Stefano Cafarotti

EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation.

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs). This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.

Is 18F-FDG PET useful in predicting the WHO grade of malignancy in thymic epithelial tumors? A meta-analysis

AIM To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs). METHODS A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUVmax) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUVmax between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI). RESULTS Eleven studies were selected for the meta-analysis. The pooled WMD of SUVmax between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4-2.0). The pooled WMD of SUVmax between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4-6.1). Finally, the pooled WMD of SUVmax between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7-4.3). CONCLUSIONS (18)F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUVmax between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas).

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: A systematic review and a meta-analysis

OBJECTIVE To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. METHODS A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. RESULTS Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. CONCLUSIONS (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed.

Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery

OBJECTIVE We have analyzed short- and long-term variations of pulmonary function in locally advanced non-small cell lung cancer after induction chemoradiotherapy. METHODS Twenty-seven patients with stage IIIA (N2) non-small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. RESULTS A 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, -20.50% (P < .001); forced vital capacity, -22.50% (P < .001); forced expiratory volume in 1 second, -23.00% (P < .001); peak expiratory flow, -29.0 (P < .001); forced expiratory flow 25% to 75%, -13.7% (P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% (P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase (P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. CONCLUSIONS An impairment of respiratory function is evident in the immediate postoperative setting in patients with non-small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only.

Target Therapy in Lung Cancer.

Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way.

Late onset of pneumothorax after bronchoscopic lung volume reduction due to migration of a nitinol coil

The use of Endobronchial coils are a relatively new brochoscopic technique for lung volume reduction. They appear to be safe and effective in improving quality of life, reducing morbidity and mortality related to the primary disease, while avoiding the many risks of morbidity and mortality associated with surgery. Nevertheless, some complications, such as pneumothorax, are relatively common in the periprocedural period. We describe a case of pneumothorax that occurred several days after brochoscopic technique for lung volume reduction due to direct perforation of the visceral pleura by a coil. The patient presented with a large pneumothorax associated with significant air leak, requiring surgical intervention. Exploration of the chest cavity showed a pleural tear caused by a coil. To our knowledge, this is an adverse event that has never been described before, suggesting the possible migration of the coil from the original position.

Lung Ultrasound to Detect Residual Pneumothorax After Chest Drain Removal in Lung Resections

BACKGROUND Indication for postdrain removal imaging after lung resection is debated. Chest roentgenogram (CR) is widely used to confirm lung expansion but not evidence based. We propose to introduce lung ultrasound (LUS) as alternative to exclude significant pneumothorax (PTx) in this setting. METHODS The study enrolled 50 patients undergoing lung resections. Inclusion criteria were complete expansion of the lung at postoperative CR, pleural effusion of less than 300 mL/24 h, air leak of 10 to 20 mL/min for 6 hours. Two hours after chest drain removal, LUS was performed at the second and third intercostal spaces to assess pleural sliding. Patients with no detected PTx or with apical PTx were considered for discharge. The same patients were blindly evaluated with CR by a second operator, and a comparison between the two methods was performed. Clinical decisions were taken based on CR results. RESULTS LUS confirmed large PTxs in 7 patients, apical PTxs in 10 patients, and no PTx in 33 patients. CR confirmed 5 of 7 significant PTxs (1 chest drain reinserted, 4 patients observed), and 2 of 7 PTx were considered irrelevant. Apical PTxs were confirmed in 8 of 10 patients, and in 2 patients there was no PTx at CR. The 33 patients with no PTx at LUS had full lung expansion at CR. LUS has a negative predictive value of 100% in excluding large PTxs and a positive predictive value of 71%. CONCLUSIONS In this subgroup of patients with air leak of 10 to 20 mL/min, performing an imaging study to verify the absence of PTx is desirable; however, when LUS confirms lung expansion or the presence of apical PTx, CR does not seem to be needed.

A false positive finding on the PET of somatostatin receptor due to a chondromyxoid fibroma

a Unit of Thoracic Surgery, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy b Unit of Thoracic Surgery, Ente Ospedaliero Cantonale, Bellinzona, Switzerland c Department of Nuclear Medicine, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy d Chair of Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, Brescia, Italy e Department of Nuclear Medicine and PET/CT Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

Surgical Treatment in Patient with Non–Small-Cell Lung Cancer with Fissure Involvement: Anatomical versus Nonanatomical Resection

Objective: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non–small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. Methods: From January 2000 to January 2010, the clinical data of 40 non–small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, &khgr;2, and log-rank tests, Kaplan–Meier method, and Cox and logistic regression analyses were used for the statistical analysis. Results: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (−24.9% ± 13.5%) when compared with that in group B (−19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). Conclusions: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in “frail” patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life.

Does spinal chloroprocaine pharmacokinetic profile actually translate into a clinical advantage in terms of clinical outcomes when compared to low-dose spinal bupivacaine? A systematic review and meta-analysis

STUDY OBJECTIVE Spinal anesthesia is well suited for day-care surgery, however a persisting motor block after surgery can delay discharge. Among the new drugs available, chloroprocaine has been associated with a short onset time, and motor block duration and a quicker discharge. However, it is not clear if those outcomes are clinically significantly superior compared to those associated with the use of low-dose hyperbaric bupivacaine. DESIGN Aim of the study was to determine if spinal 2-chloroprocaine was superior to low-dose spinal bupivacaine regarding the following outcomes: onset time, block duration, time to ambulation and time to discharge. PATIENTS/INTERVENTIONS We performed a systematic literature search of the last 30 years using PubMed Embase and the Cochrane Controlled Trials Register. We included only blinded, prospective trials comparing chloroprocaine with a low dose of bupivacaine for spinal anesthesia. Low dose bupivacaine was defined as a dose of 10 mg or less. Outcomes of interest were time to motor block regression (primary outcome), time to ambulation and time to discharge (secondary outcomes), as indirect indicators of a complete recovery after spinal anesthesia. MAIN RESULTS Compared to a low dose bupivacaine, spinal 2-chloroprocaine was associated with significantly faster motor and sensory block regression (pMD = -57 min-140.3 min; P = 0.015 and <0.001 respectively), a significantly shorter time to ambulation and an earlier discharge (pMD = -84.6 min; P < 0.001 and pMD = -88.6 min and <0.001 respectively). Onset time did not differ between the two drugs (pMD = -1.1 min; P = 0.118). CONCLUSIONS Spinal 2-chloroprocaine has a shorter motor block duration, a significantly quicker time to ambulation and time to discharge compared to low dose hyperbaric bupivacaine and may be advantageous when spinal anesthesia is performed for day case surgery.