scholarly journals Atypical anaplastic astrocytoma with unique molecular features and diffuse leptomeningeal spread in a child with long-term survival

2019 ◽  
Vol 12 (2) ◽  
pp. e228153 ◽  
Author(s):  
Yasmin Aghajan ◽  
Denise M Malicki ◽  
Michael L Levy ◽  
John Ross Crawford
Keyword(s):  
Anaplastic Astrocytoma ◽  
Histological Grade ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Term Survival ◽  
Craniospinal Radiation ◽  
Molecular Features ◽  
Central Nervous System Tumours ◽  
Gene Panel Sequencing

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%–12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

PATH-08. PROGNOSTIC IMPLICATIONS FROM LONG-TERM SURVIVORS (LTS) OF GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi116-vi116
Author(s):  
Nicole Briceno ◽  
Zied Abdullaev ◽  
Elizabeth Vera ◽  
Anna Choi ◽  
Alexa Christ ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Subtotal Resection ◽  
Specific Gene ◽  
Tumor Biopsy ◽  
Term Survival ◽  
Prognostic Features ◽  
Molecular Features ◽  
Mgmt Promoter ◽  
Long Term Survivors

Abstract Glioblastoma (GBM) is the most aggressive primary brain malignancy with < 45% living a year beyond diagnosis which drops to 7% at five years. However, there have been reports of long-term survivors (LTS) living three to ten years beyond diagnosis. Few studies have reported on molecular factors in tumors from LTS cohorts. We identified GBM (IDH1/2 wildtype) patients living at least 3 years post diagnosis (N=25), including 16 with pre-treatment tumor tissue, from our Natural History Study. Available pre- or post-treatment tumors were analyzed with targeted panel sequencing and methylation analysis for classification, MGMT promoter status and copy number changes. Classical clinical prognostic features such as limited resection or older age did not preclude long-term survival as patients with tumor biopsy (n=1) or subtotal resection (n= 5) and patients > 60 were included in the LTS cohort. Furthermore, tumors with molecular features typically associated with poor prognosis were also in this GBM LTS group. MGMT promoter was unmethylated in 17% of tumors; EGFRvIII mutation in 13%, EGFR amplification in 33%, CDKN2A homozygous loss in 30% and complete chromosome 7 gain with 10 loss in 55%. Additionally, the methylation classifier found a higher-than-expected incidence of mesenchymal tumors (29%) and RTK II (57%). Tumors had a higher percent of TP53 mutations (44%) but lower pTERT (76%) compared to TCGA. These data suggest an individual patient’s prognosis cannot easily be predetermined based on classical clinical and molecular data. This underscores the need for further analyses to discover additional factors leading to their unexpected, prolonged survival and elucidate the role of factors typically associated with poor prognosis. Future work will include RNA-sequencing and germline whole genome sequencing to determine tumor specific gene expression and identify any possible genomic alterations that confer improved survival.

scholarly journals Up-to-date monitoring of childhood cancer long-term survival in Europe: central nervous system tumours

2007 ◽  
Vol 18 (10) ◽  
pp. 1734-1742 ◽  
Author(s):  
V. Arndt ◽  
P. Kaatsch ◽  
E. Steliarova-Foucher ◽  
R. Peris-Bonet ◽  
H. Brenner
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Childhood Cancer ◽  
Term Survival ◽  
Long Term Survival ◽  
Central Nervous System Tumours

scholarly journals Actual Long-Term Survival After Resection of Stage III Soft Tissue Sarcoma

2020 ◽  
Author(s):  
Do Weon Lee ◽  
Han-Soo Kim ◽  
Ilkyu Han
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Size ◽  
Poor Prognosis ◽  
Histological Grade ◽  
Stage Iii ◽  
Term Survival ◽  
Long Term Survival ◽  
Long Term Survivors

Abstract Background: Actuarial survival based on the Kaplan–Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS.Methods: We retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years.Results: Multivariate logistic regression analyses showed that a tumor size <10 cm [odds ratio (OR) 3.95, p = 0.047], histological grade of 2 (OR 8.12, p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25, p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size >10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival.Conclusions: Actual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that resection should be offered for a chance of long-term survival in these patients.

Pathology of Spinal Ependymomas

Neurosurgery ◽  
2013 ◽  
Vol 73 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Phiroz E. Tarapore ◽  
Peter Modera ◽  
Agne Naujokas ◽  
Michael C. Oh ◽  
Beejal Amin ◽  
...  
Keyword(s):  
Adjuvant Radiotherapy ◽  
Histological Grade ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
World Health ◽  
Subtotal Resection ◽  
Who Grade ◽  
Grade Ii ◽  
Health Organization ◽  
Grade Iii

AbstractBACKGROUND:Ependymomas constitute approximately 40% of primary intraspinal tumors. Current World Health Organization (WHO) grading may not correlate with observed progression-free survival (PFS).OBJECTIVE:This retrospective study of prospectively collected data examines whether PFS is influenced by the histological grade or by the extent of resection. It also analyzes the usage and effectiveness of postoperative adjuvant radiotherapy.METHODS:We reviewed 134 consecutive patients with ependymomas of all grades. Pathology slides were re-reviewed and the histological grades were confirmed by a single neuropathologist. Postoperative residual or recurrence was evaluated with follow-up magnetic resonance imaging.RESULTS:There were 85 male and 49 female patients, ranging from 10 to 79 (median 41) years of age. Thirty patients had WHO grade I tumors, 101 had grade II tumors, and 3 had grade III tumors. Kaplan-Meier analysis of PFS demonstrated a mean duration of 6 years for grade I, 14.9 years for grade II, and 3.7 years for grade III (P &lt; .001). In grade II ependymomas, mean PFS was 11.2 years with subtotal resection and 17.8 years with gross total resection (P &lt; .01). PFS of patients who underwent subtotal resection was not significantly changed by adjuvant radiotherapy (P &lt; .36).CONCLUSION:Patients with grade II ependymoma have significantly longer PFS than patients with grade I ependymoma. The extent of resection did not affect PFS in grade I ependymoma but it did in grade II. Contrary to its higher grade, WHO grade II ependymoma carries a better prognosis than WHO grade I ependymoma.

scholarly journals Actual long-term survival after resection of stage III soft tissue sarcoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Do Weon Lee ◽  
Han-Soo Kim ◽  
Ilkyu Han
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Size ◽  
Poor Prognosis ◽  
Histological Grade ◽  
Stage Iii ◽  
Term Survival ◽  
Long Term Survival ◽  
Long Term Survivors

Abstract Background Actuarial survival based on the Kaplan–Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS. Methods We retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years. Results Multivariate logistic regression analyses showed that a tumor size < 10 cm [odds ratio (OR) 3.95, p = 0.047], histological grade of 2 (OR 8.12, p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25, p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival. Conclusions Actual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.

scholarly journals A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Sherise D Ferguson ◽  
Tiffany R Hodges ◽  
Nazanin K Majd ◽  
Kristin Alfaro-Munoz ◽  
Wajd N Al-Holou ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Trial Participation ◽  
Karnofsky Performance Scale ◽  
Term Survival ◽  
Long Term Survival ◽  
Molecular Features

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. Methods A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. Results Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden (P = .0055) and PTEN mutations (P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival (P &lt; .0001). Clinical factors significantly associated with GBM survival included age (P &lt; .0001), preoperative Karnofsky Performance Scale score (P = .0001), sex (P = .0164), and clinical trial participation (P &lt; .0001). Higher preoperative T1-enhancing volume (P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival (P = .0022). Conclusions Our newly devised long-term survival-predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials.

scholarly journals Patient-derived zebrafish xenograft models reveal ferroptosis as a fatal and druggable weakness in metastatic uveal melanoma

2021 ◽  
Author(s):  
Arwin Groenewoud ◽  
Jie Yin ◽  
Maria Chiara Gelmi ◽  
Samar Alsafadi ◽  
Fariba Nemati ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Drug Sensitivity ◽  
High Sensitivity ◽  
Term Survival ◽  
Molecular Features ◽  
Metastatic Lesions ◽  
Pdx Model ◽  
Xenograft Models

Uveal melanoma (UM) is the most common intraocular melanoma, derived from transformed melanocytes of the uvea. Although treatment of primary UM is usually successful, there is a high risk (up to 50%) of liver metastasis with negligible long-term survival. There are currently no reproducible patient-derived animal models that faithfully recapitulate the latter stages of metastatic dissemination of UM, hindering the discovery of curative treatments. To overcome this problem and to accelerate the development of new metastatic UM treatments, we developed a patient-derived zebrafish xenograft (zf-PDX) model, using spheroid cultures generated from metastatic and primary UM tissues. Engrafted UM cells derived from these spheroid cultures give rise to metastatic lesions and recapitulate the molecular features of UMs and their potential drug sensitivity. Importantly, harnessing this versatile model, we reveal a high sensitivity of circulating UM cells to ferroptosis induction in vivo by Erastin and RSL3. Our findings are further corroborated by supportive analysis of patient data implicating ferroptosis as a new, and druggable, target for the treatment of metastatic UM patients, specifically in those with BAP1 loss in the tumor.

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