bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of recurrent and metastatic endometrial cancer (RMEC) treated with systemic progestins.
Authors: Kulkarni Anjali , Andrews Wright Natalie , Forget Alyssa N , Mallick Ranjeeta , Ramsay Tim O , Weberpals Johanne I 
Published: June 2022

5585 Background: Recurrent endometrial cancer has a poor prognosis with limited treatment options. Systemic therapy for RMEC includes chemotherapy, immunotherapy and hormonal therapy. Although studies on hormonal therapy have described modest results, agents such as megestrol acetate (megace) continue to be used mainly for low grade, ER+/PR+ve tumors in the advanced and recurrent setting. Overall response rates have been reported in the range of 20-25% with responses up to 25-35% in ER+/PR+ve tumors. Despite comparative response rates to chemotherapy, the use of hormonal therapy in clinical trials in RMEC is hampered by a lack of clear progression-free survival (PFS) data. The primary objective of this study is to determine the PFS in RMEC patients treated with progestins. Methods: A retrospective chart review on RMEC was conducted at The Ottawa Hospital with data sourced from medical records. Main inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥1 one line of progestin treatment. PFS was the time from initiation of progestin therapy until progression of disease (PD) by imaging, biopsy or death. Overall survival (OS) was the time from initiation of progestins until death. Median time to PFS and OS were estimated using the Kaplan-Meier method and compared using a Log-rank Test with 95% confidence interval (CI). Results: Of 2342 cases reviewed, 75 met inclusion criteria. The mean age at the time of primary diagnosis was 66.7 years and the range of follow-up was 1-199 months (mo). Sixty-six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of all patients by grade was: 1: 25 (33.3%), 2: 30 (40.0%) and 3: 20 (26.7%). The median PFS for all patients with grade 1 and 2 RMEC was 15.7 mo (95% CI: 8.0, 19.5), compared to 5.0 mo (3.0, 23.0) for grade 3 disease (p=0.28). The median OS for all patients with grade 1 and 2 versus grade 3 RMEC, was 25.9 mo (15.3, 40.3) versus 12.5 mo (5.7, 35.9), respectively (p=0.12). The number of patients treated with 0 and ≥1 line of chemotherapy was 34 (45.3%) and 41 (54.7%). The median PFS for patients who were naïve to chemotherapy was 17.9 mo (14.3, 27.0), compared to 6.2 mo (3.9, 14.8) for patients who had received ≥1 prior lines of treatment (p=0.09). The median OS was 29.1 mo (17.9, 61.1) for patients who were naïve to chemotherapy, versus 23.0 mo (10.5, 37.6) for patients who were previously exposed (p=0.64). Conclusions: This real-world data suggests that progestins for RMEC have comparable outcomes to other systemic therapies in chemotherapy-exposed patients. Progestins such as megestrol acetate may be considered in the design of RMEC clinical trials.
A phase II trial of IDO-inhibitor, BMS-986205 (IDO), and PD-1 inhibitor, nivolumab (NIVO), in recurrent or persistent endometrial cancer (EC; CA017-056).
Authors: Kyi Chrisann , Rubinstein Maria M , Shah Pooja , Zhou Qin , Iasonos Alexia , Liu Yue , Ramirez Lizbeth , Paroder Viktoriya , Green Angela , Friedman Claire Frances , Grisham Rachel N. , O'Cearbhaill Roisin Eilish , Troso-Sandoval Tiffany A. , Cohen Seth M. , Lichtman Stuart M. , Konner Jason A. , Hensley Martee Leigh , Zamarin Dmitriy , Aghajanian Carol , Makker Vicky 
Published: June 2022

5589 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) allows tumor escape through kynurenine production, which induces regulatory T cells and suppresses effector T-cell proliferation. NIVO, an anti-PD-1 inhibitor can upregulate IDO1, supporting the rationale for combining NIVO with IDO. We report results of NIVO as monotherapy and in combination with IDO inhibitor BMS-986205 in the treatment of pts with recurrent EC. Methods: In this single-institution, randomized phase 2 study, eligible pts must have received 1-4 prior lines of chemotherapy and have measurable disease by RECIST v 1.1. All EC histologies, including carcinosarcoma, were allowed. Pts with microsatellite insufficient (MSI-H) or mismatch repair (MMR)-deficient tumors were excluded. Pts were randomized to NIVO 480mg IV every 4 weeks (wks) with or without IDO 100mg orally daily. Primary endpoints were Overall Response Rate [ORR = Complete Response (CR) + Partial Response (PR)] by RECIST v 1.1. Secondary objectives were duration of response (DOR), median progression free survival (mPFS), PFS rate at 24 wks (PFS24wks) and safety. Overall survival (OS) was also evaluated. Results: Between 10/2019 and 11/2021, pts were randomized to receive either NIVO (n = 12) or NIVO + IDO (n = 12). Median age was 67 years (range 48-82) and median number of prior lines of therapy was 2 (range 1-3). Histologies included serous (n = 5, 21%), endometrioid (n = 10, 42%), clear cell (n = 1, 4.2%), carcinosarcoma (n = 6, 25%), undifferentiated (n = 1, 4.2%), and mucinous (n = 1, 4.2%). In the NIVO + IDO arm, 1 pt achieved partial response (8.3%, CI: 0.9-100%) with DOR of 17.6 months. In the NIVO arm, no responses were observed. Efficacy outcomes are summarized in the table. Treatment-related adverse events (TRAEs) grade ≥ 3 in the NIVO arm included acute kidney injury (n = 1, 8.3%), hypokalemia (n = 1, 8.3%), and thromboembolic event (n = 1, 8.3%). In the NIVO + IDO arm, TRAEs grade ≥ 3 included fatigue (n = 1, 8.3%), and elevated liver function (n = 1, 8.3%). No TRAEs led to study-drug interruption or dose reductions. Conclusions: NIVO monotherapy and in combination with IDO showed acceptable safety in pts with recurrent EC. NIVO in combination with IDO showed ORR of 8.3%. No responses were observed with NIVO monotherapy. The trial closed to accrual due to lack of observed clinical efficacy. Clinical trial information: NCT04106414. [Table: see text]
Impact of molecular features on outcome in African American or Black women with type 1 endometrial cancer.
Authors: Khalife Roy , Park So Hyeon , Erickson Stephanie , Magliocco Genevra , Magliocco Anthony Martin 
Published: June 2022

5597 Background: Among women with endometrial cancer (EC), African American or Black (AAoB) population share a disproportionate burden of cancer deaths. Previous research exploring genetic and molecular explanations revealed White (W) women with EC are more likely to have mutations in PTEN, while AAoB women have higher rates of mutations in p53. However, these studies did not stratify EC by subtype, which occur at different rates among racial groups. Here, we aim to focus on molecular differences between racial groups, specifically in Type 1 EC (T1EC). Methods: Molecular data from TCGA Uterine Corpus Endometrial Carcinoma datasets on cBioPortal was used. Cancer type was filtered to Uterine Endometrioid Carcinoma Type 1 and separated by race. A total of 711 cases were analyzed for gene alterations, expression versus copy number variations, survival curves, and OncoPrints; significant findings and differences between racial groups were noted. The Surveillance, Epidemiology, and End Results (SEER) database was used to access the frequency, rate, and survival of AAoB and W with EC. Results: The genes analyzed on cBioPortal (575 W, 136 AAoB) depicted a similar alteration rate between the two groups, except for the most altered gene, PTEN (66% altered in W, 38% in AAoB). W women with a PTEN and PIK3CA alterations had significantly increased 5-year survival periods (P-value = 1.573e-3), while these alterations had no effect survival in AAoB. Six of the ten most altered genes between the two subgroups, and 6 of the 17 most actionable genes, were statistically significant for W but not for AAoB. SEER analyses depicted a frequency of 51,677 W and 3,915 AAoB, with a rate of 5.7% and 3.9%, respectively. The observed survival was 96.1% after 1 year and 85.6% after 5 years for W, compared to 92.8% after 1 year and 76.9% after 5 years for AAoB. Conclusions: Based on 5 years of data, overall survival (OS) rates among W women with T1EC are better than AAoB. PTEN mutation confers a survival advantage in W but not in AAoB, indicating that in AAoB, PTEN may play a different role or other factors may override the PTEN advantage. Additional analyses revealed non-remarkable findings, suggesting that molecular factors play a minor role in T1EC disparities or that a larger AAoB sample size is necessary. A better understanding of the downstream signaling pathways of common mutations in T1EC is necessary to further elucidate factors that contribute to racial disparities in T1EC. [Table: see text]
Immune phenotypes and T-cell density at the invasive margin correlate with prognosis in epithelial vulvar cancer.
Authors: Burandt E C , Blessin Niclas , Rolschewski Ann-Christin , Lutz Florian , Mandelkow Tim , Yang Cheng , Bady Elena , Reiswich Viktor , Simon Ronald , Sauter Guido , Mahner Sven , de Gregorio Nikolaus , Klapdor Rüdiger , Kalder Matthias , Braicu Ioana , Fuerst Sophie , Klar Maximillian , Strauss Hans-Georg , Prieske Katharina , Woelber Linn Lena 
Published: June 2022

5599 Background: Tumor infiltrating lymphocytes (TILs) in the cancer microenvironment are of prognostic value in many solid tumors. However, only little is known about TILs infiltration and its predictive value in vulvar cancer. Methods: Immunohistochemistry and automated digital image analysis was applied to measure the densities of CD3+ (DAKO, Santa Clara, US; #IR503) and CD8+ (DAKO, Santa Clara, US; #IR623) TILs at the invasive margin (IM) and in the center of 530 vulvar carcinomas. Results: At the IM the mean immune cell density was significantly higher compared to the center of the tumor (CD3: 1772±1105, CD8: 769±644 cells/mm2 vs. CD3: 518±570, CD8: 301±445 cells/mm2, p≤0.0001). An elevated density of CD3+ T-cell at the IM was significantly associated with low tumor stage (p = 0.0012). The 2-years OS and PFS rate was significantly different between the group with a high (OS: 82%, PFS: 65%), moderate (OS: 76%, PFS: 55%), or low CD3+ T-cell density at the IM (OS: 64%, p = 0.008, PFS: 44%, p = 0.02). The prognostic impact of CD3+ cells in the center of the tumor was weaker compared to the IM (OS p = 0.046, PPS p = 0.031) and lacking for CD8+ T-cell densities at any location (p≥0.14 each). Unsupervised clustering of CD3+ and CD8+ T-cell densities identified three major subgroups corresponding to the immune desert (137 patients), immune excluded (220 patients) and immune inflamed phenotypes (133 patients). Survival analysis revealed a particular poor prognosis for the immune desert phenotype for OS (0.0071) and PFS (0.0027). Conclusions: This study demonstrates a prognostical relevance of the immunphenotype and the distribution of CD3+ T-cells in vulvar cancer. Their value for therapeutic decision making has to be determined in the future.
Clinical implications for patients with discordant oncotype and MammaPrint results.
Authors: Socoteanu Matei P. , O'Shaughnessy Joyce , Hoskins Kent , Brufsky Adam , Graham Cathy Lynne , Vukelja Svetislava J. , Misleh Jamal Ghazi , Tedesco Karen L. , Layeequr Rahman Rakhshanda , Lee June , Berrocal Julian , Sharma Kamal , Begas Albert , Crozier Jennifer , Grady Ian , D'Abreo Nina , Kuilman Midas M. , Nguyen Holly , Blumencranz Lisa Eileen , Audeh M. William ,   FLEX Investigators Group
Published: June 2022

560 Background: Genomic tests provide critical information regarding risk of recurrence and inform treatment plans by identifying those patients who may safely forgo chemotherapy (CT) or shorten endocrine therapy (ET) duration. The IMPACT trial demonstrated that the 70 -gene risk of recurrence assay MammaPrint (MP) and 80-gene subtyping assay BluePrint (BP) inform treatment planning and increase physician confidence. However, not all genomic tests yield the same results. To examine consistency among genomic tests, we analyzed therapy implications for patients who received results from both MP/BP and Recurrence Score (RS). Methods: Using the FLEX cohort (NCT03053193), we examined 723 patients who received both MP/BP, and RS genomic assays. We assessed the potential clinical impact by examining the standardized reports of RS and MP/BP results. MP classified tumors as either ultralow, low, or high risk and BP further classified them as luminal, basal, or HER2. RS classified tumors as low (RS0-10), intermediate (RS11-25), or high (RS26-100). Clinical impact was defined as discordant genomic resulting in different treatment recommendations. Undertreatment indicates patients who may not have received CT based on RS but may have based on MP/BP and overtreatment those patients who would have received CT based on RS, but not based on MP/BP. ET duration too long is indicative of those patients that are ultralow risk by MP, regardless of RS classification, as those patients may have safely reduced the duration of their ET. Although outcomes are not available, treatment impacts are presuming a patient received both tests, but the treating physician opted to guide therapy according to the RS results rather than MP/BP. Results: We observed discordant results with a clinical impact in 49% (354) of patients, with 34% (244) who may be undertreated, 2% (11) potentially overtreated, and 14% (99) who may not be given the option to decrease ET to two years based on ultralow MP genomic risk. Of 114 concordant High-Risk tumors, 14% (16) were genomically Basal, and likely to require more aggressive CT than typically used in ER+ cancers. The table below summarizes the results. Conclusions: More than half of the patients in this cohort were at potential risk for undertreatment or overtreatment. The risk to patients is far more significant in the event of undertreatment, as this may result in incurable metastatic recurrence. Discordance between RS and MP/BP most often results in potential undertreatment if RS is used for treatment decision-making. Clinical trial information: NCT03053193.
Is there a role for the oncotype DX breast recurrence score genomic assay in estrogen receptor-low positive breast cancer?
Authors: Giordano Julia , McGrath Monica , Harrison Beth , Kantor Olga , Vora Halley , Burstein Harold J. , Tolaney Sara M. , King Tari A. , Mittendorf Elizabeth A. 
Published: June 2022

564 Background: The Oncotype DX Breast Recurrence Score assay is widely used in estrogen receptor (ER)-positive breast cancer patients to help determine the potential benefit of chemotherapy. However, little is known about the value of the test in breast cancer patients who have ER-low positive (1-10%) cancers. The purpose of this study was to determine the potential utility of the Oncotype test for these patients by describing the range of Recurrence Score (RS) results and patient outcomes. Methods: Patients treated between 8/2011-8/2020 for primary non-metastatic breast cancer that was ER-low positive (10%) and HER2-negative in whom tissue from their surgical excision specimen was available to perform the Oncotype DX assay were identified. Clinicopathologic characteristics were abstracted from patient charts, and the RS result was determined. Results: 38 women with ER-low positive breast cancer and available tissue were identified. The median age was 56.5 (range 36-94); 34 patients were Caucasian, 2 Black, 1 Asian and 1 Hispanic. Thirty-seven patients underwent surgery as their initial intervention and 1 received neoadjuvant chemotherapy. The final pathologic anatomic stage was IA in 26 (68.4%), IB in 10 (26.3%) and IIA in 2 (5.3%); the pathologic nodal status was pN0 in 24 (63.2%), pN0i+ in 3 (7.9%), pN1mi in 1 (2.6%), pN1 in 6 (15.8%) and pNx in 4 (10.5%). The average and median RS was 49 with a range of 23-72; only 2 patients had a RS 25. One patient with RS = 24 was a 64yo with pT1cN0 disease who received chemotherapy + endocrine therapy therefore could potentially have been spared chemotherapy based on the RS result and the TAILORx trial data. Six patients had previously had a RS determined on their diagnostic core biopsy (RS = 46, 58, 45, 47, 51 and 52); the RS on their surgical specimen was concordant (RS = 45, 54, 47, 48, 47, and 50). The ER status as determined by the Oncotype DX assay was positive for 8 (21%) patients. Adjuvant therapy included: chemotherapy and endocrine therapy in 13 (34.2%), chemotherapy alone in 13 (34.2%) and endocrine therapy alone in 4 (10.5%). 8 (21.1%) received no adjuvant therapy. After a median follow-up of 40 months (range 3-106), 3 patients have experienced a recurrence; all 3 had received chemotherapy. The 3-year recurrence free survival rate was 97.0% (95% CI: 96.9-97.1%). All 3 of these patients had a local recurrence; 2 also had a distant recurrence which they ultimately succumbed to. The 3-year disease-specific survival rate was also 97.0% (95% CI: 96.9-97.1%). Conclusions: The majority of the patients with low ER+/HER2- breast cancer had RS > 25 suggesting these tumors are high-risk, more similar to ER- disease. The RS result is of limited utility in ER-low positive patients, as these data indicate that most would benefit from chemotherapy.
Impact of neighborhood disadvantage on biological and clinical indicators of anxiety among newly diagnosed patients with breast cancer.
Authors: Goel Neha , Ream Molly , Antoni Michael 
Published: June 2022

568 Background: Women living in disadvantaged neighborhoods consistently having worse breast cancer (BC) survival. Recent studies have identified that disparities by neighborhood disadvantage persist after controlling for patient, tumor, and National Comprehensive Cancer Network-guideline concordant treatment. This persistent disparity suggests unaccounted mechanisms by which neighborhood disadvantage “gets under the skin” to impact to shorter BC survival. Methods: Women with stage 0-3 BC between 1998-2005 were enrolled in a clinical trial for stress management 2-10 weeks post-surgery and before initiating adjuvant treatment. At baseline, women provided an evening-time serum cortisol sample and were administered a structured clinical interview of anxiety symptoms (Hamilton Anxiety Rating Scale; HAM-A). Of the 240 women who enrolled in the study and completed baseline procedures, home addresses were provided by 225 women (93.8%). The addresses were used to determine the Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage, using the University of Wisconsin Neighborhood Atlas. Women were categorized as low (1-3) versus high (4-10) ADI. Linear regression analyses was used to assess the relationship between ADI and serum cortisol and logistic regression to assess whether ADI group predicted the presence of clinically significant anxiety per the HAM-A. Results: The average age of our population was 50.4 years old (range 23-70 years) and the majority were non-Hispanic White (63.6%). Most patients had stage 1 (37.8%) or 2 (38.2%) disease. The majority lived in advantaged neighborhoods (low ADI, 77.8%). On the HAM-A, 46.8% of women reported clinically significant anxiety symptoms. When controlling for age, stage, and type of surgery, women with a high ADI had higher cortisol levels than women in with a low ADI (Beta =.19, t(117) = 2.18, p=.031). Moreover, accounting for age, stage, and type of surgery, women with a high ADI were nearly two times as likely to have clinically significant anxiety symptoms in the HAM-A clinical interview (OR 1.99, 95%CI 1.01, 3.90, p =.046). Conclusions: This study identified that neighborhood disadvantage is significantly associated with higher levels of cortisol and clinical anxiety. Future studies need to evaluate stress pathways as a potential mechanism by which neighborhood disadvantage "gets under the skin" to impact BC-specific survival.
Mode of detection of second breast cancers in patients undergoing surveillance after treatment of ductal carcinoma in situ.
Authors: Waites Bethany , Lyon Liisa , Kuehner Gillian , Odele Patience , Habel Laurel A. , Shirazi Aida , Liu Raymond 
Published: June 2022

571 Background: The incidence of ductal carcinoma in situ (DCIS) has increased, resulting in more women undergoing post-treatment surveillance for second breast cancers. National Comprehensive Cancer Network (NCCN) guidelines recommend annual breast imaging and physical exam every 6-12 months for five years, and then annually. We assessed mode of detection (imaging, patient-reported, or physical exam) of secondary DCIS and/or invasive breast cancer in a large cohort of DCIS patients undergoing surveillance after treatment of primary DCIS. Methods: We performed a retrospective cohort study of DCIS patients treated between 1/1/2008 and 1/1/2011 within a large integrated health care system. Patients had a minimum of 5 years of follow up. Patient demographics, treatment for primary DCIS, and tumor characteristics (of both primary DCIS and secondary cancer) were obtained from the electronic health record or from manual chart review. Chart review also included mode of detection of secondary breast cancers. Results: Our study cohort consisted of 1561 women with DCIS, with a median age of 59 years (range 32-92) at time of diagnosis. Among initial DCIS tumors, tumor grade was low/intermediate in 942 (60.3%) and high in 619 (39.7%); 1274 (81.6%) were estrogen receptor positive, and 988 (63.3%) progesterone receptor positive. Surgical treatment for the initial DCIS included lumpectomy (n=1134, 72.6%), unilateral mastectomy (n=320, 20.5%), or bilateral mastectomy (n=61, 3.9%), and included sentinel lymph node biopsy in 211 (14%) of patients. Additionally, 691 (44.3%) received radiation therapy and 440 (28.2%) received endocrine therapy. The cohort was followed for a median of 120 months, during which we identified 179 women (11.5%) with a secondary cancer detected at a median time of 57 months. Of the second breast cancers, 77 (43.0%) were ipsilateral, 98 (54.8%) contralateral, and 4 (2.2%) presented with distant metastases; 110 (61.5%) were invasive, 65 (36.3%) were DCIS, and 4 (2.2%) Paget’s disease. See table for mode of detection of second breast cancers. Conclusions: In our cohort of patients undergoing surveillance following initial diagnosis and treatment of DCIS, 2% of secondary breast cancers were detected by clinical breast exam, a rate similar to incidental detection at time of plastic surgery. These results can help inform future recommendations for surveillance of second breast cancers in DCIS patients. [Table: see text]