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Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted.

In order to confer adhesive properties to commercial polypropylene (PP) meshes, a surface plasma-induced deposition of poly-(acrylic acid) (PPAA) is performed. Once biomaterials were functionalized, different postdeposition treatments (i.e. water washing and/or thermal treatments) were investigated with the aim of monitoring the coating degradation (and therefore the loss of adhesion) after 3 months of aging in both humid/oxidant (air) and inert (nitrogen) atmospheres. A wide physicochemical characterization was carried out in order to evaluate the functionalization effectiveness and the adhesive coating homogeneity by means of static water drop shape analysis and several spectroscopies (namely, FTIR, UV–Visible and X-ray Photoemission Spectroscopy). Themodification of the adhesion properties after post-deposition treatments aswell as aging under different storage atmospheres were investigated by means of Atomic Force Microscopy (AFM) used in Force/Distance (F/D) mode. This technique confirms itself as a powerful tool for unveiling the surface adhesion capacity as well as the homogeneity of the functional coatings along the fibers. Results obtained evidenced that post-deposition treatments are mandatory in order to remove all oligomers produced during the plasma-treatment, whereas aging tests evidenced that these devices can be simply stored in presence of air for at least three months without a meaningful degradation of the original properties.

Stefano De Santis,1 Cristina Borghesi,1 Serena Ricciardi,2 Daniele Giovannoni,1 Alberto Fulvi,2 Maria Rita Migliorino,2 Claudio Marcassa3 1Palliative Care and Cancer Pain Service, Oncological Pulmonary Unit, 2Oncological Pulmonary Unit, San Camillo-Forlanini Hospitals, Rome, 3Cardiologia Fondazione Maugeri IRCCS, Novara, Italy Introduction: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very sa

Bruno Gori1, Serena Ricciardi1, Alberto Fulvi1, Salvatore Intagliata2, Ester Del Signore1, Filippo de Marinis11Oncological-Pulmonary Unit 1st, San Camillo Hospital, Rome, Italy; 2Department of Medical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Lung cancer is the leading cause of mortality worldwide. Non-small cell lung cancer (NSCLC) is a particularly aggressive cancer, the optimum management of which is still being determined. In the metastatic disease, the standard therapy is a platinum-based combination chemotherapy; however, in spite of available treatment options for patients who progress beyond first-line therapy, prognosis remains poor. Angiogenesis is a tightly regulated process which comprises a complex, complementary, and overlapping network. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. Antiangiogenic strategy includes: monoclonal antibodies against vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR), small molecule inhibitors of VEGF tyrosine kinase activity, VEGF Trap, and a new class named “vascular disrupting agents,” tested in ongoing clinical trials which will further define their role in the management of NSCLC. BIBF 1120 is an investigational orally administered receptor tyrosine kinase inhibitor that has shown antiangiogenic and antineoplastic activity, inhibiting VEGFR, platelet-derived growth factor receptor, and fibroblast growth factor receptor tyrosine kinases, preventing tumor growth and interfering with the angiogenesis-signaling cascade and overcoming drug resistances.Keywords: NSCLC, angiogenesis, oral antiangiogenic agents, VEGF, PDGF, FGF

Serena Ricciardi1, Silverio Tomao2, Filippo de Marinis11Thoracic-Oncology Unit 1st, Lung Diseases Department, San Camillo-Forlanini High Specialization Hospitals, Rome, Italy; 2Sperimental Medicine Department, La Sapienza University, Rome, ItalyAbstract: Lung cancer is the leading cause of cancer deaths worldwide. Targeting the epidermal growth factor receptor (EGFR) has played a central role in advancing non-small-cell lung cancer (NSCLC) research, treatment, and patient outcome over the last few years. Erlotinib is a human epidermal growth factor receptor Type 1/EGFR tyrosine kinase inhibitor. Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after the failure of at least one prior chemotherapy regimen. We present the results of phase I, II, III, and IV trials. Erlotinib monotherapy has shown a significant improvement in median survival, quality of life, and related symptoms in an unselected population of patients in second- and third-line therapy as a single agent. Most commonly reported erlotinib-related adverse effects were rash and diarrhea. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and nonsmokers have a better response when treated with erlotinib. Ongoing trials seek to improve therapy with this agent in monotherapy or in combination regimens and better understanding of predictors of benefit with therapy.Keywords: erlotinib, NSCLC, targeted therapy

Serena Ricciardi1, Silverio Tomao2, Filippo de Marinis11Thoracic-Oncology Unit 1st, Lung Diseases Department, San Camillo-Forlanini High Specialization Hospitals, Rome, Italy; 2Sperimental Medicine Department, Rome, ItalyAbstract: Pemetrexed is a new cytotoxic agent that is a standard of care for the second-line treatment of non-small cell lung cancer (NSCLC) and in combination with cisplatin in treatment of malignat pleural mesothelioma. It has been studied in numerous phase II and III trials in combination with different drugs or as single agent. Recently, pemetrexed has been approved in combination with cisplatin for the first-line treatment of patients with locally advanced or metastatic NSCLC other than squamous cell histology. The toxicity is acceptable and similar to that of other NSCLC regimens. The postinduction maintenance therapy with pemetrexed is being evaluated in a phase III, double-blind, placebo-controlled study.Keywords: pemetrexed, non-small cell lung cancer, non-squamous carcinoma, first-line setting