Prognostic value of metabolic tumor volume and total lesion glycolysis from 18 F-FDG PET/CT in lymph node metastases and risk stratification of endometrial carcinoma

Dou-dou Liu; Jianfang Li; Xiaomao Li; Liangjun Xie; Luping Qin; Fangyu Peng; Mu-hua Cheng

doi:10.3802/jgo.2019.30.e89

Journal List > J Gynecol Oncol > v.30(6) > 1134475

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Liu, Li, Li, Xie, Qin, Peng, and Cheng: Prognostic value of metabolic tumor volume and total lesion glycolysis from 18 F-FDG PET/CT in lymph node metastases and risk stratification of endometrial carcinoma

Original Article

J Gynecol Oncol 2019;30(6):e89.

Published online: 4 November 2019

DOI: https://doi.org/10.3802/jgo.2019.30.e89

Prognostic value of metabolic tumor volume and total lesion glycolysis from ¹⁸ F-FDG PET/CT in lymph node metastases and risk stratification of endometrial carcinoma

Dou-dou Liu^1,^2,^*, Jianfang Li^1,^*, Xiaomao Li³, Liangjun Xie¹, Luping Qin¹, Fangyu Peng⁴, Mu-hua Cheng^1,

¹Department of Nuclear Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

²Department of Radiology, FUWAI Central China Cardiovascular Hospital, Zhengzhou, China

³Department of Gynecology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

⁴Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA

Correspondence to Mu-hua Cheng Department of Nuclear Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. E-mail: chmarka@163.com

^* Dou-dou Liu and Jianfang Li contributed equally to this work as the co-first authors.

Received 7 January 2019 Revised 1 March 2019 Accepted 18 April 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), measured by preoperative ¹⁸ F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸ F-FDG PET/CT), in risk stratification of patients with endometrial carcinoma (EC).

Methods

The patients with pathological diagnosis of EC who underwent preoperative ¹8 F-FDG PET/CT imaging were retrospectively selected for analysis of the prognostic values of PET parameters in risk classification and lymph node metastases (LNMs). Receiver-operating-characteristic analysis was used to analyze the correlation of PET parameters cutoff values with deep myometrial invasion (MI), lymphovascular space involvement and LNM for prognostic values in risk stratification.

Results

The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of LNM are 83.3%, 99.7%, 90.9%, 99.5% and 99.2%, respectively. The MTV and TLG of primary lesion of EC in the patients with LNM are notably higher than those in patients without LNM, p<0.010. The MTV and TLG of the EC primary lesions in high-risk patients are significantly higher than those in low-risk patients (p<0.010), but the maximum standardized uptake value (SUVmax) is not. The MTV and TLG of primary lesions were superior to SUVmax for predicting of deep MI, LNM and high-risk of EC (p<0.005).

Conclusion

MTV and TLG of primary lesions are more valuable in predicting risk stratification of EC patients. Preoperative ¹⁸ F-FDG PET/CT imaging is useful in predicting the LNM of EC and may help guide pelvic lymphadenectomy to avoid unnecessary pelvic lymphadenectomy in EC patients with low-risk stratification.

Keywords: Endometrial Carcinoma, Lymphatic Metastases, Tumor Volume, Metabolism, Risk Assessment

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66:7–30.

2. Tirumani SH, Shanbhogue AK, Prasad SR. Current concepts in the diagnosis and management of endometrial and cervical carcinomas. Radiol Clin North Am. 2013; 51:1087–110.

3. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66:115–32.

4. Boyraz G, Salman MC, Gultekin M, Basaran D, Cagan M, Ozgul N, et al. Incidence of lymph node metastasis in surgically staged FIGO Ia G1/G2 endometrial cancer with a tumor size of more than 2 cm. Int J Gynecol Cancer. 2017; 27:486–92.

5. Kitajima K, Suenaga Y, Ueno Y, Maeda T, Ebina Y, Yamada H, et al. Preoperative risk stratification using metabolic parameters of ¹⁸ F-FDG PET/CT in patients with endometrial cancer. Eur J Nucl Med Mol Imaging. 2015; 42:1268–75.

6. Lindqvist E, Wedin M, Fredrikson M, Kjølhede P. Lymphedema after treatment for endometrial cancer – A review of prevalence and risk factors. Eur J Obstet Gynecol Reprod Biol. 2017; 211:112–21.

7. Lee HJ, Lee JJ, Park JY, Kim JH, Kim YM, Kim YT, et al. Prognostic value of metabolic parameters determined by preoperative ¹⁸ F-FDG PET/CT in patients with uterine carcinosarcoma. J Gynecol Oncol. 2017; 28:e43.

8. Atri M, Zhang Z, Dehdashti F, Lee SI, Marques H, Ali S, et al. Utility of PET/CT to evaluate retroperitoneal lymph node metastasis in high-risk endometrial cancer: results of ACRIN 6671/GOG 0233 trial. Radiology. 2017; 283:450–9.

9. Pulman KJ, Dason ES, Philp L, Bernardini MQ, Ferguson SE, Laframboise S, et al. Comparison of three surgical approaches for staging lymphadenectomy in high-risk endometrial cancer. Int J Gynaecol Obstet. 2017; 136:315–9.

10. Todo Y, Takeshita S, Okamoto K, Yamashiro K, Kato H. Implications of paraaortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis. J Gynecol Oncol. 2017; 28:e59.

11. Kikuchi A, Yanase T, Sasagawa M, Honma S. The role of paraaortic lymphadenectomy in stage IIIC endometrial cancer: a single-institute study. J Obstet Gynaecol. 2017; 37:510–3.

12. Lee HJ, Ahn BC, Hong CM, Song BI, Kim HW, Kang S, et al. Preoperative risk stratification using ¹⁸ F-FDG PET/CT in women with endometrial cancer. Nucl Med (Stuttg). 2011; 50:204–13.

13. Bae HS, Lim MC, Lee JS, Lee Y, Nam BH, Seo SS, et al. Postoperative lower extremity edema in patients with primary endometrial cancer. Ann Surg Oncol. 2016; 23:186–95.

14. Achouri A, Huchon C, Bats AS, Bensaid C, Nos C, Lécuru F. Complications of lymphadenectomy for gynecologic cancer. Eur J Surg Oncol. 2013; 39:81–6.

15. Zhang C, Wang C, Feng W. Clinicopathological risk factors for pelvic lymph node metastasis in clinical early-stage endometrioid endometrial adenocarcinoma. Int J Gynecol Cancer. 2012; 22:1373–7.

16. Winer I, Ahmed QF, Mert I, Bandyopadhyay S, Cote M, Munkarah AR, et al. Significance of lymphovascular space invasion in uterine serous carcinoma: what matters more; extent or presence? Int J Gynecol Pathol. 2015; 34:47–56.

17. Sudo S, Hattori N, Manabe O, Kato F, Mimura R, Magota K, et al. FDG PET/CT diagnostic criteria may need adjustment based on MRI to estimate the presurgical risk of extrapelvic infiltration in patients with uterine endometrial cancer. Eur J Nucl Med Mol Imaging. 2015; 42:676–84.

18. Nakamura K, Hongo A, Kodama J, Hiramatsu Y. The measurement of SUVmax of the primary tumor is predictive of prognosis for patients with endometrial cancer. Gynecol Oncol. 2011; 123:82–7.

19. Nakamura K, Kodama J, Okumura Y, Hongo A, Kanazawa S, Hiramatsu Y. The SUVmax of ¹⁸ F-FDG PET correlates with histological grade in endometrial cancer. Int J Gynecol Cancer. 2010; 20:110–5.

20. Husby JA, Reitan BC, Biermann M, Trovik J, Bjørge L, Magnussen IJ, et al. Metabolic tumor volume on ¹8 F-FDG PET/CT improves preoperative identification of high-risk endometrial carcinoma patients. J Nucl Med. 2015; 56:1191–8.

21. Shim SH, Kim DY, Lee DY, Lee SW, Park JY, Lee JJ, et al. Metabolic tumour volume and total lesion glycolysis, measured using preoperative ¹⁸ F-FDG PET/CT, predict the recurrence of endometrial cancer. BJOG. 2014; 121:1097–106.

22. Tamandl D, Ta J, Schmid R, Preusser M, Paireder M, Schoppmann SF, et al. Prognostic value of volumetric PET parameters in unresectable and metastatic esophageal cancer. Eur J Radiol. 2016; 85:540–5.

23. Liao S, Penney BC, Zhang H, Suzuki K, Pu Y. Prognostic value of the quantitative metabolic volumetric measurement on ¹⁸ F-FDG PET/CT in Stage IV nonsurgical small-cell lung cancer. Acad Radiol. 2012; 19:69–77.

24. Sun Y, Lu P, Yu L. The volume-metabolic combined parameters from ¹⁸ F-FDG PET/CT may help predict the outcomes of cervical carcinoma. Acad Radiol. 2016; 23:605–10.

25. Ghooshkhanei H, Treglia G, Sabouri G, Davoodi R, Sadeghi R. Risk stratification and prognosis determination using ¹⁸ F-FDG PET imaging in endometrial cancer patients: a systematic review and meta-analysis. Gynecol Oncol. 2014; 132:669–76.

26. Wang ZQ, Wang JL, Shen DH, Li XP, Wei LH. Should all endometrioid uterine cancer patients undergo systemic lymphadenectomy? Eur J Surg Oncol. 2013; 39:344–9.

27. Mariani A, Webb MJ, Keeney GL, Haddock MG, Calori G, Podratz KC. Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary? Am J Obstet Gynecol. 2000; 182:1506–19.

28. Antonsen SL, Jensen LN, Loft A, Berthelsen AK, Costa J, Tabor A, et al. MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer – a multicenter prospective comparative study. Gynecol Oncol. 2013; 128:300–8.

29. Signorelli M, Crivellaro C, Buda A, Guerra L, Fruscio R, Elisei F, et al. Staging of high-risk endometrial cancer with PET/CT and sentinel lymph node mapping. Clin Nucl Med. 2015; 40:780–5.

Fig. 1.

A high-risk EC patient, 55 years, EC G3, FIGO stage IIIC1, with positive LNM and LVSI. The SUVmax, MTV and TLG of primary lesion (A) are 22.39, 61.24 and 589.74, respectively. The SUVmax in left external iliac LNM (B) is 5.34, more than the 5.22 of cutoff value, confirmed as LNM, but the SUVmax in left common iliac lymph node (C) is 4.05, less than the 5.22 of cutoff value, confirmed as negative LNM by pathology. EC, endometrial carcinoma; FIGO, International Federation of Gynecology and Obstetrics; LNM, lymph node metastasis; LVSI, lymphovascular space involvement; MTV, metabolic tumor volume; SUVmax, maximum standardized uptake value; TLG, total lesion glycolysis.

Fig. 2.

ROC curves for various tumor quantifications for prediction of MI (A), LNMs (B), LVSI (C) and risk stratification (D) in patients with endometrial carcinoma. The p-values refer to test of equal areas under the curve across tumor quantifications AUCs. AUC, area under the curve; LNM, lymph node metastasis; LVSI, lymphovascular space involvement; MI, myometrial invasion; MTV, metabolic tumor volume; ROC, receiver-operating-characteristic; SUV, standardized uptake value; TLG, total lesion glycolysis.

Table 1.

The histopathological data of patients with EC (n=41)

Characteristic	Case (%)
Histopathology type
Type I	37 (90.2)
Type II	4 (9.8)
Histopathology grade
G1	22 (53.7)
G2	11 (26.8)
G3	8 (19.5)
FIGO stage
Stage I	27 (65.9)
Ia	21 (51.2)
Ib	6 (14.6)
Stage II	3 (7.3)
Stage III	11 (26.8)
MI
<1/2	27 (65.9)
≥1/2	14 (34.1)
LVSI
Negative	32 (78.1)
Positive	9 (21.9)
LNM
Negative	34 (82.9)
Positive	7 (17.1)
Risk stratification
Low-risk	22 (53.7)
High-risk	19 (46.3)

Histopathology type: type I is endometrial adenocarcinoma; type II is serous cell carcinoma, clear cell carcinoma, sarcomas and low-differentiated endometrial adenocarcinoma, etc. Histopathology grade: G1 is high differentiated tumor, G2 is middle differentiated tumor and G3 is low differentiated tumor. MI: MI<1/2 indicated that the focus of EC be limited to a depth of less than half of the endometrium or the infiltrating muscle layer, MI≥1/2 indicated that the depth of invasive myometrium of endometrial carcinoma is greater than half. The EC patient with FIGO stage Ia and superficial MI (MI<1/2) was classified to low-risk group, otherwise to the high-risk group.

EC, endometrial carcinoma; FIGO, International Federation of Gynecology and Obstetrics; MI, myometrial invasion; LNM, lymph node metastasis; LVSI, lymphovascular space involvement.

Table 2.

TLG, MTV and SUVmax in MI, LNM, LVSI and risk stratification group

Group	Case (%)	SUVmax	MTV	TLG
MI
<1/2	27 (65.9)	10.95±5.71	7.08±5.96	46.21±52.53
≥1/2	14 (34.1)	14.55±5.33	39.37±44.06	387.17±523.56
p-value		>0.050	<0.001	<0.005
LVSI
Negative	32 (78.1)	10.79±5.48	7.45±5.75	48.90±45.84
Positive	9 (21.9)	17.12±3.90	55.98±47.69	566.99±587.00
p-value		<0.005	<0.001	<0.001
LNM
Negative	34 (82.9)	11.80±5.65	10.94±15.35	84.13±132.56
Positive	7 (17.1)	14.03±6.51	52.90±54.43	543.89±695.25
p-value		>0.050	<0.001	<0.001
Risk stratification
Low-risk	22 (53.7)	11.11±6.02	6.73±6.21	47.54±59.42
High-risk	19 (46.3)	13.41±5.38	31.28±40.01	295.88±471.65
p-value		>0.050	<0.010	<0.050

LNM, lymph node metastasis; LVSI, lymphovascular space involvement; MI, myometrial invasion; MTV, metabolic tumor volume; SUVmax, maximum standardized uptake value; TLG, total lesion glycolysis.

Table 3.

The ROC curve parameters of primary lesion of EC in different groups

Group	AUCs (95% CI)	p-value	Cutoff	Sensitivity (%)	Specificity (%)
Deep MI
SUVmax	0.709 (0.538–0.880)	0.030	12.4	78.6	66.7
MTV	0.817 (0.672–0.962)	0.001	11.8	71.4	85.2
TLG	0.831 (0.682–0.979)	0.001	98.3	71.4	92.6
LVSI
SUVmax	0.609 (0.366–0.852)	0.368	14.9	57.1	73.5
MTV	0.832 (0.679–0.985)	0.006	17.2	71.4	85.3
TLG	0.782 (0.589–0.974)	0.020	79.8	71.4	80.6
LNM
SUVmax	0.784 (0.634–0.934)	0.014	14.2	66.8	71.9
MTV	0.898 (0.774–1.000)	0.001	19.8	77.8	93.7
TLG	0.909 (0.794–1.000)	0.001	166.9	75.0	96.9
Risk stratification
SUVmax	0.639 (0.463–0.815)	0.129	11.3	78.9	63.6
MTV	0.787 (0.641–0.933)	0.002	9.5	73.7	81.8
TLG	0.778 (0.627–0.928)	0.002	51.7	84.2	77.3

AUC, area under the curve; CI, confidence interval; EC, endometrial cancer; LNM, lymph node metastasis; LVSI, lymphovascular space involvement; MI, myometrial invasion; MTV, metabolic tumor volume; ROC, receiver-operating-characteristic; SUVmax, maximum standardized uptake value; TLG, total lesion glycolysis.

TOOLS

Similar articles