Induction Chemotherapy Improved Long Term Outcomes in Stage IV Locoregional Advanced Nasopharyngeal Carcinoma

Abstract

We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). Methods: From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC added to CCRT or CCRT as the upfront treatment in all LANPC stage III and LANPC IV patients. The failure free survival (FFS), overall survival (OS), local relapse free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), first failure site, and other prognostic factors were analyzed. Results: The median follow-up time of all treated LANPC patients was 59 months. For all LANPC patients, there was a significant difference only in the DMFS favoring IC group (91.5% vs 79.4%, p=0.013). In the subgroup study, for the stage III group, there was no significant difference between the groups for overall OS (IC group 71.3% vs CCRT group 78.7%), FFS (71.5% vs 62.4%) and RRFS (91.9% vs 90.9%). However, inferior LRLS (71.7% vs 91.5%; p = 0.03) was noted for the IC group. In contrast, for stage IV, there were significantly longer OS (75.8% vs 52.6%), FFS (66.8% vs 46.8%), and DMFS (86.0% vs 69.6%; p = 0.02, p = 0.04, and p = 0.03, respectively) rates in the IC group. Conclusion: Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT.

Research status and prospects of biomarkers for nasopharyngeal carcinoma in the era of high‑throughput omics (Review)

“…Great progress has been made in clinical trials of this disease and the NCCN guidelines have been rewritten (12). Conversely, biomarker research based on liquid biopsies is lagging, especially in the fields of proteomics and metabolomics, which limits the advancement of relevant research to a certain extent (7)(8)(9)(13)(14)(15)17,100,124,125). For example, IC, as a standard initial method for systemic treatment of LA-NPC, the results of clinical trials show that not all patients can benefit from its use (15).…”

“…Compared with CCRT alone, the prognosis of a considerable number of LA-NPC patients has not been significantly improved due to the addition of IC, indicating that they have suffered unnecessary over treatment ( 22 ). Conversely, in those who have extended the survival by IC+CCRT, 20-30% patients with LA-NPC still present tumor relapse and metastasis, suggesting that the current clinical application of IC may also provide insufficient treatment ( 13 , 14 ). Therefore, it is urgent to identify molecular biomarkers to predict the short-term efficacy of IC.…”

“…Radiotherapy (RT) alone is the standard treatment for early NPC, while for patients with stages III-IVa, induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) or CCRT followed by adjuvant chemotherapy (AC) are the preferred category 2A treatment regimen (4,12). A number of clinical trials have investigated the effectiveness of these treatment methods (10,(13)(14)(15). Although the 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) are improved to various degrees by the application of RT or the one of the various chemotherapy (CT) regimens, there are still many controversies in the clinical application of these treatment methods because of the lack of accurate efficacy evaluation indicators.…”

“…Although the 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) are improved to various degrees by the application of RT or the one of the various chemotherapy (CT) regimens, there are still many controversies in the clinical application of these treatment methods because of the lack of accurate efficacy evaluation indicators. For example: i) Some patients still have tumor recurrence or distant metastasis after receiving radical RT or IC+CCRT/CCRT+AC, indicating that a more effective treatment should be developed (16)(17)(18)(19); ii) IC+CCRT improves the OS and DMFS of patients with LA-NPC to a limited degree, but most patients do not benefit from it, suggesting overtreatment (13)(14)(15); iii) patients have poor tolerance to toxic side effects of the treatment, which could lead to delays or interruptions in treatment, thus increasing the risk of tumor progression or drug resistance (1,(20)(21)(22); and iv) the clinical use of Response Evaluation Criteria in Solid Tumors (RECIST) can only provide a reference for the NPC treatment effect evaluation through generalized remission or progression, and cannot provide quantifiable prediction indexes for NPC recurrence and metastasis. Moreover, the prognosis model based on the TNM staging system cannot provide an objective assessment for the risk of disease progression for patients with NPC (23,24).…”

Relationship between Climate Variables and New Daily COVID-19 Cases in Dhaka, Bangladesh

“…Clinical diagnosis has identified that COVID-19 patients have similar indications to other coronavirus affected patients, e.g. MERS and SARS [6]. The initial indication of COVID-19 infection is cough, fever, and short breath, and in the late stage, it can damage the kidney, cause pneumonia, and unexpected death.…”