• Anaesthesia for phaeochromocytoma: does a single high blood pressure reading in the anaesthetic room matter?

  Jackson, T.; Adam, Safwaan; Gulamhusein, Aziz; Beards, Susan; The Christie NHS Foundation Trust, Manchester, United Kingdom (2024)

  BackgroundRacial and ethnic inequities exist in cancer clinical trial participation. Low recruitment across ethnically diverse communities contributes to health inequalities further disproportionately affecting these groups. Understanding barriers and enablers to clinical trial participation for ethnic minorities is key to developing strategies to address this problem.ObjectiveTo explore, evaluate, and synthesize qualitative research surrounding patients' lived experiences and perceptions of participating in cancer clinical trials from ethnically diverse groups.MethodsNoblit and Hare's 7-stage metaethnography was used. Seven databases were searched. Inclusion criteria were as follows: qualitative studies published in English from January 1, 2012, to January 31, 2022; patients from any ethnic minority 18 years and older with a cancer diagnosis; and cancer patients' carers and healthcare professionals (HCPs)/healthcare leaders involved in the delivery of cancer clinical trials.ResultsThe majority of included articles were conducted in the United States. Interpretive qualitative synthesis resulted in 7 categories including patient perceptions and beliefs and HCP perception of trial burden and social determinants of health. Four lines of argument were established.ConclusionsThe findings capture the experience and perceptions of ethnic minority patients, their carers, HCPs, and healthcare leaders in this area of research. Incongruities exist between patient-reported barriers and those perceived by HCPs. Published empirical research outside the United States is limited.Implications for PracticeWhen developing strategies to increase clinical trial participation, research literacy, cultural safety, and unconscious biases within healthcare need to be addressed. Further research to examine intersectionality and the role of faith in decision-making among ethnic groups is warranted.
• Rapid early progression in glioblastoma: a comprehensive review of clinical, imaging and histopathological features

  Waqar, M.; Roncaroli, F.; O'Leary, C.; Forte, G.; Wright, J.; Parikh, Shefali; Sudell, Lindsay; Coope, D.; Djoukhadar, I.; Borst, Gerben; et al. (2024)

  Background and Purpose: Radiotherapy for paediatric posterior fossa tumours may cause complications in the brainstem and upper spinal cord due to high doses. With proton therapy (PT) this risk may increase due to higher relative biological effectiveness (RBE) from elevated linear energy transfer (LET). This study assesses variations in LET in the brainstem and spinal cord in proton treatment plans from European centres. Materials and Methods: Ten European PT centres using spot-scanning PT planned two paediatric posterior fossa cases: One overlapping partly with the brainstem and upper spinal cord, prescribed 54 Gy(RBE), and the second wrapping around these organs, prescribed 59.4 Gy(RBE). Dose-averaged LET distributions were assessed in volumes of the brainstem and spinal cord irradiated to over 50 Gy(RBE = 1.1). The maximum hinge angle effect on near-maximum RBE-weighted doses using the Unkelbach RBE model was also investigated. Results: In the first case, the mean LET in brainstem volumes receiving more than 50 Gy(RBE = 1.1) ranged from 2.8 keV/mu m to 3.6 keV/mu m across centres (median: 3.3 keV/mu m). In the second case, treatment plans showed a narrower range of mean LET in the brainstem, from 2.5 keV/mu m to 2.8 keV/mu m (median: 2.7 keV/mu m). There was no statistically significant impact of the maximum hinge angle. Conclusions: LET distributions vary across centres due to different techniques but are also influenced significantly by factors like shape and position of the target volume.
• 

  Neurofibromatosis type 2 presenting as symptomatic gallbladder hydrops: a rare case report and literature review

  Hafez, B.; Alwan, J. S.; El Hout, Walid; Koussa, K.; El Annan, T.; Noun, D.; Zaghal, A.; The Christie NHS Foundation Trust, Manchester, United Kingdom (2024)
• Health-related quality of life and cognitive functioning in survivors of oligodendroglioma: an international cross-sectional investigation

  Boele, F.; Frances, S.; Darlix, A.; Ducray, F.; Tabouret, E.; Burger, M.; Ryden, I.; Malmstrom, A.; Vauleon, E.; Kazda, T.; et al. (2024)
• Metastatic bifocal germinoma: a case highlighting dramatic early radiological response to steroids and rebound following discontinuation, and the utility of circulating mir-371a-3p quantification and vinblastine monotherapy prior to definitive craniospinal irradiation

  Scarpini, C.; Ward, D.; Phyu, P.; Jalloh, I.; Thorp, Nicky; Fisher, B.; Hendriks, E.; Salisbury, L.; Nicholson, J.; Ajithkumar, T.; et al. (2024)

  Background: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using B & ouml;hm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. Methods: A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. Results: Of 586 eligible patients, 393 underwent DPS and had a CRS reported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95-4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14-0.91; P = 0.0291). Conclusions: Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.
• 

  Variations in linear energy transfer distributions within a European proton therapy planning comparison of paediatric posterior fossa tumours

  Laegdsmand, P.; Matysiak, W.; Muren, L. P.; Lassen-Ramshad, Y.; Maduro, J. H.; Vestergaard, A.; Righetto, R.; Pettersson, E.; Kristensen, I.; Dutheil, P.; et al. (2024)
• 

  The barriers and enablers to participation in oncology clinical trials for ethnically diverse communities

  Turner, Lorraine; Taylor, Sally; Ward, Ashleigh; Thistlethwaite, Fiona; Yorke, Janelle; Christie NHS Foundation Trust, Deptartment Research & Innovation, Patterson Building, Wilmslow Road, Manchester M20 4BX, Christie NHS Foundation Trust, Christie Patient Centred Research, Manchester, England Department of Medical Oncology, The Christie NHS Foundation Trust and Division of Cancer Sciences, School of Medical Sciences, The University of Manchester, Manchester, United Kingdom (2024)

  Introduction KRAS(G12C) and KRAS(G12D) inhibitors represent a major translational breakthrough for non-small cell lung cancer (NSCLC) and cancer in general by directly targeting its most mutated oncoprotein. However, resistance to these small molecules has highlighted the need for rational combination partners necessitating a critical understanding of signaling downstream of KRAS mutant isoforms. Methods We contrasted tumor development between Kras(G12C) and Kras(G12D) genetically engineered mouse models (GEMMs). To corroborate findings and determine mutant subtype-specific dependencies, isogenic models of Kras(G12C) and Kras(G12D) initiation and adaptation were profiled by RNA sequencing. We also employed cell line models of established KRAS mutant NSCLC and determined therapeutic vulnerabilities through pharmacological inhibition. We analysed differences in survival outcomes for patients affected by advanced KRAS(G12C) or KRAS(G12D)-mutant NSCLC. Results KRAS(G12D) exhibited higher potency in vivo, manifesting as more rapid lung tumor formation and reduced survival of KRAS(G12D) GEMMs compared to KRAS(G12C). This increased potency, recapitulated in an isogenic initiation model, was associated with enhanced PI3K-AKT-mTOR signaling. However, KRAS(G12C) oncogenicity and downstream pathway activation were comparable with KRAS(G12D) at later stages of tumorigenesis in vitro and in vivo, consistent with similar clinical outcomes in patients. Despite this, established KRAS(G12D) NSCLC models depended more on the PI3K-AKT-mTOR pathway, while KRAS(G12C) models on the MAPK pathway. Specifically, KRAS(G12D) inhibition was enhanced by AKT inhibition in vitro and in vivo. Conclusions Our data highlight a unique combination treatment vulnerability and suggest that patient selection strategies for combination approaches using direct KRAS inhibitors should be i) contextualised to individual RAS mutants, and ii) tailored to their downstream signaling.<br />
• In current smokers with COPD, LABA plus LAMA is superior to LABA plus ICS, regardless of blood eosinophils. Data from the FLAME trial

  Mathioudakis, A.; Higham, A.; Bate, S.; Chatzimavridou-Grigoriadou, Victoria; Sivapalan, P.; Jensen, J. U.; Felton, T.; Vestbo, J.; Singh, D.; Christie Hospital NHS Foundation Trust, Manchester, United Kingdom (2024)
• 

  The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRAS<SUP>G12D</SUP>-driven non-small cell lung cancer

  McDaid, William J; Wilson, Leah; Adderley, Helen; Martinez-Lopez, A.; Baker, Martin J; Searle, Joshua; Ginn, Lucy; Budden, Timothy; Aldea, M.; Marinello, A.; et al. (2024)

  Recommendations are based on available scientific data and the authors’ collective expert opinion.
• Impact of dose in oligometastatic liver SABR: a UK single-centre experience

  Oong, Zhu C; Yeo, Geok G; Kumar, Shaarven; Brocklehurst, Andrew; Hall, Rachael; Turpin, Zoe; Whitehurst, Philip; Forshaw, Laura; Triffitt, Clare; Chander, Amarjot; et al. (2024)
• Evaluation of DIR strategies for OAR dose accumulation in MR-guided pancreas SABR

  Daly, Mairead; Osorio, Eliana V; Choudhury, Ananya; McWilliam, Alan; Radhakrishna, Ganesh; Eccles, Cynthia L; Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom; Department of Clinical Oncology, Radiotherapy Department, The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom (2024)
• SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in <i>KRAS</i> G12C-mutant advanced NSCLC

  Nishio, M.; Negrao, M. V.; Arbour, K. C.; Burns, T. F.; Cappuzzo, F.; Dingemans, A. M. C.; Girard, N.; Gronberg, B. H.; Hochmair, M.; Leal, T.; et al. (2024)

  Neuroendocrine neoplasms of different origins, parathyroid carcinoma and intrathyroid thymic neoplasms are included.
• Hypofractionated radiotherapy for the definitive management of locally advanced non-small cell lung cancer: a systematic review

  Said, B. I.; Bang, A.; Schuffeneger, P.; Louie, A.; Badiyan, S.; Bezjak, A.; Chua, K.; Faivre-Finn, Corinne; Geng, Y. M.; Kong, F. M.; et al. (2024)

  The guideline covers clinical imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.
• MITOPE: Phase 2 evaluation of RSO-021, a novel mitochondrial PRX3 inhibitor, as a monotherapy and in combination with paclitaxel in patients with malignant pleural effusion due to mesothelioma or other advanced solid tumors

  Naumov, G.; Dulloo, S.; Fennell, D.; Lord, S.; Thistlethwaite, Fiona; Maskell, N.; Popat, S.; Blyth, K.; Szlosarek, P.; Aujayeb, A.; et al. (2024)
• Eftilagimod alpha (soluble LAG-3) and pembrolizumab in first-line recurrent or metastatic head and neck squamous cell carcinoma: primary results from cohort B (CPS less-than 1) of the TACTI-003 study

  Metcalf, Robert; Laban, S.; Kristensen, C. A.; Ciuleanu, T. E.; Braña, I.; Rivas, A. S.; Dieter, S. M.; Bols, A.; Forster, M. D.; Covela, M. R.; et al. (2024)
• NEXUS-01, a phase 1 study of LY4052031, an antibody-drug conjugate targeting nectin-4 in participants with advanced or metastatic urothelial carcinoma or other solid tumors (trial in progress)

  Baldini, C.; Patnaik, A.; Lakhani, N.; Call, J.; Galsky, M.; Garmezy, B.; Wei, A.; Carter, Louise; Powles, T.; Siefker-Radtke, A.; et al. (2024)
• Glioblastoma in older adults, a need for bolder treatment in selected patients?

  Robinson, S. D.; Hooper, C.; Maccoll, J.; Ryan, K.; Ajah, H.; Williams, S. T.; Aktar, N. J.; Lathangue, H.; Carter, T.; Conkey, D.; et al. (2024)
• The approach trial (analysis of proton vs photon radiotherapy in oligodendroglioma and assessment of cognitive health): open and recruiting in the UK

  Murray, L. J.; Boele, F.; Brown, S.; Powell, J.; Borland, M.; Bruce, A.; Bulbeck, H.; Burnet, Neil; Chang, Y.; Colaco, Rovel; et al. (2024)
• A UK-wide survey of the holistic needs of self-identified clinically vulnerable patients with a new diagnosis of glioma

  Lorimer, C.; Jameson, M.; Thomson, A.; Ali, U.; Bulbeck, H.; Byrne, A.; Cooper, S.; Meldrum, S.; Melhuish, S.; Mills, S.; et al. (2024)
• Glioblastoma in 2021, developing a large individual patient database to investigate outcomes and treatment patterns

  Robinson, S. D.; Clark, M.; Rathbone, M.; Black, L.; Kovacs, B.; Augustine, P.; Hatton, R.; Lathangue, H.; Wontumi, S.; Conkey, D.; et al. (2024)

View more