MR- PET Guided Biologically Optimised Interstitial Brachytherapy

Study Overview
=================
Brief Summary
-----------------
The proposed two stage study will evaluate patterns of local recurrence after EBRT and brachytherapy in spatial reference to baseline functional MRI and FLT/F-Miso PET scan in patients undergoing chemoradiotherapy for postoperative recurrences of cervical cancer. The first stage of the study will focus on developing MR guided interstitial brachytherapy and validating the concept of high risk gross tumor volume (on the basis of functional imaging features). The second stage thereafter will focus on developing biologically modulated interstitial brachytherapy. In the proposed two staged study the investigators intend to prospectively evaluate and validate concept of HRGTV and develop technique of biologically dose modulated brachytherapy. The demonstration of technical feasibility and clinical safety of biologically modulated image guided radiotherapy in this pilot study for may pave the way for improving local control in patients with postoperative recurrences.

Detailed Description
-----------------
Aims Stage I Aim 1: To spatially characterize biologically heterogenous subvolumes within the gross tumor through multimodality (18 F-Miso/FLT/Functional MR) image fusion. Aim 2: To evaluate post external beam radiotherapy (EBRT) response in spatial reference to biological heterogeneous sub-volumes on imaging. Stage II: Aim 3: To evaluate technical feasibility of delivering dose modulated biologically optimized interstitial brachytherapy. Aim 4: To evaluate acute and late toxicity and quality of life associated with biologically optimized brachytherapy

Official Title
-----------------
MR-PET Guided Biologically Optimised Interstitial Brachytherapy for Postoperative Recurrent Cervical Cancers

Conditions
-----------------
Cervical Cancer

Intervention / Treatment
-----------------
* Radiation: MR PET Guided Brachytherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years. ECOG 0 or 1. Residual/ Recurrent tumor after hysterectomy of cervical cancer. No visceral metastasis. No known contraindication to contrast enhanced MRI/PET scan. Fit for radical treatment (radiotherapy+/-chemotherapy). Exclusion Criteria: Expected survival less than 3 years due to coexisting morbid medical conditions precluding radical chemoradiotherapy. Inguinal or extra-pelvic nodal metastasis (Patients with common iliac nodal enlargement in the absence of paraaortic nodal metastasis on PET-CT may be included in the study).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>The study arm will undergo baseline multifunctional PET and MRI scans, before brachytherapy and at follow up | Radiation: MR PET Guided Brachytherapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Response in spatial reference to High Risk GTV (as identified by functional imaging) |  | 3 months after treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade III rectal and bladder toxicity with biologically dose modulated brachytherapy | Stage II involves dose modulated brachytherapy wherein higher dose will be delivered to biologically high risk target volume. Saftey will be assessed initially by an interim analysis undertaken at 50 % accrual(median follow up 1 yr). If incidence of grade III-IV rectal and bladder toxicity >15% than the trial will be stopped else continued till target accrual. The technique will be considered to be safe if Grade III bladder and bowel toxicity remain to be under 15%. | 2 years after treatment conclusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
FLT PET, Diffusion Weighted MRI, F-Miso PET, Image Guided Brachytherapy, Cervix, Postoperative Residual Disease/Postoperative recurrences