Breast cancer stromal clotting activation (Tissue Factor and thrombin): A pre-invasive phenomena that is prognostic in invasion
Author(s) Shaker H.; Bundred N.J.; Castle J.; Kirwan C.C.; Landberg G. et al.
Source Cancer Medicine; Mar 2020; vol. 9 (no. 5); p. 1768-1778
Background: Tumor stroma, of which fibroblasts are the most abundant cell, resembles a non-healing wound, where a procoagulant environment creates a permissive milieu for cancer growth. We aimed to determine if tumor expression of coagulation factors (procoagulant phenotype), and systemic hypercoagulability, occur at the preinvasive (ductal carcinoma in situ; DCIS) stage and correlate with breast cancer subtype, disease-free survival (DFS), and overall survival (OS).
Spirometry performed as part of the Manchester community-based lung cancer screening programme detects a high prevalence of airflow obstruction in individuals without a prior diagnosis of COPD
Author(s) Balata H.; Harvey J.; Barber P.V.; Duerden R.; Evison M. et al.
Source Thorax; May 2020
BACKGROUND: COPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme.
Author(s) Mateo J.; Perez-Lopez R.; Seed G.; Bertan C.; Rescigno P. et al.
Source Journal of Clinical Investigation; Apr 2020; vol. 130 (no. 4); p. 1743-1751
The genomics of primary prostate cancer differ from those of metastatic castration-resistant prostate cancer (mCRPC). We studied genomic aberrations in primary prostate cancer biopsies from patients who developed mCRPC, also studying matching, same-patient, diagnostic, and mCRPC biopsies following treatment. We profiled 470 treatment-naive prostate cancer diagnostic biopsies and, for 61 cases, mCRPC biopsies, using targeted and low-pass whole-genome sequencing (n = 52). Descriptive statistics were used to summarize mutation and copy number profile. Prevalence was compared using Fisher's exact test. Survival correlations were studied using log-rank test. TP53 (27%) and PTEN (12%) and DDR gene defects (BRCA2 7%; CDK12 5%; ATM 4%) were commonly detected. TP53, BRCA2, and CDK12 mutations were markedly more common than described in the TCGA cohort. Patients with RB1 loss in the primary tumor had a worse prognosis. Among 61 men with matched hormone-naive and mCRPC biopsies, differences were identified in AR, TP53, RB1, and PI3K/AKT mutational status between same-patient samples. In conclusion, the genomics of diagnostic prostatic biopsies acquired from men who develop mCRPC differ from those of the nonlethal primary prostatic cancers. RB1/TP53/AR aberrations are enriched in later stages, but the prevalence of DDR defects in diagnostic samples is similar to mCRPC.Copyright © 2020, Mateo et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Exploring health care professionals views on alternative approaches to cancer follow-up and barriers and facilitators to implementation of a recovery package
Author(s) Williamson S.; Beaver K.; Langton S.
Source European journal of oncology nursing : the official journal of European Oncology Nursing Society; Apr 2020; vol. 46 ; p. 101759
PURPOSE: To meet the long-term needs of cancer survivors the focus of recent cancer care reform in the United Kingdom (UK) has been the implementation of alternative follow-up strategies to relieve the growing pressures threatening to overwhelm cancer services. In 2013, the UK's National Cancer Survivorship Initiative recommended an integrated package of care called the Recovery Package to meet cancer survivors' psychosocial and information needs and supported self-management.
5 year Longitudinal Surgical performance in excisions of non melanoma head and neck skin cancer (NMHNSC)
Author(s) Chandran A.; Bhanji A.; Rao J.
Source British Journal of Oral and Maxillofacial Surgery; Dec 2019; vol. 57 (no. 10)
Introduction/Aims A surgeon's experience undertaking larger case volumes is often linked to better performance. The aim was to assess a single surgeons performance in NMHNSC excisions over five years. We analysed time and case number to reach a consistent competency with regards to excision margins. Materials/Methods Skin pathology data sets were collected retrospectively from 2014 to 2018 The data collected involved a single surgeon operating in multiple hospitals and settings. Information regarding patient demographics, histological features of NMHNSC and excision margins were collected from pathology reports for each operation.
Results/Statistics The results showed from January 2014 to April 2014 there was a 6.8% involved margin rate and a 11.4% close margin rate. This improved with further case volume over the five years. By September2018 to December 2018it was noted that the involved margin rate had reduced to 3.8% and the close margin rate had increased slightly to 13.4%. We present the longitudinal statistics.
Conclusions/Clinical relevance This study has shown that there appears to be improvement in performance of excisions of NMHNSC as the surgeon gains experience over time to reach a consistent performance. There was a clear initial learning curve to achieve this which took several cases. This likely differs from numbers presented in the literature believed to achieve competency in other bodily surgical procedures.Copyright © 2019
The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis
Author(s) Ryan N.A.J.; Crosbie E.J.; Evans D.G.; Glaire M.A.; Blake D. et al.
Source Genetics in Medicine; Oct 2019; vol. 21 (no. 10); p. 2167-2180
Purpose: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS.
Method(s): Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies.
Result(s): Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25-0.28, I2: 71%) and 0.26 (95% CI 0.25-0.27, I2: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25-0.33, I2: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses.
Conclusion(s): The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS.Copyright © 2019, The Author(s).
Hepatic steatosis in patients undergoing resection of colorectal liver metastases: A target for prehabilitation? A narrative review
Author(s) Doherty D.T.; Coe P.O.; Rimmer L.; Subar D.A.; Lapsia S. et al.
Source Surgical Oncology; Sep 2019; vol. 30 ; p. 147-158
The prevalence of elevated intra-hepatic fat (IHF) is increasing in the Western world, either alone as hepatic steatosis (HS) or in conjunction with inflammation (steatohepatitis). These changes to the hepatic parenchyma are an independent risk factor for post-operative morbidity following liver resection for colorectal liver metastases (CRLM). As elevated IHF and colorectal malignancy share similar risk factors for development it is unsurprisingly frequent in this cohort. In patients undergoing resection IHF may be elevated due to excess adiposity or its elevation may be induced by neoadjuvant chemotherapy, termed chemotherapy associated steatosis (CAS). Additionally, chemotherapy is implicated in the development of inflammation termed chemotherapy associated steatohepatitis (CASH). Following cessation of chemotherapy, patients awaiting resection have a 4-6 week washout period prior to resection that is a window for prehabilitation prior to surgery. In patients with NAFLD dietary and pharmacological interventions can reduce IHF within this timeframe but this approach to modifying IHF is untested in this population. In this review, the aetiology of CAS and CASH is reviewed with recommendations to identify those at risk. We also focus on the post-chemotherapy washout period, reviewing dietary interventions applied to the metabolic population and suggest this window may be used as an opportunity to optimise IHF with such a regime as part of a pre-operative prehabilitation programme to produce improved patient outcomes.Copyright © 2019 Elsevier Ltd
Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial
Author(s) Clarke N.W.; Hoyle A.; Ali A.; Ingleby F.C.; Amos C.L. et al.
Source Annals of oncology : official journal of the European Society for Medical Oncology; Sep 2019
BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naive prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
METHOD(S): We randomly allocated patients in 2:1 ratio to standard-of-care (SOC; control group) or SOC+docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.
RESULT(S): Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n=724) or SOC+docetaxel (n=362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR=0.81, 95% CI 0.69-0.95, P=0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P=0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR=0.66, 95% CI 0.57-0.76, P<0.001) and progression-free survival (HR=0.69, 95% CI 0.59-0.81, P<0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P>0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1year without prior progression).
CONCLUSION(S): The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naive prostate cancer patients regardless of metastatic burden.Copyright © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Hepatic steatosis in patients undergoing resection of colorectal liver metastases: A target for prehabilitation? A narrative review
Author(s): Doherty D.T.; Coe P.O.; Rimmer L.; Subar D.A.; Lapsia S.; Krige A.
Source: Surgical Oncology; 2019
Publication Date: 2019
Publication Type(s): Review
Available at Surgical Oncology - from ClinicalKey
Abstract:The prevalence of elevated intra-hepatic fat (IHF) is increasing in the Western world, either alone as hepatic steatosis (HS) or in conjunction with inflammation (steatohepatitis). These changes to the hepatic parenchyma are an independent risk factor for post-operative morbidity following liver resection for colorectal liver metastases (CRLM).
Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial
Author(s): Parker C.C.; Dearnaley D.P.; James N.D.; Brawley C.D.; Ritchie A.W.S.; Gilson C.; Langley R.E.; Millman R.; Amos C.L.; Parmar M.K.B.; Sydes M.R.; Clarke N.W.; Hoyle A.P.; Ali A.; Tran A.T.H.; Attard G.; Chowdhury S.; Cross W.; Gillessen S.; Jones R.J.; Russell J.M.; Malik Z.I.; Eswar C.; Mason M.D.; Matheson D.; Thalmann G.N.; Alonzi R.; Bahl A.; Birtle A.; Din O.; Douis H.; Gale J.; Gannon M.R.; Jonnada S.; Khaksar S.; Lester J.F.; O'Sullivan J.M.; Parikh O.A.; Pedley I.D.; Pudney D.M.; Sheehan D.J.; Srihari N.N.
Source: The Lancet; Dec 2018; vol. 392 (no. 10162); p. 2353-2366
Publication Date: Dec 2018
Publication Type(s): Article
Abstract:Background: Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy. Method(s): We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer.
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