Positron Emission Tomography and Circulating Tumor Cells to Monitor a Dramatic Response to Gefitinib
Authors: Alessandro Morabito, Claudia Sandomenico, Raffaele Costanzo, Agnese Montanino, Corradina Caraco, Elisabetta De Lutio, Simona Bevilacqua, Raffaella Pasquale, Antonietta Caronna, Gerardo Botti, Nicola Normanno, Gaetano Rocco
Journal: Journal of Thoracic Oncology (2012)

Positron emission tomography (PET) with [(18)F]fluorodeoxyglucose is increasingly used in early assessment of tumor response in non–small-cell lung cancer (NSCLC).1Takahashi R Hirata H Tachibana I et al.Early [18F]fluorodeoxyglucose positron emission tomography at two days of gefitinib treatment predicts clinical outcome in patients with adenocarcinoma of the lung.Clin Cancer Res. 2012; 18: 220-228Crossref PubMed Scopus (76) Google Scholar Circulating tumor cells (CTCs) are detectable in patients with NSCLC and might provide early indication of response to therapy.2Krebs MG Sloane R Priest L et al.Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer.J Clin Oncol. 2011; 29: 1556-1563Crossref PubMed Scopus (712) Google Scholar This report describes the role of PET and CTCs in monitoring the response to gefitinib in a patient affected by metastatic lung adenocarcinoma harboring an activating epidermal growth factor receptor (EGFR) mutation and with an extremely poor performance status. On November 2010, a 41-year-old man, a former light smoker, was admitted to our institution for a right lung nodule with pleural effusion, pericardial effusion, disseminated intravascular coagulation, and renal and hepatic failure. The Eastern Cooperative Oncology Group performance status was 4. PET scan demonstrated tracer accumulation in the right lung, pleural, supraclavicular and mediastinic lymph nodes, bone and liver (Fig. 1A). The patient underwent pericardial drainage and started therapy with steroids, diuretics, low–molecular-weight heparin, antithrombin III, and fresh frozen plasma. Cytologic evaluation of pericardial effusion demonstrated a lung adenocarcinoma. A single slide containing 20 stained tumor cells was available for EGFR mutational analysis. By using highly sensitive fragment analysis and polymerase chain reaction/sequencing techniques, it was possible to demonstrate in exon 19 of the EGFR gene a c.2235–2249 deletion, producing the aminoacidic deletion p.E746-A750. Finally, analysis of 7.5 mL of peripheral blood sample with the CellSearch system (Veridex, Raritan, NJ) revealed the presence of 32 CTCs, in which the same EGFR deletion identified in the primary tumor was detected. On December 15, we started therapy with gefitinib 250 mg/day, with a rapid and dramatic improvement of clinical conditions. After 2 weeks of treatment, the CTC count was 0. The PET scan after 3 months of therapy showed only a minimal tracer accumulation at the basis of the right lung (standardized uptake value 3.3) (Fig. 1B), and became negative after 7 months of therapy (Fig. 1C). Response to gefitinib was maintained for 11 months, until November 2011, when a total body PET/computed tomography scan showed a liver progression of disease, whereas CTC count was still negative. Six randomized clinical trials demonstrated the efficacy of gefitinib and erlotinib in patients with EGFR-mutation–positive NSCLC and good performance status (Eastern Cooperative Oncology Group 0–1).3Costanzo R Piccirillo MC Sandomenico C et al.Gefitinib in non small cell lung cancer.J Biomed Biotechnol. 2011; 2011: 815269Crossref PubMed Scopus (29) Google Scholar Some reports showed that Asian patients with advanced NSCLC and poor performance status can be responsive to gefitinib.4Inoue A Kobayashi K Usui K North East Japan Gefitinib Study Group et al.First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy.J Clin Oncol. 2009; 27: 1394-1400Crossref PubMed Scopus (444) Google Scholar This case confirms the possibility of successful treatment in a patient with an EGFR mutation and a poor performance status. More importantly, our findings highlight the importance of applying highly sensitive testing methods to allow the identification of EGFR mutations even in samples containing a low number of tumor cells, especially in patients who present clinical characteristics associated with a high incidence of EGFR mutations. In this regard, the assessment of EGFR mutations in CTCs might represent an alternative approach in patients for whom samples from the primary tumor are not available.5Maheswaran S Sequist LV Nagrath S et al.Detection of mutations in EGFR in circulating lung-cancer cells.N Engl J Med. 2008; 359: 366-377Crossref PubMed Scopus (1473) Google Scholar Finally, this study also suggests that both PET analysis and CTC count might have a relevant role in monitoring the response to molecular-targeted agents.