The long-term survival of the doublet regimen of concurrent chemoradiation therapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective study

NPC is sensitive to both radiotherapy and chemotherapy. The 3-year PFS of radiotherapy for early-stage nasopharyngeal carcinoma was 90–100% [7, 8], while the 3-year PFS of single platinum-based concurrent chemoradiation therapy for locoregionally advanced NPC was merely 70–80% [4,5,6]. Our results revealed that taxane combined with platinum-based concurrent chemoradiation therapy showed promising antitumor activity against locally advanced NPC, with a favorable long-term survival, progression-free survival outcome and tolerated toxicity profile.

This study mainly enrolled locally advanced NPC patients with T3 and T4 disease to minimize the impact of tumor clinical stage on treatment results. Among them, there were 57 patients with stage T3 disease and 47 patients with stage T4 disease. Unfortunately, only 18 people received concurrent chemoradiation therapy, and 86 received concurrent chemoradiation therapy plus 2 to 4 cycles of adjuvant chemotherapy, which may bias the ultimate survival outcome.

Platinum-based concurrent chemoradiation therapy is the backbone of treatment for locoregionally advanced NPC. According to the latest research, the 3-year PFS, OS, locoregional recurrence-free survival (LRFS) and DMFS rates of single platinum-based concurrent chemoradiation therapy alone for locoregionally advanced NPC patients were 76.5%, 90.3%, 91.0% and 84.4%, respectively [3]. However, in our study, the 3-year PFS, OS, LRRFS and DMFS rates were 85.9%, 96.0%, 96.0% and 90.8%, respectively. These results suggest that taxane combined with platinum-based concurrent chemoradiation therapy may be better than platinum-based concurrent chemoradiation therapy alone. Unfortunately, our study is a single-arm retrospective study. A prospective study is needed to further validate the survival benefit of taxane combined with platinum-based concurrent chemoradiation therapy strategies.

Additionally, we conducted a subgroup analysis of stage III and IVa patients and found that the 3-year PFS, OS, LRRFS and DMFS rates for stage III versus stage IVa were 97.8% versus 75.5% (P = 0.001), 100% versus 92.5% (P = 0.004), 100% versus 92.4% (P = 0.015) and 97.8% versus 82.8% (P = 0.002), respectively. The long-term survival of stage III NPC patients was significantly better than that of stage IVa patients. More interestingly, we found that the 3- and 5-year LRRFS and OS rates for stage III NPC were both 100%, and only two patients had distant metastases, which achieved the same therapeutic effect as the treatment of stage I nasopharyngeal carcinoma (5-year LRFS: 100%) [7, 14]. Although the 3- and 5-year LRRFS rates for stage IVa (T3N3M0 and T4N1-3M0) NPC were 92.4% and 87.2%, respectively, which were similar to previous historical data (the 3- and 5-year LRFS rates of induction chemotherapy combined with single platinum-based concurrent chemoradiation therapy and adjuvant chemotherapy for T1-4N3M0 NPC were 92.2% and 89.4%) [15], 31% of the patients were stage T1-2 NPC patients in a historical study [15]. These results suggested the synergistic sensitization effect of taxane combined with platinum-based chemotherapy and made a great contribution to LRRFS.

Other scholars have also performed exploratory studies on the doublet regimen of chemotherapy combined with radiotherapy. The survival rates in our study are longer than those reported in historical data [5, 16, 17], and the reasons are as follows: (1) the prescribed doses were 60 Gy/33 fractions for CTV1, and almost all patients were irradiated in the whole neck lymph node area; and (2) 86/104 (82.7%) patients received 2–4 cycles of adjuvant chemotherapy in this study, which contributed to the long-term survival of locally advanced NPC [18].

For late adverse events, the most common adverse event was xerostomia (65.9%), followed by deafness (44.7%), skin damage (34.1%), and temporal-lobe necrosis (20.0%). The highest incidence of grade 3 late radiotherapy toxicity was deafness at 4.7%. We suspect that this is mainly related to the wide range of tumor lesions in patients, and the auditory system is exposed to radiation doses that exceed the safe dose prescribed by the RTOG. The incidence of skin damage was 34.1%, which is related to the high neck radiation dose (60 Gy) of CTV1, while in other studies, the dosage was 54–56 Gy [5, 19, 20]. In addition, the mean number of days of radiotherapy was 47.5 (range, 45 to 50), and the normal radiotherapy time was 45 days. The patients’ radiotherapy time was prolonged for the following reasons: machine malfunctions and radiation toxicity.

Our findings should also be considered in the context of the limitations of this retrospective study. We found that taxane combined with platinum-based concurrent chemoradiation therapy with or without adjuvant chemotherapy markedly improved the locoregional recurrence-free survival for locally advanced NPC, which even reached a 100% control rate, especially for stage III NPC patients. However, the sample size of the subgroup was relatively small, and the 5-yearS follow-up rate was merely 62.5%. In addition, although the sample of stage III and stage IVa patients with concurrent chemotherapy regimens was balanced, the treatment regimens of all patients were not completely unified, which is a disadvantage in this study. The ideal treatment method should be the same protocol and the same chemotherapeutic drugs and treatment equipment. This will be further improved in our future prospective study to provide higher-level clinical data.

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