The prognostic values of staging parameters require continual re-assessment amid changes in diagnostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non-metastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. We reviewed the data from 749 patients with newly diagnosed, biopsy-proven, non-metastatic NPC in our cancer center (South China, an NPC endemic area) between January 2003 and December 2007. All patients underwent magnetic resonance imaging (MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insignificant explanatory variables. The 5-year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5-year survival rates were as follows: local relapse-free survival, 94.6%; nodal relapse-free survival, 97.0%; distant metastasis-free survival, 82.6%; disease-free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only significant prognostic factor for local failure (P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho’s location of the cervical lymph nodes were significant prognostic factors for both distant failure and disease failure (all P < 0.05). Intracranial extension had significant prognostic value for distant failure (P = 0.040). The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the significant prognostic parameters for local control have also been altered substantially.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Background: To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT). Methods: Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed. Results: Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V₇₅ (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V₁₀ and V₂₀ (P = 0.552 and 0.11, respectively) were the only non-significant predictors from V₁₀ to V₇₀ for TLI. D_0.5cc (dose to 0.5 ml of the TLV) was an independent predictor for TLI (P < 0.001) in multivariate analysis; the area under the ROC curve for D_0.5cc was 0.843 (P < 0.001), and the cutoff point 69 Gy was deemed as the radiation dose limit. The distribution of high dose ‘hot spot’ regions and the location of TLI were consistent. Conclusions: A D_0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose ‘hot spots’ in the TL; physicians should be cautious of such ‘hot spots’ in the TL during IMRT treatment plan optimization, review and approval.