A Randomized, Double-Blind, Biomarker- Selected, Phase II Clinical Trial of Maintenance Poly ADP-Ribose Polymerase Inhibition With Rucaparib Following Chemotherapy for Metastatic Urothelial Carcinoma
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2022 Aug 12, pp. JCO2200405. Date of Electronic Publication: 2022 Aug 12.
Publication Model: Ahead of Print
Purpose: A DNA repair deficiency (DRD) phenotype exists within a subset of metastatic urothelial carcinomas (mUC) predicting benefit from platinum-based chemotherapy. We tested switch maintenance therapy with the poly ADP-ribose polymerase inhibitor rucaparib, following chemotherapy, for DRD biomarker-positive mUC.
Methods: DRD biomarker-positive mUC patients, within 10 weeks of chemotherapy, and without cancer progression, were randomly assigned (1:1) to maintenance rucaparib 600 mg twice a day orally, or placebo, until disease progression. The primary end point was progression-free survival (PFS). Statistical analysis targeted a hazard ratio of 0.5 with a 20% one-sided α for this signal-seeking trial. PFS (RECIST 1.1) was compared between trial arms, by intention to treat, within a Cox model.
Results: Out of 248 patients, 74 (29.8%) were DRD biomarker-positive and 40 were randomly assigned. A total of 12 (60%) and 20 (100%) PFS events occurred in the rucaparib and placebo arms, respectively (median follow-up was 94.6 weeks in those still alive). Median PFS was 35.3 weeks (80% CI, 11.7 to 35.6) with rucaparib and 15.1 weeks (80% CI, 11.9 to 22.6) with placebo (hazard ratio, 0.53; 80% CI, 0.30 to 0.92; one-sided P = .07). In the safety population (n = 39) treatment-related adverse events were mostly low grade. Patients received a median duration of 10 rucaparib or six placebo cycles on treatment. Treatment-related adverse events (all grades) of fatigue (63.2% v 30.0%), nausea (36.8% v 5.0%), rash (21.1% v 0%), and raised alanine aminotransferase (57.9% v 10%) were more common with rucaparib.
Conclusion: Maintenance rucaparib, following platinum-based chemotherapy, extended PFS in DRD biomarker-selected patients with mUC and was tolerable. Further investigation of poly ADP-ribose polymerase inhibition in selected patients with mUC is warranted.
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The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta-analysis.
Authors: Atwal A; Snowsill T; Dandy MC et al.
Source: International journal of cancer [Int J Cancer] 2022 Jun 15. Date of Electronic Publication: 2022 Jun 15.
Ovarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five-year survival for OC is around 45% increasing the need for innovative treatments. Checkpoint inhibitors have shown significant clinical efficacy in mismatch repair deficient (MMRd) cancers and could be a powerful treatment in OC. However, their application in OC is limited due to the lack of data on the prevalence of MMRd. The aim of our study was to conduct a systematic review of the literature and meta-analysis to provide an accurate estimate of the prevalence of MMRd in OC.
Full text available here
A cohort study of duplicate faecal immunochemical testing in patients at risk of colorectal cancer from North-West England.
Authors: Hunt N; Rao C; Logan R;
Source: BMJ open [BMJ Open] 2022 Apr 13; Vol. 12 (4), pp. e059940. Date of Electronic Publication: 2022 Apr 13.
Objectives: We sought to investigate if duplicate faecal immunochemical testing (FIT) sampling improves the negative and positive predictive value of patients thought to be at risk of colorectal cancer (CRC). Specifically, we aimed to investigate whether the proportion of FIT-negative CRC missed by a single FIT test in symptomatic patients could be reduced by duplicate FIT testing.
Design: A retrospective service evaluation cohort study of the diagnostic accuracy of duplicate FIT testing.
Setting: Patients referred from primary care with suspected CRC to four secondary care trusts in North-West England.
Participants: 28 622 patients over 18-years-old with lower gastrointestinal symptoms suggestive of CRC who completed two FIT samples.
Primary and Secondary Outcome Measures: The performance of duplicate FIT for detecting CRC at a threshold of 10 µgHb/g.
Results: The sensitivity if either test was >10 µgHb/g was 0.978 (0.955-0.989), specificity was 0.662 (0.657-0.668), positive predictive value 0.031 (0.028-0.035) and negative predictive value 1.00 (0.999-1.00). Despite two-thirds of patients (18952) being negative following two tests, at this threshold only seven CRC were missed over a 26-month period. All seven patients had other high-risk features which should have prompted investigation.
Conclusions: This study suggests that in routine NHS practice, a duplicate FIT sample strategy together with clinical evaluation for evidence of anaemia and weight loss is superior to a single FIT sample alone and would allow symptomatic patients to be managed in primary care without the need for urgent referral to secondary care for urgent colonic imaging.
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‘It’s always in the back of my mind’: understanding the psychological impact of recovery following pancreaticoduodenectomy for cancer: a qualitative study
Taylor AK; School of Medicine, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK firstname.lastname@example.org.
Chang D; Department of General Surgery, Royal Blackburn Hospital, East Lancashire Hospitals NHS Trust, Blackburn, UK.
Chew-Graham C; School of Medicine, Keele University, Keele, UK.
Rimmer L; Department of General Surgery, Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, UK.
Kausar A; Department of General Surgery, Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, UK.
Source: BMJ open 2021 Dec 16; Vol. 11 (12), pp. e050016. Date of E-Publication: 2021 Dec 16.
Publication Type: Journal Article
Objectives: Ten per cent of patients diagnosed with pancreatic cancer undergo pancreaticoduodenectomy. There is limited previous research focusing on psychological well-being; unmet support needs impact negatively on quality of life. This paper reports the psychological impact of a pancreatic cancer diagnosis and subsequent pancreaticoduodenectomy, exploring how patients' lives alter following surgery and how they seek support.
Design: Inductive qualitative study involving in-depth semistructured interviews with 20 participants who had undergone pancreaticoduodenectomy for pancreatic or distal biliary duct cancer. Interviews were audiorecorded, transcribed and anonymised, and thematic analysis used principles of constant comparison.
Setting: Single National Health Service Trust in Northwest England.
Participants: Patients were eligible for inclusion if they had had pancreaticoduodenectomy for head of pancreas cancer, periampullary cancer or distal cholangiocarcinoma between 6 months and 6 years previously, and had completed adjuvant chemotherapy.
Results: Analysis identified the following main themes: diagnosis and decision making around surgery; recovery from surgery and chemotherapy; burden of monitoring and ongoing symptoms; adjusting to 'a new normal'; understanding around prognosis; support-seeking. Participants seized the chance to have surgery, often without seeming to absorb the risks or their prognosis. They perceived that they were unable to control their life trajectory and, although they valued close monitoring, experienced anxiety around their appointments. Participants expressed uncertainty about whether they would be able to return to their former activities. There were tensions in their comments about support-seeking, but most felt that emotional support should be offered proactively.
Conclusions: Patients should be made aware of potential psychological sequelae, and that treatment completion may trigger the need for more support. Clinical nurse specialists (CNSs) were identified as key members of the team in proactively offering support; further training for CNSs should be encouraged. Understanding patients' experience of living with cancer and the impact of treatment is crucial in enabling the development of improved support interventions.
Available at BMJ Open
Home Based Pre-Rehabilitation in Hepatic & Pancreatic Oncological Surgery- A Way Forward for Improved Patient Outcome
Author(s) Ahmed N.; Obeidallah R.; Subar D.
Institution(s) (Ahmed, Obeidallah, Subar) Royal Blackburn Hospital, Blackburn, United Kingdom
Source British Journal of Surgery; Oct 2021; vol. 108
AbstractAims: To ascertain the impact of ''Cost effective home-based pre-rehabilitation'' on post-operative outcomes in patients undergoing major hepatic and pancreatic oncological surgery. Method(s): In this non-randomized comparative study (2019-2021), we included 36 patients having pancreatic or hepatic malignancy. In group I, patients were signed up for home-based pre-rehabilitation program and dietary modification. Group II; included patients who did not have rehabilitation. The two groups were compared for post-operative outcomes (post-operative complications, length of ITU and hospital stay) Results: Mean age was 69.05+/-9.68 years in group I and 67.50+/-8.75 years in group II (p-value 0.61). Open approach was used in 02 (11.0%) patients in group I and in 09 (50%) patients in group II (p-value 0.01). More patients in group II needed admission in intensive care unit (ICU); 18 (100%) versus 11 (61.1%) in group II (p-value 0.0003). The group I had shorter length of hospital stay as compared to Group II (p-value 0.0001). There was no significant difference in post-operative complications between the groups. Conclusion(s): Home based pre-rehabilitation, has shown beneficial outcomes in terms of less requirement for ITU admission post operatively, shorter length of hospital stay and cost effective method of pre rehabilitation.
Diagnostic Utility of MRI in the evaluation of potential malignancy in patients presented with nipple discharge
Author(s) Yang N.P.C.; Nijjar P.S.; Phyu S.; Barkeji M.; Butt M.A.J.
Institution(s) (Yang, Nijjar, Phyu, Barkeji) West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
(Butt) Royal Blackburn Hospital
Source British Journal of Surgery; Oct 2021; vol. 108
AbstractAims: Nipple discharge is a presentation commonly seen at breast clinics. It is conventionally evaluated with physical examination and sonography( or mammography). The aim of this study is to investigate the diagnostic value of magnetic resonance imaging (MRI) as an additional imaging tool in the evaluation of potential malignancy in patients presented with nipple discharge. Method(s): A retrospective evaluation of 85 patients with nipple discharge who underwent breast ultrasound (USS) and MRI between 04/ 06/2008 and 25/10/2019 was conducted. Clinical notes, radiographic reports and biopsy results were reviewed. Sensitivity, specificity, positive predictive value and negative predictive value of USS and MRI were calculated. Result(s): Out of the 85 patients (all female; mean age 45.33 +/- 12.93 years old) with nipple discharge, 11 were found to have biopsy-proven malignancy (invasive ductal carcinoma/ ductal carcinoma in situ; 12.94% risk). USS failed to identify seven malignancies (27.27% sensitivity) while MRI missed three malignancies (72.72% sensitivity). USS falsely identified four malignancies from 74 patients with no malignancy (94.59% specificity) while MRI only falsely identified one case (98.65% specificity). For patients with negative USS results (U1/U2/U3) or negative MRI results (BI-RADS category 1,2 or 3), the negative predictive values of USS is 89.74% while that of MRI is 96.05%. The positive predictive values of USS and MRI are 42.86% and 88.88% respectively. Conclusion(s): Compared to USS, MRI has a higher sensitivity, specificity, positive predictive value and predictive value. It will be a valuable addition to the standard nipple discharge evaluation workup to help rule out malignancy.
Examples of the great mimickers of breast carcinoma and their sonographic appearances
Author(s) West S.
Source Breast Cancer Research; 2021; vol. 23
Breast carcinomas can take on a multitude of appearances that display the features of a true carcinoma. These being: shape, orientation, echo pattern and posterior features. However, some benign entities can mimic these appearances on ultrasound. This pictorial review demonstrates some of the great mimickers that display the worrying features. Diabetic Mastopthy-Disease with fibro inflammatory processes of the breast. Features can include hard, irregular hypoechoic mass with posterior shadowing. Fat Necrosis-Known as a benign non-supparitive inflammatory process. This process occurs due to breast trauma. Some of the common causes are: radiotherapy, surgery or trauma. Sonographically, the appearance may display an irregular complex mass, edge shadowing or a hyper-echoic irregular mass. Tuberculosis-The most frequent mode of infection is spread from the axillary nodes. Appearances can present as nodular, diffuse and sclerosing. The nodular type of Tuberculosis can manifest as an ill defined hypoechoic mass. The diffuse type can simulate inflammatory carcinoma, and the sclerosing type can be associated with areas of architectural distortion. Granular Cell tumour-A benign neoplasm derived from perineural scwann cell of peripheral nerves. On ultrasound, the appearances can present as an irregular or ill defined mass with posterior acoustic shadowing. Fibromatosis-This is a benign tumour that can occur in the breast. The definitive eitology is unclear but can be associated with Gardeners' syndrome. On Ultrasound, this can present as an irregular hypoechoic mass with a thick echogenic rim and posterior shadowing.
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
Author(s) Alurralde C.; Caram E.L.; Eskinazi D.; Badra R.; Garcia J.S. et al.
Source Colorectal Disease; Mar 2021; vol. 23 (no. 3); p. 732-749
Aim: This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic.
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).
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