Effect of Radiotherapy and Chemotherapy on the Risk of Mucositis During Intensity-Modulated Radiation Therapy for Oropharyngeal Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 83; no. 1; pp. 235 - 242
• Main Authors: Sanguineti, Giuseppe, M.D, Sormani, Maria Pia, Ph.D, Marur, Shanthi, M.D, Gunn, G. Brandon, M.D, Rao, Nikhil, M.D, Cianchetti, Marco, M.D, Ricchetti, Francesco, M.D, McNutt, Todd, Ph.D, Wu, Binbin, Ph.D, Forastiere, Arlene, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2012; Elsevier
• Subjects: Acute toxicity; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cetuximab; CHEMOTHERAPY; Cisplatin - administration & dosage; Cisplatin - adverse effects; Confidence Intervals; Dasatinib; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; HAZARDS; Hematology, Oncology and Palliative Medicine; Humans; Induction Chemotherapy - adverse effects; Induction Chemotherapy - methods; Intensity-modulated radiation therapy; Male; MEDICAL PERSONNEL; Medical sciences; Middle Aged; Mouth Mucosa - drug effects; Mouth Mucosa - pathology; Mouth Mucosa - radiation effects; Mucositis; MUCOUS MEMBRANES; MULTIVARIATE ANALYSIS; NECK; NEOPLASMS; Odds Ratio; Organs at Risk - diagnostic imaging; Oropharyngeal Neoplasms - drug therapy; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - radiotherapy; Otorhinolaryngology. Stomatology; PATIENTS; Pyrimidines - administration & dosage; RADIATION DOSES; Radiography; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted - methods; Radiotherapy, Intensity-Modulated - adverse effects; Stomatitis - etiology; Stomatitis - pathology; Taxoids - administration & dosage; Taxoids - adverse effects; Thiazoles - administration & dosage; TOXICITY; Tumor Burden; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Intensity-modulated radiation therapy; Chemotherapy; Mucositis; Oropharynx cancer; Malignant tumor; Intensity modulated radiotherapy; Treatment; Cancerology; Risk factor; ENT disease; Pharynx disease; Mucosa disease; Cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2011.06.2000

Purpose 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 and Materials 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.