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dc.contributor.authorNimalasena, S
dc.contributor.authorGothard, L
dc.contributor.authorAnbalagan, S
dc.contributor.authorAllen, S
dc.contributor.authorSinnett, V
dc.contributor.authorMohammed, K
dc.contributor.authorKothari, G
dc.contributor.authorMusallam, A
dc.contributor.authorLucy, C
dc.contributor.authorYu, S
dc.contributor.authorNayamundanda, G
dc.contributor.authorKirby, A
dc.contributor.authorRoss, G
dc.contributor.authorSawyer, E
dc.contributor.authorCastell, F
dc.contributor.authorCleator, S
dc.contributor.authorLocke, I
dc.contributor.authorTait, D
dc.contributor.authorWestbury, C
dc.contributor.authorWolstenholme, V
dc.contributor.authorBox, C
dc.contributor.authorRobinson, SP
dc.contributor.authorYarnold, J
dc.contributor.authorSomaiah, N
dc.date.accessioned2020-06-23T10:27:35Z
dc.date.issued2020-11
dc.identifier.citationInternational journal of radiation oncology, biology, physics, 2020, 108 (4), pp. 1019 - 1029
dc.identifier.issn0360-3016
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3772
dc.identifier.eissn1879-355X
dc.identifier.doi10.1016/j.ijrobp.2020.06.022
dc.description.abstractPurpose Hydrogen peroxide (H 2 O 2 ) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H 2 O 2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action.Methods and materials Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H 2 O 2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H 2 O 2 was mixed in 1% sodium hyaluronate gel (final H 2 O 2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis.Results Compliance with H 2 O 2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1β, IL-4, and MIP-1α with tumor response.Conclusions Intratumoral H 2 O 2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.
dc.formatPrint-Electronic
dc.format.extent1019 - 1029
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleIntratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial.
dc.typeJournal Article
dcterms.dateAccepted2020-06-12
rioxxterms.versionofrecord10.1016/j.ijrobp.2020.06.022
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfInternational journal of radiation oncology, biology, physics
pubs.issue4
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy/Breast Cancer Radiotherapy (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy/Breast Cancer Radiotherapy (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume108
pubs.embargo.termsNot known
icr.researchteamBreast Cancer Radiotherapyen_US
icr.researchteamPre-Clinical MRIen_US
icr.researchteamTranslational Breast Radiobiologyen_US
dc.contributor.icrauthorAnbalagan, Selvakumaren
dc.contributor.icrauthorSomaiah, Navitaen
dc.contributor.icrauthorKirby, Annaen
dc.contributor.icrauthorRobinson, Simonen


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