title: Effect of radiotherapy and chemotherapy on the risk of mucositis during intensity-modulated radiation therapy for oropharyngeal cancer.
abstract: OBJECTIVE
  To define the roles of radiotherapy and chemotherapy on the risk of Grade 3+ mucositis during intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer.
  
  
  METHODS
  164 consecutive patients treated with IMRT at two institutions in nonoverlapping treatment eras were selected. All patients were treated with a dose painting approach, three dose levels, and comprehensive bilateral neck treatment under the supervision of the same radiation oncologist. Ninety-three patients received concomitant chemotherapy (cCHT) and 14 received induction chemotherapy (iCHT). Individual information of the dose received by the oral mucosa (OM) was extracted as absolute cumulative dose-volume histogram (DVH), corrected for the elapsed treatment days and reported as weekly (w) DVH. Patients were seen weekly during treatment, and peak acute toxicity equal to or greater than confluent mucositis at any point during the course of IMRT was considered the endpoint.
  
  
  RESULTS
  Overall, 129 patients (78.7%) reached the endpoint. The regions that best discriminated between patients with/without Grade 3+ mucositis were found at 10.1 Gy/w (V10.1) and 21 cc (D21), along the x-axis and y-axis of the OM-wDVH, respectively. On multivariate analysis, D21 (odds ratio [OR] = 1.016, 95% confidence interval [CI], 1.009-1.023, p < 0.001) and cCHT (OR = 4.118, 95% CI, 1.659-10.217, p = 0.002) were the only independent predictors. However, V10.1 and D21 were highly correlated (rho = 0.954, p < 0.001) and mutually interchangeable. cCHT would correspond to 88.4 cGy/w to at least 21 cc of OM.
  
  
  CONCLUSIONS
  Radiotherapy and chemotherapy act independently in determining acute mucosal toxicity; cCHT increases the risk of mucosal Grade 3 toxicity ≈4 times over radiation therapy alone, and it is equivalent to an extra ≈6.2 Gy to 21 cc of OM over a 7-week course.
authors: Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, USA. gsangui1@jhmi.edu
authors: Giuseppe
authors: G
authors: Sanguineti
authors: Maria Pia
authors: MP
authors: Sormani
authors: Shanthi
authors: S
authors: Marur
authors: G Brandon
authors: GB
authors: Gunn
authors: Nikhil
authors: N
authors: Rao
authors: Marco
authors: M
authors: Cianchetti
authors: Francesco
authors: F
authors: Ricchetti
authors: Todd
authors: T
authors: McNutt
authors: Binbin
authors: B
authors: Wu
authors: Arlene
authors: A
authors: Forastiere
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D016001:Confidence Intervals; D000069439:Dasatinib; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D016017:Odds Ratio; D058958:Organs at Risk / Q000000981:diagnostic imaging; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011743:Pyrimidines / Q000008:administration & dosage; D011859:Radiography; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D013280:Stomatitis / Q000209:etiology* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage; D047368:Tumor Burden
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011743:Pyrimidines; D043823:Taxoids; D013844:Thiazoles; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin; D000069439:Dasatinib; D005472:Fluorouracil