Probiotics supplementation for the prevention of gastrointestinal radiation-induced side effects: the time is now.

To the Editor: We read with great interest the article by Ringel et al. ( 1 ) providing a narrative review on the use of probiotics in the management of gastrointestinal diseases. As stated in the introduction section, authors based their review on selected high-quality articles, mainly randomized controlled trials (RCT), systematic reviews, and meta-analyses. It is probable for this reason that the authors omitted to mention the eff ects that probiotics supplementation could exert for the prevention of radiation-induced gastrointestinal side eff ects, since high-quality studies are almost lacking. Although pelvic cancers are among the most frequently diagnosed cancers worldwide and it is well known that up to 20 % of patients develop gastrointestinal side eff ects within 10 years from the end of radiation treatment, surprisingly, the academic and industry researchers have little interest to spend time (and funds) on well-performed, high-quality studies investigating how to prevent the development of pelvic radiation disease ( 2 ). In 2009, we attempted to systematically review the existing literature and provide a quantitative summary of the published RCTs that investigated the eff ect of probiotics for the prevention of radiation-induced diarrhea ( 3 ). Unfortunately, only three trials, involving 632 patients, were available with substantial heterogeneity and several limitations that did not allow any defi nitive conclusion. However, the largest randomized, double-blind, placebo-controlled trial that included 490 patients, concluded that VSL # 3 supplementation could reduce the incidence and severity of radiationinduced diarrhea ( 4 ). Our conclusion was that more well-performed studies were needed. Since 2009, only one small RCT has been published, that investigated the preventive eff ect of Lactobacillus acidophilus plus Bifi dobacterium bifi dum in 63 patients scheduled for radiation treatment for cervical cancer; although based on a small sample, the results confi rmed that the severity of diarrhea was signifi cantly less severe in patients on probiotics preventive treatment than in those on placebo ( 5 ). Of the 446 trials, actually registered on ClinicalTrials.gov investigating the effi - cacy of probiotics for the prevention and treatment of several diseases, only 1 study is focused on the prevention of gastrointestinal complications following pelvic radiation therapy, thus, representing a step forward since 3 years ago no study was planned at all. Several cellular and molecular alterations responsible for the development of radiation-induced side eff ects might theoretically be prevented by probiotics supplementation ( 6 ), but large, well-performed, high-quality studies are still awaited to confi rm it. Are probiotics and pelvic radiation disease ready for prime time?