Biopsy and Personalized Medicine in Non-Small-Cell Lung Cancer (NSCLC)

By Raymond Thornton, MD  |  Thursday, November 14, 2013

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. Core biopsy Core biopsy of a sub-centimeter right lower lobe lung nodule.

Core biopsy two Core biopsy of a left upper lobe lung nodule.

  1. Moreira AL, Thornton RH. Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing. Clin Lung Cancer. 2012 Sep;13(5):334-9.
  2. Travis WD, Rekhtman N, Riley GJ, et al. Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift.J Thorac Oncol. 2010 Apr;5(4):411-4
  3. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91.
  4. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51.
  5. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57.
  6. Wang ZJ, An TT, Mok T, et al. Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer. J Cancer Res. 2011 Jun;23(2):112-7.
  7. Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005 Sep 1;23(25):5900-9.
  8. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-70
  9. Solomon SB, Zakowski MF, Pao W, et al. Core needle lung biopsy specimens: adequacy for EGFR and KRAS mutational analysis. AJR Am J Roentgenol. 2010 Jan;194(1):266-9.
  10. Sigel CS, Moreira AL, Travis WD, et al. Subtyping of non-small cell lung carcinoma: a comparison of small biopsy and cytology specimens. J Thorac Oncol. 2011 Nov;6(11):1849-56.
  11. Arcila ME, Oxnard GR, Nafa K, et al. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res. 2011 Mar 1;17(5):1169-80.