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Risk prediction models based on hematological/body parameters for chemotherapy-induced adverse effects in Chinese colorectal cancer patients

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Abstract

Purpose

To determine risk factors and develop novel prediction models for chemotherapy-induced adverse effects (CIAEs) in Chinese colorectal cancer (CRC) patients receiving capecitabine.

Methods

A total of 233 Chinese CRC patients receiving post-operative chemotherapy with capecitabine were randomly divided into a training set (70%) and a validation set (30%). CIAE-related hematological/body parameters were screened by univariate logistic regression. Based on a set of factors selected from LASSO (least absolute shrinkage and selection operator) logistic regression, stepwise multivariate logistic regression was applied to develop prediction models. Area under the receiver operating characteristic (ROC) curve and Hosmer–Lemeshow (HL) test were used to evaluate the discriminatory ability and the goodness of fit of each model.

Results

In total, 35 variables were identified to be associated with CIAEs in univariate analysis. Developed multivariable models had AUCs (area under curve) ranging from 0.625 to 0.888 and 0.428 to 0.760 in the training and validation set, respectively. The grade ≥ 1 anemia multivariable model achieved the best discriminatory ability with AUC of 0.760 (95%CI: 0.609–0.912) and good calibration with HL P value of 0.450. Then, a nomogram was constructed to predict grade ≥ 1 anemia, which included variables of age, pre-operative hemoglobin count, and pre-operative albumin count, with C-indexes of 0.775 and 0.806 in the training and validation set, respectively.

Conclusions

This study identified valuable hematological/body parameters related to CIAEs. A nomogram based on the multivariable model including three hematological/body predictors can accurately predict grade ≥ 1 anemia, facilitating clinicians to implement personalized medicine early for Chinese CRC patients receiving post-operative chemotherapy for better safety treatment.

Trial registration

This study was registered as a clinical trial at www.clinicaltrials.gov (NCT03030508).

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Data availability

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

Code availability

All codes for data cleaning and analysis associated with the current study are available from the corresponding author on reasonable request.

Abbreviations

AD:

Abdominal distension

ALB:

Albumin

ALT:

Alanine aminotransferase

AP:

Abdominal pain

AST:

Aspartate aminotransferase

AUC:

Area under the curve

BMI:

Body mass index

BMS:

Bone marrow suppression

CI:

Confidence interval

CIAE:

Chemotherapy-induced adverse effect

CINV:

Chemotherapy-induced nausea and vomiting

CRC:

Colorectal cancer

CRP:

C-reactive protein

Delta:

Difference between pre- and post-operation

EMR:

Electronic medical record

HFS:

Hand-foot syndrome

HGB:

Hemoglobin

HL:

Hosmer–Lemeshow

HSC:

Hematopoietic stem cell

IALT:

Alanine aminotransferase increased

IAST:

Aspartate aminotransferase increased

LASSO:

Least absolute shrinkage and selection operator

LY:

Lymphocyte

MON:

Monocyte

NEU:

Neutrophil

NLR:

Neutrophil to lymphocyte ratio

OR:

Odds ratio

PCDI:

Per capita disposable income

PLR:

Platelet to lymphocyte ratio

PLT:

Platelet

Post:

Post-operative

Pre:

Pre-operative

RBC:

Red blood cell

ROC:

Receiver operating characteristic

SD:

Standard deviation

TCP:

Thrombocytopenia

WBC:

White blood cell

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Acknowledgements

The authors thank all the participants in this study and the staff of the Department of General Surgery of Shanghai Changzheng Hospital of China for assistance with the clinical data collection.

Funding

This work was supported by the Shanghai Science and Technology Commission Research Project of China (Grant No. 13DZ1930602); International Scientific and Technological Cooperation Project of China (Grant No. 2015DFA31810); Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center of China (Grant No. SHDC12015120); National Major Scientific and Technological Special Project for “Significant New Drugs Development” (Grant No. 2020ZX09101001); and National Key Research and Development Program of China (Grant No. 2019YFC1711102).

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Author notes

  1. Mingming Li, Jiani Chen, and Yi Deng contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China

    Mingming Li, Jiani Chen, Yi Deng, Hua Wei & Wansheng Chen

  2. School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China

    Jiani Chen, Haixia Gu & Yanjun Zhou

  3. College of Chemical and Biological Engineering, Yichun University, Jiangxi, 336000, China

    Tao Yan

  4. Department of General Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China

    Houshan Yao

  5. Department of Pharmacy, 905th Hospital of PLA Navy, Naval Medical University, Shanghai, 200052, China

    Hua Wei

  6. Traditional Chinese Medicine Resource and Technology Center, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Wansheng Chen

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Contributions

Houshan Yao, Hua Wei, and Wansheng Chen designed and supervised the study. Mingming Li, Jiani Chen, and Yi Deng analyzed and interpreted the data, and wrote the original draft. Tao Yan, Haixia Gu, and Yanjun Zhou collected the data and visualized the data. All authors contributed to the writing of this manuscript. All authors read and approved of the final manuscript.

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Correspondence to Houshan Yao, Hua Wei or Wansheng Chen.

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Patients in this study were selected from a registered clinical trial (registered at www.clinicaltrials.gov, NCT03030508) at Shanghai Changzheng Hospital from January 2016 to June 2019. The ethics of this study was approved by the Biomedical Research Ethics Committee of Shanghai Changzheng Hospital (No. 2016SL007).

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Li, M., Chen, J., Deng, Y. et al. Risk prediction models based on hematological/body parameters for chemotherapy-induced adverse effects in Chinese colorectal cancer patients. Support Care Cancer 29, 7931–7947 (2021). https://doi.org/10.1007/s00520-021-06337-z

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