A national survey to assess the state of anatomy teaching in France across various disciplines and professions.

PURPOSE: To investigate the current practices in anatomy teaching at French universities in 2023. METHODS: On January 10, 2023, a questionnaire was sent to all members of the official list of the French Medical College of Professors of Anatomy. Each Anatomy centre was asked to complete this online form only once. The questionnaire covered several key themes, including broad questions, dissections practices, "virtual" dissections, teaching methods and teaching staff. RESULTS: The questionnaire was completed by 26/28 anatomy centres. Access to body donor dissection is reported to be mandatory in 15 of the 26 centers (58%), optional in 10 centers (38%), and "tolerated" in one center (4%). Fifteen of 26 centers (58%) reported having a virtual dissection table for teaching anatomy. Concerning the teaching of anatomy via live ultrasound, 10 out of 26 centers (38%) reported providing it. Regarding the teaching methods used for medical students, chalk and board lectures are the most common method, although the intensity of use varies. Most lectures are given with chalk and board in 42% (11/26) of the centers. In about 73% (19/26) of the centers, tablet lectures are used. Regarding anatomy teachers, it was reported that in 24/26 anatomy centres (92%), more than 50% of the courses for medical students are taught by professors holding the chair of anatomy (21/26 professors (81%), 3/26 associate professors (12%)). CONCLUSION: The present study endeavors to contribute to the existing body of knowledge on anatomy education by offering insights into the current practices in French universities.

Mismatch Between Brain MRIs and 18 F-DOPA PET/CT : Impact on the Management of a Long Survivor With EGFR-Mutated Lung Adenocarcinoma.

ABSTRACT: After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18 F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18 F-DOPA uptake. Five additional 18 F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.

Social cognition in adult survivors of brain tumors: studying the relationship between theory of mind and quality of life.

OBJECTIVE: The present study is the first to examine theory of mind (ToM) sequelae in a sample of adult survivors of primary brain tumors, and to investigate the assumed relationship between ToM and health-related quality of life (HRQoL). METHOD: Participants were 40 long-term adult survivors of primary brain tumors and 40 matched healthy controls. They completed ToM tests (Faux-Pas test and Advanced ToM task) and two questionnaires assessing HRQoL (36-Item Short-Form Health Survey and EORTC QLQ-C30/QLQ-BN20). Their relatives also completed an observer-rated version of the SF-36 questionnaire. RESULTS: Survivors performed worse than controls only on the Advanced ToM task. Overall, patients and caregivers reported more problems than healthy controls and their relatives regarding both global HRQoL and its social/emotional aspects. No relationship was found between ToM and HRQoL scores. CONCLUSION: Adult survivors of primary brain tumors may exhibit ToM deficits several years after treatment and report more problems on social/emotional HRQoL components. Our findings highlight the need to consider these late effects in survivors' long-term follow-up, even if the clinical involvement of ToM deficits still needs to be elucidated. The assessment of ToM deficits and their potential impact on survivors' everyday life is thoroughly discussed.

Cadaveric study of flexor digitorum profundus and superficialis and flexor pollicis longus innervation patterns for application in selective neurectomy.

PURPOSE: Spasticity management in finger flexors (flexor digitorum profundus and superficialis and flexor pollicis longus) is a challenge. Recent studies demonstrated the short- and long-term efficacy of selective and hyperselective neurectomy for the spastic upper limb. However, hyperselective neurectomy of flexor digitorum profundus and flexor digitorum superficialis branches was incomplete, without impairing their muscular body and function. This cadaveric study describes a novel medial approach in the forearm, to reach all the muscular branches: flexor digitorum superficialis and profundus and flexor pollicis longus. MATERIAL AND METHODS: Fourteen cadaveric fresh frozen upper limbs were used. The feasibility of the medial surgical approach was studied, as well as the number, length and point of emergence of the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis. RESULTS: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, in all cases. A Martin Gruber communicating branch was found in 7 cases out of 14. CONCLUSION: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerve to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, without extensive transmuscular dissection of the pronator teres or flexor digitorum superficialis muscles. This approach opens the way for selective neurectomy of the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis muscles. LEVEL OF EVIDENCE: IV.

A modular system for the synchronized multimodal data acquisition during Awake Surgery: towards the emergence of a dedicated clinical database.

Awake Surgery (AS) is considered the best treatment for brain tumors located in or near eloquent areas. During this intervention, Direct Electrical Stimulations (DES) are delivered by the surgeon on the patient's brain in order to obtain an accurate brain mapping of the patient. The patient is asked to perform various tasks (e.g. counting, object naming, emotion recognition) through neuropsychological tests during these stimulations. These DES may cause a reversible lesion inducing deficits on the patient which can be observed during these tasks by the medical staff. The resection is then performed or not according to the patient's response. The intraoperative deficits can take several forms and can be difficult to analyze and identify. The development of new solutions allowing the automatic detection of these deficits could be therefore essential. However, still today, no structured and organized AS dedicated database is available that could be used to train and test these algorithms. We propose a modular system allowing the synchronized multimodal acquisition of various information including physiological measurements, DES signals and parameters, and task-related data to create such database.Clinical relevance- Acquiring synchronized multimodal data during AS will allow the creation of a dedicated database that could then be used to reveal new correlations between DES and the patient's response, and to develop and test new algorithms for the automatic detection of deficits.

Transfer of the palmaris brevis motor branch to the thenar motor branch: A cadaveric preliminary study.

OBJECTIVE: High median nerve injuries can lead to poor distal recovery, especially poor functioning of median innervated thenar muscles involved in thumb opposition and palmar abduction. The palmaris brevis (PB) is a small subcutaneous muscle innervated by ulnar nerve. Innervation of the PB is in most of cases provided by the ulnar digital nerve to the little finger. The purpose of this study is to assess the feasibility of transferring the PB motor branch (PBMB) to the median nerve thenar motor branch (TMB), in order to allow for early restoration of thumb palmar abduction and opposition, through a preliminary cadaveric study. METHODS: Twenty-five cadaver upper limbs were dissected under magnification. The length of the PBMB and TMB, and their origin were recorded. Nerve transfer from PBMB to TMB was conducted, and evaluated on 2 parameters: surgical feasibility, and distance from the coaptation site to the recipient nerve muscle entry point. The PBMB and TMB were harvested, fixated in formalin, then embedded in paraffin. They were sectioned transversely, and stained with a combination of hematoxylin-eosin and Luxol fast blue. Myelinated axons were counted in each specimen and the donor-to-recipient axon ratio was recorded. RESULTS: The PBMB was constant and originated from the ulnar digital nerve of the little finger in all cases. The transfer from PBMB to TMB was feasible in all cases. Mean myelinated axon counts of PBMB and TMB were 253±142 and 356±198, respectively (p=0.06). The donor-to-recipient axon ratio was 1:1.41. The mean distance from coaptation of the PBMB to the recipient thenar muscles was 23.1±3.0mm. CONCLUSIONS: Based on our results, PBMB to TMB transfer is feasible. The PBMB has the advantage over other distal nerve transfer donors to be constant and superficial, allowing for an easier harvest. Moreover, this procedure does not sacrifice any intrinsic function of the hand, and the proximity of the PBMB with the carpal tunnel allows for a single incision procedure. Therefore, early restoration of the median innervated thenar muscles may be feasible by the PBMB to TMB transfer in cases of high median nerve lesions. LEVEL OF EVIDENCE: IV.

Assessment of using ultrasonography to teach abdominal and cervical anatomy in French medical curricula.

PURPOSE: The objective of this work was to assess, in a quantitative and qualitative way, the teaching of cervical and abdominal anatomy via ultrasound for medical students. METHODS: For several years, tutorials on the study of anatomy through use of ultrasound on the living organism have been given at the Medical School of Brest. These sessions have focused on cervical anatomy and abdominal anatomy. Students were invited to quantitatively assess these lessons by taking two tests containing questions on both cervical and abdominal anatomy and ultrasound technique: a pre-test administered at the beginning of the year and a post-test at the end of the year. In addition, a qualitative assessment was carried out at the end of the year. Ten statements were presented, and students were asked to indicate their agreement or disagreement to a four-point Likert scale. RESULTS: One hundred and twelve students answered all the questions on the pre-test with an average of 13.4 correct answers out of 20. Forty-eight students answered all the questions on the post-test with an average of 14.6/20. Twenty-six students who benefited from the courses gave positive feedback about the workshops on the qualitative assessment at the end of the year (median scores > = 3/4). CONCLUSION: The results of this work suggest that the use of ultrasound makes a positive contribution to the teaching of anatomy. The students interviewed think this type of tutorial should be an integral part of the anatomy curriculum at our university. In addition, this type of instruction can serve to introduce the use of ultrasound itself in a practical learning setting.

Pruritus and brain tumours: A prospective and descriptive study.

Background: Pruritus, especially localised to the nostrils, has been reported as a specific sign of brain tumours. Objectives: The main goal of this study was to estimate the prevalence of pruritus in a group of patients with brain tumours. The second outcome was to better characterise this pruritus with a specific questionnaire and a skin examination. Methods: From June 2020 to September 2021, all patients with a diagnosis of brain tumour were included in this prospective, monocentric study. If the patient suffered from pruritus, a dermatological examination was performed. Results: Two hundred patients with brain tumours were included. Thirty-five of them suffered from pruritus (17.5%). Among them, 15 patients did not present with any skin disease, and 8 could have neuropathic pruritus according to the NP5 questionnaire. No patients presented with pruritus of the nostrils. Discussion: This study did not show clear evidence of specifically localised pruritus induced by brain tumours. Conclusion: Pruritus observed in patients with brain tumours seems not to be caused by the brain malignancies in most cases. The specific localization to the nostrils cannot be considered a specific marker.

Associations between Adult Primary Brain Tumor Survivors' Behavioral Executive Functions, Health Related Quality of Life and their Caregivers' Health Related Quality : A cross-sectional study.

The present study focused on adult primary brain tumor (PBT) survivors' caregivers. The main objective was to study associations between PBT survivors' health-related quality of life (HRQOL), their behavioral executive functions (EF) and their caregivers' HRQOL. Forty PBT survivors of PBT and 37 caregivers (mostly patient's spouses 81.08%; n = 30) participated in the study. PBT survivors completed a cancer related Quality of Life (QOL) questionnaire. Caregivers completed informant rated HRQOL and behavioral EF reports relating to PBT survivors and a self-rated HRQOL questionnaire relating to themselves. Correlational and multiple regression analyses were conducted. No associations were found between caregivers' physical HRQOL and PBT survivors' HRQOL nor behavioral EF. Analyses yielded several significant correlations between caregivers' mental HRQOL and variables pertaining to PBT survivors' HRQOL and behavioral EF. Multiple regression analyses showed that caregivers' mental HRQOL is predicted by PBT survivors' mental HRQOL, global cancer-related QOL scores and global behavioral EF scores. This study provides evidence suggesting that during the survivorship phase, at an average of 3.67 (SD = 2.31) years following treatment for a PBT, caregivers mental HRQOL is linked to PBT survivors' long-term effects. These findings shed some light regarding post-cancer care for both PBT survivors and their caregivers.

Natural history of spinal cord metastasis from brain glioblastomas.

BACKGROUND AND OBJECTIVES: Spinal cord metastasis arising from an intracranial glioblastoma is a rare and late event during the natural course of the disease. These pathological entities remain poorly characterized. This study aimed to identify and investigate the timeline, clinical and imaging findings, and prognostic factors of spinal cord metastasis from a glioblastoma. METHODS: Consecutive histopathological cases of spinal cord metastasis from glioblastomas in adults entered in the French nationwide database between January 2004 and 2016 were screened. RESULTS: Overall, 14 adult patients with a brain glioblastoma (median age 55.2 years) and harboring a spinal cord metastasis were included. The median overall survival as 16.0 months (range, 9.8-22.2). The median spinal cord Metastasis Free Survival (time interval between the glioblastoma diagnosis and the spinal cord metastasis diagnosis) was 13.6 months (range, 0.0-27.9). The occurrence of a spinal cord metastasis diagnosis greatly impacted neurological status: 57.2% of patients were not ambulatory, which contributed to dramatically decreased Karnofsky Performance Status (KPS) scores (12/14, 85.7% with a KPS score ≤ 70). The median overall survival following spinal cord metastasis was 3.3 months (range, 1.3-5.3). Patients with a cerebral ventricle effraction during the initial brain surgery had a shorter spinal cord Metastasis Free Survival (6.6 vs 18.3 months, p = 0.023). Out of the 14 patients, eleven (78.6%) had a brain IDH-wildtype glioblastoma. CONCLUSIONS: Spinal cord metastasis from a brain IDH-wildtype glioblastoma has a poor prognosis. Spinal MRI can be proposed during the follow-up of glioblastoma patients especially those who have benefited from cerebral surgical resection with opening of the cerebral ventricles.

Anatomic Study of the Integrity of the Breast Lymphatic Network With Indocyanine Green in Breast Implant Surgery Through the Axillary Approach.

INTRODUCTION: The performance of a prosthetic breast augmentation through the axilla always makes the surgeon fear the possibility of damage to the breast lymphatic network. Indocyanine green is a fluorescent marker allowing the analysis of the lymphatic system. This anatomical work aims at demonstrating, thanks to the use of indocyanine green, whether the realization of a prosthetic breast augmentation by axillary way leads to lesions of the breast lymphatic network and also seeks to show the feasibility of detecting the axillary sentinel node after axillary breast augmentation. MATERIAL AND METHOD: This is an anatomical study. After injection of indocyanine green in the periareolar area, a prosthetic breast augmentation was performed through the axilla. At the end of the procedure, a change in the distribution of indocyanine green in the skin or its abnormal presence was sought: at the level of the skin incision, the prosthetic space, or in contact with the prosthesis itself. The presence of green in these situations was synonymous with a lesion of the lymphatic network. In the opposite case, we considered that the lymphatic system was respected. After sampling, an axillary lymph node we also looked for the presence of indocyanine green at its contact. RESULTS: We performed 22 breast injections. The lymphatic network could be demonstrated in 15 of them. Among these 15 injections, 12 (80%) were in favor of a preservation of the lymphatic network, whereas 3 (20%) evoked a lesion of the lymphatic network. In all subjects (100%), an axillary lymph node was found with the presence of indocyanine green within it. CONCLUSION: Our study is in favor of a preservation of the lymphatic network during a prosthetic breast augmentation by axillary way. Furthermore, with the collection of an axillary lymph node containing the dye from each subject, this work demonstrates the feasibility of axillary sentinel node detection with indocyanine green after axillary breast augmentation. Further work on live subjects and on a larger number of subjects would be necessary to confirm these results.

Re-Irradiation by Stereotactic Radiotherapy of Brain Metastases in the Case of Local Recurrence.

PURPOSE: To evaluate the efficacy and safety of a second course of stereotactic radiotherapy (SRT2) treatment for a local recurrence of brain metastases previously treated with SRT (SRT1), using the Hypofractionated Treatment Effects in the Clinic (HyTEC) reporting standards and the European Society for Radiotherapy and Oncology guidelines. METHODS: From December 2014 to May 2021, 32 patients with 34 brain metastases received salvage SRT2 after failed SRT1. A total dose of 21 to 27 Gy in 3 fractions or 30 Gy in 5 fractions was prescribed to the periphery of the PTV (99% of the prescribed dose covering 99% of the PTV). After SRT2, multiparametric MRI, sometimes combined with 18F-DOPA PET-CT, was performed every 3 months to determine local control (LC) and radionecrosis (RN). RESULTS: After a median follow-up of 12 months (range: 1-37 months), the crude LC and RN rates were 68% and 12%, respectively, and the median overall survival was 25 months. In a multivariate analysis, the performance of surgery was predictive of a significantly better LC (p = 0.002) and survival benefit (p = 0.04). The volume of a normal brain receiving 5 Gy during SRT2 (p = 0.04), a dose delivered to the PTV in SRT1 (p = 0.003), and concomitant systemic therapy (p = 0.04) were associated with an increased risk of RN. CONCLUSION: SRT2 is an effective approach for the local recurrence of BM after initial SRT treatment and is a potential salvage therapy option for well-selected people with a good performance status. Surgery was associated with a higher LC.

Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study.

BACKGROUND AND OBJECTIVES: Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited. METHODS: PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected. RESULTS: Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance. DISCUSSION: Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

Feasibility of the abductor pollicis longus hemitendon transfer for thumb opposition: An anatomical study.

INTRODUCTION: The abductor pollicis longus (APL) presents two muscle bellies and multiple accessory tendons available for transfer, amongst these an accessory tendon inserting on the thenar aponeurosis (APLTh). Edgerton described an opponensplasty using the whole APL tendon, but its results were limited due to the short size of the donor tendon. HYPOTHESIS: The purpose of this study is to assess the feasibility of transferring the APLTh for thumb opposition. MATERIAL AND METHODS: Eleven cadaver upper limbs were dissected to assess the presence of the two heads of the APL as well as their main and accessory tendon insertions. The accessory tendon of the APL inserting on the thenar aponeurosis (APLTh) was harvested with a slip of the thenar aponeurosis. The length of the transplant, the number of tendon slips and their location, as well as pre and postoperative radial and palmar abduction provided by the APL were assessed. RESULTS: The APL was present in all cadavers whereas its insertion on the thenar aponeurosis was absent in 18% of the cases. When the APLTh was present and could be used for opponensplasty, the mean gain in palmar abduction was 16 degrees, and the mean loss in radial abduction was 21 degrees. DISCUSSION: Although the experiments revealed a variability in APL anatomy, when present, the APLTh represents a suitable donor for the restoration of thumb opposition. In some cases of high median nerve palsies, thumb opposition can't be restored using median innervated muscles. In these cases, when the APLTh is present, it can be used to restore thumb opposition without functional loss. LEVEL OF EVIDENCE: IV; anatomical feasibility study.

Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study.

BACKGROUND: Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described. METHODS: We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression. RESULTS: In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions. CONCLUSION: In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.

Characteristics, Patterns of Care and Predictive Geriatric Factors in Elderly Patients Treated for High-Grade IDH-Mutant Gliomas: A French POLA Network Study.

Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (<70 years) and of elderly patients IDHwt HGG. Geriatric features were collected. Results: Out of 1433 HGG patients included, 119 (8.3%) were ≥70 years. Among them, 39 presented with IDHm HGG. The main characteristics of elderly IDHm HGG were different from those of elderly IDHwt HGG but similar to those of younger IDHm HGG. In contrast, their therapeutic management was different from those of younger IDHm HGG with less frequent gross total resection and radiotherapy. The median progression-free survival (PFS) and overall survival (OS) were longer for elderly patients IDHm HGG (29.3 months and 62.1 months) than elderly patients IDHwt HGG (8.3 months and 13.3 months) but shorter than those of younger patients IDHm HGG (69.1 months and not reached). Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, body mass index, and autonomy. Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, and body mass index, and autonomy. Conclusion: the outcome of IDHm HGG in elderly patients is better than that of IDHwt HGG. Geriatric assessment may be particularly important to optimally manage these patients.

Detection of NTRK fusions in glioblastoma: fluorescent in situ hybridisation is more useful than pan-TRK immunohistochemistry as a screening tool prior to RNA sequencing.

Glioblastomas are frequent malignant brain tumours with a very poor prognosis and a need for new and efficient therapeutic strategies. With the approval of anti-TRK targeted therapies to treat patients with advanced NTRK-rearranged cancers, independent of the type of cancer, potential new treatment opportunities are available for the 0.5-5% of patients with NTRK-rearranged glioblastomas. Identification of these rare NTRK-rearranged glioblastomas requires efficient diagnostic tools and strategies which are evaluated in this study. We compared the results of NTRK1, NTRK2 and NTRK3 fluorescent in situ hybridisation (FISH) assays to those of pan-TRK immunohistochemistry (IHC) using two EPR17341 and A7H6R clones in a set of 196 patients with glioblastomas. Cases with at least 15% of positive nuclei using FISH analyses were further analysed using RNA sequencing. Above the 15% threshold, seven positive glioblastomas (3.57%) were identified by FISH assays (4 NTRK1, 3 NTRK2, no NTRK3). NTRK rearrangements were confirmed by RNA sequencing analyses in four cases [1 LMNA-NTRK1, 1 PRKAR2A-NTRK2, 1 SPECC1L-NTRK2 and 1 NACC2-NTRK2 fusions, i.e., 4/196 (2%) of NTRK-rearranged tumours in our series] but no rearrangement was detected in three samples with less than 30% of positive tumour nuclei as determined by NTRK1 FISH. Pan-TRK immunostaining showed major discrepancies when using either the EPR17341 or the A7H6R clones for the following criteria: main intensity, H-Score based scoring and homogeneity/heterogeneity of staining (Kappa values <0.2). This led to defining adequate criteria to identify NTRK-rearranged gliomas exhibiting strong and diffuse immunostaining contrasting to the variable and heterogeneous staining in non-NTRK-rearranged gliomas (p<0.0001). As assessing NTRK rearrangements has become crucial for glioma therapy, FISH seems to be a valuable tool to maximise access to TRK testing in patients with glioblastomas. In contrast to other cancers, pan-TRK IHC appears of limited interest in this field because there is no 'on/off' IHC positivity criterion to distinguish between NTRK-rearranged and non-NTRK-rearranged gliomas. RNA sequencing analyses are necessary in FISH positive cases with less than 30% positive nuclei, to avoid false positivity when scoring is close to the detection threshold.

Relationships between executive functioning and health-related quality of life in adult survivors of brain tumor and matched healthy controls.

INTRODUCTION: Few studies have considered health-related quality of life (HRQOL) as a primary outcome measure in adult survivors of primary brain tumor (PBT), and fewer still have studied the cognitive factors that may influence it. Research suggests that executive functions (EFs) are associated with HRQOL, but there is scant evidence to support this. The present study was conducted to (1) extend prior findings about HRQOL limitations in a sample of stable, long-term adult survivors of PBT, (2) investigate the associations between objective/reported EFs and HRQOL, and (3) identify the EFs that contribute most to HRQOL. METHOD: We recruited 40 survivors of PBT (> 2 years post-treatment) and 40 matched healthy controls. Participants completed an objective EF assessment (inhibition, working memory, shifting, and rule detection) and two self-report questionnaires probing EFs (Behavior Rating Inventory of Executive Function-Adult) and HRQOL (Medical Outcomes Study Short-Form 36). Participants' relatives completed observer-rated versions of these questionnaires. RESULTS: Patients' objective EF performances were relatively intact. However, patients and caregivers reported significantly more problems than healthy controls and their relatives, for both EFs and HRQOL. There were only negligible links between objective EFs and HRQOL, whereas numerous associations were found between reported EFs and HRQOL components. ANCOVA models revealed that specific reported EF processes contributed to both the physical and mental components of HRQOL, regardless of group. CONCLUSIONS: From a clinical point of view, this study demonstrates that even several years after end of treatment, adult PBT survivors experience substantial problems across different HRQOL domains. HRQOL assessment should therefore be part of the long-term follow-up of PBT survivors, and clinicians should consider EF limitations when designing appropriate survivorship care plans. These findings indicate that cognitive interventions targeting EFs could improve HRQOL.

Patient-reported functional executive challenges and caregiver confirmation in adult brain tumor survivors.

PURPOSE: The main objective of this study was to provide further information concerning the validity of patient-reported executive function (EF) in survivors of primary brain tumor (PBT) compared with a report provided by each patient's caregiver. METHODS: Forty survivors of PBT, 40 non-cancer controls and their proxies completed an assessment of functional executive disorders (e.g., planning, inhibition, shifting, action initiation). Comparisons of self and informant EF reports were examined, for both patients and non-cancer controls. The extent of the concordance between patients' reports and their caregivers' reports was also determined. RESULTS: PBT survivors and their caregivers reported more problems related to EF in contrast with the non-cancer comparison group (significant differences). There was a high level of agreement between patients' and caregivers' ratings within the patient group. CONCLUSIONS: This study provides evidence suggesting that at an average of 3.67 (SD = 2.31) years following treatment for a PBT, EF difficulties are reported by patients and their caregivers. This study establishes a consistency between what is reported by survivors and what is reported by those who frequently interact with them. Further research investigating the link between these ratings and quality of life as well as other functions is encouraged. IMPLICATIONS FOR CANCER SURVIVORS: This study's results demonstrate the importance of listening to PBT survivors' perception of EF difficulties. While not confirmed by neuropsychological evaluations, the functional executive challenges reported by these survivors' close relatives reflect what PBT survivors themselves report. Specialists should pay close attention to these difficulties to guarantee optimal post-cancer care.