L. Vervueren

[18F]FDG Positron Emission Tomography within Two Weeks of Starting Erlotinib Therapy Can Predict Response in Non-Small Cell Lung Cancer Patients

Purpose The aim of this prospective study was to evaluate whether [18F]FDG-PET/CT, performed within two weeks of starting erlotinib therapy can predict tumor response defined by RECIST 1.1 criteria after 8 weeks of treatment in patients with inoperable (stage IIIA to IV) non-small cell lung cancer patients. Patients and Methods Three [18F]FDG-PET/CT scans were acquired in 12 patients before (5±4 days) and after 9±3 days (early PET) and 60±6 days (late PET) of erlotinib therapy. Conventional evaluation, including at least chest CT (baseline versus after 8 weeks of treatment), was performed according to RECIST 1.1 criteria. Change in [18F]FDG uptake was compared with conventional response, progression-free survival (PFS), and overall survival (OS). Results By using ROC analysis, the Area Under the Curve for prediction of metabolic non-progressive disease (mNP) by early PET was 0.86 (95% CI, 0.62 to 1.1; P = 0.04) at a cut-off of 21.6% reduction in maximum Standardized Uptake Value (SUVmax). This correctly classified 11/12 patients (7 with true progressive disease; 4 with true non-progressive disease; 1 with false progressive disease). Non-progressive disease after 8 weeks of treatment according to RECIST 1.1 criteria was significantly more frequent in patients classified mNP (P = 0.01, Fishers exact test). mNP patients showed prolonged PFS (HR = 0.27; 95% CI, 0.04 to 0.59; P<0.01) and OS (HR = 0.34; 95% CI, 0.06 to 0.84; P = 0.03). Late PET analysis provided concordant results. Conclusion Morphologic response, PFS and OS survival in non-small cell lung cancer patients can be predicted by [18F]FDG-PET/CT scan within 2 weeks after starting erlotinib therapy.

First case of A859T epidermal growth factor receptor mutation responding to erlotinib.

59-year-old smoker consulted for a pulmonary nodule. Computed tomography (CT) scan lung biopsy diagnosed a non-small cell lung cancer (NSCLC) of adenocarcinoma subtype. Positron emission tomography demonstrated a left adrenal metastasis. First-line chemotherapy with a combination of pemetrexed and carboplatin was performed. After four cycles, a partial response was observed according to RECIST 1.1 criteria. During the same period, epidermal growth factor receptor (EGFR) mutations were characterized according to a sensitive method based on high-performance liquid chromatography and sequencing (Figures 1A, B). The rare mutation A859T was observed. Erlotinib was introduced after a wash-out period of 4 weeks. Tolerance was excellent. Eight weeks later, CT scan demonstrated a partial response (criteria RECIST 1.1 41%). Maximal standard uptakes of 18F-fluorodeoxyglucose (FDG) showed a reduction for primary and secondary tumors, 3.9 to 1.0 and 2.9 to 2.3, respectively (Figure 2). The radiographic response was confirmed with a CT scan 3 months later. To date, the duration of response is 3 months. Activating EGFR mutations are predictive responses for the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The most frequent deletions and mutations, located in exon 19 and 21, are observed from 10% in Caucasian populations 1 up to 40 to 60% in female, nonsmoking Asian populations. 2 Alongside the most frequent activating EGFR mutations, many other less frequent mutations have been described. 3 In general, little is known about the sensitivity or the lack of sensitivity to TKIs in humans. A859T EGFR mutation has already been reported twice and has been associated with the absence of sensitivity to gefitinib. 4,5 Functional analysis of A859T EGFR mutation exposed to erlotinib based on a cellular assay concluded that this variant could be a silent polymorphism. 6 To the contrary of all these published data, our case supports the evidence of a therapeutic effect of erlotinib in a NSCLC patient bearing A859T EGFR mutation. The proofs are a tumor size reduction and a decrease of the FDG maximal uptake after 8 weeks of treatment and confirmed 3 months later. Although the follow-up of our case is limited, our observation seems similar to patients with TKI-sensitive adenocarcinomas harboring a frequent EGFR mutation: significant shrinking tumor size after TKI introduction, long period of stable disease, and good tolerance. For all the reasons, we consider that A859T EGFR mutation could be an activating mutation-associated response to erlotinib. Because of the lack of a reliable tool to predict EGFR mutation sensitivity of current TKIs, we recommend that physicians test both/ several TKIs for every NSCLC patient harboring a rare/ new EGFR mutation.

American consensus recommendations for gastric scintigraphy: curve fitting with only a few points remains an easy and accurate method to obtain reliable and reproducible gastric emptying estimates.

BackgroundIn 2008, American consensus recommendations for performing gastric emptying (GE) scintigraphy were published. It was recommended that data are acquired only at 0, 1, 2, and 4 h and that the results are expressed as percentages of meal retention. Until now, it was established that the GE time–activity curves should have many points (every 10, 15, or 20 min) to reflect the GE process accurately and to be optimally adjusted by a mathematical model. In this study, we have evaluated the curve fitting using only a few points as proposed by the consensus protocol. Materials and methodsGE scintigraphy tests of 224 patients were retrospectively analyzed. Two curve fittings were done for each patient, either using data acquired every 20 min or using data acquired every hour. A comparison of these two methods was made based on the values of the computed GE parameters. ResultsWe observed strong correlations between the two methods (r=0.81–0.99, P<0.05). Using the Bland–Altman analysis, more than 95% of the differences were included in the mean difference 95% confidence interval. The mean differences were weak with a relatively small SD and Cohens k coefficients ranging from 0.84 to 0.93, indicating an excellent agreement between the two methods. ConclusionOur results showed the feasibility and accuracy of curve fitting using only a few points. The curve fitting is easy to perform and allows the computation of reliable and reproducible parameters that reflect the whole GE process.

Long-term prognostic significance of right bundle-branch morphology ventricular ectopy induced during stress test in patients with intermediate to high probability of coronary artery disease

Aims Stress-induced right bundle-branch block morphology ventricular ectopy (SI-RBVE) may be caused by left ventricular myocardial anomalies. While frequent ventricular ectopy (FVE) has been linked to poor outcomes, the prognostic value of SI-RBVE has not been established. The study aims to determine whether SI-RBVE is associated with increased mortality. Methods and results Three hundred forty-three patients with an intermediate to high probability of coronary artery disease were prospectively included. Patients were referred for a single-photon emission computed tomography and underwent a stress test according to standard protocols. Stress-induced right bundle-branch block morphology ventricular ectopy (VE) was defined as one or more induced premature beats with positive predominance in V1. Frequent VE was defined as the presence of seven or more ventricular premature beats per minute or any organized ventricular arrhythmia. During a mean follow-up of 4.5 ± 1.3 years, 59 deaths occurred. The death rate was higher in the SI-RBVE group (23.4% vs. 14.0%, P = 0.021). Age [odds ratio (OR) = 1.09 (95% CI: 1.06-1.13), P < 0.001] and peripheral artery disease [OR = 2.47 (95% CI: 1.35-4.50) P = 0.003] were independent factors of mortality, but single-photon emission computed tomography findings were not. There was an interaction between SI-RBVE and left ventricular ejection fraction (LVEF). In patients with LVEF > 50%, SI-RBVE was an incremental risk factor for mortality [OR = 2.83 (95% CI: 1.40-5.74), P = 0.004]. Stress-induced right bundle-branch block morphology VE patients also presented higher rates of known coronary artery disease, ischaemia, scar, and ST-segment changes. Frequent VE was not related to mortality. Conclusion Stress-induced right bundle-branch block morphology VE is associated with an increased mortality in patients with preserved LVEF.