Neoadjuvant chemo-radiotherapy for locally advanced esophageal cancer: a monocentric study.
OBJECTIVE
Multimodal therapy is a keystone of care in advanced esophageal cancer. Although neoadjuvant chemoradiotherapy is known to provide a survival advantage in selected cases, reliable prognostic and response predictive factors remain elusive. We report the outcome in a series of esophageal cancer patients treated at our center and the results of a retrospective analysis of epidermal growth factor receptor (EGFR) expression and EGFR/HER2 gene copy numbers taken as possible prognostic and predictive factors.


METHODS
Between 2001 and 2009, a total of 40 consecutive patients (34 men and 6 women; median age, 59 years) were treated for esophageal cancer.


METHODS
cisplatin, 80 mg/m² day 1, and 5-fluorouracil, 800 mg/m²/24 h on days 1-5, every 21 days, concomitant with 3D-conformal radiotherapy (54-59.4 in 30-33 fractions) for three up to four cycles. Surgery was performed in eligible patients 6-8 weeks after chemoradiation. EGFR expression and EGFR/HER2 amplification and gene copy number were studied by immunohistochemical analysis and fluorescence in situ hybridization, respectively.


RESULTS
Acceptable toxicity following chemoradiation was recorded, with G3-G4 hematological toxicity in 20% of patients and G3-G4 dysphagia in less than 10%; 14 (35%) patients achieved complete response and 19 (48%) partial response; 18 underwent surgery after chemoradiation, of which 8 (20%) achieved pathologic complete response. The median survival was 29 months (95% CI, 25.7-32.1): 42 months for the resected and 20 for the unresected patients. EGFR and HER2 analysis in 28 patients showed that 89% had immunohistochemical EGFR expression, with 5 cases of EGFR and 10 of HER2 gene gain without a significant difference in response rate and survival in these patient subgroups.


CONCLUSIONS
Our results suggest a better outcome in patients who underwent surgery after chemoradiation. A larger sample size is necessary to clarify the role of EGFR and HER2 gene gain in predict response and survival.
Department of Onco-Hematology, Oncology Unit, San Giovanni Battista Hospital, Turin, Italy. mschena@molinette.piemonte.it
Marina
M
Schena
Erika
E
La Rovere
Dino
D
Solerio
Sara
S
Bustreo
Carla
C
Barone
Lorenzo
L
Daniele
Lucio
L
Buffoni
Paolo
P
Bironzo
Anna
A
Sapino
Guido
G
Gasparri
Libero
L
Ciuffreda
Umberto
U
Ricardi
D000230:Adenocarcinoma / Q000628:therapy; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D002945:Cisplatin; D066246:ErbB Receptors; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human