The European Society of Medical Oncology (ESMO) Sarcoma & GIST Symposium 2022 took place from 31 January to 2 February 2022. The Myrovlytis Trust were delighted to attend the symposium and witness researchers from across the globe coming together to share their research and discuss how we can positively change the outcomes for those diagnosed with sarcoma and gastrointestinal stromal tumours (GIST).
Osteosarcoma
The Adolescent and Young Adult sessions were of particular interest as osteosarcoma, the most common paediatric bone cancer is one of the key conditions the Myrovlytis Trust focuses on. Since the introduction of neo(-adjuvant) therapy in the 1970s, treatment regimens have not changed and there is an urgent need for new effective and non-toxic treatments. Paediatric haemato-oncologist Professor Stefan Bielack (Stuttgart Cancer Center, Germany) explored the history of clinical research into osteosarcoma and emphasised that ‘we need to move on’. He demonstrated that in the last 10 years the majority of phase 2 clinical trials have been unsuccessful and although tyrosine kinase inhibitors (TKIs) have shown promise they are not enough on their own (1). He suggested that moving forward there should be a focus on testing combination therapies in osteosarcoma and that trying new things, even if they don’t work, is paramount to moving forward in osteosarcoma.
Immunotherapy
Another key interest of the Myrovlytis Trust is immunotherapy. Medical oncologist Professor Robert Maki (Hospital of the University of Pennsylvania, USA) discussed the use of single immune-oncology agents in sarcoma. Research into checkpoint inhibitors (CPIs) has been unsuccessful to date in sarcoma, with only a small number of sarcoma subsets showing any response. However, even when trials have been designed to target specific subsets of patients there has been no evidence of long term benefit. The PEMBROSARC trial assessed the effectiveness of PD-1 inhibitors in patients with tertiary lymphoid structure (TLS) positive sarcomas, found most commonly in Liposarcoma, Undifferentiated pleomorphic sarcoma and leiomyosarcoma. 26% of participants had a response to the therapy but the potential long term benefits were not conclusive (2). Focus is therefore turning towards combination therapy including the combination of immune-oncological agents with alternative agents such as TKIs.
Diagnosis
During the bone cancer session, pathologist Professor Daniel Baumhoer (Universitatsspital Basel, Switzerland) described an alternative technique for classifying bone tumours. He explained that DNA methylation could be an effective way to diagnose sarcoma (3). He described DNA methylation as a fuse box with only 2 possible values. Each CpG site is allotted a value of 1 or 2 depending on its methylation status. A machine-learning algorithm then classifies the tumour depending on these numbers. This classification system (DKFZ Sarcoma Classifier) has since been validated as a potentially powerful diagnostic tool (4). Classifying bone tumours is important for determining treatment plans and using methylome profiling in addition to histology could be an effective way to not only accurately diagnose bone tumours but discover new subtypes.
Collaboration
Lastly, during the symposium, there were discussions about the importance of collaboration as we move forward. Medical oncologist Professor Emanuela Palmerini (Istituto Ortopedico Rizzoli , Italy) discussed the challenges of researching rare cancers. Small cancer cohorts mean that it is challenging to recruit enough participants for clinical trials and gather enough evidence for drugs to be approved by regulatory bodies. She then shared some of the collaborative projects that have the potential to advance research including the new FOSTER consortium, a European consortium dedicated to osteosarcoma and HIBISCUS, a project harmonising osteosarcoma data. These collaborative approaches can involve larger patient cohorts in trials and gather larger data sets to better understand and ultimately develop new treatments for osteosarcoma.
Take-Home Messages
There is an urgent need to improve outcomes in osteosarcoma. Although current research has had little success understanding the mechanisms of how different treatments work and the possibility of combining them opens up new avenues of research and therapeutic strategies. The Myrovlytis Trust is committed to advancing research into osteosarcoma to rapidly bring novel and effective treatments to the clinic. We are now accepting applications for small pilot studies and PhD studentships into osteosarcoma. Please visit our website for more information on our funding streams or contact us by email.
References
1. Gaspar N, Campbell-Hewson Q, Gallego Melcon S, Locatelli F, Venkatramani R, Hecker-Nolting S, et al. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆. ESMO Open [Internet]. 2021 Oct 1 [cited 2022 Feb 10];6(5):2059–7029. Available from: /pmc/articles/PMC8477142/
2. Italiano A, Bessede A, Bompas E, Piperno-Neumann S, Chevreau C, Penel N, et al. PD1 inhibition in soft-tissue sarcomas with tertiary lymphoid structures: A multicenter phase II trial. https://doi.org/101200/JCO20213915_suppl11507. 2021 May 28;39(15_suppl):11507–11507.
3. Koelsche C, Schrimpf D, Stichel D, Sill M, Sahm F, Reuss DE, et al. Sarcoma classification by DNA methylation profiling. Nature communications [Internet]. 2021 Dec 1 [cited 2022 Feb 10];12(1). Available from: https://pubmed.ncbi.nlm.nih.gov/33479225/
4. Lyskjær I, de Noon S, Tirabosco R, Rocha AM, Lindsay D, Amary F, et al. DNA methylation‐based profiling of bone and soft tissue tumours: a validation study of the ‘DKFZ Sarcoma Classifier.’ The Journal of Pathology: Clinical Research [Internet]. 2021 Jul 1 [cited 2022 Feb 10];7(4):350. Available from: /pmc/articles/PMC8185366/
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