Background: We conducted a multicenter prospective study (NCT02575547) to investigate the association between longitudinal nutritional status and survival in locally advanced nasopharynx cancer (LA-NPC) treated with induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT). Methods: All patients with biopsy-proven LA-NPC and planned for IC-CCRT were recruited from ten institutions. IC entailed 2 cycles of docetaxel 75mg/m²/3w and cisplatin 75mg/m²/3w; CCRT entailed 2-3 cycles cisplatin 100mg/m²/3w and IMRT (70-72Gy/30-32fr). Study parameters included weight loss (WL), % of ideal body weight (%IBW), body mass index (BMI), nutrition risk screening 2002 (NRS2002), patient-generated subjective global assessment (PG-SGA), and EORTC QLQ-C30 that were collected at the following time-points: baseline (T1), 1 w pre-2^nd IC (T2), 1 w pre-CCRT (T3), 4 w mid-CCRT (T4), end-CCRT (T5), 3 mo post-CCRT (T6), 1 y post-CCRT (T7), 2 y post-CCRT (T8). Results: 186 patients were recruited; 171 were eligible for analysis. Median follow-up was 35.8 mo (range 12.3-46.1 mo). Compliance rates were 97.7% (167/171) and 87.7% (150/171) for IC and CCRT, respectively; all except one completed RT. Longitudinal assessment indicated the worst nutritional status at T5, followed by recovery at T8: 27.1% with %IBW <90%; 69.2% with WL ≥5%, which was also associated with a worsened QOL (OR = 6.23 for QOL change ≥25.0, P = 0.012). Interestingly, T1 nutritional status was not associated with prognosis (P >0.05 for all). However, nutritional parameters at T5 were significantly associated with survival; %IBW <90% was the strongest predictor for inferior DMFS (HR = 2.669) and OS (HR = 4.661) among all parameters (multivariable-adjusted P <0.05). Subgroup analyses revealed that %IBW <90%, WL ≥10% at T5 represented the most adverse subset of patients (Table). Conclusions: Here, we show that poor nutrition despite systemic intensification leads to inferior QOL and disease control in LA-NPC patients. This is counter-intuitive and highlights the crucial importance of paracrine factors in optimising treatment efficacy. Clinical trial information: NCT02575547