br ACCEPTED MANUSCRIPT br clinical setting using specific
clinical setting using specific clinical information of patients, which was likely to be available to the surgeon, to evaluate prognosis.
Via univariate and multivariate Cox analyses, which were used to identify independent prognostic factors for OS and CSS respectively, several clinical characteristics were proved to be independent prognostic factors for OS or CSS in the present study, including patient age, primary site, histology, tumor stage, use of surgery, and tumor size. Our study discovered that increased patient age is correlated with a worse survival for patients with chordoma. Tian et al also indicated that patients older than 25 years had poorer neurologic status and survival outcomes . In the present study, X tile software was applied in data 9(S)-HODE of age and tumor size according to survival time and status. X-tile software is an alternative method that was initially developed to determine best cutoff points of variables in breast malignancy . The optimal age cutoff values of patients with chordoma in the current study were 38.54 and 66 years. With regard to tumor size, Bergh et al. had reported that patients with chordoma of the sacrum and mobile spine and with a large tumor size had the poorest survival . In our study, X-tile software was also applied to determine the best cutoff points of chordoma tumor size. The optimal cutoff values of chordoma tumor size in the current study were identified as 2.9 and 10.0 cm. Our study showed that larger tumor size was an independent prognostic factor for survival in patients with chordoma. Larger tumor size was correlated with poorer survival.
Surgical stage and use of surgery were also identified as independent prognostic factors in the present study. Localized stage was correlated with better survival compared to regional and distant stage. With regard to surgical treatment, several previous literatures have reported that patients with chordoma who received surgical resection would have a better rate of survival compared with patients who did not receive surgery [25-27]. Surgical treatment is the most effective treatment for chordoma at present. The application of primary or adjuvant radiotherapy in these patients is controversial because of chordoma’s radioresistance . Chemotherapy including cisplatin, anthracyclines, and alkylating agents has been applied in patients with chordoma, and these treatments have not been shown to be effective [1 29].
There are three different histological subtypes in chordoma according to microscopic morphology: conventional, chondroid, and dedifferentiated. Among all the subtypes, dedifferentiated chordoma is the most aggressive subtype, which
significantly affects overall survival . Subtype has been shown in the present study to significantly affect survival outcomes .
Including independent prognostic factors identified from multivariate analysis, we constructed a nomogram that can estimate 3- and 5-year OS and CSS for patients with chordoma. Individual survival probability of these patients at certain time points can be evaluated precisely via these nomograms. To our knowledge, no such prognostic nomogram has been reported for patients with chordoma. A practicable nomogram can help surgeons to estimate the precise likelihood of survival at different time intervals. And, such a prognostic nomogram can increase the surgeon’s ability to identify patients who are at higher risk of early death.
Several potential limitations of this study should still be considered. First, we used only 3-and 5-year survival as the primary endpoints, but did not consider local recurrence, which is not available in the SEER database. Second, the information we applied to construct and validate the nomograms was from the same SEER database, which can reduce the reliability of the nomogram; pollen grains would be useful to validate the prognostic nomograms in the present study with another dataset.
Age at diagnosis, primary site, histology, tumor stage, use of surgery, and tumor size were identified as independent prognostic factors for both OS and CSS of patients with chordoma. We incorporated these prognostic factors to construct prognostic nomograms that can estimate 3- and 5-year OS and CSS for these patients. The nomogram constructed in present study can serve as an effective and convenient evaluation tool to help surgeons create personalized survival evaluations and mortality risk identification in patients with chordoma.
Declarations of interest: none r> ACCEPTED MANUSCRIPT
1. Lebellec L, Aubert S, Zairi F, Ryckewaert T, Chauffert B, Penel N. Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses. Critical reviews in oncology/hematology 2015;95(1):125-31 doi: 10.1016/j.critrevonc.2015.01.010[published Online First: Epub Date] .