Citation: Journal of Cancer Education. 2020 Jan 28[Online ahead of print]
Author: Catherine Walshe, Diane Roberts, Lynn Calman, Lynda Appleton, Robert Croft, Guillermo Perez Algorta, Suzanne Skevington, Mari Lloyd-Williams, Gunn Grande
Abstract: Peer mentors may offer distinctive forms of support to people with advanced cancer. Whilst peer mentor programmes are known, little is understood about recruiting and training peer mentors to support those with advanced cancer. The purpose of this study is to determine the feasibility of recruiting and training peer mentors for a novel peer mentor intervention to promote well-being in people with advanced cancer. Feasibility study testing proactive introduction to a trained peer mentor for 12 weeks in the context of a randomized controlled two-arm trial and nested qualitative process evaluation was used. Peer mentors have/had cancer, recruited via an open call. Two-day training included a new bespoke module on coping with cancer. Descriptive recruitment and training data were captured, supplemented by qualitative interviews, analysed thematically. Forty-eight people expressed interest, mostly female (69%), with breast cancer (32%), and recruited via social media (49%). Twelve people completed training, with attrition often due to availability or mentors' own health; many had advanced cancer themselves. They wanted to 'give something back', but also formed supportive bonds with fellow mentors. It is feasible to recruit and train people with lived experience of cancer to be peer mentors, but those with particular characteristics may predominate. Broad social media based recruitment may have merit in widening the pool of potential peer mentors.
Keywords: Cancer; Feasibility study; Palliative care; Peer Mentor; Recruitment; Volunteer.
Link to PubMed record
Thursday 27 February 2020
CCC publication: Advanced Intrahepatic Cholangiocarcinoma: Post Hoc Analysis of the ABC-01, -02, and -03 Clinical Trials
Citation: Journal of the National Cancer Institute. 2020, 112(2), 200-210
Author: Angela Lamarca, Paul Ross, Harpreet S Wasan, Richard A Hubner, Mairéad G McNamara, Andre Lopes, Prakash Manoharan, Daniel Palmer, John Bridgewater, Juan W Valle
Abstract: Background: The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with first-line cisplatin-gemcitabine chemotherapy (current standard of care).
Methods: Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistical tests were two-sided.
Results: Of 534 patients recruited into the ABC-01, -02, and -03 studies, 109 (20.4%) had iCCA. Most patients (n = 86, 78.9%) had metastatic disease at the time of recruitment; 52 patients (47.7%) had liver-only disease. Following random assignment, 66 (60.6%) iCCA patients received cisplatin and gemcitabine. The median progression-free and overall survival (OS) were 8.4 months (95% confidence interval [CI] = 5.9 to 8.9 months) and 15.4 months (95% CI = 11.1 to 17.9 months), respectively. Of these 66 patients, 34 patients (51.5%) had liver-only disease. Following chemotherapy, 30 (45.5%) and 21 (31.8%) were progression-free at 3 and 6 months from chemotherapy commencement, respectively. The median OS for patients with liver-only iCCA at diagnosis and after 3 and 6 months of chemotherapy was 16.7 months (95% CI = 8.7 to 20.2 months), 17.9 months (95% CI = 11.7 to 20.9 months), and 18.9 months (95% CI = 16.7 to 25.9 months), respectively. Multivariable analysis confirmed that iCCA had a longer OS compared with other non-iCCA biliary tract cancers (hazard ratio = 0.58, 95% CI = 0.35 to 0.95, P value = .03); liver-only iCCA patients also showed longer OS even though findings did not reach statistical significance (hazard ratio = 0.65, 95% CI = 0.36 to 1.19, P value = .16).
Conclusions: Patients diagnosed with advanced iCCA have a better OS compared with other biliary tract cancers; a similar trend was identified for patients diagnosed with liver-only iCCA. These findings are to be considered for future clinical trial design.
Link to PubMed record
Author: Angela Lamarca, Paul Ross, Harpreet S Wasan, Richard A Hubner, Mairéad G McNamara, Andre Lopes, Prakash Manoharan, Daniel Palmer, John Bridgewater, Juan W Valle
Abstract: Background: The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with first-line cisplatin-gemcitabine chemotherapy (current standard of care).
Methods: Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistical tests were two-sided.
Results: Of 534 patients recruited into the ABC-01, -02, and -03 studies, 109 (20.4%) had iCCA. Most patients (n = 86, 78.9%) had metastatic disease at the time of recruitment; 52 patients (47.7%) had liver-only disease. Following random assignment, 66 (60.6%) iCCA patients received cisplatin and gemcitabine. The median progression-free and overall survival (OS) were 8.4 months (95% confidence interval [CI] = 5.9 to 8.9 months) and 15.4 months (95% CI = 11.1 to 17.9 months), respectively. Of these 66 patients, 34 patients (51.5%) had liver-only disease. Following chemotherapy, 30 (45.5%) and 21 (31.8%) were progression-free at 3 and 6 months from chemotherapy commencement, respectively. The median OS for patients with liver-only iCCA at diagnosis and after 3 and 6 months of chemotherapy was 16.7 months (95% CI = 8.7 to 20.2 months), 17.9 months (95% CI = 11.7 to 20.9 months), and 18.9 months (95% CI = 16.7 to 25.9 months), respectively. Multivariable analysis confirmed that iCCA had a longer OS compared with other non-iCCA biliary tract cancers (hazard ratio = 0.58, 95% CI = 0.35 to 0.95, P value = .03); liver-only iCCA patients also showed longer OS even though findings did not reach statistical significance (hazard ratio = 0.65, 95% CI = 0.36 to 1.19, P value = .16).
Conclusions: Patients diagnosed with advanced iCCA have a better OS compared with other biliary tract cancers; a similar trend was identified for patients diagnosed with liver-only iCCA. These findings are to be considered for future clinical trial design.
Link to PubMed record
CCC publication: TG01/GM-CSF and Adjuvant Gemcitabine in Patients With Resected RAS-mutant Adenocarcinoma of the Pancreas (CT TG01-01): A Single-Arm, Phase 1/2 Trial
Citation: British Journal of Cancer. 2020, 122(7), 971-77. Epub 2020 Feb 17.
Author: Daniel H Palmer, Juan W Valle, Yuk Ting Ma, Olusola Faluyi, John P Neoptolemos, Trine Jensen Gjertsen, Berit Iversen, Jon Amund Eriksen, Anne-Sophie Møller, Anne-Kirsti Aksnes, Robert Miller, Svein Dueland
Abstract: Background: TG01 is the first cancer immunotherapy targeting KRAS oncogenic mutations. This study assessed the safety and efficacy of TG01/GM-CSF in patients with resected pancreatic adenocarcinoma.
Methods: Patients with stage I or II pancreatic adenocarcinoma who had undergone surgical resection (R0 or R1) received adjuvant gemcitabine with TG01/GM-CSF using two schedules of vaccination. Immune response was defined as a positive delayed-type hypersensitivity (DTH) response and/or positive T-cell proliferation assay.
Results: Thirty-two patients were enrolled between February 2013 and May 2016. Nineteen were treated with the high antigen burden, with four serious adverse reactions considered possibly related to TG01 treatment, including three allergic reactions. On this basis, a further 13 patients received a modified vaccination schedule with reduced antigen burden, with no serious adverse events related to TG01. Ninety-five percent patients in the main cohort and 92% in the modified cohort had a positive immune response. Median overall survival (OS) was 33.1 months, and median disease-free survival (DFS) was 13.9 months for the main cohort. For the modified cohort, the median OS was 34.3 months and median DFS was 19.5 months.
Conclusions: TG01/GM-CSF with gemcitabine was well tolerated, with high levels of immune activation. OS and DFS compare favourably with published data for adjuvant gemcitabine.
Clinical trial registration: This clinical trial was registered at ClinicalTrials.gov (NCT02261714).
Link to PubMed record
Author: Daniel H Palmer, Juan W Valle, Yuk Ting Ma, Olusola Faluyi, John P Neoptolemos, Trine Jensen Gjertsen, Berit Iversen, Jon Amund Eriksen, Anne-Sophie Møller, Anne-Kirsti Aksnes, Robert Miller, Svein Dueland
Abstract: Background: TG01 is the first cancer immunotherapy targeting KRAS oncogenic mutations. This study assessed the safety and efficacy of TG01/GM-CSF in patients with resected pancreatic adenocarcinoma.
Methods: Patients with stage I or II pancreatic adenocarcinoma who had undergone surgical resection (R0 or R1) received adjuvant gemcitabine with TG01/GM-CSF using two schedules of vaccination. Immune response was defined as a positive delayed-type hypersensitivity (DTH) response and/or positive T-cell proliferation assay.
Results: Thirty-two patients were enrolled between February 2013 and May 2016. Nineteen were treated with the high antigen burden, with four serious adverse reactions considered possibly related to TG01 treatment, including three allergic reactions. On this basis, a further 13 patients received a modified vaccination schedule with reduced antigen burden, with no serious adverse events related to TG01. Ninety-five percent patients in the main cohort and 92% in the modified cohort had a positive immune response. Median overall survival (OS) was 33.1 months, and median disease-free survival (DFS) was 13.9 months for the main cohort. For the modified cohort, the median OS was 34.3 months and median DFS was 19.5 months.
Conclusions: TG01/GM-CSF with gemcitabine was well tolerated, with high levels of immune activation. OS and DFS compare favourably with published data for adjuvant gemcitabine.
Clinical trial registration: This clinical trial was registered at ClinicalTrials.gov (NCT02261714).
Link to PubMed record
CCC publication: Real-world experience of regorafenib in patients with hepatocellular carcinoma: A multicenter United Kingdom study
Citation: Journal of Clinical Oncology. 2020, 38(4)
Author: Ross P.J.; Ma Y.T.; Palmer D.H.; Lythgoe M.P.; Merrick S.; Samson A.; Rao A.R.; Basu B.; Prasad D.; Dhillon T.; Lau D.; Darby S.; Orr J.; Margetts J.; Hubner R.; Baijal S.; Sharma R.; Faluyi O.O.; Lee L.; Thillai K.
Abstract: Conference Abstract
Author: Ross P.J.; Ma Y.T.; Palmer D.H.; Lythgoe M.P.; Merrick S.; Samson A.; Rao A.R.; Basu B.; Prasad D.; Dhillon T.; Lau D.; Darby S.; Orr J.; Margetts J.; Hubner R.; Baijal S.; Sharma R.; Faluyi O.O.; Lee L.; Thillai K.
Abstract: Conference Abstract
CCC publication: Effects of Plaque Brachytherapy and Proton Beam Radiotherapy on Prognostic Testing: A Comparison of Uveal Melanoma Genotyped by Microsatellite Analysis
Citation: The British Journal of Ophthalmology. 2020, 104(10), 1462-66. [Online ahead of print 2020 Feb 5]
Author: Sophie Thornton, Sarah E Coupland, Heinrich Heimann, Rumana Hussain, Carl Groenewald, Andrzej Kacperek, Bertil Damato, Azzam Taktak, Antonio Eleuteri, Helen Kalirai
Abstract: Background/aims: Proton beam radiotherapy and plaque brachytherapy are commonly applied in primary uveal melanoma (UM); however, their effect on chromosome 3 classification of UM by microsatellite analysis (MSA) for prognostication purposes is unknown, where the tumour is sampled post-irradiation. This study examined the prognostic accuracy of genotyping UM biopsied before or after administration of radiotherapy, by MSA.
Methods: 407 UM patients treated at the Liverpool Ocular Oncology Centre between January 2011 to December 2017, were genotyped for chromosome 3 by MSA; 172 and 176 primary UM were sampled prior to and post irradiation, respectively.
Results: Genotyping by MSA was successful in 396/407 (97%) of UM samples (196 males, 211 females; median age of 61 years (range 12 to 93) at primary treatment). There was no demonstrable association between a failure of MSA to produce a chromosome 3 classification and whether radiation was performed pre-biopsy or post-biopsy with an OR of 0.96 (95% CI 0.30 to 3.00, p=0.94). There was no evidence of association (measured as HRs) between risk of metastatic death and sampling of a primary UM before administration of radiotherapy (HR 1.1 (0.49 to 2.50), p=0.81). Monosomy 3 (HR 12.0 (4.1 to 35.0), p<0.001) was significantly associated with increased risk of metastatic death.
Conclusions and relevance: This study revealed that successful genotyping of UM using MSA is possible, irrespective of irradiation status. Moreover, we found no evidence that biopsy prior to radiotherapy increases metastatic mortality.
Keywords: diagnostic tests/investigation; eye (globe); genetics; iris; neoplasia.
Link to PubMed record
Author: Sophie Thornton, Sarah E Coupland, Heinrich Heimann, Rumana Hussain, Carl Groenewald, Andrzej Kacperek, Bertil Damato, Azzam Taktak, Antonio Eleuteri, Helen Kalirai
Abstract: Background/aims: Proton beam radiotherapy and plaque brachytherapy are commonly applied in primary uveal melanoma (UM); however, their effect on chromosome 3 classification of UM by microsatellite analysis (MSA) for prognostication purposes is unknown, where the tumour is sampled post-irradiation. This study examined the prognostic accuracy of genotyping UM biopsied before or after administration of radiotherapy, by MSA.
Methods: 407 UM patients treated at the Liverpool Ocular Oncology Centre between January 2011 to December 2017, were genotyped for chromosome 3 by MSA; 172 and 176 primary UM were sampled prior to and post irradiation, respectively.
Results: Genotyping by MSA was successful in 396/407 (97%) of UM samples (196 males, 211 females; median age of 61 years (range 12 to 93) at primary treatment). There was no demonstrable association between a failure of MSA to produce a chromosome 3 classification and whether radiation was performed pre-biopsy or post-biopsy with an OR of 0.96 (95% CI 0.30 to 3.00, p=0.94). There was no evidence of association (measured as HRs) between risk of metastatic death and sampling of a primary UM before administration of radiotherapy (HR 1.1 (0.49 to 2.50), p=0.81). Monosomy 3 (HR 12.0 (4.1 to 35.0), p<0.001) was significantly associated with increased risk of metastatic death.
Conclusions and relevance: This study revealed that successful genotyping of UM using MSA is possible, irrespective of irradiation status. Moreover, we found no evidence that biopsy prior to radiotherapy increases metastatic mortality.
Keywords: diagnostic tests/investigation; eye (globe); genetics; iris; neoplasia.
Link to PubMed record
CCC publication: NET-02 Trial Protocol: A Multicentre, Randomised, Parallel Group, Open-Label, Phase II, Single-Stage Selection Trial of Liposomal Irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic Acid or Docetaxel as Second-Line Therapy in Patients With Progressive Poorly Differentiated Extrapulmonary Neuroendocrine Carcinoma (NEC)
Citation: BMJ Open. 2020, 10(2), e034527
Author: Zoe Craig, Jayne Swain, Emma Batman, Jonathan Wadsley, Nicholas Reed, Olusola Faluyi, Judith Cave, Rohini Sharma, Ian Chau, Lucy Wall, Angela Lamarca, R Hubner, Wasat Mansoor, Debashis Sarker, Tim Meyer, David A Cairns, Helen Howard, Juan W Valle, Mairéad G McNamara
Abstract: Introduction: Poorly differentiated (PD), extrapulmonary (EP), neuroendocrine carcinomas (NECs) are rare but aggressive neuroendocrine neoplasms. First-line treatment for advanced disease is an etoposide and platinum-based chemotherapy combination. There is no established second-line treatment for patients with PD-EP-NEC, and this is an area of unmet need.
Methods and analysis: NET-02 is a UK, multicentre, randomised (1:1), parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive PD-EP-NEC. One hundred and two eligible participants will be randomised to receive either nal-IRI/5-FU/folinic acid or docetaxel. The primary objective is to determine the 6-month progression-free survival (PFS) rate. The secondary objectives of this study are to determine PFS, overall survival, objective response rate, toxicity, quality of life and whether neuron-specific enolase is predictive of treatment response. If either treatment is found to have a 6-month PFS rate of at least 25%, that treatment will be considered for a phase III trial. If both treatments meet this target, prespecified selection criteria will be applied to establish which treatment to take forward.
Ethics and dissemination: This study has ethical approval from the Greater Manchester Central Research Ethics Committee (reference no. 18/NW/0031) and clinical trial authorisation from the Medicine and Healthcare Products Regulatory Agency. Results will be published in peer-reviewed journals and uploaded to the European Union Clinical Trials Register.
Trial registration numbers: ISRCTN10996604, NCT03837977, EudraCT Number: 2017-002453-11.
Keywords: docetaxel; liposomal irinotecan; neuroendocrine carcinoma; randomised; single-stage.
Link to PubMed record
Author: Zoe Craig, Jayne Swain, Emma Batman, Jonathan Wadsley, Nicholas Reed, Olusola Faluyi, Judith Cave, Rohini Sharma, Ian Chau, Lucy Wall, Angela Lamarca, R Hubner, Wasat Mansoor, Debashis Sarker, Tim Meyer, David A Cairns, Helen Howard, Juan W Valle, Mairéad G McNamara
Abstract: Introduction: Poorly differentiated (PD), extrapulmonary (EP), neuroendocrine carcinomas (NECs) are rare but aggressive neuroendocrine neoplasms. First-line treatment for advanced disease is an etoposide and platinum-based chemotherapy combination. There is no established second-line treatment for patients with PD-EP-NEC, and this is an area of unmet need.
Methods and analysis: NET-02 is a UK, multicentre, randomised (1:1), parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive PD-EP-NEC. One hundred and two eligible participants will be randomised to receive either nal-IRI/5-FU/folinic acid or docetaxel. The primary objective is to determine the 6-month progression-free survival (PFS) rate. The secondary objectives of this study are to determine PFS, overall survival, objective response rate, toxicity, quality of life and whether neuron-specific enolase is predictive of treatment response. If either treatment is found to have a 6-month PFS rate of at least 25%, that treatment will be considered for a phase III trial. If both treatments meet this target, prespecified selection criteria will be applied to establish which treatment to take forward.
Ethics and dissemination: This study has ethical approval from the Greater Manchester Central Research Ethics Committee (reference no. 18/NW/0031) and clinical trial authorisation from the Medicine and Healthcare Products Regulatory Agency. Results will be published in peer-reviewed journals and uploaded to the European Union Clinical Trials Register.
Trial registration numbers: ISRCTN10996604, NCT03837977, EudraCT Number: 2017-002453-11.
Keywords: docetaxel; liposomal irinotecan; neuroendocrine carcinoma; randomised; single-stage.
Link to PubMed record
CCC publication: Challenges Conveying Clinical Equipoise and Exploring Patient Treatment
Citation: The Oncologist. 2020 Feb 11[Online ahead of print]
Author: Frances C Sherratt, Stephen L Brown, Brian J Haylock, Priya Francis, Helen Hickey, Carrol Gamble, Michael D Jenkinson, Bridget Young
Abstract: Introduction: Providing balanced information that emphasizes clinical equipoise (i.e., uncertainty regarding the relative merits of trial interventions) and exploring patient treatment preferences can improve informed consent and trial recruitment. Within a trial comparing adjuvant radiotherapy versus active monitoring following surgical resection for an atypical meningioma (ROAM/EORTC-1308), we explored patterns in communication and reasons why health practitioners may find it challenging to convey equipoise and explore treatment preferences.
Materials and methods: Qualitative study embedded within ROAM/EORTC-1308. Data were collected on 40 patients and 18 practitioners from 13 U.K. sites, including audio recordings of 39 patients' trial consultations, 23 patient interviews, and 18 practitioner interviews. Qualitative analysis drew on argumentation theory.
Results: Practitioners acknowledged the importance of the research question that the trial aimed to answer. However, they often demonstrated a lack of equipoise in consultations, particularly with eligible patients who practitioners believed to be susceptible to side effects (e.g., cognitive impairment) or inconvenienced by radiotherapy. Practitioners elicited but rarely explored patient treatment preferences, especially if a patient expressed an initial preference for active monitoring. Concerns about coercing patients, loss of practitioner agency, and time constraints influenced communication in ways that were loaded against trial participation.
Conclusions: We identified several challenges that practitioners face in conveying equipoise and exploring patient treatment preferences in oncology, and particularly neuro-oncology, trials with distinct management pathways. The findings informed communication about ROAM/EORTC-1308 and will be relevant to enhancing trial communication in future oncology trials. Qualitative studies embedded within trials can address difficulties with communication, thus improving informed consent and recruitment. ROAM/EORTC-1308 RCT: ISRCTN71502099.
Implications for practice: Oncology trials can be challenging to recruit to, especially those that compare treatment versus monitoring. Conveying clinical equipoise and exploring patient treatment preferences can enhance recruitment and patient understanding. This study focused on the challenges that practitioners encounter in trying to use such communication strategies and how practitioners may inadvertently impede patient recruitment and informed decision making. This article provides recommendations to support practitioners in balancing the content and presentation of trial management pathways. The results can inform training to optimize communication, especially for neuro-oncology trials and trials comparing markedly different management pathways.
Keywords: Clinical equipoise; Clinical trial; Communication; Neuro-oncology; Qualitative; Radiotherapy.
Link to PubMed record
Author: Frances C Sherratt, Stephen L Brown, Brian J Haylock, Priya Francis, Helen Hickey, Carrol Gamble, Michael D Jenkinson, Bridget Young
Abstract: Introduction: Providing balanced information that emphasizes clinical equipoise (i.e., uncertainty regarding the relative merits of trial interventions) and exploring patient treatment preferences can improve informed consent and trial recruitment. Within a trial comparing adjuvant radiotherapy versus active monitoring following surgical resection for an atypical meningioma (ROAM/EORTC-1308), we explored patterns in communication and reasons why health practitioners may find it challenging to convey equipoise and explore treatment preferences.
Materials and methods: Qualitative study embedded within ROAM/EORTC-1308. Data were collected on 40 patients and 18 practitioners from 13 U.K. sites, including audio recordings of 39 patients' trial consultations, 23 patient interviews, and 18 practitioner interviews. Qualitative analysis drew on argumentation theory.
Results: Practitioners acknowledged the importance of the research question that the trial aimed to answer. However, they often demonstrated a lack of equipoise in consultations, particularly with eligible patients who practitioners believed to be susceptible to side effects (e.g., cognitive impairment) or inconvenienced by radiotherapy. Practitioners elicited but rarely explored patient treatment preferences, especially if a patient expressed an initial preference for active monitoring. Concerns about coercing patients, loss of practitioner agency, and time constraints influenced communication in ways that were loaded against trial participation.
Conclusions: We identified several challenges that practitioners face in conveying equipoise and exploring patient treatment preferences in oncology, and particularly neuro-oncology, trials with distinct management pathways. The findings informed communication about ROAM/EORTC-1308 and will be relevant to enhancing trial communication in future oncology trials. Qualitative studies embedded within trials can address difficulties with communication, thus improving informed consent and recruitment. ROAM/EORTC-1308 RCT: ISRCTN71502099.
Implications for practice: Oncology trials can be challenging to recruit to, especially those that compare treatment versus monitoring. Conveying clinical equipoise and exploring patient treatment preferences can enhance recruitment and patient understanding. This study focused on the challenges that practitioners encounter in trying to use such communication strategies and how practitioners may inadvertently impede patient recruitment and informed decision making. This article provides recommendations to support practitioners in balancing the content and presentation of trial management pathways. The results can inform training to optimize communication, especially for neuro-oncology trials and trials comparing markedly different management pathways.
Keywords: Clinical equipoise; Clinical trial; Communication; Neuro-oncology; Qualitative; Radiotherapy.
Link to PubMed record
CCC publication: Lenalidomide, Dexamethasone and Alemtuzumab or Ofatumumab in High-Risk Chronic Lymphocytic Leukaemia: Final Results of the NCRI CLL210 Trial
Citation: Haematologica. 2020, 105(12), 2868-2871. 2020 Feb 13[Online ahead of print]
Author: Andrew R Pettitt, Richard Jackson, Silvia Cicconi, Fotis Polydoros, Christina Yap, James Dodd, Matthew Bickerstaff, Michael Stackpoole, Umair T Khan, Stacey Carruthers, Melanie Oates, Ke Lin, Sarah E Coupland, Geetha Menon, Nagesh Kalakonda, Helen McCarthy, Adrian Bloor, Anna Schuh, Andrew Duncombe, Claire Dearden, Christopher Fegan, Ben Kennedy, Renata Walewska, Scott Marshall, Christopher P Fox, Peter Hillmen
Abstract: Keywords: Chronic Lymphocytic Leukemia; alemtuzumab; clinical trial; lenalidomide; ofatumumab.
Link to PubMed record
Author: Andrew R Pettitt, Richard Jackson, Silvia Cicconi, Fotis Polydoros, Christina Yap, James Dodd, Matthew Bickerstaff, Michael Stackpoole, Umair T Khan, Stacey Carruthers, Melanie Oates, Ke Lin, Sarah E Coupland, Geetha Menon, Nagesh Kalakonda, Helen McCarthy, Adrian Bloor, Anna Schuh, Andrew Duncombe, Claire Dearden, Christopher Fegan, Ben Kennedy, Renata Walewska, Scott Marshall, Christopher P Fox, Peter Hillmen
Abstract: Keywords: Chronic Lymphocytic Leukemia; alemtuzumab; clinical trial; lenalidomide; ofatumumab.
Link to PubMed record
CCC publication: Corrigendum to Addition of Docetaxel to Hormonal Therapy in Low- And High-Burden Metastatic Hormone Sensitive Prostate Cancer: Long-Term Survival Results From the STAMPEDE Trial: Ann Oncol 2019; 30: 1992-2003
Citation: Annals of Oncology. 2020, 31(3), 442
Author: N W Clarke, A Ali, F C Ingleby, A Hoyle, C L Amos, G Attard, C D Brawley, J Calvert, S Chowdhury, A Cook, W Cross, D P Dearnaley, H Douis, D Gilbert, S Gillessen, R J Jones, R E Langley, A MacNair, Z Malik, M D Mason, D Matheson, R Millman, C C Parker, A W S Ritchie, H Rush, J M Russell, J Brown, S Beesley, A Birtle, L Capaldi, J Gale, S Gibbs, A Lydon, A Nikapota, A Omlin, J M O'Sullivan, O Parikh, A Protheroe, S Rudman, N N Srihari, M Simms, J S Tanguay, S Tolan, J Wagstaff, J Wallace, J Wylie, A Zarkar, M R Sydes, M K B Parmar, N D James, STAMPEDE investigators
Link to PubMed record
Author: N W Clarke, A Ali, F C Ingleby, A Hoyle, C L Amos, G Attard, C D Brawley, J Calvert, S Chowdhury, A Cook, W Cross, D P Dearnaley, H Douis, D Gilbert, S Gillessen, R J Jones, R E Langley, A MacNair, Z Malik, M D Mason, D Matheson, R Millman, C C Parker, A W S Ritchie, H Rush, J M Russell, J Brown, S Beesley, A Birtle, L Capaldi, J Gale, S Gibbs, A Lydon, A Nikapota, A Omlin, J M O'Sullivan, O Parikh, A Protheroe, S Rudman, N N Srihari, M Simms, J S Tanguay, S Tolan, J Wagstaff, J Wallace, J Wylie, A Zarkar, M R Sydes, M K B Parmar, N D James, STAMPEDE investigators
Link to PubMed record
CCC publication: CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations
Citation: European Journal of Cancer. 2020, 127, 160-172
Author: Enriqueta Felip, Andrea Ardizzoni, Tudor Ciuleanu, Manuel Cobo, Konstantin Laktionov, Maria Szilasi, Raffaele Califano, Enric Carcereny, Richard Griffiths, Luis Paz-Ares, Renata Duchnowska, Miriam Alonso Garcia, Dolores Isla, Jacek Jassem, Wiebke Appel, Janusz Milanowski, Jan P Van Meerbeeck, Juergen Wolf, Ang Li, Angelic Acevedo, Sanjay Popat
Abstract: Background: CheckMate 171 (NCT02409368) is an open-label, multicentre, phase 2 trial of nivolumab in previously treated advanced squamous non-small cell lung cancer (NSCLC), conducted as part of a post-approval commitment to the European Medicines Agency (EMA). We report outcomes from this trial.
Methods: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and disease progression during/after ≥1 systemic treatment (≥1 being platinum-based chemotherapy) for advanced or metastatic disease were treated with nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary end-point was incidence of grade 3-4 treatment-related select adverse events (AEs). Other end-points included overall survival (OS) and safety.
Results: Of 811 patients treated, 103 had ECOG PS 2; 278 were aged ≥70 years and 125 were ≥75 years of age. Minimum follow-up was ~18 months. Safety was similar across populations; the most frequent grade 3-4 treatment-related select AEs in all treated patients were diarrhoea (1%), increased alanine aminotransferase (ALT, 1%), pneumonitis (0.7%), colitis (0.6%) and increased aspartate aminotransferase (AST, 0.5%). Median OS was similar in all treated patients and those aged ≥70 and ≥75: 10.0 months, 10.0 months and 11.2 months, respectively. Median OS was 5.2 months in patients with ECOG PS 2.
Conclusion: These results suggest that nivolumab is well tolerated and active in patients with advanced, relapsed squamous NSCLC, including the elderly, with OS outcomes consistent with phase 3 data. In patients with ECOG PS 2, nivolumab had similar tolerability, but outcomes were worse, as expected in this difficult-to-treat, poor prognosis population.
Clinical trial registration: NCT02409368.
Keywords: Comorbidity; Elderly; Health status indicators; Nivolumab; Non-small cell lung cancer.
Link to PubMed record
Author: Enriqueta Felip, Andrea Ardizzoni, Tudor Ciuleanu, Manuel Cobo, Konstantin Laktionov, Maria Szilasi, Raffaele Califano, Enric Carcereny, Richard Griffiths, Luis Paz-Ares, Renata Duchnowska, Miriam Alonso Garcia, Dolores Isla, Jacek Jassem, Wiebke Appel, Janusz Milanowski, Jan P Van Meerbeeck, Juergen Wolf, Ang Li, Angelic Acevedo, Sanjay Popat
Abstract: Background: CheckMate 171 (NCT02409368) is an open-label, multicentre, phase 2 trial of nivolumab in previously treated advanced squamous non-small cell lung cancer (NSCLC), conducted as part of a post-approval commitment to the European Medicines Agency (EMA). We report outcomes from this trial.
Methods: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and disease progression during/after ≥1 systemic treatment (≥1 being platinum-based chemotherapy) for advanced or metastatic disease were treated with nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary end-point was incidence of grade 3-4 treatment-related select adverse events (AEs). Other end-points included overall survival (OS) and safety.
Results: Of 811 patients treated, 103 had ECOG PS 2; 278 were aged ≥70 years and 125 were ≥75 years of age. Minimum follow-up was ~18 months. Safety was similar across populations; the most frequent grade 3-4 treatment-related select AEs in all treated patients were diarrhoea (1%), increased alanine aminotransferase (ALT, 1%), pneumonitis (0.7%), colitis (0.6%) and increased aspartate aminotransferase (AST, 0.5%). Median OS was similar in all treated patients and those aged ≥70 and ≥75: 10.0 months, 10.0 months and 11.2 months, respectively. Median OS was 5.2 months in patients with ECOG PS 2.
Conclusion: These results suggest that nivolumab is well tolerated and active in patients with advanced, relapsed squamous NSCLC, including the elderly, with OS outcomes consistent with phase 3 data. In patients with ECOG PS 2, nivolumab had similar tolerability, but outcomes were worse, as expected in this difficult-to-treat, poor prognosis population.
Clinical trial registration: NCT02409368.
Keywords: Comorbidity; Elderly; Health status indicators; Nivolumab; Non-small cell lung cancer.
Link to PubMed record
CCC publication: A study of childhood cancer survivors' engagement with long-term follow-up care: ‘To attend or not to attend, that is the question’
Citation: European Journal of Oncology Nursing. February 2020
Author: Katherine Knighting, Jennifer A. Kirton, Nicola Thorp, James Hayden, Lynda Appleton, Lucy Bray
Abstract: In the UK, there are over 40,000 childhood cancer survivors (CCS); this figure grows approximately 1,300 annually. Two-thirds are at risk of developing serious disabling or life-threatening conditions due to adverse late effects of the cancer or treatment received in childhood. Life-long, follow-up care for the surveillance and management of late effects is recommended. This study explored CCS’ views and experiences of long-term follow-up (LTFU) care within a cancer centre. Methods Paper questionnaires (n=113) and qualitative interviews (n=13). Results The majority (n=83, 80%) of CCS reported being satisfied with their LTFU care and felt that it was important to attend long-term survivorship follow-up (n=97, 86%). However, some were not well informed about their cancer treatment history, purpose for attending the clinic or the potential for late effects. Barriers associated with LTFU included; provision of information, lack of interpersonal relationships, practical and logistic challenges. Conclusions Barriers identified can be addressed through strategies including provision of verbal and written information and care plans to increase CCS’ knowledge of their cancer history, risk of late effects and the purpose of LTFU care, both at transition and throughout their survivorship journey; patient-centred services that enhance patient choice and flexibility of access to multiple specialities; and use of risk stratified pathways to encourage supported self-management based on cancer type, co-morbidity, and level of professional involvement required. Improving regular provision of information at critical time-points, and exploring a flexible, patient-centred delivery of LFTU care based on risk, could increase attendance and self-management in CCS. KEYWORDS Childhood cancer; adolescent; survivorship; long-term follow-up; late effects; health services
Author: Katherine Knighting, Jennifer A. Kirton, Nicola Thorp, James Hayden, Lynda Appleton, Lucy Bray
Abstract: In the UK, there are over 40,000 childhood cancer survivors (CCS); this figure grows approximately 1,300 annually. Two-thirds are at risk of developing serious disabling or life-threatening conditions due to adverse late effects of the cancer or treatment received in childhood. Life-long, follow-up care for the surveillance and management of late effects is recommended. This study explored CCS’ views and experiences of long-term follow-up (LTFU) care within a cancer centre. Methods Paper questionnaires (n=113) and qualitative interviews (n=13). Results The majority (n=83, 80%) of CCS reported being satisfied with their LTFU care and felt that it was important to attend long-term survivorship follow-up (n=97, 86%). However, some were not well informed about their cancer treatment history, purpose for attending the clinic or the potential for late effects. Barriers associated with LTFU included; provision of information, lack of interpersonal relationships, practical and logistic challenges. Conclusions Barriers identified can be addressed through strategies including provision of verbal and written information and care plans to increase CCS’ knowledge of their cancer history, risk of late effects and the purpose of LTFU care, both at transition and throughout their survivorship journey; patient-centred services that enhance patient choice and flexibility of access to multiple specialities; and use of risk stratified pathways to encourage supported self-management based on cancer type, co-morbidity, and level of professional involvement required. Improving regular provision of information at critical time-points, and exploring a flexible, patient-centred delivery of LFTU care based on risk, could increase attendance and self-management in CCS. KEYWORDS Childhood cancer; adolescent; survivorship; long-term follow-up; late effects; health services
Wednesday 26 February 2020
WUTH publication: Insidious onset of headache, diplopia and Horner's syndrome: a rare case of petrous bone osteomyelitis
Citation: BMJ Case Reports. 2019, 12(9), e231062
Author: Biart S, Panicker J
Abstract: We present an unusual case of skull base osteomyelitis in an 88-year-old woman. She presented with gradual onset unilateral headache and diplopia. On examination, there was evidence of a left-sided Horner's and ipsilateral sixth nerve palsy. In addition to persistent raised inflammatory markers, an MRI neck identified signal change in the petrous bone confirming a diagnosis of skull base osteomyelitis. Skull base osteomyelitis should be considered in presentations of subacute raised inflammatory markers in the context of ipsilateral cranial nerve signs.
© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: cranial nerves; headache (including migraines); infection (neurology)
Link to PubMed record
Author: Biart S, Panicker J
Abstract: We present an unusual case of skull base osteomyelitis in an 88-year-old woman. She presented with gradual onset unilateral headache and diplopia. On examination, there was evidence of a left-sided Horner's and ipsilateral sixth nerve palsy. In addition to persistent raised inflammatory markers, an MRI neck identified signal change in the petrous bone confirming a diagnosis of skull base osteomyelitis. Skull base osteomyelitis should be considered in presentations of subacute raised inflammatory markers in the context of ipsilateral cranial nerve signs.
© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: cranial nerves; headache (including migraines); infection (neurology)
Link to PubMed record
Monday 17 February 2020
WUTH publication: The use of oral antibiotics and mechanical bowel preparation in elective colorectal resection for the reduction of surgical site infection
Citation: Colorectal Disease. 2020 Feb 14. [Epub ahead of print]
Author: Duff SE, Battersby CLF, Davies RJ, Hancock L, Pipe J, Buczacki S, Kinross J, Acheson AG, Walsh CJ
Link to PubMed record
Author: Duff SE, Battersby CLF, Davies RJ, Hancock L, Pipe J, Buczacki S, Kinross J, Acheson AG, Walsh CJ
Link to PubMed record
Wednesday 12 February 2020
WUTH publication: Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis
Citation: Heart failure reviews. 2020 Feb 6. [Epub ahead of print]
Author: Lakhani I, Wong MV, Hung JKF, Gong M, Waleed KB, Xia Y, Lee S, Roever L, Liu T, Tse G, Leung KSK, Li KHC
Abstract: Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00-1.16; P = 0.04; I2 = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61-3.96; P < 0.0001; I2 = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04-1.47; P = 0.01; I2 = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53-2.06; P < 0.00001; I2 = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02-1.06; P = 0.003; I2 = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.
KEYWORDS: C-reactive protein; Diastolic heart failure; HFpEF; Meta-analysis
Link to PubMed record
Author: Lakhani I, Wong MV, Hung JKF, Gong M, Waleed KB, Xia Y, Lee S, Roever L, Liu T, Tse G, Leung KSK, Li KHC
Abstract: Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00-1.16; P = 0.04; I2 = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61-3.96; P < 0.0001; I2 = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04-1.47; P = 0.01; I2 = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53-2.06; P < 0.00001; I2 = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02-1.06; P = 0.003; I2 = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.
KEYWORDS: C-reactive protein; Diastolic heart failure; HFpEF; Meta-analysis
Link to PubMed record
Thursday 6 February 2020
WUTH publication: The Chief Registrar role in the UK: leadership capacity and development of hybrid leaders.
Citation: Journal of Health Organization and Management. 2020 Jan 23, ahead-of-print
Author: Snelling I, Exworthy M, Ghezelayagh S
Abstract: PURPOSE: The purpose of the study is to evaluate the first cohort of the Royal College of Physicians' (RCP) Chief Registrar programme in 2016/7. Chief Registrars provide medical leadership capacity through leadership development posts.
DESIGN/METHODOLOGY/APPROACH: The study adopted a mixed methods design, comprising a monthly survey of the 21 Chief Registrars in the first cohort, interviews with Chief Registrars, and six cases studies where Chief Registrars and colleagues were interviewed.
FINDINGS: Chief Registrars enjoyed high levels of practical, professional, and leadership support from their employing organisations, the RCP, and the Faculty of Medical Leadership and Management. They had high degrees of autonomy in their roles. As a result, roles were enacted in different ways, making direct comparative evaluation problematic. In particular, we identified variation on two dimensions: first, the focus on medical leadership generally, or quality improvement more specifically, and second, the focus on personal development or organisational leadership capacity.
RESEARCH LIMITATIONS/IMPLICATIONS: The data are limited and drawn from the first cohort's experience. The Chief Registrar scheme, unlike many other leadership fellowships, maintains a high level of clinical practice (with a minimum 40 per cent leadership work). This suggests a clearer preparation for future hybrid leadership roles.
PRACTICAL IMPLICATIONS: This paper may offer some support and guidance for Chief Registrars and those who work with and support them.
ORIGINALITY/VALUE: This study adds to the literature on leadership development for doctors in hybrid roles, and highlights the distinctiveness of the scheme compared with other schemes.
© Emerald Publishing Limited.
KEYWORDS: Doctors; Hospitals; Hybrid; Leadership; Learning; NHS
Link to PubMed record
Author: Snelling I, Exworthy M, Ghezelayagh S
Abstract: PURPOSE: The purpose of the study is to evaluate the first cohort of the Royal College of Physicians' (RCP) Chief Registrar programme in 2016/7. Chief Registrars provide medical leadership capacity through leadership development posts.
DESIGN/METHODOLOGY/APPROACH: The study adopted a mixed methods design, comprising a monthly survey of the 21 Chief Registrars in the first cohort, interviews with Chief Registrars, and six cases studies where Chief Registrars and colleagues were interviewed.
FINDINGS: Chief Registrars enjoyed high levels of practical, professional, and leadership support from their employing organisations, the RCP, and the Faculty of Medical Leadership and Management. They had high degrees of autonomy in their roles. As a result, roles were enacted in different ways, making direct comparative evaluation problematic. In particular, we identified variation on two dimensions: first, the focus on medical leadership generally, or quality improvement more specifically, and second, the focus on personal development or organisational leadership capacity.
RESEARCH LIMITATIONS/IMPLICATIONS: The data are limited and drawn from the first cohort's experience. The Chief Registrar scheme, unlike many other leadership fellowships, maintains a high level of clinical practice (with a minimum 40 per cent leadership work). This suggests a clearer preparation for future hybrid leadership roles.
PRACTICAL IMPLICATIONS: This paper may offer some support and guidance for Chief Registrars and those who work with and support them.
ORIGINALITY/VALUE: This study adds to the literature on leadership development for doctors in hybrid roles, and highlights the distinctiveness of the scheme compared with other schemes.
© Emerald Publishing Limited.
KEYWORDS: Doctors; Hospitals; Hybrid; Leadership; Learning; NHS
Link to PubMed record
Time to Change 6th February 2020
The more we talk about mental
health, the better life is for all of us.
That’s why our library is
choosing to talk this #timetotalk
Day on 6 Feb
@timetochange
Visit our colouring in station for some mindful colouring, see our range of helpful books and pick up a word search or a Sussed game card and spark a conversation!
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