Younger age associated with genetic alterations in lung adenocarcinoma

Oncogenic genetic alterations occurred more frequently among patients aged younger than 40 years with lung adenocarcinoma than older patients, according to results of a retrospective study.

“Young patients with adenocarcinoma may be prime candidates for precision medicine strategies, because they tend to have more genetic alterations that can be treated with existing targeted therapies, leading to a compatible prognosis,” Kosuke Tanaka, MD, from the department of thoracic oncology at Aichi Cancer Center Hospital in Japan, and colleagues wrote.

Young age at diagnosis of various cancers has shown unique disease biology. For example, data show that young patients with breast cancer have an increased frequency of BRCA1/2 mutations, as well as increased likelihood of HER-2 overexpression and triple-negative disease. Young patients diagnosed with colon cancer demonstrated increased rates of microsatellite instability and demonstrated aggressive disease.

However, lung adenocarcinoma diagnosis in young individuals has been poorly understood.

Tanaka and colleagues screened 1,746 consecutive patients diagnosed with stage I through stage IV adenocarcinoma between 2009 and 2015 at Aichi Cancer Center Hospital in Japan. Most patients had an ECOG performance status of 0 or 1 (96%).

Of these patients, 81 (median age, 36 years; range, 26-40; 44% men) were aged 40 years or younger at diagnosis. Forty-four percent of younger patients had never smoked.

Researchers performed a driver genetic alteration analysis to determine any correlation between younger age prognosis, driver genetic alterations and other patient characteristics.

The genetic alteration analysis showed 33 patients (41%) had ALK translocations, 24 (30%) had epidermal growth factor receptor mutations and two (2%) had KRAS mutations.

Significantly more younger patients than older patients harbored ALK translocations (41% vs. 4%; P < .001), whereas EGFR (30% vs. 45%; P = .006) and KRAS (2% vs. 10%; P = .026) mutations occurred less frequently.

“It is noteworthy that an ALK translocation was the most common driver oncogene identified in young patients with adenocarcinoma, and most were diagnosed at an advanced stage,” the researchers wrote. “Recent data have suggested that ALK translocations are associated with the onset of lung cancer in young patients.”

Researchers also identified and analyzed rare oncogenic genetic alterations in patients who had wild-type ALK/EGFR/KRAS adenocarcinoma; of these, four patients had HER-2 mutations, two had RET translocations and two had ROS1 translocations.

HER-2 mutations occurred more frequently among younger patients (25% vs. 5.3%; P < .001), as did RET (22.2% vs. 5.4%) and ROS1 (22.2% vs. 2.7%; P = .033) translocations.

The rate of oncogenic genetic alterations was significantly higher in younger than older patients (83% vs. 61%; P < .001). Overall, oncogenic genetic alterations (P < .001), ALK translocation (P < .001), ROS1 translocation (P = .033) and HER-2 mutation (P < .001) were associated with younger age.

Younger patients who had lung adenocarcinoma without genetic alterations had shorter OS than older patients without genetic alterations (8.9 months vs. 16.4 months; P < .001), and patients with genetic alterations (24.9 months; P < .001).

“Comprehensive oncogenic genetic alteration screening is especially recommended for personalized medicine strategies in this population,” the researchers wrote. – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.