Pub Date : 2024-04-09eCollection Date: 2024-10-01DOI: 10.1093/noajnl/vdae045
Soichiro Takamiya, Anahita Malvea, Abdullah H Ishaque, Karlo Pedro, Michael G Fehlings
The spinal cord occupies a narrow region and is tightly surrounded by osseous and ligamentous structures; spinal tumors can damage this structure and deprive patients of their ability to independently perform activities of daily living. Hence, imaging is vital for the prompt detection and accurate diagnosis of spinal tumors, as well as determining the optimal treatment and follow-up plan. However, many clinicians may not be familiar with the imaging characteristics of spinal tumors due to their rarity. In addition, spinal surgeons might not fully utilize imaging for the surgical planning and management of spinal tumors because of the complex heterogeneity of these lesions. In the present review, we focus on conventional and advanced spinal tumor imaging techniques. These imaging modalities include computed tomography, positron emission tomography, digital subtraction angiography, conventional and microstructural magnetic resonance imaging, and high-resolution ultrasound. We discuss the advantages and disadvantages of conventional and emerging imaging modalities, followed by an examination of cutting-edge medical technology to complement current needs in the field of spinal tumors. Moreover, machine learning and artificial intelligence are anticipated to impact the application of spinal imaging techniques. Through this review, we discuss the importance of conventional and advanced spinal tumor imaging, and the opportunity to combine advanced technologies with conventional modalities to better manage patients with these lesions.
{"title":"Advances in imaging modalities for spinal tumors.","authors":"Soichiro Takamiya, Anahita Malvea, Abdullah H Ishaque, Karlo Pedro, Michael G Fehlings","doi":"10.1093/noajnl/vdae045","DOIUrl":"10.1093/noajnl/vdae045","url":null,"abstract":"<p><p>The spinal cord occupies a narrow region and is tightly surrounded by osseous and ligamentous structures; spinal tumors can damage this structure and deprive patients of their ability to independently perform activities of daily living. Hence, imaging is vital for the prompt detection and accurate diagnosis of spinal tumors, as well as determining the optimal treatment and follow-up plan. However, many clinicians may not be familiar with the imaging characteristics of spinal tumors due to their rarity. In addition, spinal surgeons might not fully utilize imaging for the surgical planning and management of spinal tumors because of the complex heterogeneity of these lesions. In the present review, we focus on conventional and advanced spinal tumor imaging techniques. These imaging modalities include computed tomography, positron emission tomography, digital subtraction angiography, conventional and microstructural magnetic resonance imaging, and high-resolution ultrasound. We discuss the advantages and disadvantages of conventional and emerging imaging modalities, followed by an examination of cutting-edge medical technology to complement current needs in the field of spinal tumors. Moreover, machine learning and artificial intelligence are anticipated to impact the application of spinal imaging techniques. Through this review, we discuss the importance of conventional and advanced spinal tumor imaging, and the opportunity to combine advanced technologies with conventional modalities to better manage patients with these lesions.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily Y Kim, A. Vāvere, Scott E Snyder, J. Chiang, Yimei Li, T. Patni, I. Qaddoumi, T. E. Merchant, G. Robinson, Joseph Holtrop, Barry L. Shulkin, A. Bag
[11C]-Methionine PET ([11C]-MET-PET) is principally used for the evaluation of brain tumors in adults. Although amino acid PET tracers are more commonly used in evaluation of pediatric brain tumors, data on [11C]-MET-PET imaging of pediatric low-grade gliomas (pLGG) is scarce. This study aimed to investigate roles of [11C]-MET-PET in evaluation of pLGGs. Eighteen patients with newly diagnosed pLGG and twenty-six previously treated pLGG patients underwent [11C]-MET-PET met the inclusion and exclusion criteria. Tumor-to-brain uptake ratio (TBR) and metabolic tumor volumes (MTV) were assessed for diagnostic performances (newly diagnosed, 15; previously treated 26), change with therapy (newly diagnosed, 9; previously treated 7), and variability among different histology (n=12) and molecular markers (n=7) of pLGGs. The sensitivity of [11C]-MET-PET for diagnosing pLGG, newly diagnosed, and previously treated combined was 93% for both TBRmax and TBRpeak, 76% for TBRmean, and 95% for qualitative evaluation. TBRmax showed a statistically significant reduction after treatment, while other PET parameters showed a tendency to decrease. Median TBRmax, TBRpeak, and TBRmean values were slightly higher in the BRAFV600E mutated tumors compared to the BRAF fused tumors. Median TBRmax, and TBRpeak in diffuse astrocytomas were higher compared to pilocytic astrocytomas, but median TBRmean, was slightly higher in pilocytic astrocytomas. However, formal statistical analysis was not done due to the small sample size. Our study shows that [11C]-MET-PET reliably characterizes new and previously treated pLGGs. Our study also shows that quantitative parameters tend to decrease with treatment, and differences may exist between various pLGG types.
{"title":"[11C]-Methionine PET in the Evaluation of Pediatric Low-grade Gliomas","authors":"Emily Y Kim, A. Vāvere, Scott E Snyder, J. Chiang, Yimei Li, T. Patni, I. Qaddoumi, T. E. Merchant, G. Robinson, Joseph Holtrop, Barry L. Shulkin, A. Bag","doi":"10.1093/noajnl/vdae056","DOIUrl":"https://doi.org/10.1093/noajnl/vdae056","url":null,"abstract":"\u0000 \u0000 \u0000 [11C]-Methionine PET ([11C]-MET-PET) is principally used for the evaluation of brain tumors in adults. Although amino acid PET tracers are more commonly used in evaluation of pediatric brain tumors, data on [11C]-MET-PET imaging of pediatric low-grade gliomas (pLGG) is scarce. This study aimed to investigate roles of [11C]-MET-PET in evaluation of pLGGs.\u0000 \u0000 \u0000 \u0000 Eighteen patients with newly diagnosed pLGG and twenty-six previously treated pLGG patients underwent [11C]-MET-PET met the inclusion and exclusion criteria. Tumor-to-brain uptake ratio (TBR) and metabolic tumor volumes (MTV) were assessed for diagnostic performances (newly diagnosed, 15; previously treated 26), change with therapy (newly diagnosed, 9; previously treated 7), and variability among different histology (n=12) and molecular markers (n=7) of pLGGs.\u0000 \u0000 \u0000 \u0000 The sensitivity of [11C]-MET-PET for diagnosing pLGG, newly diagnosed, and previously treated combined was 93% for both TBRmax and TBRpeak, 76% for TBRmean, and 95% for qualitative evaluation. TBRmax showed a statistically significant reduction after treatment, while other PET parameters showed a tendency to decrease. Median TBRmax, TBRpeak, and TBRmean values were slightly higher in the BRAFV600E mutated tumors compared to the BRAF fused tumors. Median TBRmax, and TBRpeak in diffuse astrocytomas were higher compared to pilocytic astrocytomas, but median TBRmean, was slightly higher in pilocytic astrocytomas. However, formal statistical analysis was not done due to the small sample size.\u0000 \u0000 \u0000 \u0000 Our study shows that [11C]-MET-PET reliably characterizes new and previously treated pLGGs. Our study also shows that quantitative parameters tend to decrease with treatment, and differences may exist between various pLGG types.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140738977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae055
Prajwal Ghimire, Ben Kinnersley, Golestan Karami, Prabhu Arumugam, Richard Houlston, Keyoumars Ashkan, Marc Modat, Thomas C Booth
Background: Immunotherapy is an effective "precision medicine" treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma.
Methods: A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered: CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis.
Results: Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed.
Conclusions: Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.
{"title":"Radiogenomic biomarkers for immunotherapy in glioblastoma: A systematic review of magnetic resonance imaging studies.","authors":"Prajwal Ghimire, Ben Kinnersley, Golestan Karami, Prabhu Arumugam, Richard Houlston, Keyoumars Ashkan, Marc Modat, Thomas C Booth","doi":"10.1093/noajnl/vdae055","DOIUrl":"https://doi.org/10.1093/noajnl/vdae055","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy is an effective \"precision medicine\" treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma.</p><p><strong>Methods: </strong>A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered: CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis.</p><p><strong>Results: </strong>Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed.</p><p><strong>Conclusions: </strong>Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Feucht, P. Haas, M. Skardelly, F. Behling, D. Rieger, Paula Bombach, F. Paulsen, E. Hoffmann, Till-Karsten Hauser, Benjamin Bender, M. Renovanz, Maximilian Niyazi, Ghazaleh Tabatabai, M. Tatagiba, Constantin Roder
Little is known about growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival. We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined multivariably. Out of 749 patients screened, thirteen had ≥3 preoperative MRI, 70 had two MRI and met the inclusion criteria. A curve estimation regression model showed best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho=-0.59, p<0.001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log rank: p=0.010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox-regression model for patients after tumor resection. Especially small lesions suggestive for glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.
{"title":"Preoperative growth dynamics of untreated glioblastoma – Description of an exponential growth-type, correlating factors and association with postoperative survival","authors":"Daniel Feucht, P. Haas, M. Skardelly, F. Behling, D. Rieger, Paula Bombach, F. Paulsen, E. Hoffmann, Till-Karsten Hauser, Benjamin Bender, M. Renovanz, Maximilian Niyazi, Ghazaleh Tabatabai, M. Tatagiba, Constantin Roder","doi":"10.1093/noajnl/vdae053","DOIUrl":"https://doi.org/10.1093/noajnl/vdae053","url":null,"abstract":"\u0000 \u0000 \u0000 Little is known about growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival.\u0000 \u0000 \u0000 \u0000 We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined multivariably.\u0000 \u0000 \u0000 \u0000 Out of 749 patients screened, thirteen had ≥3 preoperative MRI, 70 had two MRI and met the inclusion criteria.\u0000 A curve estimation regression model showed best fit for exponential tumor growth.\u0000 Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho=-0.59, p<0.001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log rank: p=0.010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox-regression model for patients after tumor resection.\u0000 \u0000 \u0000 \u0000 Especially small lesions suggestive for glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Isabel Barros Guinle, Jeffrey J Nirschl, Yao Lulu Xing, E. A. Nettnin, Sophia Arana, Zhi-Ping Feng, Emon Nasajpour, Anna Pronina, Cesar A. Garcia, Gerald A. Grant, Hannes Vogel, Kristen W. Yeom, L. Prolo, C. Petritsch
Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma (DIG/DIA) are low-grade glial/glioneuronal tumors occurring predominantly in the cerebral hemispheres of infants. DIG/DIA exhibit BRAF or RAF1 alterations leading to oncogenic mitogen-activated protein kinase (MAPK) pathway activation. Here, we report the discovery of the novel CDC42BPA::BRAF fusion in a three-month-old patient with left frontotemporal DIA using DNA sequencing. Independent validation was performed through RNA sequencing. This fusion joins the kinase domains of BRAF and CDC42BPA, potentially constitutively activating both. It marks the first report of a fusion involving the actomyosin regulatory kinase CDC42BPA/MRCKα in brain tumors, suggesting potential involvement of actin remodeling defects in DIG/DIA. Surgical excision is curative for DIG/DIA, but incomplete resection, recurrence, malignant transformation, or metastases may necessitate adjuvant chemotherapy, posing risks. Identifying and excluding molecular alterations is crucial for selecting targeted therapies, such as BRAF and MEK inhibitors. These options present potential treatments with lower toxicity compared to conventional chemotherapy.
去鳞屑性婴儿神经节胶质瘤/去鳞屑性婴儿星形细胞瘤(DIG/DIA)是主要发生在婴儿大脑半球的低级别胶质/神经元肿瘤。DIG/DIA表现出BRAF或RAF1改变,导致致癌的丝裂原活化蛋白激酶(MAPK)通路激活。在此,我们报告了通过 DNA 测序在一名三个月大的左侧额颞叶 DIA 患者身上发现的新型 CDC42BPA::BRAF 融合体。通过 RNA 测序进行了独立验证。这种融合连接了 BRAF 和 CDC42BPA 的激酶结构域,可能会构成性地激活两者。这是首次报道脑肿瘤中涉及肌动蛋白调节激酶CDC42BPA/MRCKα的融合,表明肌动蛋白重塑缺陷可能参与了DIG/DIA。手术切除可治愈 DIG/DIA,但切除不彻底、复发、恶性转化或转移可能需要辅助化疗,从而带来风险。识别和排除分子改变对于选择 BRAF 和 MEK 抑制剂等靶向疗法至关重要。与传统化疗相比,这些方案提供了毒性较低的潜在治疗方法。
{"title":"CDC42BPA::BRAF Represents a Novel Fusion in Desmoplastic Infantile Ganglioglioma/Desmoplastic Infantile Astrocytoma","authors":"Maria Isabel Barros Guinle, Jeffrey J Nirschl, Yao Lulu Xing, E. A. Nettnin, Sophia Arana, Zhi-Ping Feng, Emon Nasajpour, Anna Pronina, Cesar A. Garcia, Gerald A. Grant, Hannes Vogel, Kristen W. Yeom, L. Prolo, C. Petritsch","doi":"10.1093/noajnl/vdae050","DOIUrl":"https://doi.org/10.1093/noajnl/vdae050","url":null,"abstract":"\u0000 Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma (DIG/DIA) are low-grade glial/glioneuronal tumors occurring predominantly in the cerebral hemispheres of infants. DIG/DIA exhibit BRAF or RAF1 alterations leading to oncogenic mitogen-activated protein kinase (MAPK) pathway activation. Here, we report the discovery of the novel CDC42BPA::BRAF fusion in a three-month-old patient with left frontotemporal DIA using DNA sequencing. Independent validation was performed through RNA sequencing. This fusion joins the kinase domains of BRAF and CDC42BPA, potentially constitutively activating both. It marks the first report of a fusion involving the actomyosin regulatory kinase CDC42BPA/MRCKα in brain tumors, suggesting potential involvement of actin remodeling defects in DIG/DIA. Surgical excision is curative for DIG/DIA, but incomplete resection, recurrence, malignant transformation, or metastases may necessitate adjuvant chemotherapy, posing risks. Identifying and excluding molecular alterations is crucial for selecting targeted therapies, such as BRAF and MEK inhibitors. These options present potential treatments with lower toxicity compared to conventional chemotherapy.","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140364437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiffany M Juarez, Jaya M Gill, Annie Heng, J. Carrillo, Naveed Wagle, Natsuko Nomura, Minhdan Nguyen, J. Truong, Lucia Dobrawa, Walavan Sivakumar, G. Barkhoudarian, Daniel F Kelly, Santosh Kesari
Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase 2 dose in patients with progressive or recurrent brain cancers. Afatinib was taken orally once every four days or once every seven days depending on dose cohort, until disease progression or unacceptable toxicity. A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase 2 dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, two patients (9.5%) exhibited partial response based on RANO criteria and disease stabilization was seen in three patients (14.3%). Afatinib taken orally was safe and well-tolerated up to 280 mg every seven days in brain cancer patients.
{"title":"A Phase I Dose Escalation Study of Pulsatile Afatinib in Patients with Recurrent or Progressive Brain Cancer","authors":"Tiffany M Juarez, Jaya M Gill, Annie Heng, J. Carrillo, Naveed Wagle, Natsuko Nomura, Minhdan Nguyen, J. Truong, Lucia Dobrawa, Walavan Sivakumar, G. Barkhoudarian, Daniel F Kelly, Santosh Kesari","doi":"10.1093/noajnl/vdae049","DOIUrl":"https://doi.org/10.1093/noajnl/vdae049","url":null,"abstract":"\u0000 \u0000 \u0000 Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase 2 dose in patients with progressive or recurrent brain cancers.\u0000 \u0000 \u0000 \u0000 Afatinib was taken orally once every four days or once every seven days depending on dose cohort, until disease progression or unacceptable toxicity.\u0000 \u0000 \u0000 \u0000 A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase 2 dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, two patients (9.5%) exhibited partial response based on RANO criteria and disease stabilization was seen in three patients (14.3%).\u0000 \u0000 \u0000 \u0000 Afatinib taken orally was safe and well-tolerated up to 280 mg every seven days in brain cancer patients.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140362791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandra N Demetriou, Frances Chow, David W Craig, Michelle G Webb, D. Ormond, James Battiste, A. Chakravarti, H. Colman, J. Villano, Bryan P. Schneider, James K C Liu, Michelle L Churchman, Gabriel Zada
Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes. Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student’s t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups. Key findings include an association of MUC17, SYNE1 and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher EGFR mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS >2 years; and two transcripts associated with OS <1 year. Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.
{"title":"Profiling the molecular and clinical landscape of glioblastoma utilizing the ORIEN brain cancer database","authors":"Alexandra N Demetriou, Frances Chow, David W Craig, Michelle G Webb, D. Ormond, James Battiste, A. Chakravarti, H. Colman, J. Villano, Bryan P. Schneider, James K C Liu, Michelle L Churchman, Gabriel Zada","doi":"10.1093/noajnl/vdae046","DOIUrl":"https://doi.org/10.1093/noajnl/vdae046","url":null,"abstract":"\u0000 \u0000 \u0000 Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes.\u0000 \u0000 \u0000 \u0000 Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student’s t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups.\u0000 \u0000 \u0000 \u0000 Key findings include an association of MUC17, SYNE1 and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher EGFR mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS >2 years; and two transcripts associated with OS <1 year.\u0000 \u0000 \u0000 \u0000 Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140374612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sherry Liu Jiani, Bengt Karlsson, B. Vellayappan, Yvonne Ang, Wu Peng, T. Yeo, Vincent Nga
The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM. The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively. The median survival time was nine months. Two grade 3 complications occurred, one resolved and one did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT three times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC. GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post GKS intracranial disease progression once it occurred rather than trying to prevent it by using adjunct WBRT.
{"title":"Is Gamma Knife Surgery, omitting adjunct WBRT, feasible for patients with 20 or more brain metastases?","authors":"Sherry Liu Jiani, Bengt Karlsson, B. Vellayappan, Yvonne Ang, Wu Peng, T. Yeo, Vincent Nga","doi":"10.1093/noajnl/vdae047","DOIUrl":"https://doi.org/10.1093/noajnl/vdae047","url":null,"abstract":"\u0000 \u0000 \u0000 The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM.\u0000 \u0000 \u0000 \u0000 The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively.\u0000 \u0000 \u0000 \u0000 The median survival time was nine months. Two grade 3 complications occurred, one resolved and one did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT three times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC.\u0000 \u0000 \u0000 \u0000 GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post GKS intracranial disease progression once it occurred rather than trying to prevent it by using adjunct WBRT.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140377211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Dos Santos, J. Deverdun, Thierry Chaptal, A. Darlix, H. Duffau, L. V. van Dokkum, Arthur Coget, M. Carrière, Eve Denis, Margaux Verdier, Nicolas Menjot de Champfleur, E. Le Bars
Radiological follow-up of diffuse low-grade gliomas (LGGs) growth is challenging. Approximative visual assessment still predominates over objective quantification due to the complexity of the pathology. The infiltrating character, diffuse borders and presence of surgical cavities demand LGG based linear measurement rules to efficiently and precisely assess LGG evolution over time. We compared optimized 1D, 2D and 3D linear measurements with manual volume segmentation as a reference to assess LGG tumor growth in 36 patients with LGG (340 MRI scans), using the clinically important Mean Tumor Diameter (MTD) and the Velocity Diameter Expansion (VDE). LGG specific progression thresholds were established using the high-grade gliomas based RECIST, Macdonald and RANO criteria, comparing the sensitivity to identify progression/non-progression for each linear method compared to the ground truth established by the manual segmentation. 3D linear volume approximation correlated strongly with manually segmented volume. It also showed the highest sensitivity for progression detection. The MTD showed a comparable result, whereas the VDE highlighted that caution is warranted in case of small tumors with multiple residues. Novel LGG specific progression thresholds, or the critical change in estimated tumor volume, were increased for the 3D (from 40% to 52%) and 2D methods (from 25% to 33%) and decreased for the 1D method (from 20% to 16%). Using the 3D method allowed a ~5-minute time gain. While manual volumetric assessment remains the gold standard for calculating growth rate, the 3D linear method is the best time-efficient standardized alternative for radiological evaluation of LGGs in routine use.
{"title":"Diffuse low-grade glioma: what is the optimal linear measure to assess tumor growth?","authors":"Thomas Dos Santos, J. Deverdun, Thierry Chaptal, A. Darlix, H. Duffau, L. V. van Dokkum, Arthur Coget, M. Carrière, Eve Denis, Margaux Verdier, Nicolas Menjot de Champfleur, E. Le Bars","doi":"10.1093/noajnl/vdae044","DOIUrl":"https://doi.org/10.1093/noajnl/vdae044","url":null,"abstract":"\u0000 \u0000 \u0000 Radiological follow-up of diffuse low-grade gliomas (LGGs) growth is challenging. Approximative visual assessment still predominates over objective quantification due to the complexity of the pathology. The infiltrating character, diffuse borders and presence of surgical cavities demand LGG based linear measurement rules to efficiently and precisely assess LGG evolution over time.\u0000 \u0000 \u0000 \u0000 We compared optimized 1D, 2D and 3D linear measurements with manual volume segmentation as a reference to assess LGG tumor growth in 36 patients with LGG (340 MRI scans), using the clinically important Mean Tumor Diameter (MTD) and the Velocity Diameter Expansion (VDE). LGG specific progression thresholds were established using the high-grade gliomas based RECIST, Macdonald and RANO criteria, comparing the sensitivity to identify progression/non-progression for each linear method compared to the ground truth established by the manual segmentation.\u0000 \u0000 \u0000 \u0000 3D linear volume approximation correlated strongly with manually segmented volume. It also showed the highest sensitivity for progression detection. The MTD showed a comparable result, whereas the VDE highlighted that caution is warranted in case of small tumors with multiple residues. Novel LGG specific progression thresholds, or the critical change in estimated tumor volume, were increased for the 3D (from 40% to 52%) and 2D methods (from 25% to 33%) and decreased for the 1D method (from 20% to 16%). Using the 3D method allowed a ~5-minute time gain.\u0000 \u0000 \u0000 \u0000 While manual volumetric assessment remains the gold standard for calculating growth rate, the 3D linear method is the best time-efficient standardized alternative for radiological evaluation of LGGs in routine use.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140376506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-14eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae022
Vicky Parmar, Johannes Haubold, Luca Salhöfer, Mathias Meetschen, Karsten Wrede, Martin Glas, Maja Guberina, Tobias Blau, Denise Bos, Anisa Kureishi, René Hosch, Felix Nensa, Michael Forsting, Cornelius Deuschl, Lale Umutlu
Background: Primary central nervous system lymphomas (PCNSL) pose a challenge as they may mimic gliomas on magnetic resonance imaging (MRI) imaging, compelling precise differentiation for appropriate treatment. This study focuses on developing an automated MRI-based workflow to distinguish between PCNSL and gliomas.
Methods: MRI examinations of 240 therapy-naive patients (141 males and 99 females, mean age: 55.16 years) with cerebral gliomas and PCNSLs (216 gliomas and 24 PCNSLs), each comprising a non-contrast T1-weighted, fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted sequence were included in the study. HD-GLIO, a pre-trained segmentation network, was used to generate segmentations automatically. To validate the segmentation efficiency, 237 manual segmentations were prepared (213 gliomas and 24 PCNSLs). Subsequently, radiomics features were extracted following feature selection and training of an XGBoost algorithm for classification.
Results: The segmentation models for gliomas and PCNSLs achieved a mean Sørensen-Dice coefficient of 0.82 and 0.80 for whole tumors, respectively. Three classification models were developed in this study to differentiate gliomas from PCNSLs. The first model differentiated PCNSLs from gliomas, with an area under the curve (AUC) of 0.99 (F1-score: 0.75). The second model discriminated between high-grade gliomas and PCNSLs with an AUC of 0.91 (F1-score: 0.6), and the third model differentiated between low-grade gliomas and PCNSLs with an AUC of 0.95 (F1-score: 0.89).
Conclusions: This study serves as a pilot investigation presenting an automated virtual biopsy workflow that distinguishes PCNSLs from cerebral gliomas. Prior to clinical use, it is necessary to validate the results in a prospective multicenter setting with a larger number of PCNSL patients.
{"title":"Fully automated MR-based virtual biopsy of primary CNS lymphomas.","authors":"Vicky Parmar, Johannes Haubold, Luca Salhöfer, Mathias Meetschen, Karsten Wrede, Martin Glas, Maja Guberina, Tobias Blau, Denise Bos, Anisa Kureishi, René Hosch, Felix Nensa, Michael Forsting, Cornelius Deuschl, Lale Umutlu","doi":"10.1093/noajnl/vdae022","DOIUrl":"10.1093/noajnl/vdae022","url":null,"abstract":"<p><strong>Background: </strong>Primary central nervous system lymphomas (PCNSL) pose a challenge as they may mimic gliomas on magnetic resonance imaging (MRI) imaging, compelling precise differentiation for appropriate treatment. This study focuses on developing an automated MRI-based workflow to distinguish between PCNSL and gliomas.</p><p><strong>Methods: </strong>MRI examinations of 240 therapy-naive patients (141 males and 99 females, mean age: 55.16 years) with cerebral gliomas and PCNSLs (216 gliomas and 24 PCNSLs), each comprising a non-contrast T1-weighted, fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted sequence were included in the study. HD-GLIO, a pre-trained segmentation network, was used to generate segmentations automatically. To validate the segmentation efficiency, 237 manual segmentations were prepared (213 gliomas and 24 PCNSLs). Subsequently, radiomics features were extracted following feature selection and training of an XGBoost algorithm for classification.</p><p><strong>Results: </strong>The segmentation models for gliomas and PCNSLs achieved a mean Sørensen-Dice coefficient of 0.82 and 0.80 for whole tumors, respectively. Three classification models were developed in this study to differentiate gliomas from PCNSLs. The first model differentiated PCNSLs from gliomas, with an area under the curve (AUC) of 0.99 (F1-score: 0.75). The second model discriminated between high-grade gliomas and PCNSLs with an AUC of 0.91 (F1-score: 0.6), and the third model differentiated between low-grade gliomas and PCNSLs with an AUC of 0.95 (F1-score: 0.89).</p><p><strong>Conclusions: </strong>This study serves as a pilot investigation presenting an automated virtual biopsy workflow that distinguishes PCNSLs from cerebral gliomas. Prior to clinical use, it is necessary to validate the results in a prospective multicenter setting with a larger number of PCNSL patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}