Effect of dose escalation in neoadjuvant chemoradiotherapy of locally advanced rectal cancer on clinical and pathologic Response: A Systematic review and meta-analysis of randomized controlled trials

Management of locally advanced rectal cancer (LARC) increasingly highlights necessity of organ functionality preservation, with the achievement of a complete clinical or pathological response (CR) regarded as a fundamental treatment target. While established concurrent chemoradiation (CRT) is effective, it often results in only modest complete response rates, thus prompting exploration into the possible benefits of raising radiation dosages to boost clinical results. This <i>meta</i>-analysis of randomized controlled trials sought to elucidate whether dose-escalated neoadjuvant CRT augments tumor response and to evaluate its accompanying toxicity profile. By extracting data from 12 trials encompassing 1,803 patients, we discerned that the overall effect on a composite CR endpoint-incorporating both pathological and clinical complete responses-did not achieve statistical significance (RR 1.26, 95% CI: 0.95-1.68). Notably, the subgroup evaluation showed that in clinical trials with a uniform chemotherapy strategy for both control and experimental populations, raising the dosage led to an elevation in CR rates which was not statistically significant (RR 1.46, 95% CI: 1.00-2.12). Conversely, studies that altered concurrent chemotherapy did not show these benefits. Also, the assessment showed that raised radiation doses did not independently result in a marked rise in severe acute toxicity (RR 0.92, 95% CI: 0.53 - 1.59); instead, the gravity of toxicity appeared to be more directly associated with the chemotherapy methods used. These findings suggest that increasing radiation dose may modestly enhance tumor response in LARC. This technique corresponds with the progressing framework towards preserving organ function in rectal cancer.