Antioxidanttillskott i samband med malign sjukdom - vad är en myt och vad är sanning enligt dagens forskning?

Episode: Antioxidanttillskott i samband med malign sjukdom.

Lyssna på ett samtal mellan Martin O. Bergö, PhD, Professor, Prorektor, Institutionen för Medicin, Huddinge (MedH), KI, Christopher Melén, Bitr Överläkare, PhD, ME Hematologi, KS och Lisa Ekesiöö, Kontaktsjuksköterska, ME Hematologi, KS om antioxidanter i samband med maligna sjukdomar, främst hematologiska. Hur kan man säkerställa att användningen av antioxidanter inte stimulerar cancer medan man åtgärdar en brist? Hur bör man bäst bemöta en patient som har förtroende för kosttillskott? Bör man agera proaktivt?

Full episode – 44 min

_{References: 1. Alpha-Tocopherol BCCPSG (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330: 1029–35. 2. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, et al (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475: 106–9. 3. Kashif M, Yao H, Schmidt S, Chen X, Truong M, Tüksammel E, Liu Y & Bergo MO (2023) ROS-lowering doses of vitamins C and A accelerate malignant melanoma metastasis. Redox Biol 60: 102619. 4. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, et al (2011) Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306: 1549–56. 4. Le Gal K, Ibrahim MX, Wiel C, Sayin VI, Akula MK, Karlsson C, Dalin MG, Akyürek LM, Lindahl P, Nilsson J, et al (2015) Antioxidants can increase melanoma metastasis in mice. Sci Transl Med 7: 308re8. 5. Lignitto L, LeBoeuf SE, Homer H, Jiang S, Askenazi M, Karakousi TR, Pass HI, Bhutkar AJ, Tsirigos A, Ueberheide B, et al (2019) Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1. Cell 178: 316-329 e18. 6. Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ & Morrison SJ (2015) Oxidative stress inhibits distant metastasis by human melanoma cells. Nature 527: 186–91. 7. Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P & Bergo MO (2014) Antioxidants accelerate lung cancer progression in mice. Sci Transl Med 6: 221ra15. 8. Wiel C, Le Gal K, Ibrahim MX, Jahangir CA, Kashif M, Yao H, Ziegler DV, Xu X, Ghosh T, Mondal T, et al (2019) BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis. Cell 178: 330-345.e22. 9. Yao H, Chen X, Wang T, Kashif M, Qiao X, Tüksammel E, Larsson LG, Okret S, Sayin VI, Qian H, et al (2023) A MYC-controlled redox switch protects B lymphoma cells from EGR1-dependent apoptosis. Cell Rep 42: 112961.10. Yuan X, Duan Y, Xiao Y, Sun K, Qi Y, Zhang Y, Ahmed Z, Moiani D, Yao J, Li H, et al (2022) Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1. Cancer Discov 12: 1742–1759. 11. Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio I, Giannopoulou EG, Rago C, et al (2015) Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350: 1391–6. 12. Zou ZV, Le Gal K, El Zowalaty AE, Pehlivanoglu LE, Garellick V, Gul N, Ibrahim MX, Bergh PO, Henricsson M, Wiel C, et al (2021) Antioxidants Promote Intestinal Tumor Progression in Mice. Antioxid Basel 10.}

_{https://www.livsmedelsverket.se/livsmedel-och-innehall/kosttillskott}

_{https://www.livsmedelsverket.se/livsmedel-och-innehall/kosttillskott/vem-behover-extra-vitaminer}

_{https://www.livsmedelsverket.se/matvanor-halsa--miljo/kostrad/gravida}

Cardiovascular risk management in CLL

In this podcast series of 2 episodes you will learn more about practical implications of cardiovascular risk and manifest cardiovascular disease when treating CLL. The discussions are led by Dr Mattias Mattsson, Senior consultant in Hematology, Hematology Department, Uppsala University Hospital, Sweden.

Episode: Management of comorbidities in CLL from a Hematologist’s perspective

Dr Mattsson and Dr Carsten Niemann, PhD, Clinical Ass. Prof. and Head of the CLL Research Laboratory at Rigshospitalet in Copenhagen, Denmark, discuss treatment considerations in CLL patients with comorbidities. This episode addresses questions such as; What to consider in patients who have high risk of infection, cardiovascular diseases, renal impairment and secondary primary malignancies? How important is the quality of life vs keeping the patients free from symptoms or adverse events?

Short episode – 10 min

Full episode – 45 min

References: 1. (RCC), R.C.i.S., Remissrunda – Nationellt vårdprogram för kronisk lymfatisk leukemi (KLL). 2024.2. Kater, A.P., et al., Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION): primary analysis of an open-label, randomised, phase 2 trial. Lancet Oncol, 2022. 23(6): p. 818-828. 3. Eichhorst, B., et al., First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. N Engl J Med, 2023. 388(19): p. 1739-1754. 4. Eichhorst, B., et al., First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol, 2016. 17(7): p. 928-942. 5. Skarzynski, M., et al., Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy. Clin Cancer Res, 2016. 22(1): p. 86-95.

Episode: Cardiovascular risk management in CLL from a Cardiologist’s perspective

What measures should be taken to optimize CLL treatment with consideration to cardiovascular risk factors? How important is presence, management and follow-up of atrial fibrillation and hypertension in CLL?

Welcome to listen to Dr Mattsson and Dr Manan Pareek, Fellow in cardiovascular medicine, Copenhagen University Hospital - Rigshospitalet, Denmark, discussing the importance and implications of cardiovascular risk stratification and management in chronic lymphocytic leukemia.

References: 1. Lyon, A.R., et al.European Heart Journal, 2022. 43(41): p. 4229-4361. 2. Pudil, R., Card Fail Rev. 2017 Nov; 3(2): 140–142. 3. Asteggiano, R., et al. Eur Heart J, 2020. 41(2): p. 205-206. 4. Sadler, D., et al. JACC: CardioOncology, 2020. 2(3): p. 535-538. 5. Larsson, K., et al. Br J Haematol, 2020. 190(4): p. e245-e248. 6. Zheng, H. and H. Zhan. JACC: CardioOncology, 2023. 5(1): p. 149-152. 7. Lubitz, S.A., et al. Circulation, 2022. 146(19): p. 1415-1424. 8. McDonagh, T.A., et al. Eur Heart J, 2021. 42(36): p. 3599-3726. 9. Tang, C.P.S., et al. British Journal of Haematology, 2022. 196(1): p. 70-78. 10. Quartermaine, C., et al. JACC: CardioOncology, 2023. 5(5): p. 570-590. 11. Awan, F.T., et al. Blood Advances, 2022. 6(18): p. 5516-5525. 12. Awan, F.T., et al. Blood Adv, 2019. 3(9): p. 1553-1562. 13. Hillmen, P., et al.The Lancet Oncology, 2023. 24(5): p. 535-552. 14. Capranzano, P. European Heart Journal Supplements, 2022. 24(Supplement_I): p. I54-I56. 15. Williams, B., et al. European Heart Journal, 2018. 39(33): p. 3021-3104. 16. AlAsmari, A.F., et al. Int J Mol Sci, 2022. 23(11). 17. Amitai, I., et al. Hematol Oncol, 2021. 39(2): p. 215-221.

COVID-19 and Hematological patients

A podcast sequence consisting of two episodes. The aim is to shed light on who the high-risk patients are, breaking down what unmet needs and guidelines there are for these high-risk patients and deep diving into how to interpret, align and make clinical decisions based on the antibody and T-cell responses of hematological patients. The discussions are led by Dr Anna Maria Frustaci, Hematologist MD, Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan.

Episode: Identification of High-Risk patients with Covid-19

In this episode we highlight the issues that immunocompromised patients are/will be facing in light of COVID-19. The episodes identify the patient population(s) most at risk for severe infection and hospitalization or death. Also, deep diving within the hematological patients, identifying who are the most at risk and why? Which unmet needs are there for these patients today in the “post pandemic” era? Which guidelines are in place? What are the most important clinical considerations for hematological patients today? What are the lessons learned so far from the pandemic?

References:
1. Carrara E et al, Hematological Oncology, 2023;41:16–25. 2. Blennow O et al, Am J Hematol.2022;97:E312–E317. 3. Infante MS et al, Front Oncol. 2022 Oct 3;12:992137. 4. Pagano L et al, J Hematol Oncol. 2021 Oct 14;14(1):168. 5. Cheok KPL et al, Leuk Lymphoma. 2022 Aug;63(8):1980-1984. 6. Levin MJ et al, N Engl J Med. 2022 Jun 9;386(23):2188-2200. 7. Stuver R et al. Cancer Cell. 2022 Jun 13;40(6):590-591. 8. Kamar N et al, N Engl J Med. 2021 Aug 12;385(7):661-662. 9. https://www.legeforeningen.no/foreningsledd/fagmed/norsk-forening-for-infeksjonsmedisin/aktuelt/2022/antivirale-og-immunmodulerende-midler-ved-covid-19-v16

Episode: Antibodies and T-cell responses in Covid-19 patients

This episode deep-dives into immune responses of hematological patients, with a special focus on the most high-risk patients within this group. What do we know with regards to antibody responses in these patients? How is it measured and interpreted? Where are the gaps in terms of interpretation and clinical decision making based on antibody responses in CLL patients/hematological patients? What do we know about T-cell responses in these patients and how can this be used in clinical decision making? Which guidelines are in place? What do we know of the potential T-cell dysfunction in CLL patients? Finally, what are the unmet needs with regards to management of COVID-19 in these patients?

References:
1. Williamson EJ et al. Nature. 2020;584(7821):430-436. 2. Langerbeins P et al, Blood vol. 140,3 (2022): 236-252. 3. Obeid M et al. JAMA oncology vol. 8,5 (2022): e220446. 4. Benning L et al. Clinical journal of the American Society of Nephrology, vol. 17,1 (2022): 98-106. 5. Jiménez M et al. Blood advances vol. 6,3 (2022): 774-784. 6. Mellinghoff SC et al. Haematologica vol. 107,10 2480-2484. 1 Oct. 2022. 7. Wherry EJ et al, Science vol. 377,6608 (2022): 821-822.

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