sought to determine the optimal hypofractionated regimens of moderately hypofractionated (HFRT) versus conventionally fractionated (CFRT) external beam radiotherapy for localized prostate cancer (LPCA), having as primary endpoints the 5-year biochemical failure (BF) and late gastrointestinal (GI) and genitourinary (GU) toxicity. Methods and materials: We performed a systematic literature review of the Medline and National Library of Medicine databases according to the PRISMA guidelines. Only phase III trials of CFRT versus moderate HFRT for LPCa, reporting 5-year BF and/or minimum 3-year late ≥G2 toxicity rates were considered. Results: A total of 11 manuscripts reporting the outcomes of 8145 patients gathered from 9 randomized trials met the eligibility criteria. No significant difference between CFRT and HFRT was found in any of the investigated outcome measures. 80%, 15% and 29% isolevel curves for freedom from BF (FFBF), GI and GU toxicity, respectively, resulting from grouping the median values of all endpoints, were calculated as a function of both total dose (Dtot) and dose per fraction (d). Trials using fractionation schedules (d × n) lying above the FFBF and below toxicity isolevels are expected to produce the best therapeutic ratio. Conclusions: Our analysis indicates an optimal therapeutic window within which Dtot, d and n can be safely adjusted. Owing to both the risks of uncertainty due to inclusion of trials with d up to 3.5 Gy, and the exploitation of different cell killing mechanisms associated to larger d, the extrapolation to extremely hypo-fractionated regimens is not warranted.
Original languageItalian
Pages (from-to)22-29
Number of pages8
JournalCancer Treatment Reviews
Volume70
DOIs
Publication statusPublished - Nov 1 2018

Cite this

Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer. / Arcangeli, Giorgio; Arcangeli, Stefano; Pinzi, Valentina; Benassi, Michaela; Benassi, Marcello; Strigari, Lidia.

In: Cancer Treatment Reviews, Vol. 70, 01.11.2018, p. 22-29.

Research output: Contribution to journalArticle

Arcangeli, Giorgio ; Arcangeli, Stefano ; Pinzi, Valentina ; Benassi, Michaela ; Benassi, Marcello ; Strigari, Lidia. / Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer. In: Cancer Treatment Reviews. 2018 ; Vol. 70. pp. 22-29.
@article{7570793e9ccb48e3a106a8476e17a9b8,
title = "Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer",
abstract = "Purpose: We sought to determine the optimal hypofractionated regimens of moderately hypofractionated (HFRT) versus conventionally fractionated (CFRT) external beam radiotherapy for localized prostate cancer (LPCA), having as primary endpoints the 5-year biochemical failure (BF) and late gastrointestinal (GI) and genitourinary (GU) toxicity. Methods and materials: We performed a systematic literature review of the Medline and National Library of Medicine databases according to the PRISMA guidelines. Only phase III trials of CFRT versus moderate HFRT for LPCa, reporting 5-year BF and/or minimum 3-year late ≥G2 toxicity rates were considered. Results: A total of 11 manuscripts reporting the outcomes of 8145 patients gathered from 9 randomized trials met the eligibility criteria. No significant difference between CFRT and HFRT was found in any of the investigated outcome measures. 80{\%}, 15{\%} and 29{\%} isolevel curves for freedom from BF (FFBF), GI and GU toxicity, respectively, resulting from grouping the median values of all endpoints, were calculated as a function of both total dose (Dtot) and dose per fraction (d). Trials using fractionation schedules (d × n) lying above the FFBF and below toxicity isolevels are expected to produce the best therapeutic ratio. Conclusions: Our analysis indicates an optimal therapeutic window within which Dtot, d and n can be safely adjusted. Owing to both the risks of uncertainty due to inclusion of trials with d up to 3.5 Gy, and the exploitation of different cell killing mechanisms associated to larger d, the extrapolation to extremely hypo-fractionated regimens is not warranted.",
keywords = "Biochemical failure, Hypofractionated radiotherapy, Late toxicity, Localized prostate cancer, Scheduling",
author = "Giorgio Arcangeli and Stefano Arcangeli and Valentina Pinzi and Michaela Benassi and Marcello Benassi and Lidia Strigari",
year = "2018",
month = "11",
day = "1",
doi = "10.1016/j.ctrv.2018.07.003",
language = "Italian",
volume = "70",
pages = "22--29",
journal = "Cancer Treatment Reviews",
issn = "0305-7372",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer

AU - Arcangeli, Giorgio

AU - Arcangeli, Stefano

AU - Pinzi, Valentina

AU - Benassi, Michaela

AU - Benassi, Marcello

AU - Strigari, Lidia

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Purpose: We sought to determine the optimal hypofractionated regimens of moderately hypofractionated (HFRT) versus conventionally fractionated (CFRT) external beam radiotherapy for localized prostate cancer (LPCA), having as primary endpoints the 5-year biochemical failure (BF) and late gastrointestinal (GI) and genitourinary (GU) toxicity. Methods and materials: We performed a systematic literature review of the Medline and National Library of Medicine databases according to the PRISMA guidelines. Only phase III trials of CFRT versus moderate HFRT for LPCa, reporting 5-year BF and/or minimum 3-year late ≥G2 toxicity rates were considered. Results: A total of 11 manuscripts reporting the outcomes of 8145 patients gathered from 9 randomized trials met the eligibility criteria. No significant difference between CFRT and HFRT was found in any of the investigated outcome measures. 80%, 15% and 29% isolevel curves for freedom from BF (FFBF), GI and GU toxicity, respectively, resulting from grouping the median values of all endpoints, were calculated as a function of both total dose (Dtot) and dose per fraction (d). Trials using fractionation schedules (d × n) lying above the FFBF and below toxicity isolevels are expected to produce the best therapeutic ratio. Conclusions: Our analysis indicates an optimal therapeutic window within which Dtot, d and n can be safely adjusted. Owing to both the risks of uncertainty due to inclusion of trials with d up to 3.5 Gy, and the exploitation of different cell killing mechanisms associated to larger d, the extrapolation to extremely hypo-fractionated regimens is not warranted.

AB - Purpose: We sought to determine the optimal hypofractionated regimens of moderately hypofractionated (HFRT) versus conventionally fractionated (CFRT) external beam radiotherapy for localized prostate cancer (LPCA), having as primary endpoints the 5-year biochemical failure (BF) and late gastrointestinal (GI) and genitourinary (GU) toxicity. Methods and materials: We performed a systematic literature review of the Medline and National Library of Medicine databases according to the PRISMA guidelines. Only phase III trials of CFRT versus moderate HFRT for LPCa, reporting 5-year BF and/or minimum 3-year late ≥G2 toxicity rates were considered. Results: A total of 11 manuscripts reporting the outcomes of 8145 patients gathered from 9 randomized trials met the eligibility criteria. No significant difference between CFRT and HFRT was found in any of the investigated outcome measures. 80%, 15% and 29% isolevel curves for freedom from BF (FFBF), GI and GU toxicity, respectively, resulting from grouping the median values of all endpoints, were calculated as a function of both total dose (Dtot) and dose per fraction (d). Trials using fractionation schedules (d × n) lying above the FFBF and below toxicity isolevels are expected to produce the best therapeutic ratio. Conclusions: Our analysis indicates an optimal therapeutic window within which Dtot, d and n can be safely adjusted. Owing to both the risks of uncertainty due to inclusion of trials with d up to 3.5 Gy, and the exploitation of different cell killing mechanisms associated to larger d, the extrapolation to extremely hypo-fractionated regimens is not warranted.

KW - Biochemical failure

KW - Hypofractionated radiotherapy

KW - Late toxicity

KW - Localized prostate cancer

KW - Scheduling

U2 - 10.1016/j.ctrv.2018.07.003

DO - 10.1016/j.ctrv.2018.07.003

M3 - Articolo

VL - 70

SP - 22

EP - 29

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

SN - 0305-7372

ER -