title: Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis.
abstract: OBJECTIVE
  We conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval.
  
  
  METHODS
  PubMed, EMBASE and Cochrane libraries were searched with the terms 'radiotherapy', 'boost' and 'rectal cancer' and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier.
  
  
  RESULTS
  The search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8-24.5%), with low heterogeneity (I2 0.0%, 95% CI 0.00-84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4-18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2-95.3%).
  
  
  CONCLUSIONS
  Dose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.
authors.affiliation: Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands. Electronic address: j.p.m.burbach-2@umcutrecht.nl.
authors.forename: Johannes Peter Maarten
authors.initials: JP
authors.lastname: Burbach
authors.affiliation: Department of Radiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Annemarie Maria
authors.initials: AM
authors.lastname: den Harder
authors.affiliation: Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Intven
authors.affiliation: Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van Vulpen
authors.affiliation: Trial Bureau Imaging Division, University Medical Center, Utrecht, The Netherlands.
authors.forename: Helena Marieke
authors.initials: HM
authors.lastname: Verkooijen
authors.affiliation: Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Onne
authors.initials: O
authors.lastname: Reerink
mesh_terms: D000368:Aged; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D011300:Preoperative Care / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome
keywords: Boost radiation; Locally advanced rectal cancer; Meta-analysis; Pathologic complete response; Systematic review