Hypofractionated dose-painting intensity modulated radiation therapy with chemotherapy for nasopharyngeal carcinoma: a prospective trial

Abstract

Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction.

Methods and materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial.

Results: Patient and disease characteristics are as follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection.

Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.

Fig. 1

Local control for 25 patients treated with dose-painting intensity-modulated radiation therapy.

Fig. 2

Overall survival for 25 patients treated with dose-painting intensity-modulated radiation therapy.

Fig 3

Degree of sensorineural hearing loss with a median follow-up of 14 months after intensity modulated radiation therapy for 50 ears in 25 patients, according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0.(23)

Fig 4

Degree of xerostomia with a median follow-up of 33 months for 25 patients, according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0.(23)

Fig 5

Axial CT^*-based planning slice (left) through the PTV^† of a patient with intracranial tumor extension who developed temporal lobe necrosis (MRI^‡ right) in a region that received prescription dose. Abbreviations: * = Computed tomography; † = Planning target volume; ‡ = Magnetic resonance imaging.