Heterogeneity in quality of life among patients receiving first postoperative chemotherapy for gastric cancer: A latent profile analysis of psychosocial and symptom pathways

Technical Summary: Heterogeneity in Quality of Life Among Gastric Cancer Patients Undergoing First Postoperative Chemotherapy

Problem Statement
Gastric cancer remains a significant global health burden, particularly in East Asia. While surgery combined with systemic therapy is the standard of care, the initiation of first postoperative chemotherapy represents a vulnerable period where patients face concurrent recovery from surgery and the symptom burden of chemotherapy. Existing research on health-related quality of life (HRQoL) in this population has predominantly relied on variable-centered approaches, focusing on mean scores and single predictors. These methods often obscure meaningful heterogeneity in patient-reported outcomes. Furthermore, prior person-centered studies in gastric cancer have largely focused on symptom clusters or distress trajectories in advanced disease, rarely integrating both symptom-related and psychosocial pathway analyses within a single framework to understand how factors like resilience, fear of progression, and social support jointly shape HRQoL heterogeneity during early postoperative chemotherapy.

Methodology
This study employed a multicenter, cross-sectional design involving 453 patients hospitalized for their first postoperative chemotherapy admission at three tertiary hospitals in Jiangsu, China. Data were collected via face-to-face interviews using a standardized electronic data capture system.

• Measures:
  • HRQoL: Assessed using the Quality of Life Instruments for Cancer Patients–Stomach Cancer (QLICP-ST), covering physical, psychological, social, symptom/side-effect, and specific domains.
  • Psychosocial Variables: Fear of progression (FoP-12), General Self-Efficacy (GSES), Resilience (CD-RISC), and Social Support (SSRS).
  • Symptom Burden: Measured via the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), reverse-coded so higher scores indicate lighter burden.
  • Functional Status: Assessed using the Karnofsky Performance Status (KPS).
• Statistical Analysis:
  • Latent Profile Analysis (LPA): Performed using the mclust package in R to identify unobserved subgroups based on the five QLICP-ST domain scores. Model selection utilized AIC, BIC, adjusted BIC, entropy, and likelihood ratio tests.
  • Correlates: Multinomial logistic regression was used to examine demographic, clinical, and psychosocial factors associated with profile membership, using the intermediate profile as the reference.
  • Pathway Analysis: Structural Equation Modeling (SEM) using the lavaan package tested hypothesized indirect pathways linking social support, resilience, self-efficacy, fear of progression, symptom experience, and HRQoL. Indirect effects were assessed via bootstrap resampling (2,000 iterations).

Key Results
The analysis identified three distinct latent profiles of HRQoL:

1. Psychosocially Supported but Physically Vulnerable (17.7%): Characterized by the lowest physical function scores but the highest psychological and social function scores and the lightest symptom burden.
2. Functionally Preserved but Symptomatically and Psychologically Challenged (22.1%): Showed the highest physical function scores but the lowest psychological function scores and the heaviest symptom burden.
3. Intermediate Adaptation (60.3%): Displayed intermediate scores across all five domains and constituted the largest subgroup.

Correlates of Profile Membership:
Functional status (KPS), symptom burden, and social support were the most consistent differentiating correlates.

• Membership in the Physically Vulnerable profile was significantly associated with lighter symptom burden, higher social support, and lower KPS.
• Membership in the Functionally Preserved profile was associated with heavier symptom burden, lower social support, higher KPS, higher resilience, and lower fear of progression.

Structural Equation Modeling Findings:
The SEM demonstrated a good fit (CFI = 0.990, RMSEA = 0.045).

• A statistically significant chained indirect association was identified from social support to HRQoL through resilience, fear of progression, and symptom experience ($B = 0.006$, 95% CI: 0.002–0.011).
• The indirect pathway through self-efficacy was not significant.
• Symptom burden contributed the largest proportion of explained variance in quality of life (64.6%).

Significance and Claims
The authors claim that HRQoL during first postoperative chemotherapy for gastric cancer is heterogeneous and cannot be adequately represented by a single average pattern. The study posits that this heterogeneity reflects distinct constellations of adaptation rather than a simple severity gradient. Specifically, the findings suggest that patients at the same treatment stage may arrive at markedly different adaptation states through different pathways, involving a mismatch between bodily recovery and psychological adjustment.

The paper concludes that supportive care should be person-centered, integrating functional, symptom, and psychological assessments from the outset of chemotherapy. It argues that screening should move beyond total HRQoL scores to include specific domains such as functional status, symptom burden, fear of progression, and psychosocial resources. The authors emphasize that social support may operate as a compensatory mechanism in response to vulnerability rather than a uniformly protective factor, and that fear of progression is closely linked to symptom salience and quality of life.

Limitations Acknowledged
The study acknowledges that its cross-sectional design precludes causal inference, meaning the SEM represents hypothesized associations rather than temporal mechanisms. Generalizability may be limited due to convenience sampling from a single province. Additionally, the heterogeneity of chemotherapy regimens (where XELOX and SOX accounted for only 40.8% of the sample) represents an unmeasured source of variability. Finally, the use of self-reported psychosocial variables and a China-specific QoL instrument may introduce response bias and limit direct comparability with international studies.