An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma
<i>Background</i> Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/13/3241 |
| _version_ | 1797528443206762496 |
|---|---|
| author | Colin Watts Keyoumars Ashkan Michael D. Jenkinson Stephen J. Price Thomas Santarius Tomasz Matys Ting Ting Zhang Alina Finch Peter Collins Kieren Allinson Sarah J. Jefferies Daniel J. Scoffings Athanasios Zisakis Mark Phillips Katharina Wanek Paul Smith Laura Clifton-Hadley Nicholas Counsell |
| author_facet | Colin Watts Keyoumars Ashkan Michael D. Jenkinson Stephen J. Price Thomas Santarius Tomasz Matys Ting Ting Zhang Alina Finch Peter Collins Kieren Allinson Sarah J. Jefferies Daniel J. Scoffings Athanasios Zisakis Mark Phillips Katharina Wanek Paul Smith Laura Clifton-Hadley Nicholas Counsell |
| author_sort | Colin Watts |
| collection | DOAJ |
| description | <i>Background</i> Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. <i>Methods</i> We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. <i>Results</i> Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (<i>n</i> = 3), death (<i>n</i> = 3), lost to follow-up/withdrew (<i>n</i> = 3), clinical decision (<i>n</i> = 1), poor performance status (<i>n</i> = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4–9.8) and median overall survival was 14.7 months (95% CI: 11.7–16.8). <i>Conclusions</i> Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies. |
| first_indexed | 2024-03-10T09:58:23Z |
| format | Article |
| id | doaj.art-106f56619c9e40e080fcc96e8ef1b5e5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:58:23Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-106f56619c9e40e080fcc96e8ef1b5e52023-11-22T02:07:52ZengMDPI AGCancers2072-66942021-06-011313324110.3390/cancers13133241An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary GlioblastomaColin Watts0Keyoumars Ashkan1Michael D. Jenkinson2Stephen J. Price3Thomas Santarius4Tomasz Matys5Ting Ting Zhang6Alina Finch7Peter Collins8Kieren Allinson9Sarah J. Jefferies10Daniel J. Scoffings11Athanasios Zisakis12Mark Phillips13Katharina Wanek14Paul Smith15Laura Clifton-Hadley16Nicholas Counsell17Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UKDepartment of Neurosurgery, King’s College Hospital, London SE5 9RS, UKDepartment of Neurosurgery, The Walton Centre, Liverpool L9 7LJ, UKAcademic Neurosurgery Department, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Clinical Neurosciences, Cambridge University Hospitals Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals Foundation Trust, Cambridge CB2 0QQ, UKInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UKDepartment of Clinical Neurosciences, Cambridge University Hospitals Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Histopathology, Cambridge University Hospitals Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Clinical Neurosciences, Cambridge University Hospitals Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Neurosurgery, Queen Elizabeth Hospital, Birmingham B15 2WB, UKCancer Institute, University College London, London WC1E 6DD, UKCancer Research UK and University College London Cancer Trials Centre, London W1T 4TJ, UKCancer Research UK and University College London Cancer Trials Centre, London W1T 4TJ, UKCancer Research UK and University College London Cancer Trials Centre, London W1T 4TJ, UKCancer Research UK and University College London Cancer Trials Centre, London W1T 4TJ, UK<i>Background</i> Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. <i>Methods</i> We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. <i>Results</i> Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (<i>n</i> = 3), death (<i>n</i> = 3), lost to follow-up/withdrew (<i>n</i> = 3), clinical decision (<i>n</i> = 1), poor performance status (<i>n</i> = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4–9.8) and median overall survival was 14.7 months (95% CI: 11.7–16.8). <i>Conclusions</i> Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.https://www.mdpi.com/2072-6694/13/13/3241glioblastoma5-aminolevulinic acidBCNU waferschemoRTfeasibility trial |
| spellingShingle | Colin Watts Keyoumars Ashkan Michael D. Jenkinson Stephen J. Price Thomas Santarius Tomasz Matys Ting Ting Zhang Alina Finch Peter Collins Kieren Allinson Sarah J. Jefferies Daniel J. Scoffings Athanasios Zisakis Mark Phillips Katharina Wanek Paul Smith Laura Clifton-Hadley Nicholas Counsell An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma Cancers glioblastoma 5-aminolevulinic acid BCNU wafers chemoRT feasibility trial |
| title | An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma |
| title_full | An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma |
| title_fullStr | An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma |
| title_full_unstemmed | An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma |
| title_short | An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma |
| title_sort | evaluation of the tolerability and feasibility of combining 5 amino levulinic acid 5 ala with bcnu wafers in the surgical management of primary glioblastoma |
| topic | glioblastoma 5-aminolevulinic acid BCNU wafers chemoRT feasibility trial |
| url | https://www.mdpi.com/2072-6694/13/13/3241 |
| work_keys_str_mv | AT colinwatts anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT keyoumarsashkan anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT michaeldjenkinson anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT stephenjprice anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT thomassantarius anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT tomaszmatys anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT tingtingzhang anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT alinafinch anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT petercollins anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT kierenallinson anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT sarahjjefferies anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT danieljscoffings anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT athanasioszisakis anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT markphillips anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT katharinawanek anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT paulsmith anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT lauracliftonhadley anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT nicholascounsell anevaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT colinwatts evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT keyoumarsashkan evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT michaeldjenkinson evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT stephenjprice evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT thomassantarius evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT tomaszmatys evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT tingtingzhang evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT alinafinch evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT petercollins evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT kierenallinson evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT sarahjjefferies evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT danieljscoffings evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT athanasioszisakis evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT markphillips evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT katharinawanek evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT paulsmith evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT lauracliftonhadley evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma AT nicholascounsell evaluationofthetolerabilityandfeasibilityofcombining5aminolevulinicacid5alawithbcnuwafersinthesurgicalmanagementofprimaryglioblastoma |