CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES
Abstract Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiati...
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| Veröffentlicht in: | Neuro-oncology (Charlottesville, Va.) Va.), 2019-11, Vol.21 (Supplement_6), p.vi55-vi56 |
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| creator | Jonathan Yang, T Wolden, Suzanne Yamada, Josh Mehallow, Michelle Skakodub, Anna Young, Robert Gavrilovic, Igor Lin, Andrew Santomasso, Bianca Grommes, Christian Piotrowski, Anna Schaff, Lauren Stone, Jacqueline Boire, Adrienne Pentsova, Elena |
| description | Abstract
Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for >9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response. |
| doi_str_mv | 10.1093/neuonc/noz175.222 |
| format | Article |
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Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for >9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noz175.222</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>CNS Metastasis</subject><ispartof>Neuro-oncology (Charlottesville, Va.), 2019-11, Vol.21 (Supplement_6), p.vi55-vi56</ispartof><rights>The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847617/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847617/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1584,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Jonathan Yang, T</creatorcontrib><creatorcontrib>Wolden, Suzanne</creatorcontrib><creatorcontrib>Yamada, Josh</creatorcontrib><creatorcontrib>Mehallow, Michelle</creatorcontrib><creatorcontrib>Skakodub, Anna</creatorcontrib><creatorcontrib>Young, Robert</creatorcontrib><creatorcontrib>Gavrilovic, Igor</creatorcontrib><creatorcontrib>Lin, Andrew</creatorcontrib><creatorcontrib>Santomasso, Bianca</creatorcontrib><creatorcontrib>Grommes, Christian</creatorcontrib><creatorcontrib>Piotrowski, Anna</creatorcontrib><creatorcontrib>Schaff, Lauren</creatorcontrib><creatorcontrib>Stone, Jacqueline</creatorcontrib><creatorcontrib>Boire, Adrienne</creatorcontrib><creatorcontrib>Pentsova, Elena</creatorcontrib><title>CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES</title><title>Neuro-oncology (Charlottesville, Va.)</title><description>Abstract
Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for >9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response.</description><subject>CNS Metastasis</subject><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqNkNFKwzAUhosoOKcP4F0ewG5J2jTtjRC3bAt0bWmzC69Cm7Y62drROkWf3syK4J1w4Bz4z_cfzm9ZtwhOEAycaVMd20ZPm_YTUTLBGJ9ZI0SwYxPf886_Z2z7BNFL66rvXyDEiHhoZL3P1lzaGE0AA8mKZRyIB5DJzfwRxAuQpLGMIzBLWSTiLBERC4FIUzYXTAojLOIUyBUHMuVMrnkkT1AWh2IO5GZtxJAnMjaCiJbcsOYWy0zx7Nq6qPNdX9389LG1WXA5W9lhvBQzFtoaUYptjXFJSUW1a570oM7dIkAFwRS62rxQu6jGtc41xV4e-BCW1AuIT4vaLQsHEuKMrfvB93As9lWpq-a1y3fq0G33efeh2nyr_irN9lk9tW_K813qIWoM0GCgu7bvu6r-ZRFUp-jVEL0aolcmesPcDUx7PPxj_QsH84AS</recordid><startdate>20191111</startdate><enddate>20191111</enddate><creator>Jonathan Yang, T</creator><creator>Wolden, Suzanne</creator><creator>Yamada, Josh</creator><creator>Mehallow, Michelle</creator><creator>Skakodub, Anna</creator><creator>Young, Robert</creator><creator>Gavrilovic, Igor</creator><creator>Lin, Andrew</creator><creator>Santomasso, Bianca</creator><creator>Grommes, Christian</creator><creator>Piotrowski, Anna</creator><creator>Schaff, Lauren</creator><creator>Stone, Jacqueline</creator><creator>Boire, Adrienne</creator><creator>Pentsova, Elena</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20191111</creationdate><title>CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES</title><author>Jonathan Yang, T ; Wolden, Suzanne ; Yamada, Josh ; Mehallow, Michelle ; Skakodub, Anna ; Young, Robert ; Gavrilovic, Igor ; Lin, Andrew ; Santomasso, Bianca ; Grommes, Christian ; Piotrowski, Anna ; Schaff, Lauren ; Stone, Jacqueline ; Boire, Adrienne ; Pentsova, Elena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1772-c22d75e7c409360ca4b91b52704c021f41f2fcac726a9800d769587bf4db30553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>CNS Metastasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jonathan Yang, T</creatorcontrib><creatorcontrib>Wolden, Suzanne</creatorcontrib><creatorcontrib>Yamada, Josh</creatorcontrib><creatorcontrib>Mehallow, Michelle</creatorcontrib><creatorcontrib>Skakodub, Anna</creatorcontrib><creatorcontrib>Young, Robert</creatorcontrib><creatorcontrib>Gavrilovic, Igor</creatorcontrib><creatorcontrib>Lin, Andrew</creatorcontrib><creatorcontrib>Santomasso, Bianca</creatorcontrib><creatorcontrib>Grommes, Christian</creatorcontrib><creatorcontrib>Piotrowski, Anna</creatorcontrib><creatorcontrib>Schaff, Lauren</creatorcontrib><creatorcontrib>Stone, Jacqueline</creatorcontrib><creatorcontrib>Boire, Adrienne</creatorcontrib><creatorcontrib>Pentsova, Elena</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jonathan Yang, T</au><au>Wolden, Suzanne</au><au>Yamada, Josh</au><au>Mehallow, Michelle</au><au>Skakodub, Anna</au><au>Young, Robert</au><au>Gavrilovic, Igor</au><au>Lin, Andrew</au><au>Santomasso, Bianca</au><au>Grommes, Christian</au><au>Piotrowski, Anna</au><au>Schaff, Lauren</au><au>Stone, Jacqueline</au><au>Boire, Adrienne</au><au>Pentsova, Elena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><date>2019-11-11</date><risdate>2019</risdate><volume>21</volume><issue>Supplement_6</issue><spage>vi55</spage><epage>vi56</epage><pages>vi55-vi56</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract
Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for >9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response.</abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1093/neuonc/noz175.222</doi><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); PubMed Central |
| subjects | CNS Metastasis |
| title | CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES |
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