This retrospective study was approved by the ethics committee of the First People’s Hospital of Foshan, Foshan, China. The inclusion criteria were as follows: patients with newly diagnosed, nonmetastatic, and histologically proven NPC. Patients were treated with RT alone or concurrent chemoradiotherapy (CCRT), but did not receive neoadjuvant chemotherapy or adjuvant chemotherapy. In addition, all patients underwent nasopharyngeal fiberscope and magnetic resonance imaging (MRI) scan of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT. Between June 2004 and November 2009, 188 eligible patients were included in the study, including 138 male and 50 female patients (male:female, 2.8:1). The median age was 50 years (range, 14–85 years). Histologically, 98.9% of patients had nonkeratinizing NPC, 0.5% had keratinizing NPC, and the remainder (0.5%) had other types. All patients underwent pretreatment evaluation that included complete history, physical and neurological examinations, hematology and biochemistry profiles, nasopharyngeal fiberscopy, nasopharynx and neck MRI, chest radiography, and abdominal sonography. Medical and imaging records were retrospectively reviewed and all patients were restaged according to the 7th edition of the AJCC staging system
. The TNM stage distribution of all patients was T1 in 19.7%, T2 in 10.1%, T3 in 37.8%, and T4 in 32.4%; N0 in 6.9%, N1 in 50.0%, N2 in 42.6%, and N3 in 0.5%; Stage I in 2.7%, Stage II in 14.9%, Stage III in 49.5%, and Stage IVA-B in 33.0%.
All patients underwent MRI using a 1.0 Tesla scanner (Siemens Magnetom Impact, Siemens Healthcare, Erlangen, Germany). The area from the suprasellar cistern to the inferior margin of the sternal end of the clavicle was examined using a head and neck segregate coil. T1-weighted fast spin-echo images in the axial, coronal, and sagittal planes (repetition time, 500 ms; echo time, 12 ms) and T2-weighted fast spin-echo MR images in the axial plane (repetition time, 3,304 ms; echo time, 96 ms) were obtained before the injection of contrast material. After intravenous injection of gadopentetate dimeglumine (Gd-DTPA; 0.1 mmol/kg body weight; Magnevist, Schering, Berlin, Germany), spin-echo T1-weighted axial and sagittal sequences and spin-echo T1-weighted fat-suppressed coronal sequences were performed sequentially using similar parameters to those used prior to Gd-DTPA injection. We used a section thickness of 5 mm and a 256 × 256 matrix size.
Two radiologists with clinical focus on head and neck cancer and certifications for professional diagnostic imaging in China, who have been on staff for 10 years, evaluated the MR images separately. Any discord in evaluation was resolved by consensus every two weeks. Tumor soft tissue had low signal intensity on T1-weighted images; it had intermediate signal intensity superior to the muscle signal on T2-weighted images; tumor soft tissues had moderate enhancement on contrast-enhanced T1-weighted images, replacing the normal anatomy of the structure. Tumor regression was evaluated by the change in the maximum primary tumor diameter (MPTD) on the same plane after RT. The method applied to measure MPTD was as follows
: firstly, MPTD was measured on post-Gd-DTPA T1-weighted images. Secondly, tumor signal was not interrupted, but continuous on the maximum diameter. Finally, the maximum diameters in the axial, coronal and sagittal planes were measured separately; the largest value was recorded as the MPTD. Tumor regression was divided into four levels: CR, PR, SD, and PD, according to RECIST
All patients were treated with definitive-intent RT. One hundred and five patients (55.9%) were treated with conventional 2-dimensional RT (2-DRT) and 83 (44.1%) were treated with 3-dimensional conformal RT (3-DCRT). The accumulated doses were 68–70 Gy to the gross tumor, 60–62 Gy to involved areas of the neck, and 50 Gy to uninvolved areas. Boost irradiation to the parapharyngeal space, skull-base, and primary or nodal sites were administered if indicated, and did not exceed 16 Gy. Ninety patients (57.7%) were treated with boost irradiation.
Platinum-based concomitant chemotherapy was administered to 130 patients with Stage III or Stage IVA-B disease (classified as T3-T4 or N2-N3). The remaining 25 patients with advanced-stage disease did not receive chemotherapy due to advanced age, heart disease, hepatitis, severe diabetes, inadequate renal function, patient refusal, or economic problems. When possible, salvage treatment (including afterloading, surgery, and chemotherapy) was provided in the event of documented relapse or if the disease persisted despite therapy.
Patients were assessed every two months during the first year, every three months for the next two years, and every six months thereafter until death. All events were measured from the date of commencement of treatment. The following end points (time to the first defining event) were assessed: OS, local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS). Local recurrence was established by fiberoptic endoscopy and biopsy and/or MRI. Distant metastases were diagnosed based on clinical symptoms, physical examination, and imaging methods, including chest radiography, bone scan, computed tomography, and abdominal sonography.
All statistical analyses were performed using Statistical Package for the Social Sciences version 12.0 (SPSS, Chicago, IL, USA). Actuarial rates were calculated using the Kaplan-Meier method and differences were compared using the log-rank test. Multivariate analyses with the Cox proportional hazards model were used to test for independent significance by backward elimination of insignificant explanatory variables. Demographic characteristics (age, sex) were introduced into the models as covariates for all statistical tests. No correction for multiple testing was performed. The criterion for statistical significance was set at α = 0.05; P-values were based on two-sided tests.