Cancer Res Treat.  2019 Oct;51(4):1313-1323. 10.4143/crt.2018.503.

The Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio before Radical Radiotherapy in Patients with Non-metastatic Nasopharyngeal Carcinoma: A Propensity Score Matching Analysis

• Kim JS
• Keam B
• Heo DS
• Han DH
• Rhee CS
• Kim JH
• Jung KC
• Wu HG

• KMID: 2460581
• DOI: http://doi.org/10.4143/crt.2018.503

Abstract

PURPOSE
We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients.
MATERIALS AND METHODS
The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed.
RESULTS
The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse-free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively).
CONCLUSION
The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.

Keyword

Albumin-to-alkaline phosphatase ratio; Nasopharyngeal carcinoma; Prognosis; Radical radiotherapy; Propensity score matching

MeSH Terms

Alkaline Phosphatase
Chemoradiotherapy
Cisplatin
Cohort Studies
Disease-Free Survival
Drug Therapy
Follow-Up Studies
Hematologic Tests
Humans
Prognosis
Propensity Score*
Prospective Studies
Radiotherapy*
Retrospective Studies
Alkaline Phosphatase
Cisplatin

Figure

• 

  Fig. 1. The Kaplan-Meier survival curves of overall survival (A), progression-free survival (B), locoregional relapse–free survival (C), and distant metastasis–free survival (D) comparing patients with nasopharyngeal carcinoma according to the albumin-to-alkaline phosphatase ratio (AAPR) after propensity score matching.

• 

  Fig. 2. The Kaplan-Meier survival curves of overall survival (A), progression-free survival (B), locoregional relapse–free survival (C), and distant metastasis–free survival (D) comparing patients with locoregionally advanced nasopharyngeal carcinoma according to the albumin-to-alkaline phosphatase ratio (AAPR) after propensity score matching.

Reference

References

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65:87–108.

2. Altun M, Fandi A, Dupuis O, Cvitkovic E, Krajina Z, Eschwege F. Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects. Int J Radiat Oncol Biol Phys. 1995; 32:859–77.

3. Mao YP, Xie FY, Liu LZ, Sun Y, Li L, Tang LL, et al. Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009; 73:1326–34.

4. Zhang LN, Gao YH, Lan XW, Tang J, OuYang PY, Xie FY. Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a large scale propensity-matched study. Oral Oncol. 2015; 51:950–6.

5. Huncharek M, Kupelnick B. Combined chemoradiation versus radiation therapy alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis of 1,528 patients from six randomized trials. Am J Clin Oncol. 2002; 25:219–23.

6. Teo PM, Chan AT. Treatment strategy and clinical experience. Semin Cancer Biol. 2002; 12:497–504.

7. Tang LL, Li WF, Chen L, Sun Y, Chen Y, Liu LZ, et al. Prognostic value and staging categories of anatomic masticator space involvement in nasopharyngeal carcinoma: a study of 924 cases with MR imaging. Radiology. 2010; 257:151–7.

8. Higashi K, Ueda Y, Arisaka Y, Sakuma T, Nambu Y, Oguchi M, et al. 18F-FDG uptake as a biologic prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer. J Nucl Med. 2002; 43:39–45.

9. Au JS, Law CK, Foo W, Lau WH. In-depth evaluation of the AJCC/UICC 1997 staging system of nasopharyngeal carcinoma: prognostic homogeneity and proposed refinements. Int J Radiat Oncol Biol Phys. 2003; 56:413–26.

10. Lo YM, Chan AT, Chan LY, Leung SF, Lam CW, Huang DP, et al. Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA. Cancer Res. 2000; 60:6878–81.

11. Borda F, Borda A, Jimenez J, Zozaya JM, Prieto C, Gomez M, et al. Predictive value of pre-treatment hypoalbuminemia in prognosis of resected colorectal cancer. Gastroenterol Hepatol. 2014; 37:289–95.

12. Lim WS, Roh JL, Kim SB, Choi SH, Nam SY, Kim SY. Pretreatment albumin level predicts survival in head and neck squamous cell carcinoma. Laryngoscope. 2017; 127:E437–42.

13. Hung HY, Chen JS, Chien Y, Tang R, Hsieh PS, Wen S, et al. Preoperative alkaline phosphatase elevation was associated with poor survival in colorectal cancer patients. Int J Colorectal Dis. 2017; 32:1775–8.

14. Li G, Gao J, Liu ZG, Tao YL, Xu BQ, Tu ZW, et al. Influence of pretreatment ideal body weight percentile and albumin on prognosis of nasopharyngeal carcinoma: long-term outcomes of 512 patients from a single institution. Head Neck. 2014; 36:660–6.

15. Li G, Gao J, Tao YL, Xu BQ, Tu ZW, Liu ZG, et al. Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma. Chin J Cancer. 2012; 31:197–206.

16. Xie Y, Wei ZB, Duan XW. Prognostic value of pretreatment serum alkaline phosphatase in nasopharyngeal carcinoma. Asian Pac J Cancer Prev. 2014; 15:3547–53.

17. Chan AW, Chan SL, Mo FK, Wong GL, Wong VW, Cheung YS, et al. Albumin-to-alkaline phosphatase ratio: a novel prognostic index for hepatocellular carcinoma. Dis Markers. 2015; 2015:564057.

18. Nie M, Sun P, Chen C, Bi X, Wang Y, Yang H, et al. Albuminto-alkaline phosphatase ratio: a novel prognostic index of overall survival in cisplatin-based chemotherapy-treated patients with metastatic nasopharyngeal carcinoma. J Cancer. 2017; 8:809–15.

19. Pu N, Gao S, Xu Y, Zhao G, Lv Y, Nuerxiati A, et al. Alkaline phosphatase-to-albumin ratio as a prognostic indicator in pancreatic ductal adenocarcinoma after curative resection. J Cancer. 2017; 8:3362–70.

20. Cai X, Chen Z, Chen J, Ma X, Bai M, Wang T, et al. Albumin-to-alkaline phosphatase ratio as an independent prognostic factor for overall survival of advanced hepatocellular carcinoma patients without receiving standard anti-cancer therapies. J Cancer. 2018; 9:189–97.

21. Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, et al. Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One. 2012; 7:e51862.

22. Wee CW, Keam B, Heo DS, Sung MW, Won TB, Wu HG. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy. Radiat Oncol J. 2015; 33:98–108.

23. Tang LL, Tang XR, Li WF, Chen L, Tian L, Lin AH, et al. The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement. Oral Oncol. 2017; 69:68–73.

24. Hung TM, Fan KH, Chen EY, Lin CY, Kang CJ, Huang SF, et al. An elective radiation dose of 46 Gy is feasible in nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: a long-term follow-up result. Medicine (Baltimore). 2017; 96:e6036.

25. Yang H, Chen X, Lin S, Rong J, Yang M, Wen Q, et al. Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a prospective, multi-center, randomized clinical trial. Radiother Oncol. 2018; 126:37–42.

26. Arroyo V, Garcia-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol. 2014; 61:396–407.

27. Chandra RK. Nutrition and immunology: from the clinic to cellular biology and back again. Proc Nutr Soc. 1999; 58:681–3.

28. Reiss I, Inderrieden D, Kruse K. Measurement of skeletal specific alkaline phosphatase in disorders of calcium metabolism in childhood. Monatssch Kinderheilkd. 1996; 144:885–90.

29. Al-Batran S, Wirtz RM, Pauligk C, Steinmetz K, Probst S, Hartmann JT, et al. Association of elevated matrix metalloproteinase-9 (MMP-9) mRNA expression levels with resistance to chemotherapy and survival in patients with metastatic gastric cancer receiving first-line chemotherapy: results from the FLO versus FLP gastric cancer phase III trial of the AIO. J Clin Oncol. 2008; 26(15 Suppl):4544.