• Risk of premature menopause after treatment for Hodgkin's lymphoma.

      Swerdlow, A; Cooke, R; Bates, A; Cunningham, D; Falk, S; Gilson, D; Hancock, B; Harris, S; Horwich, A; Hoskin, P; et al. (2014-08)
      Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited.
    • Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the acute leukemia working party of the EBMT.

      Battipaglia, G; Labopin, M; Candoni, A; Fanin, R; El Cheikh, J; Blaise, D; Michallet, M; Ruggeri, A; Contentin, N; Ribera, J; et al. (2017-01-16)
      Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.Bone Marrow Transplantation advance online publication, 16 January 2017; doi:10.1038/bmt.2016.302.
    • Risk of subsequent primary cancers in patients with carcinoma of the Ampulla of Vater.

      Moran, Anthony; Collins, Stuart; Evans, D Gareth R; Davies, R; Centre for Cancer Epidemiology, University of Manchester, Christie Hospital NHS Trust, UK. (1997)
      Data were collected on subsequent primary cancers occurring in 194 individuals diagnosed with ampullary carcinoma during 1979-92 in the north western region of England, UK. Four cancers were identified compared with 6.62 expected (relative risk 0.60), suggesting that individuals with ampullary carcinoma are not at increased risk of developing subsequent primary cancers.
    • Risk reducing mastectomy: outcomes in 10 European centres.

      Evans, D Gareth R; Baildam, Andrew D; Anderson, Elizabeth; Brain, Anne; Shenton, Andrew; Vasen, H F A; Eccles, Diana; Lucassen, A; Pichert, G; Hamed, H; et al. (2009-04)
      BACKGROUND: Increasingly women at high risk of breast cancer are opting for risk reducing surgery. The aim of this study was to assess the effectiveness of this approach in women at high risk in both carriers and non-carriers of BRCA1/2. METHODS: Data from 10 European centres that offer a genetic counselling and screening service to women at risk were obtained prospectively from 1995. Breast cancer risks were estimated from life tables and a control group of women at risk who did not undergo surgery. RESULTS: The combined centres have data on 550 women who have undergone risk reducing mastectomy with greater than 3334 women years of follow-up. Operations were carried out on women with lifetime risks of 25-80%, with an average expected incidence rate of 1% per year. No breast cancers have occurred in this cohort in the "at risk" unaffected breast, whereas >34 would have been expected. A high rate (2-3.6%) of occult disease was identified in the at risk breast at the time of surgery. INTERPRETATION: We conclude that risk reducing surgery is highly effective.
    • Risk scores for outpatient management of febrile neutropenia: Is the MASCC slipping?

      Cooksley, Timothy J; Ahn, S; Knight, T; Rice, T; The Christie, Manchester, UK (2017-12-04)
    • Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation

      Parry, MG; Cowling, TE; Sujenthiran, A; Nossiter, J; Berry, B; Cathcart, P; Aggarwal, A; Payne, H; van der Meulen, J; Clarke, Noel W; et al. (2020)
      Background: The five-tiered Cambridge Prognostic Group (CPG) classification is a better predictor of prostate cancer-specific mortality than the traditional three-tiered classification (low, intermediate, and high risk). We investigated radical treatment rates according to CPG in men diagnosed with non-metastatic prostate cancer in England between 2014 and 2017. Methods: Patients diagnosed with non-metastatic prostate cancer were identified from the National Prostate Cancer Audit database. Men were risk stratified according to the CPG classification. Risk ratios (RR) were estimated for undergoing radical treatment according to CPG and for receiving radiotherapy for those treated radically. Funnel plots were used to display variation in radical treatment rates across hospitals. Results: A total of 61,999 men were included with 10,963 (17.7%) in CPG1 (lowest risk group), 13,588 (21.9%) in CPG2, 9452 (15.2%) in CPG3, 12,831 (20.7%) in CPG4, and 15,165 (24.5%) in CPG5 (highest risk group). The proportion of men receiving radical treatment increased from 11.3% in CPG1 to 78.8% in CGP4, and 73.3% in CPG5. Men in CPG3 were more likely to receive radical treatment than men in CPG2 (66.3% versus 48.4%; adjusted RR 1.44; 95% CI 1.36-1.53; P < 0.001). Radically treated men in CPG3 were also more likely to receive radiotherapy than men in CPG2 (59.2% versus 43.9%; adjusted RR, 1.18; 95% CI 1.10-1.26). Although radical treatment rates were similar in CPG4 and CPG5 (78.8% versus 73.3%; adjusted RR 1.01; 95% CI 0.98-1.04), more men in CPG5 had radiotherapy than men in CPG4 (79.9% versus 59.1%, adjusted RR 1.26; 95% CI 1.12-1.40). Conclusions: The CPG classification distributes men in five risk groups that are about equal in size. It reveals differences in treatment practices in men with intermediate-risk disease (CPG2 and CPG3) and in men with high-risk disease (CPG4 and CPGP5) that are not visible when using the traditional three-tiered risk classification. Keywords: CPG; Cambridge Prognostic Groups; Non-metastatic disease; Prostate cancer; Risk stratification; Treatment selection.
    • Risk-based breast cancer screening strategies in women

      Harkness, EF; Astley, SM; Evans, D Gareth R; Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK (2019)
      The incidence of breast cancer continues to increase worldwide. Population-based screening is available in many countries but may not be the most efficient use of resources, thus interest in risk-based/stratified screening has grown significantly in recent years. An important part of risk-based screening is the incorporation of mammographic density (MD) and single nucleotide polymorphisms (SNPs) into risk prediction models to be combined with classical risk factors. In this article, we discuss different measures of MD and risk prediction models that are available. Risk-stratified screening options including supplemental or alternative screening modalities including digital breast tomosynthesis (DBT), automated ultrasound (ABUS) and magnetic resonance imaging (MRI) are discussed, as well as potential risk-based interventions (diet and lifestyle, chemoprevention and risk-reducing surgery). Furthermore, we look at risk feedback in practice and the cost-effectiveness and acceptability of risk-based screening, highlighting some of the current challenges.
    • Risk-reducing laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for low-grade appendiceal mucinous neoplasm: early outcomes and technique.

      Fish, Rebecca; Selvasekar, Chelliah; Crichton, Peter; Wilson, Malcolm S; Fulford, Paul E; Renehan, Andrew G; O'Dwyer, Sarah T; Peritoneal Tumour Service, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. (2013-09-06)
      Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion of pseudomyxoma peritonei, which, if treated suboptimally, may later disseminate throughout the abdominal cavity. We previously demonstrated the role of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) to reduce the dissemination risk. Here we describe the feasibility and safety of minimal access cytoreductive surgery (MACRS) and HIPEC as an alternative to the open approach.
    • Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral.

      Ingham, S; Sperrin, M; Baildam, A; Ross, Gary L; Clayton, R; Lalloo, F; Buchan, I; Howell, Anthony; Evans, D (2013-12)
      The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.
    • Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma.

      Gisselbrecht, C; Schmitz, N; Mounier, N; Singh Gill, D; Linch, D; Trneny, M; Bosly, A; Milpied, N; Radford, John A; Ketterer, N; et al. (2012-10-22)
      PURPOSEThe standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. PATIENTS AND METHODSIn total, 477 patients with CD20(+) DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. RESULTS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01). CONCLUSIONIn relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.
    • Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles.

      Cunningham, D; Hawkes, E; Jack, A; Qian, W; Smith, P; Mouncey, P; Pocock, C; Ardeshna, K; Radford, John A; McMillan, A; et al. (2013-05-25)
      Dose intensification with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) every 2 weeks improves outcomes in patients older than 60 years with diffuse large B-cell lymphoma compared with CHOP every 3 weeks. We investigated whether this survival benefit from dose intensification persists in the presence of rituximab (R-CHOP) in all age groups.
    • Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial.

      Gleeson, M; Hawkes, E; Cunningham, D; Chadwick, N; Counsell, N; Lawrie, A; Jack, A; Smith, P; Mouncey, P; Pocock, C; et al. (2016-08-01)
      We performed a subgroup analysis of the phase III UK National Cancer Research Institute R-CHOP-14 versus R-CHOP-21 (two- versus three-weekly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) trial to evaluate the outcomes for 50 patients with World Health Organization 2008 classified primary mediastinal B-cell lymphoma identified from the trial database. At a median follow-up of 7·2 years the 5-year progression-free survival and overall survival was 79·8% and 83·8%, respectively. An exploratory analysis raised the possibility of a better outcome in those who received R-CHOP-14 and time intensification may still, in the rituximab era, merit testing in a randomised trial in this subgroup of patients.
    • RIVA - a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial.

      Lim, SH; Linton, Kim M; Collins, GP; Dhondt, J; Caddy, J; Rossiter, L; Vadher, K; Fines, K; Rogers, LE; Fernando, D; et al. (2018)
      BACKGROUND: Over 12,000 new cases of B-cell malignancies are diagnosed in the UK each year, with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) being the most common subtypes. Standard frontline therapy consists of immunochemotherapy with a CD20 monoclonal antibody (mAb), such as rituximab, delivered in combination with multi-agent chemotherapy. Despite being considered a treatable and potentially curable cancer, approximately 30% of DLBCL cases will relapse after frontline therapy. Advanced stage FL is incurable and typically has a relapsing and remitting course with a frequent need for re-treatment. Based on supportive preclinical data, we hypothesised that the addition of varlilumab (an anti-CD27 mAb) to rituximab (an anti-CD20 mAb) can improve the rate, depth and duration of the response of rituximab monotherapy in patients with relapsed or refractory B-cell malignancies. METHODS/DESIGN: Combination treatment of varlilumab plus rituximab, in two different dosing regimens, is being tested in the RIVA trial. RIVA is a two-stage open-label randomised phase IIa design in up to 40 patients with low- or high-grade relapsed or refractory CD20+ B-cell lymphoma. The study is open to recruitment in the UK. Enrolled patients are randomised 1:1 to two different experimental varlilumab to rituximab combinations. The primary objective is to determine the safety and tolerability of the combination and the anti-tumour activity (response) in relapsed or refractory B-cell malignancies. Secondary objectives will include an evaluation of the duration of the response and overall survival. Tertiary translational objectives include assessment of B-cell depletion, changes in immune effector cell populations, expression of CD27 as a biomarker of response and pharmacokinetic properties. Analyses will not be powered for formal statistical comparisons between treatment arms. DISCUSSION: RIVA will determine whether the combination of rituximab and varlilumab in relapsed or refractory B-cell malignancies is active and safe prior to future phase II/III trials. TRIAL REGISTRATION: EudraCT, 2017-000302-37. Registered on 16 January 2017. ISRCTN, ISRCTN15025004 . Registered on 16 August 2017.
    • Rivaroxaban thromboprohylaxis in ambulatory patients with pancreatic cancer: results from a prespecified subgroup analysis of the CASSINI study

      Vadhan-Raj, S; McNamara, Mairead G; Venerito, M; Riess, H; O'Reilly, EM; Overman, MJ; Zhou, X; Vijapurkar, U; Kaul, S; Wildgoose, P; et al. (2019)
    • Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre-specified subgroup analysis of the randomized CASSINI study

      Vadhan-Raj, S.; McNamara, Mairead G; Venerito, M.; Riess, H.; O'Reilly, E. M.; Overman, M. J.; Zhou, X.; Vijapurkar, U.; Kaul, S.; Wildgoose, P.; et al. (2020)
      Background: Pancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established. Methods: This trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ?2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep-vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE-related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis-defined major bleeding. Results: In total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double-blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34-1.43; P = .328) in up-to-day-180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13-0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D-dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo (P < .01). Conclusions: In ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE-related death in the 180-day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting.
    • A roadmap for the clinical implementation of optical-imaging biomarkers

      Waterhouse, D; Fitzpatrick, C; Pogue, B; O'Connor, James P B; Bohndiek, S; Department of Physics, University of Cambridge, Cambridge, UK (2019)
      Clinical workflows for the non-invasive detection and characterization of disease states could benefit from optical-imaging biomarkers. In this Perspective, we discuss opportunities and challenges towards the clinical implementation of optical-imaging biomarkers for the early detection of cancer by analysing two case studies: the assessment of skin lesions in primary care, and the surveillance of patients with Barrett's oesophagus in specialist care. We stress the importance of technical and biological validations and clinical-utility assessments, and the need to address implementation bottlenecks. In addition, we define a translational roadmap for the widespread clinical implementation of optical-imaging technologies.
    • Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England.

      Nossiter, J; Sujenthiran, A; Charman, S; Cathcart, P; Aggarwal, A; Payne, H; Clarke, Noel W; van der Meulen, J; Department of Health Services Research & Policy, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK (2018-01-18)
      Robot-assisted radical prostatectomy (RARP) has been rapidly adopted without robust evidence comparing its functional outcomes against laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP) approaches. This study compared patient-reported functional outcomes following RARP, LRP or ORP.
    • Robotic assisted hysterectomy in obese patients: a systematic review.

      Iavazzo, Christos; Gkegkes, I; Gynaecological Oncology Department, Christie Hospital, Manchester, UK (2016-02-10)
      Robotic hysterectomy is an alternative approach to the management of female genital tract pathology.
    • Robotic assisted surgery in horseshoe kidneys: a safety and feasibility multicentre case series

      Ng, A.; Nathan, A.; Campain, N.; Yuminaga, Y.; Mumtaz, F.; Gulamhusein, A.; Tran, M.; Barod, R.; Patki, P.; UCL Medical School, University College London, London, United Kingdom (2021)
      Introduction Horseshoe kidneys (HSK) are the most common renal fusion abnormality. However, they are only present in 0.2% of the population. Due to anatomical variation in vasculature, ectopia and malrotation, surgery has traditionally been performed via an open approach. We aimed to assess the safety and feasibility of robot-assisted surgery for HSK. Method Six patients (four female, two male) with HSKs were operated on between 2016 and 2019 across two high-volume centres by high-volume surgeons. All operations were robot-assisted, with three partial nephrectomies and one nephroureterectomy for renal masses and two benign nephrectomies for non-functioning kidneys. 3D reconstruction using CT renal angiograms was used to help identify vasculature and tumour location (where appropriate). Results The median age was 53 years (IQR 47-58.3) and the median BMI was 25 (IQR 25-25.8). Median tumour size in the four patients with renal masses was 35.5 mm (IQR 25.3-44.8). Median console time was 120 minutes (IQR 117-172.5) and the median estimated blood loss was 150 mL (IQR 112.5-262.5). The median pre-operative eGFR was 76 (IQR 70-86.5) and median post-operative eGFR was 65.5 (IQR 59.3-80.8). All operations were uneventful, there were no perioperative transfusions and no complications reported. Length of stay was two days for all patients. Conclusions We report the largest series of mixed robotic-assisted surgery on HSK. Robotic surgery is safe and feasible for HSK in high-volume centres with acceptable perioperative outcomes. Further prospective, longer-term, multi-centre studies are required to evaluative if robotic surgery for HSK is superior to open surgery.