New research debunks perceived benefits of overweight/obesity in lung cancer patients
In Buffalo, New York, the widely held belief that having overweight or obesity could have protective benefits for lung cancer patients has been critically re-examined by researchers at the Roswell Park Comprehensive Cancer Center. Despite obesity being linked to an increased risk and poorer prognosis in at least thirteen different cancer types, lung cancer has been noted as a striking exception. Previous studies suggested that patients with a higher Body Mass Index (BMI) faced a reduced risk of disease recurrence and enjoyed longer survival rates post-surgery, a phenomenon dubbed “the obesity paradox”. This has raised questions about the paradoxical role of obesity in lung cancer outcomes compared to its universally acknowledged negative impact on other cancer types.
Sai Yendamuri, MD, MBA, FACS, the Chair of Thoracic Surgery at Roswell Park, spearheaded a research initiative that has shed light on crucial “confounding factors” that distorted earlier conclusions, suggesting a beneficial link between overweight conditions and lung cancer patient prognoses. Dr. Yendamuri, along with a distinguished team including Santosh Patnaik, MD, PhD, Assistant Professor of Oncology in the Department of Thoracic Surgery, and Joseph Barbi, PhD, Assistant Professor of Oncology in the Department of Immunology, presented their groundbreaking findings at the annual American Association for Cancer Research (AACR) symposium held in San Diego, California, from April 5 to 10, 2024.
The research illuminated the inadequacy of BMI as a reliable measure of obesity, pinpointing it as one of the key factors leading to the misinterpretation of previous studies’ results. BMI, a simple calculation based on height and weight, fails to accurately represent the body’s fat percentage, its distribution, or differentiate between fat types. Through a meticulous case-control study utilising CT imaging, the team discovered that early-stage lung cancer patients exhibited a greater fat content without necessarily having a higher BMI, compared to high-risk individuals without lung cancer.
Moreover, the study revealed a heightened risk of disease recurrence in surgically treated lung cancer patients with substantial volumes of visceral fat—the dangerous type lodged between abdominal organs—regardless of their BMI status. Laboratory findings complemented these observations, suggesting that the rapid growth of lung tumours might be facilitated by an obesity-induced increase in suppressor leukocytes, which dampen the immune system’s ability to fight cancer.
Further investigations into patients categorised as having obesity through CT imaging rather than BMI calculations confirmed the suppression of the immune response within the lung microenvironment, allowing for unchecked cancer cell proliferation. These insights underscore the urgency for developing more precise obesity measurement methods to better understand its impact on lung cancer patients and tailor treatment approaches accordingly.
Dr. Yendamuri advocated for the exploration of blood-based testing as a future direction for accurately assessing obesity, circumventing the limitations of CT scans not typically conducted for all cancer patients. Identifying blood-based biomarkers correlating with imaging-derived fat measurements could revolutionise how obesity is gauged, facilitating more informed treatment decisions.
Another aspect of the study addressed the observed effects of certain medications, like metformin used for diabetes management, which appeared to offer additional anticancer benefits exclusively to patients with obesity. Laboratory and retrospective analyses supported the notion that in individuals with obesity, metformin could enhance the vulnerability of lung carcinoma tumours to immunotherapy, particularly immune checkpoint inhibitors (ICIs), promoting a more effective antitumor immune response.
Reflecting on the broader implications of their work, Dr. Yendamuri highlighted the necessity of re-evaluating the design of future studies to account for the limitations of BMI as an obesity measure and the distinct effects of medications in patients with obesity. Addressing the “obesity paradox” can pave the way for clearer, more beneficial patient recommendations, thereby potentially enhancing patient outcomes significantly. The team’s research, backed by both public and private funding, including support from the Roswell Park Alliance Foundation and National Institutes of Health agencies, marks a significant step forward in demystifying the complex interplay between obesity and lung cancer.