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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 7  |  Page : 176-180

Iodine-125 radioactive seed tissue implantation as a remedy treatment for recurrent cervical cancer


Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China

Date of Web Publication21-Feb-2017

Correspondence Address:
Junye Wang
Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.200611

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 > Abstract 

Purpose: This study was designed to discuss feasibility, short-term efficacy, and complications of iodine-125 radioactive seed tissue implantation for remedying recurrent cervical cancer.
Materials and Methods: From June 2009 to December 2010, 17 patients with recurrent cervical cancer received radioactive seed implantation under computed tomography (CT) guidance. Matched peripheral dose was 145 Gy, while the number of implanted seeds was from 6 to 68 with a median of 20. Efficacy was determined based on the results of CT and 18 F-fluorodeoxyglucose positron emission tomography/CT.
Results: Postoperative follow-ups were from 4 to 18 months with a median follow-up time of 9.5 months. Nine patients died during follow-up while remaining patients survived during the follow-up period. Evaluation of efficacy: six patients had a complete response, four patients had a partial response, and seven patients had progressive disease, clinical efficacy rate as 58% (10/17). No patients had complications of radiation injury. Rate of 6 months and 1-year survival period was 74.8% and 18.3%, respectively. Comparing to patients who responded ineffectively to radioactive seed implantation, patients who responded effectively to radioactive seed implantation had a longer survival period (median 7.2 vs. median 10.4), in which the difference was statistically significant (P = 0.038).
Conclusion: Iodine-125 radioactive seed tissue implantation is a feasible, effective, and safe treatment method for remedying or palliative treatment of recurrent cervical cancer. Patients who have recurrent cervical cancer and responded effectively to radioactive seed implantation will have a longer survival period.

Keywords: Cervical cancer, radioactive seeds, tissue implantation


How to cite this article:
Han L, Li C, Wang J, He X, Zhang X, Yang J, Liu G. Iodine-125 radioactive seed tissue implantation as a remedy treatment for recurrent cervical cancer. J Can Res Ther 2016;12, Suppl S3:176-80

How to cite this URL:
Han L, Li C, Wang J, He X, Zhang X, Yang J, Liu G. Iodine-125 radioactive seed tissue implantation as a remedy treatment for recurrent cervical cancer. J Can Res Ther [serial online] 2016 [cited 2021 Mar 6];12:176-80. Available from: https://www.cancerjournal.net/text.asp?2016/12/7/176/200611


 > Introduction Top


Cervical cancer is one of the most common malignant tumors among women and the second leading cause of death among women of developing countries. A considerable number of patients with cervical cancer can be cured after surgery or radiation therapy, but about one-third of patients have relapses,[1] thus the treatment for recurrent cervical cancer is a relatively difficult clinical problem. Most recurrent cervical cancer has no surgical indications, thus the main treatment method is radiotherapy. The area of recurrent cervical cancer where previously received radiation cannot receive another radiation, but chemotherapy can only play a role as palliative care, while the median survival period is ≤10 months. Recurrence of cervical cancer has become an important limitation factor for cervical cancer survival rate, thus exploring new treatments for recurrent cervical cancer is particularly important. Iodine-125 radioactive seed implanted to lesion was a new treatment strategy of brachytherapy for recurrent cancer.[2],[3] During remedy treatment for recurrent cervical cancer, the treatment had achieved relatively good efficacy, and results were reported as below.


 > Materials and Methods Top


Materials

Clinical data

Case selection: From June 2009 to December 2010, 17 patients with recurrent cervical cancer received computed tomography (CT)-guided iodine-125 radioactive seed implantation. Patients' age ranged from 28 to 72 years with a median age of 48 years, and Karnofsky performance status score was >80. Sixteen patients underwent surgical treatment before relapse, whereas all patients underwent radiotherapy before relapse. Eleven patients had solitary lesion, whereas six patients had multiple lesions. For pathological type, 15 cases were squamous cell carcinoma, whereas 2 cases were adenocarcinoma. A total of 24 recurrent lesions were detected by whole-body 18 F-fluorodeoxyglucose positron emission tomography/CT (18 F-FDG PET/CT) scan. There were twenty pelvic lesions including one cervical lesion, six vaginal cuff lesions, and thirteen pelvic lymph node lesions, as well as four lesions outside pelvic including two abdominal paraaortic lesions and two pulmonary lesions. After seed implantation, four patients received additional 4–6 courses platinum-based chemotherapy. The specific conditions of patients and cancer were listed in [Table 1]. All patients underwent preoperative routine tests include blood test, clotting function test, liver function test, kidney function test, and electrocardiogram.
Table 1: Seventeen patients with recurrent cervical cancer and conditions of cancer

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Medical device

Philips Brilliance 16-slice spiral CT scanner produced by Philips. Radioactive seed treatment planning system (TPS) was provided by Beijing Yuanbo Biotech Company. Seed implantation equipment were Mick seed gun and 18-gauge seed implantation needle. Implantation protective equipment including lead aprons, lead glasses, lead collar, and lead gloves. The 6711 type iodine-125 radioactive seeds were provided by Beijing Atomic Hi-Tech Co., Ltd., which was sealed in a cylindrical titanium shape package with a length of 4.5 mm, diameter of 0.8 mm, half-life of 59.6 days, average photon energy of 27–35 keV, and activity of 0.8 mCi.

Methods

Develop preoperative radioactive seed implantation plan

Radioactive seed TPS was used to develop implantation plan based on the following steps: (1) tumor was scanned by CT with 5 mm thickness, then the image was transferred to TPS; (2) based on radioactive concentration areas displayed by PET/CT, gross tumor volume (GTV) and organs at risk were outlined in each CT cross-section and re-built in three-dimensions; (3) planning target volume was defined as the areas extended 5–10 mm outside GTV; (4) dosage requirement for tumor area was defined as matched peripheral dose (MPD) which surrounds target area with the MPD as 145 Gy; (5) dose distribution curves and dose-volume histograms were obtained through TPS; (6) the dose for target tumor area, needle entering position, number of seeds, and space distribution were determined [Figure 1].
Figure 1: Preoperative treatment planning system for recurrent cervical cancer lesions (after radiotherapy). Computed tomographic imaging showed the distribution of seeds and ways of inserting needles. The dose-volume histogram curve showed planning target volume (red line) as well as dose distribution in rectum (yellow line) and bladder (blue line)

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Preoperative preparation and intraoperative implantation process

Before radioactive seed implantation, instructions regarding radiation protection and signed consent were given to patients and their families. Bowel preparation was conducted before the treatment of pelvic lesions. Needle path and surgical approach position were determined based on preoperative treatment plan. After CT scan of lesions, needle puncture points, inserting angle, and inserting depth were determined in CT image; and then puncture points were marked on the patients' body surface based on CT laser positioning line. After patients received routine disinfection, draping of puncture points and local anesthesia for puncture points with 1% lidocaine, the 18-gauge seeds puncture needle was inserted based on the planned inserting angle and depth. The space between radioactive seeds implanted was 0.5 cm. Each patient was implanted 9–45 seeds with a median of 20.5. The median total activity of each seed implanted was 16.4 mCi. CT scan was immediately conducted after implantation to verify the dose, and supplementary seeds were implanted into dose cold spots.

Treatment after seed implantation

Two to six courses of chemotherapy after seed implantation were given to 4 patients, whereas the remaining 13 patients did not receive other treatments after seed implantation.


 > Results Top


Clinical efficacy assessment

One month after operation, CT was conducted every 2–3 months, and PET-CT scan was conducted every 6 months. For lesions assessed by CT, efficacy was assessed based on the WHO efficacy evaluation criteria.[4],[5] For lesions assessed by PET-CT, reference efficacy was assessed based on European Organization for Research and Treatment of Cancer criteria.[6] Complete response (CR): all lesions disappeared or lesions' intensity of 18 FDG intake disappeared. Partial response (PR): lesions narrowed or lesions' intensity of 18 FDG intake reduced while other parts had no new lesions. Progressive disease (PD): lesions' intensity of 18 FDG intake increased or lesions became larger. Stable disease: lesions' intensity of 18 FDG intake did not increase, tumor volume did not increase, and new lesions did not appear.

Intraoperative complications

Assessment should consider postoperative complications occurred within 30 days. Assessment of radiation injury to the rectum was based on criteria recommended by Radiation Therapy Oncology Group: Grade I, tenesmus and mucus; Grade II, intermittent rectal bleeding; Grade III, ulcer; and Grade IV, intestinal obstruction, intestinal fistula, and need of blood transfusion.[7]

Follow-up

Follow-up period started after the date of radioactive seeds implanted. Kaplan–Meier analysis statistical method was used for analyzing survival rate. The study endpoint events occurred when patients died due to various causes. Log-rank test was used to compare the efficacy of radioactive seeds implantation and patients' progressive survival period after radioactive seed implantation.

Postoperative follow-up results

Clinical efficacy

Nine patients died during follow-up period while the remaining patients survived during the follow-up period. Among the 17 patients, 6 patients had CR, 4 patients had PR, and 7 patients had PD, thus the clinical efficacy rate was 58% (10/17). Rate of 6 months and 1-year survival period was 74.8% and 18.3%, respectively [Figure 2]. Patients who responded effectively to radioactive seed implantation (CR + PR) had a longer survival period (median 7.0 vs. median 12.0), with statistically significant difference (P = 0.029) [Figure 3]. The efficacy of radioactive seed implantation was shown in [Table 2].
Figure 2: Survival curves of 17 patients with cervical cancer

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Figure 3: Patients responded effectively to radioactive seed implantation had a longer survival period

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Table 2: Treatment and follow - up record of 17 patients

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Complication observation

After operation, two patients had symptoms of sciatic nerve injury. All patients had neither severe rectal complications nor urinary complications.


 > Discussion Top


The cervical cancer is the third most common cancer among women and the second leading cause of cancer death among women, of which 78% cervical cancer occurred in developing country. After standard anticancer treatment, 5-year survival rate of early-stage cervical cancer can be up to 90%; but about 29%–38% of cervical cancer patients had relapses after treatments.[1] Patients with recurrent cervical cancer had a poor prognosis, and the 5-year survival rate was between 3.2% and 13%.[8] Most patients with recurrent cervical cancer had undergone radiotherapy, and a small number of patients could select surgical treatment; the 5-year survival rate of these patients could reach 54%.[9],[10] However, most patients had pelvic wall recurrence or distant metastasis which was difficult to be resected by surgery, with <10% 5-year survival rate and the median survival expectancy was only 8 months.[11] Another treatment method other than conventional radiotherapy and surgery needs to be found so that it can effectively treat patients with recurrent cervical cancer.

Iodine-125 radioactive seed tissue implantation can be used to treat recurrent lesions and unresectable lesions which cannot be controlled by radiotherapy because this treatment has the following advantages: (1) maximize tumor killing and less tissue damage: dose of iodine-125 radioactive seed brachytherapy decreases as distance increases, which follows inverse square law. Dose is highly concentrated in target tumor area while dose decreased relatively rapidly outside the target tumor area so that dose of iodine-125 radioactive seed highly conforms to target area. Longer dose release time gives normal tissue sufficient time to repair itself so that damage to normal tissue is greatly reduced. (2) Obvious radiobiology advantages: for vitro-cultured tumor cells irradiated by radioactive seeds, cell cycle can be blocked in G2/M phase in certain range of dose;[12] cells in this phase are more sensitive to radiation, leading to greater damage of tumor cell. During radioactive seed tumor treatment, low-dose irradiation of iodine-125 leads to inverse dose-rate effect which increases radiosensitivity of irradiated cells and even ameliorates radiation resistance.

Radioactive seed implantation has a 100 years' history for treating cancers, but cervical cancer seed implantation still stops at the brachytherapy step during surgery. The literature was limited to that 20 years ago, Sharma et al.[13] reported 21 cases of recurrent gynecologic cancer (11 cases of cervical cancer, 52%) and Monk et al.[14] reported 20 cases of gynecologic cancer (18 cases of cervical cancer, 90%). Most cervical cancer patients received radiotherapy before recurrence, but radiotherapy-induced fibrosis increased the difficulty for identifying lesions during operation; thus feasibility of seed implantation was poor. Since the 1980s, due to the emergence of CT and three-dimensional TPS, radioactive seed tissue implantation for cancer treatment has become less invasive, with more accurate positioning, less complications, and expanded indications; clinical application of the treatment for treating lung cancer, liver cancer, and intestine cancer had achieved significant efficacy.[15],[16],[17] Based on the previous studies, this study applied modern image-guided method into brachytherapy of recurrent cervical cancer and achieved satisfactory results.

In this study, among the 17 patients, 6 patients had CR, 4 patients had PR, and 7 patients had PD, thus the clinical efficacy rate was 58% (10/17). Rate of 6 months and 1-year survival period was 74.8% and 18.3%, respectively [Figure 1]. Patients who responded effectively to radioactive seed implantation (CR + PR) had a longer survival period (median 7.0 vs. median 12.0), with statistically significant difference (P = 0.029). The result showed that radioactive seed implantation was an effective treatment for recurrent cervical cancer.

At the same time, this study did not have severe complications of radiation enteritis, while Sharma reported four cases of rectovaginal fistula during iodine-125 radioactive seed implantation treating 21 cases of recurrent gynecologic cancer. In Sharma's report of radioactive seed implantation for treating recurrent gynecologic cancer, 11 cases (27%) had postoperative complications such as intraoperative bleeding, intraoperative respiratory distress syndrome, small intestinal obstruction, and intestinal fistula. During CT-guided percutaneous seed implantation, tumor boundary displayed more clearly, iodine-125 radioactive seed distributed evenly inside tumor space, dose distribution was more suitable to the shape of tumor, and dose to sensitive organs was reduced effectively.


 > Conclusion Top


Iodine-125 radioactive seed tissue implantation is a feasible, effective, and safe method for palliative treatment of unresectable recurrent cervical cancer. As a minimally invasive treatment, the CT-guided radioactive seed tissue implantation has advantages such as accurate positioning, easy acceptance by patients, and reducing the development of lesions safely and effectively.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Goncalves A, Fabbro M, Lhommé C, Gladieff L, Extra JM, Floquet A, et al. A phase II trial to evaluate gefitinib as second- or third-line treatment in patients with recurring locoregionally advanced or metastatic cervical cancer. Gynecol Oncol 2008;108:42-6.  Back to cited text no. 1
    
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Martínez-Monge R, Nag S, Martin EW. 125-Iodine brachytherapy for colorectal adenocarcinoma recurrent in the pelvis and paraortics. J Radiat Oncol Biol Phys 1998;42:545-50.  Back to cited text no. 3
    
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Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (Version 1.1). Eur J Cancer 2009;45:228-47.  Back to cited text no. 4
    
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Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: Review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999;35:1773-82.  Back to cited text no. 6
    
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Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). J Radiat Oncol Biol Phys 1995;31:1341-6.  Back to cited text no. 7
    
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Kesic V. Management of cervical cancer. Eur J Surg Oncol 2006;32:832-7.  Back to cited text no. 8
    
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Jaz T, Eifel PJ, Burke T, Oswald MJ. Radiation therapy of pelvic recurrence after radical hysterectomy for cervical carcinoma. Gynecol Oncol 1998;70:241-6.  Back to cited text no. 9
    
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Berek JS, Howe C, Lagasse LD, Hacker NF. Pelvic exenteration for recurrent gynecologic malignancy: Survival and morbidity analysis of the 45-year experience at UCLA. Gynecol Oncol 2005;99:153-9.  Back to cited text no. 10
    
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Höckel M, Sclenger K, Hamm H, Knapstein PG, Hohenfellner R, Rösler HP. Five-year experience with combined operative and radiotherapeutic treatment of recurrent gynecologic tumors infiltrating the pelvic wall. Cancer 1996;77:1918-33.  Back to cited text no. 11
    
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Zhuang HQ, Wang JJ, Liao AY, Wang JD, Zhao Y. The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells. J Exp Clin Cancer Res 2009;28:12.  Back to cited text no. 12
    
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Sharma SK, Forgione H, Isaacs JH. Iodine-125 interstitial implants as salvage therapy for recurrent gynecologic malignancies. Cancer 1991;67:2467-71.  Back to cited text no. 13
    
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Monk BJ, Tewari KS, Puthawala AA, Syed AM, Haugen JA, Burger RA. Treatment of recurrent gynecologic malignancies with iodine-125 permanent interstitial irradiation. J Radiat Oncol Biol Phys 2002;52:806-15.  Back to cited text no. 14
    
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Nag S, DeHaan M, Scruggs G, Mayr N, Martin EW. Long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy. Int J Radiat Oncol Biol Phys 2006;64:736-44.  Back to cited text no. 15
    
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Wang ZM, Lu J, Liu T, Chen KM, Huang G, Liu FJ. CT-guided interstitial brachytherapy of inoperable non-small cell lung cancer. Lung Cancer 2011;74:253-7.  Back to cited text no. 16
    
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Wang JJ, Yuan HS, Li JN, Jiang WJ, Jiang YL, Tian SQ. Interstitial permanent implantation of 125I seeds as salvage therapy for re-recurrent rectal carcinoma. J Colorectal Dis 2009;24:391-9.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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