High-dose vs standard radiotherapy in rectal cancer: Effects on tumour response, toxicity, and organ preservation

doi:10.4251/wjgo.120904

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Aug 15, 2026; 18(8): 120904
Published online Aug 15, 2026. doi: 10.4251/wjgo.120904

Table 1 Summary of efficacy and safety outcomes for high-dose vs standard-dose radiotherapy in rectal cancer

Outcome	Studies included (n)	Patients (HDRT/SDRT)	Effect model	Pooled effect [RR (95%CI)]	P value	Heterogeneity I² (%)
Tumour response
cCR	4	586 (351/235)	Random	1.34 (1.00-1.80)	0.05	74
pCR	4	531 (261/270)	Fixed	1.07 (0.77-1.50)	0.67	2
TRG 1-2	2	296 (144/152)	Fixed	1.52 (1.16-1.99)	0.002	0
Efficacy
Local recurrence	4	558 (278/280)	Fixed	1.35 (0.81-2.24)	0.25	30
Distant metastasis	3	465 (233/232)	Fixed	0.90 (0.64-1.28)	0.57	0
Organ preservation	4	670 (398/272)	Random	1.17 (0.95-1.43)	0.15	71
Survival
OS	4			NS¹
DFS	4			NS¹
Safety
Grade ≥ 3 toxicity	4	391 (195/196)	Fixed	1.40 (0.90-2.18)	0.13	0

¹NS indicates no statistically significant difference between groups; quantitative pooling was not performed due to heterogeneous follow-up durations (3-5 years).

cCR: Clinical complete response; DFS: Disease-free survival; HDRT: High-dose radiotherapy; I²: I-squared statistic (heterogeneity measure); NS: Not significant; OS: Overall survival; pCR: Pathological complete response; RR: Risk ratio; SDRT: Standard-dose radiotherapy; TRG: Tumour regression grade.

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Table 2 Baseline characteristics of included studies, n (%)/median (range)

Ref.	Trial	NCT	Country	Age (years)	Arm	n	Neoadjuvant regimen	RT technology	EQD₂, Gy (α/β = 10)	Tumour stage			Lymph node status
Ref.	Trial	NCT	Country	Age (years)	Arm	n	Neoadjuvant regimen	RT technology	EQD₂, Gy (α/β = 10)	T2	T3	T4	N0	N+
Couwenber et al[19], 2020	RECTAL-BOOST	01951521	Dutch	62.0 (56-71)	SDRT	64	CRT: 50 Gy/25F + Cape	VMAT	50	5 (7.8)	39 (60.9)	20 (31.3)	9 (14.1)	55 (85)
Couwenber et al[19], 2020	RECTAL-BOOST	01951521	Dutch	64.5 (55-69)	HDRT	64	RT: 15 Gy/5F to CRT: 50 Gy/25F + Cape	VMAT + SBRT boost	66.3	2 (3.1)	51 (79.7)	11 (17.2)	5 (7.8)	59 (92.2)
Appelt et al[20], 2014			Denmark	62 (35-77)	SDRT	111	CRT: 50.4 Gy/28F + UFT/Leucovorin	3DRT	49.6	-	90 (81)	21 (19)	10 (9)	101 (91)
Appelt et al[20], 2014			Denmark	64 (38-78)	HDRT	110	CRT: 50.4 Gy/28F + HDRBT: 10 Gy/2F to concurrent UFT/Leucovorin	3DRT + HDRBT	62.1	-	93 (85)	17 (15)	13 (12)	95 (86)
Garant et al[21], 2022	MORPHEUS	03051464	Canada	67.5 (42-89)	SDRT	20	CRT: 45 Gy/25F EBRT + 5-FU/Cape to 9 Gy/5F EBRT boost	3DRT	53.1	8 (40)	12 (60)	-	20 (100)	-
Garant et al[21], 2022	MORPHEUS	03051464	Canada	64.5 (46-87)	HDRT	20	CRT: 45 Gy/25F EBRT + 5-FU/Cape to 30 Gy/3F IGAEBT boost	3DRT + IGAEBT boost	94.3	6 (30)	14 (70)	-	20 (100)	-
Gerard et al[16], 2023	OPERA	02505750	France	69 (61–74)	SDRT	69	CRT: 45 Gy/25F EBRT + Cape to 9 Gy/5F EBRT boost	EBRT (3D-CRT or IMRT)	53.1	44 (64)	25 (36)	-	49 (71)	19 (28)
Gerard et al[16], 2023	OPERA	02505750	France	70 (60–74)	HDRT	72	CRT: 45 Gy/25F EBRT + Cape to 90 Gy/3F CXB boost	EBRT + CXB	344.3	47 (65)	25 (35)	-	55 (76)	17 (24)
Wang et al[18], 2019	FDRT-002	01064999	China	-	SDRT	60	CRT: 50 Gy/25F + CapeOX	IMRT	50	-	40 (66.70)	20 (33.3)	14 (23.30)	46 (76.7)
Wang et al[18], 2019	FDRT-002	01064999	China	-	HDRT	60	CRT: 55 Gy/25F + CapeOX¹ to CapeOX (1)	IMRT	55.9	-	45 (75.0)	15 (25.0)	14 (23.3)	46 (76.7)
Yariv et al[17], 2024	OPRA	02008656	United States	57 (50-66)	SDRT	93	CRT: 50-50.4 GY + Cape/5FU to FOLFOX or CapeOX	-	49.6¹	-	-	-	-	-
Yariv et al[17], 2024	OPRA	02008656	United States	58 (50-68)	HDRT	210	CRT: 54-56 GY + Cape/5-FU to FOLFOX or CapeOX	-	54.9²	-	-	-	-	-
Rouanet et al[22], 2022	GRECCAR 4	01333709	France	61 (22-82)	SDRT	52	FOLFIRINOX (4) to CRT (50 Gy + Cape)	3D-RT	50³	-	40 (76.9)	12 (23.1)	2 (3.8)	50 (96.2)
Rouanet et al[22], 2022	GRECCAR 4	01333709	France	62 (22-80)	HDRT	51	FOLFIRINOX (4) to CRT (60 Gy + Cape)	3D-RT	60³	-	38 (74.5)	13 (25.5)	1 (2.0)	4 (98.0)

¹Equivalent dose in 2 Gy calculated assuming radiotherapy was delivered at 1.8 Gy per fraction (upper limit dose).

²Equivalent dose in 2 Gy calculated assuming radiotherapy was delivered at 1.8 Gy per fraction (median boost dose).

³Equivalent dose in 2 Gy calculated assuming radiotherapy was delivered at 2 Gy per fraction. Numbers in parentheses indicate the number of chemotherapy cycles.

Cape: Capecitabine; CapeOX: Capecitabine plus oxaliplatin; CRT: Chemoradiotherapy; CXB: Contact X-ray brachytherapy; EBRT: External beam radiotherapy; EQD2: Equivalent dose in 2 Gy; FOLFOX: Folinic acid, fluorouracil, and oxaliplatin; FOLFIRINOX: Folinic acid, fluorouracil, irinotecan, and oxaliplatin; HDRBT: High-dose-rate brachytherapy; HDRT: High-dose radiotherapy; IGAEBT: Image-guided adaptive endorectal brachytherapy; IMRT: Intensity-modulated radiotherapy; NCT: ClinicalTrials.gov identifier; RT: Radiotherapy; SBRT: Stereotactic body radiotherapy; SDRT: Standard-dose radiotherapy; UFT: Tegafur-uracil; VMAT: Volumetric modulated arc therapy; 3DRT: Three-dimensional conformal radiotherapy; 5-FU: 5-fluorouracil.

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Citation: Long T, Gao H, He WQ, Xiao WW, Wang XC. High-dose vs standard radiotherapy in rectal cancer: Effects on tumour response, toxicity, and organ preservation. World J Gastrointest Oncol 2026; 18(8): 120904
URL: https://www.wjgnet.com/1948-5204/full/v18/i8/120904.htm
DOI: https://dx.doi.org/10.4251/wjgo.120904

Long T, Gao H, He WQ, Xiao WW, Wang XC. High-dose vs standard radiotherapy in rectal cancer: Effects on tumour response, toxicity, and organ preservation. World J Gastrointest Oncol 2026; 18(8): 120904 [DOI: 10.4251/wjgo.120904]

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