Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes

Hearn, N.; Atwell, Daisy; Cahill, K.; Elks, J.; Vignarajah, D.; Lagopoulos, Jim; Min, Myo

doi:10.1016/j.clon.2020.06.008

Cited by 28 publications

(29 citation statements)

References 87 publications

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“…According to RTOG/CTCAE scale in our review the mean ≥ G3 toxicity was 11.06% and, differently of Hearn et al [ 25 ] review, we did not find any correlation between EQD2 (alpha/beta 10 Gy) dose prescription and ≥ G3 toxicities.…”

Section: Discussioncontrasting

confidence: 75%

“…In our review R0 rates were higher (98.88%) in confront of Hearn et al [ 25 ] results (90.7%). This finding can be explain because we included only studies which used inverse-planning technique, in fact, in Hearn et al [ 25 ] meta-analyses was reported a significantly positively correlation between the use of inverse planning techniques and R0 rate in univariate regression analysis.…”

Section: Discussionsupporting

confidence: 41%

“…An interesting systematic review and meta-analysis was performed recently by Hearn et al [ 25 ] which analyzed dose escalation for the treatment of neoadjuvant LARC, screening studies for radiotherapy prescription dose > 54 Gy. In this meta-analysis authors reported a pool estimated of pCR of 24.1% in all studies and 25.7% in inverse planning studies without a statistically differences between techniques.…”

Section: Discussionmentioning

confidence: 99%

“…Otherwise, Hearn et al [ 25 ] in a systematic review and meta-analyses did not identified a survival benefit with radiotherapy dose escalation.…”

Section: Discussionmentioning

confidence: 99%

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Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

Delishaj

Fumagalli

Ursino

et al. 2021

WJCC

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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.

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionsupporting

confidence: 41%

Section: Discussionmentioning

confidence: 99%

“…Otherwise, Hearn et al [ 25 ] in a systematic review and meta-analyses did not identified a survival benefit with radiotherapy dose escalation.…”

Section: Discussionmentioning

confidence: 99%

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Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

Delishaj

Fumagalli

Ursino

et al. 2021

WJCC

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“…Despite this dose escalation trials in LCCRT have had mixed results, the RECTAL-BOOST study reporting no increase in pCR rates using a sequential boost technique [20] . Encouragingly a systematic review of inverse planned techniques found improved pCR rates with doses greater than 54 Gy [21] . This supports the trend towards organ preservation strategies, with potential in both the LCCRT and SCRT settings for dose escalation to avoid surgical morbidity, a permanent stoma and improve patient’s quality of life (QOL) [22] .…”

Section: Introductionmentioning

confidence: 99%

The in-silico feasibility of dose escalated, hypofractionated radiotherapy for rectal cancer

Devlin¹,

Grocutt²,

Hunter³

et al. 2022

Clinical and Translational Radiation Oncology

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Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach

et al. 2022

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Purpose As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery. Methods Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1‑3, N0‑1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10–13 × 3 Gy EBRT followed by HDR-BT delivering 12–18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis. Results Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8–60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date. Conclusion Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery.

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Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes

Cited by 28 publications

References 87 publications

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

The in-silico feasibility of dose escalated, hypofractionated radiotherapy for rectal cancer

Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach

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