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The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer., Patients and Methods: Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m(2), day 1) intravenously and capecitabine (1000 mg/m(2) twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated., Results: Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred., Conclusions: Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

Background: Survival differences in stomach cancer are depended on patient, tumour and treatment factors. Some populations are more prone to develop stomach cancer, such as people with low socioeconomic status (SES). The aim of this population based study was to assess whether differences in socioeconomic status (SES) alone, after adjusting for confounding factors, also influence survival., Methods: From 1989 to 2007 all patients with stomach cancer were selected from the cancer registry of the Comprehensive Cancer Centre North-East. Postal code at diagnosis was used to determine SES, dividing patients in three groups; low, intermediate and high SES. Associations between age, localization, grade, stage, and treatment were determined using Chi-square analysis. Relative survival analysis was used to estimate relative excess risk (RER) of dying according to SES., Results: In low SES neighbourhoods diagnosis was established at older age. More distal tumours were detected in patients with low SES, whereas pathology showed more poorly differentiated tumours in patients with high SES. Overall, more resections were performed in, and more chemotherapy was administrated to patients in high SES neighbourhoods. After adjusting for confounding factors, the risk of dying was lower for patients with high SES (RER 0.89, 95% Confidence Interval 0.81-0.98) compared to patients with low SES., Conclusion: SES proved to be an independent prognostic factor for survival in patients with stomach cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Surgical resection is an important factor in the curative treatment of gastric cancer. However a variety of aspects of surgical treatment that potentially influence outcome are still not well defined. This study aims to assess the influence of hospital type, referral pattern and proximal or distal location of the tumour on the ultimate survival., Methods: From January 1994 to January 2007, a total of 5245 patients were diagnosed with gastric adenocarcinoma in the region of the Comprehensive Cancer Centre North-East Netherlands. Hospitals in this region were categorized into three types: teaching university (TU), teaching non-university (TNU), and non-teaching hospitals (NT). The influence of hospital type, referral for surgery and location of the tumour on the relative survival of operated patients was studied., Results: Of the 5245 patients, 2334 patients underwent surgery. For operated patients, the 5-year relative survival was 42.5% for the TU versus 34.0% and 35.5% for respectively TNU and NT hospitals (p = 0.064), with no difference (p = 0.38) in relative survival (25.6-31.9%) in the proximal tumours. A significant difference was found between the hospitals in the 5-year relative survival in the distal tumours; 59.7% in the TU versus 36.4% in the TNU and 36% in the NT (p = 0.03 univariate), however this was not confirmed in the multivariate analysis (p = 0.184). High referral centres did not perform better as far as survival is concerned than low referral hospitals. In conclusion the hospital type in our region did not significantly influence outcome of surgery for gastric cancer., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Molecular imaging of breast cancer can potentially be used for breast cancer screening, staging, restaging, response evaluation and guiding therapies. Techniques for molecular breast cancer imaging include magnetic resonance imaging (MRI), optical imaging, and radionuclide imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT). This review focuses on PET and SPECT imaging which can provide sensitive serial non invasive information of tumor characteristics. Most clinical data are gathered on the visualization of general processes such as glucose metabolism with the PET-tracer [(18)F]fluorodeoxyglucose (FDG) and DNA synthesis with [18F]fluoro-L-thymidine (FLT). Increasingly more breast cancer specific targets are imaged such as the estrogen receptor (ER), growth factors and growth factor receptors. Imaging of the ER with the PET tracer 16-alpha-[(18)F]fluoro-17-beta-estradiol (FES) has shown a good correlation between FES tumor uptake and ER density. (111)In-trastuzumab SPECT to image the human epidermal growth factor receptor 2 (HER2) showed that in most patients with metastatic HER2 overexpressing disease more lesions were detected than with conventional staging procedures. The PET tracer (89)Zr-trastuzumab showed excellent, quantifiable, and specific tumor uptake. (111)In-bevacizumab for SPECT and (89)Zr-bevacizumab for PET-imaging have been developed for vascular endothelial growth factor (VEGF) imaging as an angiogenic marker. Lastly, tracers for the receptors EGFR, IGF-1R, PDGF-betaR and the ligand TGFbeta are under development. Although molecular imaging of breast cancer is still not commonly used in daily clinical practice, its application portfolio is expanding rapidly.

Background: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer., Patients and Methods: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-infusion, FA 200 mg/m(2), 1-h infusion. 5-FU 2600 mg/m(2), 24-h infusion day 1, q 2 wk. The primary endpoint was response rate (RR)., Results: The median follow-up is 31.8 months, 90.4% of the patients have died. Confirmed RR, progression free survival (PFS; months) and median overall survival (OS; months) in 5FU/LV versus 5FU/LV/oxaliplatin were respectively 18.5% versus (vs) 33.8% (P = 0.004), 5.6 vs 6.7 (P = 0.016) and 13.3 vs 13.8 (P = 0.619). In the 5FU/LV/oxaliplatin arm less grade (3/4) toxicity was measured for diarrhoea, stomatitis, an increase in idiosyncratic side effects and neurosensory events compared with 5FU/LV. The quality of life (QOL) was equal in both arms. Second line treatment was given in 62% of the patients, crossover of 5FU/LV to 5FU/LV/oxaliplatin occurred in 14%., Conclusions: Oxaliplatin in the first-line resulted in an increased RR and PFS with less grade 3/4 mucositis/diarrhoea compared with 5FU/LV alone. Idiosyncratic side effects deserve attention with oxaliplatin. Despite a low treatment cross over rate, OS in both groups was comparable.

Angiogenesis plays an important role in physiology and pathology. It is a tightly regulated process, influenced by the microenvironment and modulated by a multitude of pro- and anti-angiogenic factors. A thorough understanding of the angiogenic process may lead to novel therapies to target ischemic vascular diseases as well as diseases characterised by excessive angiogenesis such as rheumatoid arthritis, psoriasis or tumours. This review gives an overview of the (groups of) factors involved in different steps of the angiogenic process, divided into factors affecting endothelial proliferation and migration and factors affecting blood coagulation, fibrinolysis and the degradation of basement membranes and the extra-cellular matrix, with a specific emphasis on angiopoietins and their related growth factors. The therapeutic implications of these factors are discussed.

Purpose: Assessment of the results and prognostic factors in patients with locally recurrent rectal cancer treated with curative intent., Patients and Methods: Forty patients with an isolated pelvic recurrence of rectal cancer were studied retrospectively. The treatment consisted of radiotherapy alone or combined with chemotherapy and/or surgery performed between January 1992 and July 2001. Radiotherapy was given with a 3-4 fields technique (6-15 MV), five times a week. The median radiation dose was 50 Gy (range 25-66.6 Gy). Twenty-five patients underwent salvage surgery. Five patients were treated with concomitant chemotherapy (5-fluoro-uracil/leucovorin) (5FU/LV) during the 1st and 5th week of radiotherapy., Results: Twenty-two of the 40 patients were male. The local recurrence free survival after 3 and 5 years, respectively, was 49 and 39%. Male gender was the only independent factor associated with failure of local control. The 3 and 5-year overall survival of the total group was 36 and 19%, respectively, with a median survival of 26 months., Conclusion: In a selection of patients in the treatment of locally recurrent rectal cancer valuable local palliation if not cure, can be reached. A multimodality approach seems to offer the best chances in this threatening situation.

In rats, the relationship between [(18)F]FHPG accumulation and HSVtk expression was studied with PET and autoradiography. [(18)F]FHPG distribution closely corresponded with HSVtk immunohistochemical staining. ROI analysis of tracer uptake 2 hours p.i. and Patlak graphical analysis were applied to quantify the PET data. For both analysis methods, the [(18)F]FHPG PET signal correlated well with the fraction of HSVtk expressing cells implanted, but showed a plateau when plotted against HSVtk protein levels. This might be due to rate limiting [(18)F]FHPG membrane transport.

[(11)C]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([(11)C]FMAU) and [(18)F]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk) enzyme activity after gene transfer and as tracers for localization of active human cytomegalovirus (HCMV) infections. In vitro accumulation experiments revealed that both [(11)C]FMAU and [(18)F]FHPG accumulated significantly more in HSV-tk expressing cells than they did in control cells. [(18)F]FHPG uptake in HSV-tk expressing cells, however, was found to depend strongly on the cell line used, which might be due to cell type dependent membrane transport or cell type dependent substrate specific susceptibility of the enzyme. In vitro, both tracers exhibited a good selectivity for accumulation in HCMV-infected human umbilical vein endothelial cells over uninfected cells. In contrast to [(18)F]FHPG, [(11)C]FMAU uptake in control cells was relatively high due to phosphorylation of the tracer by host kinases. Therefore, [(18)F]FHPG appears to be the more selective tracer not only to predict HSV-tk gene therapy outcome, but also to localize active HCMV infections with PET.