Patient-derived cancer organoids have taken a prominent role in pre-clinical and translational research and have been generated for most common solid tumors. Cancer organoids have been shown to retain key genetic and phenotypic characteristics of their tissue of origin, tumor subtype and maintain intratumoral heterogeneity and therefore have the potential to be used as predictors for individualized treatment response. In this review, we highlight studies that have used cancer organoids to compare the efficacy of standard-of-care and targeted combination treatments with clinical patient response. Furthermore, we review studies using cancer organoids to identify new anti-cancer treatments using drug screening. Finally, we discuss the current limitations and improvements needed to understand the full potential of cancer organoids as avatars for clinical management of cancer therapy.

Background Previous studies have recognized temporal muscle thickness (TMT) as a prognostic marker in glioblastoma, but clinical implementation is hampered due to studies’ heterogeneity and lack of established cutoff values. The aim of this study was to assess the validity of recent proposed sex-specific TMT cutoff values in a real-world population of genotyped primary glioblastoma patients. Methods We measured TMT in preoperative MR images of 328 patients. Sex-specific TMT cutoff values were used to divide patients in ‘at risk of sarcopenia’ or ‘normal muscle status’. Kaplan-Meier analyses and stepwise multivariate Cox-Regression analyses were used to assess the association with overall survival (OS) and progression free survival (PFS). The association with occurrence of complications and discontinuation of glioblastoma treatment was investigated using odds ratios (OR). Results Patients at risk of sarcopenia had a significantly higher risk of progression and death than patients with normal muscle status, which remained significant in the multivariate analyses (OS HR=1.437; 95%CI: 1.046-1.973; p=0.025 and PFS HR=1.453; 95%CI: 1.037-2.036; p=0.030). Patients at risk of sarcopenia also had a significantly higher risk of early discontinuation of treatment (OR=2.45; 95%CI: 1.011-5.952; p=0.042) and a significantly lower chance of receiving second line treatment (OR=0.23; 95%CI: 0.09-0.60; p=0.001). There was no association with the occurrence of complications. Conclusions Our study confirms external validity of the use of proposed sex-specific TMT cutoff values as an independent prognostic marker in newly diagnosed glioblastoma patients. This simple, noninvasive marker could improve patient counselling and aid in treatment decision processes or trial stratification.

Glioblastoma is the most aggressive adult primary brain tumor which is incurable despite intensive multimodal treatment. Inter- and intratumoral heterogeneity poses one of the biggest barriers in the diagnosis and treatment of glioblastoma, causing differences in treatment response and outcome. Noninvasive prognostic and predictive tests are highly needed to complement the current armamentarium. Noninvasive testing of glioblastoma uses multiple techniques that can capture the heterogeneity of glioblastoma. This set of diagnostic approaches comprises advanced MRI techniques, nuclear imaging, liquid biopsy, and new integrated approaches including radiogenomics and radiomics. New treatment options such as agents targeted at driver oncogenes and immunotherapy are currently being developed, but benefit for glioblastoma patients still has to be demonstrated. Understanding and unraveling tumor heterogeneity and microenvironment can help to create a treatment regime that is patient-tailored to these specific tumor characteristics. Improved noninvasive tests are crucial to this success. This review discusses multiple diagnostic approaches and their effect on predicting and monitoring treatment response in glioblastoma.