Radiographic Number of Positive Pelvic Lymph Nodes as a Prognostic Factor in Cervical Cancer Treated With Definitive Concurrent Chemoradiotherapy or Intensity-Modulated Radiotherapy

Shih-Chang Wang, Li-Ching Lin, Yu-Ting Kuo, Yu-Wei Lin, Shih-Chang Wang, Li-Ching Lin, Yu-Ting Kuo, Yu-Wei Lin

Abstract

Background: This study aims to assess the prognostic significance of radiographic numbers of positive pelvic lymph nodes (PLNs) in patients with cervical cancer treated with definitive concurrent chemoradiotherapy (CCRT) or intensity-modulated radiotherapy (IMRT). Methods: We conducted a retrospective study that included 164 eligible adult patients with cervical cancer who were treated with definitive CCRT or IMRT at our institution from 2009 to 2016. After exclusion of 50 patients, a total of 114 patients whose clinicopathological data and follow-up were finally analyzed. The radiographic numbers of positive PLNs were assessed by pretreatment magnetic resonance imaging (MRI) or computed tomography (CT). The criterion for a positive lymph node was defined as a short-axis diameter >1 cm. Using the Kaplan-Meier method and the Cox proportional hazards regression model, we assessed the overall survival (OS), cancer-specific survival (CSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Results: The median follow-up duration was 40 (range: 2-100) months. For patients with 0, 1-2, and ≥3 positive PLNs, the estimated 3-year OS were 85.4% vs. 82.4% vs. 59.7% (p = 0.035), CSS were 90.1% vs. 86.1% vs. 62.9% (p = 0.010), DMFS were 89.4% vs. 91.3% vs. 49.6% (p < 0.001), and LRFS were 77.8% vs. 73.4% vs. 70% (p = 0.690). Per the multivariate Cox regression, positive PLNs ≥3 (HR, 2.51; 95% CI: 1.09-5.80; p = 0.031) and non-squamous cell carcinoma type (HR, 2.82; 95% CI: 1.19-6.69; p = 0.018) were unfavorable factors for the OS. Besides, positive PLNs ≥3 was the independent factor for the CSS (HR, 3.38; 95% CI: 1.32-8.67; p = 0.011) and DMFS (HR, 6.83; 95% CI: 2.62-17.83; p < 0.001). The patients that were treated without intracavitary brachytherapy exhibited inferior LRFS (HR, 13.15; 95% CI: 2.66-65.10; p = 0.002). Conclusions: The radiographic number of positive PLNs (≥ 3) is an independent prognostic factor for OS, CSS, and DMFS in patients treated with definitive CCRT or IMRT.

Keywords: CCRT; IMRT; cervical cancer; pelvic lymph node; positive lymph nodes; radiographic finding; survival.

Figures

Figure 1
Figure 1
FigureKaplan–Meier curve of overall survival, cancer-specific survival, distant metastasis-free survival, and locoregional relapse-free survival for all patients.
Figure 2
Figure 2
Kaplan–Meier analysis of (A) overall survival, (B) cancer-specific survival, (C) distant metastasis-free survival, and (D) locoregional relapse-free survival for patients with cervical cancer stratified by number(s) of positive pelvic lymph nodes (PLNs).

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer (2015) 136:E359–86. 10.1002/ijc.29210
    1. Global Burden of Disease Cancer C, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. (2017) 3:524–48. 10.1001/jamaoncol.2016.5688
    1. Duenas-Gonzalez A, Campbell S. Global strategies for the treatment of early-stage and advanced cervical cancer. Curr Opin Obstet Gynecol. (2016) 28:11–7. 10.1097/GCO.0000000000000234
    1. Lv Y, Wang F, Yang L, Sun G. Intensity-modulated whole pelvic radiotherapy provides effective dosimetric outcomes for cervical cancer treatment with lower toxicities. Cancer Radiother. (2014) 18:745–52. 10.1016/j.canrad.2014.08.005
    1. Cihoric N, Tsikkinis A, Tapia C, Aebersold DM, Zlobec I, Lossl K. Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer. Radiat Oncol. (2015) 10:240. 10.1186/s13014-015-0551-0
    1. Ouyang Y, Wang Y, Chen K, Cao X, Zeng Y. Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer. Oncol Lett. (2017) 14:7069–76. 10.3892/ol.2017.7077
    1. Chen CC, Lin JC, Jan JS, Ho SC, Wang L. Definitive intensity-modulated radiation therapy with concurrent chemotherapy for patients with locally advanced cervical cancer. Gynecol Oncol. (2011) 122:9–13. 10.1016/j.ygyno.2011.03.034
    1. Lee J, Lin JB, Chang CL, Sun FJ, Wu MH, Jan YT, et al. . Impact of para-aortic recurrence risk-guided intensity-modulated radiotherapy in locally advanced cervical cancer with positive pelvic lymph nodes. Gynecol Oncol. (2018) 148:291–8. 10.1016/j.ygyno.2017.12.003
    1. Vargo JA, Kim H, Choi S, Sukumvanich P, Olawaiye AB, Kelley JL, et al. . Extended field intensity modulated radiation therapy with concomitant boost for lymph node-positive cervical cancer: analysis of regional control and recurrence patterns in the positron emission tomography/computed tomography era. Int J Radiat Oncol Biol Phys. (2014) 90:1091–8. 10.1016/j.ijrobp.2014.08.013
    1. Horn LC, Fischer U, Raptis G, Bilek K, Hentschel B. Tumor size is of prognostic value in surgically treated FIGO stage II cervical cancer. Gynecol Oncol. (2007) 107:310–5. 10.1016/j.ygyno.2007.06.026
    1. Chandeying N, Hanprasertpong J. The prognostic impact of histological type on clinical outcomes of early-stage cervical cancer patients whom have been treated with radical surgery. J Obstet Gynaecol. (2017) 37:347–54. 10.1080/01443615.2016.1245279
    1. Hoskin PJ, Rojas AM, Peiris SN, Mullassery V, Chong IY. Pre-treatment haemoglobin and peripheral blood lymphocyte count as independent predictors of outcome in carcinoma of cervix. Clin Oncol. (2014) 26:179–84. 10.1016/j.clon.2013.11.023
    1. Kasamatsu T, Onda T, Sawada M, Kato T, Ikeda S. Radical hysterectomy for FIGO stage IIB cervical cancer: clinicopathological characteristics and prognostic evaluation. Gynecol Oncol. (2009) 114:69–74. 10.1016/j.ygyno.2009.03.026
    1. Tseng JY, Yen MS, Twu NF, Lai CR, Horng HC, Tseng CC, et al. . Prognostic nomogram for overall survival in stage IIB-IVA cervical cancer patients treated with concurrent chemoradiotherapy. Am J Obstet Gynecol. (2010) 202:174e1–7. 10.1016/j.ajog.2009.09.028
    1. Xia X, Xu H, Wang Z, Liu R, Hu T, Li S. Analysis of prognostic factors affecting the outcome of stage IB-IIB cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy. Am J Clin Oncol. (2016) 39:604–8. 10.1097/COC.0000000000000100
    1. Yan X, Li G, Shang H, Lin F, Yang X, Zheng F. Outcome and prognostic factors of laparoscopic radical hysterectomy and pelvic lymphadenectomy in 148 patients with stage IB1 cervical cancer. Int J Gynecol Cancer (2012) 22:286–90. 10.1097/IGC.0b013e318233d549
    1. Chittithaworn S, Hanprasertpong J, Tungsinmunkong K, Geater A. Association between prognostic factors and disease-free survival of cervical cancer stage IB1 patients undergoing radical hysterectomy. Asian Pac J Cancer Prev. (2007) 8:530–4.
    1. Kim HJ, Rhee WJ, Choi SH, Nam EJ, Kim SW, Kim S, et al. . Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer. Radiat Oncol J. (2015) 33:126–33. 10.3857/roj.2015.33.2.126
    1. Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. (1990) 38:352–7. 10.1016/0090-8258(90)90072-S
    1. Monk BJ, Cha DS, Walker JL, Burger RA, Ramsinghani NS, Manetta A, et al. . Extent of disease as an indication for pelvic radiation following radical hysterectomy and bilateral pelvic lymph node dissection in the treatment of stage IB and IIA cervical carcinoma. Gynecol Oncol. (1994) 54:4–9. 10.1006/gyno.1994.1157
    1. Zhou J, Wu SG, Sun JY, Liao XL, Li FY, Lin HX, et al. . Incorporation of the number of positive lymph nodes leads to better prognostic discrimination of node-positive early stage cervical cancer. Oncotarget (2017) 8:26057–65. 10.18632/oncotarget.15220
    1. Stock RG, Chen AS, Flickinger JC, Kalnicki S, Seski J. Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure. Int J Radiat Oncol Biol Phys. (1995) 31:31–6. 10.1016/0360-3016(94)00391-W
    1. Horn LC, Schierle K, Schmidt D, Ulrich U, Liebmann A, Wittekind C. [Current TNM/FIGO classification for cervical and endometrial cancer as well as malignant mixed mullerian tumors. Facts and background]. Pathologe (2011) 32:239–43. 10.1007/s00292-010-1273-6
    1. Odicino F, Pecorelli S, Zigliani L, Creasman WT. History of the FIGO cancer staging system. Int J Gynaecol Obstet. (2008) 101:205–10. 10.1016/j.ijgo.2007.11.004
    1. Hosaka M, Watari H, Mitamura T, Konno Y, Odagiri T, Kato T, et al. . Survival and prognosticators of node-positive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy. Int J Clin Oncol. (2011) 16:33–8. 10.1007/s10147-010-0123-0
    1. Hsu HC, Li X, Curtin JP, Goldberg JD, Schiff PB. Surveillance epidemiology and end results analysis demonstrates improvement in overall survival for cervical cancer patients treated in the era of concurrent chemoradiotherapy. Front Oncol. (2015) 5:81. 10.3389/fonc.2015.00081
    1. Liang JA, Chen SW, Chang WC, Hung YC, Yeh LS, Yang SN, et al. . Risk stratification for failure in patients with advanced cervical cancer after concurrent chemoradiotherapy: another way to optimise treatment results. Clin Oncol. (2008) 20:683–90. 10.1016/j.clon.2008.06.007
    1. Endo D, Todo Y, Okamoto K, Minobe S, Kato H, Nishiyama N. Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort. J Gynecol Oncol. (2015) 26:12–8. 10.3802/jgo.2015.26.1.12
    1. Kudaka W, Nagai Y, Toita T, Inamine M, Asato K, Nakamoto T, et al. . Long-term results and prognostic factors in patients with stage III-IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study. Int J Clin Oncol. (2013) 18:916–21. 10.1007/s10147-012-0457-x
    1. Datta NR, Stutz E, Liu M, Rogers S, Klingbiel D, Siebenhuner A, et al. . Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: a systematic review and meta-analysis. Gynecol Oncol. (2017) 145:374–85. 10.1016/j.ygyno.2017.01.033
    1. Mileshkin LR, Narayan K, Moore KN, Rischin D, King M, Kolodziej I, et al. A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: outback (ANZGOG0902/GOG0274/RTOG1174). J Clin Oncol. (2014) 32(Suppl. 15):5632. 10.1200/jco.2014.32.15
    1. Lee JY, Kim YT, Kim S, Lee B, Lim MC, Kim JW, et al. . Prognosis of cervical cancer in the era of concurrent chemoradiation from national database in Korea: a comparison between squamous cell carcinoma and adenocarcinoma. PLoS ONE (2015) 10:e0144887. 10.1371/journal.pone.0144887
    1. Yokoi E, Mabuchi S, Takahashi R, Matsumoto Y, Kuroda H, Kozasa K, et al. . Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma. J Gynecol Oncol. (2017) 28:e19. 10.3802/jgo.2017.28.e19
    1. Viswanathan AN, Beriwal S, De Los Santos JF, Demanes DJ, Gaffney D, Hansen J, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy. Brachytherapy (2012) 11:47–52. 10.1016/j.brachy.2011.07.002

Source: PubMed

3
購読する