Personalized Sarcoma Care

Background

Patients with high-grade sarcoma (bone tumour) of the extremities, often face a difficult decision in the shared decision making of their surgical treatment, since risk prediction models balancing both cure of the sarcoma and quality of life are not only scarce, but also have little validity. Radiotherapy and wide surgical resection are the main treatments; surgical tumour margins are necessary for cure, but the degree of surgical morbidity is also largely determined by these surgical margins. Both determine quality of life after intervention. The prognostic relevance of surgical margins and local recurrence on survival, in the context of specific subgroups of patients with high-grade soft tissue sarcomas differs largely. 

Prognostic models

Prognostic models in cancer treatment focus on prognosis at one well-defined baseline moment, mainly at time of diagnosis. It is at this time that the most important decisions on primary treatment are made. However, once the primary surgical treatment has been provided, patient’s prognosis may change over time. Clinical events such as local recurrence or distant metastasis that may occur after surgery must be taken into account. 

Aims

Within this project a dynamic prognostic model predicting the risk for local recurrence and/or distant metastases for different treatment protocols in soft tissue sarcoma, given patient and tumour related risk factors, identified at diagnosis and collected during the follow up, will be developed. An online prediction tool will be made available for clinicians collaborating to the project via hospital websites through a user-friendly web application and an app.

Relevance for cancer research 

The methodology of this research project can be applied to soft tissue sarcoma to be used by other multidisciplinary teams to improve prognosis and patients care. The model will be made available to other collaborating research groups.

Project Outcomes

• Rueten-Budde AJ, van de Sande M, van Praag VM & Fiocco M; PERSARC Study Group (2021). External validation and adaptation of a dynamic prediction model for patients with high-grade extremity soft tissue sarcoma.  J Surg Oncol, 123(4):1050-1056. doi: 10.1002/jso.26337 

• Hagenmaier HSF, van Beeck AGK, Haas RL, van Praag VM, van Bodegom-Vos L, van der Hage JA, Krol S, Speetjens, FM, Cleven AHG, Navas A, Kroon HM, Moeri-Schimmel RG, Leyerzapf NAC & van de Sande MAJ (2021). The Influence of Personalised Sarcoma Care (PERSARC) Prediction Modelling on Clinical Decision Making in a Multidisciplinary Setting. In C. Verhoef (Ed.), Sarcoma, 1–6. Hindawi. doi: 10.1155/2021/8851354

• Rueten-Budde AJ (2020, March 10). Personalised medicine for multiple outcomes: methods and application. [Doctoral Thesis]

• Smolle MA, van de Sande MAJ, Callegaro D, Wunder J, Hayes A, Leitner L, Bergovec M, Tunn PU, van Praag V, Fiocco M, Panotopoulos J, Willegger M, Windhager R, Dijkstra SPD, van Houdt WJ, Riedl JM, Stotz M, Gerger A, Pichler M, Stöger H, Liegl-Atzwanger B, Smolle J, Andreou D, Leithner A, Gronchi A, Haas RL, Szkandera J (2019). Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models. Cancers, 12(1):47. doi: 10.3390/cancers12010047

• Rueten-Budde AJ, van Praag VM, PERSARC studygroup, van de Sande MAJ & Fiocco M (2018). Dynamic prediction of overall survival for patients with high-grade extremity soft tissue sarcoma. Surgical Oncology, 27(4):695-701.  doi: 10.1016/j.suronc.2018.09.003

• van Praag VM, Rueten-Budde AJ, Ho V, Dijkstra P, van der Geest IC, Bramer  JA, Schaap GR, Jutte PC, Schreuder HB, Ploegmakers J, Fiocco M & van de Sande MAJ (2018). Incidence, outcomes and prognostic factors during 25 years of treatment of chondrosarcomas. Surgical Oncology,  27(3):402–408. doi: 10.1016/j.suronc.2018.05.009

• van Praag VM, Rueten-Budde AJ, Jeys LM, Laitinen MK, Pollock R, Aston W, van der Hage JA, Dijkstra PS, Ferguson PC, Griffin AM, Willeumier JJ, Wunder JS, van de Sande MAJ & Fiocco M (2017). A prediction model for treatment decisions in high-grade extremity soft-tissue sarcomas: Personalised sarcoma care (PERSARC). European Journal of Cancer, 83:313-323. doi: 10.1016/j.ejca.2017.06.032

• Willeumier JJ, Rueten-Budde AJ, Jeys LM, Laitinen M, Pollock R, Aston W, Dijkstra PS, Ferguson PC, Griffin AM, Wunder JS, Fiocco M & van de Sande MAJ (2017). Individualised risk assessment for local recurrence and distant metastases in a retrospective transatlantic cohort of 687 patients with high-grade soft tissue sarcomas of the extremities: a multistate model. BMJ open, 7(2):e012930.  doi: 10.1136/bmjopen-2016-012930 

Team

• Dr. M. Fiocco (PI), Mathematical Institute Leiden University, Department of Biomedical Data Sciences Leiden University Medical Center & Princess Máxima Center for Pediatric Oncology 

• V. van Praag, MD, Leiden University Medical Centre, Department of Orthopaedics

• A. J. Rüten-Budde, PhD candidate at Mathematical Institute Leiden University

• Dr. M.A.J. van de Sande (PI), MD, Orthopaedic Surgeon at the Leiden University Medical Center