“You are only as old as you feel.” German researchers have already lent weight to this statement in 2021 with a longitudinal study. It suggests that feeling “younger” protects middle-aged and older adults from harmful stress.
Lung cancer is generally considered a disease of the elderly, with the average age of diagnosis in the United States being 70. But what happens when a disease that is associated with a more “old” population occurs in younger people? In an overview in the ASCO TextbookLaura Mezquita, MD, PhD, of the Hospital Clinic of Barcelona in Spain, and colleagues noted that “young-onset lung cancer remains poorly understood due to a lack of comprehensive data on its complex nature, with emerging evidence pointing to age-related differences that impact outcomes and prognosis.”
However, it remains to be hoped that data from the YOUNG LUNG trial will change this. The trial, which will start in 2023, will investigate the biology of the disease in people under 45 years of age. Recruitment for the trial is currently ongoing and it is expected to be completed in August 2027.
Meanwhile, Mezguita’s group pointed out that younger patients with lung cancer have critical needs, such as career and life goals, not to mention a higher likelihood of physical and emotional stress that can result from concerns about fertility problems, for example.
In their review, the authors highlighted the “complexity of lung cancer in young adults,” including:
- Given the multitude of risk factors or carcinogens for lung cancer – tobacco smoke, other environmental factors and occupational exposures – “it is important to perform a comprehensive medical history that includes information on lifestyle habits, any occupational or environmental exposures, and personal and family history of cancer. This allows a holistic understanding of the relationship between disease and risk factors, which may contribute to better knowledge of lung cancer and its treatment,” the team wrote.
- A cancer onset at a young age should be a warning sign of a possible genetic disorder. “Genetic predisposition plays a role in a subset of patients, with an estimated 5% to 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 doctors can follow the National Comprehensive Cancer Network guidelines for genetic counseling and germline testing in non-small cell lung cancer (NSCLC), the authors said.
- Oncofertility should be part of the treatment continuum when appropriate, and discussion of the risks of treatment-related gonadal toxicity in lung cancer “should follow the same approach as in women and men with other tumor types,” which may include cryopreservation of ovarian tissue and sperm.
- “A serious diagnosis at a young age can change a patient’s mindset, transforming them from someone in the summer of their life to someone facing questions of mortality – questions that were rarely considered before diagnosis,” Mezquita and co-authors emphasized. They pointed out that younger patients are more likely to find information about lung cancer online and seek support through social media, so providers should “remain vigilant and engage patients where they are online, which could mean additional social media platforms in the future.”
Finally, it is important to perform a comprehensive tumor profile in young patients with lung cancer as the likelihood of having attackable genomic alterations has increased, the team said, and priority should therefore be given to next-generation sequencing (NGS) with “simultaneous analysis of the most clinically relevant alterations in NSCLC, as recommended in international guidelines.”
In a related presentation at the 2024 ASCO Annual Meeting, Aaron Pruitt, MD, of the University of Kentucky at Lexington, and colleagues presented a poster on “oncogenic drivers and immune landscapes” of young adults (YA) with NSCLC, grouping them by age into 18–30, 31–40, and 41–50 versus over 50. Below are some highlights from this presentation.
What was the impetus for the study?
Approximately 5% of NSCLC cases occur in patients aged 50 years or younger, which has distinct clinicopathological features. Reports of genomic alterations are rare. A total of 42,326 NSCLC samples were analyzed by NGS of DNA or RNA. The composition of the tumor microenvironment was estimated using bulk RNA sequencing. Real-world survival with osimertinib (Osi-OS; Tagrisso) was derived from insurance claims and calculated from the start of Osi treatment to the last contact and compared between ages 18–50 and >50 years.
What were the key findings?
NSCLC in young adults was more common in women and non-smokers and was associated with adenocarcinoma histology. Among the driving forces were ALCOHOL(IHC+), ROS1, RETAnd NTRK1 Fusion were enriched and KRAS Mutations were reduced in YA.
Interestingly, the prevalence of KRASG12D from the transition (non-smoking-related) and EGFRE746_A750 decreasing with age, KRASG12C by transversion increased with age in young adults.
NSCLC in YA was also associated with an improvement in OS – median 37.4 months versus 32 months in patients over 50 years of age.
We report an increased prevalence of RET And NTRK1 Mergers in YA and important differences in the distribution of frequent KRAS And EGFR Mutations in young people (compared to people over 50) along with reduced expression of immune-related genes in the tumor microenvironment. The implications are currently being actively investigated.
Read the review here.
Mezquita disclosed relationships with and/or support from Roche, Takeda, AstraZeneca Spain, Janssen, MSD Oncology, Bristol Myers Squibb Spain, Janssen Oncology, Pfizer, Inivata, Amgen and Gilead Sciences.
Pruitt stated that he had no financial relationships; several co-authors reported relationships with industry.
