Cervical cancer is a worldwide public health problem and significant cause of mortality, with over 500,000 women diagnosed each year. Optimal curative treatment for women with locally advanced disease calls for treatment with external beam radiation (EBRT) followed by brachytherapy. Brachytherapy allows delivering larger dose into the tumor with interstitial catheters, which are placed into the residual tumors that survive EBRT. The placement of these catheters, hollow plastic tubes with metal rods placed inside for pushing through body tissue, is typically done without any guidance, and complications due to inadvertent insertion into normal tissues (blood vessels, rectum, bladder), rather than into residual tumor, may result. Magnetic resonance-guided brachytherapy (MRBT) has significantly improved survival and reduced complications caused by inadvertently radiating neighboring tissues. In order to locate the catheters properly and to calculate radiation dose, a CT is required after the MRBT. This lengthens an already complex and labor- intensive procedure, which also suffers from imperfect methods to identify residual tumor after EBRT and before MRBT. Identifying normal tissues as residual tumor before MRBT may result in inadvertent treatment with radiation of healthy tissues, which increases complications. MRI multi-parametric identification of post- EBRT residual tumor, combined with actively-tracked catheter placement into the disease as seen on MR scanning, can result in a more precise treatment volume, and faster and more accurate MRBT catheter placement, leading to better outcomes and reduced complications. This should increase the use of MRBT in treating cervical cancer, as well as recurrent endometrial, vaginal, prostate, and other cancers. The proposed procedure utilizes several novel tools: (a) MRI sequences that map the tissue parameters perfusion, diffusion, fibrosis and oxygenation in the post-EBRT pelvis, which are analyzed by expert clinicians, and used to develop a method for providing refined remnant tumor maps; (b) a novel active- obturator MRI coil which is placed in the vagina, that reduces MRI scan times by >50%; (c) flexible actively- tracked metallic catheters, integrated with the new Elekta Venezia applicator, improving localization precision and accelerating placement; and, (d) instantaneous intraoperative dose mapping, where catheter locations at any time during placement are used to predict and guide what the clinician's best next move should be, such as changing current catheter locations or adding more catheters. Together, these methods will culminate in dose-optimized catheter placements that will lower tumor recurrence and limit radiation side effects. This project is a collaboration between Johns Hopkins University and Elekta Inc. JHU radiation oncologists, radiologists, medical physicists and MRI physicists, along with a panel of experts in identifying remnant tumor, will work jointly with Elekta engineers to develop an innovative platform with broad applications in radiation oncology. The tools developed are validated in a 20-patient cohort of cervical cancer patients.

Public Health Relevance

Cervical cancers are a leading cause of death among women worldwide. Treatment by implantation of radioactivity into the tumor with MR-guidance (MR- brachytherapy) has significantly improved survival. We accelerate MR- bracytherapy with better tumor detection and real-time dose optimization during implantation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA237005-02
Application #
10116323
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Redmond, George O
Project Start
2020-03-01
Project End
2025-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218