Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.
BACKGROUND
Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC.


METHODS
Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied.


RESULTS
After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%.


CONCLUSIONS
For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols.


BACKGROUND
NCT02720614, the date of registration: March 23, 2016.
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Xiao-Cang
XC
Ren
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Quan-Yu
QY
Wang
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Rui
R
Zhang
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Xue-Ji
XJ
Chen
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Na
N
Wang
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Yue-E
YE
Liu
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China.
Jie
J
Zong
Department of Radiology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu, Hebei Province, 062552, P.R. China.
Zhi-Jun
ZJ
Guo
Department of Cardiovascular Medicine, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu, Hebei Province, 062552, P.R. China.
Dong-Ying
DY
Wang
Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province, 062552, P.R. China. billhappy001@163.com.
Qiang
Q
Lin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*
Accelerated hypofractionated radiotherapy; Concurrent radiochemotherapy; Maximum tolerated dose; Non-small cell lung cancer; Three-dimensional conformal radiation therapy