Clinicopathological features and relation between anaplastic lymphoma kinase (ALK) mutation and histological subtype of lung adenocarcinoma in Eastern European Caucasian population.

Introduction: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status. Patients and methods: This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients. Results: Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively. Conclusions: ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation.

A pilot study-is there a role for mitoxantrone pleurodesis in the management of pleural effusion due to lung cancer?

BACKGROUND: Lung cancer is the leading cause of malignant pleural effusion (MPE). Management of MPEs remains a clinical challenge due to recurrence and poor quality of life. An ideal sclerosing agent has yet to be found. The aim of this cohort pilot study was to evaluate the role of mitoxantrone pleurodesis (MP) as an alternative to talc sclerotherapy for managing MPEs in lung cancer patients. METHODS: A retrospective chart review was conducted on consecutively admitted patients with MPE to the Department of Post-Intensive Care at the Clinic for Respiratory Diseases "Jordanovac", University Hospital Centre Zagreb, in Croatia. RESULTS: Of 34 patients with MPE, twenty-one (64.8±9.46 years; 47-84 years) with primary lung carcinoma who received MP (30 mg of mitoxantrone) between December 2003 and February 2009 were included in this study. Chest radiographs taken prior to sclerotherapy and at 1-, 2-, and 3-month follow-up were compared. At the post-sclerotherapy evaluation periods, overall success (OS) rates of MP were 88.2% [17.6%, complete response (CR); 70.6%, partial response (PR)], 53.9% (7.7% CR; 46.2% PR), and 45.5% (PR), respectively. Kaplan-Meier median survival from MP until death was 5.2 months, while that from diagnosis of primary lung cancer was 12.3 months. CONCLUSIONS: MP may be a safe and effective method of managing MPE due to lung cancer. Future randomized controlled studies comparing mitoxantrone and talc pleurodesis in lung cancer patients are warranted to elucidate whether a significant difference exists between these agents. Factors affecting success, survival probability, and quality of life also require further investigation.

EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA-IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data.

Autofluorescence videobronchoscopy (AFI) for the assessment of tumor extension in lung cancer.

The major objective of our study was to determine the specificity and sensitivity of AFI videobronchoscopy vs. white light videobronchoscopy, in the assessment of lung cancer extent. Secondary objective was to investigate whether or not AFI can reveal greater extension of the tumor, and can it influence therapy making decision. Autofluorescence videobronchoscopy systems are new technology for visualization of bronchial mucosa, and the proper indications for such systems will be determined in the near future. In this prospective trial we have enrolled 27 patients with suspected lung cancer in whom we performed 108 diagnostic biopsies and 54 control biopsies. All patients underwent WL videobronchoscopy followed by Auto Fluorescence Imaging (AFI) examination of tracheobronchial tree. We were using videobronchoscope BF-F260 and EVIS LUCERA SPECTRUM processor unit. Overall specificity for AFI in the diagnostics of lung cancer was found to be 85%, sensitivity was 90%, positive predictive value (PPV) 78%, and negative predictive value (NPV) 94%. Specificity, sensitivity, PPV, and NPV for WL videobronchoscopy in lung cancer diagnostics were 54%, 64%, 51%, and 69%, respectively. Relative sensitivity ratio of AFI over WL videobronchoscopy, which is calculated to be 1.41, confirmed superiority of AFI in lung cancer diagnostics. We confirmed significant correlation between the greater extension of the tumor (assessed with AFI) and the therapeutical decision in lung cancer treatment (p = 0.01). Influence of AFI on therapeutical decision was significant (p = 0.034). AFI videobronchoscopy system yields significantly higher sensitivity and specificity for the assessment of lung cancer extent than WLB videobronchoscopy alone. It had shown to be able to influence therapeutic option for lung cancer treatment. Further studies are needed to evaluate and validate these results.

Differential diagnosis of tuberculous and malignant pleural effusions: what is the role of adenosine deaminase?

The objective of this study was to evaluate the utility of invasive and noninvasive diagnostic procedures in tuberculous pleurisy (TPE) in an area with intermediate incidence of tuberculosis. The aim was to determine the cutoff value for adenosine deaminase (ADA) and the sensitivity and specificity of ADA and evaluate pleural fluid cytology and pleural biopsy in the differential diagnosis of malignant and tuberculous pleurisy. The study included 121 patients. TPE was confirmed in 54 patients and malignant effusion in 67 patients. Criteria used for TPE diagnosis were positive cultures of effusion or biopsy specimen, tuberculous granulomas, or positive sputum cultures without other explanation for pleural effusion. Malignancy was diagnosed by either cytology or biopsy. The cutoff value of ADA in TPE was 49 U/L, sensitivity was 89.2%, specificity was 70.4%, positive predictive value (PPV) was 84.4%, and negative predictive value (NPV) was 78.4%. ADA activity below 16 U/L suggests that TPE is highly unlikely with sensitivity=38.5%, specificity=100%, PPV=100%, and NPV=57.4%. ADA effusion/serum ratio reached a cutoff in TPE of 1.7 (sensitivity=84.6%, specificity=72.2%, PPV=81.4%, NPV=71.4%). Sensitivity, specificity, PPV, and NPV of cytology evaluation for TPE are 72.2%, 70.1%, 66.1%, and 75.8%, respectively. Pleuroscopy-guided pleural biopsy had sensitivity=66.7%, specificity=100%, PPV=100%, and NPV=78.8%. In 27.8% of TPE cases, pleural fluid cultures were positive. There is no doubt that pleuroscopy-guided biopsy is of great value for TPE diagnosis; however, sensitivity and specificity of noninvasive tests, especially ADA, can help to distinguish between TB and malignancy.