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Purpose Current guideline recommends a uniform method of delineation of subclinical disease within the primary clinical target volume (CTVp) for all stages of nasopharyngeal carcinoma (NPC). We performed a prospective observational study to investigate the outcomes with a reduced CTVp and radiation dose for early-stage NPC. Methods and Materials Patients with newly diagnosed, biopsy-proven World Health Organization type II-III and American Joint Committee on Cancer/Union for International Cancer Control sixth edition stage T1-2N0-1 disease were enrolled. All patients were treated with intensity modulated radiation therapy alone. We categorized CTVp into CTVp1 (high risk) and CTVp2 (low risk). CTVp1 comprised of gross tumor (on magnetic resonance imaging or contrast-enhanced computed tomography) plus a 5-mm margin (3-mm posteriorly) and was prescribed to 60 Gy in 30 fractions (fr). CTVp2 was generated from CTVp1 plus a 5-mm margin (3 mm posteriorly), excluding the maxillary and cavernous sinuses, and was prescribed to 54 Gy in 30 fr. The prescribed doses to the primary and nodal gross tumor volume (GTVp and GTVn) were 68 Gy in 30 fr and 60 to 66 Gy in 30 fr, respectively. Primary endpoint was local recurrence-free survival. This study was registered in ClinicalTrials.gov , number NCT03839602 . Results From May 2001 to August 2006, 103 patients were recruited and completed IMRT. With a median follow-up of 15.2 years (range, 2.1-18.1 years), only 1 patient had local failure. Ten-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival were 90.3%, 88.3%, 90.3%, and 91.2%, respectively. Among late IMRT-related adverse events, we recorded 2 patients with G1 cranial nerve injury, 3 patients with G3 hearing loss, and 3 patients with G3 subcutaneous fibrosis. No patients had temporal lobe necrosis, brain stem injury, or trismus. Conclusions Decreased CTV margins and radiation doses can achieve long-term tumor control with mild late toxicities for patients with early-stage NPC.

// An-Chuan Li 1,2,* , Wei-Wei Xiao 1,* , Guan-Zhu Shen 1,* , Lin Wang 1 , An-An Xu 1,3 , Yan-Qing Cao 1,4 , Shao-Min Huang 1 , Cheng-Guang Lin 1 , Fei Han 1 , Xiao-Wu Deng 1 and Chong Zhao 1 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China 3 Department of Radiation Oncology, Cancer Center of Guangzhou Medical University, Guangzhou, China 4 Department of Radiation Oncology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Fei Han, email: // Xiao-Wu Deng, email: // Chong Zhao, email: // Keywords : nasopharyngeal carcinoma, distant metastasis, intensity-modulated radiotherapy, chemotherapy Received : March 24, 2015 Accepted : May 22, 2015 Published : May 28, 2015 Abstract Purpose: To report the distant metastasis (DM) risk and patterns for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to analyze the benefits of chemotherapy based on DM risk. Materials and Methods: 576 NPC patients were analyzed. The DM rates were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences. The patients were divided into different risk subclassifications according to DM hazard ratios. Results: 91 patients developed DM after treatment, with bone as the most common metastatic sites. 82.4% of DMs occurred within 3 years of treatment. Patients were classified as low-risk, intermediate-risk and high-risk, and the corresponding 5-year DM rates were 5.1%, 13.1% and 32.4%, respectively ( P < 0.001). Chemotherapy failed to decrease the DM rate in the low-risk subclassification, but decreased the DM risk in the intermediate-risk subclassification ( P = 0.025). In the high-risk subclassificaiton, the DM rate was 31.9% though chemotherapy was used, which was significantly higher than that of other two subclassifications. Conclusions: DM is the dominant treatment failure in NPC treated by IMRT, with similar occurrence times and distributions to those that occurred in the era of conventional radiotherapy. Further studies on treatment optimization are needed in high-risk patients.

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4 months. The 5-year DM rate was 15.1 %. N2–3, primary tumour volume of nasopharynx (GTVnx) >24.56 cm3, haemoglobin change after treatment (ΔHGB) >25.8 g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245 U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0–2), intermediate risk (3–4) and high risk (5–8). The 5-year DM rates were 4.6, 21.8 and 50.8 %, respectively (P

Background Intensity modulated radiation therapy (IMRT) is the standard of care for nasopharyngeal carcinoma (NPC). Part of the IMRT quality assurance process involves accurate target volume delineation, which is crucial for local control and survival. Current practice utilizes a uniform contouring method for clinical target volume (CTV) for all stages of NPC. Here, we conducted a single-arm phase 2 trial investigating the tumor control rates of reduced CTV margins and corresponding doses in low-risk, early-stage NPC. Methods Patients with biopsy-proven stage I-IIb (6th UICC/AJCC) NPC were enrolled. All patients were treated with IMRT alone. Two CTVs (CTV1 [high risk] and CTV2 [low risk]) were outlined; CTV1 was defined by grossly identified tumour (on MRI or CT) plus 5-mm margin (3-mm posteriorly); CTV2 was CTV1 plus 5-mm margin (3-mm posteriorly). 60 Gy and 50–54 Gy in 30 fractions were prescribed to CTV1 and CTV2, respectively. Primary end-point was locoregional recurrence free survival (LRRFS). Results From May 2001 to August 2006, 103 patients were recruited; all patients completed IMRT as planned (time duration 39-61 days). At a median follow-up of 12.6 years, five patients developed locoregional failures; of which one was in-field, and four were regional recurrence (two in-field and two marginal). 10-year LRRFS, distant metastasis free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 95.0% and 94.1%, 94.0% and 91.1%, respectively. The most common grade 1-2 late toxicities included subcutaneous fibrosis (79.6%), hearing loss (53.4%) and skin dystrophy (43.2%); grade 3 included subcutaneous fibrosis (2.9%) and hearing loss (2.9%); and no grade 4 late toxicity. Conclusions Reduced CTV margins and corresponding doses results in optimal long-term tumour control, with minimal late adverse events. Clinical trial identification NCT03839602. Legal entity responsible for the study Chong Zhao. Funding National Natural Science Foundation of China [No. 81872469]; Science and Technology Project of Guangdong Province [No. 2014A020212433]. Disclosure M.L.K. Chua: Honoraria (institution), Advisory / Consultancy: Janssen, Astellas, Varian, Ferring Singapore and AstraZeneca; Research grant / Funding (institution), Structured research agreement/Research funding - Ferring Singapore, GenomeDx Biosciences, Varian, MedLever.: Ferring Singapore, GenomeDx Biosciences, Varian, MedLever. All other authors have declared no conflicts of interest.