Development and validation of a nomogram to predict long-term cancer-specific survival for patients with osteosarcoma
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OPEN
Development and validation
of a nomogram to predict
long‑term cancer‑specific survival
for patients with osteosarcoma
Yali Yu 1, Shaohua Wang 2, Jia Liu 3, Jiejie Ge 4 & Hongya Guan 3*
The present work aimed to establish a new model to accurately estimate overall survival (OS) as
well as cancer-specific survival (CSS) of osteosarcoma. Osteosarcoma cases were collected from the
Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2017 and randomized
as training or validation sets. Then, the OS- and CSS-related variables were discovered through
multivariate Cox regression analysis to develop new nomograms to predict the 1-, 3- and 5-year OS
and CSS. Besides, consistency index (C-index), decision curve analysis (DCA), along with calibration
curve were adopted for assessing the predicting ability of our constructed nomograms after calibrating
for 1-, 3- and 5-year OS and CSS. Altogether, 1727 osteosarcoma cases were enrolled in the present
study and randomly divided as training (n = 1149, 70%) or validation (n = 576, 30%) set. As shown
by univariate as well as multivariate Cox regression analyses, age, grade, T stage, M stage, surgery,
chemotherapy, and histological type were identified to be the adverse factors to independently
predict OS and CSS among the osteosarcoma cases. Besides, based on results of multivariate Cox
regression analysis, we constructed the OS and CSS prediction nomograms. The C-index in training
set was 0.806 (95% CI 0.769–0.836) for OS nomogram and 0.807 (95% CI 0.769–0.836) for CSS
nomogram. In the meantime, C-index value in validation set was 0.818 (95% CI 0.789–0.847) for OS
nomogram, while 0.804 (95% CI 0.773–0.835) for CSS nomogram. Besides, those calibration curves
regarding the 3- and 5-year CSS of our constructed nomogram were highly consistent between the
predicted values and the measurements in the training set as well as the external validation set. Our
constructed nomogram outperformed the TNM stage in prediction. Our constructed nomogram is
facile, creditable, and feasible; it efficiently predicts OS and CSS for osteosarcoma cases and can assist
clinicians in assessing the prognosis for individuals and making decisions.
Osteosarcoma is among the frequently occurring primary bone cancers, which particularly affects adolescents
aged below 24 years and has an estimated annual prevalence of 0.34/100,000. Osteosarcoma is marked by its
aggressiveness1,2, which manifests in the early lung metastasis and fast local invasion, resulting in high relapse
and mortality rates3. After the emergence of adjuvant chemotherapy as well as limb salvage surgery, patients’
survival rate increased by 50% to about 70% in the most recent two d
ecades4,5. Nonetheless, most osteosarcomas
lead to disease- and treatment-associated morbidities or mortalities. Identification of the high-risk patients early
is very important so as to offer a suitable clinical option or adjuvant therapy. Osteosarcoma can have a unique
challenge in a clinical setting; as a result, it is urgently needed to establish the prognostic approaches to precisely
estimate survival rates from osteosarcoma.
Currently, the TNM classification system is commonly employed to predict osteosarcoma p
rognosis6. Typically, the TNM classification system, released by the American Joint Commission on Cancer (AJCC), has been
extensively employed to classify cancer patient survivals according to tumor invasion (T), regional lymph node
(N) as well as distant metastasis (M)7,8. However, it is limited to evaluate cancer prognosis using the TNM
1
Department of Clinical Laboratory, Zhengzhou Orthopaedics Hospital, Zhengzhou 450000, Henan,
China. 2Department of Joint Surgery, Zhengzhou Orthopaedics Hospital, Zhengzhou 450000, Henan,
China. 3Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou
University, Zhengzhou 450007, Henan, People’s Republic of China. 4Department of Clinical Laboratory,
Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, Henan, China. *email:
Scientific Reports |
(2023) 13:10230
| https://doi.org/10.1038/s41598-023-37391-8
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classification system alone, which may not comprehensively assess the clinicopathological variables, including
sex, age, race, or additional factors and is commonly employed to predict prognosis of osteosarcoma in extremities. It might not suitable to be used in axial location. Nomogram represents the statistical approach to determine
the clinical event probabilities through taking into account those pre-weight values of all factors9,10. Recently,
nomogram is extensively utilized for predicting diverse cancer survival11–15. In recent years, the massive data
of cancer patients based on open-accessed data and bioinformatics methods make it possible for us to explore
the independent risk factors for cancer p
rognosis16–18. The publically accessible SEER database includes cancer
patient data across 18 registered sites that cover about almost 28% USA population19,20. This work was conducted
to construct a creditable nomogram for predicting overall survival (OS) as well as cancer-specific survival (CSS)
of osteosarcoma cases21; thus, assisting clinicians in providing better-customized treatment options to reduce
the rate of metastasis and improve the survival rate of patients.
Materials and methods
Patients selection. The osteosarcoma cases in this work were selected from the SEER database, and their
corresponding anonymous clinical data were extracted accordingly. The SEER*Stat software designed by the
National Cancer Institute (version 8.3.6, https://seer.cancer.gov/seerstat/) was utilized, which covered the SEER
18 Regs custom data containing more therapeutic fields and the Nov 2018 Sub database (covering 2004–2016
data).
In this work, osteosarcoma cases conforming to the following inclusion criteria were selected: (1) Those with
the diagnosis of osteosarcoma as the primary malignant tumor from 1983 to 2014 based on the International
Classification of Diseases for Oncology [ICD-O] 9180–9187, 9192–919422; (2) Those whose osteosarcomas were
confirmed histologically; (3) Those with osteosarcoma in extremities (long/short bones in the four extremities) or
at the axial location (skull, ribs, spine, and pelvis); (4) Those whose histological type was determined; (5) Those
with estimated survival time or identified cause of mortality after they were diagnosed.
Exclusion criteria. Patients whose survival time was unavailable or unclear were excluded from this study.
The patient clinicopathological characteristics, such as age, gender, race, grade, histological type, tumor site,
size, surgery, stage of surgery, chemotherapy, radiotherapy, and survival time, were harvested. As for age, the cases
were divided as 0–24, 25–59 and > 59 years groups. The races were classified as black, white, or ot (...truncated)