Correct!
3. PCR for EGFR mutations and fluorescence in situ hybridization (FISH) for anaplastic lymphoma kinase (ALK) translocation

According to guidelines from the National Comprehensive Cancer Network (NCCN), all patients with lung adenocarcinoma, large cell carcinoma, or non-small cell cancer not otherwise specified should undergo testing for EGFR mutation and ALK rearrangement (5). Patients who benefit most from EGFR-directed therapies are those with activating and sensitizing EGFR mutations (6).  ALK rearrangements are less common than mutations in EGFR, but their detection changes treatment. Crizotinib, an ALK inhibitor, has been approved for patients whose tumors contain an ALK rearrangement (7).

The patient’s cells from the thoracentesis showed a wild type on EGFR analysis. Additional FISH analysis of the ALK gene locus was positive for rearrangement in 92% of 50 nucleoli. Therefore, the patient was started on crizotinib in July 2012. Follow up CT scan in October 2012 demonstrated an excellent clinical response (Figure 5).

Figure 5. Follow up chest CT scan in October 2012 showing shrinkage of the left pleural effusion.

This case demonstrates that current assessment and treatment of non small cell lung cancer requires adequate tissue for histology and molecular profiling of the tumor.  As more mutations affecting therapeutic decisions are discovered, such as the ROS 1 mutation, cancer care moves closer to the era of true personalized medicine. (8).

References

  1. Subramanian J, Govindan R. Lung cancer in never smokers: a review. J Clin Oncol 2007;25:561-70.
  2. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-98.
  3. 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;26:3543-51.
  4. 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;22:2184-91.
  5. Ettinger DS, ed. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Fort Washington, PA: National Comprehensive Cancer Network; 2012.
  6. Keedy VL, Temin S, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol 2011;29:2121-7.
  7. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269856.htm (accessed 11-19-12).
  8. Beregethon K, Shaw AT, Ignatious Ou S, et al. ROS 1rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012;30:863-70.


Home/Pulmonary