6.0) BRIEF RESUME OF THE INTENDED WORK:
6.1) NEED FOR THE STUDY:
Radiotherapy is one of the important treatment modalities in Carcinoma Cervix delivered in the form of External Beam Radiation Therapy as well as Brachytherapy. Brachytherapy is a crucial component in definitive Radiation therapy for CarcinomaCervix. Intracavitary Brachytherapy is a time tested and widely practised form of Brachytherapy in Carcinoma Cervix. During planning of Radiation Therapy, the doses received by normal tissues (organs at risk) reflect the toxicity associated with the treatment. Bowel toxicity manifesting as rectal bleed, congested mucosa, telangiectasia, ulceration, stricture and necrosis are well documented.
Sigmoid colon by virtue of its close proximity to central tandem in Intracavitary Brachytherapy is at high risk of receiving excessive dose, the clinical significance of which has not been well studied. In this study we analyse the dose received by sigmoid colon during External Beam Radiation Therapy and Brachytherapy and correlate with mucosal changes observed on flexible sigmoidoscopy.
6.2) REVIEW OF LITERATURE:
Carcinoma Cervix is the most common cancer affecting Indian women with an estimated age-adjusted incidence of 30.7 per 1,00,000 women and 1,32,082 new cases in a year. By 2025, the no. of new cervical cancer cases in India is projected to 2,26,084. India accounts for one-third of global burden of cervical cancer deaths.1
As per NCI alert 1999, Radiation Therapy along with concurrent Chemotherapy forms the Gold Standard treatment for Carcinoma Cervix. Sigmoid colon is a relatively immobile structure that repeatedly and invariably receives Radiation dose in excess of 70% of point A dose. Hence it forms an important organ at risk while planning Intracavitary Brachytherapy in Carcinoma Cervix.2
With the availability of 3-dimensional imaging modalities like Computed-Tomography scan, the Sigmoid colon can be separately contoured as an organ at risk and the dose received can be quantified. The median sigmoid dose EQD2 D0.1cc and D2cc as reported by L.Holloway et al3 were 84Gy and 68.3Gy respectively in both External Beam Radiation Therapy and Brachytherapy 40.8Gy and 25.3Gy respectively in Brachytherapy alone. A similar study by SUB KOOM et al4 showed D0.1cc and D2cc of 82±20Gy and 67±11Gy respectively which showed a statistically significant correlation on sigmoidoscopic scoring system.
A six scaled scoring system (Vienna Rectoscopy score) for radiation induced proctitis is proposed by medical university of Vienna based on five elementary components of mucosal damage –congested mucosa, telangiectasia, ulceration, stricture and necrosis.5
6.3) OBJECTIVES OF THE STUDY:
1. To assess the combined dose received by sigmoid colon with Radical treatment.
2. To assess the mucosal changes on Flexible Sigmoidoscopy at six months after treatment.
3. To correlate the radiation dose to sigmoid colon with the mucosal changes.
7.0) MATERIALS AND METHODS:
7.1) SOURCE OF STUDY:
Patients receiving Radical Radiotherapy at M.S. RAMAIAH HOSPITALS, Bangalore from November 2013 to Dec 2014.
7.2) METHODS OF COLLECTION OF DATA:
SAMPLE SIZE:
Based on the literature review a study conducted on “computed tomography –based high dose rate Intracavitary Brachytherapy for uterine cervical cancer: preliminary demonstration of correlation between dose volume parameters and rectal mucosal changes observed by flexible sigmoidoscopy”, it was found that the mean value of the dose volume parameters D2cc was 69±9 Gy (mean ± standard deviation ) with the relative precision of 5% and with the confidence level of 95% the sample size worked out to be 26. However considering the drop out rate of 10%it was decided to include 30 subjects for the present study.
INCLUSION CRITERIA:
a) Histologically confirmed cases of Carcinoma Cervix
b) Patients undergoing Radical Radiation therapy.
EXCLUSION CRITERIA:
a) Post-operative and Recurrent cases of Carcinoma Cervix.
b) History of Inflammatory Bowel Disease.
c) History of co-morbidities like Chronic Renal Failure, Chronic Lung Disease and Cardiovascular dysfunction.
7.3) DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.
Yes. Flexible Sigmoidoscopy.
7.4) HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION?
Yes. (Copy enclosed)
7.5) METHOD:
All eligible patients according to the inclusion and exclusion criteria will be enrolled and informed consent for participation will be taken. Baseline investigations will be done. Baseline Flexible Sigmoidoscopy before start of External Beam Radiation Therapy will be performed. Contrast enhanced planning CT of the abdomen and pelvis will be done once before External Beam Radiation Therapy and once before Intracavitary Brachytherapy. Sigmoid colon will be contoured. Dose Volume Histograms are generated after the treatment planning. All patients will receive concurrent Chemoradiation followed by Intracavitary Brachytherapy. Clinical follow-up and follow up Flexible Sigmoidoscopy will be done at 6 months following completion of Intracavitary Brachytherapy. Changes in sigmoid mucosa will be analysed and correlated with Dose Volume Histogram. The 6-scale scoring system(Vienna Rectoscopy score) proposed by Medical University of Vienna determined from the Endoscopic terminology of world organisation for digestive endoscopy which is used for rectum will be used for sigmoid colon too since both sigmoid colon and rectum are part of large intestine and also they are in continuity.
8) LIST OF REFERENCES:
1) Satija A. Cervical Cancer in India. 2009. p. 1-32
2) Booz HA, Boiangiu I, Appleby H, French C, Coomber H, HumpheryPet al. Sigmoid colon is an unexpected organ at risk in Brachytherapy for cervical cancer. Journal of Egyptian Nat Cancer Inst. 2006; 18:156-160
3) Holloway CL, Racine ML, Cormack RA, O’Farrell DA,Vishwanathan AN. Sigmoid dose using 3D imaging in cervical cancer Brachytherapy. Radiotherapy and Oncology. 2009;93:307-310
4) Koom WS,Sohn DK, Kim JY, Kim JW, Shin KH, Yoon SM. Computed Tomography-Based High Dose Rate IntracavitaryBrachytherapy for uterine cervical cancer: Preliminary demonstration of correlation between Dose-Volume parameters and rectal mucosal changes observed by flexible sigmoidoscopy. IntJ.Radiation Oncology Biol. Phys. 2007;68:1446-1454
5) Watcher S, Gerstner N, Goldner G, Potzi R,Wambersie A, Potter R. Endosopic scoring of late rectal mucosal damage after conformal radiotherapy for prostatic Carcinoma. Radiotherapy and Oncology.2000;54:11-19