Rebecca Previs

Positions:

Assistant Professor of Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2009

University of Virginia School of Medicine

Residency, Obstetrics And Gynecology

Duke University School of Medicine

Fellow, Gynecologic Oncology

University of Texas MD Anderson Cancer Center

Grants:

Evaluation of homologous recombination deficiency in uterine serous cancer

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
Awarded By
Myriad Genetics, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy.

Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the pro-angiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody. Mice treated with a CSF1R inhibitor (AC708) after anti-VEGF antibody resistance had little to no measurable tumor burden upon completion of the experiment while those that did not receive a CSF1R inhibitor still had abundant tumor. To mimic clinically used regimens, mice were also treated with anti-VEGF antibody and paclitaxel until resistance emerged, and then a CSF1R inhibitor was added. The addition of a CSF1R inhibitor restored response to anti-angiogenesis therapy, resulting in 83% lower tumor burden compared to treatment with anti-VEGF antibody and paclitaxel alone. Collectively, our data demonstrate that the addition of a CSF1R inhibitor to anti-VEGF therapy and taxane chemotherapy results in robust anti-tumor effects.
Authors
Lyons, YA; Pradeep, S; Wu, SY; Haemmerle, M; Hansen, JM; Wagner, MJ; Villar-Prados, A; Nagaraja, AS; Dood, RL; Previs, RA; Hu, W; Zhao, Y; Mak, DH; Xiao, Z; Melendez, BD; Lizee, GA; Mercado-Uribe, I; Baggerly, KA; Hwu, P; Liu, J; Overwijk, WW; Coleman, RL; Sood, AK
MLA Citation
Lyons, Yasmin A., et al. “Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy.Oncotarget, vol. 8, no. 57, Nov. 2017, pp. 96496–505. Pubmed, doi:10.18632/oncotarget.20410.
URI
https://scholars.duke.edu/individual/pub1482686
PMID
29228548
Source
pubmed
Published In
Oncotarget
Volume
8
Published Date
Start Page
96496
End Page
96505
DOI
10.18632/oncotarget.20410

Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Endometrial cancer uncommonly presents at an advanced stage and little prospective evidence exists to guide the management thereof. We aimed to summarize the evidence about primary cytoreductive surgery in the treatment of advanced stage endometrial cancer. DATA SOURCES: MEDLINE, Embase, and Scopus databases were searched from inception to September 11, 2020, using search terms representing the themes "endometrial cancer," "advanced stage," and "primary cytoreductive surgery." STUDY ELIGIBILITY CRITERIA: We included full-text, English reports that included ≥10 patients undergoing primary cytoreductive surgery for advanced stage endometrial cancer and that reported on the outcomes of primary cytoreductive surgery and survival rates based on the residual disease burden. METHODS: Two reviewers independently screened the studies and with disagreements between the reviewers resolved by a third reviewer. Data were extracted using a standardized form. The percentage of cases reaching maximal (no gross residual disease) and optimal (<1 cm or <2 cm residual disease) cytoreduction were assessed by summing binomials proportions, and the association with survival was assessed using an inverse variance-weighted meta-analysis of logarithmic hazard ratios. RESULTS: From 1219 unique records identified, 34 studies were selected for inclusion. Studies consisted of single or multi-institutional cohorts of patients collected over a period of 6 to 24 years and included various mixes of histologies (endometrioid, serous, clear cell, and carcinosarcoma) and disease stages (III or IV). In a meta-analysis of the extent of residual disease after primary cytoreductive surgery, we found that 52.1% of cases reached no gross residual disease status (n=18 studies; 1329 patients) and 75% reached <1 cm residual disease status (n=27 studies; 2343 patients). The proportion of cytoreduction for both thresholds was lower for studies of stage IV vs stage III to IV disease (41.4% vs 69.8% for no gross residual disease; 63.2% vs 82.2% for <1 cm residual disease) but did not vary notably by histology. In a meta-analysis of the reported hazard ratios, submaximal (any gross residual disease vs no gross residual disease) and suboptimal (≥1 cm vs <1 cm) cytoreduction thresholds were associated with worse progression-free survival (submaximal hazard ratio, 2.16; 95% confidence interval, 1.45-3.21; I2=68%; suboptimal hazard ratio, 2.55; 95% confidence interval, 1.93-3.37; I2=63%) and overall survival rates (submaximal hazard ratio, 2.57; 95% confidence interval, 2.13-3.10; I2=1%; suboptimal hazard ratio, 2.62; 95% confidence interval, 2.20-3.11; I2=15%). Sensitivity analyses limited to high-quality studies demonstrated consistent results. CONCLUSION: Among cases of advanced stage endometrial cancer undergoing primary cytoreductive surgery, a significant proportion of patients are left with residual disease, which is associated with worse survival outcomes. Further investigations about the roles of neoadjuvant chemotherapy and primary cytoreductive surgery in prospective trials is warranted in this population.
Authors
Albright, BB; Monuszko, KA; Kaplan, SJ; Davidson, BA; Moss, HA; Huang, AB; Melamed, A; Wright, JD; Havrilesky, LJ; Previs, RA
MLA Citation
Albright, Benjamin B., et al. “Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis.Am J Obstet Gynecol, vol. 225, no. 3, Sept. 2021, pp. 237.e1-237.e24. Pubmed, doi:10.1016/j.ajog.2021.04.254.
URI
https://scholars.duke.edu/individual/pub1482001
PMID
33957111
Source
pubmed
Published In
American Journal of Obstetrics and Gynecology
Volume
225
Published Date
Start Page
237.e1
End Page
237.e24
DOI
10.1016/j.ajog.2021.04.254

Use and outcomes of neoadjuvant chemotherapy for metastatic uterine cancer.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) has emerged as an alternative to primary cytoreductive surgery (PCS) for stage IV uterine cancer. We examined utilization, perioperative outcomes and survival for NACT and PCS for stage IV uterine cancer. METHODS: The Surveillance, Epidemiology, End Results-Medicare database was used to identify women with stage IV uterine cancer treated from 2000 to 2015. Women were classified as NACT or PCS. Interval cytoreductive surgery (after NACT) or chemotherapy (after PCS) were recorded. The extent of surgery and perioperative outcomes were estimated for the groups. Multivariable proportional hazards models and Kaplan-Meier analyses were used to examine survival. RESULTS: Among 3037 women, 1629 (53.6%) were treated with primary cytoreductive surgery, 554 (18.2%) with NACT, and 854 (28.1%) received no treatment. Use of NACT increased from 9.5% to 29.2%. After NACT, interval hysterectomy was performed in 159 (28.6%), while within the PCS group, 1052 (64.6%) received chemotherapy. Extended cytoreductive procedures were performed in 71.7% of women who received NACT vs. 79.1% after PCS (P = 0.03). The complication rate was 52.8% for NACT versus 56.2% for PCS (P = 0.42); medical complications were more frequently seen in the PCS group (39.4% versus 28.9%; P = 0.01). There was no difference in cancer specific (P = 0.48) or overall survival (P = 0.25) in women who received both chemotherapy and surgery regardless of whether the initial treatment was NACT or PCS. CONCLUSION: Use of NACT is increasing for advanced stage uterine cancer. There was no difference in survival between NACT and primary cytoreductive surgery and NACT was associated with fewer perioperative medical complications.
Authors
Wright, JD; Huang, Y; Melamed, A; Albright, BB; Hillyer, GC; Previs, R; Hershman, MSDL
MLA Citation
Wright, Jason D., et al. “Use and outcomes of neoadjuvant chemotherapy for metastatic uterine cancer.Gynecol Oncol, vol. 162, no. 3, Sept. 2021, pp. 599–605. Pubmed, doi:10.1016/j.ygyno.2021.06.016.
URI
https://scholars.duke.edu/individual/pub1486016
PMID
34158181
Source
pubmed
Published In
Gynecol Oncol
Volume
162
Published Date
Start Page
599
End Page
605
DOI
10.1016/j.ygyno.2021.06.016

Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia.

In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue. Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.
Authors
Mueller, JL; Morhard, R; DeSoto, M; Chelales, E; Yang, J; Nief, C; Crouch, B; Everitt, J; Previs, R; Katz, D; Ramanujam, N
MLA Citation
Mueller, Jenna L., et al. “Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia.Sci Rep, vol. 11, no. 1, Aug. 2021, p. 16869. Pubmed, doi:10.1038/s41598-021-96223-9.
URI
https://scholars.duke.edu/individual/pub1494616
PMID
34413378
Source
pubmed
Published In
Scientific Reports
Volume
11
Published Date
Start Page
16869
DOI
10.1038/s41598-021-96223-9

Editor's Note: Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer.

Authors
Roh, J-W; Huang, J; Hu, W; Yang, X; Jennings, NB; Sehgal, V; Sohn, BH; Han, HD; Lee, SJ; Thanapprapasr, D; Bottsford-Miller, J; Zand, B; Dalton, HJ; Previs, RA; Davis, AN; Matsuo, K; Lee, J-S; Ram, P; Coleman, RL; Sood, AK
MLA Citation
Roh, Ju-Won, et al. “Editor's Note: Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer.Clin Cancer Res, vol. 27, no. 15, Aug. 2021, p. 4449. Pubmed, doi:10.1158/1078-0432.CCR-21-2115.
URI
https://scholars.duke.edu/individual/pub1493070
PMID
34341054
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
4449
DOI
10.1158/1078-0432.CCR-21-2115