Does location matter? Characterisation of the anatomic locations, molecular profiles, and clinical features of gliomas

Background. Neuroanatomic locations of gliomas may influence clinical presentations, molecular profiles, and patients’ prognoses. Methods. We investigated our institutional cancer registry to include patients with glioma over a 10-year period. Statistical tests were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. Survival analysis methods were then used to assess associations between location and overall survival in the full cohort, as well as in relevant subgroups. Results. 182 gliomas were identified. Of the tumours confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and seven occipital tumours (3.8%) identified. Tumours affecting the temporal lobe were associated with reduced overall survival when compared to all other tumours (11 months vs. 13 months, log-rank p = 0.0068). In subgroup analyses, this result was significant for males [HR (95%CI) 2.05 (1.30, 3.24), p = 0.002], but not for females [HR (95%CI) 1.12 (0.65, 1.93), p = 0.691]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in six frontal, two temporal, one thalamic, and one multifocal tumour. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, nine of which were frontal lobe tumours. MGMT methylation was assessed in 45 cases; 7/14 frontal tumours and 6/13 temporal tumours were methylated. Conclusion. Our results support the hypothesis that the anatomical locations of gliomas influence patients’ clinical courses. Temporal lobe tumours were associated with poorer survival, though this association appeared to be driven by these patients’ more aggressive tumour profiles and higher risk baseline demographics. Independently, female patients who had temporal lobe tumours fared better than males. Molecular analysis was limited by the low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas. Importance of this study. The specific neuroanatomic location of tumours in the brain is thought to be predictive of treatment options and overall prognosis. Despite evidence for the clinical significance of this information, there is relatively little information available regarding the incidence and prevalence of tumours in the different anatomical regions of the brain. This study has more fully characterised tumour prevalence in different regions of the brain. Additionally, we have analysed how this information may affect tumours’ molecular characteristics, treatment options offered to patients, and patients’ overall survival. This information will be informative both in the clinical setting and in directing future research

Prognostic Significance of Growth Kinetics in Newly Diagnosed Glioblastomas Revealed by Combining Serial Imaging with a Novel Biomathematical Model

Glioblastomas (GBMs) are the most aggressive primary brain tumors characterized by their rapid proliferation and diffuse infiltration of the brain tissue. Survival patterns in patients with GBM have been associated with a number of clinico-pathologic factors, including age and neurological status, yet a significant quantitative link to in vivo growth kinetics of each glioma has remained elusive. Exploiting a recently developed tool for quantifying glioma net proliferation and invasion rates in individual patients using routinely available magnetic resonance images (MRIs), we propose to link these patient-specific kinetic rates of biological aggressiveness to prognostic significance. Using our biologically-based mathematical model for glioma growth and invasion, examination of serial pre-treatment MRIs of 32 GBM patients allowed quantification of these rates for each patient’s tumor. Survival analyses revealed that even when controlling for standard clinical parameters (e.g., age, KPS) these model-defined parameters quantifying biologically aggressiveness (net proliferation and invasion rates) were significantly associated with prognosis. One hypothesis generated was that the ratio of the actual survival time after whatever therapies were employed to the duration of survival predicted (by the model) without any therapy would provide a “Therapeutic Response Index” (TRI) of the overall effectiveness of the therapies. The TRI may provided important information, not otherwise available, as to the effectiveness of the treatments in individual patients. To our knowledge, this is the first report indicating that dynamic insight from routinely obtained pre-treatment imaging may be quantitatively useful in characterizing survival of individual patients with GBM. Such a hybrid tool bridging mathematical modeling and clinical imaging may allow for statifying patients for clinical studies relative to their pretreatment biological aggressiveness

Patient-Specific Metrics of Invasiveness Reveal Significant Prognostic Benefit of Resection in a Predictable Subset of Gliomas

Object Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas. Methods In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness. Results We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors). Conclusions These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection

The State of Neuro-Oncology During the COVID-19 Pandemic: A Worldwide Assessment

To assess the impact of the pandemic on the field, we performed an international web-based survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents from April 24 through May 17. Of 582 respondents, 258 (45%) were in the US, and 314 (55%) were international. 80.4% were affiliated with academic institutions. 94% respondents reported changes in clinical practice; 95% reported conversion to telemedicine for at least some appointments. However, almost 10% practitioners felt the need to see patients in person specifically because of billing concerns and perceived institutional pressure. Over 50% believed neuro-oncology patients were at increased risk of contracting COVID-19. 67% practitioners suspended enrollment for at least one clinical trial: 53% suspended phase II and 62% suspended phase III trial enrollment. 71% clinicians feared for their or their families’ safety, specifically because of their clinical duties. 20% percent said they did not have enough PPE to work safely; about the same percentage were unhappy with their institutions’ response to the pandemic. 43% believed the pandemic would negatively affect their academic career, and 52% fellowship program directors were worried about losing funding for their training programs. While 69% respondents reported increased stress, 44% were offered no psychosocial support. 37% had their salary reduced. 36% researchers had to temporarily close their laboratories. In contrast, the pandemic created positive changes in perceived patient and family satisfaction, quality of communication, and use of technology to deliver care and interactions with other practitioners. CONCLUSIONS: The pandemic has altered standard treatment schedules and limited investigational treatment options for patients. In some cases, clinicians felt institutional pressure to continue conducting billable in-person visits when telemedicine visits would have sufficed. A lack of institutional support created anxiety among clinicians and researchers. We make specific recommendations to guide clinical and scientific infrastructure moving forward

Supportive care for patients with brain metastases from lung cancer.

Lung cancer is the most common cause of intracranial metastases (ICM). Metastases in the brain can result in a broad range of uncomfortable symptoms and significant morbidity secondary to neurological disability. Treatment options can range from surgical resection of solitary metastases to radiotherapy and more recently systemic targeted therapies and immunotherapy. Patient survival continues to improve with innovations made in treatments for this condition, but each of these treatments carry their own adverse effects that must be appropriately managed. These patients can benefit greatly from multidisciplinary care throughout the course of their disease. Clinicians involved in their care must be equipped with the ability to communicate skillfully and compassionately and set expectations for the road ahead, including symptoms, treatment plans, and prognosis. Involvement of a palliative care team can be very helpful, especially for patients who are nearing the terminal stages of the disease. Palliative care skills may be invaluable in the management of symptoms and can ease suffering for patients and their caregivers, thus allowing for maximum quality of life for as long as possible. End of life may bring its own complications and challenges; and opinion of an experienced and knowledgeable clinician can alleviate the pain and distress of the patient and also bring peace to the caregivers and loved ones