Positron Emission Tomography and Circulating Tumor Cells to Monitor a Dramatic Response to Gefitinib

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). Some reports showed that Asian patients with advanced NSCLC and poor performance status can be responsive to gefitinib. 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. 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.