Tomotherapy vs Conventional Radiation for Adjuvant Pelvic RT in Ca Cervix

Study Overview
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Brief Summary
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The study tests Tomtherapy based Image Guided Radiation against conventional radiation techniques for it's ability to reduce long term small bowel toxicity.

Detailed Description
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Postoperative pelvic radiotherapy (+/- chemotherapy) leads to reduction in the risk of local recurrence and improves progression free survival (PFS) in patients with post-operative intermediate and high risk factors following Wertheim's hysterectomy. However, adjuvant external beam radiotherapy and vaginal cuff brachytherapy increase the risk of small bowel toxicity such that patients undergoing external beam pelvic radiotherapy and vaginal cuff brachytherapy may have 15-18% incidence of late RTOG ≥ grade II small bowel toxicity. Phase II studies using new techniques like Intensity Modulated Radiotherapy (IMRT) have reported up to 50% reduction in small bowel doses with up to 30% reduction in ≥ grade II acute toxicity. However, there is no randomized data demonstrating the benefit of highly specific and conformal techniques like image guided (IG)-IMRT in reducing radiation induced small bowel toxicity in patients with cervical cancers. The present study is being proposed to test if use of IG-IMRT with Tomotherapy is associated with reduced small bowel late toxicity

Official Title
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Phase III Randomized Trial of Image Guided Intensity Modulated Radiotherapy (IG-IMRT) and Conventional Radiotherapy for Late Toxicity Reduction After Postoperative Radiotherapy in Ca Cervix.

Conditions
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Cancer Cervix

Intervention / Treatment
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* Radiation: Conventional Radiation
* Radiation: Tomotherapy based IGRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological diagnosis of carcinoma cervix with postoperative intermediate or high risk features. Age >18 years. Planned for Wertheim's hysterectomy or has already undergone Wertheim's hysterectomy OR has undergone Simple Hysterectomy with no evidence of residual nodes on MRI/PET imaging+/- confirmatory nodal biopsy. No evidence of paraaortic nodal metastasis. Exclusion Criteria: History of multiple previous abdominal surgeries placing patient at baseline high risk of bowel toxicity or any other medical condition with baseline bowel movement disorder. Rectal Polyps or extensive hemorrhoids.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients enrolled are randomized to either conventional arm or tomotherapy arm for treatment after stratification according to type of surgery the patient underwent and the indication of chemotherapy along with radiation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional RT<br>Patients in this arm will receive conventional radiation with or without chemotherapy | Radiation: Conventional Radiation<br>* Standard Pelvic Radiation 50 Gy/ 25 fractions over 5 weeks<br>|
| Experimental: Tomotherapy based IGRT<br>Patients in this arm will receive Tomotherapy based IGRT with or without chemotherapy | Radiation: Tomotherapy based IGRT<br>* Patients in this arm will received Tomotherapy based Image Guided Intensity Modulated Radiotherapy to a dose of 50 Gy/25 fractions/5 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late bowel toxicity ≥ Grade II | Time to event and severity of late bowel toxicity are assessed | Median follow up of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify small bowel dose volume characteristics that predict for ≥ Grade II late toxicity | Data on dosimetric analysis of small bowel dose in reference to volume are collected in both arms and assessed for predicting dose prescription for ≥ grade II late bowel toxcity | Median follow up of 3 years | 
| To evaluate acute toxicity difference in two study arms using CTCAE version 3.0 | Acute toxicity will be reported using CTCAE V.3.0. CTCAE forms will be filled before starting radiation, weekly during radiation treatment and on each scheduled follow-up. If any toxicity occurs at another time point additional forms will be filled to capture the same. Acute toxicity difference will be calculated between the two study arms. | Within 90 days | 
| Preoperative functional imaging features that predict for local and distant recurrence will be identified | Images acquired pre-operatively are analysed for features that predict local and distant recurrence. | 3 years after completion of accrual | 
| To compare quality of life between Tomotherapy vs conventional radiotherapy arm using EORTC QLQ C30 | Assessment is done for all enrolled patients to compare the quality of life after treatment with tomotherapy and conventional radiation . EORTC QLQC30 module will be used for evaluating QOL of patients. QOL scoring will be done as per standard recommendations outlined in EORTC QLQ C30 scoring manual. All patients will undergo QOL evaluation at baseline, after treatment and at subsequent follow-up. Scale- Not at all-1 , A little Bit-2, Quite a bit-3, very much-4. 1 will be considered as better outcome & 4 will be considered as worst outcome. | 3 years from completion of accrual | 
| To compare quality of life between Tomotherapy vs conventional radiotherapy arm using EORTC QLQ CX24 | Assessment is done for all enrolled patients to compare the quality of life after treatment with tomotherapy and conventional radiation. EORTC QLQCX24 module will be used to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer. CX24 QOL scoring will be done as per standard recommendations outlined in EORTC QLQ CX24 scoring manual. All patients will undergo QOL evaluation at baseline, after treatment and at subsequent follow-up. Scale- Not at all-1 , A little Bit-2, Quite a bit-3, very much-4. 1 will be considered as better outcome & 4 will be considered as worst outcome. | 3 years from completion of accrual | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IGRT,Postoperative, Cervix, Late toxicity, Bowel