Predictors of Distant Metastasis in Patients with Cervical Cancer Treated with Definitive Radiotherapy

Xiaoliang Liu, Qingyu Meng, Weiping Wang, Ziqi Zhou, Fuquan Zhang, Ke Hu, Xiaoliang Liu, Qingyu Meng, Weiping Wang, Ziqi Zhou, Fuquan Zhang, Ke Hu

Abstract

Objective: To identify the predictors of distant metastasis in patients with cervical cancer treated with definitive radiotherapy and develop a model for predicting distant metastasis. Methods: We reviewed the clinical records of patients with cervical cancer treated with definitive radiotherapy (IMRT) at Peking Union Medical College Hospital between January 2011 and December 2015. Eligible patients were randomly assigned into model development cohort and validation cohort in a 2:1 ratio. Distant metastasis rate (DMR) was calculated with Kaplan-Meier method. Univariate and multivariate analyses using cox proportional hazard model was performed to identify the risk factors of distant relapse. Based on the identified risk factors for distant metastasis, a model for predicting distant metastasis was developed and validated. A two-side P<0.05 was defined as statistically significant. Results: A total of 1193 patients were eligible for this analysis including 797 patients in the model development cohort and 396 patients in the validation cohort. The median follow-up durations of the model development cohort and the validation cohort were 28.7 months (range: 2.5-83.9 months) and 30.9 months (1.9-83.5 months). The 2-year distant metastasis rates (DMR) for patients in the model development cohort and validation cohort were 13.3% and 12.8%. Non-squamous cell carcinoma (non-Scc), common iliac lymph nodes metastasis (LNM) and bilateral pelvic LNM (PLNM) were identified as risk factors for distant metastasis. In the model development cohort, significant difference between high-risk group (with 2-3 risk factors) and low-risk group (with 0-1 risk factor) regarding DMR was observed (39.3% vs 19.3%, P<0.001). Similar conclusions were observed in the validation cohort (high-risk group vs low-risk group, 47.6% vs 10.9%, P<0.001) Conclusion: We successfully developed a model for predicting distant metastasis in patients with cervical cancer receiving definitive radiotherapy based on the three identified risk factors for distant metastasis. This model would help us distinguish patients with high risk of distant relapse from others.

Keywords: Cervical cancer; distant metastasis; prognostic factors; radiotherapy.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Distant metastasis rate for patients in the model development cohort and validation cohort
Figure 2
Figure 2
Distant metastasis rate for patients with Scc and non-Scc in the model development cohort
Figure 3
Figure 3
Distant metastasis rate for patients with positive and negative common iliac lymph nodes in the model development cohort
Figure 4
Figure 4
Distant metastasis rate for patients with no PLNM, unilateral PLNM and bilateral PLNM in the model development cohort
Figure 5
Figure 5
Distant metastasis rate for patients in low-risk and high-risk groups from the model development cohort
Figure 6
Figure 6
Distant metastasis rate for patients in low-risk and high-risk groups from the validation cohort

References

    1. 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.
    1. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd. et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999;340:1154–61.
    1. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE. et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340:1137–43.
    1. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA. et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340:1144–53.
    1. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr. et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999;17:1339–48.
    1. Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS. et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18:1606–13.
    1. Kato S, Ohno T, Thephamongkhol K, Chansilpa Y, Cao J, Xu X. et al. Long-term follow-up results of a multi-institutional phase 2 study of concurrent chemoradiation therapy for locally advanced cervical cancer in east and southeast Asia. Int J Radiat Oncol Biol Phys. 2013;87:100–5.
    1. Varia MA, Bundy BN, Deppe G, Mannel R, Averette HE, Rose PG. et al. Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys. 1998;42:1015–23.
    1. Jouglar E, Thomas L, de la Rochefordiere A, Noel G, Le Blanc-Onfroy M, Delpon G. et al. Toxicity and early clinical outcomes in cervical cancer following extended field helical tomotherapy to para-aortic lymph nodes. Cancer Radiother. 2016;20:794–800.
    1. Wang W, Zhang F, Hu K, Hou X. Image-guided, intensity-modulated radiation therapy in definitive radiotherapy for 1433 patients with cervical cancer. Gynecol Oncol. 2018;151:444–8.
    1. Tan LT, Coles CE, Hart C, Tait E. Clinical impact of computed tomography-based image-guided brachytherapy for cervix cancer using the tandem-ring applicator - the Addenbrooke's experience. Clin Oncol (R Coll Radiol) 2009;21:175–82.
    1. Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M. et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. The Lancet. 2001;358:781–6.
    1. Okazawa-Sakai M, Mabuchi S, Isohashi F, Kawashima A, Yokoi E, Ogawa K. et al. Predictors of distant relapse in patients with FIGO stage IIB-IVA cervical cancer treated with definitive radiotherapy. J Obstet Gynaecol Res. 2017;43:1743–50.
    1. Wang W, Liu X, Meng Q, Zhang F, Hu K. Nomogram for predicting para-aortic lymph node metastases in patients with cervical cancer. Arch Gynecol Obstet. 2018;298:381–8.
    1. Wang W, Hou X, Yan J, Shen J, Lian X, Sun S. et al. Outcome and toxicity of radical radiotherapy or concurrent Chemoradiotherapy for elderly cervical cancer women. BMC Cancer. 2017;17:510.
    1. Wang W, Meng Q, Hou X, Lian X, Yan J, Sun S. et al. Efficacy and toxicity of image-guided intensity-modulated radiation therapy combined with dose-escalated brachytherapy for stage IIB cervical cancer. Oncotarget. 2017;8:102965–73.
    1. Yin KC, Lu CH, Lin JC, Hsu CY, Wang L. Treatment outcomes of locally advanced cervical cancer by histopathological types in a single institution: A propensity score matching study. J Formos Med Assoc. 2018;117:922–31.
    1. Hu K, Wang W, Liu X, Meng Q, Zhang F. Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma of cervix after definitive radiotherapy or concurrent chemoradiotherapy. Radiat Oncol. 2018;13:249.
    1. Zhou J, Wu SG, Sun JY, Li FY, Lin HX, Chen QH. et al. Comparison of clinical outcomes of squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the uterine cervix after definitive radiotherapy: a population-based analysis. J Cancer Res Clin Oncol. 2017;143:115–22.
    1. Schmid MP, Franckena M, Kirchheiner K, Sturdza A, Georg P, Dorr W. et al. Distant metastasis in patients with cervical cancer after primary radiotherapy with or without chemotherapy and image guided adaptive brachytherapy. Gynecol Oncol. 2014;133:256–62.
    1. Li X, Wei LC, Zhang Y, Zhao LN, Li WW, Ping LJ. et al. The Prognosis and Risk Stratification Based on Pelvic Lymph Node Characteristics in Patients With Locally Advanced Cervical Squamous Cell Carcinoma Treated With Concurrent Chemoradiotherapy. Int J Gynecol Cancer. 2016;26:1472–9.

Source: PubMed

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