AccScience Publishing / ARNM / Volume 1 / Issue 1 / DOI: 10.36922/arnm.0408
Cite this article
38
Download
828
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Concurrent intensity-modulated radiation therapy and chemotherapy plus nimotuzumab for locally advanced cervical squamous cell cancer: A long-term follow-up result

Ang Qu1 Ping Jiang1 Panfeng Wang1 Muyi Zhang1 Xiuwen Deng1 Weijuan Jiang1 Xu Li1 Haitao Sun1 Weishu Hua1 Junjie Wang1*
Show Less
1 Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, P.R. China
Submitted: 8 April 2023 | Accepted: 19 June 2023 | Published: 5 July 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The study aimed to evaluate the safety and efficacy of concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy plus nimotuzumab for the treatment of locally advanced cervical squamous cell cancer (LACSCC). From December 2013 to March 2017, 34 patients with stages IB2–IVA (FIGO 2009) cervical squamous cell cancer were enrolled and received concurrent chemoradiotherapy plus nimotuzumab. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30–36 Gy to Point A was delivered with high-dose-rate brachytherapy. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously weekly. The main and secondary outcome measures were toxicity evaluated using common terminology criteria for adverse events 4.03. and the outcome evaluated using response evaluation criteria in solid tumors 1.1, respectively. The median follow-up duration was 66 months (13 – 98 months). All patients received 6 times of IMRT, brachytherapy, and nimotuzumab. Among them, 24 received six cycles of chemotherapy, while 11 received 4–5 cycles. No life-threatening toxicity was found. The incidence of acute Grade 3 bone marrow depression was 52.9% (18/34), and Grade 3 gastrointestinal tract reaction was 8.8% (3/34). The incidence of late toxicities was 58.8% (20/34), including vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, vaginal stenosis, and paresthesia. About 90% of those were Grades 1–2. Complete response was achieved in 33 cases (97.1%). The 3-year disease-free survival, local progression-free survival (LPFS), and overall survival rates were 79.4%, 91.2%, and 82.4%, respectively. The corresponding 5-year values were 79.4%, 91.2%, and 79.3%. In conclusion, concurrent IMRT and chemotherapy plus nimotuzumab may represent a well-tolerated and effective treatment regimen in patients with LACSCC.

Keywords
Intensity-modulated radiation therapy
Locally advanced cervical squamous cell cancer
Nimotuzumab
Funding
National Clinical Key Specialty Construction Program, P. R. China (2021)
References
  1. Siegel RL, Miller KD, Jemal A, 2018, Cancer statistics, 2018. CA Cancer J Clin, 68: 7–30. https://doi.org/10.3322/caac.21442

 

  1. Jemal A, Bray F, Center MM, et al., 2011, Global cancer statistics. CA Cancer J Clin, 61: 69–90. https://doi.org/10.3322/caac.20107

 

  1. Gaffney DK, Erickson-Wittmann BA, Jhingran A, et al., 2011, ACR appropriateness criteria® on advanced cervical cancer expert panel on radiation oncology-gynecology. Int J Radiat Oncol Biol Phys, 81: 609–614.

 

  1. Whitney CW, Sause W, Bundy BN, et al., 1999, 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, 17: 1339–1348. https://doi.org/10.1200/JCO.1999.17.5.1339

 

  1. Rose PG, Bundy BN, Watkins EB, et al., 1999, Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med, 340: 1144–1153. https://doi.org/10.1056/NEJM199904153401502

 

  1. Morris M, Eifel PJ, Lu J, et al., 1999, Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med, 340: 1137–1143. https://doi.org/10.1056/NEJM199904153401501

 

  1. Keys HM, Bundy BN, Stehman FB, et al., 1999, Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med, 340: 1154–1161. https://doi.org/10.1056/NEJM199904153401503

 

  1. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al., 2000, 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, 18: 1606–1613. https://doi.org/10.1200/JCO.2000.18.8.1606

 

  1. Huang XD, Yi JL, Gao L, et al., 2007, Multi-center phase Ⅱ clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Zhonghua Zhong Liu Za Zhi, 29: 197–201.

 

  1. Tsuchida Y, Therasse P, 2001, Response evaluation criteria in solid tumors (RECIST): New guidelines. Med Pediatr Oncol, 37: 1–3. https://doi.org/10.1002/mpo.1154

 

 

  1. Legge F, Chiantera V, Macchia G, et al., 2015, Clinical outcome of recurrent locally advanced cervical cancer (LACC) submitted to primary multimodality therapies. Gynecol Oncol, 138: 83–88. https://doi.org/10.1016/j.ygyno.2015.04.035

 

  1. Sturdza A, Ptter R, Fokdal LU, et al., 2016, Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Radiother Oncol, 120: 428–433. https://doi.org/10.1016/j.radonc.2016.03.011

 

  1. Peiretti M, Zapardiel I, Zanagnolo V, et al., 2012, Management of recurrent cervical cancer: A review of the literature. Surg Oncol, 21: e59–e66. https://doi.org/10.1016/j.suronc.2011.12.008

 

  1. Tewari KS, Sill MW, Penson RT, et al., 2017, Bevacizumab for advanced cervical cancer: Final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet, 390: 1654–1663. https://doi.org/10.1016/S0140-6736(17)31607-0

 

  1. Kim GE, Kim YB, Cho NH, et al., 2004, Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: A potential predictor of poor survival. Clin Cancer Res, 10: 1366–1374. https://doi.org/10.1158/1078-0432.ccr-0497-03

 

  1. Oh MJ, Choi JH, Kim IH, et al., 2000, Detection of epidermal growth factor receptor in the serum of patients with cervical carcinoma. Clin Cancer Res, 6: 4760–4763.

 

  1. Mathur SP, Mathur RS, Young RC, 2000, Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. Am J Reprod Immunol, 44: 222–230. https://doi.org/10.1111/j.8755-8920.2000.440406.x

 

  1. Kersemaekers AM, Fleuren GJ, Kenter GG, et al., 1999, Oncogene alterations in carcinomas of the uterine cervix: Overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clin Cancer Res, 5: 577–586.

 

  1. Noordhuis MG, Eijsink JJH, Ten Hoor KA, et al., 2009, Expression of epidermal growth factor receptor (EGFR) and activated EGFR predict poor response to (chemo) radiation and survival in cervical cancer. Clin Cancer Res, 15: 7389–7397. https://doi.org/10.1158/1078-0432.CCR-09-1149

 

  1. Zhu Y, Luo J, Liu L, et al., 2012, Preoperative chemoradiation with nimotuzumab and capecitabine in patients with locally advanced rectal cancer: A phase II study. J Clin Oncol, 17: 634–641. https://doi.org/10.1200/jco.2012.30.15_suppl.e14049

 

  1. Liang J, Mingyan E, Wu G, et al., 2013, Nimotuzumab combined with radiotherapy for esophageal cancer: Preliminary study of a Phase II clinical trial. Onco Targets Ther, 6: 1589–1596. https://doi.org/10.2147/OTT.S50945

 

  1. Zhai RP, Ying HM, Kong FF, et al., 2015, Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Onco Targets Ther, 8: 3383–3390. https://doi.org/10.2147/OTT.S93238

 

  1. You B, Brade A, Magalhaes JM, et al., 2011, A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies. Invest New Drugs, 29: 996–1003. https://doi.org/10.1007/s10637-010-9444-0

 

  1. Crombet T, Osorio M, Cruz T, et al., 2004, Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol, 22: 1646–1654. https://doi.org/10.1200/JCO.2004.03.089

 

  1. Hasselle MD, Rose BS, Kochanski JD, et al., 2011, Clinical outcomes of intensity-modulated pelvic radiation therapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys, 80: 1436–1445. https://doi.org/10.1016/j.ijrobp.2010.04.041

 

  1. Yu C, Zhu W, Ji Y, et al., 2015, A comparative study of intensity-modulated radiotherapy and standard radiation field with concurrent chemotherapy for local advanced cervical cancer. Eur J Gynaecol Oncol, 36: 278–282.

 

  1. Gandhi AK, Sharma DN, Rath GK, et al., 2013, Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: A prospective randomized study. Int J Radiat Oncol Biol Phys, 87: 542–548. https://doi.org/10.1016/j.ijrobp.2013.06.2059

 

  1. Erpolat OP, Alco G, Caglar HB, et al., 2014, Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: A national multi-center study. Eur J Gynaecol Oncol, 35: 62–66. https://doi.org/10.12892/ejgo23912014

 

 

  1. Poorvu PD, Sadow CA, Townamchai K, et al., 2013, Duodenal and other gastrointestinal toxicity in cervical and endometrial cancer treated with extended-field intensity modulated radiation therapy to paraaortic lymph nodes. Int J Radiat Oncol Biol Phys, 85: 1262–1268. https://doi.org/10.1016/j.ijrobp.2012.10.004

 

  1. Lee J, Lin JB, Chang CL, et al., 2017, Prophylactic lower para-aortic irradiation using intensity-modulated radiotherapy mitigates the risk of para-aortic recurrence in locally advanced cervical cancer: A 10-year institutional experience. Gynecol Oncol, 146: 20–26. https://doi.org/10.1016/j.ygyno.2017.04.016

 

  1. Choi S, Hsu ICJ, 2018, Cervial cancer. In: Hansen EK, Roach M, (eds). Handbook of Evidence-Based Radiation Oncology. 3rded. New York: Springer International Publishing, p623– 644.

 

  1. Wang W, Zhang F, Hu K, et al., 2018, Image-guided, intensity-modulated radiation therapy in definitive radiotherapy for 1433 patients with cervical cancer. Gynecol Oncol, 151: 444–448. https://doi.org/10.1016/j.ygyno.2018.09.024

 

  1. Pötter R, Georg P, Dimopoulos JCA, et al., 2011, Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol, 100: 116–123. https://doi.org/10.1016/j.radonc.2011.07.012

 

  1. Yoon HI, Cha J, Keum KC, et al., 2015, Treatment outcomes of extended-field radiation therapy and the effect of concurrent chemotherapy on uterine cervical cancer with para-aortic lymph node metastasis. Radiat Oncol, 10: 18. https://doi.org/10.1186/s13014-014-0320-5

 

  1. Ng BH, Rozita A, Adlinda A, et al., 2015, Extended field radiotherapy with or without chemotherapy in patients with cervical cancer and positive para-aortic lymph nodes: A single institution retrospective review. Asian Pac J Cancer Prev, 16: 3827–3833. https://doi.org/10.7314/apjcp.2015.16.9.3827
Conflict of interest
No potential conflicts of interest relevant to this article were reported.
Share
Back to top
Advances in Radiotherapy & Nuclear Medicine, Electronic ISSN: 2972-4392 Published by AccScience Publishing