Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series
BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a cas...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-04-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652331930717X |
| _version_ | 1819058501514690560 |
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| author | Tulika Ranjan Candace M. Howard Alexander Yu Linda Xu Khaled Aziz David Jho Jodi Leonardo Muhammad A. Hameed Stephen M. Karlovits Rodney E. Wegner Russell Fuhrer Seth T. Lirette Krista L. Denning Jagan Valluri Pier Paolo Claudio |
| author_facet | Tulika Ranjan Candace M. Howard Alexander Yu Linda Xu Khaled Aziz David Jho Jodi Leonardo Muhammad A. Hameed Stephen M. Karlovits Rodney E. Wegner Russell Fuhrer Seth T. Lirette Krista L. Denning Jagan Valluri Pier Paolo Claudio |
| author_sort | Tulika Ranjan |
| collection | DOAJ |
| description | BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21–63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0–10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. Importance of the Study: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp's protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient's derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1–10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies. |
| first_indexed | 2024-12-21T13:56:12Z |
| format | Article |
| id | doaj.art-8900699bf5f1497cb50c4ac12498f170 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-21T13:56:12Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-8900699bf5f1497cb50c4ac12498f1702022-12-21T19:01:32ZengElsevierTranslational Oncology1936-52332020-04-01134Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case SeriesTulika Ranjan0Candace M. Howard1Alexander Yu2Linda Xu3Khaled Aziz4David Jho5Jodi Leonardo6Muhammad A. Hameed7Stephen M. Karlovits8Rodney E. Wegner9Russell Fuhrer10Seth T. Lirette11Krista L. Denning12Jagan Valluri13Pier Paolo Claudio14Department of Neuro-oncology, Allegheny Health Network, Pittsburgh, PA 15212Department of Radiology, University of Mississippi Medical Center, Jackson, MS 39216Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA 15212Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA 15212Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA 15212Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA 15212Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA 15212Department of Neuro-oncology, Allegheny Health Network, Pittsburgh, PA 15212Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216Department of Anatomy and Pathology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25705Department of Biological Sciences, Marshall University, Huntington, WV 25755Department of BioMolecular Sciences, National Center for Natural Products Research, Department of Radiation Oncology, University of Mississippi Cancer Center & Research Institute, Jackson, MS 39216; Address all correspondence to: Pier Paolo Claudio, Department of BioMolecular Sciences, National Center for Natural Products Research, Department of Radiation Oncology, University of Mississippi Cancer Center & Research Institute, Jackson, MS 39126, USA.BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21–63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0–10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. Importance of the Study: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp's protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient's derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1–10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies.http://www.sciencedirect.com/science/article/pii/S193652331930717X |
| spellingShingle | Tulika Ranjan Candace M. Howard Alexander Yu Linda Xu Khaled Aziz David Jho Jodi Leonardo Muhammad A. Hameed Stephen M. Karlovits Rodney E. Wegner Russell Fuhrer Seth T. Lirette Krista L. Denning Jagan Valluri Pier Paolo Claudio Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series Translational Oncology |
| title | Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series |
| title_full | Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series |
| title_fullStr | Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series |
| title_full_unstemmed | Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series |
| title_short | Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series |
| title_sort | cancer stem cell chemotherapeutics assay for prospective treatment of recurrent glioblastoma and progressive anaplastic glioma a single institution case series |
| url | http://www.sciencedirect.com/science/article/pii/S193652331930717X |
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