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CASE REPORT
Ahead of print publication  

Successful treatment results of external radiotherapy without brachytherapy in advanced uterine cervical cancer


1 Department of Internal Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul, South Korea
2 Department of Radiation Oncology, Eulji Hospital, Eulji University School of Medicine, Seoul, South Korea

Date of Submission10-Jan-2020
Date of Decision07-Apr-2020
Date of Acceptance18-Jun-2020
Date of Web Publication07-Nov-2020

Correspondence Address:
Su Jung Shim,
Department of Radiation Oncology, Eulji Hospital, Eulji University School of Medicine, 68 Hangeulbiseok-Ro, Nowon-Gu, Seoul, 01830
South Korea
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_43_20

 > Abstract 


In advanced uterine cervical cancer, external radiotherapy with intracavitary brachytherapy has been established as a curative treatment method. However, in an environment where brachytherapy is difficult to perform, there has been an attempt to use only external radiotherapy. We report the results of eight patients over 65 years of age with advanced uterine cervical cancer who refused brachytherapy and obtained successful results through external radiotherapy alone.

Keywords: Brachytherapy, external radiotherapy, intensity-modulated radiation therapy, uterine cervical cancer



How to cite this URL:
Gong SJ, Shim SJ. Successful treatment results of external radiotherapy without brachytherapy in advanced uterine cervical cancer. J Can Res Ther [Epub ahead of print] [cited 2020 Dec 3]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=300300




 > Introduction Top


Treatment for locally advanced cervical cancer (Stage IIb–IVa) is external beam radiotherapy to the pelvis, followed by intracavitary brachytherapy, which boosts the radiotherapy dose to the cervix, uterus, and parametrium.[1] According to the data of the SEER cohort and a national cancer database from the USA, the survival rate of patients who did not receive brachytherapy was much worse than that of those who received brachytherapy.[2] However, unfortunately, the number of hospitals capable of brachytherapy applications has decreased in Korea.[3] This is because of the poor reimbursement system of brachytherapy and a variety of situations (technical or medical) in which brachytherapy cannot be carried out. External beam irradiation could be an alternative to brachytherapy in cervical cancer patients with contraindications to external irradiation and brachytherapy.[4] Intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) are now used radiotherapy techniques for various cancers and have been shown to be acceptable alternatives to brachytherapy for the treatment of gynecological malignancies when brachytherapy is not available.[5],[6],[7],[8]

In our hospital, there is no brachytherapy unit. Hence, uterine cervical cancer patients were sent to other hospitals after external radiation treatment to perform the brachytherapy boost. However, if the patients refused brachytherapy, we tried to perform external RT and IMRT boost.


 > Case Report Top


Patients and treatment

From January 2014 to December 2017, eight patients undergoing radical radiotherapy without brachytherapy were retrospectively reviewed. They had a median age of 69.5 years (range 67–72 years) and belonged to the International Federation of Gynecology and Obstetrics 2009 Stage IIB–IIIB [Table 1]. Pathologic results showed squamous cell carcinoma in all patients. The medium tumor size was 4.95 cm. During radiotherapy, five patients received concurrent chemoradiation therapy and three underwent RT alone. All of the patients were treated with whole pelvic radiotherapy, with or without chemotherapy, followed by image-guided IMRT. A median total dose of 64 Gy (range, 63–68 Gy) was administered. ERT was delivered to the whole pelvis at a median dose of 45 Gy (range 45–50 Gy)/25 fractions using a four-field box technique. An external beam boost of 1.8–2 Gy/10 fractions to the cervix mass was delivered using IMRT [Figure 1]. Weekly cisplatin (40 mg/m 2) was administered with external radiation therapy for 7 weeks. All patients were examined with magnetic resonance imaging (MRI) at 36 Gy to observe treatment response. When whole-pelvis treatment was performed, X-ray volumetric imaging (XVI) was performed weekly, and when the boost treatment was performed, XVI was performed every day to adjust the treatment position to within 1 mm.
Table 1: Patients and treatment characteristics

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Figure 1: The dose distribution of intensity-modulated radiation therapy for boost for uterine cervical cancer

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Toxicity

All patients tolerated treatment very well; no grade 3 or 4 toxicities for hematologic, genitourinary, or gastrointestinal effects were encountered (Common Terminology Criteria for Adverse Events v3.0). However, acute toxicity of grade 1 diarrhea was seen in one patient, and acute toxicity of grade 1 and grade 2 nausea and anorexia was seen in five patients who received chemotherapy. Two patients received blood transfusion due to anemia during treatment.

Treatment outcome

The median follow-up period was 33 months (range 12–48). The 2-year local control rate was 100%. Three months after treatment completion, MRI showed complete remission (CR) in all patients [Figure 2]. One patient developed para-aortic lymph node (PALN) metastasis 12 months after radiotherapy. She received radiotherapy to the PALN area and is alive without disease. All patients are alive at the last follow-up, except for one who died 1 year after radiotherapy, because of colonic perforation during endoscopy.
Figure 2: T2-weighted sagittal magnetic resonance imaging findings. (a) 5.4-sized uterine cervical mass invasion to the uterus body causing hydrometra, upper vagina with parametrial invasion at diagnosis, (b) near-complete remission at 3600 cGy of radiotherapy, (c) complete remission 3 months after complete treatment

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 > Discussion Top


In uterine cervical cancer, intracavitary brachytherapy is established as a standard treatment and is an ideal method of increasing the dose to the cervix while minimizing the dose to the surrounding organs, the rectum and the bladder. It has been used for the treatment of cervical cancer for many years and has played an important role in the cure of locally advanced cervical cancer.[2] If this treatment was not possible, efforts were made to replace the treatment with ERT. However, there is a limitation to ERT because of high median doses in the pelvic area causing >50% of serious complications.[9]

In cases of ERT alone, radiation more than 70 Gy should be investigated for local control, but chronic complications related to the rectum and bladder rapidly increase when more than 60 Gy is irradiated.[10]

Matsuura et al. treated seven patients with Stage IB–IVA disease who refused brachytherapy with accelerated hyperfractionated RT. A total of 60–73 Gy was administered over 6 weeks. Local control and actuarial overall survival rates for 2 years were exceptional at 86%. Due to bulky residual disease after external beam radiation treatment, as shown in this study, none of the alternative techniques described are excellent.[11]

Recently, advances in RT technology have been remarkable, enabling the use of IMRT treatment planning systems to perform very precise ERT. Further, SBRT with image-guided RT is a precise way of delivering radiation to a defined target volume, enabling the delivery of a lag dose to the tumor and protection to critical structures. The results of replacement of brachytherapy by SBRT with tomotherapy were reported. The results were satisfactory.[12] Studies of the NCC database reported that those who received SBRT boost had equal overall survival when compared with brachytherapy, but those who received IMRT boost had worse overall survival when compared with brachytherapy.[13],[14]

In this study, all patients were over 65 years of age and refused brachytherapy. Many patients have reported a poor treatment result without brachytherapy, but our patients had a successful result with conventional fraction IMRT boost without brachytherapy. The reason seems to be that the residual tumor volume was small because all patients showed near CR at 36 Gy. We hope that further research will be conducted to select patient who can achieve good results with ERT alone without brachytherapy. We anticipate that the response to early RT will play an important role to decide to select patient.

Although a combination of ERT and brachytherapy remains the optimal treatment for cervical cancer, this study demonstrates that an external beam boost is a reasonable option when brachytherapy cannot be performed.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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. Lancet 2001;358:781-6.  Back to cited text no. 1
    
2.
Han K, Milosevic M, Fyles A, Pintilie M, Viswanathan AN. Trends in the utilization of brachytherapy in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013;87:111-9.  Back to cited text no. 2
    
3.
Kim H, Kim JY, Kim J, Park W, Kim YS, Kim HJ, et al. Current status of brachytherapy in Korea: A national survey of radiation oncologists. J Gynecol Oncol 2016;27:e33.  Back to cited text no. 3
    
4.
Barraclough LH, Swindell R, Livsey JE, Hunter RD, Davidson SE. External beam boost for cancer of the cervix uteri when intracavitary therapy cannot be performed. Int J Radiat Oncol Biol Phys 2008;71:772-8.  Back to cited text no. 4
    
5.
Mollà M, Escude L, Nouet P, Popowski Y, Hidalgo A, Rouzaud M, et al. Fractionated stereotactic radiotherapy boost for gynecologic tumors: An alternative to brachytherapy? Int J Radiat Oncol Biol Phys 2005;62:118-24.  Back to cited text no. 5
    
6.
Albuquerque K, Tumati V, Lea J, Ahn C, Richardson D, Miller D, et al. A phase II trial of stereotactic ablative radiation therapy as a boost for locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 2020;106:464-71.  Back to cited text no. 6
    
7.
Mantz CA, Shahin FA, Sandadi S, Orr J. Stereotactic body radiation therapy as a boost alternative to brachytherapy for primary gynecological cancer: Disease control and quality of life outcomes from a phase II trial. Int J Radiat Oncol Bio Phy 2015;93:S202.  Back to cited text no. 7
    
8.
Kubicek GJ, Xue J, Xu Q, Asbell SO, Hughes L, Kramer N, et al. Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer. Biomed Res Int 2013;2013:898953.  Back to cited text no. 8
    
9.
Logsdon MD, Eifel PJ. FIGO IIIB squamous cell carcinoma of the cervix: An analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy. Int J Radiat Oncol Biol Phys 1999;43:763-75.  Back to cited text no. 9
    
10.
Hareyama M, Sakurai T, Nishio M, Suzaki K, Koshiba R, Saito A, et al. Results and complications of cervix carcinoma treated by whole pelvis external irradiation alone (author's transl). Newsl Int Coll Dent India Sect 1980;40:19-23.  Back to cited text no. 10
    
11.
Matsuura K, Tanimoto H, Fujita K, Hashimoto Y, Murakami Y, Kenjo M, et al. Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer. Gynecol Oncol 2007;104:11-4.  Back to cited text no. 11
    
12.
Hsieh CH, Tien HJ, Hsiao SM, Wei MC, Wu WY, Sun HD, et al. Stereotactic body radiation therapy via helical tomotherapy to replace brachytherapy for brachytherapy-unsuitable cervical cancer patients - A preliminary result. Onco Targets Ther 2013;6:59-66.  Back to cited text no. 12
    
13.
OʼDonnell B, Shiao JC, Pezzi TA, Waheed N, Sharma S, Bonnen MD, et al. stereotactic body radiation therapy, intensity-modulated radiation therapy, and brachytherapy boost modalities in invasive cervical cancer: A study of the National Cancer Data Base. Int J Gynecol Cancer 2018;28:563-74.  Back to cited text no. 13
    
14.
Robin TP, Amini A, Schefter TE, Behbakht K, Fisher CM. Disparities in standard of care treatment and associated survival decrement in patients with locally advanced cervical cancer. Gynecol Oncol 2016;143:319-25.  Back to cited text no. 14
    


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