Overall 779 eligible patients with LA-NPC were identified from the database. Baseline patient and pathological characteristics according to CD of cisplatin are summarized in Table 1. Majority of the patients in this cohort (99%) had WHO grades II and III disease. Approximately 50% patients underwent prophylactic feeding tube placement prior to CRT. Among those with a prophylactic feeding tube, 88% underwent percutaneous endoscopic gastrostomy, whereas 12% underwent nasogastric tube insertion. Patients who received low CD of cisplatin were significantly older at diagnosis (p<0.001) and had poorer smoking status (p=0.003), lower LN stage (p=0.016), higher incidences of comorbidities, including cardiac disease (p=0.009), diabetes mellitus (p=0.014), and hypertension (p=0.043), and higher baseline CCr (p<0.001) than other groups.
Treatments and acute complications during chemoradiotherapy
The mean CD of low-, intermediate-, and high-dose groups were 104, 207, and 287 mg/m2, respectively (Table 2). The intermediate CD group received more weekly regimens than the low and high CD groups (p=0.031). Most patients in the high CD group (98.5%) completed the planned cisplatin cycle. Only 60 patients in the low CD group (62%) received adjuvant chemotherapy, whereas 363 (88%) and 252 (93%) patients in the intermediate and high CD groups received the same, respectively (p<0.001). However, the high CD group had a significantly lower mean CD of adjuvant cisplatin than the other groups (p=0.002).
Overall, 493 patients (63%) concurrently received intensity-modulated radiation therapy (IMRT) with cisplatin as the definitive treatment, whereas 122 (16%) and 149 (19%) patients underwent 3D and 2D techniques, respectively. More patients in the intermediate CD group (72.5%) received IMRT than the low (63%) and high CD (49%) groups (p<0.001; Table 2). However, those receiving a low CD of cisplatin had a significantly low mean actual RT dose (p<0.001). Patients in the high CD group had longer duration of RT (p=0.013), whereas RT delay was more common in low CD patients (p=0.010).
Acute complication and cisplatin-related toxicity
Patients receiving a low CD of cisplatin experienced higher rates of cisplatin interruption, delay, and termination of cisplatin (p<0.001) compared with the intermediate and high CD groups (Table 2). Intermediate CD patients had the lowest incidence (4%) of hospitalization during CRT (p<0.001). Among those, in whom cisplatin was terminated, 31 (45.5%) and 8 (9.9%) in the low and intermediate CD groups subsequently received concurrent carboplatin and radiation, respectively. The low CD group had more patients with at least one acute complication (79.4%) than the other groups.
Overall, cisplatin-related toxicity occurred in 306 patients (39.3%), with the low CD group having the highest incidence (50.5%; Table 2). The most common cisplatin-related toxicities included nephrotoxicity (26.4%), grade 3–4 vomiting (4%), grade 3–4 electrolyte imbalance (3.6%), and grade 3–4 infection (including febrile neutropenia; 3.3%; Supplement 2). Mean percent drop in CCr was significantly associated with higher CD of cisplatin (p=0.001). Overall, 7% patients developed AKI during CRT, with the low CD group having the highest number (15.5%; p=0.002). Furthermore, the incidence of AKD was comparable between the high (38.2%) and low (39.1%) cisplatin groups but lower in the intermediate group (28.7%; p=0.038).
The median follow-up duration of the study was 59.4 months. Patients who received an intermediate CD of cisplatin had significantly longer median OS (64 months) than low and high (49.8 and 53.2 months, respectively) CD groups (p=0.015; Figure 1A). Moreover, 5-year OS among patients treated with low, intermediate, and high CD of cisplatin were 54%, 72%, and 60%, respectively (p=0.004). The intermediate CD group (64%) had a significantly higher 7-year OS than the low (51%) and high (53%) CD groups (p < 0.001). Subset analysis of patients who underwent IMRT showed no significant differences in OS among the cisplatin CD groups (p=0.584), whereas intermediate CD patients who underwent non-IMRT had significantly longer OS than the other groups (p=0.016; Figure 2). Those who experienced cisplatin-related toxicity during CRT had significantly shorter OS (p=0.001; Supplement 3). In addition, the intermediate CD patients had significantly longer RFS, DRFS, and LRFS than the low- and high-dose groups (Figure 1B–D).
Univariate and multivariate analyses of OS are summarized in Table 3. Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS. Multivariate analysis showed that age ³65, stage IVab at diagnosis, 2D/3D radiation technique, actual radiation dose of <6600 cGy, and hospitalization during CRT were associated with poor OS, whereas baseline BMI of ³23 kg/m2 and adjuvant chemotherapy were associated with longer OS.