Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review

Emma C. Hulshof; Lifani Lim; Ignace H. J. T. de Hingh; Hans Gelderblom; Henk-Jan Guchelaar; Maarten J. Deenen

doi:10.3389/fphar.2020.577968

Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review

Emma C. Hulshof, Lifani Lim, Ignace H. J. T. de Hingh, Hans Gelderblom, Henk-Jan Guchelaar, Maarten J. Deenen^*

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Background The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal peritoneal metastasis (CPM) has resulted in a major increase in overall survival. Nonetheless, despite critical patient selection, the majority of patients will develop recurrent disease within one year following CRS + HIPEC. Therefore, improvement of patient and treatment selection is needed and may be achieved by the incorporation of genetic biomarkers. This systematic review aims to provide an overview of genetic biomarkers in the DNA repair pathway that are potentially predictive for treatment outcome of patients with colorectal peritoneal metastases treated with CRS + HIPEC with oxaliplatin or mitomycin C. Methods A systematic review was conducted according to the PRISMA guidelines. Given the limited number of genetic association studies of intraperitoneal mitomycin C and oxaliplatin in patients with CPM, we expanded the review and extrapolated the data from biomarker studies conducted in colorectal cancer patients treated with systemic mitomycin C- and oxaliplatin-based chemotherapy. Results In total, 43 papers were included in this review. No study reported potential pharmacogenomic biomarkers in patients with colorectal cancer undergoing mitomycin C-based chemotherapy. For oxaliplatin-based chemotherapy, a total of 26 genetic biomarkers within 14 genes were identified that were signi?cantly associated with treatment outcome. The most promising genetic biomarkers wereERCC1rs11615,XPCrs1043953,XPDrs13181,XPGrs17655,MNATrs3783819/rs973063/rs4151330, MMR status, ATM protein expression,HIC1tandem repeat D17S5, andPIN1rs2233678. Conclusion Several genetic biomarkers have proven predictive value for the treatment outcome of systemically administered oxaliplatin. By extrapolation, these genetic biomarkers may also be predictive for the efficacy of intraperitoneal oxaliplatin. This should be the subject of further investigation.

Original language	English
Article number	577968
Number of pages	11
Journal	Frontiers in Pharmacology
Volume	11
DOIs	https://doi.org/10.3389/fphar.2020.577968
Publication status	Published - 6 Oct 2020

Keywords

biomarker
colorectal cancer
DNA repair
hyperthermic intraperitoneal chemotherapy
mitomycin C
oxaliplatin
treatment outcome
OXALIPLATIN-BASED CHEMOTHERAPY
COMPLETE CYTOREDUCTIVE SURGERY
SINGLE NUCLEOTIDE POLYMORPHISMS
STRAND BREAK REPAIR
CANCER PATIENTS
FOLFOX-4 TREATMENT
ASIAN PATIENTS
ERCC1
CARCINOMATOSIS
EXPRESSION

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Cite this

Hulshof, E. C., Lim, L., de Hingh, I. H. J. T., Gelderblom, H., Guchelaar, H.-J., & Deenen, M. J. (2020). Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review. Frontiers in Pharmacology, 11, Article 577968. https://doi.org/10.3389/fphar.2020.577968

@article{d2b9815144614312a3f464644287c543,

title = "Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review",

abstract = "Background The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal peritoneal metastasis (CPM) has resulted in a major increase in overall survival. Nonetheless, despite critical patient selection, the majority of patients will develop recurrent disease within one year following CRS + HIPEC. Therefore, improvement of patient and treatment selection is needed and may be achieved by the incorporation of genetic biomarkers. This systematic review aims to provide an overview of genetic biomarkers in the DNA repair pathway that are potentially predictive for treatment outcome of patients with colorectal peritoneal metastases treated with CRS + HIPEC with oxaliplatin or mitomycin C. Methods A systematic review was conducted according to the PRISMA guidelines. Given the limited number of genetic association studies of intraperitoneal mitomycin C and oxaliplatin in patients with CPM, we expanded the review and extrapolated the data from biomarker studies conducted in colorectal cancer patients treated with systemic mitomycin C- and oxaliplatin-based chemotherapy. Results In total, 43 papers were included in this review. No study reported potential pharmacogenomic biomarkers in patients with colorectal cancer undergoing mitomycin C-based chemotherapy. For oxaliplatin-based chemotherapy, a total of 26 genetic biomarkers within 14 genes were identified that were signi?cantly associated with treatment outcome. The most promising genetic biomarkers wereERCC1rs11615,XPCrs1043953,XPDrs13181,XPGrs17655,MNATrs3783819/rs973063/rs4151330, MMR status, ATM protein expression,HIC1tandem repeat D17S5, andPIN1rs2233678. Conclusion Several genetic biomarkers have proven predictive value for the treatment outcome of systemically administered oxaliplatin. By extrapolation, these genetic biomarkers may also be predictive for the efficacy of intraperitoneal oxaliplatin. This should be the subject of further investigation.",

keywords = "biomarker, colorectal cancer, DNA repair, hyperthermic intraperitoneal chemotherapy, mitomycin C, oxaliplatin, treatment outcome, OXALIPLATIN-BASED CHEMOTHERAPY, COMPLETE CYTOREDUCTIVE SURGERY, SINGLE NUCLEOTIDE POLYMORPHISMS, STRAND BREAK REPAIR, CANCER PATIENTS, FOLFOX-4 TREATMENT, ASIAN PATIENTS, ERCC1, CARCINOMATOSIS, EXPRESSION",

author = "Hulshof, {Emma C.} and Lifani Lim and {de Hingh}, {Ignace H. J. T.} and Hans Gelderblom and Henk-Jan Guchelaar and Deenen, {Maarten J.}",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Hulshof, Lim, de Hingh, Gelderblom, Guchelaar and Deenen.",

year = "2020",

month = oct,

day = "6",

doi = "10.3389/fphar.2020.577968",

language = "English",

volume = "11",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Media S.A.",

}

Hulshof, EC, Lim, L, de Hingh, IHJT, Gelderblom, H, Guchelaar, H-J & Deenen, MJ 2020, 'Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review', Frontiers in Pharmacology, vol. 11, 577968. https://doi.org/10.3389/fphar.2020.577968

Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review. / Hulshof, Emma C.; Lim, Lifani; de Hingh, Ignace H. J. T. et al.
In: Frontiers in Pharmacology, Vol. 11, 577968, 06.10.2020.

Research output: Contribution to journal › (Systematic) Review article › peer-review

TY - JOUR

T1 - Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis

T2 - A Systematic Review

AU - Hulshof, Emma C.

AU - Lim, Lifani

AU - de Hingh, Ignace H. J. T.

AU - Gelderblom, Hans

AU - Guchelaar, Henk-Jan

AU - Deenen, Maarten J.

PY - 2020/10/6

Y1 - 2020/10/6

N2 - Background The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal peritoneal metastasis (CPM) has resulted in a major increase in overall survival. Nonetheless, despite critical patient selection, the majority of patients will develop recurrent disease within one year following CRS + HIPEC. Therefore, improvement of patient and treatment selection is needed and may be achieved by the incorporation of genetic biomarkers. This systematic review aims to provide an overview of genetic biomarkers in the DNA repair pathway that are potentially predictive for treatment outcome of patients with colorectal peritoneal metastases treated with CRS + HIPEC with oxaliplatin or mitomycin C. Methods A systematic review was conducted according to the PRISMA guidelines. Given the limited number of genetic association studies of intraperitoneal mitomycin C and oxaliplatin in patients with CPM, we expanded the review and extrapolated the data from biomarker studies conducted in colorectal cancer patients treated with systemic mitomycin C- and oxaliplatin-based chemotherapy. Results In total, 43 papers were included in this review. No study reported potential pharmacogenomic biomarkers in patients with colorectal cancer undergoing mitomycin C-based chemotherapy. For oxaliplatin-based chemotherapy, a total of 26 genetic biomarkers within 14 genes were identified that were signi?cantly associated with treatment outcome. The most promising genetic biomarkers wereERCC1rs11615,XPCrs1043953,XPDrs13181,XPGrs17655,MNATrs3783819/rs973063/rs4151330, MMR status, ATM protein expression,HIC1tandem repeat D17S5, andPIN1rs2233678. Conclusion Several genetic biomarkers have proven predictive value for the treatment outcome of systemically administered oxaliplatin. By extrapolation, these genetic biomarkers may also be predictive for the efficacy of intraperitoneal oxaliplatin. This should be the subject of further investigation.

AB - Background The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal peritoneal metastasis (CPM) has resulted in a major increase in overall survival. Nonetheless, despite critical patient selection, the majority of patients will develop recurrent disease within one year following CRS + HIPEC. Therefore, improvement of patient and treatment selection is needed and may be achieved by the incorporation of genetic biomarkers. This systematic review aims to provide an overview of genetic biomarkers in the DNA repair pathway that are potentially predictive for treatment outcome of patients with colorectal peritoneal metastases treated with CRS + HIPEC with oxaliplatin or mitomycin C. Methods A systematic review was conducted according to the PRISMA guidelines. Given the limited number of genetic association studies of intraperitoneal mitomycin C and oxaliplatin in patients with CPM, we expanded the review and extrapolated the data from biomarker studies conducted in colorectal cancer patients treated with systemic mitomycin C- and oxaliplatin-based chemotherapy. Results In total, 43 papers were included in this review. No study reported potential pharmacogenomic biomarkers in patients with colorectal cancer undergoing mitomycin C-based chemotherapy. For oxaliplatin-based chemotherapy, a total of 26 genetic biomarkers within 14 genes were identified that were signi?cantly associated with treatment outcome. The most promising genetic biomarkers wereERCC1rs11615,XPCrs1043953,XPDrs13181,XPGrs17655,MNATrs3783819/rs973063/rs4151330, MMR status, ATM protein expression,HIC1tandem repeat D17S5, andPIN1rs2233678. Conclusion Several genetic biomarkers have proven predictive value for the treatment outcome of systemically administered oxaliplatin. By extrapolation, these genetic biomarkers may also be predictive for the efficacy of intraperitoneal oxaliplatin. This should be the subject of further investigation.

KW - biomarker

KW - colorectal cancer

KW - DNA repair

KW - hyperthermic intraperitoneal chemotherapy

KW - mitomycin C

KW - oxaliplatin

KW - treatment outcome

KW - OXALIPLATIN-BASED CHEMOTHERAPY

KW - COMPLETE CYTOREDUCTIVE SURGERY

KW - SINGLE NUCLEOTIDE POLYMORPHISMS

KW - STRAND BREAK REPAIR

KW - CANCER PATIENTS

KW - FOLFOX-4 TREATMENT

KW - ASIAN PATIENTS

KW - ERCC1

KW - CARCINOMATOSIS

KW - EXPRESSION

U2 - 10.3389/fphar.2020.577968

DO - 10.3389/fphar.2020.577968

M3 - (Systematic) Review article

C2 - 33117169

SN - 1663-9812

VL - 11

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 577968

ER -