Development and validation of a web-based calculator to predict individualized conditional risk of site-specific recurrence in nasopharyngeal carcinoma: Analysis of 10,058 endemic cases

Background:Conditional survival(CS)provides dynamic prognostic estimates by considering the patients existing survival time.Since CS for endemic nasopharyngeal carcinoma(NPC)is lacking,we aimed to assess the CS of endemic NPC and establish a web-based calculator to predict individualized,conditional sitespecific recurrence risk.Methods:Using an NPC-specific database with a big-data intelligence platform,10,058 endemic patients with non-metastatic stage I–IVA NPC receiving intensity-modulated radiotherapy with or without chemotherapy between April 2009 and December 2015 were investigated.Crude CS estimates of conditional overall survival(COS),conditional disease-free survival(CDFS),conditional locoregional relapse-free survival(CLRRFS),conditional distant metastasis-free survival(CDMFS),and conditional NPC-specific survival(CNPC-SS)were calculated.Covariate-adjusted CS estimates were generated using inverse probability weighting.A prediction model was established using competing risk models and was externally validated with an independent,non-metastatic stage I–IVA NPC cohort undergoing intensity-modulated radiotherapy with or without chemotherapy(n=601)at another institution.Results:The median follow-up of the primary cohort was 67.2 months.The 5-year COS,CDFS,CLRRFS,CDMFS,and CNPC-SS increased from 86.2%,78.1%,89.8%,87.3%,and 87.6%at diagnosis to 87.3%,87.7%,94.4%,96.0%,and 90.1%,respectively,for an existing survival time of 3 years since diagnosis.Differences in CS estimates between prognostic factor subgroups of each endpoint were noticeable at diagnosis but diminished with time,whereas an ever-increasing disparity in CS between different age subgroups was observed over time.Notably,the prognoses of patients that were poor at diagnosis improved greatly as patients survived longer.For individualized CS predictions,we developed a web-based model to estimate the conditional risk of local(C-index,0.656),regional(0.667),bone(0.742),lung(0.681),and liver(0.711)recurrence,which significantly outperformed the current staging system(P<0.001).The performance of this webbased model was further validated using an external validation cohort(median follow-up,61.3 months),with C-indices of 0.672,0.736,0.754,0.663,and 0.721,respectively.Conclusions:We characterized the CS of endemic NPC in the largest cohort to date.Moreover,we established a web-based calculator to predict the CS of sitespecific recurrence,which may help to tailor individualized,risk-based,timeadapted follow-up strategies.

Low-dose metronomic chemotherapy improves tumor control in nasopharyngeal carcinoma

1 BACKGROUND Nasopharyngeal carcinoma(NPC)is a unique head and neck malignancy prevalent in East Asia[1].It is highly malignant,with the non-keratinizing pathological subtype constituting approximately 95%of NPC cases in endemic areas.Chemotherapy in combination with radiotherapy is recommended for locoregionally advanced NPC(LANPC),especially in subgroups at higher risk of distant metastasis(e.g.,N2-3 vs.N0-1 diseases,high vs.low plasma Epstein-Barr virus[EBV]DNA copy number)[2,3].Concurrent chemoradiotherapy with or without induction chemotherapy is considered the backbone of the current chemoradiotherapy strategies for NPC[2,3].Nevertheless,although complete clinical remission could be achieved in more than 90%of patients after definitive chemoradiotherapy,about 20%-30%of patients will have disease recurrence subsequently[4,5],which might be caused minimal residual disease(MRD),either at locoregional or distant sites[6,7].Thus,adjuvant therapy is needed to improve tumor control.