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A nomogram to predict the cumulative risk for brain metastases in patients with limited-stage small cell lung cancer without prophylactic cranial irradiation

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Abstract

Objective

Patients with small cell lung cancer (SCLC) have a high risk of developing brain metastases (BM). Prophylactic cranial irradiation (PCI) is a standard therapy for limited-stage SCLC (LS-SCLC) patients who achieved complete or partial response after thoracic chemoradiotherapy (Chemo-RT). Recent studies have indicated that a subgroup of patients with a lower risk of BM can avoid PCI, and the present study therefore tries to construct a nomogram to predict the cumulative risk of development of BM in LS-SCLC patients without PCI.

Methods

After screening of 2298 SCLC patients who were treated at the Zhejiang Cancer Hospital from December 2009 to April 2016, a total of 167 consecutive patients with LS-SCLC who received thoracic Chemo-RT without PCI were retrospectively analyzed. The paper analyzed clinical and laboratory factors that may be correlated with BM, such as response to treatment, pretreatment serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, and TNM stage. Thereafter, a nomogram was constructed to predict 3‑ and 5‑year intracranial progression-free survival (IPFS).

Results

Of 167 patients with LS-SCLC, 50 developed subsequent BM. Univariate analysis showed that pretreatment LDH (pre-LDH) ≥ 200 IU/L, an incomplete response to initial chemoradiation, and UICC stage III were positively correlated to a higher risk of BM (p < 0.05). Multivariate analysis identified pretreatment LDH level (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.08–3.34, p = 0.026), response to chemoradiation (HR 1.87, 95% CI 1.04–3.34, p = 0.035), and UICC stage (HR 6.67, 95% CI 1.03–49.15, p = 0.043) as independent predictors for the development of BM. A nomogram model was then established, and areas under the curve of 3‑year and 5‑year IPFS were 0.72 and 0.67, respectively.

Conclusion

The present study has developed an innovative tool that is able to predict the individual cumulative risk for development of BM in LS-SCLC patients without PCI, which is beneficial for providing personalized risk estimates and facilitating the decision to perform PCI.

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Abbreviations

AJCC:

American Joint Committee on Cancer

ATP:

Adenosine triphosphate

AUC:

Area under the receiver operating characteristic curve

BM:

Brain metastasis

CCRT:

Concurrent chemoradiotherapy

Chemo-RT:

Chemoradiotherapy

CI:

Confidence interval

CR:

Complete remission

CT:

Computed tomography

ECOG-PS:

Eastern Cooperative Oncology Group performance status

ECT:

Emission computed tomography

EP:

Etoposide and cisplatin

ESTRO:

European Society of Radiation Therapy and Oncology

HR:

Hazard ratio

IMRT:

Intensity-modulated radiotherapy

IPFS:

Intracranial progression-free survival

LDH:

Lactate dehydrogenase in serum

LS-SCLC:

Limited-stage small cell lung cancer

MRI:

Magnetic resonance imaging

NCCN:

National Comprehensive Cancer Network

No BM:

Non-appearance of BMs

NSCLC:

Non-small cell lung cancer

NSE:

Neuron-specific enolase

OS:

Overall survival

PCI:

Prophylactic cranial irradiation

PET:

Positron-emission tomography

PR:

Partial response

preLDH:

Pretreatment LDH

RECIST:

Response Evaluation Criteria in Solid Tumors

ROC:

Receiver operating characteristic

ROS:

Reactive oxygen species

SCLC:

Small cell lung cancer

SD:

Stable disease

TRT:

Thoracic radiation therapy

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Acknowledgements

This work was supported by grants from the Health Science and Technology Plan Project of Zhejiang (2021KY1149) and the Shaoxing Health Science and Technology Plan (2022KY027).

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Authors and Affiliations

  1. Department of Radiation Oncology, Shaoxing People’s Hospital, 312000, Shaoxing, Zhejiang, China

    Jianjiang Liu, Dongping Wu & Bin Shen

  2. Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, No 1, East Banshan Road, Gongshu District, Hangzhou, China

    Mengyuan Chen, Xia Zhou, Guoqin Qiu, Yongling Ji, Xianghui Du & Yang Yang

  3. Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China

    Mengyuan Chen, Xia Zhou, Peng Zhang, Guoqin Qiu, Yongling Ji, Xianghui Du & Yang Yang

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  1. Jianjiang Liu
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Correspondence to Yang Yang.

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Conflict of interest

J. Liu, D. Wu, B. Shen, M. Chen, X. Zhou, P. Zhang, G. Qiu, Y. Ji, X. Du, and Y. Yang declare that they have no competing interests.

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The authors Jianjiang Liu and Dongping Wu contributed equally to the manuscript.

Supplementary Information

Figure S1. Cumulative incidence rate of brain metastasis, according to different factors.

Table S1. Univariate analysis and multivariate analysis predicting OS.

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Liu, J., Wu, D., Shen, B. et al. A nomogram to predict the cumulative risk for brain metastases in patients with limited-stage small cell lung cancer without prophylactic cranial irradiation. Strahlenther Onkol 199, 727–738 (2023). https://doi.org/10.1007/s00066-023-02073-x

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