• locally advanced rectal cancers
• neoadjuvant chemoradiation
• radiation dose escalation
• simultaneous integrated boost
• treatment intensification

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).

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

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.

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).

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.

• Rectal cancer
• Radiotherapy
• Volumetric Modulated Arc Therapy
• Image-guided radiotherapy
• Intensity-modulated radiotherapy
• Neoadjuvant radiotherapy

• Inverse planning
• locally advanced rectal cancer
• meta-analysis
• pathological complete response
• radiotherapy boost

Background: To evaluate the efficacy and treatment related morbidity of neoadjuvant chemoradiotherapy or radiotherapy in elderly patients (aged 75 years or older) with locally advanced rectal cancer (LARC).

Methods: We reviewed clinical records of elderly patients with LARC treated with neoadjuvant chemoradiotherapy or radiotherapy between January 2008 and June 2017 at our institute. A dose of 45-50Gy in 25 fractions was delivered to pelvis. The primary tumor received a dose of 55Gy concomitantly for patients receiving intensity modulated radiotherapy (IMRT). The concurrent chemotherapy included capecitabine alone and capecitabine plus oxaliplatin (Xelox). Surgery was performed for suitable patients at least 6 weeks after neoadjuvant treatment. Overall survival (OS), disease specific survival (DSS), disease free survival (DFS) and local control (LC) were calculated with Kaplan-Meier method.

Results: A total of 85 patients were enrolled in this study, the median age was 80 years old (range: 75-90 years). After neoadjuvant treatment, surgery was performed in 56 patients (65.9%). Downstaging rate was 85.7% (48/56) with T downstaging in 35 patients (62.5%) and N downstaging in 36 patients (64.3%). Twelve patients (21.4%) obtained pathological complete response (pCR). The incidence of grade 3 or greater acute hematological, gastrointestinal and genitourinary toxicities were 10.7%, 5.2% and 1.8%, respectively. Seven patients (12.5%) experienced postoperative complications. The median follow-up duration was 35.7 months (range: 4.3-100.3 months), The 3-year and 5-year OS, DSS, DFS, LC were 68.9% and 47.2%, 75.8% and 60.4%, 68.2% and 56.1%, 83.9% and 78.3%, respectively.

Conclusion: In patients aged 75 years or older with LARC, neoadjuvant chemoradiotherapy followed by surgery was well tolerated with promising survival outcomes, which should be strongly suggested if medically suitable.

• chemotherapy
• elderly
• neoadjuvant
• radiotherapy
• rectal cancer