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Caution against simultaneous integrated boost radiotherapy for upper thoracic esophageal squamous cell carcinoma: results from a single-arm phase II trial

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To explore the feasibility and safety of simultaneous integrated boost technology (SIB) with elective nodal irradiation (ENI) to the cervical and upper mediastinal lymph node (LN) regions in upper thoracic esophageal squamous cell carcinoma (ESCC).

Material and methods

Patients with pathologically proven unresectable upper thoracic ESCC were assigned 50.4 Gy/28 fractions (F) to the clinical target volume (encompassing the ENI area of cervical and upper mediastinal LN regions) and a boost of 63 Gy/28 F to the gross tumor volume. Chemotherapy consisted of courses of concurrent cisplatin (20 mg/m2) and docetaxel (20 mg/m2) weekly for 6 weeks. The primary endpoint was toxicity.


Between Jan 2017 and Dec 2019, 28 patients were included. The median follow-up time for all patients was 24.6 months (range 1.9–53.5). Radiation-related acute toxicity included esophagitis, pneumonia and radiodermatitis, all of which were well managed and reversed. Late morbidity included esophageal ulcer, stenosis, fistula and pulmonary fibrosis. Grade III esophageal stenosis and fistula was seen in 11% (3/28) and 14% (4/28) patients, respectively. The cumulative incidence rate of late esophageal toxicity was 7.7%, 19.2% and 24.6% at 6, 12 and 18 months, respectively. There was significant difference of the occurrence of severe late esophageal toxicity among the different volume levels of the esophagus, and cervical and upper mediastinal LNs which received ≥ 63 Gy stratified by the tertiles (p = 0.014).


Despite the acceptably tolerated acute toxicity of SIB in concurrent CRT with ENI to the cervical and upper mediastinal LN regions for upper thoracic ESCC, the incidence of severe late esophageal toxicity was relatively high. Cautions are provided against easy clinical application of SIB (50.4 Gy/28F to the CTV, 63 Gy/28F to the GTV) in upper thoracic ESCC. Further exploration on dose optimization is warranted.

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Data availability

The data are available from the corresponding author on reasonable request.



American joint committee on cancer


Confidence interval




Computed tomography


Clinical target volume


Eastern cooperative oncology group


Elective nodal irradiation


Esophageal squamous cell carcinoma


Endoscopic ultrasound




Gross tumor volume


Intensity-modulated radiotherapy


Lymph node


National cancer institute common terminology criteria for adverse events


Overall survival


Positron emission tomography


Progression-free survival


Planning target volume


Radiation therapy oncology group


Simultaneous integrated boost


Tumor nodes metastasis


Treatment-related toxicity

V30Gy :

The volume receiving > 30 Gy

V50.4  Gy :

The volume receiving > 50.4 Gy

V63Gy :

The volume receiving > 63 Gy


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This work was supported by a grant from National Key Research and Development Program of China (Grant number 2022YFC2505800) and a grant from the National Natural Science Foundation of China (Grant number 82003230).

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Authors and Affiliations



Conceptualization: YZ, XY and ZZ. Data curation: YZ, XY, LC, XC, JN, YL, TG. Formal analysis: YZ and TG. Methodology: XY and ZZ. Funding acquisition: ZZ. Writing—original draft: YZ and XY. Writing—review and editing: YZ and XY. Study supervision: XY and ZZ.

Corresponding authors

Correspondence to Xi Yang or Zhengfei Zhu.

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This study was approved by the Administration Committee of Fudan University Shanghai Cancer Center, China.

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Zhou, Y., Chu, L., Lu, S. et al. Caution against simultaneous integrated boost radiotherapy for upper thoracic esophageal squamous cell carcinoma: results from a single-arm phase II trial. Esophagus 20, 713–721 (2023).

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