[Reporting a cluster of lymphohaematopoietic cancers and management of the communication process with the community: the experience of a Local health Authority in Tuscany, Italy]. / Segnalazione di un cluster di neoplasie emolinfopoietiche e gestione del processo di comunicazione con la cittadinanza: l'esperienza di una Asl toscana.

In 2008, some general practitioners (GPs) in the area of Empoli (Tuscany Region, Central Italy), reported to the Local Health Authority (LHA), an unusually high frequency of leukemia deaths among their patients residing in a one of the municipalities of the area. The LHA decided to carry out an epidemiological investigation. An interdepartmental working group was set up, led by the Department of Prevention of the LHA, and made up of representatives of the Institute for Study, Prevention and Cancer Network (ISPRO, Florence), the G. Monasterio Foundation/ Institute of Clinical Physiology of the National Council for Research (CNR) of Pisa, the University of Pisa, the Regional Environmental Protection Agency and community members. Several epidemiological analyses were carried out (namely incidence and mortality analysis, assessment of the residential history of all cases and micro-geographical incidence evaluation, assessment and quantification of local environmental pressures, evaluation of congenital abnormalities). The investigation took over two years to be completed. The work agenda was shared with community members, who contributed to decision-making, study design and the communication plan. Thanks to the interaction with community members, researchers had the chance to become aware of their information needs and of local knowledge concerning the research issues. The final report was published online and presented to citizens in several public meetings. Direct involvement of the local community during project development was found to be useful to reduce the perceived distance between public authorities and the local population, as highlighted in the guidelines on cancer cluster investigations.

Sudden ventricular fibrillation and death during ibrutinib therapy-A case report.

Ibrutinib is an oral inhibitor of Bruton tyrosine kinase approved for the treatment of chronic lymphocytic leukaemia, mantle cell lymphoma and refractory Waldenstrom's disease. It increases progression-free survival, overall survival, response rate. The most frequent adverse reactions, are increased risk in of bleeding and atrial fibrillation, but several reports of more dangerous rhythm disturbances have been recently reported in literature. A case of a patient with refractory Waldenstrom's disease, who developed ventricular fibrillation while taking ibrutinib, is reported, along with a concise literature review.

Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy.

BACKGROUND: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC) followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST), due to the typically hypervascular pattern of the tumor. AIMS: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. MATERIALS AND METHODS: Three patients (pts) with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. RESULTS: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. CONCLUSION: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

Hepatic arterial chemotherapy in combination with systemic chemotherapy compared with hepatic arterial chemotherapy alone for liver metastases from colorectal cancer: results of a multi-centric randomized study.

Hepatic arterial infusion (HAI) chemotherapy is accepted to be an option in patients with non-resectable metastases from colorectal cancer confined to the liver. In a multi-istitutional trial, 76 patients were randomly assigned to receive HAI versus HAI plus systemic bolus 5-fluorouracil and leucovorin. The primary endpoint was survival, followed by response, recurrence and toxicity. Survival was longer for HAI plus systemic chemotherapy (HAI+SYC) than HAI (median, 20 vs. 14 months; p = 0.0033), as were responses (47.5% and 41.7%; p = 0.09) and time to hepatic progression (12 vs. 8 months; p = 0.039). Side effects included haematological toxicity that was mostly mild and reversible in 432 cases. Neutropenia grade 3 occurred in four patients in the HAI+SYC arm and one in the HAI arm. Diarrhoea occurred in 20% and 7% of patients and stomatitis occurred in 18% and 2%, respectively. On the contrary biliary toxicity was significant; twelve patients had evidence of bilirubin elevations of more than 3 mg/dl (six in each arm), and two had asymptomatic arterial biliary-tree fistulae: one in the HAI+SYC arm and one in the HAI arm. Grade 3 elevation in alkaline phosphatase and aminotransferase levels occurred in 26% and 24%, respectively. In conclusion, the combination of HAI+SYC is active and safe showing a clinical advantage with respect to simple HAI, increasing overall survival, response rate and time to progression.

A phase II clinical study on relapsed malignant gliomas treated with electro-hyperthermia.

The purpose of this study was to evaluate the activity and toxicity of electro-hyperthermia (ET) on relapsed malignant glioma patients. Twelve patients with histologically diagnosed malignant glioma entered the study. Eight patients had glioblastoma multiforme, two had anaplastic astrocytoma grade III and two had anaplastic oligodendroglioma. All patients were pre-treated with temozolamide-based chemotherapy and radiotherapy. Hyperthermia with short radiofrequency waves of 13.56 MHz was applied using a capacitive coupling technique keeping the skin surface at 20 degrees C. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumours was above 40 degrees C for more than 90% of the treatment duration. One complete remission and 2 partial remission were achieved, with a response rate of 25%. The median duration of response was 10 months (range 4-32). The median survival of the entire patient population was 9 months, with 25% survival rate at 1 year. ET appears to have some effectiveness in adults with relapsed malignant glioma.

Oxaliplatin hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase I-II clinical study.

Oxaliplatin is a new drug active in the treatment of advanced colorectal cancer. Hepatic arterial infusion chemotherapy is under evaluation because of the high target dose and low general toxicity. Twelve patients with liver metastases from colorectal cancer were enrolled, all pretreated with evidence of progressive disease: three after a partial remission induced by oxaliplatin, folinic acid and 5-FU, three patients after a partial remission induced by irinotecan, folinic acid and 5-FU and six patients after failing a 5-FU and folinic acid regimen. They received hepatic arterial infusion chemotherapy with oxaliplatin as 30-min infusion on an outpatient basis every 3 weeks. Dose-limiting toxicity was observed at 175 mg/m2/cycle and consisted of obliteration of the hepatic artery in one patient, abdominal pain requiring morphine in one patient and severe hypotension requiring plasma expander in a third. Following phase 1, all patients received 150 mg/m2 for six cycles. We reported four cases of partial remission (33%) lasting 24, 15, 12 and 10+ weeks, respectively, 2 stabilisation of disease (17%) lasting more than 12 weeks and six progressions (50%). Six patients (50%) presented CEA reduction of > 30% and five patients (41%) showed an increase of > 8% of body weight. The median survival was 13 months (range 6-19). Oxaliplatin did not present significant toxicity for liver parenchyma and biliary tree. We advise that further studies be undertaken with oxaliplatin 150 mg/m2.

Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase II clinical study.

AIMS AND BACKGROUND: The advantage of delivering chemotherapy by hepatic arterial infusion is the acquisition of a high concentration of the drug in the target. Irinotecan (CPT-11) is active for the treatment of advanced colorectal cancer. In phase I studies, doses of 20 mg/m2/d for 5 days given every 4 weeks as continuous infusion or 200 mg/m2 as a short 30-min infusion given every 3 weeks is recommended for phase II studies. METHODS AND STUDY DESIGN: Twelve patients with a median liver substitution of 30% (20-50%) were enrolled, 6 progressed after a FOLFOX-induced partial response and 6 progressed after 5-fluorouracil and folinic acid. All patients had a surgically (n = 6) or angiographically placed port (n = 6). They received hepatic arterial infusion chemotherapy with CPT-11 (200 mg/m2) on an out-patient basis, every 3 weeks as a short 30-min infusion for six cycles. RESULTS: Four partial responses were observed (33%) lasting 24, 15, 12 and 8+ weeks, 3 stable disease (25%) lasting more than 12 weeks, and 5 progressions (41%). Six patients (50%) presented a >30% reduction in CEA. Toxicity was G2 diarrhea in 5 patients (41%) and G2 myelosuppression in 6 (50%); one patient had abdominal right upper quadrant pain requiring analgesics. CONCLUSIONS: CPT-11 is active as hepatic arterial infusion chemotherapy in liver metastases from colorectal cancer and can rescue systemically pretreated patients. Our schedule seems safe, feasible and well accepted on an out-patient basis.