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Co60 May be the Acceptable Alternative Radionuclides used in HDR Brachytherapy for the Treatment of Inoperable Carcinoma Cervix in the Treatment Modality of Concurrent Chemoradiation
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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  • Research Article   
  • J Cancer Sci Ther/Vol.11.13 309(2019), Vol 12(1)

Co60 May be the Acceptable Alternative Radionuclides used in HDR Brachytherapy for the Treatment of Inoperable Carcinoma Cervix in the Treatment Modality of Concurrent Chemoradiation

Bhuiyan MZR1*, Talukder TH2, Rahman A3 and Sharmin S1
1Department of Oncology, Bangabandhu Sheikh Mujib Medical University, Bangladesh
2Department of Radiation Oncology, National Institute of Cancer Research & Hospital (NICRH), Bangladesh
3Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, Bangladesh
*Corresponding Author: Bhuiyan MZR, Department of Oncology, Bangabandhu Sheikh Mujib Medical University, Bangladesh, Tel: +01815812627, Email: [email protected]

Received Date: Nov 09, 2019 / Accepted Date: Dec 17, 2019 / Published Date: Dec 24, 2019

Abstract

Background: Cancer of the uterine cervix is the eight most common cancer among women worldwide and third among all malignancies and the second most common cancers in female in Bangladesh. The treatment of cervical cancer requires multidisciplinary approaches Concurrent chemoradiation is the treatment of choice in locally advanced carcinoma cervix uteri. Radiotherapy is the primary local treatment for most patients having FIGO stage IIB to IVA diseases. The success of treatment depends on a careful balance between EBRT and Brachythcrapy that optimizes the dose to tumor. Iridium-192 is highly used radionuclide for modern remote after loading HDR brachytherapy till date. Recently Cobalt-60 source is available with miniature size and identical physical properties for remote afterloaders.

Methods: Ninety-eight patients with biopsy proven locally advanced carcinoma of the uterine cervix were enrolled in the study. Arm A was formed comprising 49 patients who were treated by Ir192 HDR brachytherapy and Arm B formed with equal number of 49 patients who received HDR brachytherapy treatment with Co60 radionuclide. This prospective observational study was carried out to compare the treatment effect between two Arm.

Results: 98 patients were enrolled in the study with an age ranges from 35 to 63 years. Most of the patients presented with stage IIB disease, consisting of 64 patients (65.3%). Among them 79 patients had squamous cell carcinoma (80.60%), adenocarcinoma trailing with 15 patients (15.3%) and rest were adenoid-squamous carcinoma 3 and small cell carcinoma 1. In all three insertions, urinary bladder dose distribution was slightly smaller by HDR Co60 irradiation than HDR Ir192 exposure. These differences were statistically significant in first two insertions but not in third one

Conclusion: In this study radiation dose distribution at OARs i.e. urinary bladder and rectum were compared between Arm A and Arm B. In all three insertions in urinary bladder the mean dose distribution was slightly smaller in HDR Cobalt-60 irradiation than HDR Iridium-192 exposure. These differences were statistically significant in first two insertions but not in third one. In case of rectum point, the mean dose distribution were significantly lower in all three insertions of Co60 exposure than Ir192 exposure. So that considering the long half life and low cost, Co60 can be a acceptable alternative radionuclide’s used in HDR brachytherapy.

Keywords: High dose rate brachytherapy; External beam radiotherapy; Intracavitary radiotherapy; Co60 and Ir192 radionuclides

Introduction

Cervical cancer is the fourth most common cancer in women, and the seventh overall, with an estimated incidence of 528,000 new cases and 266,000 death from the disease worldwide in 2012 [1]. Cervical cancer also contributed nearly 8% of all cancers among women and around 4% in all population. However, global cervical cancer incidence increased from 378,000 cases per year in 1980 to 454,000 cases per year in 2010, a 6% annual late of increase [2]. Cervical cancer represents approximately 1.6% c all cancer deaths in women and 13% of deaths from gynecologic cancers. However, for women aged 20 to 39 years, cervical cancer remained the second leading cause of cancer deaths after breast cancer [3].

Cervical cancer is highly prevalent in developing nations. There exist wide geographic variations. Cervical cancer is more common in Latin America and less frequent in Jewish and European women and Fiji Islanders [4]. International incidences of cervical cancer tend to reflect differences in cultural attitudes toward sexual promiscuity and differences in the penetration of mass screening programs. Countries that have well-advanced screening programs (e.g., the United States and the countries of western Europe) or strict religious regulation of sexual behavior (e.g., Muslim countries of the Middle East or Asia) tend to have low rates of invasive disease [5]. The highest: incidences tend to occur in populations that have low screening rates combined with a high background prevalence of human papillomavirus (HPV) infection and relatively liberal attitudes toward sexual behavior [6].

Although there is no national cancer registry in Bangladesh, the hospital based cancer registry of National Institute of Cancer Research and Hospital for the period of 20082010 showed that 43.95% of all registered cases were female. The male female ratio was 1.28:1. The report also revealed that cervical cancer ranks the third among all malignancies during this period an.: the second most common cancers in female (Cancer Registry Report; NICRH, 2013).

The treatment of cervical carcinoma requires multimodality approaches and depends largely on the stage of disease. Radiotherapy plays a major role in the management of locally advanced cervical cancer. Currently, the two main modalities of irradiation are external photon beam and brachytherapy. Both EBRT and ICRT are used, often in combination with chemotherapy. External irradiation is used to treat the whole pelvis and the parametrium including the common iliac and para- aortic lymph nodes, whereas cervix and parametrium is primarily irradiated with intracavitary sources. The techniques described applied, with some individualization, to most patients with cervical carcinoma.

Radiotherapy is always a tradeoff between the dose that can be delivered to malignant tissue and the dose that can be tolerated by healthy tissue. To achieve local control, and subsequently patient cure, very high doses have to be delivered to patients with locally advanced cervical cancer. Traditionally this treatment has been rather toxic and it has been reported that up to 20 - 25 % of the patients experience adverse side effects [7]. To optimize the treatment of locally advanced cervical cancer it is important to establish a firm knowledge about dose response relationship in cervical tumours as well as in OARs those are in close vicinity of the uterus. The urinary bladder and the rectum stand for most important OARs in radiation therapy of carcinoma cervix due to their anatomical position.

Brachytherapy is delivered by placing applicators in the cervix and in the top of the vagina and placing the radioactive sources inside the applicators for certain times. In this way the dose is confined locally to the tumour. The dose distribution around the sources is very in homogeneous and the dose is rapidly decreasing as the distance from the sources increases, according to ‘Inverse Square Law’. To calculate the absorbed dose to the tumour and normal tissue, it is important to know the sources location in relation to adjacent tissue. This localization process is guided by medical imaging. Consequently, for a correct dose calculation the images should be acquired with the applicator in situ.

For ICRT it is usual to prescribe treatment a dose point (the Manchester point A, in Manchester System, the dose is specific at point A) or isodose (reference isodose surface). In 1985 the ICRU published report 38 making recommendations on dose and volume specifications in intracavitary brachytherapy. Two points were defined for reporting the dose respectively the rectum and the urinary bladder.

Traditionally, High Dose Rate afterloaders have been based on Ir192 radionuclide. The high specific activity of iridium allowed very small sources to be used interstitially despite its short half-life period. Typically Ir192 source exchange is required each 4-6 months to keep the treatment times within the limits required by clinical practice. A few years ago, new HDR aftcrloaders have been introduced using Co60 instead of Ir192; which are provided with sources having the same size as the Ir192 ones and have been already implemented in some institutes which shows a clear tendency to increase their number. In fact these sources have been considered in the recent AAPM-ESTRO Report [8] with recommendations about dosimetry methodology and consensus datasets have been presented for the two commercially existing sources. The Co60 introducers claim important economic advantages because of the larger half-life period and the improved technology. At present there is no clear position on advantages or disadvantages of both HDR modalities, to be taken into account in future HDR facility implementation.

In this thesis acquired data from study subjects, dosimetrical as well as clinical data ware used to elucidate the comparison between dose distribution of two HDR brachytherapy radionuclides in the tumour and organs at risk during ICRT for cervical cancer.

Research Methodology

The study was designed as prospective observational study. The study was done during the period of July 2017 to June 2018. Target population was patients with histopathologically proven cervical cancer having FIGO stage I1B - IVA disease, at these above mentioned hospitals during the period of July 2016 to June 2017. They were convinced to participate in the study after giving written informed consent and satisfying inclusion and exclusion criteria and enrolled in the study.

Study population and sample were patients with locally advanced cervical cancer & received EBRT with concurrent chemotherapy. The objective this study was to compare the radiation dose distribution among tissue including reference point “A”, urinary bladder point and rectum point.

All patients were received EBRT 50 Gy in 25 fractions at 2 Gy per fraction with concurrent chemotherapy with low dose weekly Cisplatin 40 mg/m2 weekly. Followed by 3 insertions of intracavitary HDR brachytherapy at a dose of 7 Gy per insertion weekly. This hospital based comparative study in used histologically diagnosed 98 patients of cervical carcinoma. All the patients received external beam radiotherapy at a total dose of 50 Gy in 25 fractions, at a rate of 200 Gy per fraction, each fraction per day; five fractions per week. The EBRT treatment period was 5 weeks. All the patients also received concurrent chemotherapy with inj. Cisplatin 40 mg/m2 weekly. The 98 patients who enrolled in this study were divided in two arms. 49 patients for Arm - A and 49 patients for Arm - B. Arm -A were treated with Ir192 HDR Brachytherapy and Arm - B treated with Co60 HDR Brachytherapy.

Results

In this chapter the results of the data analysis of the study are presented. The data were collected and then processed in response to the study question. This study set out to investigate Comparison of dose distribution in organs at risk and reference point “A" in treatment of Carcinoma cervix using Co60 and Ir192 HDR Brachytherapy. The principle goal is to investigate the clinical feasibility of the two aforesaid radionuclides in treatment of advanced stage carcinoma cervix by HDR brachytherapy. The objectives were accomplished. The findings presented in this chapter demonstrate the potential for merging theory and practice.

This hospital based comparative study have done on the basis of histopathologically diagnosed 98 patients of cervical carcinoma. All the patients received external beam radiotherapy at a total dose of 50 Gy in 25 fractions, at a rate of 200 Gy per fraction, each fraction per day; five fractions per week. The EBRT treatment period was 5 weeks. All the patients also received concurrent chemotherapy with inj. Cisplatin 40 mg/m2 weekly. The 98 patients who enrolled in this study were divided in two arms. 49 patients for Arm- A and 49 patients for Arm - B. Arm - A were treated with Ir192 HDR Brachytherapy and Arm - B treated with Co60 HDR Brachytherapy. All patient in both arm completed treatment. No drop out was noticed during treatment (Tables 1-6).

Stage Frequency Percentage
IIB 64 65.30
IIIA 17 17.35
IIIB 15 15.31
IVA 02 2.04
Total 98 100.0

Table 1: Distribution of the patient by stage of the disease.

Stage Group
Ir192  (Percentage) C60  (Percentage)
IIB 33 (67.35) 32 (65.3)
>IIIA 16 (32.65) 17 (34.7)
Total 49 (100.0) 49 (100.0)

Table 2: Distribution of the patients by types of irradiation and stage of the disease.

Morphological types Frequency Percentage
Squamous cell carcinoma 79 80.6
Adenocarcinoma 15 15.30
Adeno-squamous cell carcinoma 3 3.1
Small cell carcinoma 1 1.02
Total 98 100.0

Table 3: Distribution of the patient by histopathological types of cancer.

Point of irradiation Group Mean Std. deviation  (±) t-test p-value
Bladder point 1st insertion Ir192 5.0952 1.91421 2.394 0.019
Co60 4.2704 1.42599
Bladder point 2nd   insertion Ir192 4.8400 1.30849 2.510 0.014
Co60 4.572 1.35571
Bladder point 3rd insertion Ir192 4.5037 1.63573 1.090 0.279
Co60 4.8034 1.24406

Table 4: Dose distribution at urinary bladder point of the patients.

Point of irradiation Group Mean Std. deviation  (±) t-test p-value
Rectum point 1st insertion Ir192 4.3210 1.30049 5.985 <0.001
Co60 3.0014 .80139
Rectum point 2nd insertion Ir192 4.5970 1.25732 7.053 <0.001
Co60 2.9763 .97664
Rectum point 3rd insertion Ir192 4.2416 1.27164 5.007 <0.001
Co60 3.1150 0.90191

Table 5: Dose distribution at rectum point of the patients.

Toxicities Group t-test p-value
Ir192 C60    
Nausea Yes  12 14 0.209 0.647
No 37 35
Anaemia  Mild 8 10 0.43 0.807
Moderate 29 26
Severe 12 13
S. creatinine  Normal 41 44 0.798 0.372
Raised 8 5
Rectal irritation  Yes 14  1.47 0.225
No 35 41

Table 6: Distribution of the toxicities by group of irradiation.

Discussion

Patients with locally advanced cervical cancer in stage IIB to IVA are treated with irradiation including external beam and brachytherapy combined with concurrent chemotherapy. Traditionally LDR brachytherapy was used to treat cervical cancer. But the advent remote after loader HDR brachytherapy ensures some realistic benefit over LDR. From the early ages of HDR, Iridium-192 was very much popular as radionuclide. Recently Cobalt-60 radionuclide has been introduced with equivalant structural and physical properties.

The objective this study was to compare the radiation dose distribution among the site of tissue including reference point “A”, urinary bladder point and rectum point. 98 patients were enrolled in the study with an age ranges from 35 to 63 years. Arm A was formed comprising 49 patients who were treated by Ir192 HDR brachytherapy and Arm B formed with equal number of 49 patients who received HDR brachytherapy treatment with Co60 radionuclirde.

The patients of different stages were enrolled in this study. Most of the patients presented with stage IIB disease, consisting of 64 patients (65.3%). The next leading stage was IIIA with 17(17.35%) and 15(15.31%) patients were suffering from stage IIIB disease and stage IV was 2 patients (2.04%).

The study subjects were included as histopathologically diagnosed carcinoma cervix. Different histopathological types were found. Among them 79 patients had squamous cell carcinoma (80.60%), adenocarcinoma trailing with 15 patients (15.3%) and rest were adenoid- squamous carcinoma 3 and small cell carcinoma 1.

In this study radiation dose distribution in tissues by HDR brachytherapy using Ir192 & Co60 radionuclides were compared among carcinoma cervix patient. All the patients were biopsy proven, locally advanced between stages of IIB - IVA. The brachytherapy was completed with the insertion of central uterine Tandem and two vaginal ovoids. The treatment planning being done with optimizing dose to reference point “A” to a dose of 7 Gy per insertion. Each patient received 3 insertions of intracavitary brachytherapy, to total dose 21 Gy contributing to reference point “A”. After computerized planning, 100% dose distribution was confirmed to point “A”. Thus all the patients received 7 Gy at point ‘A’ in both arm of the study subjects.

In this study radiation dose distribution at OARs in consideration i.e. urinary bladder and rectum were compared between Arm A and Arm B. Independent sample t test were done to find whether any significant difference is exist or not. In all three insertions, urinary bladder dose distribution was slightly smaller by HDR Co60 irradiation than HDR Ir192 exposure. These differences were statistically significant in first two insertions but not in third one. The analysis of data reveals that radiation dose distribution in case of rectum points, the mean dose distribution were significantly lower in all three insertions of Co60 exposure than Ir192 exposure (p<0.001). Richter compared a Co60 and Irl92 source of identical dimension and construction and discussed [9] tissue absorption, geometry function and integral dose of the two sources and revealed that the dose for Co60 sources in fat tissue is 0.4 percent higher and 0.8 percent lower for the rectum than for Ir192 sources. Islam [10] has also showed no significant advantages or disadvantages found in dosimetric aspect comparing with two sources.

The study was set out to explore the comparison of dose distribution of two radionuclides used in remote after loading HDR brachytherapy, Ir192 and Co60 respectively, at reference point `A` and OARs in the treatment of locally advanced carcinoma cervix. EBRT followed by HDR-ICRT is considered as standard radiation treatment strategy for patients with locally advanced carcinoma cervix. Especially in developing country like Bangladesh; where high number of patients with cervical cancer requires the brachytherapy service, low cost sustainable technology is utmost need.

In this study, ICRT treatment planning dose was prescribed and normalized at reference point ‘A’. So both radionuclides contributed the same dose as prescribed and achieved 100% coverage. Therefore both the radionuclides are identical at this point. Hence difference would be at OARs. Normal tissues like rectum and urinary bladder remain as organs at risk for HDR brachytherany treatment of locally advanced carcinoma cervix due to their close vicinity.

Conclusion

This observational study concerned with radiation dose distribution to OARs. The current study has revealed the dose distributions are significantly less at ICRU rectal point in patients treated by Co60 HDR brachytherapy than those treated by Ir192 HDR brachytherapy. The study also revealed that in case of Co60 source to some extent the ICRU urinary bladder point dose was lower for first two insertions not for the third than that of Ir192 source. Taking into the account of long half life of Co60 and subsequent economic considerations (low cost), distribution by the two radionuclides are comparable and Co60 can be the acceptable alternative radionuclide used in HDR brachytherapy.

References

Citation: Bhuiyan MZR, Talukder TH, Rahman A, Sharmin S (2019) Co60 May be the Acceptable Alternative Radionuclides used in HDR Brachytherapy for the Treatment of Inoperable Carcinoma Cervix in the Treatment Modality of Concurrent Chemoradiation. J Cancer Sci Ther 11: 309-312.

Copyright: © 2019 Bhuiyan MZR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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