Qiaojuan Guo1, Tianzhu Lu2, Shao Hui Huang3, Brian O'Sullivan3, Jingfeng Zong4, Youping Xiao5, Wei Xu6, Chuanben Chen4, Sufang Qiu4, Luying Xu4, Wei Zheng4, Yunbin Chen3, Shaojun Lin7, Jianji Pan8. 1. Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China. 3. Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, Canada. 4. Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China. 5. Department of Radiology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China. 6. Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. 7. Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China. Electronic address: linshaojun@yeah.net. 8. Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China. Electronic address: panjianji@126.com.
Abstract
BACKGROUND: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. METHODS: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. RESULTS: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS. CONCLUSIONS: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials.
BACKGROUND: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. METHODS: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. RESULTS: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS. CONCLUSIONS: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials.