Mucositis versus tumor control: the therapeutic index of adding chemotherapy to irradiation of head and neck cancer.
OBJECTIVE
To determine whether the addition of concurrent chemotherapy to radiation for head and neck cancer (HNSCC) improves the therapeutic ratio regarding tumor control vs. mucositis.


METHODS
Data were taken from 14 randomized trials of radiation with or without concurrent chemotherapy for HNSCC. Mucositis-bioequivalent dose (mBED) was computed for each study using mBED = D [1 + d/(alpha/beta)] - 0.693(T - Tk)/Tp. An "S-value," relating the increase in the rate of Grade 3 (confluent) mucositis to the increase in mBED with radiation alone, was determined using data from trials of radiation alone with altered fractionation. We then determined the difference in the rate of mucositis and used the S-value to estimate the apparent difference in mBED in the chemoradiation and radiation alone arms for each trial. After accounting for differences in the radiation schedules, we estimated the mBED attributable to adding chemotherapy and compared it with previously published estimates of increases in tumor BED.


RESULTS
Computed S-values ranged from 0.4 to 1.7. For S = 1, the mean increase in mBED attributable to chemotherapy was 8.3 Gy(10) (SD = 6.4). The average difference between tumor-BED and mBED was 2.8 Gy(10) (SD = 6.0). Increasing the S-value decreases the estimated increase in mBED due to chemotherapy.


CONCLUSIONS
Concurrent chemotherapy improves the therapeutic index for radiation of HNSCC. Further refinements are needed in quantifying the therapeutic gain attributable to specific radiosensitizing agents in clinical trials, notably better and more consistent reporting of treatment sequelae.
Lee
Irwin H
IH
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. ihlee@post.harvard.edu
Eisbruch
Avraham
A
D003131:Combined Modality Therapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D052016:Mucositis / Q000209:etiology / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012062:Relative Biological Effectiveness
D011838:Radiation-Sensitizing Agents