Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 26, 2021; 9(30): 9077-9089
Published online Oct 26, 2021. doi: 10.12998/wjcc.v9.i30.9077
Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature
Durim Delishaj, Ilaria Costanza Fumagalli, Stefano Ursino, Agostino Cristaudo, Francesco Colangelo, Antonio Stefanelli, Alessandro Alghisi, Giuseppe De Nobili, Romerai D’Amico, Alessandra Cocchi, Antonio Ardizzoia, Carlo Pietro Soatti
Durim Delishaj, Francesco Colangelo, Alessandro Alghisi, Giuseppe De Nobili, Romerai D’Amico, Alessandra Cocchi, Carlo Pietro Soatti, Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
Ilaria Costanza Fumagalli, Department of Radiation Oncology, San Donato Hospital, Milan 20097, Italy
Stefano Ursino, Department of Radiation Oncology, Santa Chiara University Hospital, Pisa 56126, Italy
Agostino Cristaudo, Royal Preston Hospital, Lancashire Teaching Hospital- NHS Tust, Preston PR2 9HT, United Kingdom
Antonio Stefanelli, Department of Radiation Oncology, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara 44124, Italy
Antonio Ardizzoia, Department of Clinical Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
Author contributions: Delishaj D, Ursino S and Fumagalli CI participate on drafting and searching process of the review; Fumagalli CI, Colangero F, D’Amico R, Alghisi A and De Nobili G contributed on data extraction and screening process of the review; Cocchi A and Stefanelli A revised the review critically for important intellectual content improving scientific value of the manuscript; Cristaudo A proceeded correcting all English grammar errors, improving the scientific value of review and doing the text more fluently and easier to understand from readers and reviewers; Soatti CP and Ardizzoia A give final approval of the review to be submitted and any revised version of manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Durim Delishaj, MD, Doctor, Department of Radiation Oncology, Alessandro Manzoni Hospital, Via Dell’Eremo, 9/11, Lecco 23900, Italy. d.delishaj@asst-lecco.it
Received: April 14, 2021
Peer-review started: April 14, 2021
First decision: June 3, 2021
Revised: June 27, 2021
Accepted: September 14, 2021
Article in press: September 14, 2021
Published online: October 26, 2021
Processing time: 189 Days and 19.3 Hours
Abstract
BACKGROUND

The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2).

AIM

To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques.

METHODS

In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review.

RESULTS

The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047).

CONCLUSION

Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications.

Keywords: Rectal cancer; Radiotherapy; Volumetric Modulated Arc Therapy; Image-guided radiotherapy; Intensity-modulated radiotherapy; Neoadjuvant radiotherapy

Core Tip: We analyzed the role of neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers (LARC) using innovative radiotherapy techniques. A comprehensive literature search was performed on electronic database with a period limit from January 2009 to December 2020. According to PRISMA Group (2009) screening process only studies using equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy, image-guided radiotherapy or image-guided radiotherapy techniques were included for the review. Neoadjuvant radiotherapy dose escalation using innovative techniques is safe for LARC with acceptable acute toxicity, achieving higher pathological complete response compared to standard treatment. EQD2 doses > 58.9 Gy with a BED > 70.7 Gy was associated with higher rate of surgical complications.