Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors

Piernicola Pedicini, Rocchina Caivano, Barbara Alicia Jereczek-Fossa, Lidia Strigari, Barbara Vischioni, Daniela Alterio, Marta Cremonesi, Francesca Botta, Antonio Nappi, Giuseppina Improta, Giovanni Storto, Marcello Benassi, Roberto Orecchia

Research output: Contribution to journalArticle

Abstract

Purpose. To estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr). Materials and methods. Differences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED), has been introduced to account for changes in radiosensitivity parameters (α and α/β) rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED). The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered. Results: Assuming membrane EGFr over-expression corresponds to reduced radiosensitivity (α H=0.15 Gy -1 and α HH=7.5 Gy) relative to normal radiosensitivity (α=0.2 Gy -1 and α/β=10 Gy), an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively. Conclusions: During this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies, with schedules modulated according to drug pharmacokinetics.

Original languageEnglish
Article number23
JournalTheoretical Biology and Medical Modelling
Volume9
Issue number1
DOIs
Publication statusPublished - 2012

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Monoclonal antibodies
Monoclonal Antibody
Radiation Tolerance
Growth Factors
Epidermal Growth Factor Receptor
Receptor
Inhibitor
Tumors
Tumor
Dose
Monoclonal Antibodies
Radiation
Cells
Cell
Radiotherapy
Modeling
Radiation-Sensitizing Agents
Neoplasms
Pharmacokinetics
Fractionation

ASJC Scopus subject areas

  • Health Informatics
  • Modelling and Simulation
  • Medicine(all)

Cite this

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title = "Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors",
abstract = "Purpose. To estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr). Materials and methods. Differences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED), has been introduced to account for changes in radiosensitivity parameters (α and α/β) rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED). The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered. Results: Assuming membrane EGFr over-expression corresponds to reduced radiosensitivity (α H=0.15 Gy -1 and α H /β H=7.5 Gy) relative to normal radiosensitivity (α=0.2 Gy -1 and α/β=10 Gy), an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively. Conclusions: During this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies, with schedules modulated according to drug pharmacokinetics.",
author = "Piernicola Pedicini and Rocchina Caivano and Jereczek-Fossa, {Barbara Alicia} and Lidia Strigari and Barbara Vischioni and Daniela Alterio and Marta Cremonesi and Francesca Botta and Antonio Nappi and Giuseppina Improta and Giovanni Storto and Marcello Benassi and Roberto Orecchia",
year = "2012",
doi = "10.1186/1742-4682-9-23",
language = "English",
volume = "9",
journal = "Theoretical Biology and Medical Modelling",
issn = "1742-4682",
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T1 - Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors

AU - Pedicini, Piernicola

AU - Caivano, Rocchina

AU - Jereczek-Fossa, Barbara Alicia

AU - Strigari, Lidia

AU - Vischioni, Barbara

AU - Alterio, Daniela

AU - Cremonesi, Marta

AU - Botta, Francesca

AU - Nappi, Antonio

AU - Improta, Giuseppina

AU - Storto, Giovanni

AU - Benassi, Marcello

AU - Orecchia, Roberto

PY - 2012

Y1 - 2012

N2 - Purpose. To estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr). Materials and methods. Differences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED), has been introduced to account for changes in radiosensitivity parameters (α and α/β) rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED). The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered. Results: Assuming membrane EGFr over-expression corresponds to reduced radiosensitivity (α H=0.15 Gy -1 and α H /β H=7.5 Gy) relative to normal radiosensitivity (α=0.2 Gy -1 and α/β=10 Gy), an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively. Conclusions: During this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies, with schedules modulated according to drug pharmacokinetics.

AB - Purpose. To estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr). Materials and methods. Differences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED), has been introduced to account for changes in radiosensitivity parameters (α and α/β) rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED). The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered. Results: Assuming membrane EGFr over-expression corresponds to reduced radiosensitivity (α H=0.15 Gy -1 and α H /β H=7.5 Gy) relative to normal radiosensitivity (α=0.2 Gy -1 and α/β=10 Gy), an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively. Conclusions: During this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies, with schedules modulated according to drug pharmacokinetics.

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