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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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Abstract

Purpose

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.

Results

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).

Conclusions

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.

Abbreviations

AJCC:

American joint committee on cancer

CI:

Confidence interval

CRT:

Chemoradiotherapy

CT:

Computed tomography

CTV:

Clinical target volume

ECOG:

Eastern cooperative oncology group

ENI:

Elective nodal irradiation

ESCC:

Esophageal squamous cell carcinoma

EUS:

Endoscopic ultrasound

F:

Fraction

GTV:

Gross tumor volume

IMRT:

Intensity-modulated radiotherapy

LN:

Lymph node

NCI-CTCAE:

National cancer institute common terminology criteria for adverse events

OS:

Overall survival

PET:

Positron emission tomography

PFS:

Progression-free survival

PTV:

Planning target volume

RTOG:

Radiation therapy oncology group

SIB:

Simultaneous integrated boost

TNM:

Tumor nodes metastasis

TRT:

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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Funding

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

Authors

Contributions

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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Ethical statement

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

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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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). https://doi.org/10.1007/s10388-023-01012-0

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