title: Correlation between EGFr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (TD) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  A survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr), respectively. By obtaining the TD from the above analysis and the sub-sites' potential doubling time (Tpot) from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif), was estimated.
  
  
  RESULTS
  The averages of TD were 77 (27-90)95% days in LEGFr and 8.8 (7.3-11.0)95% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites' TD were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed.
  
  
  CONCLUSIONS
  A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck sub-site.
authors.affiliation: I.R.C.C.S. C.R.O.B. Regional Cancer Hospital, Rionero in Vulture, Italy. ppiern@libero.it
authors.forename: Piernicola
authors.initials: P
authors.lastname: Pedicini
authors.forename: Antonio
authors.initials: A
authors.lastname: Nappi
authors.forename: Lidia
authors.initials: L
authors.lastname: Strigari
authors.forename: Barbara Alicia
authors.initials: BA
authors.lastname: Jereczek-Fossa
authors.forename: Daniela
authors.initials: D
authors.lastname: Alterio
authors.forename: Marta
authors.initials: M
authors.lastname: Cremonesi
authors.forename: Francesca
authors.initials: F
authors.lastname: Botta
authors.forename: Barbara
authors.initials: B
authors.lastname: Vischioni
authors.forename: Rocchina
authors.initials: R
authors.lastname: Caivano
authors.forename: Alba
authors.initials: A
authors.lastname: Fiorentino
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Improta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Storto
authors.forename: Marcello
authors.initials: M
authors.lastname: Benassi
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
mesh_terms: D000054:Acceleration; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D049109:Cell Proliferation; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors