title: Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.
abstract: OBJECTIVE
  The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost.
  
  
  METHODS
  Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale.
  
  
  RESULTS
  Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%.
  
  
  CONCLUSIONS
  Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows complete or near-complete pathological response in more than 38% of patients. However, severe acute toxicity was reported in more than one-third of patients.
authors.affiliation: Radiotherapy Unit, Research and Care Foundation "Giovanni Paolo II", Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Picardi
authors.affiliation: Radiotherapy Unit, Research and Care Foundation "Giovanni Paolo II", Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Guido
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Giaccherini
authors.affiliation: Radiotherapy Unit, Research and Care Foundation "Giovanni Paolo II", Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.affiliation: Department of Radiotherapy, "A. Gemelli" Polyclinic, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Gambacorta
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Arcelli
authors.affiliation: Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Farioli
authors.affiliation: Department of Radiotherapy, "A. Gemelli" Polyclinic, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cellini
authors.affiliation: Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Dajana
authors.initials: D
authors.lastname: Cuicchi
authors.affiliation: Medical Oncology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: DI Fabio
authors.affiliation: Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Poggioli
authors.affiliation: Medical Oncology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
authors.affiliation: Radiotherapy Department, Bellaria Hospital, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Frezza
authors.affiliation: Radiotherapy Unit, Research and Care Foundation "Giovanni Paolo II", Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Savino
authors.initials: S
authors.lastname: Cilla
authors.affiliation: Radiotherapy Unit, Radiotherapy and Nuclear Medicine Center, Businco Hospital, Cagliari, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Caravatta
authors.affiliation: Department of Radiotherapy, "A. Gemelli" Polyclinic, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fuccio
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed
keywords: Rectal cancer; chemotherapy; concomitant boost; phase II; radiotherapy