|Year : 2018 | Volume
| Issue : 3 | Page : 114-118
Three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy in carcinoma cervix
Revathi Badiginchala1, Swapna Jilla1, BV Subramanian1, Prana Bandhu Das1, Archana Prathipati1, G Sanjeeva Kumar2
1 Department of Radiotherapy, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Anaesthesia, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
|Date of Web Publication||8-Apr-2019|
Department of Radiotherapy, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Cervical cancer is the most common gynecological cancer among Indian women. 3D-CRT treatment is associated with more acute and late toxicities, because of close proximity of bladder and rectum to the cervix. The newer technique like IMRT is associated with less toxicities. Our study is to compare 3D-CRT and IMRT in terms of dosimetric parameters, toxicities and clinical outcomes.
Methods: From February 2015 to July 2016 total 40 newly diagnosed locally advanced cervical carcinoma patients were treated with concurrent chemo radiotherapy with weekly cisplatin. Those patients were randomized to arm A - 3D-CRT and arm B - IMRT.
Results: The dosimetric parameters of the bladder, rectum, bowel bag, and pelvic bone marrow were significantly decreased in the IMRT arm as compared to 3DCRT arm except for V30, V50 of bowel bag and V50 of pelvic bone marrow. The acute and late toxicities were similar among both arms. All the patients were assessed for treatment response at 6 weeks after completion of the treatment. All achieved complete clinical response. Out of 40 patients only one had brain metastasis after a median follow up of 18 months.
Conclusions: Though IMRT showed dosimetric reduction compared to 3D-CRT but it did not showed any clinical benefit. At present scenario in developing countries like India where the cancer centers are over loaded with the carcinoma cervix cases can be treated with the 3D-CRT technique without compromising clinical outcomes.
Keywords: Carcinoma cervix, intensity-modulated radiotherapy, three-dimensional conformal radiotherapy
|How to cite this article:|
Badiginchala R, Jilla S, Subramanian B V, Das PB, Prathipati A, Kumar G S. Three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy in carcinoma cervix. J Clin Sci Res 2018;7:114-8
|How to cite this URL:|
Badiginchala R, Jilla S, Subramanian B V, Das PB, Prathipati A, Kumar G S. Three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy in carcinoma cervix. J Clin Sci Res [serial online] 2018 [cited 2019 Aug 22];7:114-8. Available from: http://www.jcsr.co.in/text.asp?2018/7/3/114/255670
| Introduction|| |
Cervical cancer is the most common gynaecological cancer among Indian women. In India, most of the cervical cancer patients presented at locally advanced stage, where radiotherapy along with concurrent weekly cisplatin-based chemotherapy is the standard of care.,,,,,,
The technique of three-dimensional conformal radiotherapy (3D-CRT) provides better target coverage and significantly reduces the radiation exposure to bladder; however, this technique did not appreciably reduce the amount of radiation exposure to the intestine or rectum., With the newer technique such as intensity-modulated radiotherapy (IMRT), which uses non-uniform fields to achieve better planning target volume (PTV) while decreasing unnecessary radiation exposure to normal organs at risk (OAR).,,
Meta-analysis based on the results of 13 articles comprised 222 IMRT-treated and 233 3D-CRT-treated patients. In these patients, they compared dose-volume histograms and acute and late toxicity effects of IMRT and 3D-CRT. This study suggested that IMRT significantly reduced the average percentage of irradiated volume of the rectum receiving >30 Gy doses and the small bowel from 45 Gy. Furthermore, in the bladder and bone marrow, the advantages of IMRT over 3D-CRT were not significant for any of the radiation doses examined.
The incidence and severity of acute or late toxicities were also not significant in both the arms. With this background, we conducted a study comparing 3D-CRT versus IMRT in carcinoma cervix to report the results in terms of dosimetric parameters, acute, late toxicities and treatment response rates.
| Material and Methods|| |
This is a prospective randomised study conducted at Sri Venkateswara Institute of Medical Sciences, in Tirupati, in total 40 patients of histopathologically proven carcinoma of cervix from February 2015 to July 2016.
The International Federation of Gynaecology and Obstetrics (FIGO) Stage IB2 to III of carcinoma cervix cases was included and FIGO Stage IA, IB1 and IV were excluded. All patients were evaluated by complete history, gynaecological and systemic examination. Biopsy was done for histopathological conformation. Investigations done were complete haemogram, renal function tests, liver function tests, chest radiograph and contrast-enhanced computed tomography (CECT) abdomen and pelvis.
This study was started after getting approval from the Institutional Ethics Committee, and written informed consent was taken from all the patients before the start of treatment.
Forty newly diagnosed locally advanced cervical carcinoma patients were randomly allocated to arm A-3D-CRT and arm B-IMRT. All patients were treated with concurrent chemoradiotherapy with weekly cisplatin.
Details of radiotherapy
Patients were kept in the supine position with arms over the chest, then, immobilisation was done with thermoplastic mask (Scanoplan, Vadodara, Gujarat) on indexed couch with bladder protocol and then, planning CECT abdomen and pelvis was taken with the same bladder protocol (patient was asked to empty bladder first then drink 500 ml of water and asked to wait for 30 min), this is reproduced daily before treatment.
Target volumes are defined by the International Commission on Radiation Units and Measurements (ICRU 50 and 62)., Target volumes and normal structures were contoured according to the guidelines given by the Radiation Therapy Oncology Group (RTOG) panel atlas.
All the patients received EBRT with a dose of 50 Gy in 25 fractions at the rate of 2 Gy/fraction five fractions per week over 5 weeks. In both the arms, planning was done in such a way that 95% of the prescribed dose should cover more than or equal to 95% of the PTV. All the patients received 21 Gy of high-dose rate intracavitary brachytherapy in three fractions at the rate of 7 Gy per fraction one fraction per week.
Details of chemotherapy
All the patients received weekly cisplatin, with a dose of 40 mg/m2 body surface area per week per a glomerular filtration rate of ->60 ml/min, administered through intravenous route.
Both the arms were compared in terms of volume of bladder receiving 30 Gy, 40 Gy, 45 Gy and 50 Gy (V30, V40, V45 and V50), volume of rectum and bowel bag receiving 30 Gy, 40 Gy and 50 Gy (V30, V40 and V50) and volume of pelvic bone marrow receiving 10 Gy, 20 Gy, 30 Gy, 40 Gy and 50 Gy (V10, V20, V30, V40 and V50).
Acute genitourinary and gastrointestinal toxicities were assessed weekly by clinical examination, and haematologic toxicities were assessed by weekly blood counts (haemoglobin, neutrophils and platelet counts) during the course of the treatment and 6 weeks after completion of treatment and were graded according to the RTOG acute radiation morbidity scoring criteria. The late toxicities were assessed after 6 weeks of completion of treatment till the last follow-up and graded according to the RTOG late radiation morbidity scoring criteria. Treatment response rates (local control rates) were assessed clinically by per vaginal and per speculum examination at each follow-up over a median period of 18 months (range: 16–20 months). Patients were called for the first follow-up 6 weeks after completion of treatment, then once in a month up to 6 months, then once in 2 months up to 1 year.
The dosimetric parameters were compared between both the arms by Student's t-test on IBM SPSS version 20 and P < 0.05 is considered statistically significant.
Chi-square test was used to see the association between toxicity levels in two different techniques.
| Results|| |
The patient characteristics in both the arms were comparable [Table 1]. A total of 43 patients were included into this study. Of 43 patients, 3 patients were excluded and remaining 40 patients were allocated equally into two groups [Figure 1]. The dosimetric parameters of IMRT and 3D-CRT were calculated for different OAR [Table 2].
|Figure 1: Schema of selection, randomisation and allocation of patients into two arms |
Click here to view
|Table 2: Dosimetric parameters of bladder, rectum, bowel Step and pelvic bone marrow in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (n=20)|
Click here to view
The volume of bladder receiving radiation doses of 30 Gy, 40 Gy, 45 Gy and 50 Gy was significantly reduced in IMRT arm compared to 3D-CRT arm. For rectum, the irradiated volumes were significantly reduced in IMRT than in 3D-CRT at radiation doses of 30 Gy, 40 Gy and 50 Gy. IMRT arm showed significant reduction in the volume of bowel bag receiving 40 Gy; however, there is no significant reduction at doses of 30 Gy and 50 Gy compared to 3D-CRT arm. The volume of pelvic bone marrow receiving radiation doses of 10 Gy, 20 Gy, 30 Gy and 40 Gy was significantly reduced in IMRT arm compared to 3D-CRT, but the doses at 50 Gy showed no significant reduction. There was no significant difference in acute and late toxicities of genitourinary, gastrointestinal and haematologic toxicities in both the arms, as shown in [Table 3]. All the patients in both the arms had achieved complete clinical response at 6 weeks after the completion of treatment and over a median follow-up period of 18 months (range: 16–20 months) except one patient in 3D-CRT arm developed brain metastasis.
|Table 3: Acute toxicities in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (n=20)|
Click here to view
| Discussion|| |
Cervical cancer is the most common gynaecological cancer worldwide and in India. About 70% of the global burden falls in developing countries like India. Due to low socio-economic status, poor personal hygiene, illiteracy and lack of screening, most of the Indian women are presenting in locally advanced stage. At our centre, the incidence of cervical cancer is 30%–40% of all cancers annually and most of the cases are presenting in locally advanced stage.
The objectives of the present study were to compare dosimetric parameters, acute and late toxicities and treatment response rates in 3D-CRT and IMRT.
In the present study, bladder volumes receiving doses of 30 Gy, 40 Gy, 45 Gy and 50 Gy (V30, V40, V45 and V50) and rectum volumes receiving doses of 30 Gy, 40 Gy and 50 Gy (V30, V40 and V50) were significantly low in the IMRT arm as compared to 3D-CRT arm. These results were almost in accordance with the findings of published trials.
In our study, the volumes of bowel bag receiving doses of 30 Gy and 50 Gy did not show significant reduction in IMRT compared to 3D-CRT arm but show a statistical significant reduction at doses of 40 Gy. Our results were almost similar to the meta-analysis by Yang et al. which showed that in IMRT arm doses at 40 Gy and 45 Gy significantly low as compared to 3D-CRT. However, at 35 Gy and below, no statistically significant reduction was found.
In this study, pelvic bone marrow volumes receiving doses of 10 Gy, 20 Gy, 30 Gy and 40 Gy (V10, V20, V30 and V40) showed significant reduction in the IMRT arm compared to 3D-CRT arm but at 50 Gy (V50 Gy) did not show any reduction. Meta-analysis by Yang et al. showed non-statistically significant dose reduction to bone marrow in IMRT arm compared to 3D-CRT arm, but our results showed statistically significant reduction. This may be due to small sample size.
In our study, toxicity occurred with 3D-CRT- and IMRT-treated patients was almost similar.
There were no severe acute (Grade 3 and 4) toxicities observed in both the arms, except one patient in the 3D-CRT arm had developed Grade 3 acute haematologic toxicity. Meta-analysis study by Yang et al. showed that toxicity occurred with significantly lower frequency in the IMRT-treated patients than in the 3D-CRT patients. This may be due to small sample size and short duration of follow-up.
All patients in the study were assessed for the treatment response at 6 weeks after the completion of the treatment and over a median follow-up of 18 months (range: 16–20 months). Responses were assessed clinically. All achieved complete clinical response at 6 weeks of follow-up, but at a median follow-up of 18 months, only one patient in 3D-CRT arm developed brain metastasis, and the rest of all the patients showed complete clinical response.
Small sample size, short follow-up and overall survival rates were not reported.
Although IMRT showed dosimetric reduction compared to 3D-CRT, it did not show any clinical benefit. At present, scenario in developing countries like India where the cancer centres are overloaded the carcinoma cervix cases can be treated with the 3D-CRT technique without compromising clinical outcomes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, et al.
Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd
, et al.
Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N
Engl J Med 1999;340:1154-61.
Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr., et al.
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 1999;17:1339-48.
Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, et al.
Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N
Engl J Med 1999;340:1137-43.
Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al.
Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N
Engl J Med 1999;340:1144-53.
Peters WA 3rd
, Liu PY, Barrett RJ 2nd
, Stock RJ, Monk BJ, Berek JS, et al.
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 2000;18:1606-13.
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.
Lukka H, Hirte H, Fyles A, Thomas G, Elit L, Johnston M, et al.
Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer – A meta-analysis. Clin Oncol (R Coll Radiol) 2002;14:203-12.
Gerstner N, Wachter S, Knocke TH, Fellner C, Wambersie A, Pötter R, et al.
The benefit of beam's eye view based 3D treatment planning for cervical cancer. Radiother Oncol 1999;51:71-8.
Barillot I. Cervix carcinomas: Place of intensity-modulated radiotherapy. Cancer Radiother 2009;13:507-10.
Saw CB, Ayyangar KM, Enke CA. MIMiC-based IMRT- part I. Med Dosim 2001;26:1.
Woo SY, Sanders M, Grant W, Butler EB. Does the “peacock” have anything to do with radiotherapy? Int J Radiat Oncol Biol Phys 1994;29:213-4.
Whitton A, Warde P, Sharpe M, Oliver TK, Bak K, Leszczynski K, et al.
Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario. Clin Oncol (R Coll Radiol) 2009;21:192-203.
Yang B, Zhu L, Cheng H, Li Q, Zhang Y, Zhao Y, et al.
Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: A systematic review and meta-analysis. Radiat Oncol 2012;7:197.
Perez CA, Grigsby PW, Nene SM, Camel HM, Galakatos A, Kao MS, et al.
Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 1992;69:2796-806.
International Commission of Radiation Units and Measurements. Prescribing, Recording and Reporting Photon Beam Therapy. Report Number 50. Bethesda: ICRU; 1993.
International Commission of Radiation Units and Measurements. Prescribing, Recording and Reporting Photon Beam Therapy. Report Number 62. Bethesda: ICRU; 1999.
Gay HA, Barthold HJ, O'Meara E, Bosch WR, El Naqa I, Al-Lozi R, et al.
Pelvic normal tissue contouring guidelines for radiation therapy: A radiation therapy oncology group consensus panel atlas. Int J Radiat Oncol Biol Phys 2012;83:e353-62.
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) Int J Radiat Oncol Biol Phys 1995;31:1341-6.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al
. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11;2013.
[Table 1], [Table 2], [Table 3]