The present study was a retrospective cohort study utilizing an NPC-specific database from Sun Yat-Sen University Cancer Center between January 2006 and October 2014. We included patients if they met the following criteria: (1) newly diagnosed non-disseminated NPC; (2) Karnosfky performance score (KPS) ≥ 80; (3) no indication of distant metastases; (4) absent of secondary malignancy; (5) treated with radical intensity-modulated radiotherapy (IMRT); and (6) complete bodyweight information. This study was approved by the Institutional Review Board of Sun Yat-Sen University Cancer Center, and informed consent was obtained from all patients.
A total of 1149 patients were included in our study. The baseline assessment included full physical examination, fiberoptic nasopharyngoscopy, magnetic resonance imaging, computed tomography, abdominal ultrasonography, biochemistry profiling and hematology, whole body bone scan or 18F-fluorodeoxyglucose positron emission tomography and computed tomography. Real-time quantitative polymerase chain reaction was used to measure Epstein-Barr virus (EBV) DNA concentrations as previously described in detail . Patients were staged based on the 7th edition of the American Joint Commission on Cancer (AJCC) staging system .
Radiotherapy and chemotherapy
All patients received radical IMRT in the current study. Dose prescribed to patients were (1) 66-70 Gy at 2.12-2.27 Gy/fraction to planning target volume (PTV) of nasopharyngeal gross tumor volume (GTVnx); (2) PTV of GTV of the metastatic lymph nodes (GTVnd) received 64-70 Gy; (3) high-risk clinical target volume (CTV1) received 60-63 Gy to PTV; and (4) low-risk clinical target volume (CTV2) received 50-56 Gy to PTV. During the study period, institutional guidelines recommended no chemotherapy for patients with stage I, and concurrent chemoradiotherapy +/− neoadjuvant/adjuvant chemotherapy for stages II to IVB, as defined by the 7th edition of AJCC staging system. Neoadjuvant or adjuvant chemotherapy consisted of cisplatin (60 mg/m2), docetaxel (60 mg/m2), and 5-fluorouracil (600 mg/m2/day over 120 h), or cisplatin (80 mg/m2) plus 5-fluorouracil (800 mg/m2/day over 120 h) or cisplatin (80 mg/m2) plus docetaxel (80 mg/m2) every 3 weeks for three cycles. Concurrent chemotherapy comprised of cisplatin (80 or 100 mg/m2) given in weeks one, four, and seven of RT, or cisplatin (40 mg/m2) given weekly during radiotherapy.
Patients’ age, height, weight, sex, pre-therapy laboratory counts of serum lactate dehydrogenase (LDH), high sensitivity C-reactive protein (hs-CRP), plasma EBV DNA, pathological types, clinical stage, and treatment type were extracted from medical records. Digital electronic scale (XiangShan, EB9871) was used to measure bodyweight to the nearest 0.1 kg in light garment and without shoes. We measured patients’ bodyweight at initiation of RT and every week during RT. Bodyweight before RT (WPre-RT) was measured at initiation of RT, and WRT1,2,3,4,5,6,7 (body weight at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT) was measured at each week of RT. The RT-PWL1,2,3,4,5,6,7 (percentage of weight loss at week 1, 2, 3, 4, 5, 6, 7 of RT) was calculated using the following equation: (WPre-RT –WRT1,2,3,4,5,6,7)/WPre-RT × 100%.
Bodyweight before NAC (WPre-NAC) was also measured at initiation of NAC for patients who received NAC before RT. NAC-PWL was calculated using the following equation: (WPre-NAC – WPre-RT)/WPre-NAC × 100%.
At time of study, all patients were on 100% oral intake, where no type of enteral feeding tube or total parental nutrition were used.
Follow-up and endpoints
Patients were examined every 3 months during the first 2 years, and every 6 months for years three through five, and annually thereafter until death. Disease-free survival (DFS) was our primary endpoint, defined as time from treatment diagnos to documented recurrence of disease (either distant metastasis or locoregional disease recurrence) or mortality from any cause, whichever occurred first. Secondary endpoints consisted of (1) distant metastasis free survival (DMFS) (no documented distant metastasis); (2) locoregional relapse free survival (LRRFS) (no documented locoregional recurrence); and (3) overall survival (OS).
In this study, we dichotomized the RT-PWL7 (percentage of weight loss at week 7 of RT) based on the optimal threshold: a RT-PWL7 of 5%, which was identified using the recursive partitioning analysis (RPA). Other variables such as host factors (e.g. age, gender, smoking history, hs-CRP, LDH, and plasma EBV DNA), treatment factors (e.g. treatment modality), and tumor factors (e.g. histology type, T stage, and N stage) were also grouped according to cutoff points from prior findings [17,18,19]. We first used the Kaplan-Meier method followed by the log-rank test to display the survival rate by the follow-up time and compare the difference in survival rates between the RT-PWL7 < 5% group and the RT-PWL7 ≥ 5% group. For each time-to-event outcome, we then developed univariate COX regression models to evaluate the association between the outcome and each of the independent variables, and included those with a P < 0.1 into the multivariate COX regression model. Hazard ratios (HRs) from the multivariate COX regression models were reported to describe the potential impact of RT-PWL7 after controlling for confounders. Furthermore, we investigated the potential factors associated with RT-PWL7 using logistic regression models. All statistical tests and p-values were two-sided. Analyses were conducted in R version 4.1.0 (http://www.r-project.org/).