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Prognostic Factors in Patients with Advanced HER2-Positive Gastric Cancer Treated with Trastuzumab-Based Chemotherapy: a Cohort Study

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Abstract

Purpose

Prognostic factors for the survival of patients with advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy remain controversial. The aim of this study was to identify the clinical factors that predict prognosis in patients with advanced HER2-positive gastric cancer.

Methods

We retrospectively reviewed the medical records of HER2-positive gastric cancer patients treated with trastuzumab-based chemotherapy at our institution. Clinical features and laboratory test results that considered prognostic factors were re-examined. Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate analysis was performed with the log-rank test and multivariate analysis was performed using Cox’s proportional hazard regression model.

Results

A total of 133 patients with advanced HER2-positive gastric cancer were enrolled. The median OS in this cohort was 18.7 months. Four prognostic factors: visceral metastasis (lung or liver), levels of hemoglobin (Hb) (< 11.6 g/dl), lactate dehydrogenase (LDH) (> 222 mg/dl), and C-reactive protein (CRP) (> 0.14 mg/dl), were identified as independent prognostic factors. The patients were placed into three groups according to their number of prognostic factors. These included low (0, 1), moderate (2, 3), and high (4) risk factors. The OS was separated into three categories with a median OS of 32.0, 18.7, and 10.1 months, respectively. Compared to the low-risk group, hazard ratios for the moderate- and high-risk groups were 1.75 and 3.49, respectively.

Conclusion

Visceral metastasis and abnormal Hb, LDH, and CRP levels were associated with unfavorable OS. These findings may be beneficial for the management of advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy.

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Availability of Data and Materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ADCC:

Antibody-dependent cell cytotoxicity

ALB:

Albumin

ALP:

Alkaline phosphatase

CA:

Carbohydrate antigen

CEA:

Carcinoembriogenic antigen

CIN:

Chromosomal instability

CRP:

C-reactive protein

EBV:

Epstein-Barr virus

ECF:

Epirubicin, cispaltin, 5-fluorouracil

ECOG:

Eastern Cooperative Oncology Group

FDG-PET:

Fluorodeoxyglucose positron-emission tomography

FISH:

Fluorescent in situ hybridization

FP:

Fluorouracil + cisplatin

GPS:

Glasgow Prognostic Score

HB:

Hemoglobin

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

IHS:

Immunohistochemistry scoring

JCOG:

Japan Clinical Oncology Group

LDH:

Lactate dehydrogenase

MSI:

Microsatellite instability

OS:

Overall survival

PS:

Performance status

RMH:

Royal Marsden Hospital

SOX:

S-1 (tegafur/gimeracil/oteracil) + oxaliplatin

TCGA:

The Cancer Genome Atlas

VEGF:

Vascular endothelial growth factor

XP:

Capecitabine + cisplatin.

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Acknowledgements

We would like to thank Editage (www.editage.com) for the English language editing.

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Authors and Affiliations

  1. Department of Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan

    Shoko Marshall

  2. Department of Gastrointestinal Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Shoko Marshall, Takeru Wakatsuki, Daisuke Takahari, Tomohiro Matsushima, Izuma Nakayama, Hiroki Osumi, Mariko Ogura, Takashi Ichimura, Eiji Shinozaki, Keisho Chin & Kensei Yamaguchi

  3. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan

    Tomohiro Matsushima

  4. Department of Clinical Trial Planning and Management, Clinical Research & Medical Development Center, Tokyo, Japan

    Naoki Ishizuka

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Contributions

SM and TW wrote the manuscript. SM and TM collected the data from the medical records. NI contributed to the statistical analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takeru Wakatsuki.

Ethics declarations

Ethics Approval and Consent to Participate

This study was approved by the Cancer Institute Hospital of the Japanese Foundation for Cancer Research Institutional Review Board (2017-1044). The study followed the Declaration of Helsinki by the World Medical Association. Written informed consent was obtained from all study participants.

Consent for Publication

Not applicable

Conflict of Interest

Shoko Marshall, Takeru Wakatsuki, Tomohiro Matsushima, Naoki Ishizuka, Izuma Nakayama, Hiroki Osumi, Mariko Ogura, Takashi Ichimura, Keisho Chin declare no competing interests. Daisuke Takahari reports lecture-related fees from Taiho, Eli Lilly, Bristol-Myers Squibb, Ono, and Chugai outside the submitted work. Eiji Shinozaki reports lecture-related fees from Chugai outside the submitted work. Kensei Yamaguchi reports legal fees from Chugai outside the submitted work.

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Marshall, S., Wakatsuki, T., Takahari, D. et al. Prognostic Factors in Patients with Advanced HER2-Positive Gastric Cancer Treated with Trastuzumab-Based Chemotherapy: a Cohort Study. J Gastrointest Canc 54, 475–484 (2023). https://doi.org/10.1007/s12029-022-00815-1

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