title: Feasibility of an adaptive strategy in preoperative radiochemotherapy for rectal cancer with image-guided tomotherapy: boosting the dose to the shrinking tumor.
abstract: OBJECTIVE
  To investigate the feasibility of preoperative adaptive radiochemotherapy by delivering a concomitant boost to the residual tumor during the last 6 fractions of treatment.
  
  
  METHODS
  Twenty-five patients with T3/T4N0 or N+ rectal cancer were enrolled. Concomitant chemotherapy consisted of oxaliplatin 100 mg/m(2) on days -14, 0, and +14, and 5-fluorouracil 200 mg/m(2)/d from day -14 to the end of radiation therapy (day 0 is the start of radiation therapy). Radiation therapy consisted of 41.4 Gy in 18 fractions (2.3 Gy per fraction) with Tomotherapy to the tumor and regional lymph nodes (planning target volume, PTV) defined on simulation CT and MRI. After 9 fractions simulation CT and MRI were repeated for the planning of the adaptive phase: PTVadapt was generated by adding a 5-mm margin to the residual tumor. In the last 6 fractions a boost of 3.0 Gy per fraction (in total 45.6 Gy in 18 fractions) was delivered to PTVadapt while concomitantly delivering 2.3 Gy per fraction to PTV outside PTVadapt.
  
  
  RESULTS
  Three patients experienced grade 3 gastrointestinal toxicity; 2 of 3 showed toxicity before the adaptive phase. Full dose of radiation therapy, oxaliplatin, and 5-fluorouracil was delivered in 96%, 96%, and 88% of patients, respectively. Two patients with clinical complete response (cCR) refused surgery and were still cCR at 17 and 29 months. For the remaining 23 resected patients, 15 of 23 (65%) showed tumor regression grade 3 response, and 7 of 23 (30%) had pathologic complete response; 8 (35%) and 12 (52%) tumor regression grade 3 patients had ≤5% and 10% residual viable cells, respectively.
  
  
  CONCLUSIONS
  An adaptive boost strategy is feasible, with an acceptable grade 3 gastrointestinal toxicity rate and a very encouraging tumor response rate. The results suggest that there should still be room for further dose escalation of the residual tumor with the aim of increasing pathologic complete response and/or cCR rates.
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy. passoni.paolo@hsr.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
authors.forename: Najla
authors.initials: N
authors.lastname: Slim
authors.forename: Monica
authors.initials: M
authors.lastname: Ronzoni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ricci
authors.forename: Saverio
authors.initials: S
authors.lastname: Di Palo
authors.forename: Paola
authors.initials: P
authors.lastname: De Nardi
authors.forename: Elena
authors.initials: E
authors.lastname: Orsenigo
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamburini
authors.forename: Francesco
authors.initials: F
authors.lastname: De Cobelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Losio
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Iacovelli
authors.forename: Sara
authors.initials: S
authors.lastname: Broggi
authors.forename: Carlo
authors.initials: C
authors.lastname: Staudacher
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calandrino
authors.forename: Nadia
authors.initials: N
authors.lastname: Di Muzio
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012074:Remission Induction; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil