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Abstract. The aim of this study was to investigate the outcome of patients with muscle-invasive bladder cancer (MIBC) receiving neo-adjuvant chemotherapy (neo-CT) using a cisplatin-based regimen fractionated on days 1 and 8 of a 21-day cycle prior to organ-preservation (chemoradiation) or cystectomy. Patients with stage T2-T4, N0, M0, transitional cell carcinoma (TCC) of the bladder with a calculated glomerular filtration rate (GFR) ≥40 ml/min were eligible for inclusion in the study. Neo-CT comprised of gemcitabine (1,000 mg/m 2 d1, d8, q21) plus cisplatin (35 mg/m 2 d1, d8, q21) for four cycles. Following the administration of neo-CT, patients underwent surgery or radiotherapy (RT) with or without concurrent chemotherapy (CRT), based on the response to neo-CT and clinician and patient preference. A total of 23 patients were recruited: 21 males and 2 females; median age, 69 years (range, 49-85); stage T2=11, T3A=7, T3B=5, grade 2=1, grade 3=22. One patient progressed prior to neo-CT. In total, 75 cycles of neo-CT were administered. Treatment was well-tolerated with only one episode of neutropenic sepsis. Three of 22 patients developed early progression and did not receive radical treatment. For the remaining 19 patients, choice of definitive treatment (surgery vs. RT/CRT) was based on response to neo-CT. Eight patients had residual disease at cystoscopy following the completion of neo-CT; six patients underwent surgery and two underwent RT/CRT. A total of 11 patients had a complete response (CR) to neo-CT, nine of whom were treated by RT/CRT, with the remaining two declining radical treatment. Median follow-up for alive patients was 57 months (range, 4.4-68.5). Three-year survival was 37% (95% CI 17-58%) and 5-year survival was 31% (95% CI 15-52%). Neo-CT is effective and well-tolerated in MIBC. This split-dose cisplatin regimen facilitates treatment in an outpatient setting and allows inclusion of patients with compromised GFR. IntroductionBladder cancer is the second most common genitourinary malignancy and is a significant cause of morbidity and mortality. Almost 25% of patients have muscle-invasive disease at presentation (1,2). In North America, the treatment of choice for muscle invasive bladder cancer is radical cystectomy and bilateral pelvic lymph node dissection. Although surgery may be curative, approximately 50% of all patients with muscle invasive transitional cell carcinoma (TCC) develop metastatic disease within 2 years of cystectomy and subsequently succumb to the disease, presumably due to a significant proportion of patients harboring micrometastatic disease (3). On this basis, neo-adjuvant and adjuvant chemotherapy have been tested in numerous phase II and a few phase III studies (4-7).There are two principal rationales for neo-adjuvant chemotherapy: i) to improve survival in patients with micrometastatic disease and ii) to preserve the bladder by shrinking the primary tumour to facilitate radiotherapy as an alternative definitive therapy to surgery (8). The results of the South Western Oncol...

BackgroundThe use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study.MethodsMR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra- and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data.ResultsThe intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 – 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 – 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength.ConclusionThe overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.

Abstract. The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8 + tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8

Protein tyrosine kinases are enzymes which catalyze the phosphorylation of tyrosine residues and activate a downstream cascade of cellular signalling pathways which regulate cell proliferation, differentiation and apoptosis and a wide variety of cellular functions. Clinical developments over the past decade have identified several novel therapeutic agents which inhibit tyrosine kinase activity, either by direct receptor inhibition or indirect inhibition of tyrosine kinase controlled pathways. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI), such as gefitinib and erlotinib have been studied extensively in patients with refractory non-small cell lung cancer (NSCLC). Early studies with gefitinib showed undoubted clinical activity but failed to show a survival benefit, whereas studies with erlotinib showed a small but statistically significant benefit in overall survival. Subsequent studies explored the possibility of synergistic activity between targeted agents (gefitinib or erlotinib) and conventional chemotherapy drugs reporting disappointing results. Clinical trial results with gefitinib and erlotinib, either as monotherapy or in combination with chemotherapy, have failed to match the encouraging results noted in the pre-clinical setting. It is now increasingly recognised that clinical exploration of molecular targeted agents may not conform well to traditional phase I/II/III drug trial designs. Therapeutic responses may be limited to a small subpopulation of patients, therefore diluting the overall therapeutic effect. Hypothesising a genetic basis for the heterogeneity in trial results, biomarkers (such as EGFR gene mutation analysis, EGFR protein expression, and increased EGFR gene copy number) have been studied with a view to identifying a target population most likely to benefit from these drugs. Future clinical trials with targeted agents need to be carefully designed to incorporate correlative translational research elements that will allow selection of appropriate treatment strategies for individual patients. For assessment of phase III trial results in advanced disease, progression free survival may serve as a more appropriate end-point than response rate in an adequately designed trial in the appropriately selected population, although there should be no substitute for the overall survival and quality of life end points. The role of EFGR TKI in NSCLC will be discussed in detail and data from these studies will be used to illustrate the challenges in designing clinical trials and interpreting outcomes.

From 1999, the NHS Ayrshire and Arran Health Board implemented an innovative nurse-led collaborative care model for the management of patients with prostate cancer (PC). This article describes the model and presents the results of a local evaluation to assess its impact. The evaluation comprised a retrospective audit of the service against national standards for PC management, undertaken in 2012. Seventy-one patients, who were under the care of the service during June 2008, were included. Patient and staff satisfaction were also assessed using questionnaires distributed to 75 patients undergoing outpatient or telephone reviews during April 2012 and 7 one-to-one semi-structured staff interviews. The patient audit showed good compliance with standards relating to selection of appropriate PC treatments according to tumour stage and grade; radiotherapy dosing and referral-to-treatment times. Areas requiring improvement were the documentation of patients' risk and performance status and provision of verbal and written information to patients and carers. Seventy-three per cent of the patient questionnaires were returned, with 96% of respondents rating their overall care as 'excellent' or 'very good'. Staff satisfaction was also high and interviewees described many benefits of the service for patients, hospital staff, GPs and the NHS/health board. Negative responses related mainly to demand/capacity issues. Overall, the evaluation showed good compliance with many national standards and high levels of patient and staff satisfaction. This suggests that with trained and competent nursing staff and collaborative multidisciplinary team working, safe and appropriate care can be achieved for more complex, as well as very stable PC patients.

Background: Collecting duct carcinoma (CDC) is a rare and aggressive variant of renal cell carcinoma (RCC), which has poor response to cytokine therapy and chemotherapy. Introduction of tyrosine kinase inhibitors (TKIs), in particular sorafenib and sunitinib, is changing the treatment paradigm for management of RCC. However, patients with CDC have been excluded from the majority of randomised trials involving the use of TKIs. Case Report: Our patient with metastatic CDC was treated with sorafenib, and demonstrated an excellent response, both clinically and radiologically. She continues on sorafenib treatment with minimal toxicity, and has demonstrated a progressionfree survival exceeding 13 months. Conclusions: This is the first reported case of a patient with CDC responding to sorafenib treatment. Therefore, the role of sorafenib in the management of metastatic CDC needs prospective evaluation.

This study suggested that RTRs with variant homozygous IFN-γ AA genotype were at risk of CMV infection, whereas the high producer IFN-γ +874 TT genotype appears to be associated with lower risk of CMV infection.