Safety and efficacy of semiextended field intensity-modulated radiation therapy and concurrent cisplatin in locally advanced cervical cancer patients: An observational study of 10-year experience

Jie Lee, Jhen-Bin Lin, Fang-Ju Sun, Yu-Jen Chen, Chih-Long Chang, Ya-Ting Jan, Meng-Hao Wu, Jie Lee, Jhen-Bin Lin, Fang-Ju Sun, Yu-Jen Chen, Chih-Long Chang, Ya-Ting Jan, Meng-Hao Wu

Abstract

Patients with locally advanced cervical cancer (LACC) are at risk of para-aortic lymph node (PALN) metastasis. Pelvic concurrent chemoradiotherapy, the current standard treatment for LACC, has a PALN failure rate of 9% according to the Radiation Therapy Oncology Group Trial 90-01, suggesting that it may not completely eliminate all microscopic tumors in the PALNs. To minimize the toxicities associated with conventional prophylactic extended-field radiotherapy, our institute use prophylactic semiextended field radiotherapy that includes only the PALNs below the level of the renal vessels. Use of intensity-modulated radiotherapy (IMRT) is another means of reducing the incidence of toxicity. This study evaluated the safety and efficacy of prophylactic semiextended field IMRT (SEF-IMRT) and concurrent cisplatin chemotherapy in patients with LACC.We retrospectively assessed survival and toxicity in 76 patients with stage IB2-IVA cervical cancer and negative PALNs who received prophylactic SEF-IMRT and concurrent weekly cisplatin (40 mg/m) between 2004 and 2013. The region targeted by SEF-IMRT included the PALNs below the level of the renal vessels, and the prescribed dose was 50.4 Gy in 28 fractions. Brachytherapy was administered at a dose of 30 Gy in 6 fractions. Survival outcomes were calculated by using the Kaplan-Meier method, and acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0.All patients completed the planned SEF-IMRT, as well as brachytherapy. Acute grade ≥3 gastrointestinal, genitourinary, and hematologic toxicities were observed in 2, 0, and 41 patients, respectively. The median follow-up time after SEF-IMRT was 55 (range, 11-124) months. Eight patients developed out-field distant recurrences without PALN failure, and 1 patient experienced out-field PALN failure with simultaneous distant metastasis. No patients had late genitourinary toxicities, and 3 patients had late grade 3 gastrointestinal toxicities. The 5-year overall survival, disease-free survival, local failure-free survival, regional failure-free survival, PALN failure-free survival, and distant metastasis-free survival rates were 85.0%, 84.4%, 96.0%, 97.3%, 98.6%, and 88.4%, respectively.For patients with LACC, prophylactic PALN irradiation up to the level of the renal vessels reduced PALN recurrence and resulted in favorable outcomes with few severe toxicities.

Conflict of interest statement

The authors have no conflicts of interest to disclose

Figures

Figure 1
Figure 1
Kaplan–Meier survival curves for the 76 patients analyzed in this study. (A) Overall survival. (B) Disease-free survival.

References

    1. Gouy S, Morice P, Narducci F, et al. Nodal-staging surgery for locally advanced cervical cancer in the era of PET. Lancet Oncol 2012;13:e212–20.
    1. Gouy S, Morice P, Narducci F, et al. Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer undergoing laparoscopic para-aortic lymphadenectomy before chemoradiotherapy in the era of positron emission tomography imaging. J Clin Oncol 2013;31:3026–33.
    1. Vandeperre A, Van Limbergen E, Leunen K, et al. Para-aortic lymph node metastases in locally advanced cervical cancer: comparison between surgical staging and imaging. Gynecol Oncol 2015;138:299–303.
    1. Berman ML, Keys H, Creasman W, et al. Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study). Gynecol Oncol 1984;19:8–16.
    1. Liu Z, Hu K, Liu A, et al. Patterns of lymph node metastasis in locally advanced cervical cancer. Medicine 2016;95:e4814.
    1. Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol 2004;22:872–80.
    1. Hong JH, Tsai CS, Lai CH, et al. Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone. Int J Radiat Oncol, Biol Phys 2005;63:492–9.
    1. Huang EY, Wang CJ, Chen HC, et al. Multivariate analysis of para-aortic lymph node recurrence after definitive radiotherapy for stage IB–IVA squamous cell carcinoma of uterine cervix. Int J Radiat Oncol Biol Phys 2008;72:834–42.
    1. Liang JA, Chen SW, Chang WC, et al. Risk stratification for failure in patients with advanced cervical cancer after concurrent chemoradiotherapy: another way to optimise treatment results. Clin Oncol (Royal College of Radiologists (Great Britain)) 2008;20:683–90.
    1. Rotman M, Pajak TF, Choi K, et al. Prophylactic extended-field irradiation of para-aortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas. Ten-year treatment results of RTOG 79-20. JAMA 1995;274:387–93.
    1. Haie C, Pejovic MH, Gerbaulet A, et al. Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group. Radiother Oncol 1988;11:101–12.
    1. Malfetano JH, Keys H, Cunningham MJ, et al. Extended field radiation and cisplatin for stage IIB and IIIB cervical carcinoma. Gynecol Oncol 1997;67:203–7.
    1. Grigsby PW, Heydon K, Mutch DG, et al. Long-term follow-up of RTOG 92-10: cervical cancer with positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys 2001;51:982–7.
    1. Sood BM, Gorla GR, Garg M, et al. Extended-field radiotherapy and high-dose-rate brachytherapy in carcinoma of the uterine cervix: clinical experience with and without concomitant chemotherapy. Cancer 2003;97:1781–8.
    1. Chung YL, Jian JJ, Cheng SH, et al. Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study. Gynecol Oncol 2005;97:126–35.
    1. Uno T, Mitsuhashi A, Isobe K, et al. Concurrent daily cisplatin and extended-field radiation therapy for carcinoma of the cervix. Int J Gynecol Cancer 2008;18:80–4.
    1. Ring KL, Young JL, Dunlap NE, et al. Extended-field radiation therapy with whole pelvis radiotherapy and cisplatin chemosensitization in the treatment of IB2-IIIB cervical carcinoma: a retrospective review. Am J Obstet Gynecol 2009;201:109.e101–6.
    1. Beadle BM, Jhingran A, Yom SS, et al. Patterns of regional recurrence after definitive radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2010;76:1396–403.
    1. Kuku S, Fragkos C, McCormack M, et al. Radiation-induced bowel injury: the impact of radiotherapy on survivorship after treatment for gynaecological cancers. Brit J Cancer 2013;109:1504–12.
    1. Jensen LG, Hasselle MD, Rose BS, et al. Outcomes for patients with cervical cancer treated with extended-field intensity-modulated radiation therapy and concurrent cisplatin. Int J Gynecol Cancer 2013;23:119–25.
    1. Liang JA, Chen SW, Hung YC, et al. Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2–IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes. Int J Gynecol Cancer 2014;24:901–7.
    1. Choi J, Yoon HI, Lee J, et al. Optimal extent of prophylactic irradiation of paraaortic lymph nodes in patients with uterine cervical ancer. PloS One 2015;10:e0145158.
    1. Kidd EA, Siegel BA, Dehdashti F, et al. Lymph node staging by positron emission tomography in cervical cancer: relationship to prognosis. J Clin Oncol 2010;28:2108–13.
    1. Grigsby PW, Siegel BA, Dehdashti F. Lymph node staging by positron emission tomography in patients with carcinoma of the cervix. J Clin Oncol 2001;19:3745–9.
    1. Tsai CS, Chang TC, Lai CH, et al. Preliminary report of using FDG-PET to detect extrapelvic lesions in cervical cancer patients with enlarged pelvic lymph nodes on MRI/CT. Int J Radiat Oncol Biol Phys 2004;58:1506–12.
    1. Sakurai H, Suzuki Y, Nonaka T, et al. FDG-PET in the detection of recurrence of uterine cervical carcinoma following radiation therapy—tumor volume and FDG uptake value. Gynecol Oncol 2006;100:601–7.
    1. Tsai CS, Lai CH, Chang TC, et al. A prospective randomized trial to study the impact of pretreatment FDG-PET for cervical cancer patients with MRI-detected positive pelvic but negative para-aortic lymphadenopathy. Int J Radiat Oncol Biol Phys 2010;76:477–84.
    1. Lin SY, Tsai CS, Chang YC, et al. The role of pretreatment FDG-PET in treating cervical cancer patients with enlarged pelvic lymph node(s) shown on MRI: a phase 3 randomized trial with long-term follow-up. Int J Radiat Oncol Biol Phys 2015;92:577–85.

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