Giulia Pasello

Gefitinib and erlotinib were shown to be particularly effective in a clinically selected subpopulation of non-small cell lung cancer patients (NSCLC): adenocarcinoma histology, non-smoking status, Asian origin and female gender have been associated with improved clinical benefit compared to the unselected NSCLC population. The aim of the present study was to investigate the prognostic and predictive role of EGFR and KRAS analysis in advanced lung adenocarcinomas, selected according to clinical features associated to better response to EGFR tyrosine kinase inhibitors (TKIs), namely female gender and non-smoker or former light smoker status. EGFR and KRAS mutations and EGFR FISH status were assessed in 67 surgical samples. EGFR and KRAS mutations were found in 16 (26.7%) and 12 (17.9%) patients, respectively. FISH analysis was positive in 34 (56.7%) patients. EGFR-mutated patients showed significantly longer survival when treated with EGFR TKIs (p = 0.002, hazard ratio (HR) = 0.036, 9...

The objective of this study was the retrospective evaluation of tolerability and activity of pemetrexed with carboplatin (AC) or cisplatin (AP) as neoadjuvant chemotherapy in a consecutive series of patients with malignant pleural mesothelioma (MPM). Patients with operable MPM received three cycles of AC or AP followed by surgery and radiotherapy. Since 2005, 51 patients have been treated with AC (27) and AP (24). We observed higher incidence of grade 3 anaemia, cumulative grade 2-3 asthenia and worsening of performance status in the AP group. Response to AC and AP were; complete: 4% vs. 0%, partial: 18% vs. 17%, stable disease: 74% vs. 79%, progressive disease: 4%; the resection rate was 81% vs. 79%. AC and AP are active and feasible neoadjuvant regimens. Progression-free survival, response, disease control and resection rate were similar in the two treatment groups. The lower tolerability to AP treatment could impair the clinical condition of patients undergoing surgery.

Induction therapy (IT) has gained popularity in recent years, becoming a standard of treatment in resectable lymph node-positive NSCLC. IT aims to downstage the disease (shrinkage of tumour and clearance of lymph node-metastases), clear distant micrometastases and prolong survival. Potential disadvantages are increased morbidity and/or mortality after surgery and risk of progression of disease that could have been initially resected. The purpose of this study was to evaluate the outcomes and prognostic factors in a series of patients with lymph node-positive NSCLC receiving IT followed by surgery. A total of 86 patients (75.6% males, median age 63 years) affected by NSCLC in clinical stage IIIA (n = 80) or IIIB (n = 6), with pathologically proven lymph node involvement, underwent platinum-based IT followed by surgery between 2000 and 2009. Eighty (93%) patients received a median of 3 cycles of chemotherapy, and 6 (7%) underwent induction chemoradiotherapy. Response to IT was complet...

Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo. In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice. Results demonstrated a significant increase of apoptosis in cell lines treated with CPT compared with those receiving CP or T as single agents. This synergistic effect was dependent on the ability of CP to increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The CPT ...

Adenocarcinoma comprises a group of diseases with heterogeneous clinical and molecular characteristics. COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients. Our aim was to study COPD-associated adenocarcinoma phenotypes mainly focusing on morphological and molecular aspects, in comparison to smoke-related cancer without COPD. From 2010 to 2013, 54 patients with adenocarcinoma (20 COPD and 34 smokers) were prospectively studied. Each patient underwent a complete clinical and instrumental assessment. Morphological studies included analysis of growth pattern, cell proliferation (Ki-67/MIB1 expression) and parameters of intra- and peri-tumoral remodelling (inflammation, fibrosis and necrosis). Genetic analysis of EGFR and KRAS mutations was also performed. The two groups were comparable for the main demographic and biohumoral parameters except for increased blood basophil cell count in the COPD group. Compared to COPD, tumours of smokers presented an increased percentage of solid component (median: 20% vs 5%, p=0.02), a reduced percentage of lepidic pattern (median: 0% vs 10%, p=0.06) and higher Ki-67/MIB1 median value (55% vs 30%, p=0.02). In multivariate analysis lepidic and solid histological pattern were significantly influenced by clinical group (p=0.03 and 0.05, respectively). Concerning EGFR mutation, no differences were found between groups while KRAS mutation presented a trend of higher percentage in smokers compared to COPD (41% vs 20%, p=NS). Adenocarcinoma with KRAS mutation showed a higher value of Ki-67/MIB1 (65% vs 35%, p=0.048) and prevalent solid pattern (35% vs 10%, p=0.019) in comparison to wild-type form. COPD-related adenocarcinoma presents molecular and morphological features of lower aggressiveness (increased lepidic component, reduced solid pattern, lower cell proliferation and less frequent KRAS mutation) compared to smokers. Different molecular mechanisms could be associated with the development of COPD associated cancer.

The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients. Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan. Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%). Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.

Pancoast tumour is a rare neoplasia in which the optimal therapeutic management is still controversial. The traditional treatment of Pancoast tumour (surgery, radiotherapy or a combination of both) have led to an unsatisfactory outcome due to the high rate of incomplete resection and the lack of local and systemic control. The aim of the study was to determine the efficacy of the trimodality approach. Fifty-six patients (male/female ratio: 47/9, median age: 64 years) in stage IIB to IIIB were treated during a period between 1994 and 2013. Induction therapy consisted of 2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30-44 Gy). After restaging, eligible patients underwent surgery 2 to 4-week post-radiation. Thirty-two (57.1%) patients were cT3 and 24 (42.9%) cT4, 47 (83.9%) were N0 and 9 (16.1%) N+. Forty-eight (85.7%) patients underwent R0 resection and 10 (17.9%) had a complete pathological response (CPR). Thirty-day mortality rate was 5.4%, major surgical...