ABSTRACT
PURPOSE: We previously reported excellent local control for treating medulloblastoma with a limited boost to the tumor bed. In order to decrease ototoxicity, we subsequently implemented a tumor-bed boost using intensity-modulated radiation therapy (IMRT), the clinical results of which we report here. PATIENTS AND METHODS: A total of 33 patients with newly diagnosed medulloblastoma, 25 with standard risk, and 8 with high risk, were treated on an IMRT tumor-bed boost following craniospinal irradiation (CSI). Six standard-risk patients were treated with an institutional protocol with 18 Gy CSI in conjunction with intrathecal iodine-131-labeled monoclonal antibody. The majority of patients received concurrent vincristine and standard adjuvant chemotherapy. Pure-tone audiograms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Median age was 9 years old (range, 4-46 years old). Median follow-up was 63 months. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) rates for standard-risk patients who received 23.4 or 36 Gy CSI (not including those who received 18 Gy CSI with radioimmunotherapy) were 81.4% and 88.4%, respectively, at 5 years; 5-year PFS and OS rates for high-risk patients were both 87.5%. There were no isolated posterior fossa failures outside of the boost volume. Posttreatment audiograms were available for 31 patients, of whom 6%, at a median follow-up of 19 months, had developed Grade 3 hearing loss. CONCLUSION: An IMRT tumor-bed boost results in excellent local control while delivering a low mean dose to the cochlea, resulting in a low rate of ototoxicity.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Cerebellar Neoplasms/radiotherapy , Cochlea/radiation effects , Iodine Radioisotopes/therapeutic use , Medulloblastoma/radiotherapy , Radiotherapy, Intensity-Modulated/adverse effects , Adolescent , Adult , Cerebellar Neoplasms/drug therapy , Cerebellar Neoplasms/mortality , Chemotherapy, Adjuvant/methods , Child , Child, Preschool , Cranial Irradiation/methods , Disease-Free Survival , Female , Follow-Up Studies , Hearing/physiology , Hearing/radiation effects , Humans , Male , Medulloblastoma/drug therapy , Medulloblastoma/mortality , Middle Aged , New York City , Radioimmunotherapy/methods , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Combined modality therapy has become the standard of care for nasopharyngeal carcinoma, yet the combined ototoxic effects of radiation and cisplatin are poorly understood. The incidence and severity of sensorineural hearing loss (SNHL) with combined modality therapy was evaluated and the dose-response relation between radiation and hearing loss was investigated. METHODS: Patients with newly diagnosed AJCC Stage II-IVB nasopharynx carcinoma treated from 1994-2003 were identified. The records of 44 ears in 22 patients who received a preirradiation pure tone audiogram and followup audiograms 12+ months postirradiation were included in the analysis. All patients were treated with conformal radiotherapy to 70 Gy and received platinum-based chemotherapy similar to the Intergroup 0099 trial. Composite cochlear dose distributions were calculated. Ototoxicity was measured using intrasubject audiogram comparisons and SNHL was defined as per the American Speech and Hearing Association guidelines, with standard range of speech between 2000-4000 Hz. SNHL was analyzed using Fisher exact test and linear and logistic regression models. PATIENT CHARACTERISTICS: median age, 45; 27% Asian; 68% male; 64% WHO III. Median audiologic followup was 29 months (range, 12-76 mos). Mean cochlear dose (Dmean) ranged from 28.4-70.0 Gy (median, 48.5 Gy). SNHL was detected in 25 of the 44 ears (57%) studied. There was an increased risk of SNHL for ears receiving Dmean > 48 Gy compared with those receiving < or = 48 Gy at all frequencies within the range of speech (P = 0.04). Using univariate logistic regression analysis, Dmean to the cochlea, cycles of cisplatin, and time postradiotherapy were independently significant factors in determining the incidence of SNHL (P = 0.02, P = 0.03, and P = 0.04, respectively). In univariate and multivariate linear regression analysis, Dmean was statistically significant at all frequencies in affecting degree of SNHL, whereas the significance of cisplatin and time was variable. CONCLUSIONS: There was a significant increase in risk of SNHL among patients receiving > 48 Gy, suggesting a threshold in cochlear radiation dose-response in the setting of combined modality therapy. This dose should serve as a Dmean constraint maximum for intensity-modulated radiotherapy treatment of nasopharynx carcinoma.
