Abstract
Background
Small cell lung cancer (SCLC) is characterized by a high risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI).
Methods
This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan–Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival.
Results
Of the total patients, 28 had higher pretreatment LDH levels and mLDH levels were increased in 95 patients during treatment. In patients in the normal and elevated mLDH groups, the 1‑, 2‑, and 5‑year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had a higher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73–8.63; P < 0.01) and worse overall survival (HR 2.59; 95% CI 1.67–4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95% CI 1.57–7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95% CI 1.22–4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95% CI 1.56–3.86; P < 0.001), IIIB stage (HR 1.75; 95% CI 1.06–2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95% CI 1.04–2.65; P = 0.034).
Conclusion
The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification.
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Abbreviations
- ATP:
-
Adenosine-triphosphate
- BED:
-
Biologically effective dose
- BM:
-
Brain metastasis
- CCRT:
-
Concurrent chemoradiotherapy
- CI:
-
Confidence interval
- CR:
-
Complete response
- CT:
-
Computed tomography
- ECOG-PS:
-
Eastern Cooperative Oncology Group performance status
- ECPFS:
-
Extracranial progression-free survival
- ECT:
-
Emission computed tomography
- ED:
-
Extensive disease
- EP:
-
Etoposide and platinum
- HR:
-
Hazard ratio
- IMRT:
-
Intensity-modulated radiotherapy
- IPFS:
-
Intracranial progression-free survival
- LD:
-
Limited disease
- LDH:
-
Lactate dehydrogenase
- LS-SCLC:
-
Limited-stage small cell lung cancer
- mLDH:
-
Maximal serum LDH levels
- MRI:
-
Magnetic resonance imaging
- NCCN:
-
National Comprehensive Cancer Network
- NSCLC:
-
Non-small cell lung cancer
- NSE:
-
Neuron-specific enolase
- OS:
-
Overall survival
- PCI:
-
Prophylactic cranial irradiation
- PET:
-
Positron-emission tomography
- PR:
-
Partial response
- Pro-GRP:
-
Prosoma gastric secretin release peptide
- PS:
-
Performance status
- ROS:
-
Reactive oxygen species
- SCLC:
-
Small cell lung cancer
- SCRT:
-
Sequential chemotherapy and radiotherapy
- SD:
-
Standard dose
- TRT:
-
Thoracic radiotherapy
- ULN:
-
Upper limit of normal value
- WBRT:
-
Whole-brain radiation therapy
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Acknowledgements
We thank all members of the Department of Thoracic Radiation Oncology.
Funding
This work was supported by Natural Science Foundation of Zhejiang Province (no. LY20H160006).
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Jianjiang Liu and Dongping Wu are responsible for data collation and paper writing, Yang Yang is responsible for paper guidance and revision, and the remaining authors are responsible for paper revision.
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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.
Ethical standards
This study has been approved by the Ethics Committee of the Zhejiang Cancer Hospital. For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case. Consent for publication: All authors agree to publish.
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The authors Jianjiang Liu and Dongping Wu contributed equally to the manuscript.
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The data of this study have been recorded in the Science and Education Department of Zhejiang Cancer Hospital in Excel format.
Supplementary Information
66_2022_1977_MOESM1_ESM.tif
Supplementary figures (A, B, and C). Kaplan–Meier curves of groups of higher and normal LDH levels for extracranial progression-free survival (ECPFS). (A): Kaplan–Meier survival curve of ECPFS of higher mLDH and normal groups during treatment; (B): Kaplan–Meier survival curve of ECPFS of higher pretreatment LDH and normal groups; (C): Kaplan–Meier survival curve of ECPFS of elevated and deceased groups after comparison between pretreatment and maximum LDH level during treatment
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Liu, J., Wu, D., Shen, B. et al. Serum lactate dehydrogenase predicts brain metastasis and survival in limited-stage small cell lung cancer patients treated with thoracic radiotherapy and prophylactic cranial irradiation. Strahlenther Onkol 198, 1094–1104 (2022). https://doi.org/10.1007/s00066-022-01977-4
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DOI: https://doi.org/10.1007/s00066-022-01977-4