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Predictive factors, preventive implications, and personalized surgical strategies for bone metastasis from lung cancer: population-based approach with a comprehensive cancer center-based study

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Abstract

Background

Bone metastasis (BM) and skeletal-related events (SREs) happen to advanced lung cancer (LC) patients without warning. LC-BM patients are often passive to BM diagnosis and surgical treatment. It is necessary to guide the diagnosis and treatment paradigm for LC-BM patients from reactive medicine toward predictive, preventive, and personalized medicine (PPPM) step by step.

Methods

Two independent study cohorts including LC-BM patients were analyzed, including the Surveillance, Epidemiology, and End Results (SEER) cohort (n = 203942) and the prospective Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 59). The epidemiological trends of BM in LC patients were depicted. Risk factors for BM were identified using a multivariable logistic regression model. An individualized nomogram was developed for BM risk stratification. Personalized surgical strategies and perioperative care were described for FUSCC cohort.

Results

The BM incidence rate in LC patients grew (from 17.53% in 2010 to 19.05% in 2016). Liver metastasis was a significant risk factor for BM (OR = 4.53, 95% CI = 4.38–4.69) and poor prognosis (HR = 1.29, 95% CI = 1.25–1.32). The individualized nomogram exhibited good predictive performance for BM risk stratification (AUC = 0.784, 95%CI = 0.781–0.786). Younger patients, males, patients with high invasive LC, and patients with other distant site metastases should be prioritized for BM prevention. Spine is the most common site of BM, causing back pain (91.5%), pathological vertebral fracture (27.1%), and difficult walking (25.4%). Spinal surgery with personalized spinal reconstruction significantly relieved pain and improved daily activities. Perioperative inflammation, immune, and nutrition abnormities warrant personalized managements. Radiotherapy needs to be recommended for specific postoperative individuals.

Conclusions

The presence of liver metastasis is a strong predictor of LC-BM. It is recommended to take proactive measures to prevent BM and its SREs, particularly in young patients, males, high invasive LC, and LC with liver metastasis. BM surgery and perioperative management are personalized and required. In addition, adjuvant radiation following separation surgery must also be included in PPPM-guided management.

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Data availability

Data for the SEER cohort were extracted from the Surveillance, Epidemiology, and End Results Program (https://seer.cancer.gov/). Data for the FUSCC cohort were available from the corresponding authors upon appropriate request.

Code availability

Not applicable

Abbreviations

BM:

Bone metastasis

LC:

Lung cancer

SREs:

Skeletal-related events

SEER:

Surveillance, Epidemiology, and End Results

FUSCC:

Fudan University Shanghai Cancer Center

MDT:

Multidisciplinary team

PVP:

Percutaneous vertebroplasty

TES:

Total en bloc spondylectomy

NOS:

Not otherwise specified

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

BMI:

Body mass index

NRS:

Numerical rating scale

CT:

Computed tomography

MRI:

Magnetic resonance imaging

ECT:

Radionuclide bone scanning

PET-CT:

Positron emission tomography-computed tomography

SUVmax:

Maximum standard uptake value

ALP:

Alkaline phosphatase

LDH:

Lactate dehydrogenase

ALT:

Alanine transaminase

AST:

Aspartate aminotransferase

TBIL:

Total bilirubin

ASA:

American Society of Anesthesiologists

FDG:

Fluorodeoxyglucose

HE staining:

Hematoxylin–eosin staining

IHC:

Immunohistochemistry

OR:

Odds ratio

HR:

Hazards ratio

CI:

Confidence interval

ROC:

Receiver operator characteristic curve

AUC:

Area under the curve

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Funding

This work was supported by the National Natural Science Foundation of China (Number: 81872179; Recipients: Wangjun Yan).

Author information

Author notes

  1. Xianglin Hu, Wending Huang and Zhengwang Sun contributed equally to this work

Authors and Affiliations

  1. Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Xianglin Hu, Wending Huang, Zhengwang Sun, Yangbai Sun & Wangjun Yan

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Xianglin Hu, Wending Huang, Zhengwang Sun, Yangbai Sun & Wangjun Yan

  3. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Hui Ye

  4. Department of General Surgery, University Hospital of Macau University of Science and Technology, Macau, 999078, China

    Kwong Man

  5. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Qifeng Wang

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  1. Xianglin Hu
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Contributions

Wangjun Yan and Yangbai Sun contributed to the study conception and design. Xianglin Hu, Wending Huang, Zhengwang Sun, Hui Ye, Kwong Man, and Qifeng Wang retrieved, analyzed, and interpreted the data. Xianglin Hu drafted the manuscript. Wangjun Yan and Yangbai Sun revised the manuscript. All authors read and approved the submission.

Corresponding authors

Correspondence to Yangbai Sun or Wangjun Yan.

Ethics declarations

Ethics approval

This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center, Shanghai, 200032, China. All procedures performed in the study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to participate

Informed consent for participation in the FUSCC cohort was obtained in this study.

Consent for publication

All authors read and approved the submission.

Conflict of interest

The authors declare no competing interests.

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Highlights

The current study introduces a predictive, preventive, and personalized medicine (3PM) viewpoint throughout lung cancer (LC)-bone metastasis (BM) management.

1. Predictive diagnostics: Liver metastasis is a significant risk factor for BM. the individualized nomogram established in our study can well stratify a patient’s BM risk.

2. Targeted prevention: Young patients, males, patients with high invasive LC, and patients with other distant site metastases must be the key population for BM prevention.

3. Personalization of medical services: Personalized spinal metastasis surgery with spinal reconstruction significantly relieves pain and improves daily activities.

4. Personalization of medical services: Perioperative managements such as anti-inflammation and blood transfusion must be individualized to prevent vital organs injury. Radiotherapy needs to be recommended for specific postoperative individuals

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Hu, X., Huang, W., Sun, Z. et al. Predictive factors, preventive implications, and personalized surgical strategies for bone metastasis from lung cancer: population-based approach with a comprehensive cancer center-based study. EPMA Journal 13, 57–75 (2022). https://doi.org/10.1007/s13167-022-00270-9

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