Quality of Life as a Mediator between Cancer Stage and Long-Term Mortality in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Radiotherapy

Abstract

Background: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Patients and methods: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny's method were used to assess the investigated effects.

Results: Advanced AJCC stage (III-IV) patients revealed a 2.26-fold (95% CI-1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I-II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8-9.8% at pre-IMRT but at 2 years post-IMRT were 39.4-49.4% by global health QoL and QoL-HN35 symptoms.

Conclusions: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.

Keywords: Baron and Kenny’s method; intensity modulated radiotherapy; mediator; mortality; nasopharyngeal carcinoma; quality of life.

Figure 1

Cumulative mortality rates of nasopharyngeal cancer patients associated with AJCC stages. Note: Cumulative mortality rates were estimated from the Kaplan–Meier estimators. Log-rank test was used to test the equality of cumulative mortality rates between AJCC stages (difference in 4 AJCC stages, χ² = 61.65, p < 0.001; difference in AJCC stage I–II versus III–IV, χ² = 22.66, p < 0.001). CI, confidence interval.

Figure 2

Distributions of adjusted quality of life (QoL) mean scores associated with AJCC stage (I–II/III–IV) at different intensity-modulated radiotherapy (IMRT)-related time points for nasopharyngeal cancer patients. (A) Global health QoL; (B) Functioning QoL; (C) QoL-C30 symptom; (D) QoL-HN35 symptom. Note: The investigated time periods included the pre-IMRT, during IMRT (40 Gy), and 3 months, 1 year, and 2 years post IMRT. The QoL scores were adjusted for age, gender, ethnicity, educational level, body mass index, Charlson comorbidity index, chemotherapy, and IMRT treatment period. * denotes significant difference in the adjusted QoL mean scores between AJCC stage I–II and III–IV. GHQoL, Global Health QoL, FQoL, Functioning QoL, QoL-C30 symptom, and QoL-HN35 symptom denoted the average QoL scores obtained from the EORTC QLQ-C30 global QoL scale, 5 functional scales, and 9 symptom scales/items, and EORTC QLQ-HN35 18 symptom scales/items, respectively. IMRT, intensity-modulated radiotherapy; yrs, years; EORTC, European organization for research and treatment of cancer; QoL-C30, the core QoL questionnaire of EORTC; QoL-HN35, the head and neck cancer-specific QoL questionnaire module of EORTC.

Figure 3

The intermediated paths of quality of life (QoL) scales at different intensity-modulated radiation therapy (IMRT)-related time points on the association between advanced AJCC stage (III–IV) and higher mortality risk in nasopharyngeal cancer patient follow-up cohort (intermediated path: Advanced AJCC stage to QoL score to Mortality risk). Note: Effect change (EC) was the excessive effect explained by a specific QoL scale at a time period. Global health QoL, QoL-C30 symptom, and QoL-HN35 symptom denoted the average QoL scores obtained from the EORTC QLQ-C30 global QoL scale, 9 symptom scales/items, and EORTC QLQ-HN35 18 symptom scales/items, respectively. AJCC, American Joint Committee on Cancer; EORTC, European organization for research and treatment of cancer; QoL-C30, the core QoL questionnaire of EORTC; QoL-HN35, the head and neck cancer-specific QoL questionnaire module of EORTC.