Association between Postoperative Adjuvant Chemotherapy and Disease-Specific Survival in Women with Ovarian Sex Cord-Stromal Tumors: A SEER-based Study

doi:10.21203/rs.3.rs-794550/v1

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Association between Postoperative Adjuvant Chemotherapy and Disease-Specific Survival in Women with Ovarian Sex Cord-Stromal Tumors: A SEER-based Study

https://doi.org/10.21203/rs.3.rs-794550/v1

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Background

Ovarian sex cord-stromal tumors (SCSTs) are relatively rare tumor. The standard treatment is surgery, while adjuvant chemotherapy remains controversial. This study evaluated the effect of adjuvant chemotherapy and disease-specific survival (DSS) in patients with SCSTs.

Methods

323 Patients with SCSTs were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic and clinicopathological characteristics were compared using Mann–Whitney U-test, Fisher’s exact test, and chi-square test. DSS were estimated by Kaplan–Meier and compared with the log-rank test. Cox proportional hazards model was used to control for confounders.

Results

A total of 323 patients were included in this study, and the mean age was 44 years (range, 10-89 years). The most common histologic subtype was granulosa cell tumor (GCT) (n=197, 61%). 60.7% were diagnosed with stage IA or IB disease and 18% with stage IC disease. Among them, 62.2% of patients (n=201) received chemotherapy. The Median follow-up time was 71 months (range,1-224 months). 12.7% (41/323) of patients experienced death. Patients who did not received chemotherapy (n=122) had better DSS compared to those who received chemotherapy, 5-year DSS rates were 93.5% VS 80.3% (P = 0.0005), 10-year DSS rates were 93.0% and 78.69% (P = 0.0002). Multiple Cox regression analysis showed that higher stage (p＜0.001), poor differentiation（P=0.24）, larger tumor size(size＞10cm) （P=0.018） were independently associated with an increased hazard of death，while histological subtype（P=0.082）,adjuvant chemotherapy(p=0.762), complete staging surgery（p=0.554）was not associated with prognosis.

Conclusion

Chemotherapy could not improve the prognosis and may be associated with poorer DSS. Age, histopathologic subtype, complete staging surgery, lymphadenectomy are not associated with prognosis.

Obstetrics & Gynecology

Oncology

Ovarian Sex Cord-Stromal Tumors

adjuvant chemotherapy

disease-specific survival

SEER database

Ovarian sex cord-stromal tumors (SCSTs) represent 2–5% of all ovarian cancers with several subtypes. Granulosa cell tumor (GCT) is the most common subtype of SCSTs (70%),and there are several rare subtypes ,such as Sertoli-Leydig cell tumor(SLCT)༈5–10%༉, Sex cord tumor with annular tubules༈1.4%༉, Sertoli cell carcinoma, Leydig cell tumor, etc. SCSTs are usually diagnosed at early stage, and are characterized by late recurrence, and the median time to recurrence is 6 years, as late 30 years, after the initial diagnosis and treatment.

Based on the National Comprehensive Cancer Network (NCCN) guideline, surgery represents the most important therapeutic arm, and adjuvant treatment with platinum-based chemotherapy can be considered for patients with high-risk and intermediate risk stage I disease, such as ruptured stage Ic or poorly differentiated stage I or heterologous elements. However, patients with stage II-IV or recurrence disease should receive adjuvant chemotherapy in addition to surgery. The most common chemotherapy regimens include bleomycin, etoposide, and cisplatin (BEP), cisplatin and etoposide(EP), or carboplatin with paclitaxel (TC). However, the recommendation of NCCN guideline for adjuvant chemotherapy is based on the results of various clinical trials^{(1) (2)}, retrospective studies, review ^{(3, 4)}, a systematic review ⁽⁵⁾, consensus ⁽⁶⁾ published in 2007–2018, and with a level 2B category of evidence. There is no evidence supporting that adjuvant treatment results in survival benefit of ovarian GCT based on recent research results.

Some studies have suggested that patients might benefit from chemotherapy⁽⁷⁾,while others failed to show chemotherapy's effect on survival or relapse ^{(8, 9)}.

Accordingly, this study aimed to evaluate the association between postoperative chemotherapy and DSS in patients with SCSTs from a large cohort of patients extracted from the SEER database.

This study collected data from the SEER database. The SEER*Stat version 8.3.8. was used to find patients with SCSTs from SEER18 Regs Customs Data (with additional treatment fields). Nov 2018 Sub (1975–2016 varying). All patients were diagnosed with SCSTs based on the histopathology codes (8590/3, 8593/3, 8620/3, 8622/3, 8623/3, 8631/3, 8634/3, 8640/3, 8650/3, and 8670/3) were included. A total of 2597 patients were initially identified. We excluded patients with unknown tumor grade (n = 2084), without pathologically confirmed tumors (n = 4), unknown stage and surgery status (n = 79), who died of other causes,(n = 68), with secondary tumor(n = 30) or unknown survival time (n = 4). The detailed procedure for selecting patients is shown in the flow chart (Fig. 1). According to our inclusion and exclusion criteria, 323 patients with SCSTs were included in the final analysis.

Demographic (age, year of diagnosis), clinicopathological(tumor size, histology, stage and grade), treatment (surgery, chemotherapy, lymphadenectomy), and survival data (follow-up time and endpoint) were extracted using the “case listing” option.

The raw data was converted and processed for analysis. Age was categorized into 10-year age intervals. Tumor size (when available) was dichotomized into < 10 cm and ≥ 10 cm. Histopathology was categorized into GCT, SLCT, and others. Stages were defined based on the SEER-modified 3rd edition of AJCC staging for patients diagnosed between 1988 and 2003, the derived 6th edition of the AJCC staging for those diagnosed 2004–2009, the derived 7th edition of the AJCC staging system for patients between 2010 and 2015, and the tumor grade was recorded into well-differentiated (grade 1), moderately differentiated (grade 2), poorly differentiated (grade 3) and undifferentiated (grade 4) tumors. During analysis, patients were divided into subgroups based on the extent of surgery (Table 1). According to the chemotherapy record, patients divided into chemotherapy and non-chemotherapy groups. DSS is defined as the time between the date of initial treatment and the date of death due to the disease.

Table 1

Distribution of clinicopathological features in patients triaged to adjuvant chemotherapy versus no treatment
Category	Overall No. of patients (n = 323)	CT (n = 201)	NCT ( n = 122)	p-value
Age(mean)		43	46	0.1225
Histopathology, n(%)
Granulosa cell tumor	197(61.0)	148(75.1)	49(24.9)	P<0.001
Sertoli-Leydig cell tumor (poorly differentiated)	104(32.2)	44(42.3)	60(57.7)
Others	22(6.8)	13(59.0)	9(41.0)
FIGO stage, n (%)
IA-IB	196(60.7)	146(74.5)	50(25.5)	P<0.001
IC	58(18.0)	31(53.4)	27(46.6)
II	28(8.7)	9(32.1)	19(67.9)
III	25(7.7)	10(40.0)	15(60.0)
IV	16(5.0)	5(31.3)	11(68.7)
Grade, n(%)
G1: Well differentiated	90(27.9)	78(86.7)	12(13.3)	P<0.001
G2: Moderately differentiated	77(23.8)	46(59.7)	31(40.3)
G3: Poorly differentiated	139(43.0)	68(48.9)	71(51.1)
G4: Undifferentiated	17(5.3)	9(52.9)	8(47.1)
Tumor size, n(%)
Size ≥ 10cm	189(58.5)	76(56.7)	58(43.3)	0.085
Size<10cm	134(41.5)	125(66.1)	64(33.9)
Surgical procedure type, n (%)
CYS/SO	102(31.6)	69(67.6)	33(32.4)	0.02
TAH-SO	78(24.1)	55(70.5)	23(29.5)
CSS	143(44.3)	77(53.8)	66(46.2)
Lymphadenectomy, n (%)
yes	178(55.1)	73(41.0)	105(59.0)	0.224
no	145(44.9)	49(33.8)	96(66.2)
Data are presented as median or n (%); FIGO = International Federation of Gynecology and Obstetrics; CT = Chemotherapy; NCT = Non-chemotherapy; CYS = cystectomy; SO = unilateral / bilateral salpingo-oophorectomy; TAH-SO = Hysterectomy and unilateral / bilateral salpingo-oophorectomy; CSS = complete staging surgery.

Categorical variables were examined with the Fisher’s exact test and chi-square. Mann–Whitney U-test was employed to analyze continuous variables. DSS was evaluated using Kaplan-Meier curves and compared with the log-rank test. Univariate or multivariate Cox proportional hazards models were applied to determine the effect of other risk factors on DSS. Subgroup analysis was performed by risk factors affecting the prognosis. Two-sided P values < 0.05 were considered statistically significant. Statistical analysis was performed with the R language R-4.0.4, RStudio software, and STATA 15.

Baseline patient and treatment characteristics

Table 1 shows the baseline patient and treatment characteristics. A total of 323 patients were included in this study, and the mean age was 44 (range,10–89 years). Among them, 62.2% of patients (n = 201) received chemotherapy. Patients treated with chemotherapy were younger, with a median age of 43 years, compared with 46 years for nontreated patients (p = 0.1225). The most common histologic subtype was GCT (n = 197, 61%,) followed by SLCT (n = 104, 32.2%), and other (n = 22, 6.8%). The majority of patients (n = 254,78.6%%) had the early-stage disease(Stage I), 60.7% were initially diagnosed with stage IA or IB disease, and 18% with stage IC disease. The remaining 12.7% had stage II–IV disease at diagnosis. 48.3% had high-grade tumors.143 patients (44.3%) underwent a complete surgical staging procedure, and 180 (55.7%) did not. 183(56.7%) patients underwent fertility spring surgery (FSS). The distribution of different extents of surgery is shown in Table 2. Approximately half (n = 178,55.1%) of the patients received lymphadenectomy (LND), but only 4 (2.25%) of them had pathologically positive lymph nodes. The median follow-up time was 71 months (range,1-224). 12.7% (41/323) of patients experienced death.

Table 2

Distribution of different extent of surgery
Extent of surgery	Number of patients	%
Total removal of the tumor or single ovary without hysterectomy	14	4.3
Unilateral salpingo-oophorectom without hysterectomy	74	22.9
Bilateral salpingo-oophorectomy without hysterectomy	14	4.3
Unilateral or bilateral salpingo- oophorectomy with omentectomy without hysterectomy	38	11.8
Total removal of the tumor or single ovary with hysterectomy	2	0.6
Unilateral salpingo-oophorectom with hysterectomy	14	4.3
Bilateral salpingo-oophorectomy with hysterectomy	62	19.2
Unilateral or bilateral (salpingo-) oophorectomy with omentectomy with hysterectomy	81	25.1
Cytoreductive surgery, Pelvic exenteration	24	7.4

Overall Analysis

Survival analysis

Based on the results of survival analysis, patients who did not received chemotherapy (n = 41) had better DSS compared to those who did ,5-year DSS rates were 93.5% vs 80.3% (P = 0.0005),10-year DSS rates were 93.0% and 78.69% (P = 0.0002) (Fig. 2).

Univariate And Multivariate Cox Modeling

The univariate analyses also revealed that chemotherapy worsened the DSS (HR = 1.43, CI = 1–2.04, P = 0.052). Stage (HR1.07,95% CI 1.03–1.11,P<0.001), pathological grade(HR 2.96༌95% CI 1.94–4.5,P<0.001), histological subtype HR 2.04,95% CI 1.34–3.1,P = 0.001 , tumor larger than 10cm HR 6.99༌95% CI 2.11–23.15,P = 0.001 were significant prognostic factors for death, and patients who underwent complete staging surgery (CSS) had poor prognosis HR 2.66༌95% CI 1.4–5.08,p = 0.03. Age P = 0.703, lymphadenectomy(P = 0.395), FSS (P = 0.494) had no association with prognosis. Cystectomy CYS or salpingo-oophorectomy SO versus radical surgery RS had no bearing on OS(P = 0.493). Multiple Cox regression analysis showed that higher stage(P<0.001)༌poor differentiation P = 0.024, larger tumor size(size>10cm) P = 0.018 were independently associated with an increased hazard of death༌while histological subtype P = 0.082 ༌adjuvant chemotherapy(p = 0.726),CSS p = 0.554 was not associated with prognosis (Table 3) Figure 3 .

Table 3

Univariate and multivariate analysis of patients stratified by administration of Chemotherapy
Factors	Univariate		Multivariate
Factors	HR(95% CI)	P	HR(95% CI)	P
Age	1 (0.98–1.01)	0.703
Age Per 10 years	0.99 (0.83–1.18)	0.877
Tumor size	6.99(2.11–23.15)	0.001		0.018
Size<10cm			Reference
Size ≥ 10cm			2.21(1.15–4.26)
FIGO stage	1.07(1.03–1.11)	<0.001		<0.001
IA-IB			Reference
IC			1.97(0.70–5.56)
II			3.22(0.90-11.52)
III			15.00(5.65–39.81)
IV			13.93(4.86–39.89)
Grade	2.96(1.94–4.5)	<0.001		0.024
G1:Well differentiated			Reference
G2:Moderately differentiated			5.57(0.66–47.04)
G3:Poorly differentiated			8.34(1.06–65.75)
G4:Undifferentiated			21.09(2.35-189.52)
Histopathology	2.04(1.34–3.1)	0.001		0.082
Granulosa cell tumor			Reference
Sertoli-Leydig cell tumor (poorly differentiated)			2.18(0.92–5.14)
Others			2.74(0.96–7.81)
Surgical procedure type
CYS/SO	1.25(0.66–2.33)	0.493
RS
Surgical procedure type
FSS	1.245(0.664–2.331)	0.494
Non-FSS
Surgical procedure type				0.554
Non-CSS	2.66 (1.4–5.08)	0.003	Reference
CSS			1.24(0.60–2.56)
Lymphadenectomy	0.76(0.41–1.42)	0.395
yes
no
Chemotherapy	1.43(1-2.04)	0.052		0.726
yes			Reference
no			0.87(0.40–1.89)
FIGO = International Federation of Gynecology and Obstetrics; CYS = cystectomy; SO = unilateral / bilateral salpingo-oophorectomy; RS = Radical surgery; FSS = Fertility-spring surgery; TAH-SO = Hysterectomy and unilateral / bilateral salpingo-oophorectomy ; CSS = complete staging surgery.

Subgroup Analysis

Subgroup analysis demonstrated a similar trend that adjuvant chemotherapy could not improve the prognosis. For patients with early-stage (IA–IB) disease, there were no significant differences in DSS between those who received chemotherapy and those who did not (P = 0.26). Analysis of the patients with Stage IC(P = 0.76) and stage II-IV(P = 0.42) demonstrated a similar trend (Fig. 4).

The DSS rate was lower in patients who received chemotherapy among well-differentiated tumors patients (grade 1) (10-years DSS 91.7% vs. 100%, P = 0.0047). However, only one patient died among patients with grade 1; thus, the effect of chemotherapy was not statistically significant. For patients with grade 2 (P = 0.23), grade 3(P = 0.18), grade 4(P = 0.31) disease, there was no difference in DSS (Fig. 5).

The DSS for patients with tumors less than 10cm who received chemotherapy versus no chemotherapy was 74.1% and 86.84%, respectively(P = 0.0019). There was no statistically significant difference in DSS of patients with tumors at least 10 cm (p = 0.081) (Fig. 6). After excluding the influence of confounding factors such as stage, grade, histopathologic subtype, the extent of surgery, no statistically significant effects of chemotherapy on DSS were found (P = 0.555 and P = 167 in size<10cm and size >10cm group, respectively) (Table S2).

For patients with GCTs, patients who did not receive chemotherapy had a better prognosis, 5-years DSS rates were 95.9% vs. 83.7%(P = 0.0076) (Fig. 7a), 10-years DSS rate was 95.5% vs. 81.63%(P = 0.002). However, based on multivariate Cox regression analyses, adjuvant chemotherapy was not significantly associated with prognosis (P = 0.609) (Table S3). There was no statistically significant difference in DSS of patients with STCT (P = 0.36) and others(P = 0.45) (Fig. 7).

In subgroup analysis according to different surgical extents, chemotherapy contributes to poor survival in patients who underwent complete staging surgery (Non-chemotherapy (NCT) vs. chemotherapy (CT), 10-years DSS 88.31% vs. 74.24%, P = 0.021) and who did not (NCT vs. CT ,10-years DSS 95.97% vs. 85.7%, P = 0.027). Moreover, chemotherapy decrease survival of patients underwent FSS (NCT vs CT ,10-years DSS 94.19 % vs. 81.48%, P = 0.035)non-FSS(NCT vs. CT ,10-years DSS 92.17% vs. 76.47%, P = 0.003), hysterectomy and bilateral salpingo-oophorectomy(TAH-SO)(NCT vs. CT ,10-years DSS 98.18% VS 86.96%, P = 0.038 ) according to K-M survival analysis. Chemotherapy was not significantly associated with prognosis among patients who underwent CYS/SO (P = 0.22) and FSS-staging surgery (P = 0.15). (Fig. 8). Multivariate analysis showed chemotherapy was not associated with prognosis (P > 0.05 each) (Table S4-8). Moreover, CYS/SO versus FSS-staging surgery had no bearing on DSS(P = 0.344). Patients underwent CSS had better outcome compared with those underwent TAH-SO in univariate analysis (P = 0.007). However, there was no difference in survival of patients who underwent the two different extent of surgery based on multivariate analysis (Table S9).

Some studies suggest that chemotherapy can improve the outcome of patients. A previous study shows that the patients of malignant non-GC SCST with stage III–IV disease who received chemotherapy had a longer median survival time than those who did not ⁽⁷⁾.

However, several studies found that adjuvant chemotherapy cannot improve prognosis. They also analyzed patients with stage I-II malignant non-GC SCST, indicating that chemotherapy had no more clear benefit of overall survival(OS) ⁽⁷⁾. Another study shows no significant difference in OS between the chemotherapy group and the observation group in patients with stage II-IV disease(10). A retrospective study showed that adjuvant chemotherapy was not associated with improved disease-free survival (DFS), analyzing 60 patients with stage IC adult granulosa cell tumor(AGCT), and the number of chemotherapy cycles was not associated with recurrence rate. ⁽⁸⁾ Another study analyzed the clinical data of 40 patients with stage IC primary GCT of the ovary treated in MITO centers reported the similar conclusion that there was no significant difference in DFS between patients who received adjuvant chemotherapy versus no treatment. ⁽⁹⁾Another retrospective study also implied that Adjuvant chemotherapy was not associated with recurrence rate or survival in stage IA disease (11). Meisel et al. also recognized that after controlling for stage, adjuvant therapy did not improve recurrence-free interval; however, mostly stage II disease patients were included in this study, and only 11 patients received chemotherapy in this study; thus making impossible any reliable evaluation of prognosis according to adjuvant chemotherapy administration(12).

Moreover, a recent study analyzed SCST patients who underwent surgery from 2004 to 2015 were enrolled from the SEER database, developed a nomogram for prognostic prediction of OS in postoperative patients with SCST, and revealed that chemotherapy affects OS. Further analysis stratified by tumor stage found that in stages IA and IB, chemotherapy had poor OS than those who did not receive chemotherapy (P = 0.031), while OS showed no significant difference in another stage.

This retrospective study is the first to assess the impact of chemotherapy on DSS in patients with OSCSTs,and analyzed the relationship between chemotherapy and DSS stratified by stage, grade, tumor size, histopathology subtype, the extent of surgery using data from the SEER database between 1998–2016. With 323 patients, our result showed that

chemotherapy is associated with poorer DSS based on K-M survival analysis. The reverse effects were still significant in patients with Grade 1, tumor size༜10cm,GCTs ༌CSS group ༌Non- CSS group༌FSS group, Non-FSS group, and TAH-SO group. After controlling with confounding factors of tumor size, stage, grade, histopathology and surgery, there was no significant difference in DSS with and without postoperative adjuvant chemotherapy, and adjuvant chemoradiotherapy did not improve survival.

In the present study, age, whether a continuous variable or a categorical variable, did not affect the survival rate. However, some researchers believed that the age older than 40 years old, 50 years old ^{(11, 13, 14)} or 60-year-old ⁽¹⁴⁾ is a risk factor that can affect prognosis. For juvenile granulosa cell tumors (JGCT), age < 10 years old is an independent prognosis factor. ⁽¹⁵⁾ In our study, large size (> 10 cm) is an unfavorable prognostic factor. One study draws similar conclusions ⁽¹³⁾, while another study reported that large size (> 15 cm) is an unfavorable prognostic factor ⁽¹⁶⁾. Some studies reported a one-centimeter increase in tumor size was associated with 4% (2–6%) increased risk of death.⁽¹⁷⁾ Tumor stage and degree of differentiation are consistently associated with prognosis (11, 17, 18). The histologic subtype is a risk factor in univariate analyses. However, histologic subtype showed no significant association with DSS both in multivariate analyses. A recent study revealed that SLCTs were associated with worse cancer-specific mortality than GCTs using the same database(19). Based on the results of the present study, completeness of surgical staging is not a prognostic factor for DSS. However, a previous study shows that patients who underwent FSS(CYS、USO) had a poor DFS than those who underwent RS(20). Our results revealed that lymphadenectomy was not associated with DSS. Other studies also reported no benefit of LND on DFS or OS in these patients, and LND is always associated with many complications(10, 14, 21, 22).

The poor prognosis of patients who received chemotherapy can be attributed to the side effects of conventional chemotherapy and inherent limitations associated with retrospective analyses.

Firstly, Patients were not randomly assigned to a treatment; they were grouped into chemotherapy group or non-chemotherapy group. Furthermore, we do not know whether the patients recorded as “No/Unknown” actually received chemotherapy. The regimens, duration of chemotherapy, the toxicity and other side effects of chemotherapy were not recorded in SEER database, and information about recurrence was also not available. Additionally, ,patients who received chemotherapy may have risk factors, such as elevated tumor marker, incomplete surgical staging⁽²³⁾, the presence of residual disease, tumor rupture, etc.; however, that information was not recorded in the SEER database. Moreover, no information about other factors that could affect prognosis is provided, including heterologous elements(24), presence of a retiform subtype, nuclear atypia(25), mitotic index (MI)༞5,TPRT mutations, KMT2D, P16 overexpression, high expression of SMAD3 and so on(26).

These results may also be explained by being insensitive to chemotherapy of patients with SCSTs. The majority of present studies show that postoperative adjuvant chemotherapy cannot improve the prognosis of patients with this disease(7–11). In a retrospective study with small sample size, among 27 patients treated with BEP, the response rate was only 22%. Moreover, the researchers performed a meta-analysis in parallel, which show that response rate of chemotherapy was 50%; however, there were 21 different chemotherapy regimens in the analysis (27). Thus, single-agent chemotherapy, or hormonal and targeted therapies need to be assessed in further prospective studies

Generally, our study has several innovative advantages. The strength of this study is that it is based on a large cohort of patients from the SEER database with strict inclusion and exclusion criteria. The follow-up time was long enough to estimate survival and it determinants. Multivariate Cox regression models and stratification were constructed to control for confounders, such as tumor size, stage, grade, histopathology, and surgical procedure type. Our study used the DSS as the endpoint to exclude the impact of other causes of survival prognosis. Despite the limitation to our study, it may help in clinical decision-making .

Chemotherapy could not improve the prognosis, and may be associated with poorer DSS.

In addtion, age, histopathologic subtype, complete staging surgery, fertility-spring surgery, lymphadenectomy are not associated with prognosis. Further investigation should be carried out to confirm this finding. The lack of clear benefits from chemotherapy also calls for targeted treatment and hormonal therapy for SCST.

SEER

Surveillance, Epidemiology, and End Results;

SCSTs

Sex cord-stromal tumors;

DSS

Disease-specific survival;

GCT

Granulosa cell tumor;

NCCN

National Comprehensive Cancer Network;

BEP

Bleomycin, Etoposide and Cisplatin;

Etoposide and Cisplatin;

Carboplatin with paclitaxel;

SLCTs

Sertoli–Leydig cell tumors;

FSS

Fertility preservation surgery;

LND

Lymphadenectomy;

CSS

Complete staging surgery;

CYS

cystectomy;

salpingo-oophorectomy;

Radical surgery;

Non-CT

Non-chemotherapy;

chemotherapy;

TAH-SO

hysterectomy and salpingo-oophorectomy;

Non-GC SCST

Non-granulosa cell sex cord-stromal tumors;

overall survival;

DFS

Disease free survival;

AGCT

adult granulosa cell tumor;

JGCT

Juvenile granulosa cell tumor;

USO

unilateral salpingo-oophorectomy;

FIGO

International Federation of Gynaecology and Obstetrics;

Ethics approval

Due to the retrospective nature of the study and data being from a public database, this study was exempt from review by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University

Consent for publication

Not applicable

Availability of data and materials

The datasets analyzed during the current study are available in the [SEER database] repository, [https://seer.cancer.gov/ ]

Competing interests

The authors declare that they have no competing interests

Funding

Not applicable

Authors' contributions

JW and LJ conceived the concept. LJW and SMM collected and analyzed data. LJW and SMM participated in interpretation of results. LJW wrote the manuscript. All authors have read and approved the final version of the manuscript.

Acknowledgements

The authors thank the Surveillance, Epidemiology, and EndResults (SEER) program for providing open access to the SEER database.

Brown J, Brady WE, Schink J, Van Le L, Leitao M, Yamada SD, et al. Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group. Cancer. 2014;120(3):344-51.'doi:'10.1002/cncr.28421 https://doi.org/10.1002/cncr.28421
Burton ER, Brady M, Homesley HD, Rose PG, Nakamura T, Kesterson JP, et al. A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG Oncology/ Gynecologic Oncology Group Study. Gynecol Oncol. 2016;140(1):48-52.'doi:'10.1016/j.ygyno.2015.11.027 https://doi.org/10.1016/j.ygyno.2015.11.027
Al Harbi R, McNeish IA, El-Bahrawy M. Ovarian sex cord-stromal tumors: an update on clinical features, molecular changes, and management. Int J Gynecol Cancer. 2021;31(2):161-8.'doi:'10.1136/ijgc-2020-002018 https://doi.org/10.1136/ijgc-2020-002018
Kottarathil VD, Antony MA, Nair IR, Pavithran K. Recent advances in granulosa cell tumor ovary: a review. Indian journal of surgical oncology. 2013;4(1):37-47.'doi:'10.1007/s13193-012-0201-z https://doi.org/10.1007/s13193-012-0201-z
Gurumurthy M, Bryant A, Shanbhag S. Effectiveness of different treatment modalities for the management of adult-onset granulosa cell tumours of the ovary (primary and recurrent). The Cochrane database of systematic reviews. 2014;2014(4):Cd006912.'doi:'10.1002/14651858.CD006912.pub2 https://doi.org/10.1002/14651858.CD006912.pub2
Ray-Coquard I, Brown J, Harter P, Provencher DM, Fong PC, Maenpaa J, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for ovarian sex cord stromal tumors. Int J Gynecol Cancer. 2014;24(9 Suppl 3):S42-7.'doi:'10.1097/igc.0000000000000249 https://doi.org/10.1097/igc.0000000000000249
Nasioudis D, Orfanelli T, Frey MK, Chapman-Davis E, Caputo TA, Witkin SS, et al. Role of adjuvant chemotherapy in the management of non-granulosa cell ovarian sex cord-stromal tumors. J Gynecol Oncol. 2019;30(2):e19.'doi:'10.3802/jgo.2019.30.e19 https://doi.org/10.3802/jgo.2019.30.e19
Wang D, Xiang Y, Wu M, Shen K, Yang J, Huang H, et al. Is adjuvant chemotherapy beneficial for patients with FIGO stage IC adult granulosa cell tumor of the ovary? J Ovarian Res. 2018;11(1):25.'doi:'10.1186/s13048-018-0396-x https://doi.org/10.1186/s13048-018-0396-x
Mangili G, Ottolina J, Cormio G, Loizzi V, De Iaco P, Pellegrini DA, et al. Adjuvant chemotherapy does not improve disease-free survival in FIGO stage IC ovarian granulosa cell tumors: The MITO-9 study. Gynecol Oncol. 2016;143(2):276-80.'doi:'10.1016/j.ygyno.2016.08.316 https://doi.org/10.1016/j.ygyno.2016.08.316
Nasioudis D, Kanninen TT, Holcomb K, Sisti G, Witkin SS. Prevalence of lymph node metastasis and prognostic significance of lymphadenectomy in apparent early-stage malignant ovarian sex cord-stromal tumors. Gynecol Oncol. 2017;145(2):243-7.'doi:'10.1016/j.ygyno.2017.03.005 https://doi.org/10.1016/j.ygyno.2017.03.005
Karalok A, Turan T, Ureyen I, Tasci T, Basaran D, Koc S, et al. Prognostic Factors in Adult Granulosa Cell Tumor: A Long Follow-Up at a Single Center. Int J Gynecol Cancer. 2016;26(4):619-25.'doi:'10.1097/igc.0000000000000659 https://doi.org/10.1097/igc.0000000000000659
Meisel JL, Hyman DM, Jotwani A, Zhou Q, Abu-Rustum NR, Iasonos A, et al. The role of systemic chemotherapy in the management of granulosa cell tumors. Gynecol Oncol. 2015;136(3):505-11.'doi:'10.1016/j.ygyno.2014.12.026 https://doi.org/10.1016/j.ygyno.2014.12.026
Wang JY, Li J, Chen RF, Lu X. Contribution of lymph node staging method and prognostic factors in malignant ovarian sex cord-stromal tumors: A world wide database analysis. Ejso. 2018;44(7):1054-61.'doi:'10.1016/j.ejso.2018.03.027 https://doi.org/10.1016/j.ejso.2018.03.027
Bryk S, Farkkila A, Butzow R, Leminen A, Heikinheimo M, Anttonen M, et al. Clinical characteristics and survival of patients with an adult-type ovarian granulosa cell tumor: a 56-year single-center experience. Int J Gynecol Cancer. 2015;25(1):33-41.'doi:'10.1097/igc.0000000000000304 https://doi.org/10.1097/igc.0000000000000304
Pommert L, Bradley W. Pediatric Gynecologic Cancers. Curr Oncol Rep. 2017;19(7):44.'doi:'10.1007/s11912-017-0604-7 https://doi.org/10.1007/s11912-017-0604-7
Huo Z, Guo L-N, Shi X-H, Liang Z-Y, Wang J-H, Liu X-G, et al. A Clinicopathological Study on Stage I Ovarian Adult Granulosa Cell Tumors with Recurrence within 5 Years. Chinese Medical Journal. 2018;131(23):2877-9.'doi:'10.4103/0366-6999.246066 https://doi.org/10.4103/0366-6999.246066
Seagle BL, Ann P, Butler S, Shahabi S. Ovarian granulosa cell tumor: A National Cancer Database study. Gynecol Oncol. 2017;146(2):285-91.'doi:'10.1016/j.ygyno.2017.05.020 https://doi.org/10.1016/j.ygyno.2017.05.020
You D, Zhang Z, Cao M. Development and Validation of a Prognostic Prediction Model for Postoperative Ovarian Sex Cord-Stromal Tumor Patients. Medical science monitor : international medical journal of experimental and clinical research. 2020;26:e925844.'doi:'10.12659/msm.925844 https://doi.org/10.12659/msm.925844
Nasioudis D, Mastroyannis SA, A FH, E MK, Latif NA. Ovarian Sertoli-Leydig and granulosa cell tumor: comparison of epidemiology and survival outcomes. Arch Gynecol Obstet. 2020;302(2):481-6.'doi:'10.1007/s00404-020-05633-z https://doi.org/10.1007/s00404-020-05633-z
Bergamini A, Cormio G, Ferrandina G, Lorusso D, Giorda G, Scarfone G, et al. Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study. Gynecol Oncol. 2019;154(2):323-7.'doi:'10.1016/j.ygyno.2019.05.029 https://doi.org/10.1016/j.ygyno.2019.05.029
Erkilinc S, Taylan E, Karatasli V, Uzaldi I, Karadeniz T, Gokcu M, et al. Does lymphadenectomy effect postoperative surgical morbidity and survival in patients with adult granulosa cell tumor of ovary? J Obstet Gynaecol Res. 2019;45(5):1019-25.'doi:'10.1111/jog.13928 https://doi.org/10.1111/jog.13928
Cheng H, Peng J, Yang Z, Zhang G. Prognostic significance of lymphadenectomyin malignant ovarian sex cord stromal tumor: A retrospective cohort study and meta-analysis. Gynecol Oncol. 2018;148(1):91-6.'doi:'10.1016/j.ygyno.2017.10.022 https://doi.org/10.1016/j.ygyno.2017.10.022
Melero Cortes LM, Martinez Maestre MA, Vieites Perez-Quintela MB, Gambadauro P. Ovarian Sertoli-Leydig cell tumours: How typical is their typical presentation? J Obstet Gynaecol. 2017;37(5):655-9.'doi:'10.1080/01443615.2017.1291590 https://doi.org/10.1080/01443615.2017.1291590
Burnik Papler T, Frkovic Grazio S, Kobal B. Sertoli - Leydig cell tumor with retiform areas and overgrowth of rhabdomyosarcomatous elements: case report and literature review. J Ovarian Res. 2016;9(1):46.'doi:'10.1186/s13048-016-0257-4 https://doi.org/10.1186/s13048-016-0257-4
Farkkila A, Haltia UM, Tapper J, McConechy MK, Huntsman DG, Heikinheimo M. Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary. Ann Med. 2017;49(5):435-47.'doi:'10.1080/07853890.2017.1294760 https://doi.org/10.1080/07853890.2017.1294760
Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, et al. Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review. Cancers. 2020;12(6).'doi:'10.3390/cancers12061398 https://doi.org/10.3390/cancers12061398
van Meurs HS, Buist MR, Westermann AM, Sonke GS, Kenter GG, van der Velden J. Effectiveness of chemotherapy in measurable granulosa cell tumors: a retrospective study and review of literature. Int J Gynecol Cancer. 2014;24(3):496-505.'doi:'10.1097/igc.0000000000000077 https://doi.org/10.1097/igc.0000000000000077

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Association between Postoperative Adjuvant Chemotherapy and Disease-Specific Survival in Women with Ovarian Sex Cord-Stromal Tumors: A SEER-based Study

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