The Centers for Disease Control and Prevention (CDC) reports that around 13,000 new diagnoses of cervical cancer and approximately 4,000 cervical cancer-related deaths occur annually in the United States. The recommended treatment for locally advanced cervical cancer, which is cancer that has spread just beyond the cervix, involves a combination of external beam radiation (EBRT) and internal brachytherapy. EBRT is the most common form of radiation therapy that is administered externally from a distance, while brachytherapy delivers radiation up close, inside the patient’s body. Brachytherapy provides a concentrated radiation dose directly to the primary cervical cancer tumor while sparing adjacent healthy tissues from receiving toxic side effects from the treatment. 

Brachytherapy is as old as radiotherapy itself. The treatment emerged in the early 1900s alongside the pioneering discoveries of radium by Marie and Pierre Curie. Although brachytherapy is well-established as an integral component in the standard of care for cervix cancer and receipt of brachytherapy is associated with higher overall survival and better disease control, it is an underutilized treatment method, especially among Black women. 

This underutilization can be attributed to several challenges associated with brachytherapy. These include limited exposure to the procedure during residency training, insufficient infrastructure in low-volume centers, constraints in advanced imaging techniques, and financial barriers. Addressing these challenges is essential to ensuring broader access to and utilization of brachytherapy and ultimately improving outcomes for women facing cervical cancer.

Stanford Cancer Institute member Elizabeth Kidd, MD, Stanford associate professor of radiation oncology, is spearheading new tools to facilitate the broader adoption of brachytherapy.

Financial barriers and disparities

Evaluating data from the National Cancer Database, Kidd and her team found that Black women with cervical cancer were significantly less likely to receive brachytherapy. Additionally, women undergoing treatment at a community hospital, as opposed to an academic cancer center, were also significantly less likely to receive brachytherapy. Many low-volume centers do not offer brachytherapy, either due to a lack of resources or comfort with the procedure.

Financial toxicity poses a significant barrier for women needing brachytherapy when treatment facilities are far away. The costs of travel, accommodation, and potential work disruption can create a burden, causing the recommended treatment to become inaccessible and compromising the quality of care received.

As Kidd notes, “Brachytherapy is more often available at academic medical centers. I see patients from Fresno, California, all the way to Eureka, California.” That is approximately a span of 450 miles. 

Training hurdles

Unlike external radiation, which is more commonly used across various cancers, brachytherapy is applied in specific cases such as gynecologic cancers and prostate cancer. Brachytherapy requires special equipment, infrastructure, and procedural expertise.

“Not all radiation oncologists feel comfortable or well-trained in brachytherapy because it involves a more procedural approach,” notes Kidd.

Limited experience with brachytherapy may lead some practitioners to opt to administer only EBRT. However, National Cancer Data Base data confirms that patients who don't receive brachytherapy have significantly compromised survival.

Kidd emphasizes, “Not receiving brachytherapy is actually more detrimental than not receiving concurrent chemotherapy for cervix cancer patients. Without using brachytherapy, they can't get enough dose to adequately treat the tumor.”

Interstitial needle placement challenges

Traditionally, brachytherapy is delivered to the cervix by applicators placed in and around the cervix that create a pear-shaped dose distribution around the cervix. The applicator consists of a tandem (thin tube placed within the cervix and central uterine canal) and a ring or ovoid applicator (placed up against the cervix).

Over the last 15 years, the shift from 2D to 3D imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), has revealed that this traditional dosing may not produce optimal tumor coverage. 

Supplemental interstitial needles, offering additional targeted radiation delivery, were introduced alongside the standard applicator to better shape the dose to the tumor region. However, there are challenges in precisely placing the needles for optimal dosage due to the confined, limited space within the vaginal canal. Placing the needles freehand requires careful maneuvering and trial and error for accurate positioning, adding complexity to an already challenging procedure. While there are some commercially available templates to help guide the needles into place, they often do not place needles in optimal locations or are too large for patient anatomy. 

Needle innovation

Kidd and her team designed a 3D-printed template known as the Tandem Anchored Radially Guiding Interstitial Template (TARGIT).  

“It is a small 3D-printed template which attaches to a standard tandem. In essence, it is a needle guide,” explains Kidd.

TARGIT simplified needle placement by guiding needles into pre-defined holes. This simplified approach reduced the reliance on trial and error. Kidd found that TARGIT significantly improved tumor coverage without increasing the dose to the nearby normal tissues, such as the bladder, rectum, and bowel, compared to non-TARGIT techniques. 

Setting out to improve on the original design, Kidd and her team developed the TARGIT-Flexible-eXtended (TARGIT-FX), which aims to simplify the process of interstitial needle insertion for cervical cancer brachytherapy. A study published in 2023 found that TARGIT-FX decreased procedure times while increasing tumor coverage compared to TARGIT. Furthermore, the improved template improved residents’ learning curve for interstitial needle placement during cervical cancer brachytherapy.

Economical and efficient

The initial TARGIT templates were fabricated using a 3D-printing process, costing approximately $10 to $20 per template. Kidd and her team engineered three distinct TARGIT templates, each equipped with three needle placement holes to accommodate accurate needle placement across diverse patient anatomies.

Capitalizing on the iterative design potential of 3D printing, TARGIT-FX was developed. The TARGIT-FX consolidates the original three TARGIT templates into one comprehensive design. TARGIT-FX increases needle positioning possibilities by including nine needle guides within the single template design. The updated template iteration has broadly simplified cervical cancer brachytherapy procedures.

Streamlining needle adjustments

In the previous smaller TARGIT design, repositioning interstitial needles was cumbersome. An important enhancement in the TARGIT-FX design involved lengthening the applicator to the vaginal introitus, the opening into the vaginal canal. This extension allows for the easy insertion and external adjustment or addition of needles.

“Before the TARGIT-FX, making needle adjustments based on CT imaging would necessitate transferring an anesthetized patient back to the procedure room. This process significantly complicated modifying needle positions. However, with the improved TARGIT-FX design that extends beyond the vaginal introitus, needle adjustments can now be made directly on the CT table," highlights Kidd.

Kidd found that procedure times for TARGIT-FX implants were 30% shorter on average than for those using the original TARGIT, likely due to the improved flexibility of needle position options and the simplicity of placing needles. 

Training advancements

Kidd’s study revealed universally positive feedback from residents in Stanford's radiation oncology program. All residents who used TARGIT-FX found the template needle insertion template user-friendly and expressed a desire to incorporate it into their future brachytherapy practice. This feedback emphasizes the practicality of the TARGIT-FX for practitioners less versed in advanced cervical brachytherapy techniques and highlights its relevance for those operating in settings with lower cervical cancer patient volumes.

“At Stanford, we function as an academic training center. The procedural aspects of radiation oncology can be time-intensive for residents to master. Historically, placing needles was among the last skills residents developed comfort with, particularly when done freehand, with some residents never reaching this stage. The ease of placing needles from the vaginal introitus, as opposed to at the apex or top of the vagina, allows residents to start this aspect as early as the first week of their rotation. The simplicity has transformed needle placement from one of the most challenging aspects to one of the more straightforward components of the procedure,” states Kidd.

Several institutions have reached out to Kidd to learn more about how the TARGIT-FX and 3D printing can be adapted to their process to simplify their brachytherapy procedures. While acknowledging that Stanford's workflow may not be transferable across all medical settings, Kidd hopes that TARGIT-FX can help broaden access to brachytherapy for all women with locally advanced cervix cancer.

January 2024 by Sarah Pelta