The Leeds Teaching Hospitals Repository contains research, organisational learning and information generated by LTH staff and colleagues and departments.

Recent Submissions

FOxTROT: Predictive effects of ERBB2 and ERBB3 on neoadjuvant panitumumab benefit in RAS/BRAF wild-type (-wt) locally advanced colon cancer (LACC).
(2026-06-04) Appleyard, J.W.; Seligmann, J.F.; Morton, D.; Elliott, F.; Handley, K.; Glimelius, B.; Hemmings, G.; Bottomley, D.; Quirke, P.; Magill, L.; West, N.; Beggs, A.D.; Williams, C.; Appleyard, Jordan; Seligmann, Jenny; Quirke, Philip; West, Nick
17Background: The FOxTROT trial reported advantages of neoadjuvant chemotherapy in LACC. An embedded phase II trial tested neoadjuvant FOLFOX+panitumumab vs FOLFOX and reported a trend towards a TTR benefit and a significant DFS and OS benefit from panitumumab (pan) in RAS/BRAF-wt patients (pts). ERBB2 and ERBB3 overexpression have putative negative and positive predictive effects on pan efficacy, respectively. Here we examined whether ERBB2/3 could improve patient selection for neoadjuvant pan. The additional impact of AREG/EREG expression (EGFR ligands) on pan efficacy was tested. Method(s): In FOxTROT, 279 pts with cT3-4 N0-2 M0, KRAS-wt LACC were randomized 1:1 to neoadjuvant FOLFOX+/-pan (6 weeks). All pts received FOLFOX post-op. 169 (61%) were confirmed RAS/BRAF-wt by NGS. ERBB2/3 and AREG/EREG were tested by RNAseq. Endpoints in this exploratory analysis were TTR, DFS, CCSS and OS. Result(s): 157 (93%) pts had available ERBB2/3 data. Median follow-up was 49 months. There were no associations between ERBB2/3 and stage, primary tumor location or MMR status. ERBB2 and ERBB3 were dichotomized using internally derived cut-points at the 50th and 40th percentiles respectively. Trends were consistent across all endpoints but strongest for DFS and OS, presented here. ERBB2 expression had no association with pan efficacy: trends towards benefit from FOLFOX+pan vs FOLFOX were similar in ERBB2-high (DFS: HR 0.45 [95% CI 0.17-1.19], P= 0.11; OS: 0.40 [0.12-1.38], P= 0.15) and -low pts (DFS: 0.60 [0.23-1.59], P= 0.30; OS: 0.24 [0.05-1.18], P= 0.08). ERBB3 enabled improved patient selection for neoadjuvant pan: ERBB3-high pts had significant benefit from FOLFOX+pan vs FOLFOX (DFS: 0.37 [0.14-0.97], P=0.04; OS: 0.16 [0.04-0.75], P=0.02), whereas ERBB3-low pts did not (DFS: 0.80 [0.29-2.22], P=0.67; OS: 0.71 [0.18-2.84], P=0.63). Tests for interaction did not reach significance in this subgroup analysis (DFS: Pinteraction=0.28; OS: Pinteraction=0.14). We have previously reported the ability of AREG/EREG to predict pan benefit in this dataset. ERBB3 strengthened the predictive effect of AREG/EREG: AREG, EREG and/or ERBB3-high pts had significant benefit from FOLFOX+pan vs FOLFOX (DFS: 0.38 [0.17-0.82], P=0.01; OS: 0.22 [0.07-0.67], P=0.008), while there was a trend towards disbenefit from pan in AREG, EREG and ERBB3-low pts (DFS: 2.58 [0.50-13.31], P=0.26; OS: 3.05 [0.32-29.35], P=0.33). Biomarker-treatment interactions were significant (DFS: Pinteraction=0.03; OS: Pinteraction=0.045). AREG/EREG and ERBB3 were not correlated, suggesting differing underlying biology. Conclusion(s): High ERBB3 expression predicted benefit from neoadjuvant FOLFOX+pan. ERBB3 augmented the known predictive effect of the EGFR ligands, AREG/EREG. Validation in a biomarker-enriched trial is warranted. There was no association between ERBB2 expression and pan efficacy. Clinical trial information: NCT00647530.
The Risks of Non-Medical Professionals Holding Medical Consultant Responsibility for Hospital Inpatients.
(2026-06-04) Sivan, M.; Ajina, S.; Harriss, J.; Sivan, Manoj
Participant lived experiences of high-intensity interval training in UK cardiac rehabilitation (HIIT or MISS UK): A qualitative study.
(2026-06-18) Williams, C.; Neil, R.; Powell, R.; Begg, B.; Birkett, S.; Nichols, S.; Ennis, S.; Banerjee, P.; Ingle, L.; Shave, R.; McGregor, G.; Ingle, Lee
Background Exercise programmes are an important component of comprehensive cardiac rehabilitation (CR). High Intensity Interval Training (HIIT) has been proposed as an alternative to conventional moderate intensity steady state (MISS) exercise. In the 'HIIT or MISS UK' trial, low-volume HIIT was safe, and clinically and cost effective. However, there is a lack of insight into the lived experiences of those who engage in non-conventional approaches to CR exercise training. The aim of this research was to explore the benefits and challenges associated with HIIT and MISS in CR. Materials and methods A qualitative descriptive methodology was adopted to document participant lived experiences. Participants were purposefully recruited from two 'HIIT or MISS UK' trial CR centres. After consent, participants took part in semi-structured interviews conducted via Voice over Internet Protocol (VoIP) technologies (e.g., Microsoft Teams (MT), Skype or Zoom). A critical realist approach to inductive thematic analysis was used to analyse the data. Findings 19 people took part (8 MISS and 11 HIIT; male 18 [95%]; age 59.6 years [SD 10.4]). Analysis revealed a range of perceived psychosocial (e.g., enjoyment, confidence, purpose) and physiological (e.g., weight loss, increased fitness) benefits that were present across both groups (i.e., HIIT and MISS). Participants in both groups identified challenges, for example, a need for exercise to continue beyond what was offered in the trial. There were notable differences across the groups, namely HIIT participants enjoyed feeling challenged, yet grappled with feelings of monotony, whilst MISS participants experienced increased social interaction. Conclusion HIIT in CR offered a range of perceived psychosocial and physiological benefits. Integrating more opportunities for social interaction into the HIIT program could enhance participant experience. Practitioners could investigate the feasibility of support for patients after CR has finished.
Modern Hodgkin lymphoma treatments to reduce second cancer risks: Influence of risk-adapted screening.
(2026-06-18) Macklin-Doherty, A.; Cunningham, D.; Chau, I.; Bates, A.T.; Bower, M.; Brunt, A.M.; Follows, G.; Fox, C.; Frew, J.A.; Gribben, J.G.; Hoskin, P.; Irwin, C.; Lowry, L.; Radford, J.; Syndikus, I.; Thomas, E.; Zarkar, A.; Jones, M.; Berrington de Gonzalez, A.; Swerdlow, A.; Thomas, Emma
7053 Background: Second primary malignancies (SPMs) are the leading cause of long-term treatment-related mortality in Hodgkin Lymphoma (HL). Although substantial improvements have been made to treatments over recent decades, few studies have demonstrated reduced SPM risk, particularly following modern treatments, and how risks should inform screening. Method(s): We assembled a national cohort of 7, 428 women treated for HL aged <36 across England & Wales 1954-2010, with 99% complete follow-up until 2018. We analyzed SPM incidence from national cancer registry linkage. Treatment data were collated from >250 treatment centers. Standardized incidence ratios (SIRs) and Absolute Excess Risks (AERs) for SPMs were calculated, and multivariable analyses (Hazard Ratios, HR) were undertaken to assess the impact of changes in treatment and assess changing incidence trends over time. Result(s): Twelve hundred women (16%) developed 1, 467 SPMs with mean follow-up of 22 years (range 0-62 years). Overall SIR to develop any SPM was 3.3 (95% CI 3.1-3.5), with breast cancer contributing the greatest excess risk (AER 30.8 95% CI 27.7-34.1). Radiotherapy use halved from 1954-1980 to 2000-2010 (98% to 47%) and mean dose dropped from 48Gy to 33Gy. Conversely chemotherapy use doubled from 55% to 97%, with anthracyclines used in 94% and classic alkylators in 31% of treatments in the most recent period compared with 6% and 48% respectively pre-1980. Radiotherapy conferred the greatest treatment-specific risk factor for SPMs, (SIR 3.5 95% 3.3-3.7), with a strong dose-response relationship trend (HR 1.01/Gy p<0.001), and highest relative risks seen in those treated with radiotherapy aged <15years (SIR 7.4 (95% CI 5.7-9.1). There was a 25% reduction in SPM risk from the earliest treatment period (<1990) to most recent (2000-2010) and 34% reduction in solid SPM risk (Table). The decrease in risk for SPMs became smaller and non-significant after adjusting for reduced radiotherapy use and dose (HR 0.89, ptrend 0.11). There was no attenuation after adjustment for chemotherapy. Despite declining risks, risks remained significantly elevated beyond 40 years after treatment. Conclusion(s): Modern HL treatments are associated with a substantial reduction in SPM risks, which appears to be largely attributable to decreased radiotherapy use and dose. However large persistent excess risks, particularly for breast and lung cancers, underscore the need for targeted screening in high-risk survivors treated in more recent eras. [Table Presented]
Early outcomes of the PLATO ACT5 randomised trial: Personalizing anal cancer radiotherapy dose.
(2026-06-04) Hawkins, M.A.; Gilbert, A.; Adams, R.; Berkman, L.; Copeland, J.; Gilbert, D.C.; Harrison, M.; Glynne-Jones, R.; Goh, V.; Gaul, C.; Renehan, A.; Muirhead, R.; Norris, M.; Rao, S.; Richman, S.D.; Ruddock, S.; Webster, J.; Brown, S.R.; Sebag-Montefiore, D.; Gilbert, Alexandra; Sebag-Montefiore, David
1Background: The optimal dose of radiotherapy (RT) in advanced anal squamous cell carcinoma (ASCC) is uncertain. Cure rates need to improve, but higher dose RT may result in significant morbidity. Method(s): PLATO ACT5 is a seamless pilot/phII/phIII prospective, multi-centre, 3-arm RCT investigating dose-escalated intensity modulated radiotherapy (de-IMRT) with chemotherapy in patients (pts) with T3/4N0 and TanyN+ ASCC. Primary outcome is 3-year locoregional failure (LRF). We report planned 6-month endpoints: acute toxicity (CTCAEv5), treatment compliance, radiological and clinical complete response rates (cCR) and patient reported outcomes (PROs; EORTC-QLQ C30 and ANL27). Pts were randomised 1:1:1 in 28 fractions to standard dose IMRT (sd-IMRT; 53.2Gy), de1-IMRT (58.8Gy) or de2-IMRT (61.6 Gy) with concurrent mitomycin 12mg/m2 day (D) 1 & capecitabine (CAP) 825mg/m2 BD on RT days or 5FU 1000mg/m2 D1-4 & D29-32. 459 pts including 10% drop out were required to compare each experimental arm against sd-IMRT for 3-year LRF-free survival. Result(s): 463 pts were recruited from 34 UK sites (sd-IMRT n=154; de1-IMRT n=155; de2-IMRT n=154) between Feb 2017 - Aug 2023. 82% received CAP RT and 18% received 5FU RT. Pts characteristics were balanced across 3 arms: Overall median age was 62 years (range 29-81); 73% ECOG 0; 73% female; 30% T4; 45%/18%/21% N1/2/3 respectively; 21% required pre-RT stoma; 1.5% HIV positive. >=G3 acute toxicity was reported in 57% (sd-IMRT; n=90), 56% (de1-IMRT n=86) and 58, and at 6 mo 19 patients (5/5/9 respectively) reported >=G3. 460 completed per protocol RT. RT interruptions: sd-IMRT n=40 (26.1%), de1-IMRT n=33 (21.4%), de2-IMRT n=39 (25.7%) of which 25% were due toxicity. 70 (36%) had CAP reduction/omission (sd-IMRT n=13/50; de1-IMRT n=12/47 de2-IMRT n=39/9 respectively); the majority were due to toxicity (46-58%). 6 mo cCR: (MRI TRG 1&2 with no visible T2 weighted pelvic lymph nodes) are: sd-IMRT =100 (65%); de1-IMRT =103 (67%); de2-IMRT= 101 (66%). For PROs, there was a similar large deterioration in pain, fatigue, bowel function, quality of life, physical, role and social function at the end of CRT across all arms which resolved to baseline by 6 months in all arms. Conclusion(s): Dose escalation has similar toxicity, but does not improve early outcomes. Further stage stratification and novel biology approaches for personalisation are needed. Clinical trial information: ISRCTN88455282.

Communities in LTHT Repository

Select a community to browse its collections.

Now showing 1 - 2 of 2