A patient-centred approach in neuro-oncology: definition and measurement of clinical outcome in brain tumor patient

Brain tumors, independently from histology, share a similar progressive growth pattern that often requires multiple treatment modalities. Surgery, radiotherapy, chemotherapy and medications are often administered in close proximity to one another or, sometimes, contemporaneously. For that reason, the assessment of the effectiveness of any single treatment is extremely difficult. Brain tumors are a rare cancer but they are among the most devastating forms of cancer and afflict the very core of the person. Optimizing the life style of patients should become essential and on a par with the life prolongation goal of anti-cancer therapy. A potential solution to this problem is a patient-centered approach to different tumor types and treatments in which the comprehensive patient assessment is included in the outcome set. Traditionally, clinical trials of treatments for gliomas have relied on measures such as the reduction in tumor size, or on time-dependent metrics including the progression-free survival and the overall survival. The procedure used to evaluate of treatment effects by means of these measures can be complemented by the assessment of clinical outcomes such as measurements of the functional or symptomatic effects of the condition on the person. Unfortunately, the most commonly reported outcome measures are not necessarily the most appropriate. They are often selected and motivated since they are widely cited in the literature; this is an incorrect approach on a scientific ground and also precludes new and more effective instruments to be introduced and accepted. The instruments currently used in neuro-oncology are influenced by notions anchored to the type of treatment (such as chemotherapy or radiotherapy) rather than to tumor and, particularly, to patient characteristics. The utility of patient-reported outcome data can be maximized with standardization of methods to assess, analyze, interpret and report results. Nevertheless, neuro-oncological guidelines do not mention instruments and parameters but rather generically prescribe “neurological monitoring”. A paradox is that, while new therapies and diagnostics are improving survival rates, much remains unknown about the patient clinical conditions and performance at an instrumental level. However, in the last years, a growing interest on cognitive response in clinical trials has been observed and the cognitive performance is now considered as an important patient-related outcome to assess response to treatments. Tracking symptoms and function can inform clinicians about whether a treatment results in measurable benefits or adverse effects to patients. 6 We should not forget that patients want to live longer, but they also want to continue to function as well as possible for as long as possible. This research. arose from the considerations set forth above. The aim of the thesis is to provide an overview of the clinical outcome assessment of patients with brain tumors. The thesis analyzes the role of the assessment in collecting information about the direct impact of neoplastic invasion of the cerebral parenchyma and in monitoring the effects of therapies. This thesis is composed of three different studies. The first study describes the characteristics of clinical trials on gliomas and the outcome profile (objective, endpoints, domains, categories and instruments), since the 1990 (the advent of evidence based medicine) to 2019. The second study describes the neuropsychological tests mainly used in the brain tumor clinical trials published over the last 30 years and tries to evaluate the methodological quality of studies on measurement properties by means of the COSMIN checklist. Finally, the third study focuses on the neuropsychological assessment of language in multilingual people. Due to the increasingly widespread integration, this has become a crucial issue in neuro-oncology, especially in the perioperative evaluation of patients undergoing surgical treatment for brain cancer. The aim is to verify to what extent the variables that affect linguistic processing in multilingual speakers have been considered during planning and decision making in awake surgery for brain tumors.