麻豆传媒

"You're only as old as you feel." Back in 2021, German researchers gave some weight to that expression with a suggesting that feeling "younger" protects middle-age and older adults against damaging stress.

Lung cancer is generally viewed as an older person's disease, with an in the U.S. But what happens when a disease that is tied to a more "vintage" population crops up in younger people? In a review in the , Laura Mezquita, MD, PhD, of the Hospital Clinic of Barcelona in Spain, and colleagues noted that "young-onset lung cancer remains underexplored, lacking comprehensive data on its complex nature, with emerging evidence revealing age-related differences that affect outcomes and prognosis."

Hopefully, though, data from the will change those circumstances. Launched in 2023, the trial will look at the biology of the disease in those less than 45. The study is currently recruiting and has an estimated completion date of August 2027.

In the meantime, Mezguita's group pointed out that younger patients with lung cancer have critical needs, such as career and life goals, not to mention the higher chance for physical and emotional stress from, say, worrying about fertility issues.

In their review, the authors highlighted the "complexities of lung cancer in young adults," including:

• Given the multitude of lung cancer risk factors or carcinogens -- tobacco smoke, other environmental factors, and occupational exposures -- "it is important to conduct a comprehensive medical history that includes information on lifestyle habits, occupational or environmental exposures, if any, as well as personal and family history of cancer. This allows for a holistic understanding of the disease-risk factor context, which can contribute to better knowledge of the lung cancer and management," the team wrote.

• Cancer onset at an early age should be a red flag for a possible genetic disorder. "Genetic predisposition plays a role in a subset of patients, with an estimated 5%-10% of all cancers associated with inherited alterations in cancer predisposition genes. However, there are no criteria for referring young and/or high-risk patients for genetic testing," although clinicians can follow guidance from the National Comprehensive Cancer Network for genetic counseling and germline testing for non-small cell lung cancer (NSCLC), the authors said.

• Oncofertility should be part of the care continuum, when appropriate, and a discussion on the risks of treatment-induced gonadotoxicity in lung cancer "should follow the same approach as for women and men with other tumor types," which can include ovarian tissue cryopreservation and sperm cryopreservation.

• "A grave diagnosis at a young age can alter a patient's mindset, plunging their identity from someone in the summer of life to someone facing questions of mortality -- questions unlikely to have been considered before diagnosis," Mezquita and co-authors emphasized. They pointed out that because younger patients are more likely to find information about lung cancer online and to seek support via social media, providers should "remain vigilant in meeting patients where they are online, which could mean additional social media platforms in the future."

Finally, "the altered likelihood of harboring targetable genomic alterations underlies the importance of performing comprehensive tumor profiling in young patients with lung cancer," the team said, so next-generation sequencing (NGS) with "simultaneous analysis of the most clinical relevant alterations in NSCLC, as recommended in international guidelines," should be prioritized.

In a related presentation at ASCO's 2024 annual meeting, Aaron Pruitt, MD, of the University of Kentucky in Lexington, and colleagues shared a poster on of young adults (YA) with NSCLC, grouping them by age as 18-30, 31-40, and 41-50 versus over 50. Below are some highlights from that presentation.

What was the impetus for the study?

Approximately 5% of NSCLC occurs in patients age 50 or younger, representing distinct clinicopathological features. Reports characterizing genomic alterations are scarce. A total of 42,326 NSCLC specimens were analyzed using NGS of DNA or RNA. Composition of tumor microenvironment was estimated from bulk RNA sequencing. Real-world survival on osimertinib (Osi-OS; Tagrisso) was obtained from insurance claims and calculated from initiation of Osi treatment to last contact and was compared between ages 18-50 and >50 years.

What were some of the main findings?

NSCLC in YA was more prevalent in females and non-smokers, and was associated with adenocarcinoma histology. Among driver alterations, ALK(IHC+), ROS1, RET, and NTRK1 fusion were enriched and KRAS mutations were reduced in YA.

Interestingly, while the prevalence of KRAS^G12D from transition (non-smoker related) and EGFR^E746_A750 decreased with age, KRAS^G12C from transversion increased with age in YA.

NSCLC in YA was also associated with improved Osi-OS -- median 37.4 months versus 32 months in patients over age 50.

We report an increased prevalence of RET and NTRK1 fusions in YA and key differences in distributions of frequent KRAS and EGFR mutations in YA (versus ages >50) along with decreased expression of immune-related genes in the tumor microenvironment. The implications are under active investigation.

Read the review here.