34 research outputs found
Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?
Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions
Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study
BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC
New strategies and designs in pancreatic cancer research : consensus guidelines report from a European expert panel
Two-Stage Surgical Treatment of Unresectable Obstructive Rectal Cancer with Synchronous Hepatic Metastases
Sixteen-year follow-up of Barrett's esophagus, endoscopically treated with argon plasma coagulation.
OBJECTIVE: The thermal destruction of non-dysplastic Barrett’s esophagus (BE) and its replacement by squamous epithelium is an attractive, but unproven strategy to avoid further development of dysplasia or cancer. The goal of this study was to estimate the persistence of restoration of squamous epithelium and the risk of cancer in BE that was eradicated using argon plasma coagulation (APC) in the absence of high-grade dysplasia, 16 years after its application.
DESIGN: We followed 32 patients with BE who underwent eradication of metaplastic epithelium using APC, up to 16 years later.
RESULTS: At the end of the initial treatment, 25 of 32 patients (78%) had complete endoscopic eradication, there was partial squamous re-epithelialization in four patients (13%) and it was absent in three patients (9%). We observed buried metaplastic glands under new squamous epithelium in 6 of the 25 patients who had complete endoscopic eradication. At follow-up, sustained complete endoscopic eradication was observed in 16 of 32 patients (50%), partial eradication in 11 of 32 patients (35%); there were two patients (6%) lost to follow-up and three patients (9%) developed esophageal adenocarcinoma. Two of the latest cases arose from the buried glands under neosquamous epithelium after complete eradication and one arose from a small remaining Barrett’s segment.
CONCLUSIONS: We observed long-term re-epithelialization in the majority of patients who had previously had complete eradication of Barrett’s esophagus. This did not provide protection against cancer development, as the incidence of cancers arising from buried glands or from residual Barrett’s esophagus was similar to that observed in patients undergoing no specific treatment.</p
289 Phase II study of cetuximab combined with FOLFIRI (bi-weekly irinotecan plus infusional 5-FU and folinic acid (FA) in patients (pts) with metastatic, Epidermal growth factor receptor (EGFR)-expressing colorectal cancer (CRC)
1086 Cetuximab in a randomized phase II trial as a single agent or in combination with irinotecan in patients with epidermal growth factor receptor (EGFR)-expressing, irinotecan-refractory metastatic colorectal cancer (CRC)
Ki-ras oncogene mutations in chronic pancreatitis: which discriminating ability for malignant potential?
Ki-ras mutations are found in the majority of pancreatic adenocarcinomas (85-100%). Ki-ras analysis was increasingly used in ERCP samples in order to differentiate between chronic pancreatitis and pancreatic cancer. However, its sensitivity was recently reported to be low due to a high prevalence of ras mutations in patients with chronic pancreatitis (25-37%). Detection of Ki-ras mutations in microdissected pancreata confirmed their high frequency (55-83%) in pancreatic intraductal lesions (PILs) observed in chronic pancreatitis specimens and in the vicinity of invasive pancreatic carcinoma. There is now molecular evidence that PILs can be precursors of invasive carcinoma, since they can harbor genetic alterations identical to those of the adjacent carcinoma. Similarly, we observed 2 patients with chronic pancreatitis who developed pancreatic cancer 18 and 24 months after the evidence of Ki-ras mutations in pancreatic brushings. However, besides these findings, ras mutations were also identified in nondiseased pancreata coming from autopsy series. The current data on ras analysis in pancreatic juice and brushings or in microdissected pancreata suggest that PILs with Ki-ras mutations do not inevitably lead toward invasive carcinoma. Ki-ras mutations probably have a low discriminating ability for malignant potential and their detection in pancreatic juice is not justified routinely for differentiating between benign and malignant pancreatic diseases. However, prospective follow-up of patients with chronic pancreatitis harboring a mutant ras is probably of major interest by combining the search for other genetic markers that have the ability to characterize patients with the greater risk of malignant transformation.Journal ArticleReviewFLWINinfo:eu-repo/semantics/publishedCell and Molecular Biology of Pancreatic Carcinomaa: Recent Developments in Research and Experimental Therap