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In early NSCLC, comorbidities linked to survival



Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.

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