Severe late esophagus toxicity in NSCLC patients treated with IMRT and concurrent chemotherapy.
OBJECTIVE
We reported the incidence of severe late esophagus toxicity (LET) in locally advanced NSCLC patients treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. Acute esophagus toxicity (AET) and the dose to the esophagus were analyzed for their associations with severe LET.


METHODS
Two hundred and thirty-one patients treated from 2008 to 2011 with hypofractionated IMRT (66Gy/24fx) and concurrent daily low dose cisplatin were included. The association between AET and severe LET (grade ≥ 3 RTOG/EORTC) was tested through Cox-proportional-hazards model. Equivalent uniform dose (EUD) to the esophagus and the volume percentage receiving more than x Gy (Vx) were applied by Lyman-Kutcher-Burman (LKB) model.


RESULTS
A total of 171 patients were eligible for this study. Severe LET was observed in 6% patients. Both the maximum grade and the recovery rate of AET were significantly associated with severe LET. In the EUDn-LKB model, the fitted values and 95% confidence intervals (CIs) were TD50=76.1 Gy (73.2-78.6), m=0.03 (0.02-0.06) and n=0.03 (0-0.08). In the Vx-LKB model, the fitted values and 95% CIs were Tx50=23.5% (16.4-46.6), m=0.44 (0.32-0.60) and x=76.7 Gy (74.7-77.5).


CONCLUSIONS
Severe AET, EUD (n=0.03) and V76.7 to the esophagus were significantly associated with severe LET. An independent validation study is required.
Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Chun
C
Chen
Wilma
W
Uyterlinde
Jan-Jakob
JJ
Sonke
Josien
J
de Bois
Michel
M
van den Heuvel
José
J
Belderbos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004947:Esophagus / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009426:Netherlands; D011832:Radiation Injuries / Q000175:diagnosis / Q000473:pathology*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors
D002945:Cisplatin
Acute esophagus toxicity; Concurrent chemoradiation; IMRT; Late esophagus toxicity; NTCP; Non small cell lung cancer (NSCLC)