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Three-Course Neoadjuvant Chemotherapy Associated with Unfavorable Survival of Non-responders to the First Two Courses for Locally Advanced Esophageal Cancer

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Three-course neoadjuvant chemotherapy (NAC) followed by surgery has become a standard of care for locally advanced esophageal cancer (EC). However, some patients occasionally experience a poor tumor response to the third course and have a poor clinical outcome.

Methods

An exploratory analysis of data from the authors’ recent multicenter randomized phase 2 trial compared patients with locally advanced EC who received two courses (n = 78) and those who received three courses (n = 68) of NAC. The association between tumor response and clinico-pathologic factors, including survival, was evaluated to identify risk factors in the three-course group.

Results

Of 68 patients who received three courses of NAC, 28 (41.2%) had a tumor reduction rate lower than 10% during the third course. This rate was associated with unfavorable overall survival (OS) and progression-free survival (PFS) compared with a tumor reduction rate of 10% or higher (2-year OS rate: 63.5% vs. 89.3%, P = 0.007; 2-year PFS rate: 52.6% vs. 79.7%, P = 0.020). The independent prognostic factors for OS were tumor reduction rate lower than 10% during the third course (hazard ratio [HR], 2.735; 95% confidence interval [CI] 1.041–7.188; P = 0.041) and age of 65 years or older (HR, 9.557, 95% CI 1.240–73.63; P = 0.030). Receiver operating characteristic curve and multivariable logistic regression analyses identified a tumor reduction rate lower than 50% after the first two courses as an independent predictor of a tumor reduction rate lower than 10% during the third course of NAC (HR, 4.315; 95% CI 1.329–14.02; P = 0.015).

Conclusion

Continuing NAC through a third course may worsen survival for patients who do not experience a response to the first two courses in locally advanced EC.

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Acknowledgement

The authors sincerely appreciate all participating investigators for their valuable assistance with data collection.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

    Yuto Kubo MD, PhD, Tomoki Makino MD, PhD, Koji Tanaka MD, PhD, Kotaro Yamashita MD, PhD, Hidetoshi Eguchi MD, PhD & Yuichiro Doki MD, PhD

  2. Department of Surgery, Kansai Medical University, Hirakata, Japan

    Makoto Yamasaki MD, PhD

  3. Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan

    Osamu Shiraishi MD, PhD & Takushi Yasuda MD, PhD

  4. Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan

    Keijiro Sugimura MD, PhD

  5. Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan

    Hiroshi Miyata MD, PhD & Masahiko Yano MD, PhD

  6. Department of Surgery, Osaka General Medical Center, Osaka, Japan

    Masaaki Motoori MD, PhD & Kazumasa Fujitani MD, PhD

  7. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Atsushi Takeno MD, PhD & Motohiro Hirao MD, PhD

  8. Department of Surgery, Kindai University Nara Hospital, Nara, Japan

    Yutaka Kimura MD, PhD

  9. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan

    Taroh Satoh MD, PhD

  10. Department of Surgery, Suita Municipal Hospital, Osaka, Japan

    Masahiko Yano MD, PhD

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  1. Yuto Kubo MD, PhD
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Correspondence to Tomoki Makino MD, PhD.

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Fig. S1. Flow chart of patient eligibility for the study. (PDF 18 kb)

10434_2023_13548_MOESM2_ESM.pdf

Fig. S2. Survival with tumor reduction (cutoff, 10%) during the third course of neoadjuvant chemotherapy by age (cutoff, 65 years). (PDF 32 kb)

10434_2023_13548_MOESM3_ESM.pdf

Fig. S3. Receiver operating characteristic curve analysis of the reduction rate after the first two courses of neoadjuvant chemotherapy that predicted a tumor reduction rate lower than 10% during the third course of neoadjuvant chemotherapy. (PDF 19 kb)

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Kubo, Y., Makino, T., Yamasaki, M. et al. Three-Course Neoadjuvant Chemotherapy Associated with Unfavorable Survival of Non-responders to the First Two Courses for Locally Advanced Esophageal Cancer. Ann Surg Oncol 30, 5899–5907 (2023). https://doi.org/10.1245/s10434-023-13548-7

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