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Papillary thyroid carcinoma (PTC) is the most common histotype among the thyroid cancer types. Although PTC is a curable malignancy, many patients relapse after treatment. Thus, there is a need to identify novel factors involved in the pathogenesis of PTC that may be used as targets for new therapies. The MAPK pathway has been implicated in the pathogenesis of PTC. Therefore, in this review, we summarize the role of the BRAF V600E mutation in the development and progression of thyroid cancer. The cinical implication of this molecular abnormality is also discussed. It is evident that the detection of the BRAF V600E mutation is crucial in order to identify novel avenues for thyroid cancer treatment.

Sebastiano Bordonaro Fabio Raiti, Annamaria Di Mari, Calogera Lopiano, Fabrizio Romano, Vitalinda Pumo, Sebastiano Rametta Giuliano, Margherita Iacono, Eleonora Lanteri, Elena Puzzo, Sebastiano Spada, Paolo TralongoUOC Medical Oncology, RAO, ASP 8 Siracusa, ItalyBackground: Active home-based treatment represents a new model of health care. Chronic treatment requires continuous access to facilities that provide cancer care, with considerable effort, particularly economic, on the part of patients and caregivers. Oral chemotherapy could be limited as a consequence of poor compliance and adherence, especially by elderly patients.Methods: We selected 30 cancer patients referred to our department and treated with oral therapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate). This pilot study of oral therapy in the patient’s home was undertaken by a doctor and two nurses with experience in clinical oncology. The instruments used were clinical diaries recording home visits, hospital visits, need for caregiver support, and a questionnaire specially developed by the European Organization for Research and Treatment of Cancer (EORTC), known as the QLQ-C30 version 2.0, concerning the acceptability of oral treatment from the patient’s perspective.Results: This program decreased the need to access cancer facilities by 98.1%, promoted better quality of life for patients, as reflected in increased EORTC QLQ-C30 scores over time, allowing for greater adherence to oral treatment as a result of control of drug administration outside the hospital. This model has allowed treatment of patients with difficult access to care (elderly, disabled or otherwise needed caregivers) that in the project represent the majority (78% of these).Conclusions: This model of active home care improves quality of life and adherence with oral therapy, reduces the need to visit the hospital, and consequently decreases the number of lost hours of work on the part of carers. Management of the service by the professionals involved revealed excellent control of the process by nursing staff, with minimal visits involving doctors.Keywords: cancer, treatment, home-based, quality of life, compliance

376 Background: Prostate cancer is the most common cancer among adult men. Bones are the main metastatic site of prostate cancer. Radium-223 is indicated to treat metastatic castrate-resistant prostate cancer ( mCRPC) with symptomatic skeletal metastases. We evaluate the tolerability of Ra223 treatment in real life setting. Methods: We reported the cases of 38 consecutive non-selected patients with mCRPC symptomatic bone metastases treated in two Italian hospital cancer center from August 2016 to October 2017. The cause of Ra 223 treatment discontinuation in elderly prostate cancer patients were evaluated. Results: due bones metastases, 38 patients were treated with Radium-223; 20 were ≥75 years old (range 75-85 yrs). Patients characteristics and main toxicity are reported (Table). Regarding the elderly patients, hematologic toxicity were the most common adverse events reported. Anemia G2-G3 was observed in 10 pts (50%), thrombocytopoenia G3 in 2 patients (10%) and neutropenia G3 in 4 patients (20%); 12/20 patients interrupted the treatment, of which 10 were ECOG PS2. The number of patients who discontinued the drug because of hematologic adverse events was higher than ALSYMPCA clinical trial. Fatigue G1-G2 incidence was 32%. Unexpectedly we did not record any cases of gastrointestinal toxicity (diarrhea, nausea or constipation). Conclusions: In patients ≥75 years old, anemia G2-G3 was more frequent than data reported in literature, while diarrhea is not found. The data of this experience suggest that elderly vulnerable patients are more exposed to hematologic toxicity that may compromise the outcome of the treatment. For these patients surveillance for early supportive care is relevant. Characteristics of patients with ≥75y. [Table: see text]

e14617 Background: Nivo is a novel therapeutic option in 2nd line NSCLC. However, predictive biomarkers are lacking. The presence of systemic inflammation correlated with poor outcome in many cancer types, including NSCLC. We aimed to evaluate whether there is a correlation between some indicators of inflammation and response in patients (pts) treated with Nivo or Docetaxel (D). Methods: 23 consecutive pts with NSCLC receiving Nivo were analyzed. Baseline white cell count (WBC) and ANC were collected and correlated with tumor response. 27 NSCLC pts treated with D were used as controls. An ANC ≥ 7500 cell/µl was defined neutrophilia. dNLR was calculated as: ANC/(WBC-ANC). Platelet count (PLT) ≥ 450 × 103/μL was defined as thrombocytosis. PLR ratio was defined as PLT/lymphocyte count. dNLR ≥3 and PLR ≥160 were defined high. Results: Baseline characteristics: median age 66 years (range 45-82); sex M 74%; histology squamous 42%, adenocarcinoma 48%, and 10% mixed histology/NOS. Smoking status: 90% smokers/former smokers. Among non-squamous pts, 13,7% were EGFR mutated and 10,3% were KRAS-mutated, with an equal distribution in both treatment groups. Lines of therapies: range 2-8 in Nivo group and 2-3 in D group. Overall response rate (ORR): 13.6% with Nivo vs. 7.7% with D; 9% of pts with Nivo experienced unconventional responses. Baseline neutrophilia (17.4% with Nivo and 27% with D) and thrombocytosis (4.3% and 3.8%, respectively) were not associated with response (ORR 0%). High dNLR (13% and 38% with Nivo and D) correlated with no response (0% ORR), whereas high PLR correlated with no responses to D and reduced ORR to Nivo (10%). Conclusions: The results of this preliminary study suggest that baseline neutrophilia, thrombocytosis and high dNLR are associated with no response to both D and Nivo, whereas high PLR is associated with no response to D and reduced activity with Nivo. Given their relative easy estimation, baseline evaluation of these indicators of inflammation should be included before 2nd line therapy start, especially for highly expensive treatments, such as immunotherapy.

The tumor microenvironment has been largely studied as a dynamic system orchestrated by inflammatory cells, including cancer cells, stroma as well as the extracellular matrix. It is useful to describe and predict the phenotypic characteristics of cancer. Furthermore, a better understanding of its interplay with the various aspects of the tumor cells may be utilized for the discovery of novel molecular targets. Liver cancer is considered a model of the relation occurring between the tumor micro-environment and tumor development. The chronic inflammatory status of the liver, sustained by the infection of hepatitis viruses, as well as the production of cytokines and growth factors within the parenchyma, lead to an intricate microenvironment. The identification of novel molecular therapeutic targets may improve the outcome of patients with liver cancer as it remains the third leading cause of cancer death worldwide. In the present study, the tumor microenvironment in hepatocellular carcinoma (HCC) was explored by a review of the literature. Studies on hepatitis virus infections and the consequent chronic inflammatory status were examined. In this context, immune-mediated and/or virus-related molecular mechanisms have been hypothesized as being responsible for liver cancer development. The interlink among HCC microenvironment components, comprising cellular elements, cytokines, growth factors and several proteins is also described together with the role of matrix metalloproteinases in HCC development. Finally, the rationale for targeting tumor-stromal interface is summarized in the context of new therapeutic opportunities.