Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Jul;28(7):3951-3960.
doi: 10.1245/s10434-020-09372-y. Epub 2020 Nov 28.

Effect of Extending the Original CROSS Criteria on Tumor Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients: A National Multicenter Cohort Analysis

Helena Hong Wang  1   2 , Ellen C de Heer  2 , Jan Binne Hulshoff  3 , Gursah Kats-Ugurlu  4 , Johannes G M Burgerhof  5 , Boudewijn van Etten  1 , John Th M Plukker  1 , Geke A P Hospers  6 ; Dutch Upper Gastrointestinal Cancer Audit (DUCA) Group
Affiliations
Multicenter Study

Effect of Extending the Original CROSS Criteria on Tumor Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients: A National Multicenter Cohort Analysis

Helena Hong Wang et al. Ann Surg Oncol. 2021 Jul.

Abstract

Background: Extending the original criteria of the Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) in daily practice may increase the treatment outcome of esophageal cancer (EC) patients. This retrospective national cohort study assessed the impact on the pathologic complete response (pCR) rate and surgical outcome.

Patients and methods: Data from EC patients treated between 2009 and 2017 were collected from the national Dutch Upper Gastrointestinal Cancer Audit database. Patients had locally advanced EC (cT1/N+ or cT2-4a/N0-3/M0) and were treated according to the CROSS regimen. CROSS (n = 1942) and the extended CROSS (e-CROSS; n = 1359) represent patients fulfilling the original or extended CROSS criteria, respectively. The primary outcome was total pCR (ypT0N0), while secondary outcomes were local esophageal pCR (ypT0), surgical radicality, and postoperative morbidity and mortality.

Results: Overall, CROSS and e-CROSS did not differ in total or local pCR rate, although a trend was observed (23.2% vs. 20.4%, p = 0.052; and 26.7% vs. 23.8%, p = 0.061). When stratifying by histology, the pCR rate was higher in the CROSS group compared with e-CROSS in squamous cell carcinomas (48.2% vs. 33.3%, p = 0.000) but not in adenocarcinomas (16.8% vs. 16.9%, p = 0.908). Surgical radicality did not differ between groups. Postoperative mortality (3.2% vs. 4.6%, p = 0.037) and morbidity (58.3% vs. 61.8%, p = 0.048) were higher in e-CROSS.

Conclusion: Extending the CROSS inclusion criteria for neoadjuvant chemoradiotherapy in routine clinical practice of EC patients had no impact on the pCR rate and on radicality, but was associated with increased postoperative mortality and morbidity. Importantly, effects differed between histological subtypes. Hence, in future studies, we should carefully reconsider who will benefit most in the real-world setting.

PubMed Disclaimer

Conflict of interest statement

Geke A.P. Hospers received consulting and advisory role fees from Amgen, Roche, MSD, BMS, Pfizer, Novartis, and Pierre Fabry, paid to the institution [University Medical Center Groningen (UMCG)]; and research grants from BMS and Seerave, also paid to the institution (UMCG). Helena Hong Wang, Ellen C. de Heer, Jan Binne Hulshoff, Gursah Kats-Ugurlu, Johannes G.M Burgerhof, Boudewijn van Etten, and John Th. M. Plukker have declared no conflicts of interest.

References

    1. Van Hagen P, Hulshof MCCM, Van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. New Engl J Med. 2012;366(22):2074–2084. doi: 10.1056/NEJMoa1112088. - DOI - PubMed
    1. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–1098. doi: 10.1016/S1470-2045(15)00040-6. - DOI - PubMed
    1. de Heer EC, Hulshoff JB, Klerk D, et al. Effect of extending the original eligibility criteria for the CROSS neoadjuvant chemoradiotherapy on toxicity and survival in esophageal cancer. Ann Surg Oncol. 2017;24(7):1811–1820. doi: 10.1245/s10434-017-5797-3. - DOI - PMC - PubMed
    1. Toxopeus E, van der Schaaf M, van Lanschot J, et al. Outcome of patients treated within and outside a randomized clinical trial on neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: extrapolation of a randomized clinical trial (CROSS) Ann Surg Oncol. 2018;25(8):2441–2448. doi: 10.1245/s10434-018-6554-y. - DOI - PMC - PubMed
    1. Blum Murphy M, Xiao L, Patel VR, et al. Pathological complete response in patients with esophageal cancer after the trimodality approach: the association with baseline variables and survival—the University of Texas MD Anderson Cancer Center experience. Cancer. 2017;123(21):4106–4113. doi: 10.1002/cncr.30953. - DOI - PubMed

Publication types