Predicting the effect of accelerated fractionation in postoperative radiotherapy for head and neck cancer based on molecular marker profiles: data from a randomized clinical trial.
OBJECTIVE
To determine the prognostic and predictive values of molecular marker expression profiles based on data from a randomized clinical trial of postoperative conventional fractionation (p-CF) therapy versus 7-day-per-week postoperative continuous accelerated irradiation (p-CAIR) therapy for squamous cell cancer of the head and neck.


METHODS
Tumor samples from 148 patients (72 p-CF and 76 p-CAIR patients) were available for molecular studies. Immunohistochemistry was used to assess levels of EGFR, nm23, Ki-67, p-53, and cyclin D1 expression. To evaluate the effect of fractionation relative to the expression profiles, data for locoregional tumor control (LRC) were analyzed using the Cox proportional hazard regression model. Survival curves were compared using the Cox f test.


RESULTS
Patients who had tumors with low Ki-67, low p-53, and high EGFR expression levels and oral cavity/oropharyngeal primary cancer sites tended to benefit from p-CAIR. A joint score for the gain in LRC from p-CAIR based of these features was used to separate the patients into two groups: those who benefited significantly from p-CAIR with respect to LRC (n = 49 patients; 5-year LRC of 28% vs. 68%; p = 0.01) and those who did not benefit from p-CAIR (n = 99 patients; 5-year LRC of 72% vs. 66%; p = 0.38). The nm23 expression level appeared useful as a prognostic factor but not as a predictor of fractionation effect.


CONCLUSIONS
These results support the studies that demonstrate the potential of molecular profiles to predict the benefit from accelerated radiotherapy. The molecular profile that favored accelerated treatment (low Ki-67, low p-53, and high EGFR expression) was in a good accordance with results provided by other investigators. Combining individual predictors in a joint score may improve their predictive potential.
Suwinski
Rafal
R
Department of Radiation Oncology, Center of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland. rafals@io.gliwice.pl
Jaworska
Magdalena
M
Nikiel
Barbara
B
Grzegorz
Wozniak
W
Bankowska-Wozniak
Magdalena
M
Wojciech
Majewski
M
Krzysztof
Skladowski
S
Dariusz
Lange
L
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D019938:Cyclin D1 / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007822:Laryngeal Neoplasms / Q000737:chemistry / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000532:radiotherapy; D054778:NM23 Nucleoside Diphosphate Kinases / Q000032:analysis; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000532:radiotherapy; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000379:methods; D011879:Radiotherapy Dosage; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D054778:NM23 Nucleoside Diphosphate Kinases; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D066246:ErbB Receptors; C517938:NME1 protein, human