Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy

C J van der Zijden; P C van der Sluis; B Mostert; J J M E Nuyttens; V M C W Spaander; R Valkema; J P Ruurda; B P L Wijnhoven; S M Lagarde

doi:10.1245/s10434-024-14912-x

Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy

C J van der Zijden^*, P C van der Sluis, B Mostert, J J M E Nuyttens, V M C W Spaander, R Valkema, J P Ruurda, B P L Wijnhoven, S M Lagarde

^*Corresponding author for this work

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Abstract

BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment.

OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin.

METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up.

RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively.

CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

Original language	English
Pages (from-to)	3813-3818
Number of pages	6
Journal	Annals of surgical oncology
Volume	31
Issue number	6
Early online date	20 Jan 2024
DOIs	https://doi.org/10.1245/s10434-024-14912-x
Publication status	Published - Jun 2024

Keywords

Adjuvant therapy
Esophageal cancer
Neoadjuvant chemoradiotherapy
Tumor-positive resection margin

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van der Zijden, C. J., van der Sluis, P. C., Mostert, B., Nuyttens, J. J. M. E., Spaander, V. M. C. W., Valkema, R., Ruurda, J. P., Wijnhoven, B. P. L., & Lagarde, S. M. (2024). Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy. Annals of surgical oncology, 31(6), 3813-3818. https://doi.org/10.1245/s10434-024-14912-x

@article{86156f74f52a4bc58b8009ecc32b9079,

title = "Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy",

abstract = "BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment.OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin.METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up.RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively.CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.",

keywords = "Adjuvant therapy, Esophageal cancer, Neoadjuvant chemoradiotherapy, Tumor-positive resection margin",

author = "{van der Zijden}, {C J} and {van der Sluis}, {P C} and B Mostert and Nuyttens, {J J M E} and Spaander, {V M C W} and R Valkema and Ruurda, {J P} and Wijnhoven, {B P L} and Lagarde, {S M}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jun,

doi = "10.1245/s10434-024-14912-x",

language = "English",

volume = "31",

pages = "3813--3818",

journal = "Annals of surgical oncology",

issn = "1068-9265",

publisher = "Springer New York",

number = "6",

}

van der Zijden, CJ, van der Sluis, PC, Mostert, B, Nuyttens, JJME, Spaander, VMCW, Valkema, R, Ruurda, JP, Wijnhoven, BPL & Lagarde, SM 2024, 'Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy', Annals of surgical oncology, vol. 31, no. 6, pp. 3813-3818. https://doi.org/10.1245/s10434-024-14912-x

TY - JOUR

T1 - Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy

AU - van der Zijden, C J

AU - van der Sluis, P C

AU - Mostert, B

AU - Nuyttens, J J M E

AU - Spaander, V M C W

AU - Valkema, R

AU - Ruurda, J P

AU - Wijnhoven, B P L

AU - Lagarde, S M

PY - 2024/6

Y1 - 2024/6

N2 - BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment.OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin.METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up.RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively.CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

AB - BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment.OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin.METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up.RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively.CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

KW - Adjuvant therapy

KW - Esophageal cancer

KW - Neoadjuvant chemoradiotherapy

KW - Tumor-positive resection margin

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U2 - 10.1245/s10434-024-14912-x

DO - 10.1245/s10434-024-14912-x

M3 - Article

C2 - 38245648

SN - 1068-9265

VL - 31

SP - 3813

EP - 3818

JO - Annals of surgical oncology

JF - Annals of surgical oncology

IS - 6

ER -

Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy

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