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ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 5  |  Page : 1172-1178

Adjuvant therapy fails to show survival benefit for patients with spindle cell carcinoma: Evidence from the surveillance, epidemiology, and end results database


1 Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute; Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China
2 Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, P.R. China
3 Academy of Preventive Medicine (Institute of Radiation Medicine), Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, P.R. China
4 Department of Oncology, Yuncheng Honesty Hospital, Heze, P.R. China
5 Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute; Center for Data Science in Health and Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, P.R. China

Date of Submission26-Nov-2020
Date of Decision04-Mar-2021
Date of Acceptance12-Oct-2021
Date of Web Publication27-Nov-2021

Correspondence Address:
Jing Liang
Department o Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan 250014
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1701_20

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 > Abstract 


Background: Spindle cell carcinoma (SpCC) is a rare tumor type with poor prognosis, and standard treatment modalities are not available yet. However, large-scale studies on this topic are sparse. In this study, data from the surveillance, epidemiology, and end results (SEER) database were used to determine cancer-specific survival (CSS) rates of SpCC and to investigate the impact of different therapeutic strategies including surgery with or without chemotherapy, radiotherapy, or chemoradiotherapy on patient outcome.
Methods: A total of 665 cases of SpCC, diagnosed from 1996 to 2015, were extracted from the SEER database. Kaplan–Meier survival curves and log-rank tests were used to assess CSS rates and differences on survival curves. Multiple COX-proportional hazards models were used to analyze the association between various treatments and prognosis of SpCC patients classified by organs or systems.
Results: Different treatments for SpCC in different organ or system were associated with prognosis of SpCC patients. Surgery alone exhibits survival benefit, whereas adjuvant therapy fails to show survival benefit for patients with SpCC.
Conclusions: The prognosis of SpCC patients varied significantly with different clinical treatments. Adjuvant radiotherapy or chemotherapy did not show survival benefit, even increasing the risk of mortality for SpCC patients.

Keywords: Adjuvant therapy, spindle cell carcinoma, surgery, surveillance epidemiology and end results, survival analysis, treatment modalities


How to cite this article:
Li T, Xie Q, Li J, Li Z, Xiao J, Liu M, Wang J, Li Y, Tang F, Liang J. Adjuvant therapy fails to show survival benefit for patients with spindle cell carcinoma: Evidence from the surveillance, epidemiology, and end results database. J Can Res Ther 2021;17:1172-8

How to cite this URL:
Li T, Xie Q, Li J, Li Z, Xiao J, Liu M, Wang J, Li Y, Tang F, Liang J. Adjuvant therapy fails to show survival benefit for patients with spindle cell carcinoma: Evidence from the surveillance, epidemiology, and end results database. J Can Res Ther [serial online] 2021 [cited 2022 May 28];17:1172-8. Available from: https://www.cancerjournal.net/text.asp?2021/17/5/1172/331306

Authors Ting Li and Qi Xie contributed equally to this work.





 > Introduction Top


Spindle cell carcinoma (SpCC), a fairly unusual subtype of squamous cell carcinoma (SCC),[1],[2],[3] occurred in various organs. It is considered to be a biphasic malignant neoplasm consisting of SCC and SpCC with sarcomatous appearance,[4] and it is also called sarcomatoid carcinoma, pseudosarcoma, or pleomorphic carcinoma.[1],[5],[6] Previous studies suggested that SpCC is a monoclonal tumor that is characterized histopathologically with variable proportion of mesenchymal sarcomatoid and epithelial carcinomatous component.[7]

In general, surgery is considered to be the mainstay treatment,[8] whilst the benefit of adjuvant chemotherapy, radiotherapy or chemoradiotherapy is still in argument. Some studies suggested that adjuvant radiotherapy and chemotherapy were more likely to cause decreased survival rates compared with surgery alone, whereas others indicated that radiotherapy and chemotherapy promoted long-term survival.[5],[9],[10],[11],[12],[13] Because of the low incidence of the SpCC, previous data were mainly from retrospective studies with small sample size or case reports. Therefore, standard clinical treatment strategy for SpCC has not been established yet.

Surveillance, epidemiology, and end results (SEER) is a reliable source for cancer statistics in the United States which includes incidence, prevalence, mortality, and population-based variables of cancers. SEER database provides information on cancer statistics embraces the data from 18 population-based registries (1975-2016) and consists of 27.8% cancer patients approximately in the United States.[14]

In this study, data from a large sample of SpCC in SEER database from 1996 to 2015 were used to examine the association between different clinical treatments and prognosis.


 > Meterials and Methods Top


Data source and study population

The SEER database collects data from 18 cancer-based registries and covers about 30% cancer patients in the United States.[15] The database we used was Incidence-SEER 18 Regs Custom Data (with additional treatment fields), November 2018 Sub (1975-2016 varying), which record the demographics, clinicopathological data, treatment information, and prognosis of patients from 1975 to 2016. Indeed, the data of the current study are from 1996 to 2015 due to the missing information about surgery from 1975 to 1995. The criterion we used to identify the eligible patients was as follows: age, race, sex, primary site, tumor histological subtype, pathological grade, tumor size, treatment modalities, follow-up time, and vital status. The SEER Summary Stage 2000 was used to classify the neoplasm staging. Moreover, the tumor histological subtype was determined as SpCC, NOS (8032/3), according to the International Classification of Disease for Oncology 3rd Edition (ICD- O -3 code). Survival months were defined from the time of diagnosis to death of SpCC or being alive in the end of follow-up time. December 31, 2016, was the most recent date active follow-up and determined as the study cutoff. The following conditions were excluded: the survival time less than 1 month or unknown; multiple primaries; the patients who were diagnosed in 2016 with a follow-up time of less than one year; the patients whose records of treatments were all NO/Unknown and received chemotherapy alone or radiation alone. Finally, 665 eligible cases were acquired by the criterion above.

Analyses were adjusted for the following demographic and clinicopathologic factors: age, sex, race, years of diagnosis, tumor histological subtype, pathological grade, stage and tumor size. The age was classified into three categories: ≤45 years old, 46–65 years old, and >65 years old. The race was categorized into three groups: white, black, and others. The pathological grade was classified into the following categories: (1) low-grade, including moderately differentiated and well differentiated, (2) high-grade, including undifferentiated and poorly-differentiated, and (3) unknown. The SEER summary stage was categorized as localized, regional, distant, and unknown. Tumor size was classified into ≤5 cm, >5.0 cm, and unknown. The treatment modalities were divided into four groups: surgery alone, surgery plus chemotherapy, surgery plus radiation, and surgery plus chemoradiotherapy. The primary tumor sites were classified into six categories, including head and neck, chest, breast, alimentary system, urinary system, and other organs [Supplementary Table 1].



Statistical analysis

Chi-square tests were used to examine the differences of characteristics for SpCC. Cancer-specific survival (CSS) were calculated from the date of diagnosis to the date of death attributed to SpCC. Kaplan−Meier survival curves and log-rank test were conducted to assess the differences among survival curves. The hazard ratios and 95% confidence intervals 95% were estimated from the adjusted multivariate Cox proportional hazards regression models controlling for the effects of covariates. All analyses were carried out using the SPSS statistics 24.0 (IBM Corporation, Armonk, NY, USA).


 > Results Top


From 1996 to 2015, a total of 665 cases were identified from the SEER database comprising 298 males (mean age = 68.5 years old, standard deviation [SD] =14.3) and 367 females (mean age = 68 years old, SD = 15.6). The median follow-up time was 22 months. 21.2% of the cases occurred in the chest, followed by the breast (18.6%). Overall, 55.5% of the patients received surgery alone and 44.5% of the patients accepted adjuvant therapy including radiotherapy, chemotherapy, or chemoradiotherapy [Table 1].
Table 1: Demographic and clinicophologic characteristics by tumor location classification

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Survival analysis

Significant differences on CSS were observed according to various clinical treatments for SpCC. Patients who underwent surgery alone exhibited more favorable survival compared to those who underwent adjuvant chemoradiotherapy [[Figure 1], P < 0.01]. As shown in [Table 2], the 5-years CSS for whom had surgery alone was 58.5%, followed by surgery plus radiation (37.9%) and surgery plus chemotherapy (23.8%). SpCC patients who have undertaken surgery alone presented the predominant CSS rate in head and neck and urinary system [Figure 2].
Figure 1: Kaplan–Meier survival curves for spindle cell carcinoma patients with different clinical treatments. Patients with spindle cell carcinoma were subdivided into four groups according to various clinical treatments: surgery alone; surgery plus chemotherapy; surgery plus radiation; surgery plus chemoradiathrepy. Cancer-specific survival rate for each group were compared, P < 0.05 was regarded as significant

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Table 2: The cancer - specific survival of various treatments in spindle cell carcinoma of different organs or systems

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Figure 2: Kaplan–Meier survival curves for classified spindle cell carcinoma patients with clinical treatments. Patients with spindle cell carcinoma were classified into six groups according to the site where the tumor occurred: (a) head and neck; (b) chest; (c) breast; (d) alimentary system; (e) urinary system; (f) other organs. For each group, cancer-specific survival rate for different clinical treatments were compared. A P < 0.05 is statistically significant

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The multivariate Cox-proportional hazards regression models were performed to assess the prognosis of different treatments after adjusting for age, sex, years of diagnosis, grade, stage, and tumor size. Surgery plus chemotherapy and surgery plus chemoradiotherapy were the poor prognostic indicators for SpCC in the head and neck. For SpCC in the breast, surgery plus radiation and surgery plus chemoradiotherapy could increase the risk of mortality. There are no statistically difference on CSS among different treatments in the chest, alimentary system, urinary system, and other organs [Table 3].
Table 3: Multivariate COX proportional hazards analysis for cancer - specific survival of treatments

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 > Discussions Top


The present study has examined the CSS rates of SpCC patients and the association between different clinical treatments and prognosis using SEER database which can provide adequate samples to inspect this uncommon malignant neoplasm. To our knowledge, it is the first study to investigate the association between comprehensive treatments and prognosis of SpCC patients.

Previous studies have suggested that surgery alone is considered to be the better choice for treatment of SpCC patients in most organs or systems. As for head and neck SpCC, our research found that patients who had surgery alone exhibited longer survival, whilst patients who received surgery plus chemotherapy or surgery plus chemoradiotherapy presented increased mortality. This result is consistent with the previous literature.[5],[16],[17],[18] The recent research reported that 3 of the 4 patients with SpCC in the head and neck underwent chemoradiation had a 75% recurrence rate, and all were salvaged with surgery.[11] On the contrary, other research reported that the 5-year disease-specific survival for whom had surgery combined with radiation was 84.2%, followed by surgery alone (84.0%) and radiation alone (60.5%).[9] Further research should be conducted to reevaluate the role of different clinical strategies in head and neck SpCC treatments. Regarding SpCC in breast, multivariate analysis of CSS in our study revealed that CSS of patients who underwent surgery plus radiation or surgery plus chemoradiotherapy was significantly worse when compared to those who underwent surgery alone. Prior studies showed that patients who underwent mastectomy had better survival benefit.[12],[19],[20] Ambria S et al. pointed out that patients with early-stage disease received surgery had similar 10-year survival rates no matter whether they received adjuvant radiation or not, whilst for the late-stage disease, patients underwent surgery plus radiation had worse survival rates compared to those who underwent surgery alone.[12]

Importantly, our study found that there were no statistically significance on CSS among adjuvant chemotherapy and radiation in the chest, alimentary system, urinary system and other organs. Indeed, the clinical benefit of adjuvant treatment remains controversial. In the chest, Nagla et al. reported that patients with SpCC in the pulmonary underwent surgery alone had the longest overall survival of 713.5 days compared to other treatments,[21] also, other research found that adjuvant radiotherapy and chemotherapy have no survival benefit.[22],[23] which might be partially explained by the fact the majority of SpCC exhibited high resistance to first-line chemotherapy.[24],[25] However, some researchers pointed out that radiotherapy could alleviate the development of SpCC[26] and combined treatments should be considered due to the high rate of local recurrence and metastasis.[27] As for alimentary system, Zhang et al. reported that the patients with SpCC in esophagus received chemoradiotherapy had worse 5-year survival rates than those who did not received chemoradiotherapy.[28] However, other studies reported that chemoradiotherapy could decrease recurrence and improve survival.[29],[30] Besides, one research indicated that patients with subsequent adjuvant chemoradiotherapy after surgery presented survival benefit compared to those who only had surgery.[31] In the urinary system, adjuvant therapy for SpCC was conducted and exhibited survival benefit.[32],[33],[34] As for SpCC in other organs, few studies were obtained and most of them were case reports,[35],[36],[37] which hinders further research on prognosis as lacks of information. The following reasons may explain such contradictory results above. First, patients underwent surgery might have poor physical condition to receive adjuvant treatments; second, sample size in previous studies might be inadequate to define the appropriate treatment modalities for SpCC patients. Therefore, further research with large number of SpCC paients are needed to investigate the effect of adjuvant treatments and to explore the appropriate therapy for SpCC patients.

The main strength of current study is based on the fact that SpCC patients were strictly screened and classified, and adequate sample size was provided by SEER database. However, there are still some limitations in our study. First, the main limitation is the retrospective nature. Second, detailed clinical information was not provided, such as family history, past history, and comorbidities, which may affect the choice of treatment modalities. Moreover, there are lacks of detailed information on surgical technique, chemotherapy regimen, subsequent treatment and recurrence rate, which would be more valuable data for further study.[38]


 > Conclusion Top


The main interest of our study is to investigate the prognosis of SpCC patients with various clinical treatments in different organs or systems. Above all, surgery alone is the main treatment in most organ, which promotes long-term survival, whereas adjuvant chemoradiotherapy provides no survival benefit. Future research on tumor characteristics, recurrence rate and long-term survival is needed to guide clinical treatments for SpCC.

Acknowledgments

This work was supported by the Major Science and Technology Innovation Project of Shandong Province (2018CXGC1220); Shandong Provincial Key Research and Development Program (GG201809230187); National Natural Science Foundation of China (71804093); Tradtionanl Chinese Medicine Science and Technology Development Plan of Shandong Province (2019-0377), and Qianfoshan Grant (QYPY2020NSFC1015, QYPY2020NSFC0821).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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