Cancer Res Treat.  2018 Jul;50(3):777-790. 10.4143/crt.2017.255.

Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area

• Xu C
• Yang SP
• Zhang Y
• Tang LL
• Zhou GQ
• Liu X
• Mao YP
• Guo R
• Li WF
• Chen L
• Lin AH
• Sun Y
• Ma J

• KMID: 2417867
• DOI: http://doi.org/10.4143/crt.2017.255

Abstract

PURPOSE
The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC).
MATERIALS AND METHODS
Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1-induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1-induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS.
RESULTS
Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel-cisplatin-5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin-5-fluorouracil (PF) (PF and docetaxel-cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1-induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect.
CONCLUSION
Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Keyword

Induction chemotherapy; Nasopharyngeal carcinoma; Neutropenia; Lymphocyte; Prognosis; Survival

MeSH Terms

Chemoradiotherapy
Disease-Free Survival
Humans
Induction Chemotherapy*
Lymphocytes
Neutropenia*
Neutrophils
Prognosis

Figure

• 

  Fig. 1. Kaplan-Meier survival curves for overall survival (A-D) and disease-free survival (E-H) stratified by grade of neutropenia. The columns represent subgroups receiving PF (B, F), TPF (C, G), and TP (D, H), respectively. PF, cisplatin–5-fluorouracil; TPF, docetaxel–cisplatin–5-fluorouracil; TP, docetaxel–cisplatin.

• 

  Fig. 2. Cumulative incidence rate (A) and frequency distribution (B) of myelosuppression events and minimal value of the post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). (A) Kaplan-Meier estimates of the time-to-occurrence over the 21-day cycle of the first cycle of induction chemotherapy (IC-1). (B) Histogram and line chart of number of patients suffering myelosuppression events and high post-NLRmin in first/second/third weeks of IC-1. TPF, docetaxel–cisplatin–5-fluorouracil; TP, docetaxel–cisplatin; PF, cisplatin–5-fluorouracil.

• 

  Fig. 3. Kaplan-Meier survival curves for overall survival (A, C, E) and disease-free survival (B, D, F) after adjustment for covariates. Patients were stratified by timing of neutropenia (absent and first/second/third week of the first cycle of induction chemotherapy) (A, B), number of myelosuppression events (group 1, none; group 2, one; group 3, two/three) (C, D), and minimal value of the post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin, < 1.33 and ≥ 1.33) (E, F). p-values for overall survival (disease-free survival) were calculated using multivariate Cox regression analyses adjusted for World Health Organization histologic type, Epstein-Barr virus DNA titer and clinical stage (all of these covariates plus neutrophil-to-lymphocyte ratio).

• 

  Fig. 4. Forest plots depicting adjusted hazard ratios (AHRs) (squares) and 95% confidence intervals (CIs) (bars) of the association between the first-cycle of induction chemotherapy (IC-1)–induced neutropenia and overall/disease-free survival. Blue and red squares individually indicate all patients and subgroups receiving different regimens. AHRs for overall survival (disease-free survival) was adjusted for timing of neutropenia, IC-1–induced anemia, IC-1–induced thrombocytopenia, minimal value of the post-treatment neutrophil-to-lymphocyte ratio, World Health Organization histologic type, Epstein-Barr virus DNA titer and clinical stage (all covariates plus neutrophil-to-lymphocyte). Ref., reference; PF, cisplatin–5-fluorouracil; TPF, docetaxel–cisplatin–5-fluorouracil; TP, docetaxel–cisplatin.

Reference

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