Clinical Service Line 11 - Cancer & End of Life, Clinical Oncology, Chemo

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    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.
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    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.
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    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, Amit
    Background: 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.
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    Mental wellbeing and quality of life in prostate cancer (MIND-P): Protocol for a multi-institutional prospective cohort study.
    (2023) Brunckhorst, Oliver; Liszka, Jaroslaw; James, Callum; Fanshawe, Jack B; Hammadeh, Mohamed; Thomas, Robert; Khan, Shahid; Sheriff, Matin; Ahmed, Hashim U.; Van Hemelrijck, Mieke; Muir, Gordon; Stewart, Robert; Dasgupta, Prokar; Ahmed, Kamran
    Background: The mental wellbeing implications of a prostate cancer diagnosis are increasingly being realised. Significant mental health symptoms such as depression and anxiety, along with related constructs such as fear of cancer recurrence, body image and masculine self-esteem issues are prevalent. However, less is understood about potential prognostic factors for these outcomes in prostate cancer patients. Therefore, this study aims to primarily explore potential treatment, patient and oncological factors associated with mental wellbeing outcomes in the initial prostate cancer follow-up period. Methods: MIND-P is a multi-institutional prospective cohort study recruiting newly diagnosed prostate cancer patients for 12-month follow up. It will aim to recruit a final sample of 300 participants undergoing one of four treatment options: active surveillance, radical prostatectomy, radical radiotherapy, or hormone monotherapy. Questionnaire-based data collection consists of multiple validated mental, physical, and social wellbeing outcomes at baseline and 3-monthly intervals until study completion. Primary analysis will include evaluation of treatment undergone against multiple mental wellbeing outcomes. Secondary analysis will additionally explore multiple patient and oncological prognostic factors of potential importance, along with the cumulative incidence of these outcomes, symptom trajectory and their association with subsequent functional and social outcomes. Conclusion: This cohort study aims to add to the existing limited literature evaluating significant prognostic factors for multiple mental wellbeing outcomes in newly diagnosed prostate cancer patients. This may be of potential use for guiding future prognosis research and of clinical use for identifying individuals potentially requiring additional surveillance or support during routine cancer follow up. Study registration: This study was prospectively registered on ClinicalTrials.gov (NCT04647474).
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    Immune-related thyroid dysfunction in lung cancer patients treated with PD-1/PD-L1 checkpoint inhibitors.
    (2023-04) Bulusu, Venkata; Jessop, Susan; Paul, Sherin; Chapman, Timothy; Aslam, Shahzeena; Jeffs, Yvonne; Punnen, Geethu; Geetha, Anil; Hutka, Margaret
    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.