Changes in gene expression predicting local control in cervical cancer: results from Radiation Therapy Oncology Group 0128.
OBJECTIVE
To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation.


METHODS
Tissue biopsies were collected from patients participating in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation for locally advanced cervical cancer. Gene expression profiling was done and signatures of pretreatment, mid-treatment (before the first implant), and "changed" gene expression patterns between pre- and mid-treatment samples were determined. The ability of the gene signatures to predict local control versus local failure was evaluated. Two-group t test was done to identify the initial gene set separating these end points. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave-one-out and 2-fold cross-validation.


RESULTS
Twenty-two patients had suitable material from pretreatment samples for analysis, and 13 paired pre- and mid-treatment samples were obtained. The changed gene expression signatures between the pre- and mid-treatment biopsies predicted response to treatment, separating patients with local failures from those who achieved local control with a seven-gene signature. The in-sample prediction rate, leave-one-out prediction rate, and 2-fold prediction rate are 100% for this seven-gene signature. This signature was enriched for cell cycle genes.


CONCLUSIONS
Changed gene expression signatures during therapy in cervical cancer can predict outcome as measured by local control. After further validation, such findings could be applied to direct additional therapy for cervical cancer patients treated with chemotherapy and radiation.
Weidhaas
Joanne B
JB
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut, USA. Joanne.weidhaas@yale.edu
Li
Shu-Xia
SX
Winter
Kathryn
K
Ryu
Janice
J
Jhingran
Anuja
A
Miller
Bridgette
B
Dicker
Adam P
AP
Gaffney
David
D
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068579:Celecoxib; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D013449:Sulfonamides / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D002945:Cisplatin