Primary Spinal Cord Astrocytomas Research Articles

Independent Prognostic Factors and Nomogram Prediction of Cancer-Specific Survival in Postoperative Patients With Spinal Cord Astrocytoma.

Retrospective cohort study. Spinal cord astrocytoma (SCA) is a rare central nervous system malignancy that typically requires early surgical intervention. However, the substantial frequency of relapse and bad outcomes limit the surgical advantage for patients. Herein, we aimed to determine the independent prognostic factors of cancer-specific survival (CSS) in post-surgical patients with primary SCA and to develop a new method to estimate the chances of CSS in these patients at 3-, 5- and 10-year. A total of 364 postoperative patients with SCA were recruited from the Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validation sets. Univariate and multivariate Cox regression assessments were used to identify independent prognostic indicators. Second, a nomogram was established by integrating these indicators to estimate 3-, 5-, and 10-year CSS in patients with SCA who underwent surgery. Subsequently, the discriminatory power and predictive performance of the nomogram were assessed using the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Finally, a mortality risk stratification system was generated. Age, tumor stage, histological type, and radiotherapy were recognized as potential predictive indicators of CSS for postoperative patients with SCA. The ROC curve and DCA indicate that the nomogram has good accuracy and high clinical utility. Furthermore, the mortality risk stratification system efficiently divides patients into 3 risk subgroups. The nomogram could accurately anticipate the 3-, 5-, and 10-year percentages of CSS in postoperative patients with SCA. It could assist clinicians with personalized medical counseling, risk stratification management, and clinical decision-making, improving the clinical outcomes of these patients.

Detection of Glioma-Related Hotspot Mutations Through Sequencing of Cerebrospinal Fluid (CSF)-Derived Circulating Tumor DNA: A Pilot Study on CSF-Based Liquid Biopsy for Primary Spinal Cord Astrocytoma.

Although cerebrospinal fluid (CSF)-based liquid biopsy was proved to be practical in molecular analysis of intracranial gliomas, liquid biopsy of primary intramedullary astrocytoma was rarely reported. Given the distinct genomic profiles between primary intramedullary glioma and intracranial astrocytoma, whether the feasibility of CSF-based molecular analysis of intracranial gliomas can be replicated in primary spinal cord astrocytoma needs to be investigated. The aim of this pilot study is to evaluate the feasibility of molecular analysis of primary intramedullary astrocytoma through sequencing CSF-derived circulating tumor DNA (ctDNA). Two grade IV diffuse midline gliomas, 1 grade II, and 1 grade I astrocytoma were included. Intraoperative collection of peripheral blood and CSF samples was conducted, along with postoperative collection of matched tumor tissues. A panel covering the 1,021 most common driver genes of solid tumors was used for targeted DNA sequencing. CSF-derived ctDNA was detected in 3 CSF samples (2 grade IV diffuse midline gliomas and 1 grade I astrocytoma), 5 mutations were found in both tumor tissues and CSF samples, while 11 mutations and 20 mutations were detected exclusively in tumor tissues and CSF samples, respectively. Importantly, hotspot genetic alterations, including H3F3A K28M, TP53, and ATRX, were identified in CSF and the average mutant allele frequency was often higher in CSF than in tumor tissues. CSF-based liquid biopsy showed potential feasibility for molecular analysis of primary intramedullary astrocytoma through sequencing of ctDNA. This approach may assist in diagnosis and prognostic evaluation of this rare spinal cord tumor.

Mutational landscape of primary spinal cord astrocytoma.

Primary spinal cord astrocytoma (SCA) is a rare disease. Knowledge about the molecular profiles of SCAs mostly comes from intracranial glioma; the pattern of genetic alterations of SCAs is not well understood. Herein, we describe genome-sequencing analyses of primary SCAs, aiming to characterize the mutational landscape of primary SCAs. We utilized whole exome sequencing (WES) to analyze somatic nucleotide variants (SNVs) and copy number variants (CNVs) among 51 primary SCAs. Driver genes were searched using four algorithms. GISTIC2 was used to detect significant CNVs. Additionally, recurrently mutated pathways were also summarized. A total of 12 driver genes were identified. Of those, H3F3A (47.1%), TP53 (29.4%), NF1 (19.6%), ATRX (17.6%), and PPM1D (17.6%) were the most frequently mutated genes. Furthermore, three novel driver genes seldom reported in glioma were identified: HNRNPC, SYNE1, and RBM10. Several germline mutations, including three variants (SLC16A8 rs2235573, LMF1 rs3751667, FAM20C rs774848096) that were associated with risk of brain glioma, were frequently observed in SCAs. Moreover, 12q14.1 (13.7%) encompassing the oncogene CDK4 was recurrently amplified and negatively affected patient prognosis. Besides frequently mutated RTK/RAS pathway and PI3K pathway, the cell cycle pathway controlling the phosphorylation of retinoblastoma protein (RB) was mutated in 39.2% of patients. Overall, a considerable degree of the somatic mutation landscape is shared between SCAs and brainstem glioma. Our work provides a key insight into the molecular profiling of primary SCAs, which might represent candidate drug targets and complement the molecular atlas of glioma. © 2023 The Pathological Society of Great Britain and Ireland.

Deep learning based on preoperative magnetic resonance (MR) images improves the predictive power of survival models in primary spinal cord astrocytomas.

Prognostic models for spinal cord astrocytoma patients are lacking due to the low incidence of the disease. Here, we aim to develop a fully automated deep learning (DL) pipeline for stratified overall survival (OS) prediction based on preoperative MR images. A total of 587 patients diagnosed with intramedullary tumors were retrospectively enrolled in our hospital to develop an automated pipeline for tumor segmentation and OS prediction. The automated pipeline included a T2WI-based tumor segmentation model and 3 cascaded binary OS prediction models (1-year, 3-year, and 5-year models). For the tumor segmentation model, 439 cases of intramedullary tumors were used to model training and testing using a transfer learning strategy. A total of 138 patients diagnosed with astrocytomas were included to train and test the OS prediction models via 10 × 10-fold cross-validation using CNNs. The dice of the tumor segmentation model with the test set was 0.852. The results indicated that the best input of OS prediction models was a combination of T2W and T1C images and the tumor mask. The 1-year, 3-year, and 5-year automated OS prediction models achieved accuracies of 86.0%, 84.0%, and 88.0% and AUCs of 0.881 (95% CI 0.839-0.918), 0.862 (95% CI 0.827-0.901), and 0.905 (95% CI 0.867-0.942), respectively. The automated DL pipeline achieved 4-class OS prediction (<1 year, 1-3 years, 3-5 years, and >5 years) with 75.3% accuracy. We proposed an automated DL pipeline for segmenting spinal cord astrocytomas and stratifying OS based on preoperative MR images.

Primary Spinal Cord Astrocytomas: Two-Center Clinical Experience of Low- and High-Grade Lesions

Primary spinal cord astrocytomas are rare, fatal, and poorly studied. This study included a 2-center, retrospective analysis of primary spinal cord astrocytoma patients from 1997 to 2020. Patients with drop metastases or without at least one follow-up were excluded. Seven World Health Organization grade I, 6 grade II, 7 grade III, and 4 grade IV astrocytoma patients were included. Older patients had higher grades (median 20years in grade I vs. 36.5 in grade IV). The median follow-up was 15months. Thirteen patients were discharged to rehabilitation. Eight patients demonstrated radiographic progression. Adjuvant therapy was utilized more in higher grades (5 of 13 grades III vs. all 11 grades IIIIV). Six patients died (1 death in grades III vs. 5 in grades IIIIV). Ten patients had worsened symptoms at the last follow-up. The median progression-free survival in grade I, II, III, and IV tumors was 116, 36, 8, and 8.5months, respectively. The median overall survival in grade I, II, III, and IV tumors was 142, 69, 19, and 12months, respectively. Thrombotic complications occurred in 2 patients, one with isocitrate dehydrogenasewild type glioblastoma. Outcomes worsen with higher grades and lead to difficult postoperative periods. Clinicians should be vigilant for thromboembolic complications. Further research is needed to understand these rare tumors.

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review.

Simple SummaryAdult primary spinal cord astrocytoma (SCA) is a very rare disease, with no standardized consensus about its therapy. We focus on treatment efficacy based on systematic review: only 18 papers were eligible for the analysis, including 285 patients. No clinical trials results were available. Not enough data were extracted to determine a univocal treatment plan for SCA. Given the rarity of these diseases, a collaboration among institutions is mandatory to establish a standard for study conduction (homogenous inclusion criteria and method of analysis), to perform homogenous studies and define future evidence-based recommendation. Contextually, multicentric clinical trials with molecular investigations are strongly advised to better manage SCA and unveil their biology.The issue: Gliomas are primary tumors arising from supporting cells of the central nervous system (CNS), usually in the brain. The 2021 World Health Organization (WHO) classifies gliomas as adult-type diffuse gliomas or circumscribed astrocytic gliomas depending on their histology and molecular features. Spinal astrocytic gliomas are very rare, and nowadays no standard of therapy is available. Treatment options are limited: surgery is often not radical, and adjuvant therapies include mostly radiotherapy (RT) or systemic chemotherapy (CHT). There is lack of knowledge about the efficacy and safety of therapies and their multidisciplinary approaches. The aim of the review: A systematic review of the literature from January 2000 to June 2021 was performed, including both clinical trials and observational studies on histological adult primary spinal cord astrocytomas (SCA), with a minimum follow-up of 6 months and reporting the overall survival, progression-free survival or clinical neurological outcome after any therapeutic approach (surgery, RT or CHT). What are the main findings? A total of 1197 citations were identified by the Medline search and additional records; based on our inclusion criteria, 18 studies were included with a total of 285 adult patients. We documented the lack of any clinical trial. What are the conclusions? The available literature data are limited to series/retrospective studies, including heterogeneous patients, i.e., astrocytoma as well as ependymoma or pediatric/adult age, with scanty data on the outcomes of interest. No clinical trials have been run. Due to the rarity of this disease, multicentric clinical trials with molecular investigations are mandatory to better manage such a rare disease.

Prognostic factors and nomogram prediction of survival probability in primary spinal cord astrocytoma patients.

Knowledge on the management of spinal cord astrocytoma (SCA) remains scarce. Here, the authors constructed and validated a predictive nomogram, often used for individualized prognosis and evaluations, to estimate cancer-specific survival (CSS) and overall survival (OS) for patients with SCA. Epidemiological characteristics were compared between low-grade SCA (LGSCA) and high-grade SCA (HGSCA) patients from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for CSS and OS were determined using univariate and multivariate analyses and Kaplan-Meier curves. A nomogram was developed to individually predict the 3-, 5-, and 10-year CSS and OS rates. The clinical usefulness of the nomogram was assessed using calibration plots, the concordance index (C-index), and time-dependent receiver operating characteristic curves. A total of 468 LGSCA and 165 HGSCA patients were eligible for inclusion. LGSCA and HGSCA patients demonstrated differences in age, tumor extension, insurance status, adjuvant treatment, and survival. Multivariate analysis demonstrated that in the LGSCA group, tumor extension, surgery type, and adjuvant therapy were individually associated with CSS. The distance of tumor extension and WHO grade were individually associated with CSS in the HGSCA group. The prognostic variables were further demonstrated using the Kaplan-Meier method, which also suggested that adjuvant treatment provided no advantage to HGSCA patients. A nomogram was constructed, and the C-index for CSS was 0.84 by internal validation (95% CI 0.79-0.90). This research suggests that the distance of tumor extension, type of surgery, and adjuvant therapy are significant risk factors for CSS using multivariate analysis in the LGSCA group. Adjuvant treatment provided no advantages for CSS or OS in patients with HGSCAs. The nomogram may be clinically useful to healthcare providers.

Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas

Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

Primary Spinal Astrocytomas: A Literature Review.

Primary spinal astrocytoma is a subtype of glioma, the most common spinal cord tumor found in the intradural intramedullary compartment. Spinal astrocytomas account for 6-8% of all spinal cord tumors and are primarily low grade (World Health Organization grade I (WHO I) or WHO II). They are seen in both the adult and pediatric population with the most common presenting symptoms being back pain, sensory dysfunction, or motor dysfunction. Magnetic Resonance Imaging (MRI) with and without gadolinium is the imaging of choice, which usually reveals a hypointense T1 weighted and hyperintense T2 weighted lesion with a heterogeneous pattern of contrast enhancement. Further imaging which may aid in surgical planning includes computerized tomography, diffusion tensor imaging, and tractography. Median survival in spinal cord astrocytomas ranges widely. The factors most significantly associated with poor prognosis and shorter median survival are older age at initial diagnosis, higher grade lesion based on histology, and extent of resection. The mainstay of treatment for primary spinal cord astrocytomas is surgical resection, with the goal of preservation of neurologic function, guided by intraoperative neuromonitoring. Adjunctive radiation has been shown beneficial and may increase overall survival. The role of adjunctive chemotherapy is employed, however, its benefit has not been clearly defined. Primary spinal cord astrocytomas are rare and challenging to treat. The gold standard treatment is surgical resection. Second-line treatments include radiation and chemotherapy, although, the optimal regimen for adjunctive therapy has not yet been clearly defined.

Prognostic factors and survival in low grade gliomas of the spinal cord: A population-based analysis from 2006 to 2012

PurposePrimary spinal cord tumors are rare, and evidence-based management of these patients remains a source of controversy. This study used a large cohort of low-grade spinal cord astrocytomas to determine the effectiveness of prognostic factors and survival. MethodsThe Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify patients with WHO grade I-II primary spinal cord astrocytomas from 1973 to 2012; however, patients before 2006 were excluded due to ambiguity diagnosis. Univariate and multivariate Cox proportional hazard models were created to compare survival across covariates and summarized using the Kaplan-Meier method. ResultsA total of 561 patients with low-grade glioma (astrocytoma) were identified. Among these, 15.5% of patients received a gross total resection (GTR), 26.1% subtotal resection (STR), and 46.2% unidentified extent of resection. 59.4% did not receive any radiation therapy at any point of the treatment course, while 40.6% underwent radiation therapy. In our cohort, only patients with GTR demonstrated statistically improved survival (HR: 0.22, P < 0.001). Patients with STR had nearly identical survival compared to patients with no surgery (HR: 0.98), and radiotherapy was associated with increased odds of mortality (HR: 1.47, P < 0.001). Multivariate analysis demonstrated a significant survival benefit among patients with younger age, GTR and absence of radiotherapy. Histologic grade did not statistically impact survival. ConclusionOur study suggests that GTR results in improved survival among patients with low-grade gliomas within the spinal cord. Future, considerable data research efforts will aim to better define the role of radiotherapy and tumor grading in this patient population.

Pediatric spinal cord astrocytomas: a retrospective study of 348 patients from the SEER database.

OBJECTIVE Intramedullary spinal cord tumors comprise 1%-10% of all childhood central nervous system neoplasms, with astrocytomas representing the most common subtype. Due to their rarity and poor prognosis, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of improving outcome. The authors undertook this retrospective study to explore factors that may influence survival in pediatric patients with spinal cord astrocytomas. METHODS Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a prospective cancer registry, the authors retrospectively assessed survival in histologically confirmed, primary spinal cord astrocytomas in patients 21 years of age and younger. Survival was described with Kaplan-Meyer curves, and a multivariate regression analysis was used to assess the association of several variables with survival while controlling for confounding variables. RESULTS This analysis of 348 cases showed that age (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.017), nonwhite race (HR 1.74, 95% CI 1.11-2.74, p = 0.014), high-grade tumor status (HR 14.67, 95% CI 6.69-32.14, p < 0.001), distant or invasive extension of the tumor (HR 2.37, 95% CI 1.02-5.49, p = 0.046), and radiation therapy (HR 3.74, 95% CI 2.18-6.41, p < 0.001) were associated with decreased survival. Partial resection (HR 0.37, 95% CI 0.16-0.83, p = 0.017) and gross-total resection (HR 0.39, 95% CI 0.16-0.95, p = 0.039) were associated with improved survival. CONCLUSIONS Younger age appears to be protective, while high-grade tumors have a much worse prognosis. Early diagnosis and access to surgery appears necessary for improving outcomes, while radiation therapy has an unclear role. There is still much to learn about this disease in the hope of curing children with the misfortune of having one of these rare tumors.

Primary spinal cord astrocytoma presenting as intracranial hypertension: a case report.

Increased intracranial pressure (IICP) is rarely seen in association with primary spinal tumors. We describe a 58-year-old man who was diagnosed with a primary spinal cord astrocytoma, who first presented with hypesthesia, followed by intracranial hypertension, papilledema and blurred vision. On first admission, he presented with hypesthesia but without paraparesis, headache or blurred vision. Spinal MRI showed a relatively well-enhanced solid mass with a cystic portion at the cervico-thoracic level, shown histologically to be a grade I pilocytic astrocytoma. After gross total resection of the tumor, the patient had no significant neurological changes. Nine months later, the patient was admitted with headache, blurred vision and paraparesis. An ophthalmologic examination showed papilledema and lumbar tapping revealed IICP. A spinal MRI showed recurrence of the tumor which was found to be a glioblastoma after reexplorative debulking surgery. After resection, his headaches and blurred vision improved, but his paraparesis did not. These findings show that a primary spinal cord astrocytoma may cause IICP.

Primary spinal cord glioma: a Surveillance, Epidemiology, and End Results database study

To characterize the overall survival (OS) and cause specific survival (CSS), and variables affecting outcome, in patients with primary spinal cord astrocytoma (SCA) and ependymoma (SCE). About 664 patients with SCA and 1,057 patients with SCE were analyzed using the Surveillance, Epidemiology, and End Results database. For grade 1, 2, 3 and 4 SCA, the 5-year OS was 82, 70, 28 and 14%; the 5-year CSS was 89, 77, 36 and 20%. For SCA, lower grade, younger age, and undergoing resection significantly improved OS and CSS; treatment without radiotherapy was favorable for CSS. Smaller tumor size also improved survival. For grade 1, 2, and 3 SCE, the 5-year OS was 92, 97 and 58%; the 5-year CSS was 100, 98 and 64%. For SCE, lower grade, younger age, and undergoing resection significantly improved OS and CSS; treatment without radiotherapy was favorable for OS. Smaller tumor size did not confer a survival benefit. Patients with resected grade 2 spinal cord glioma who did not receive radiotherapy fared well with respect to OS and CSS. For patients with spinal cord glioma, the variables of histology, grade, age and undergoing resection are significant predictors of outcome. Though treatment with radiotherapy was associated with worse outcomes, this may reflect a bias in that patients who underwent radiotherapy were perhaps more likely to have had adverse risk factors. Given the retrospective nature of this study, specific recommendations about which situations warrant radiotherapy cannot be determined.

Postoperative radiotherapy results in primary spinal cord astrocytomas

Background and purpose We retrospectively evaluated the therapeutic outcomes of patients with primary spinal cord astrocytomas treated with conventional radiotherapy at our institute. Patients and methods Between May 1975 and December 1997, 26 patients with histologically proven spinal cord astrocytomas were treated with conventional radiotherapy, and twenty-four eligible patients were evaluated. Median age was 19 years (2–41 years). Fourteen of astrocytomas were grade I, 6 of them grade II and 4 grade III. Ten patients had subtotal excision, and 14 had only biopsy of the primary lesion. Patients were treated with 1–2 Gy daily fractions, and given to a median total dose of 49.5 Gy (range 35–60 Gy) external radiotherapy to primary tumor. Results Median follow-up was 39 months. Seventeen patients died of their disease. Two patients have progression, and 5 patients are followed with stabile disease. Five-year overall survival was 45% and progression free survival was 40%. Among the analyzed factors only gender and age were found to be significant. Conclusions Our results are slightly worse than previous retrospective radiotherapy series in the literature. With new imaging and radiation therapy techniques, radiotherapy may have a role as an adjuvant treatment especially in subtotally resected tumors.

Radiotherapy in primary spinal cord astrocytoma

Radiotherapy in primary spinal cord astrocytoma