3'-Deoxy-3'-¹8F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer.

PURPOSE: 3'-Deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CTKSF) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. METHODS: Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. RESULTS: Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PETKSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35%). Maximum standardised uptake value at 60 min post-injection (SUV60,max) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV60,max increase of ≥ 12% resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100%, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV60,max were not predictive of survival. CONCLUSION: FLT PET/CT detected changes in proliferation, with early increase in SUV60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer.

A study of the complications of small bore 'Seldinger' intercostal chest drains.

BACKGROUND AND OBJECTIVE: Use of small bore chest drains (<14F), inserted via the Seldinger technique, has increased globally over the last few years. They are now used as first line interventions in most acute medical situations when thoracostomy is required. Limited data are available on the associated complications. In this study, the frequency of complications associated with 12F chest drains, inserted using the Seldinger technique, was quantified. METHODS: A retrospective case note audit was performed of consecutive patients requiring pleural drainage over a 12-month period. One hundred consecutive small bore Seldinger (12F) chest drain insertions were evaluated. RESULTS: Few serious complications occurred. However, 21% of the chest drains were displaced ('fell out') and 9% of the drains became blocked. This contributed to high morbidity rates, with 13% of patients requiring repeat pleural procedures. The frequency of drain blockage in pleural effusion was reduced by administration of regular normal saline drain flushes (odds ratio for blockage in flushed drains compared with non-flushed drains 0.04, 95% CI: 0.01-0.37, P < 0.001). CONCLUSIONS: Regular chest drain flushes are advocated in order to reduce rates of drain blockage, and further studies are needed to determine optimal fixation strategies that may reduce associated patient morbidity.

Oncological challenges for an ageing population living with HIV.

: Improvements in survival and changing patterns of transmission mean that the population of people living with HIV (PLWH) is ageing. Increasing age is a risk factor for many varieties of cancer, including most non-AIDS-defining malignancies. Moreover, the premature ageing described in PLWH and the development of cancer share many molecular features. As a consequence, there has been a dramatic increase in the number of PLWH who are diagnosed with cancer. The treatment of older HIV-positive patients with cancer requires careful attention to details. It is particularly important to take into account comorbidities, pharmacological drug interactions, and opportunistic infection prophylaxis when deciding on clinical management for these patients. Thus, cancer in the ageing population living with HIV poses many challenges for both HIV physicians and oncologists.

Clinical Features and Outcome in HIV-Associated Multicentric Castleman's Disease.

PURPOSE: To describe clinical features, treatment outcomes and relapse rates in HIV-associated multicentric Castleman's disease (MCD) in a sizeable mature cohort. METHODS: From a prospective database, we identified 61 HIV-seropositive patients with histologically confirmed MCD (median follow-up, 4.2 years). Since 2003, 49 patients with newly diagnosed MCD have been treated with rituximab with (n = 14) or without (n = 35) etoposide. RESULTS: At MCD diagnosis, 55 (90%) of 61 patients met proposed clinical criteria defining an attack. Four patients (7%) had histologic evidence of coexisting lymphoma, and one developed lymphoma 2 years after treatment. The incidence of lymphoma is 28 per 1,000 patient years. With rituximab-based treatment, the overall survival was 94% (95% CI, 87% to 100%) at 2 years and was 90% (95% CI, 81% to 100%) at 5 years compared with 42% (95% CI, 14% to 70%) and 33% (95% CI, 6% to 60%) in 12 patients treated before introduction of rituximab (log-rank P < .001). Four of 49 rituximab-treated patients have died; three died as a result of MCD within 10 days of diagnosis, and one died as a result of lymphoma in remission of MCD. Eight of 46 patients who achieved clinical remission suffered symptomatic, histologically confirmed MCD relapse. The median time to relapse was 2 years, and all have been successfully re-treated and are alive in remission. The 2- and 5-year progression-free survival rates for all 49 patients treated with rituximab-based therapy were 85% (95% CI, 74% to 95%) and 61% (95% CI, 40% to 82%), respectively. CONCLUSION: HIV-associated MCD is a remitting-relapsing disease. The outlook has improved dramatically in recent years with the introduction of rituximab-based therapy and yields high overall survival rates.

Anti-angiogenesis therapies: their potential in cancer management.

Angiogenesis plays an important role in normal animal growth and development. This process is also vital for the growth of tumors. Angiogenesis inhibitors have a different mechanism of action to traditional chemotherapy agents and radiation therapy. The angiogenesis inhibitors can act synergistically with conventional treatments and tend to have non-overlapping toxicities. There are four drugs which have a proven role in treating cancer patients. Bevacizumab is a humanized monoclonal antibody that binds to and neutralizes vascular endothelial growth factor (VEGF). Sunitinib and sorafenib inhibit multiple tyrosine kinase receptors that are important for angiogenesis. Thalidomide inhibits the activity of basic fibroblast growth factor-2 (bFGF). The licensed indications and the supporting evidence are discussed. Other drugs are currently being tested in clinical trials and the most promising of these drugs are discussed. Aflibercept, also known as VEGF-trap, is a recombinant fusion protein that binds to circulating VEGF. The vascular disrupting agents act by targeting established blood vessels. These exciting new treatments have the potential to transform the management of cancer.