Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes.

Glycans play a fundamental role in several biological processes, such as cell-cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, Receiver Operating Characteristics (ROC) analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.

Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program.

OBJECTIVES: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31-65 % and 2-5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. MATERIALS AND METHODS: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. RESULTS: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22-1.71] p < 0.0001). CONCLUSIONS: This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.

Diagnosis and first-line treatment of non-small cell lung cancer in the era of novel immunotherapy: recommendations for clinical practice.

INTRODUCTION: In the era of personalized cancer therapy, the sampling of adequate tumor tissue for histologic diagnosis and genomic profiling is crucial, not only at the initial diagnosis but also in the event of resistant and recurrent disease when sequential biopsies may be required to evaluate somatic mutations and histologic changes. Areas covered: The identification of genetic driver alterations led to the selection of patients who are most likely to benefit from epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and rat osteosarcoma (ROS-1) tyrosine kinase inhibitors; on the other hand, in the absence of oncogenic alterations, platinum-based doublet chemotherapy regimens were the cornerstone of treatment. However, the advent of immunotherapy has widely changed the first-line treatment. Expert commentary: An Italian Experts Panel Meeting was held to discuss on recommendations for diagnosis (optimization of the cyto/histologic tumor sample issue and management of tissue to molecular evaluation) and immunotherapy as first-line treatment of patients with advanced non-small-cell lung cancer.

Listening understanding and acting (lung): focus on communicational issue in thoracic oncology.

BACKGROUND: In the field of oncological assistance, nowadays we have to deal with a complex scenario where patients got used to obtain a huge amount of information through internet or social media and to apply them in performing their health-related decisions. This landscape requires that clinicians become able to handle therapeutical approaches and adequate skills in communication tools to satisfy the current needs. Our project aimed to build a communication model based on clinical oncologists' real experiences in order to find a simple way to share with patients all the innovative therapeutical opportunities today available in lung cancer. The final goal is to design a flexible and personalized model adaptable to clinician's personal characteristics and to the specific patient he is facing. We applied both traditional educational tools and innovative techniques in order to make the results effective and applicable to support peer learning. METHODS: The first step consisted in a Board synthesized the definition of the diagnostic process, the identification of treatment strategies and any potential communication barrier clinicians may face dealing with patients. The second step consisted in teamwork including a theoretical part and a training part. In the third step we produce five training videos and video interviews regarding communication praxis and a "Small communication manual". The last step consisted in the publication of the produced material on website and its diffusion through the social media. RESULTS: In medicine, the universal application of a single model of communication does not represent the optimal solution. By contrary, the availability of simple and practical suggestions to improve the communicative style could allow clinicians to abandon stereotyped formulas identically repurposed to all patients. The "from bottom to top" training, starting from real-life to take advantage of the clinician's experience, give the clinicians the possibility to meditate about their own communicative style and to train in the context of a protected environment. Applying these rules, we design an effective communication model, based on healthcare humanization, which could represent a fundamental support for the patient in order to be gently driven by the clinician to the most appropriate therapeutical choice, balancing efficacy and quality of life. The relational training may improve the quality of clinician-patient communication and could be widespread to other clinicians through the media. CONCLUSIONS: Considering the innovative therapeutical options available, particularly for lung cancer patients, and the increasing access of health-related information through internet or social media the clinician-patient communication has become crucial to support the achievement of the most appropriate therapeutical choice for the patient, facing the intricate illness experience. Building a shareable and easy-to-apply communication model represents a challenge aimed to help clinicians and including technology not as a threat, but as a positive tool.

Economic burden of patients affected by non-small cell lung cancer (NSCLC): the LIFE study.

PURPOSE: Non-small cell lung cancer (NSCLC) is a condition with significant clinical burden for patients and relevant economic impact. Limited evidence exists on the management costs of NSCLC patients, especially in the late phases of the disease. The main objective of this analysis was to evaluate the economic impact of clinical management of NSCLC patients in the Italian population. METHODS: This evaluation was an economic analysis of the observational and multicentre study LIFE, which described the therapeutic approach in routine clinical practice for NSCLC patients, progressing after first-line treatment. This study evaluated resource consumption in different Italian hospitals, including specialist visits, hospitalizations, accesses to first aid, pharmacological treatment, laboratory tests and palliative care. The National Healthcare Service perspective was adopted. RESULTS: In this study, N = 191 patients enrolled in the LIFE study were included. Patients were aged 64.2 years and were predominantly males (66%). In the different line of treatments, monthly costs of patients ranged between €1471 (first line) and €1788 (third line). The overall healthcare cost over the average period of observation (16.4 months) was €25,859 per patient. Overall, oncology therapy was the cost driver, although the composition of medical costs changed across the different lines of treatment, with costs for concomitant medication and palliative care being predominant in late phase of the disease. CONCLUSIONS: The economic burden of NSCLC is extremely high during the overall period of treatment, and a significant level of care is required in each stage of the disease.

Linezolid-induced bradycardia: a case report.

We report an episode of severe bradycardia that occurred in a 49-year-old woman with fever and malignant jaundice during antibiotic therapy with linezolid, a new oxazolidinone with activity against Gram-positive cocci. In our case, the strict temporal dependence between bradycardia and linezolid therapy seems to provide strong evidence for a causal relationship. To our knowledge, this is the first report of linezolid-induced bradycardia. This adverse event confirms that the new antibiotic linezolid should be administered with caution in patient with jaundice and hepatic insufficiency.

Pulmonary blastoma after liver transplant: a case report.

There is an increased risk of cancer after organ transplantation mainly due to the immunosuppressive therapy required in these patients. We report a case of biphasic pulmonary blastoma in an adult male who underwent liver transplant for hepatocellular carcinoma in March 1999, followed by immunosuppressive treatment and adjuvant chemotherapy with epirubicin. Disease-free survival lasted 18 months, then a diagnosis of biphasic pulmonary blastoma was made and the patient underwent a lung lobectomy. Five months after surgical resection a recurrence of this rare tumor was recorded and two cycles of cisplatin + etoposide and ifosfamide + etoposide and one cycle of second-line chemotherapy with vinorelbine were administered. The tolerability and the efficacy of this treatment were poor. The patient died less than one year after diagnosis. To our knowledge this is the first reported case of pulmonary blastoma in a transplant patient. Our findings confirm that organ transplant recipients deserve long-term medical surveillance also in the absence of graft complications, and that pulmonary blastoma is an aggressive tumor with a poor prognosis.

Support ellagic acid therapy in patients with hormone refractory prostate cancer (HRPC) on standard chemotherapy using vinorelbine and estramustine phosphate.

BACKGROUND: Recent phase III studies in hormone refractory prostate cancer (HRPC) showed an improvement in terms of overall survival (OS), objective response (OR) and biochemical response (BR); however, chemotherapy is usually accompanied by negative side effects that determines poor quality of life (QoL) and only marginally improves individual clinical response (ICR) in terms of pain relief and performance status. Ellagic acid is a polyphenol that is found in many species of flowering plants. It is an antioxidant that determines apoptosis, down regulation of IGF-II, activates p21 (waf1/Cip1), mediates the cumulative effect on G1/S transition phase and prevents destruction of p-53 gene by cancer cells. ENDPOINTS: The aim of this study was to assess the effects of ellagic acid support therapy on toxicity, OR, ICR and BR in HRPC patients treated with estramustine phosphate and vinorelbine. MATERIALS AND METHODS: Patients with HRPC were randomly distributed in two study groups: a control group (group A) who underwent chemotherapy with vinorelbine and estramustine phosphate, and an experimental group (group B) where chemotherapy regimen was associated with ellagic acid. RESULTS: The mean number of chemotherapy cycles/patient was 4 (range 3-8 cycles) and 6.5 (range 5-11) in group A and B patients, respectively. A reduction in systemic toxicity, statistically significant for neutropenia, associated with better results in term of OR rate, ICR, and BR were observed in group B compared with group A. On the contrary no significant difference in OS and PFS was detected between groups. CONCLUSIONS: our study suggests that the use of ellagic acid as support therapy reduces chemotherapy induced toxicity, in particular neutropenia, in HRCP patients; however, further studies are required to confirm our results.