Age-related differences of oncological outcomes in primary extremity soft tissue sarcoma: a multistate model including 6260 patients.

Anja J Rueten‐Budde ,Ibtissam Acem,Madeleine Willegger,Rick L Haas,Olga Zaikova,Jay S Wunder,Katja Maretty-Kongstad,Kazuhiro Tanaka,Myles Smith ,Emelie Styring,Winan J Van Houdt,Maria Anna Smolle ,Peter C Ferguson,Hans Gelderblom,Cornelis Verhoef,Per‐Ulf Tunn ,R Windhager ,Andrew Hayes ,Andreas Leithner,Joanna Szkandera,Michiel A J Van De Sande ,Toshifumi Ozaki,Dirk J Grünhagen,Rob Pollock,Johnny Keller,Anthony M Griffin,Han J Bonenkamp ,Will Aston,Lee Jeys ,Marta Fiocco,Veroniek M Van Praag,Minna Laitinen ,Robert J Van Ginkel,Winette Van Der Graaf,Jos A Van Der Hage,Ingrid M.E Desar

doi:10.1016/j.ejca.2020.09.021

Abstract

No studies extensively compared the young adults (YA, 18-39 years), middle-aged (40-69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-agedand elderly population in patients with primary high-grade eSTS treated with curative intent. In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression. A total of 6260 patients were included in this study. YA presented more often after 'whoops'-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.47 (95% confidence interval [CI]: 1.23-1.76) and 3.13 (95% CI: 2.59-3.78) in the elderly population, compared with YA. The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population.

Highlights

Soft tissue sarcomas (STSs) are a group of rare heterogeneous tumours of mesenchymal origin with various histologic and clinical features
The population was categorized into three age groups: the YA (n Z 841, 13.4%), the middle-aged (n Z 3217; 51.4%) and the elderly population (n Z 2202; 35.2%) (Table 1)
This study found an increased risk of local recurrence (LR) in the elderly population compared with YA, in accordance with previous reports [8,22], an increased but less evident risk of distant metastasis (DM) was found in the middle-aged and elderly population compared with YA

Summary

Introduction

Soft tissue sarcomas (STSs) are a group of rare heterogeneous tumours of mesenchymal origin with various histologic and clinical features. The estimated incidence of STS is less than 4.7 per 100,000 persons in Northern Europe per year [1]. STSs may occur in all age groups, with a relatively high incidence in patients younger than 40 years compared with other malignancies [1,2]. Clinical trials mainly focused on the middleaged population, in which STS is the most prevalent [3], whereas the AYAs and elderly population remained underrepresented in these trials [5,6]. The lack of enrolment in clinical trials of the AYAs and elderly population limits our knowledge of tumour behaviour and effectiveness of STS management in these populations

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