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 (alpha and alpha/beta) 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 (alphaH = 0.15 Gy-1 and alphaH/betaH = 7.5 Gy) relative to normal radiosensitivity (alpha = 0.2 Gy-1 and alpha/beta = 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.

Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors / P. Pedicini, R. Caivano, B.A. Jereczek-Fossa, L. Strigari, B. Vischioni, D. Alterio, M. Cremonesi, F. Botta, A. Nappi, G. Improta, G. Storto, M. Benassi, R. Orecchia, V. Fusco. - In: THEORETICAL BIOLOGY AND MEDICAL MODELLING. - ISSN 1742-4682. - 9:1(2012 Jun 19), pp. 23.1-23.13. [10.1186/1742-4682-9-23]

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

B.A. Jereczek-Fossa;R. Orecchia
Penultimo
;
2012

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 (alpha and alpha/beta) 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 (alphaH = 0.15 Gy-1 and alphaH/betaH = 7.5 Gy) relative to normal radiosensitivity (alpha = 0.2 Gy-1 and alpha/beta = 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.
epidermal-growth-factor; factor receptor expression; control probability; radiotherapy; carcinoma; cancer; head; heterogeneity; cetuximab; survival
Settore MED/36 - Diagnostica per Immagini e Radioterapia
19-giu-2012
Article (author)
File in questo prodotto:
File Dimensione Formato  
1742-4682-9-23.pdf

accesso aperto

Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 487.94 kB
Formato Adobe PDF
487.94 kB Adobe PDF Visualizza/Apri
1742-4682-9-23.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.36 MB
Formato Adobe PDF
1.36 MB Adobe PDF Visualizza/Apri
1742-4682-9-37.pdf

accesso aperto

Descrizione: Correction
Tipologia: Publisher's version/PDF
Dimensione 213.25 kB
Formato Adobe PDF
213.25 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/199570
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 11
social impact