David Barrington, MD

David Barrington, MD, obstetrics & gynecology specialist at Ohio State University Comprehensive Cancer Center, discusses the next steps for oncologists treating patients with stage 1B, grade 3 endometrial cancer.

The future of this space will rely heavily on evaluating results from various clinical trials to provide more guidance and recommendations for treatment options. Particularly, Barrington notes that immunotherapy will continue to play a large role in this setting when used alone and in combination with other treatments.

In addition, emerging clinical and preclinical data examining immunotherapy checkpoint inhibitors, molecular therapy, and immunotherapy, aim to further change the landscape for these early stage cancers.

We're starting to see immunotherapy play a larger and larger role in the recurrent setting in the ongoing clinical trials looking at immunotherapy in combination with traditional cytotoxic chemotherapy, comparing the 2 in combination to traditional cytotoxic chemotherapy. As we see it, I think we're going to continue to see immunotherapy gain traction, either in combination treatment or as a standalone therapy.

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David Barrington, MD, discusses the next steps for oncologists treating patients with stage 1B, grade 3 endometrial cancer.


Future Directions for Treating Stage 1B, Grade 3 Endometrial Cancer 

David Barrington, MD, obstetrics & gynecology specialist at Ohio State University Comprehensive Cancer Center, discusses the results investigators found in determining treatment patterns and recommendations for patients with endometrial cancer.

Using the National Cancer database, Barrington et al evaluated race, facilities, region, and more to see what factors were most associated with variation in treatment patterns for this patient population. Through examining the many factors, experts concluded that there is a lot of confusion when it comes to managing patients with 1B grade 3 tumors.

Despite this research, more is needed to determine the proper ways to care for this patient population. Experts hope that the more molecular testing is studied, the better oncologists will be able to care for their patients.

 I think it highlights the fact that there's a lot of confusion out there about what the optimal treatment for 1B grade 3 tumors is. I think we need further study to elucidate what's going to be the proper way to manage these patients moving forward. As we learn more and more about molecular characteristics, that's going to play a large role.

 Then also, knowing that the guidelines are great and the more specific we can be with guidelines, the greater chance we have of achieving optimal outcomes for a variety of patients in a variety of circumstances and helping to overcome some of that variety in treatment that may not be the best for our patients.

 We've utilized the data from the database to answer the question about treatment patterns, as well as facility location and differences in outcomes. I think looking with more granular information with a large retrospective cohort could give us some more information. Then, looking to the future clinical trial results that can guide us more on how to change the treatment we recommend.

David Barrington, MD, discusses the results investigators found in determining treatment patterns and recommendations for patients with endometrial cancer.

Questions Remain Unanswered in Treating Stage 1B Grade 3 Endometrial Cancer 

David Barrington, MD, obstetrics & gynecology specialist at Ohio State University Comprehensive Cancer Center, discusses the key takeaways regarding the factors associated with variation of adjuvant treatments for patients with stage 1B, grade 3 endometrial cancer.

While the NCCN guidelines show there to be a number of treatment options, including external beam radiation and adjuvant chemotherapy for this patient population, the standard of care remains unknown.

Through the examination of data from the National Cancer database, Barrington and other experts aimed to discover whether or not factors such as race, facilities, or region were associated with variation, treatment patterns and resulted in different recommendations for patients.

While findings showed no differences based on race and that there may be a survival benefit for patients in the academic setting using multimodal therapies, confusion surrounding what the optimal treatment for these grade 3 tumors are. Further studies are needed to determine the proper ways to manage these patients. to really elucidate what's going to be the proper way to manage these patients moving forward.

 Knowing the latitude that NCCN allows for adjuvant treatment for these 1B grade 3 endometrial cancers, we want to examine using data from the National Cancer database to see if we can identify factors that were associated with variation and treatment patterns. If there were differences around the country, or based on the type of facility, or racial demographics to see if we saw differences in what was being recommended.

We saw that certain regions and the more academic institutions were more likely to use a combination of a multimodal therapy with chemotherapy, plus or minus radiation, including external beam radiation or vaginal breaking therapy. We saw from the database, data that seemed to be a survival benefit. Of course, it's difficult to interpret these database studies because it's all retrospective in nature and doesn't control for all confounding bias, but [they are] interesting findings.

 Specifically, we saw that while there was no difference based on race, whether or not multimodal therapy was employed, the Black woman that received combined therapy, chemotherapy plus radiation, seemed to have a greater survival benefit than what we saw in other racial groups.

David Barrington, MD, discusses the key takeaways regarding the factors associated with variation of adjuvant treatments for patients with stage 1B, grade 3 endometrial cancer.


Factors Influencing Treatment Options for Stage 1B Grade 3 Endometrial Cancer

David Barrington, MD, obstetrics & gynecology specialist at Ohio State University Comprehensive Cancer Center, discusses his advice on molecular testing for patients with stage 1B, grade 3 endometrial cancer.

There are a variety of adjuvant treatment options available for this patient population, including external beam radiation, and adjuvant chemotherapy, and more. Still, the standard of care for treating these patients remains unknown, and researchers are excited to look more into the molecular characteristics of tumors in these patients.

Examining the molecular characteristics will aid in learning more about mismatch repair protein status, protein deficiencies, immunotherapy with radiation, and more. Barrington hopes that emerging clinical and preclinical data will show the relation between immunotherapy checkpoint inhibitors and radiation in order to further change the landscape for these early stage cancers.

At Ohio State, we do universal immunohistochemistry for all endometrial cancers. That gives us an immediate idea, if we see mismatch repair protein deficiency, that helps us guide clinical trial recommendations. Then, it also can help manage decisions for optimal management for treatment, a recurrent setting. Then sometimes there's emerging data that tumors with 

 mutations may exhibit a more aggressive behavior. That's something we're learning more and more about and some are incorporating those molecular characteristics into their treatments or application of their trials.

Sometimes, these grade 3 tumors are difficult to differentiate from other high grade in vitro histologies, like urine serous cancers, and sometimes 

 will be tested to help aid in diagnosis. We also know that even when the diagnosis is confirmed as grade 3, some of those patients are going to have 

 mutations as well. It's hard to say what actual clinical information we have and that we can then incorporate for the adjuvant treatment setting up upfront, but it is something that I think we're going to continue to learn more about.

 I think an important point is that we aren't routinely doing polymerase epsilon testing, but we can often see 

 mutations, and that can be difficult to interpret as well. We also have emerging data to show that 

 mutation, which can sometimes lead to worse prognosis arises because the 

 mutation can be difficult to interpret. Those tests, in an ideal setting when incorporated into clinical practice, would be done in concert with one another.

David Barrington, MD, discusses his advice on molecular testing for patients with stage 1B, grade 3 endometrial cancer.


Role of Molecular Testing in Stage 1B, Grade 3 Endometrial Cancer

David Barrington, MD, obstetrics & gynecology specialist at Ohio State University Comprehensive Cancer Center, discusses adjuvant treatments that are currently available for patients with stage 1B, grade 3 endometrial cancer.

A number of treatment options are available for patients with stage 1B, grade 3 endometrial cancer, including external beam radiation, adjuvant chemotherapy, and more. However, the ideal way to treat these patients remains unknown.


With emerging, clinical and preclinical data showing a relationship between immunotherapy checkpoint inhibitors and radiation, Barrington notes that it will be important to look into the molecular characteristics of these tumors in order for experts to determine how to best treat them.

There are a variety of different treatment options. The NCCN guidelines really cover the full gamut, including vaginal breaking therapy for some candidates, external beam radiation to include whole pelvic radiation, and the use of adjuvant chemotherapy as well. Physicians have a choice of using any or all of these modalities. We really are not at a place where we know the optimal treatment for 1B grade 3 endometrial cancer. We know that they have a high density for distant recurrence, but we also do not know the ideal way to treat these patients with adjuvant therapy.


 I think some of the things that I'm most excited about is starting to look more at the molecular characteristics of these tumors. We know that mismatch repair protein status for these cancers is an exciting opportunity for those with the mismatch repair protein deficiencies. It's an exciting opportunity to incorporate immunotherapy with radiation. We know there's been emerging clinical and preclinical data to show synergy between immunotherapy checkpoint inhibitors and radiation, so those are some of the things that are the most exciting landscape for these early stage cancers.

David Barrington, MD, discusses adjuvant treatments that are currently available for patients with stage 1B, grade 3 endometrial cancer.


David Barrington, MD | Authors

Articles

Future Directions for Treating Stage 1B, Grade 3 Endometrial Cancer

Questions Remain Unanswered in Treating Stage 1B Grade 3 Endometrial Cancer

Factors Influencing Treatment Options for Stage 1B Grade 3 Endometrial Cancer

Role of Molecular Testing in Stage 1B, Grade 3 Endometrial Cancer

Discussing Adjuvant Therapy Options for Endometrial Cancer