1. Investigating the role of Immunotherapy in locally advanced cervical cancer. Node positive cervical
cancer continues to represent an unmet medical need with poor outcomes with standard radiation and
chemotherapy. Dr. Mayadev is the national principal investigator on two NCI funded clinical trials
with U10 grant funding. She is also the co-global principal investigator on a randomized phase III
trial with AstraZeneca investigating the role of immunotherapy during and after chemoradiation. She is
also leading efforts to understand the immune mechanisms of cervical cancer through her lab
collaborations and grant funding.
My clinical and translational research is focused on the innovative combination of radiation and
immunotherapy for cervical cancer. I designed and was funded from the NCI for two phase I NRG oncology
national clinical trials. Through these trials we understand the safety and toxicity profile of
combination immunotherapy and chemoradiation. We also better understand the immune mechanisms
responsible for the recognition of cervical cancer by the immune system and the delineation of
predictors of response to CTLA-4 and PD-1 blockade.
NCI Clinical Trial Research Strategy, Harnessing of Equity, and Implementation Role: PI, Jyoti Mayadev
Funding: 887,815.00; NCI, 1 R50 CA282102-01
- Mayadev JS, Enserro D, Lin YG, et al. Sequential Ipilimumab After Chemoradiotherapy in
Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer. JAMA Oncol. 2019 Nov 27.
doi: 10.1001/jamaoncol.2019.3857
- DaSilva D, Enserro D, Mayadev J et al. Immune Activation in Patients with Locally Advanced
Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929). Clinical
Cancer Research 2020 Aug. DOI:
10.1158/1078-0432.CCR-20-0776
- Dyer BA, Zamarin D, Eskandar RN, Mayadev JS.
Role of Immunotherapy in the Management of
Locally Advanced and Recurrent/Metastatic Cervical Cancer.J Natl Compr Canc Netw. 2019
Jan;17(1):91-97. doi: 10.6004/jnccn.2018.7108. Review. PMID: 30659133
- Mayadev J, Zamarin D, Deng W et el.
Anti-PD-L1 (atezolizumab) as an immune primer
and concurrently with extended-field chemoradiotherapy for node-positive locally advanced
cervical cancer.Int J Gynecol Cancer. 2019 Dec 22. pii: ijgc- 2019-001012. doi:
10.1136/ijgc-2019-001012.
GOG 9929: A phase I trial of sequential ipilumumab after chemoradiaiton for cervical cancer, CTEP
A national phase I trial exploring the use of immunotherapy in node positive cervical cancer to
evaluate safety and tolerability in the definitive setting.
Role: National Principal Investigator
Publications: Mayadev et al.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2756224
GY-017: Anti PD-L1 (Atezolizumab) as an Immune Primer and Concurrently with Extended Field
Chemoradiotherapy for Node Positive Locally Advanced Cervical Cancer
This clinical trial examines translational aspects of T cell clonality, and tolerability of adding
immunotherapy to chemotherapy and radiation
Role: National Principal Investigator
Plenary SGO 2022:
https://www.nrgoncology.org/Home/News/Post/nrg-oncology-trial-indicates-using-atezolizumab-with-
chemoradiation-is-safe-and-demonstrates-signs-of-immune-activation-in-women-with-cervical-cancer
Plenary SGO 2023:
https://www.nrgoncology.org/Home/News/Post/the-utilization-of-atezolizumab-as-a-primer-for-
chemoradiation-results-in-promising-immune-system-alterations-for-women-with-locally-advanced-
cervical-cancer
CALLA:
Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer
(CALLA) (CALLA)
Role: International co-Principal Investigator ; Radiation Therapy Committee Chair
CALLA: Efficacy and safety of concurrent and
adjuvant durvalumab with chemoradiotherapy versus chemoradiotherapy alone in women with locally
advanced cervical cancer: a phase III, randomized, double-blind, multicenter study.
Mayadev J, Nunes AT, Li M, Marcovitz M, Lanasa MC, Monk BJ.Int J Gynecol Cancer. 2020
Jul;30(7):1065-1070. doi: 10.1136/ijgc-2019-001135. Epub 2020 May 23.
2. Immunogenomic predictors of outcomes in patients with locally advanced cervical cancer treated
with immunotherapy and chemoradiation
This series of projects will look at samples from our clinical trials in cervical cancer to
investigate the
underlying immune responses and predictors for survival after chemoradiation in node positive cervical
cancer. The NCI has funded this collaborative project through the NCI R01 mechanism with my
collaborator Dr. Dmitriy Zamarin, MD, PhD.
Immunogenomic predictors of outcomes in patients with locally advanced cervical cancer treated with
immunotherapy
and chemoradiation
Role: PI, Aim 3 Jyoti Mayadev; Co-Investigator collaboration Jyoti Mayadev
Funding: 2,147,464
1 R01 CA276087-01A1
“Investigation of the humoral B-cell response to chemoradiation therapy and checkpoint
blockade immunotherapy in locally advanced cervical cancer”
PI: Jyoti Mayadev; Co-PI: Andrew Sharabi, MD PhD, Sangwoo Kim,MD, Jing-Jing Zhou, PhD
Funding: 50K, UCSD Translational Research Grant, Jawsome Award
We will determine how the
tumor immune microenvironment evolves as a function of differential immunotherapy and CRT
sequencing. By using multi-parameter fluorescence microscopy, we will determine how
activation of T
cells and their interaction with other cells in the tumors change in response to therapy and how
these
changes predict long term outcomes.
We will also investigate T cell receptor (TCR)
repertoire sequencing as well as advanced bioinformatics techniques to evaluate how evolution
of T
cells in tumors and peripheral blood could serve as an indicator of anti-tumor immune response
and
long-term outcomes. We will establish radiographic and blood biomarkers as predictors of
outcomes in high-risk LACC patients by examining blood HPV DNA and post-treatment PET-CT
as
markers of disease burden pre- and post-therapy. Identification of early biomarkers predictive of
outcomes will be critical for risk-stratification of patients with LACC in order to guide patient
selection for
clinical trials or maintenance therapy, while minimizing the potential clinical toxicities and
financial
burden in patients at low risk for recurrence.
PUBLIC HEALTH RELEVANCE: Patients with locally-advanced cervical cancer with lymph
node
metastases exhibit poor prognosis despite the current standard of care therapy with
chemotherapy and
radiation. There is thus a critical need to develop new therapeutic strategies for patients with
high-risk
cervical cancer and to identify biomarkers that could predict which patients are more likely to
benefit.
The current proposal will take advantage of tumor and blood samples collected from high-risk
cervical
cancer patients treated on an NCI-funded clinical trial of immunotherapy combined with
chemotherapy
and radiation to determine optimal sequencing of immunotherapy and radiation and to identify
the
patients that do or do not benefit from this approach.
3. Understanding disparities and quality in locally advanced cervical cancer.
Through a series of projects and publications, Dr. Mayadev’s lab seeks to understand disparities in
brachytherapy use. Currently the lab has funding and a collaboration with San Diego State University
and Moores Cancer Center to look at trends within the San Diego region for use and outcomes of
brachytherapy.
Publications:
Global challenges of radiotherapy for the
treatment
of locally advanced cervical cancer.
Mayadev JS, Ke G, Mahantshetty U, Pereira MD, Tarnawski R, Toita T.Int J Gynecol
Cancer.
2022 Mar;32(3):436-445. doi: 10.1136/ijgc-2021-003001.
Improved survival in cervical cancer patients
receiving care at National Cancer Institute-
designated cancer centers.
McDaniels-Davidson C, Feng CH, Martinez ME, Canchola AJ, Gomez SL, Nodora JN, Patel SP,
Mundt AJ, Mayadev JS.Cancer. 2022 Oct 1;128(19):3479-3486. doi: 10.1002/cncr.34404. Epub
2022 Aug 2.
Mayadev J, Klapheke A, Yashar C, Hsu IC, Kamrava M, Mundt AJ, Mell LK, Einck J,
Benedict S, Valicenti R, Cress R. Underutilization of brachytherapy and
disparities in survival for patients with cervical cancer in California. Gynecol
Oncol. 2018 Jul;150(1):73-78. doi: 10.1016/j.ygyno.2018.04.563. Epub 2018 Apr
27. PMID:29709291
4. Understanding Radiation Induced Vaginal Stenosis and Design of an Interventional Vaginal
Prototype
Principal Investigators: Dr. Jyoti Mayadev, Dr. Karcher Morris, PhD, Dr. Milan
Makale,PhD, Professor
Frank E. Talke, PhD, Talke Mechanical Engineering Laboratory
Researcher Students: Rafaela S. Torigoe, Karcher Morris, Matthew Kohanfars
Grant from the UCSD Academic Senate office, UCSD Engineering GEM grant, MCC Office of Communiy
Engagement Pilot grant to study vaginal stenosis, a complication of radiation therapy in gynecologic
cancers, pending R21 NCI grant funding (score 13 th percentile).
We plan to harness our cervical cancer specific multidisciplinary team of UCSD physicians,
bioengineers, and mechanical engineers is addressing this unmet medical need of VS. We will
test the hypothesis “radiation induced VS is measureable and patient specific preferences will
lead to a personalized engineering device to prevent VS”. We intend to provide the input for the
engineering personalized vaginal device to mitigate VS for at home use. Our work will
eventually lead to the development of a patient specific novel vaginal canal device with a FDA
medical device application and an impactful clinical trial.
Clinical Trial Available: Quantifying Radiation Induced Vaginal Stenosis, PI
Mayadev, open to accrual UCSD
An Interdisciplinary Approach to Quantifying Radiation Induced Vaginal Stenosis in Cervical Cancers
for the
Development of a Patient-focused Biomechanical Therapeutic Device
PI: Jyoti Mayadev
Funding: 50K, UCSD MCC Community Outreach and Engagement; 50K UCSD Engineering GEM Award, R21 ward
percentile 13 th pending,
5. Automation in Gynecological Brachytherapy
Development and Evaluation of Knowledge-based Cervical Brachytherapy Treatment
Planning
Role: Jyoti Mayadev, MD Co-PI (Sandra Meyers, PhD PI)
Varian Medical Systems Award 208K
Figure 1. (A) Sagittal CT image of a cervical cancer patient with brachytherapy
applicator (green) placed into the
cervix and uterus. (B) A typical brachytherapy radiation dose distribution, where the organs are
spared of the high
dose regions.
Processing of treatment plan data (blue arrows and text) to obtain model inputs, and neural network
training workflow
(grey).