Highlights
- •Increasing age and comorbidity predict high competing risk in nasopharyngeal cancer.
- •The first competing risk nomograms for nasopharyngeal cancer were established.
- •The nomograms with good accuracy are convenient to quantitate survival difference.
- •Risk estimates can be useful in clinical decision making and patient counseling.
Abstract
Background and purpose
Lacking quantitative evaluations of competing risk data of nasopharyngeal carcinoma
(NPC), we aimed to evaluate the probability of NPC- and other cause-specific mortality
(NPC-SM; OCSM) and develop competing risk nomograms to quantify survival differences.
Material and method
Using the institutional big-data intelligence platform, 7251 NPC patients undergoing
intensity-modulated radiotherapy between 2009–2014 were identified to establish nomograms
based on Fine and Gray’s competing risk analysis.
Results
The 5-year NPC-SM and OCSM of the cohort were 13.1% and 1.2%, respectively, and elevated
5-year OCSMs were observed in patients aged ≥65 years (5.5%) or with severe comorbidities
(4.3%). Age was most predictive of OCSM: patients aged 55–64 and ≥65 years exhibited
subdistribution hazard ratios (SHRs) of 2.70 (95% confidence interval [CI], 1.64–4.4;
P < .001) and 5.78 (95% CI, 3.32–10.08; P < .001), respectively. Comorbidity measured using the Charlson Comorbidity Index
(CCI) was also strongly predictive of OCSM: patients with CCI scores of 1 and ≥2 exhibited
SHRs of 2.33 (95% CI, 1.46–3.71; P < .001) and 2.58 (95% CI, 1.16–5.73; P = .020), respectively. All validated factors were integrated into the competing nomograms:
age, sex, histology type, tumor and node stages, plasma Epstein–Barr virus-DNA level,
lactate dehydrogenase level, and C-reactive protein (CRP) level into the NPC-SM model
(concordance [c]-index = 0.743); and age, CCI, Albumin level, and CRP level into the
OCSM model (c-index = 0.793).
Conclusion
OCSM represents a significant competing event for NPC-SM in elderly patients and patients
with comorbidities. We present the first prognostic nomograms to quantify competing
risks, which may help to tailor individualized treatment.
Abbreviations:
AJCC (American Joint Commission on Cancer), ALB (albumin), ACT (adjuvant chemotherapy), CCI (Charlson Comorbidity Index), CRP (C-reactive protein), CI (confidence interval), c-index (concordance index), CCRT (concurrent chemotherapy with radiotherapy), CIF (cumulative incidence function), CID (cumulative incidence of death), EBV (Epstein–Barr virus), HNC (head and neck cancer), IMRT (intensity-modulated radiotherapy), LDH (lactate dehydrogenase), MRI (magnetic resonance imaging), NPC (nasopharyngeal carcinoma), NPC-SM (nasopharyngeal carcinoma-specific mortality), NCCN (National Comprehensive Cancer Network), NACT (neoadjuvant chemotherapy), OCSM (other cause-specific mortality), RT (radiotherapy), SYSUCC (Sun Yat-sen University Cancer Center), SHR (subdistribution hazard ratio), WHO (World Health Organization)Keywords
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References
- Global cancer statistics, 2012.CA Cancer J Clin. 2015; 65: 87-108
- Nasopharyngeal carcinoma incidence and mortality in China, 2013.Chin J Cancer. 2017; 36: 90
- Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis.Lancet Oncol. 2015; 16: 645-655
- What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis.J Clin Oncol. 2017; 35: 498-505
- Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial.Lancet Oncol. 2016; 17: 1509-1520
- Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial.Lancet Oncol. 2012; 13: 163-171
National Comprehensive Cancer Network. (NCCN) Clinical Practice Guidelines in Oncology. Head and Neck Cancer, Version 1. 2018. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. Accessed February 15, 2018.
- World report on ageing and health.World Health Organization, Geneva2015
- Competing risks: a practical perspective.John Wiley & Sons, 2006
- Nomogram for survival analysis in the presence of competing risks.Ann Transl Med. 2017; 5: 403
- Improved method to stratify elderly patients with cancer at risk for competing events.J Clin Oncol. 2016; 34: 1270-1277
- Primary cancer vs competing causes of death in survivors of head and neck cancer.JAMA Oncol. 2018; 4: 257-259
- Impact of increasing age on cause-specific mortality and morbidity in patients with stage I non–small-cell lung cancer: a competing risks analysis.J Clin Oncol. 2017; 35: 281-290
- Decreased overall and cancer-specific mortality with neoadjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: multivariate competing risk analysis.J Cancer. 2017; 8: 2587-2594
- Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram.J Clin Oncol. 2010; 28: 311-317
- Population-based study evaluating and predicting the probability of death resulting from thyroid cancer and other causes among patients with thyroid cancer.J Clin Oncol. 2013; 31: 468-474
- Nomogram predicting prostate cancer–specific mortality for men with biochemical recurrence after radical prostatectomy.Eur Urol. 2015; 67: 1160-1167
- Nomogram to predict cause-specific mortality in patients with surgically resected stage I non–small-cell lung cancer: a competing risk analysis.Clin Lung Cancer. 2018; 19: e195-e203
- Hepatitis B virus screening and reactivation and management of patients with nasopharyngeal carcinoma: a large-scale, big-data intelligence platform–based analysis from an endemic area.Cancer. 2017; 123: 3540-3549
- Amin M.B. American joint committee on cancer staging manual. 8th ed. Springer, New York2017
- The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.Ann Surg Oncol. 2010; 17: 1471-1474
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383
- Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma.J Clin Oncol. 2006; 24: 5414-5418
- Establishment and validation of prognostic nomograms for endemic nasopharyngeal carcinoma.J Natl Cancer Inst. 2015; 108
- Establishing and applying nomograms based on the 8th edition of the UICC/AJCC staging system to select patients with nasopharyngeal carcinoma who benefit from induction chemotherapy plus concurrent chemoradiotherapy.Oral Oncol. 2017; 69: 99-107
- Influence of gender and age on the survival of patients with nasopharyngeal carcinoma.BMC Cancer. 2013; 4: 226
- Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: a population-based analysis.Oral Oncol. 2017 Oct; 73: 83-87
- Aging with multimorbidity: a systematic review of the literature.Ageing Res Rev. 2011; 10: 430-439
- Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study.Lancet. 2012; 380: 37-43
- The impact of comorbidity on outcome in 12 623 Danish head and neck cancer patients: a population based study from the DAHANCA database.Acta Oncol. 2013; 52: 285-293
- Comorbidity predicts poor prognosis in nasopharyngeal carcinoma: development and validation of a predictive score model.Radiother Oncol. 2015; 114: 249-256
- Validity of the age-adjusted charlson comorbidity index on clinical outcomes for patients with nasopharyngeal cancer post radiation treatment: a 5-year nationwide cohort study.PLoS ONE. 2015; 10e0117323
- Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach.Crit Rev Oncol Hematol. 2005; 55: 231-240
- Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature.Nutr J. 2010; 22: 69
- Cancer-related inflammation.Nature. 2008; 454: 436-444
- The significant survival advantage of female sex in nasopharyngeal carcinoma: a propensity-matched analysis.Br J Cancer. 2015; 112: 1554-1561
- Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology.Ann Oncol. 2007; 18: 29-35
- Baseline serum lactate dehydrogenase levels for patients treated with intensity-modulated radiotherapy for nasopharyngeal carcinoma: a predictor of poor prognosis and subsequent liver metastasis.Int J Radiat Oncol Biol Phys. 2012; 82: e359-e365
Article Info
Publication History
Published online: September 27, 2018
Accepted:
September 10,
2018
Received in revised form:
August 30,
2018
Received:
June 16,
2018
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
