Genotyping lung cancer linked to better survival


Genetic testing for personalized treatment of lung cancer was associated with improved survival, likely due to getting targeted kinase inhibitors to the right patients, a study showed.

Patients whose tumors were genotyped had 28% better overall survival odds than those who couldn't get a genetic diagnosis for reasons like limited tissue availability (P=0.002), Roman K. Thomas, MD, of the University of Cologne in Germany, and colleagues found.

That impact was independent of stage and histology in multivariate analysis of the prospective cohort, the researchers reported in the Oct. 30 issue of Science Translational Medicine.

"Although this observation most likely results from the favorable outcome in patients treated with kinase inhibitors, it demonstrates that genotyping is mandatory for patients to benefit from targeted therapeutic intervention," they wrote.

"Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer," they added.

The group examined 1,255 clinically-annotated lung tumor specimens suitable for genetic analysis and were able to find at least one cancer-causing mutation or other alteration "potentially amenable to specific therapeutic intervention" in 55% of them.

Notably, these alterations didn't follow the traditional stratification in lung cancer of small cell lung cancer (SCLC), carcinoid, and non-small cell lung cancer (NSCLC), which is further divided into adenocarcinoma and squamous cell or large cell carcinoma.

"Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis," Thomas's group pointed out.

The genetics-based reassignment nearly eliminated the large cell carcinoma classification.

Large cell cancers had no "signature" alterations and instead harbored mutations characteristic of all other subtypes, like KRAS and STK11 mutations found in adenocarcinoma and amplification of MYCL1 and RB1 as in SCLC.

Nearly all of them clustered with other tumor subtypes rather than with each other in one analysis.

The researchers suggested combined immunohistochemical and genomic analysis to reclassify large cell carcinomas as adenocarcinoma, squamous cell carcinoma, or neuroendocrine differentiated tumors.

"Even in those cases where immunohistochemistry did not yield an unequivocal diagnosis, most remaining large cell cases could be reassigned genetically to the other lung cancer subtypes," they noted.

The same was true in a prospective set of 5,145 lung cancer patients from a molecular screening outreach program run by Network Genomic Medicine.

For the 75% who could be genotyped, treatment recommendations for genetically-tailored cancer therapy with approved drugs or in clinical trials were given.

The genotyped patients had a median overall survival of 31.6 months compared with 15.1 among those not able to be genotyped, for a multivariate-adjusted hazard ratio of 0.719 (95% confidence interval 0.588-0.879).

Compared with the original histology, genetics and immunohistochemistry reassigned 20% of the squamous cell cases to other subtypes, 16% of SCLC, and 28% of adenocarcinomas.

Together, genetics and immunohistochemistry cut the large cell group to only 1.1% of the cohort, moving most into the adenocarcinoma or squamous cell categories.

"These epidemiological results emphasize the need for broad availability of systematic and comprehensive genomic lung cancer diagnoses," the researchers concluded.

They cautioned that their study provided only observational data but noted that randomized comparisons keeping patients from targeted therapy based on genetic and immunohistochemical results is unlikely to be ethical.

Other limitations were the limited quality of data from the retrospective cohort obtained from multiple centers before the era of targeted therapies in the clinic, differences in the time of treatment and distribution of stages and rate of surgical treatment, and incomplete data on clinical features like smoking status, performance status, and treatment.


Source: MedPage Today:

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