Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO) : An Open-Label, Dose-Escalation Phase I/II Trial
BACKGROUND: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes.
OBJECTIVE: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective.
METHODS: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin.
RESULTS: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT.
CONCLUSION: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
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| Enthalten in: |
Neurosurgery - 84(2019), 1 vom: 01. Jan., Seite 41-49 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Giordano, Frank A [VerfasserIn] |
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| Links: |
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| Themen: |
Clinical Trial, Phase I |
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| Anmerkungen: |
Date Completed 03.01.2020 Date Revised 03.01.2020 published: Print ClinicalTrials.gov: NCT02685605 Citation Status MEDLINE |
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| doi: |
10.1093/neuros/nyy018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM281849307 |
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| 100 | 1 | |a Giordano, Frank A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO) |b An Open-Label, Dose-Escalation Phase I/II Trial |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 03.01.2020 | ||
| 500 | |a Date Revised 03.01.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02685605 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes | ||
| 520 | |a OBJECTIVE: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective | ||
| 520 | |a METHODS: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin | ||
| 520 | |a RESULTS: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT | ||
| 520 | |a CONCLUSION: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Clinical Trial, Phase II | |
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| 700 | 1 | |a Keller, Anke |e verfasserin |4 aut | |
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| 700 | 1 | |a Scherzinger, Elisabeth |e verfasserin |4 aut | |
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| 700 | 1 | |a Petrecca, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Wenz, Frederik |e verfasserin |4 aut | |
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