title: The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients.
abstract: There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log-rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure-free survival (FFS) (HR=0.811; P = 0.010), and loco-regional failure-free survival (LR-FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack-years was also an independent predictor of OS (HR = 0.673; P < 0.001) and FFS (HR = 0.681; P < 0.001), LR-FFS (HR = 0.663; P = 0.001). A significant positive additive effect was found for the interaction between low post-RT Hb and high SI on OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post-RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco-regional recurrence compared with light smokers with high post-RT Hb levels, and post-RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post-RT Hb level and pack-years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post-RT Hb levels in the future.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Department of Medical Imaging and Interventional Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Department of Medical Imaging and Interventional Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Lu-Jun
authors.initials: LJ
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Department of Medical Imaging and Interventional Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Statistical Analysis and Medical Records, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Department of Medical Imaging and Interventional Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Pei-Hong
authors.initials: PH
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002277:Carcinoma; D002648:Child; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects* / Q000097:blood; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; D006454:Hemoglobins
keywords: Hemoglobin; interaction; nasopharyngeal carcinoma; radiotherapy; smoking
references.citation: PLoS One. 2013 Jul 15;8(7):e68660
references.pmid: 23869226
references.citation: Acta Oncol. 2012 Apr;51(4):419-32
references.pmid: 22313317
references.citation: Control Clin Trials. 1996 Aug;17(4):343-6
references.pmid: 8889347
references.citation: Am J Clin Oncol. 2007 Oct;30(5):531-9
references.pmid: 17921716
references.citation: Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):1007-11
references.pmid: 9276366
references.citation: Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1069-75
references.pmid: 9869231
references.citation: Radiother Oncol. 2012 Apr;103(1):38-44
references.pmid: 22385797
references.citation: J Clin Oncol. 2004 Jan 1;22(1):69-76
references.pmid: 14657228
references.citation: Cancer Med. 2016 May;5(5):816-26
references.pmid: 26817420
references.citation: J Clin Diagn Res. 2015 Jun;9(6):XC14-XC18
references.pmid: 26266202
references.citation: J Natl Cancer Inst. 1995 Oct 18;87(20):1530-7
references.pmid: 7563187
references.citation: J Clin Oncol. 2007 Sep 10;25(26):4066-74
references.pmid: 17827455
references.citation: Cancer Radiother. 2015 Aug;19(5):337-46; quiz 360-1, 363
references.pmid: 26119219
references.citation: Sports Med. 1999 May;27(5):275-83
references.pmid: 10368876
references.citation: J Intern Med. 1996 May;239(5):377-82
references.pmid: 8642229
references.citation: Strahlenther Onkol. 2003 Aug;179(8):527-34
references.pmid: 14509951
references.citation: PLoS One. 2015 Mar 13;10(3):e0119593
references.pmid: 25768294
references.citation: Radiother Oncol. 2014 Mar;110(3):409-15
references.pmid: 24021341
references.citation: Clin Cancer Res. 2014 Mar 1;20(5):1345-54
references.pmid: 24452791
references.citation: Int J Radiat Oncol Biol Phys. 1999 Jul 1;44(4):749-54
references.pmid: 10386631
references.citation: Cancer. 2004 Jul 15;101(2):307-16
references.pmid: 15241828
references.citation: Head Neck. 2002 Dec;24(12):1031-7
references.pmid: 12454940
references.citation: Semin Oncol. 2001 Apr;28(2 Suppl 8):1-6
references.pmid: 11395845
references.citation: Chin J Cancer. 2013 Jun;32(6):325-33
references.pmid: 23237219
references.citation: Oral Oncol. 2007 Feb;43(2):187-92
references.pmid: 16860590
references.citation: Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1018-23
references.pmid: 17716825
references.citation: Radiology. 1996 Nov;201(2):553-8
references.pmid: 8888257
references.citation: Eur J Epidemiol. 2011 Jun;26(6):433-8
references.pmid: 21344323
references.citation: Eur J Epidemiol. 2005;20(7):575-9
references.pmid: 16119429
references.citation: Int J Radiat Oncol Biol Phys. 2005 Mar 15;61(4):1087-95
references.pmid: 15752888
references.citation: Arch Surg. 1991 Sep;126(9):1131-4
references.pmid: 1929845
references.citation: Int J Cancer. 2008 Apr 1;122(7):1679-83
references.pmid: 18059031
references.citation: Radiother Oncol. 1992 Apr;23(4):229-35
references.pmid: 1609127
references.citation: Ann Hematol. 2009 Jul;88(7):687-94
references.pmid: 19039534
references.citation: Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2285-94
references.pmid: 24252872
references.citation: Ann Oncol. 2002 Jun;13(6):965-73
references.pmid: 12123343
references.citation: JAMA. 1990 Sep 26;264(12):1556-9
references.pmid: 2395196
references.citation: Chin J Cancer. 2013 Aug;32(8):453-60
references.pmid: 23863562
references.citation: Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1115-23
references.pmid: 18037583