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Functional approach to brain tumor surgery: awake setting
19.1
Introduction
About 20,000 people/year are diagnosed with primary brain cancers in Europe. The 5-year survival rate is around 33%, additionally there is an extensive socioeconomic costs . Gliomas are the most common primary brain tumors. Historically they have been divided into low-grade and high-grade gliomas. Recent advances in molecular biology divide gliomas in two groups based on the presence of the IDH1 mutation. Gliomas in which the IDH1 mutation is not present exhibit an aggressive biological behavior as well as a poor prognosis as glioblastomas, independently from histological grade. Gliomas characterized by IDH1 mutation are characterized by a less aggressive biological behavior, and a similar clinical prognosis and show less correlation to the histological grade . They include both diffuse low-grade and intermediate-grade gliomas and have been recently defined as lower grade gliomas (LGGs) .
Treatment of gliomas is multimodal and consists of surgery, eventually followed by radiotherapy and/or chemotherapy.
19.2
Rationale of surgical treatment
The major aims of surgical treatment are (1) obtaining adequate specimens and representative tissue to reach a correct histological and molecular diagnosis; (2) achieving a cytoreduction in order to decrease the rate of recurrence, possibly prolonging survival; (3) improving the neurological symptoms of the patients; and (4) obtaining a better seizure control.
19.3
The concept of functional neuro-oncology: resection according to functional boundaries
Surgery for gliomas is aimed at maximizing tumor resection associated with full patient functional integrity . Various strategies have been developed to achieve this result. The most relevant oncological impact, both in term of amount of tissue removal and functional preservation, has been produced by the introduction of the brain mapping techniques . This term refers to a group of techniques, which allow to safely and effectively remove tumors while at the same time preserving the functional integrity of the patients. This can be achieved by the identification and preservation of cortical and subcortical structures, which are involved in specific functions. The concept of detecting and preserving the essential functional cortical and subcortical sites has been recently defined as surgery according to functional boundaries, and it is summarized with the term “functional neuro-oncological approach.”
The shift of the paradigm between image-based surgery and surgery based on functions finds its rationale on various considerations: in the case of LGGs, these tumors are located in areas of the brain traditionally defined as eloquent (language, motor) , therefore resection of tumors within these areas have to be necessarily associated with function preservation . Gliomas are highly infiltrative tumors, and cells could be found beyond the borders of the tumors as visualized in fluid attenuated inversion recovery (FLAIR) or even postcontrast T1-weighted images, which makes approaches based on pure images quite limited in term of oncological results . In the case of LGGs that are characterized by a slow speed of growth , this induces a progressive reorganization of surrounding brain areas, modifying and reshaping brain functional organization in a way that is patient specific and that cannot be fully depicted by functional images techniques [e.g., functional magnetic resonance (MR) imaging (MRI) (fMRI)] . The functional approach exploits the functional reorganization of patient brain, allowing to remove as much as tumors are feasible, possibly extending resection far beyond the tumor margins visible and detectable by conventional MR images, preserving the functional integrity . The new paradigm (or philosophy) is looking for functional brain boundaries independently from where they are located in respect to tumor borders. The functions to be mapped and preserved are not only limited to language or motor, but expand to haptic, visuospatial, visual, and cognitive, in order to maintain the full patient integrity and preserve the quality of life of the patient.
19.4
Preoperative workup
Using a functional approach, the management of the patient entering the out-patient clinic with a diagnosis of a presumptive glioma must be aimed at defining the degree of functional reorganization achieved by the patient’s brain surrounding the tumor . At the same time, in relationship with the symptoms reported by the patient, his/her neurological condition, along with the possible aggressiveness of the tumor (LGGs vs high-grade gliomas) defined by evaluating the imaging, the general treatment plan is designed and tailored to the specific situation. Overall, this approach defines the feasibility of resection and the possible degree of tumor removal that can be achieved in the individual patient. The management must therefore foresee a careful interview of the patient, associated with a detailed neuropsychological evaluation; data obtained from these analyses have to be integrated with those obtained from imaging. These data are used for making the eventual decision to treat, and for planning the resection.
19.4.1
Patient interview
This is a point of particular importance and must take into account the symptoms reported by the patient and the duration of the clinical history. The interview should detail the type of symptoms, their onset, and duration of clinical history. In the case of history mainly characterized by seizures (as in LGGs), a detailed epileptic history is mandatory. It provides information on both the progression and temporal and current extension of the neoplasm, as well as precious information on the degree of functional reorganization achieved by the surrounding brain due to the presence, growth, and extension of the neoplasm itself. For example, in the case of insular tumors, in the dominant hemisphere, the onset of focal seizures with speech arrest indicates the activity of the ventral premotor and the underlying connection bundles, indicative of a partial or not complete language reorganization in this area. Contrarily, in the same tumors, the appearance of generalized seizures in the absence of focal symptoms or focal sensory motor seizures indicates the reorganization of the language circuits in this area. Similarly, the onset of mesial temporal seizures suggests both the extension of the tumor to the temporal region and a high degree of reorganization of the circuits in this area. Consequently, in the first case a subtotal or partial removal may be expected, in the latter a complete resection can be predicted. A careful interview must also be aimed at highlighting the appearance of signs and symptoms of involvement of deep associative circuits, such as the occurrence of mood changes in the case of frontal or limbic tumors . When properly asked, the patient can report the occurrence of such symptoms several months or even years in advance of the onset of the seizures or symptom that actually brought the tumor to diagnosis . The presence of such disturbances, particularly in LGGs, highlights the need to extend the intraoperative mapping with appropriate tests capable of identifying and sparing such network, to preserve as much as possible high cognitive functions .
The patient’s interview is associated with the neurological examination. The percentage of patients with motor and/or language deficits varies according to the various series.
Other additional data to be evaluated during the patient’s interview are the patient’s educational level, job and future career development, current hobbies, future pregnancy in the case of female patients . These data, generally referred as patient needs, have to be also taken into consideration and carefully discussed with the patient for the elaboration of a tailored surgical strategy, particularly in the context of the permanent effect that surgery may exert on the quality of life .
19.4.2
Neuropsychological evaluation and psycho-oncological interview
Psychological evaluation consists of two components: neuropsychological and psycho-oncological evaluation.
The neuropsychological evaluation evaluates the degree of functional reorganization achieved by the individual patient and prepares the patient for the intraoperative testing, when this is needed. Extensive testing is used and usually explores all functional domains, comprehensive of memory, language, praxis, executive functions, and fluid intelligence . The type of tests carried out varies according to language and population (to which it must be normalized) taking also into account the age and level of education. At the same time the neuropsychological evaluation allows to prepare and select at the level of individual patient, a series of tests, to be carried out at the time of surgery, selecting among the available items those that the patient performs in a more constant and stable way . The reproducibility of the selected items must be repeated in a further evaluation usually carried out the day immediately before the procedure, to further check the reproducibility and reliability of the test and carefully calibrate them to the individual patient’s condition.
The psycho-oncological evaluation is a complementary investigation and has the function of assessing the patient’s needs, the presence of anxiety disorders, the understanding of the state of the disease and the therapeutic process to which the patients will go through, along with the ability to perform part of the procedure in local anesthesia if needed . The assessment consists of a psychological interview and the administration of welfare questionnaires or patient assessment scales. A psychotherapist is generally carrying out the psychological interview and administers the well-being questionnaires (see EORTC questionnaire for brain tumors) or those for assessing the state of anxiety and depression (see Hospital Anxiety and Depression Scale).
Data generated during patient interview and neuropsychological and psycho-oncological evaluation are then matched with those obtained by imaging.
19.4.3
Imaging workup
The imaging methods are divided into basic and advanced methods.
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