Until recently, all cases of non-small-cell lung cancer (NSCLC) were treated in a similar manner. However, recent studies have demonstrated that the histologic subtype and certain specific molecular alterations influence the response to various chemotherapies and targeted agents.(1),(2)
For example, bevacizumab, a humanized monoclonal antibody that targets endothelial growth factor, is contraindicated in patients with squamous cell carcinoma of the lung due to increased risk of pulmonary hemorrhage.(3)
Patients with adenocarcinoma also respond better to the anti-folate agent pemetrexed than do those with squamous carcinoma.(4)
In a study from East Asia, the EGFR mutation in adenocarcinoma was associated with better response to a tyrosine kinase inhibitor compared with chemotherapy in nonsmokers or former light smokers.(5)
Patients with adenocarcinoma and EGFR mutations were also shown to do better when a tyrosine kinase inhibitor is used as maintenance after first-line treatment rather than as second-line therapy.(6)
The KRAS and ALK mutations have also been shown to influence response to treatment.(7),(8)
Researchers will no doubt continue to look for, and find, ways in which the genetic makeup of a tumor affects response to various therapies and influences optimal management.
A large percentage of patients with NSCLC will be unresectable at the time of diagnosis. This means that core biopsy or fine needle aspirate specimens will provide the primary tissue for diagnosis. The tissue needs to be of sufficient quality and quantity for both diagnosis and molecular analysis.
With my colleague Stephen Solomon and members of the pathology, thoracic surgery, and thoracic oncology divisions, we performed a prospective study that showed that core biopsy using small (18-20 gauge) needles provides material adequate for EGFR and KRAS analysis in a high percentage of patients.(9)
My colleagues and I published another study showing that core biopsy with small needles and cytology (fine needle aspirate) achieve similar rates of diagnostic subtyping for NSCLC and that optimal results are achieved when both modalities are considered together.(10)
Dr. Solomon also collaborated with our pathology and thoracic oncology colleagues to show that re-biopsy of lung cancer patients with acquired resistance to EGFR inhibitors is feasible and provides enough material for mutation analysis in the majority of patients.(11)
As the era of personalized medicine becomes a reality, we are committed to providing the best specimens for pathologic and molecular analysis and are very well equipped to do so.