Clinical Service Line 11 - Cancer & End of Life, Clinical Oncology, Chemo
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Item Magnetization transfer imaging of ovarian cancer:Initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy(2022) Deen, S.S; Mclean, M.A; Gill, A.B; Crawford, R.A.F; Latimer, J; Baldwin, P; Earl, H.M; Parkinson, C.A; Smith, S; Hodgkin, C; Jiminez-Linan, M; Brodie, C.R; Patterson, I; Addley, H.C; Freeman, S.J; Moyle, P.M; Graves, M.J; Sala, E; Brenton, J.D; Gallagher, F.AObjectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment. © 2022 The Authors. Published by the British Institute of Radiology. PubMed Disclaimer Conflict of interest statement Competing interests: The authors have no conflicts of interest to declare.Item Outcomes using induction chemotherapy followed by long-course chemoradiotherapy as total neoadjuvant therapy for locally advanced rectal cancer(2022) Gatfield, E; Hughes, J; Kumaran, M; Doherty, G; Daly, M; Stancliffe, M; Jephcott, C; Wilson, C; Smith, S; Jadon, RTotal neoadjuvant therapy (TNT) for rectal cancer is being adopted worldwide as a promising means to improve outcomes for patients with locally advanced rectal cancer. However, the optimal TNT regime is not well established, with differing regimes and sequencing of radiotherapy and chemotherapy suggested in clinical trials and published series. In 2008 we adopted a TNT approach based on the EXPERT trial (Chua 2006) as a region of six oncology centres. The regime consisted of induction chemotherapy (capecitabine-oxaliplatin) followed by long-course chemoradiotherapy, total mesorectal excision, with adjuvant chemotherapy considered post-operatively. We report here our experience over 12 years with comparison to contemporary published literature. Methods Retrospective data was collected for all patients with locally advanced rectal adenocarcinoma (some of whom also had operable oligometastatic disease) treated with the EXPERT regime between 2008 and 2020. Local control and survival rates were calculated using the Kaplan-Meier method. Results 215 patients treated with the EXPERT regime are included. Median age was 60.6 years (range 27.4-79.0), and 66% were male. 69% had stage 3 disease and 20% stage 4 disease at diagnosis. 91% of patients received neoadjuvant capecitabine-oxaliplatin chemotherapy, receiving a median of 3.87 out of 4 planned cycles. 27.4% required dose reductions. Long-course radiotherapy was given with capecitabine (92.1%), 5-FU (4.2%) or raltitrexed (1.9%) and no chemotherapy (1.9%). The majority of patients received a total dose of 50Gy (range 9-54Gy). Radiological response was seen in 87.4% of patients (9.8% complete, 77.6% partial). 43.1% of patients were radiologically down-staged. 173 patients had radical surgery, with 90.2% achieving an R0 resection and 15.6% had a pathological complete response (pCR). At baseline, 76.6% had circumferential resection margin (CRM) involvement which decreased to 17.2% at surgery. 3-year progression free survival (PFS) was 62% (CI 54-69) and 5-year PFS was 56% (CI 48-65). 43.0% of patients recurred, of whom 15.7% had metastatectomies and remained disease-free at the time of analysis. 3-year recurrence free survival (RFS) out of the patients who had a complete resection at surgery was 69% (CI 62-77) and 5-year RFS was 67% (CI 59-75). Median overall survival (OS) was 118 months (CI 97-not reached), 3-year OS was 80% (CI 74-86) and 5-year OS was 69% (CI 62-77). Excluding patients with metastatic disease at presentation, median OS was 133 months (CI 118-not reached), 3-year OS was 85% (CI 79-91) and 5-year OS was 79% (CI 71-86). Conclusions Our results present the real-world outcomes of patients with rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy, demonstrating high rates of R0 resection even in CRM involved patients. The 3-year OS rates (excluding stage 4 patients) are comparable to results from both the EXPERT (83%) and RAPIDO (89%) trials. Compared to two recent meta-analyses of TNT (Kasi 2020 and Petrelli 2020), our cohort had a lower pCR rate, 15.6% compared with 29.9% and 22.4% respectively. This large series of EXPERT data, with a long median follow-up compared to other reported studies will be a useful comparator in the pursuit for improving definition of the optimal TNT regime. Legal entity responsible for the studyItem Immune-related thyroid dysfunction in lung cancer patients treated with PD-1/PD-L1 checkpoint inhibitors.(2023) Bulusu, V.; Jessop, S.; Chapman, T.; Aslam, S.; Jeffs, Y.; Punnen, G; Geetha, A.; Hutka, M.Introduction: Thyroid dysfunction as an immune related adverse event (IrAE) is the most commonly occurring endocrine IrAE. We present our experience with Thyroid IrAE in lung cancer patients treated from 2017-2022 at the Primrose Oncology Unit. Method(s): Clinical records of lung cancer patients treated with PD-1PD-L1 inhibitors in the Primrose Oncology Unit were reviewed. Demographics, histology, serial thyroid test results, type of PD-1PD-L1 inhibitor and endocrine interventions were collected. Time kinetics of thyroid dysfunction were plotted against the total number of PD-1/PD-L1 cycles received. Result(s): Number of patients treated with PD-1/PD-L1 inhibitors 140. Number of patients who had thyroid dysfunction N=62 (44%). Male: Female 32:30. Median age 66 years (range 35-80). Histology: 37 Adenocarcinoma, 20 squamous cell carcinoma, 2 small cell lung cancer and 3 pleomorphic/poorly differentiated. PD-1/PD-L1 drugs administered: Durvalumab 1, Nivolumab 1, Atezolizumab 8 and Pembrolizumab 52. Biochemical/subclinical hyperthyroidism was observed in 25/62 (40%), hypothyroidism 31/62 (50%) and hyperthyroidism followed by hypothyroidism in 6/62 (10%). No specific thyroid dysfunction related symptoms/signs were noted. 10 patients were treated with levothyroxine. The time kinetics of thyroid dysfunction are shown in Fig. 1. Thyroid dysfunction most commonly occurred in the first 3 cycles (56%) and 85% of the events occurred in the first 12 cycles. 5% of the patients experienced thyroid dysfunction after completion of PD-1/PD-L1 treatment programme. No deaths were attributable to thyroid dysfunction. [Figure presented] Conclusion(s): In our cohort treated with PD-1/PD-L1 inhibitors, thyroid dysfunction was the most common IrAE. Thyroid IrAE is characteristically early with majority of the events occurring within the first 12 cycles. There was no gender predilection. All thyroid IrAE were subclinical and only 10% had thyroxine supplementation. The cohort is too small for any exploratory hypotheses. Disclosure: No significant relationships.Item Predicting COVID‐19 infection risk in lymphoma by immune monitoring.(2023-06) Wijaya, R.; Campbell, N.; Johnson, M.; Stuart, B.; Kelly, A.; Tipler, N.; Coleman, A.; Turaj, A.; Menne, T.; Ahearne, M.; Willimott, V.; Al‐Naeeb, A. Bowzyk; Fox, C.P.; Collins, G.P.; O'Callaghan, A.; Davies, A.J.; Goldblatt, D.; Lim, S.H.ntroduction: Patients with B‐cell lymphoma have poorer antibody responses to COVID‐19 vaccines compared to patients with other malignancies. However, the immune responses are heterogeneous and its association with clinical outcomes are poorly understood. Here, we study the association between antibody and cellular re sponses with the outcomes from COVID‐19 infection from the PROSECO study. Methods: THE UK PROSECO study is a prospective observational cohort study evaluating COVID‐19 vaccine response in people with lymphoma. Peripheral blood antibody titres (anti‐spike (S) IgG by Mesoscale Discovery), antibody avidity (surface plasmon resonance) and IFNγ T‐cell responses (ELISpot) against spike protein after two to four COVID‐19 vaccines, and clinical outcomes data were collected. Results: 524 patients (92 Hodgkin lymphoma, 180 aggressive B non‐ Hodgkin lymphoma (B‐NHL), 234 indolent B‐NHL and 18 peripheral T‐cell lymphoma) were included: 334 (84·3%), 315 (79·5%) and 266 (67·1%) participants were eligible for post‐two, three and four vac cine dose analysis, respectively. Breakthrough infections (BTI) occurred in 20 (5.9%), 40 (12.7%) and 36 (13.5%) participants after two, three and four vaccine doses. Of 96 participants with BTI, 12 (12.5%) needed hospitalisation. No deaths were observed due to COVID‐19 infection. No differences were observed in T‐cell re sponses between BTI and non‐BTI groups, but 4/9 (44.5%) hospital ised BTI cases had undetectable cellular and antibody responses. There was no association between antibody titres and infection ep isodes after two vaccine doses, but antibody titres were associated with lower BTI risk after three or four vaccine doses on multivariable analysis. Intriguingly, the antibody threshold associated with infec tion risk was lower after four than three vaccine doses (41 vs. 820 BAU/mL). We also observed stronger antibody binding avidity to SARS‐CoV‐2 spike receptor‐binding domain (RBD) proteins from Wuhan and Omicron BQ.1 variants, with increasing vaccine doses, i. e., fourth versus third dose: 10‐fold increase (p: <0.01); fourth versus second dose:100‐fold‐increase than the second dose (p: <0.0001) (see Figure). Conclusion: Anti‐S antibody titres can predict the risk of COVID‐19 infection after three or more vaccine doses in patients with lym phoma. Repeated COVID‐19 vaccination drives antibody affinity maturation and consequently improves the strength of antibody binding to virus spike proteins. Nearly half of participants who required hospitalisation for COVID‐19 had undetectable antibody and cellular immunity to vaccination. Altogether, these data show the importance of booster vaccine doses and immune monitoring post COVID‐19 vaccination to identify lymphoma patients who still continue to be at risk from severe COVID‐19, and thus the best prophylactic and therapeutic strategies. 606 - SUPPLEMENT ABSTRACTS The research was funded by: the Blood Cancer UK Vaccine Research Collaborative, which is led by Blood Cancer UK in partnership with Myeloma UK, Anthony Nolan and the British Society for Haematol ogy; a Cancer Research UK Advanced Clinician Scientist Fellowship to SH Lim; Cancer Research UK/National Institute for Health Research (NIHR) Southampton Experimental Cancer Medicine Cen ter; NIHR Southampton Clinical Research Facility (Southampton Research Biorepository) and NIHR Southampton Biomedical Research Center; NIHR Great Ormond Street Biomedical Research Center and the NIHR Oxford Biomedical Research Center and CRUK Experimental Cancer Medicines Center.Item Real world prospective evaluation of clinical outcomes in patients with non-metastatic castrate resistant prostate cancer treated with darolutamide(2023) Challapalli, Amarnath; Renninson, Emily; White, Paul; Elumalai, Thiraviyam; Parikh, Omi; Vickers, Alexander; Birtle, Alison Jane; Brocklehurst, Andrew; Bhana, Rajanee; Wickramasinghe, Kanchana; Jayaprakash, Kamalram Thippu; Gray, Emma; Sephton, Matthew; Al-Naeeb, Anna Bowzyk; Foulstone, Emily; Soundy, Alexandra; Ashurst, Lauren; Bahl, AmitBackground: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular inform regarding use of next generation imaging in this setting. Methods: Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Results: 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 - 10) months. 42 patients (49.4%) had pre-treatment PSAdT of <6 months and 43 (50.6%) patients had PSAdT of ≥6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT <6 months but median duration had not been reached for patients with pre-treatment PSAdT ≥6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%); 21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusions: In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of <6 months compared with ≥6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study.