Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement ('low grade appearance') - a report of the RANO resect group

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low grade appearance' on imaging (non-CE glioblastoma). We aimed to (I) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (II) delineate outcome differences between glioblastoma patients with and without contrast enhancement. METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between post-operative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement. RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller post-operative tumor volumes were associated with more favourable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had more favourable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables. CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favourable outcome

Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection:A report of the RANO resect group

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.</p

Resection of symptomatic non-small cell lung cancer brain metastasis in the setting of multiple brain metastases

OBJECTIVE Current guidelines primarily suggest resection of brain metastases (BMs) in patients with limited lesions. With a growing number of highly effective local and systemic treatment options, this view may be challenged. The purpose of this study was to evaluate the role of metastasectomy, disregarding BM count, in a comprehensive treatment setting. METHODS In this monocentric retrospective analysis, the authors included patients who underwent resection for at least 1 BM and collected demographic, clinical, and tumor-associated parameters. Prognostic factors for local control and overall survival (OS) were analyzed with the log-rank test and Cox proportional hazards analysis. RESULTS The authors analyzed 216 patients. One hundred twenty-nine (59.7%) patients were diagnosed with a single/ solitary BM, whereas 64 (29.6%) patients had 2-3 BMs and the remaining 23 (10.6%) had more than 3 BMs. With resection of symptomatic BMs, a significant improvement in Karnofsky Performance Scale (KPS) was achieved (p = 70 (p = 0.002 and p = 0.005, respectively), systemic metastases other than BM (p = 0.004), adjuvant radiation therapy (p < 0.001), and adjuvant systemic treatment (p < 0.001) were prognostic factors. In regression analysis, the presence of extracranial metastases (HR 2.30, 95% CI 1.53-3.48, p < 0.001), adjuvant radiation therapy (HR 0.97, 95% CI 0.23-0.86, p = 0.016), and adjuvant systemic treat- ment (HR 0.37, 95% CI 0.25-0.55, p < 0.001) remained as independent factors for survival. CONCLUSIONS Surgery for symptomatic BM from non-small cell lung cancer may be indicated even for patients with multiple lesions in order to alleviate their neurological symptoms and to consequently facilitate further treatment

Clinical variety and prognosis of intracranial arachnoid cysts in children

Arachnoid cysts (AC) occur in different intracranial locations. Management and prognosis depend on the clinical presentation and treatment guidelines do not exist. With this study, we want to demonstrate the clinical variety of arachnoid cysts in children and place a focus on outcome factors in operated cases. This retrospective study of a consecutive single unit series of children, who underwent AC surgery between January 2010 and September 2019, provides demographic, clinical, imaging data, and information about surgical treatment and outcome. Overall, 63 patients (71.4 male) underwent surgery. Mean age was 50 months (0-191). Mean follow-up was 40 months (0-121). Eighty-one percent of patients presented with symptoms/signs of raised ICP. Focal neurological deficits were present in 15.9%, headache in 11.1% of children. Galassi cysts represented the predominant type (30.2%), followed by suprasellar (14.3%), quadrigeminal (12.7%), retrocerebellar, CPA and midline (each 11.1%), and hemispheric cysts (7.9%). Endoscopic and microsurgical fenestrations were performed in 27% and 58.7%, stent or shunt insertion in 6.3%/57.9% of the cases. In 33.3% of the cases one and in 12.7%, a second reintervention became necessary. Reoperation rate was significantly higher in children <1 year (p = 0.003). Cyst volume decreased in 85.7%. Seventy percent of the patients were symptom free, 5% suffered from headache, and 22% from developmental disorders. All focal neurological symptoms resolved. Complication rate and outcome are depending on age and cyst location. Recurrence and revision rates are significantly higher in young infants (p = 0.003). Midline cysts with CCA are associated with developmental disorders

Local treatment options for limited brain metastasis

Background Brain metastases comprising 1-4 lesions that are either operable or do not exceed a volume of about 15 ml when inoperable can be considered limited, especially if extracranial tumor manifestations are stable or can be treated effectively. Therapeutic procedures Resection with postoperative local irradiation, stereotactic radiosurgery and brachytherapy can be applied as sole or combined therapy for the treatment of limited brain metastasis. Adjuvant whole-brain irradiation should no longer be used routinely because of the risk for neurocognitive deficits. Local recurrences and distant brain metastases can be detected early by close magnetic resonance imaging (MRI)-based follow-up and can also be treated locally in most cases. Results Local control rates of 70-80% of the treated metastases at 1 year are achieved with local therapy techniques. Median survival rates are in the range of 10-12 months, with 20-30% of patients living longer than 3 years, and 5-10% living longer than 5 years. After radiosurgery, radiation necrosis may rarely occur and can be diagnosed by MRI follow-up, amino acid positron emission tomography (PET) or stereotactic biopsy. Conclusions Radiosurgery, resection with postoperative focal irradiation and brachytherapy are local procedures that effectively control limited cerebral metastasis, especially when used in combination or repeatedly, and provide prolonged survival to a substantial proportion of patients

Recurrent brain metastases: the role of resection of in a comprehensive multidisciplinary treatment setting

Background Treatment decision for recurrent symptomatic brain metastases (BM) is challenging with scarce data regarding surgical resection. We therefore evaluated the efficacy of surgery for pretreated, recurrent BM in a comprehensive multidisciplinary treatment setting. Methods In a retrospective single center study, patients were analyzed, who underwent surgical resection of recurrent BM between 2007 and 2019. Intracranial event-free survival (EFS) and overall survival (OS) were evaluated by Kaplan-Maier and Cox regression analysis. Results We included 107 patients with different primary tumor entities and individual previous treatment for BM. Primary tumors comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal cancer (10.3%) and other, rare entities (19.6%). The number of previous treatments of BM ranged from one to four; the adjuvant treatment modalities comprised: none, focal or whole brain radiotherapy, brachytherapy and radiosurgery. The median pre-operative Karnofsky Performance Score (KPS) was 70% (range 40-100) and improved to 80% (range 0-100) after surgery. The complication rate was 26.2% and two patients died during the perioperative period. Sixty-seven (62.6%) patients received postoperative local radio-oncologic and/or systemic therapy. Median postoperative EFS and OS were 7.1 (95%CI 5.8-8.2) and 11.1 (95%CI 8.4-13.6) months, respectively. The clinical status (postoperative KPS >= 70 (HR 0.27 95%CI 0.16-0.46; p < 0.001) remained the only independent factor for survival in multivariate analysis. Conclusions Surgical resection of recurrent BM may improve the clinical status and thus OS but is associated with a high complication rate; therefore a very careful patient selection is crucial

Surgical resection of symptomatic brain metastases improves the clinical status and facilitates further treatment

Background Brain metastases (BM) frequently cause focal neurological deficits leading to a reduced Karnofsky performance score (KPS). Since KPS is routinely used to guide the choice of adjuvant therapy, we hypothesized that improving KPS by surgical resection may improve the chance for adjuvant treatment and ultimately result in better survival. We therefore analyzed the course of a large cohort undergoing resection of symptomatic brain metastases in the context of further treatment and clinical outcome. Patients and methods In a bi-centric retrospective analysis we retrieved baseline, clinical, and treatment-related parameters of patients operated on BM between 2010 and 2019. Survival was calculated using Kaplan-Meier estimates; prognostic factors for survival were analyzed by Log-rank test and Cox proportional hazards. Results We included 750 patients with a median age of 61 (19-87) years. The functional status was significantly improved by surgical resection, with a median preoperative (KPS) of 80 (10-100) increasing to 90 (0-100) after surgery (P = 70;P < .0001). The postoperative clinical status, postoperative radiotherapy, systemic treatment, controlled systemic disease and < 4 BM were independent predictors for survival. Conclusion The resection of symptomatic BM may restore clinical status, so enhancing the likelihood of receiving adjuvant treatment, and therefore leading to improved overall survival

Ependymomas in infancy: underlying genetic alterations, histological features, and clinical outcome

Introduction Young age is an adverse prognostic factor in children with ependymomas. Treatment of these infants is challenging since beneficial therapeutic options are limited. As ependymomas are considered a biologically heterogeneous group, we aimed to characterize infant ependymomas with regard to their histological and genetic features. Materials and methods We analyzed 28 ependymomas occurring in children younger than 18 months at diagnosis enrolled into the HIT2000-E protocols with the aim to postpone irradiation until the age of 18 months if possible. All cases underwent neuropathological review, including immunohistochemical characterization. Genome-wide copy number alterations (CNA) were assessed by molecular inversion probe assays, and RELA and YAP1 fusions were detected by RT-PCR and sequencing. Results All infant ependymomas were anaplastic (WHO grade III). Twenty-one (75%) cases were located in the posterior fossa. Gross total resection was accomplished in 12 (57%) of these cases. All posterior fossa tumors showed loss of H3-K27me(3) characteristic of PFA ependymomas. CNA analysis showed a stable genome in all cases with lack of chromosome 1q gain, an adverse prognostic marker in PFA ependymomas of older children. However, after a median follow-up of 5.4 years, 15 (71%) relapsed, and 9 (43%) died. Seven ependymomas (25%) occurred in the supratentorial region. Gross total resection could be achieved in only two of these cases. Four tumors carried C11orf95-RELA fusions, and two cases had typical YAP1-MAMLD1 fusions (one case was not analyzable). The RELA-fused cases did not display CDKN2A loss as an adverse indicator of prognosis in this disease entity. Although three infants (43%) with supratentorial ependymomas relapsed, all patients survived (median follow-up, 8.0 years). Conclusion Infant ependymomas seem to fall into three biological entities, with supratentorial tumors carrying RELA or YAP fusions and PFA posterior fossa ependymomas. The latter showed a poor outcome even though chromosome 1q gain was absent

Novel rapid intraoperative qualitative tumor detection by a residual convolutional neural network using label-free stimulated Raman scattering microscopy

Determining the presence of tumor in biopsies and the decision-making during resections is often dependent on intraoperative rapid frozen-section histopathology. Recently, stimulated Raman scattering microscopy has been introduced to rapidly generate digital hematoxylin-and-eosin-stained-like images (stimulated Raman histology) for intraoperative analysis. To enable intraoperative prediction of tumor presence, we aimed to develop a new deep residual convolutional neural network in an automated pipeline and tested its validity. In a monocentric prospective clinical study with 94 patients undergoing biopsy, brain or spinal tumor resection, Stimulated Raman histology images of intraoperative tissue samples were obtained using a fiber-laser-based stimulated Raman scattering microscope. A residual network was established and trained in ResNetV50 to predict three classes for each image: (1) tumor, (2) non-tumor, and (3) low-quality. The residual network was validated on images obtained in three small random areas within the tissue samples and were blindly independently reviewed by a neuropathologist as ground truth. 402 images derived from 132 tissue samples were analyzed representing the entire spectrum of neurooncological surgery. The automated workflow took in a mean of 240 s per case, and the residual network correctly classified tumor (305/326), non-tumorous tissue (49/67), and low-quality (6/9) images with an inter-rater agreement of 89.6% (kappa = 0.671). An excellent internal consistency was found among the random areas with 90.2% (C alpha = 0.942) accuracy. In conclusion, the novel stimulated Raman histology-based residual network can reliably detect the microscopic presence of tumor and differentiate from non-tumorous brain tissue in resection and biopsy samples within 4 min and may pave a promising way for an alternative rapid intraoperative histopathological decision-making tool

Deep learning assistance increases the detection sensitivity of radiologists for secondary intracranial aneurysms in subarachnoid hemorrhage

Purpose To evaluate whether a deep learning model (DLM) could increase the detection sensitivity of radiologists for intracranial aneurysms on CT angiography (CTA) in aneurysmal subarachnoid hemorrhage (aSAH). Methods Three different DLMs were trained on CTA datasets of 68 aSAH patients with 79 aneurysms with their outputs being combined applying ensemble learning (DLM-Ens). The DLM-Ens was evaluated on an independent test set of 104 aSAH patients with 126 aneuryms (mean volume 129.2 +/- 185.4 mm(3), 13.0% at the posterior circulation), which were determined by two radiologists and one neurosurgeon in consensus using CTA and digital subtraction angiography scans. CTA scans of the test set were then presented to three blinded radiologists (reader 1: 13, reader 2: 4, and reader 3: 3 years of experience in diagnostic neuroradiology), who assessed them individually for aneurysms. Detection sensitivities for aneurysms of the readers with and without the assistance of the DLM were compared. Results In the test set, the detection sensitivity of the DLM-Ens (85.7%) was comparable to the radiologists (reader 1: 91.2%, reader 2: 86.5%, and reader 3: 86.5%; Fleiss kappa of 0.502). DLM-assistance significantly increased the detection sensitivity (reader 1: 97.6%, reader 2: 97.6%,and reader 3: 96.0%; overall P=.024; Fleiss kappa of 0.878), especially for secondary aneurysms (88.2% of the additional aneurysms provided by the DLM). Conclusion Deep learning significantly improved the detection sensitivity of radiologists for aneurysms in aSAH, especially for secondary aneurysms. It therefore represents a valuable adjunct for physicians to establish an accurate diagnosis in order to optimize patient treatment