Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy (IMRT) as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma (NPC), but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients. Endoscopic nasopharyngectomy (ENPG) was successfully applied in recurrent NPC with radiation free and relatively low medical costs. In this study, we examined whether ENPG could be an effective treatment for localized stage I NPC. METHODS: Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center. Simultaneously, the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort. The survival outcomes, quality of life (QOL), and medical costs between two groups were compared. RESULTS: After a median follow-up of 59.0 months (95% CI 53.4-64.6), no death, locoregional recurrence, or distant metastasis was observed in the 10 patients treated with ENPG. The 5-year overall survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients (100% vs. 99.1%, 100% vs. 97.7%, 100% vs. 99.0%, 100% vs. 97.4%, respectively, P > 0.05). In addition, compared with IMRT, ENPG was associated with decreased total medical costs ($ 4090.42 ± 1502.65 vs. $ 12620.88 ± 4242.65, P < 0.001) and improved QOL scores including dry mouth (3.3 ± 10.5 vs. 34.4 ± 25.8, P < 0.001) and sticky saliva (3.3 ± 10.5 vs. 32.6 ± 23.3, P < 0.001). CONCLUSIONS: ENPG alone was associated with promising long-term survival outcomes, low medical costs, and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy. However, the application of ENPG should be prudent, and prospective clinical trials were needed to further verify the results.

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial.

BACKGROUND: The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. METHODS: Patients with stage III-IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 civ d1-5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints. RESULTS: Four hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77-0.87) than the control arm (74.1%, 95% CI = 0.68-0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3-4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3-4 toxicities (P < 0.001). CONCLUSION: NACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.

Randomized study of sinusoidal chronomodulated versus flat intermittent induction chemotherapy with cisplatin and 5-fluorouracil followed by traditional radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a "MELODIE" multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2% for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1% for Arm A and 90.2%, 85.2%, and 81.7% for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.