Publications by authors named "Katherine C Kurnit"

24 Publications

  • Page 1 of 1

Successful treatment of squamous cell carcinoma arising from a presumed ovarian mature cystic teratoma with pembrolizumab.

Gynecol Oncol Rep 2021 Aug 22;37:100837. Epub 2021 Jul 22.

Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Chicago, Chicago, IL, United States.

•Metastatic SCC arising from the ovary is rare, and the optimal treatment is unknown.•Pembrolizumab successfully treated a patient with metastatic SCC.•Patients on pembrolizumab should be monitored for immune-related adverse events.
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http://dx.doi.org/10.1016/j.gore.2021.100837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326349PMC
August 2021

Low grade endometrioid endometrial cancer: complexities beyond p53abn.

Int J Gynecol Cancer 2021 09 28;31(9):1312. Epub 2021 Jul 28.

Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois, USA.

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http://dx.doi.org/10.1136/ijgc-2021-002941DOI Listing
September 2021

Pembrolizumab and lenvatinib versus carboplatin and paclitaxel as first-line therapy for advanced or recurrent endometrial cancer: A Markov analysis.

Gynecol Oncol 2021 Aug 6;162(2):249-255. Epub 2021 Jun 6.

University of Chicago Medicine, Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, 5841 S Maryland Ave, Chicago, IL 60637, USA.

Objective: To determine the cost effectiveness of pembrolizumab/lenvatinib (P/L) versus standard-of-care carboplatin/paclitaxel (C/T) as first-line systemic therapy for patients with advanced/recurrent endometrial cancer.

Methods: We designed a Markov model to simulate treatment outcomes for advanced/recurrent endometrial cancer patients whose tumors are either microsatellite stable (MSS) or have high microsatellite instability (MSI-high). We adopted a healthcare sector perspective for the analysis. Model inputs for costs, health utility, and clinical estimates were obtained from the literature including data from GOG0209 and KEYNOTE-146. Primary outcomes included costs of care, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The time-horizon was three years and the discount rate was 3% annually.

Results: In a MSS cohort, compared to C/T, first-line treatment with P/L increased treatment costs by $212,670 and decreased QALYs by 0.28 per patient. In a MSI-high cohort, compared to C/T, P/L increased costs by $313,487 and increased QALYs by 0.11 per patient, representing an ICER of $2,849,882 per QALY. Sensitivity analyses found that the price of the new drugs was the most important determinant of the ICER and that the price of the new drugs would need to decrease by 85% to $2817 per cycle to reach a $150,000/QALY threshold.

Conclusion: In the MSS model, we found that first-line therapy for advanced or recurrent endometrial cancer with P/L increased costs and worsened outcomes compared to C/T. In the MSI-high model, P/L improved survival and QALYs compared to C/T but was not cost-effective at the current cost of the drugs.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.038DOI Listing
August 2021

Differences in Sociodemographic Disparities Between Patients Undergoing Surgery for Advanced Colorectal or Ovarian Cancer.

Ann Surg Oncol 2021 May 6. Epub 2021 May 6.

Department of Surgery, University of Chicago, Chicago, IL, USA.

Background: Cytoreductive surgery (CRS) for ovarian cancer with peritoneal metastases (OPM) is an established treatment, yet access-related racial and socioeconomic disparities are well documented. CRS for colorectal cancer with peritoneal metastases (CRPM) is garnering more widespread acceptance, and it is unknown what disparities exist with regards to access.

Methods: This retrospective cross-sectional multicenter study analyzed medical records from the National Cancer Database from 2010 to 2015. Patients diagnosed with CRPM or ORP only and either no or confirmed resection were included. Patient- and facility-level characteristics were analyzed using uni- and multivariable logistic regressions to identify associations with receipt of CRS.

Results: A total of 6634 patients diagnosed with CRPM and 14,474 diagnosed with OPM were included in this study. Among patients with CRPM, 18.1% underwent CRS. On multivariable analysis, female gender (odds ratio [95% CI] 2.04 [1.77-2.35]; P < 0.001) and treatment at an academic or research facility (OR 1.55 [1.17-2.05]; P = 0.002) were associated with CRS. Among patients with OPM, 87.1% underwent CRS. On multivariable analysis, treatment at facilities with higher-income patient populations was positively associated with CRS, while age (OR 0.97 [0.96-0.98]; P < .0001), use of nonprivate insurance (OR 0.69 [0.56-0.85]; P = 0.001), and listed as Black (OR 0.62 [0.45-0.86]; P = 0.004) were negatively associated with CRS.

Conclusion: There were more systemic barriers to CRS for patients with OPM than for patients with CRPM. As CRS becomes more widely practiced for CRPM, it is likely that more socioeconomic and demographic barriers will be elucidated.
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http://dx.doi.org/10.1245/s10434-021-10086-yDOI Listing
May 2021

Chemotherapy response score as a prognostic tool in patients with advanced stage endometrial carcinoma treated with neoadjuvant chemotherapy.

Int J Gynecol Cancer 2021 06 8;31(6):852-858. Epub 2021 Apr 8.

Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois, USA

Background: Chemotherapy response score (CRS) applied to interval debulking specimens quantifies histopathologic response to neoadjuvant chemotherapy in patients with advanced ovarian carcinoma and correlates with progression-free and overall survival.

Objective: To investigate whether the chemotherapy response score could be applied to interval debulking specimens in patients with advanced endometrial carcinoma and be a prognostic indicator.

Methods: The study included patients with clinical stage III-IV endometrial carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery. Chemotherapy response scores were assigned to omental and adnexal metastases, and categorized as no/minimal (CRS1), partial (CRS2), and complete/near-complete (CRS3) response to neoadjuvant chemotherapy. Descriptive statistics were used to evaluate baseline characteristics and feasibility of chemotherapy response score assessment. Univariate analyses were used to evaluate associations between the chemotherapy response score, complete cytoreduction, and survival.

Results: This study included 40 patients. The median age was 63.5 years, and 31 patients (78%) had stage IV disease. Thirty patients had an omentectomy, 22 patients (73%) had an omental chemotherapy response score assigned. Thirty-nine patients had a bilateral salpingo-oophorectomy, 28 patients (72%) had an adnexal chemotherapy response score assigned. Omental CRS2 and CRS3 were associated with improved progression-free survival (CRS2: HR=0.18, p<0.01; CRS3: HR=0.11, p<0.01) and overall survival (CRS2: HR=0.10, p<0.01; CRS3: HR=0.16, p=0.04). Adnexal CRS2 and CRS3 were associated with improved progression-free survival (CRS2: HR=0.23, p<0.01; CRS3: HR=0.20, p=0.03). Chemotherapy response scores were also associated with an increased likelihood of having a complete cytoreduction.

Conclusion: Chemotherapy response score can be applied to omental and adnexal metastases in patients with advanced endometrial carcinoma and was associated with survival and complete cytoreduction. The score may be a prognostic indicator and help to guide first-line treatment of patients with endometrial carcinoma.
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http://dx.doi.org/10.1136/ijgc-2020-002202DOI Listing
June 2021

Loss of CD73 shifts transforming growth factor-β1 (TGF-β1) from tumor suppressor to promoter in endometrial cancer.

Cancer Lett 2021 05 17;505:75-86. Epub 2021 Feb 17.

Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address:

In many tumors, CD73 (NT5E), a rate-limiting enzyme in adenosine biosynthesis, is upregulated by TGF-β and drives tumor progression. Conversely, CD73 is downregulated in endometrial carcinomas (EC) despite a TGF-β-rich environment. Through gene expression analyses of normal endometrium samples of the uterine cancer TCGA data set and genetic and pharmacological studies, we discovered CD73 loss shifts TGF-β1 from tumor suppressor to promoter in EC. TGF-β1 upregulated CD73 and epithelial integrity in vivo in the normal endometrium and in vitro in early stage EC cells. With loss of CD73, TGF-β1-mediated epithelial integrity was abrogated. EC cells developed TGF-β1-mediated stress fibers and macromolecule permeability, migration, and invasion increased. In human tumors, CD73 is downregulated in deeply invasive stage I EC. Consistent with shifting TGF-β1 activity, CD73 loss increased TGF-β1-mediated canonical signaling and upregulated cyclin D1 (CCND1) and downregulated p21 expression. This shift was clinically relevant, as CD73/CCND1 expression associated with poor tumor differentiation, increased myometrial and lymphatic/vascular space invasion, and patient death. Further loss of CD73 in CD73 expressing advanced stage EC cells increased TGF-β-mediated stress fibers, signaling, and invasiveness, whereby adenosine A1 receptor agonist, CPA, dampened TGF-β-mediated invasion. These data identify CD73 loss as essential for shifting TGF-β activity in EC.
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http://dx.doi.org/10.1016/j.canlet.2021.01.030DOI Listing
May 2021

Updates and New Options in Advanced Epithelial Ovarian Cancer Treatment.

Obstet Gynecol 2021 01;137(1):108-121

Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, and the Department of Medicine/Section of Hematology Oncology, University of Chicago, Chicago, Illinois.

The medical and surgical treatment strategies for women with epithelial ovarian cancer continue to evolve. In the past several years, there has been significant progress backed by landmark clinical trials. Although primary epithelial ovarian cancer is still treated with a combination of surgery and systemic therapy, more complex surgical procedures and novel therapeutics have emerged as standard of care. Cytotoxic chemotherapy and maximal surgical effort remain mainstays, but targeted therapies are becoming more widespread and new data have called into question the role of surgery for women with recurrent disease. Poly ADP-ribose polymerase inhibitors have improved progression-free survival outcomes in both the frontline and recurrent settings, and their use has become increasingly widespread. The recent creation of treatment categories based on genetic changes reinforces the recommendation that all women with epithelial ovarian cancer have germline genetic testing, and new biomarker-driven drug approvals indicate that women may benefit from somatic molecular testing as well. To continue to identify novel strategies, however, enrollment on clinical trials remains of the utmost importance. With the evolving data on surgical approaches, targeted therapies such as antiangiogenics and poly ADP-ribose polymerase inhibitors, and the new therapeutic agents and combinations in development, we hope that advanced epithelial ovarian cancer will eventually transition from an almost universally fatal disease to one that can increasingly be cured.
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http://dx.doi.org/10.1097/AOG.0000000000004173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737875PMC
January 2021

Immune checkpoint inhibitors in women with gynecologic cancers: Practical considerations.

Gynecol Oncol 2020 09 5;158(3):531-537. Epub 2020 Jul 5.

Department of Medicine, Section of Hematology-Oncology, The University of Chicago, Chicago, IL, United States.

Immune checkpoint inhibitors are an exciting new class of cancer therapeutics. Recently, a PD-1 inhibitor has been approved by the Food and Drug Administration for several indications that are relevant to patients with gynecologic malignancies. In this review, we explore the clinical considerations for the use of checkpoint inhibitor therapy in this population. Specifically, we will discuss the approved indications, recommended dosing, clinical monitoring while on treatment, common adverse events, and treatment of adverse events should they arise. Additionally, we will review mechanisms of resistance and other challenges associated with the use of checkpoint inhibitors. We will conclude with a discussion of possible future directions for immunotherapy in women with gynecologic cancers.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.499DOI Listing
September 2020

PARP inhibition in the ovarian cancer patient: Current approvals and future directions.

Pharmacol Ther 2020 09 23;213:107588. Epub 2020 May 23.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address:

Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as biomarker-wildtype tumors. They have also gained momentum not only as a treatment strategy, but as a maintenance strategy as well. While PARP inhibitors were initially ev aluated in the recurrent setting, they have now moved to frontline therapy. This review will discuss the current FDA indications of the clinically available PARP inhibitors for treatment and maintenance therapies. We will then review the recently completed and ongoing clinical trials which may inform future clinical approvals.
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http://dx.doi.org/10.1016/j.pharmthera.2020.107588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331065PMC
September 2020

Slow and steady wins the race: precision medicine for low risk endometrial cancer.

Int J Gynecol Cancer 2020 06 5;30(6):724-725. Epub 2020 May 5.

Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

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http://dx.doi.org/10.1136/ijgc-2020-001467DOI Listing
June 2020

Effects of Gastrointestinal-Type Chemotherapy in Women With Ovarian Mucinous Carcinoma.

Obstet Gynecol 2019 12;134(6):1253-1259

Departments of Gynecologic Oncology and Reproductive Medicine, Biostatistics, and Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas; the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Olive View/UCLA Medical Center, Los Angeles, California; and the Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, Maryland.

Objective: To estimate whether gastrointestinal-type chemotherapy was associated with improved survival compared with standard gynecologic regimens for women with ovarian mucinous carcinoma.

Methods: We conducted a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers. Demographic and clinical information was abstracted from the medical records. Gastrointestinal-type chemotherapy contained 5-fluorouracil, capecitabine, irinotecan, or oxaliplatin. Gynecologic regimens included standard carboplatin or cisplatin. Bevacizumab treatment was allowed in both groups. Summary statistics were used to compare baseline characteristics; Kaplan-Meier product-limit estimator was used to compare survival outcomes.

Results: Fifty-two patients received either gastrointestinal-type chemotherapy (n=26; 50%) or a standard gynecologic regimen (n=26; 50%). Three-quarters of tumors were early-stage (I or II), 68% grade 1 or 2 and 88% of patients had no gross residual disease after surgery. Patients receiving gastrointestinal-type chemotherapy were more likely to receive bevacizumab (50% vs 4%; P<.001), but there were no other differences in clinical or demographic characteristics. Unadjusted overall survival analyses showed that gastrointestinal-type chemotherapy was associated with better overall survival (hazard ratio 0.2, 95% CI 0.1-0.8), as were early stage tumors and having no gross residual disease.

Conclusion: Gastrointestinal-type chemotherapy with or without bevacizumab was associated with improved survival and should be considered in patients with ovarian mucinous carcinoma requiring adjuvant therapy.
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http://dx.doi.org/10.1097/AOG.0000000000003579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100606PMC
December 2019

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

Gynecol Oncol 2019 10 16;155(1):39-50. Epub 2019 Aug 16.

Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan.

Objective: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer.

Methods: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy.

Results: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged.

Conclusion: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.
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http://dx.doi.org/10.1016/j.ygyno.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537353PMC
October 2019

Rapidly Changing Landscape of Fallopian Tube Carcinoma.

J Oncol Pract 2019 07 8;15(7):383-384. Epub 2019 Jul 8.

1 The University of Texas MD Anderson Cancer Center, Houston, TX.

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http://dx.doi.org/10.1200/JOP.19.00248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881185PMC
July 2019

Microsatellite instability in endometrial cancer: New purpose for an old test.

Cancer 2019 07 26;125(13):2154-2163. Epub 2019 Mar 26.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1002/cncr.32058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763363PMC
July 2019

Using PARP Inhibitors in the Treatment of Patients With Ovarian Cancer.

Curr Treat Options Oncol 2018 11 15;19(12). Epub 2018 Nov 15.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Dr. CPB 6.3279, Houston, TX, 77030, USA.

Opinion Statement: Use of poly(ADP-ribose) polymerase (PARP) inhibitors has greatly increased over the past 5 years. With several new Food and Drug Administration (FDA) approvals, three PARP inhibitors have entered into standard of care treatment for epithelial ovarian cancer (including ovarian, fallopian tube, and primary peritoneal cancer). Olaparib and rucaparib currently have indications for treatment of recurrent BRCA mutant ovarian cancer. Olaparib, rucaparib, and niraparib all have indications for maintenance therapy in recurrent platinum-sensitive ovarian cancer after response to platinum-based therapy. In our practice, we use both olaparib and rucaparib in the recurrent setting, and all three PARP inhibitors in the maintenance setting. Choice of which PARP inhibitor to use in either setting is largely based upon baseline laboratory values, number of prior therapies, and presence of a BRCA mutation and/or homologous recombination deficiency (HRD). As (HRD) and other biomarker assessments continue to improve, we anticipate being able to better identify which patients might most benefit from PARP inhibitor therapy in the future. The clinically available PARP inhibitors are currently undergoing extensive investigations in clinical trials. Other newer agents such as talazoparib, veliparib, 2X-121, and CEP-9722 are in earlier stages of development. As more FDA-approved indications for PARP inhibitor therapy in ovarian cancer become available, we anticipate the decision of which PARP inhibitor to use will become increasingly complex.
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http://dx.doi.org/10.1007/s11864-018-0572-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240125PMC
November 2018

Prognostic factors impacting survival in early stage uterine carcinosarcoma.

Gynecol Oncol 2019 01 8;152(1):31-37. Epub 2018 Nov 8.

Department of Gynecologic Oncology and Reproductive Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America. Electronic address:

Objective: Evaluate the impact of clinicopathologic characteristics and adjuvant treatment on survival outcomes in early stage uterine carcinosarcoma patients.

Methods: We performed a retrospective cohort study of women with stage I or II uterine carcinosarcoma at our institution between March 1990 and June 2016. All pathology had been reviewed and confirmed by gynecologic pathologists. Data were extracted from the electronic medical record. Descriptive and comparative statistics were used to compare clinicopathologic characteristics. Univariable and multivariable analyses were performed for survival outcomes.

Results: 140 patients were identified. Median age was 67 years (range: 36-91). Median follow-up was 39.1 months (2.9-297.4). The majority of patients had stage IA (67%) versus stage IB (21%) or stage II (11%) disease. The majority of patients (63%) received adjuvant treatment: vaginal brachytherapy only (14%); whole pelvic radiation therapy only (16%); chemotherapy only (n = 13, 9%); combination chemotherapy and vaginal brachytherapy (15%); combination chemotherapy and whole pelvic radiation (9%). 52 patients (37%) received no adjuvant therapy. Median overall survival (OS) was 48.0 months (95% CI 32.7-80.9). On multivariable analysis for OS, advancing age (HR 1.05, 95% CI 1.03-1.08, p < 0.001), higher stage (stage IB: HR 1.64, 95% CI 0.91-2.95, p = 0.10; stage II: HR 3.04, 95% CI 1.51-6.13, p = 0.002), and the presence of a rhabdomyosarcoma component (HR 1.66, 95% CI 1.02-2.70, p = 0.04) were significantly associated with worse OS.

Conclusions: Advancing age, stage, and the presence of a rhabdomyosarcoma component were all associated with worse OS in patients with early stage uterine carcinosarcoma. New treatment algorithms should incorporate factors aside from stage alone.
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http://dx.doi.org/10.1016/j.ygyno.2018.10.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321768PMC
January 2019

Moving From Mutation to Actionability.

Am Soc Clin Oncol Educ Book 2018 May;38:495-503

From the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; University of Toronto, Department of Medicine, Toronto, ON, Canada.

The diffusion of high-throughput next-generation sequencing technologies has sustained massive parallel sequencing of tumor tissue providing a deep insight into tumor biology and advancement of personalized medicine. A substantial number of targeted agents have been investigated in gynecologic cancer and some have received U.S. Food and Drug Administration approval, like PARP inhibitors in ovarian cancer, bevacizumab in ovarian and cervical cancers, and pembrolizumab in microsatellite-unstable or mismatch repair-deficient endometrial cancer. To improve effectiveness of targeted therapy, identification of predictive biomarkers able to guide the selection of the correct drug for the correct patient is crucial. Different limitations must be addressed to favor a more rapid implementation of a genotyping approach in treatment selection, such as the possibility to easily assess tumor heterogeneity and clonal evolution along the disease trajectory and the need for innovative trial designs like adaptive or basket trials incorporating molecular features as selection criteria. A deep dive into the genomic features of exceptional responders may also favor better understanding of tumor biology, mechanism of action of a specific target agent, and identification or predictive biomarkers for subsequent tailored studies.
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http://dx.doi.org/10.1200/EDBK_199665DOI Listing
May 2018

Nuclear β-catenin localization and mutation of the CTNNB1 gene: a context-dependent association.

Mod Pathol 2018 10 24;31(10):1553-1559. Epub 2018 May 24.

Department of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Although the majority of low-grade, early-stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes β-catenin) mutations identify a subset of low-grade, early-stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the β-catenin protein from the membrane to the nucleus and activation of Wnt/β-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of β-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wild-type tumors. Nuclear localization of β-catenin had 100% specificity in distinguishing CTNNB1 mutant from wild type, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5-10% of tumor cells with β-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. The extent of β-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of β-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of β-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. The extent of nuclear localization may be tumor type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of β-catenin is absent.
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http://dx.doi.org/10.1038/s41379-018-0080-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168348PMC
October 2018

Precision Oncology Decision Support: Current Approaches and Strategies for the Future.

Clin Cancer Res 2018 06 2;24(12):2719-2731. Epub 2018 Feb 2.

Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and highlights strategies for optimizing decision support. Specific attention is given to the assays currently available for molecular testing, as well as considerations for interpreting alteration information. This article also discusses strategies for identifying and matching patients to clinical trials, current challenges, and proposals for future development of precision oncology decision support. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004235PMC
June 2018

"Personalized Cancer Therapy": A Publicly Available Precision Oncology Resource.

Cancer Res 2017 11;77(21):e123-e126

Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.

High-throughput genomic and molecular profiling of tumors is emerging as an important clinical approach. Molecular profiling is increasingly being used to guide cancer patient care, especially in advanced and incurable cancers. However, navigating the scientific literature to make evidence-based clinical decisions based on molecular profiling results is overwhelming for many oncology clinicians and researchers. The Personalized Cancer Therapy website (www.personalizedcancertherapy.org) was created to provide an online resource for clinicians and researchers to facilitate navigation of available data. Specifically, this resource can be used to help identify potential therapy options for patients harboring oncogenic genomic alterations. Herein, we describe how content on www.personalizedcancertherapy.org is generated and maintained. We end with case scenarios to illustrate the clinical utility of the website. The goal of this publicly available resource is to provide easily accessible information to a broad oncology audience, as this may help ease the information retrieval burden facing participants in the precision oncology field. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-0341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774617PMC
November 2017

CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence.

Mod Pathol 2017 07 10;30(7):1032-1041. Epub 2017 Mar 10.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46-200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. In all, 342 patients were identified, 245 of which had endometrioid histology. For grades 1-2, stages I-II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03-1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69-13.21), and TP53 mutation (HR 4.07, 95% CI 1.57-10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grades 1-2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38-9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.
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http://dx.doi.org/10.1038/modpathol.2017.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493522PMC
July 2017

Squamous Cell Carcinoma of the Vulva Presenting as an Isolated Inguinal Lymph Node Metastasis: A Case Report.

J Reprod Med 2016 Nov-Dec;61(11-12):612-14

Background: Vulvar carcinoma is usually diagnosed after a patient notices bleeding, pruritis, or a lesion. We describe a case of vulvar carcinoma presenting as an isolated lymph node metastasis in the setting of negative pelvic examinations, with interval development of a vulvar lesion.

Case: A 45-year-old woman presented with a left groin mass, and a biopsy revealed squamous cell carcinoma of unknown primary. She underwent an extensive work-up including several evaluations by gynecologic oncologists, all with negative results. Only after 11 months of clinical monitoring did a vulvar lesion appear and the primary tumor was diagnosed.

Conclusion: Cancers of unknown primary site presenting in an inguinal lymph node are relatively rare. Vulvar carcinoma should remain in the differential diagnosis even in the setting of a previously negative pelvic examination.
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October 2018

Increased prevalence of comorbid conditions in women with uterine cancer.

Gynecol Oncol 2015 Sep 6;138(3):731-4. Epub 2015 Jul 6.

Department of Reproductive Medicine, University of California San Diego, Rebecca and John Moores Cancer Center, San Diego, CA, USA.

Objectives: To compare comorbidities of women with uterine cancer (UC) to controls so as to aid in development of survivorship care plans and programs.

Methods: Retrospective cohort study using the University HealthSystem Consortium (UHC) database that compared women who had a hysterectomy for UC to women without UC undergoing hysterectomy. Frequencies and odds ratios (ORs) of 26 comorbidities were calculated. Mantel-Haenszel stratified ORs were determined to correct for different age distributions between the UC and control groups using UHC predetermined age groups.

Results: 23,227 patients in the dataset were included in the UC cohort, and 142,601 patients served as controls. Uncorrected ORs≥2 were found for hypertension, diabetes, obesity, congestive heart failure, pulmonary circulatory diseases, peripheral vascular disease, and renal failure. Higher ORs for UC remained significant after stratification by age for hypertension (OR=1.7), diabetes (OR=2.1), obesity (OR=3.3), congestive heart failure (OR=1.5), pulmonary circulatory disorders (OR=1.7), and renal failure (OR=1.2).

Conclusions: Multiple comorbid conditions, specifically those related to the metabolic syndrome, were more prevalent in UC survivors than in the general population, and this difference persisted after adjustment for age. UC survivorship programs should plan to allocate resources to account for these differences in healthcare needs.
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http://dx.doi.org/10.1016/j.ygyno.2015.07.004DOI Listing
September 2015
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