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

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.

High-dose-rate brachytherapy as monotherapy for localized prostate cancer using three different doses - 14 years of single-centre experience.

PURPOSE: To evaluate clinical outcomes in patients with localized prostate cancer (LPC) treated with 3D conformal high-dose-rate (HDR) brachytherapy (BT) as monotherapy. MATERIAL AND METHODS: From March 2004 to November 2017, 277 men with LPC underwent 3D conformal HDR-BT as monotherapy, with a temporary implant. The dose prescription was: 38 Gy in 4 fractions (149 patients), 27 Gy in 2 fractions (41 patients), and 19-20 Gy in a single fraction (87 patients). Biochemical progression-free survival (bPFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity assessment were performed using Common Terminology Criteria for Adverse Events v5.0. RESULTS: The mean age was 67 (range, 47-81) years. Overall, 145 patients were low-risk, 116 intermediate-risk, and 16 high-risk prostate cancer. After a median follow-up of six years (range, 6-160 months), bPFS, PFS, and CSS were 81%, 96%, and 97%, respectively. Dose prescription, initial prostate specific antigen (iPSA) ≥ 9,5 ng/ml, and high-risk disease resulted in prognostic factors regarding bPFS. Only G2-G3 acute or late GI and GU toxicities were observed. CONCLUSIONS: HDR-BT as monotherapy is a valid and safe treatment modality for localized prostate cancer. After a long follow-up, patients receiving 19-20 Gy in a single fraction had a lower biochemical control rate compared to patients receiving 38 Gy in 4 fractions or 27 Gy in 2 fractions. Randomized prospective trials with a longer follow-up are necessary to confirm our results, and define total doses and dose per fraction for HDR-BT in patients with LPC.

Vaginal toxicity after high-dose-rate endovaginal brachytherapy: 20 years of results.

PURPOSE: To evaluate vaginal toxicity (primary endpoint) and local control (secondary endpoint) in patients with endometrial cancer who underwent primary surgery and adjuvant high-dose-rate (HDR) endovaginal brachytherapy (BT). MATERIAL AND METHODS: In September 2017, the authors conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus, and Cochrane library. In this systematic review, the authors included randomized trials, non-randomized trials, prospective studies, retrospective studies, and cases. The time period of the research included articles published from September 1997 to September 2017. RESULTS: Acute endovaginal toxicity occurred in less than 20.6% and all acute toxicities were G1-G2. The most common early side effects due to HDR-BT treatment were vaginal inflammation, vaginal irritation, dryness, discharge, soreness, swelling, and fungal infection. G1-G2 late toxicity occurred in less than 27.7%. Finally, G3-G4 late vaginal occurred in less than 2%. The most common late side effects consisted of vaginal discharge, dryness, itching, bleeding, fibrosis, telangiectasias, stenosis, short or narrow vagina, and dyspareunia. CONCLUSIONS: The data suggest that HDR endovaginal brachytherapy, with or without chemotherapy, is very well tolerated with low rates of acute and late vaginal toxicities. Further prospective studies with higher numbers of patients and longer follow-up are necessary to evaluate acute and late toxicities after HDR endovaginal brachytherapy.