bluuebunny/crossref_metadata_2025 huggingface dataset:
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]
The percentage of unnecessary mastectomy due to false size prediction by preoperative imaging studies in patients with breast cancer who underwent neoadjuvant chemotherapy.
Authors: Han Yireh , Han Wonshik
Published: June 2022

573

Background: It was shown that, with neoadjuvant chemotherapy (NCT), about 40-50% of breast conserving surgery (BCS) ineligible breast cancer converted to BCS-eligible. Because the estimated tumor extent with imaging after NCT tend to be discordant with pathologic extent, we assumed that proportion of unnecessary total mastectomy (TM) might be greater in NCT patients compared with non-NCT patients. We aimed to determine the proportion of TM for potential BCS candidate due to false size prediction after NCT and factors affecting that. Methods: We prospectively enrolled patients with invasive breast cancer (Stage II or III) who were scheduled for TM from 2018 to 2021 at Seoul National University Hospital (SNUH). Patients who were determined to undergo TM by only patient’s preference, who had BRCA1/2 mutation, multicentric cancer, diffuse malignant calcification over more than a quadrant, and inflammatory cancer were excluded. The decision of TM was done by operating surgeon considering the tumor extent, location, and breast size. Breast imaging including mammography, ultrasonography (USG), and MRI were done in patients. Before surgery, each surgeon recorded a hypothetic maximum tumor size (HMS) that the surgeon would have been able to try BCS if the patient had actually less than that size of tumor at that location in the patient. After operation, the HMS was compared with final pathologic total extent of the tumor including invasive and in situ cancer. In SNUH, decisions and tries of BCS led to eventual BCS with negative margin in 97.4% of patients during same period with this study. Results: Among 360 patients enrolled, 130 were patients who underwent NCT, and 230 were chemotherapy naïve as a control group. 62 of 130 (52.3%) in the NCT group and 49 of 230 (21.3%) in the non-NCT group were found to have smaller tumor extent than the pre-recorded HMS, respectively (NCT vs non-NCT p-value <0.001). Further analyses were done only for NCT group. In an analysis according to subtype, the proportion of TM with false size prediction were more in HER2-positve (63.3%) and triple-negative breast cancer (TNBC) (57.6%) than in ER-positive/HER2-negative breast cancer (25.0%) (p-value <0.001). In an imaging analysis, MRI size were larger than HMS in 73.8% of all patients. Both MRI-pathology size and USG-pathology size discrepancies were significantly associated with false decision of TM (both p<0.001), but not with mammography. Without MRI, the false decision would have been reduced by 26.1%. Conclusions: We found that 52.3% of patients who received TM after NCT were actually BCS eligible, which was significantly higher than non-NCT patients. The proportion of false prediction were more in HER2-positive and TNBC. MRI imaging contributed to false size prediction and subsequent TM for BCS eligible patients. Clinical trial information: NCT04689529.
NOHA: A sensitive, low-cost, and accessible blood-based biomarker to determine breast cancer estrogen receptor status in low-resource settings.
Authors: Mohan Srinidi , Musyoka Augustine , Guthikonda Divya , Saunders Jamie , Girata Lora , Mremi Alex , Serventi Furaha , Mbaga Blandina , Patrick Elizabeth , Jones Michael A , Emery Ivette F. , Lucas Frances L. , Miesfeldt Susan
Published: June 2022

580

Background: Significant challenges to breast cancer control in low- and middle-income countries (LMICs) include late-stage disease presentation because of few/no early detection programs, inadequately staffed and equipped pathology laboratories, and constrained treatment options. Estrogen receptor (ER) expression is critical to determining candidacy for cost efficient and accessible hormonal agents in LMICs; however, access to standard immunohistochemistry (IHC)-based ER analysis is grossly limited/nonexistent due to cost and technical requirements. We have identified Nw-hydroxy-L-Arginine (NOHA) as a low cost and accessible blood-based biomarker to distinguish estrogen-receptor negative (ER–) from estrogen-receptor positive (ER+) breast cancer, differentiate ER– high grade versus low grade tumors, and correlate ER– molecular phenotype with ethnic variation. Our studies with US patients suggest the NOHA threshold of <4nM as a reliable indicator of ER– versus ER+ disease (Table 1). Here we examine the clinical utility of NOHA as an alternative to IHC in distinguishing ER– from ER+ breast tumors in Tanzanian patients. Methods: Following informed consent, 70 newly diagnosed breast cancer patients were recruited at Kilimanjaro Christian Medical Center (KCMC; Moshi, Tanzania). Prior to any treatment, a needle prick amount of blood was collected from each patient on a Noviplex plasma card (Shimadsu, U.S.) and stored at -80˚C. Plasma cards and unstained tumor pathology slides were shipped at 2-3 months intervals to US labs for NOHA and immunohistochemistry (IHC) ER testing. Statistical difference was set at p<0.01, with NOHA and IHC assay operators blinded to patient clinical status. Results: Our early data show correlation between NOHA levels and ER IHC results, providing a means to distinguish ER– from ER+ breast cancer in the low-resource setting. Plasma cards stored at -80˚C for up to 3 months retained NOHA stability in assays involving a proprietary antibody-based ELISA, and by LC-MS. Conclusions: This study suggests the clinical utility of NOHA as a cost-effective, accessible replacement for standard IHC testing in determining ER status among breast cancer patients in LMICs, promising to extend access to cost efficient and available hormonal agents and improving outcomes and quality of life. The present study provides foundational knowledge for broader studies of NOHA utility in global breast cancer control, as well as in ongoing development of NOHA rapid-testing technologies. [Table: see text]
Collaborative federated learning behind hospitals’ firewalls for predicting histological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.
Authors: Ogier du Terrail Jean , Leopold Armand , Joly Clément , Andreux Mathieu , Maussion Charles , Schmauch Benoit , Zaslavskiy Mikhail , Wainrib Gilles , Milder Maud , Gervasoni Julie , Guérin Julien , Durand Thierry , Livartowski Alain , Moutet Kelvin , Gautier Clément , Moisson Anne-Laure , Marini Camille , Galtier Mathieu , Heudel Pierre Etienne , Bataillon Guillaume
Published: June 2022

590

Background: Triple-Negative Breast Cancer (TNBC) is characterized by high metastatic potential and poor prognosis with limited treatment options. Neoadjuvant chemotherapy (NACT) is the standard of care in non-metastastic setting due to the ability to assess pathologic responses providing important prognostic information and guidance in adjuvant therapy decisions. However, the histological response heterogeneity is still poorly understood. We investigate the use of Machine Learning (ML) to predict from diagnosis Whole-Slide Images (WSI) of early TNBC the positive histological Complete Response (pCR) to NACT on surgical specimens. To overcome the known biases of small scale studies while respecting data privacy, we conduct a study in a multi-centric fashion behind hospitals’ firewalls using collaborative Federated Learning (FL). Thereby allowing access to enough TNBC data to sustain a complete response heterogeneity investigation. Methods: We collected in both comprehensive cancer centers: Centre Léon Bérard (A)(n=99) and Institut Curie (B) (n=420), WSI of biopsies performed at diagnosis and relevant clinical variables. We use traditional Multiple Instance Learning pipelines by tiling the matter on each WSI with a pre-trained Neural Network (NN). We train a second NN to predict the NACT pCR using the mean feature of each WSI. ML trainings are performed using either one cohort in isolation (NN Local) or both cohorts using FL. We compare the performance of this federated WSI based model to the best clinical model (Clin.) simulating clinical practice (using grade and Tumor-Infiltrating Lymphocytes (TILs) percentage) on both centers. Results: Performance of models to predict NACT pCR (AUC). All results are evaluated in 5 repeated 4-folds cross validations. Conclusions: The final ML model, that was trained in a privacy preserving fashion on both hospitals, provides better prediction of NACT pCR than current clinical standards. This study shows that 1. Not all relevant information is routinely extracted from WSI and 2. Non simulated FL is possible in Healthcare and gives better results than siloed studies on open medical questions. Additional interpretability results of the model show that it has re-discovered known biomarkers such as TILs and apocrine tumor cells without any tile-level annotation, and hints at potential new biomarkers. [Table: see text]
Artificial intelligence (AI)–powered spatial analysis of tumor-infiltrating lymphocytes (TIL) for prediction of response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC).
Authors: Lee Hee Jin , Cho Soo Yoon , Cho Eun Yoon , Lim Yoojoo , Cho Soo Ick , Jung Wonkyung , Song Sanghoon , Kang Mingu , Ryu Jeongun , Ma Minuk , Park Seonwook , Paeng Kyunghyun , Ock Chan-Young , Song Sang Yong , Gong Gyungyub
Published: June 2022

595

Background: Stromal TIL are a well-recognized prognostic and predictive biomarker in breast cancer. There is a need for tools assisting visual assessment of TIL, to improve reproducibility as well as for convenience. This study aims to assess the clinical significance of AI-powered spatial TIL analysis in the prediction of pathologic complete response (pCR) after NAC in TNBC patients. Methods: H&E stained slides and clinical outcomes data were obtained from stage I – III TNBC patients treated with NAC in two centers in Korea. For spatial TIL analysis, we used Lunit SCOPE IO, an AI-powered H&E Whole-Slide Image (WSI) analyzer, which identifies and quantifies TIL within the cancer or stroma area. Lunit SCOPE IO was developed with a 13.5 x 109 micrometer2 area and 6.2 x 106 TIL from 17,849 H&E WSI of multiple cancer types, annotated by 104 board-certified pathologists. iTIL score and sTIL score were defined as area occupied by TIL in the intratumoral area (%) and the surrounding stroma (%), respectively. Immune phenotype (IP) of each slide was defined from spatial TIL calculation, as inflamed (high TIL density in tumor area), immune-excluded (high TIL density in stroma), or desert (low TIL density overall). Results: A total of 954 TNBC patients treated from 2006 to 2019 were included in this analysis. pCR (ypT0N0) was confirmed in 261 (27.4%) patients. The neoadjuvant regimens used were mostly anthracycline (97.8%) and taxane (75.1%) -based, with 116 (12.1%) patients receiving additional platinum and 41 (4.3%) patients treated as part of immune checkpoint inhibitor or PARP inhibitor clinical trials. The median iTIL score and sTIL score were 4.3% (IQR 3.2 – 5.8) and 8.1% (IQR 6.3 – 13.4), respectively. The mean iTIL score was significantly higher in patients who achieved pCR after NAC (5.8% vs. 4.5%, p < 0.001), and a similar difference was observed with sTIL score (12.1%.1 vs. 9.4%, p < 0.001). iTIL score was found to remain as an independent predictor of pCR along with cT stage and Ki-67 in the multivariable analysis (adjusted odds ratio 1.211 (95% CI 1.125 – 1.304) per 1 point (%) change in the score, p <0.001). By IP groups, 291 (30.5%) patients were classified as inflamed, 502 (52.6%) as excluded, and 161 (16.9%) as desert phenotype. The patients with inflamed phenotype were more likely to achieve pCR (44.7%) than other phenotypes (19.8%, p < 0.001). Conclusions: AI-powered spatial TIL analysis could assess TIL densities in the cancer area and surrounding stroma of TNBC, and TIL density scores and IP classification could predict pCR after NAC.
Does race influence long-term outcomes after neoadjuvant chemotherapy in breast cancer: A National Cancer Database analysis.
Authors: Roy Arya Mariam , Jiang Changchuan , Yao Song , Perimbeti Stuthi , Gandhi Shipra
Published: June 2022

606

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate predictor for long-term survival in breast cancer (BC). Patients who attain pCR have improved relapse-free and overall survival (OS) when compared to patients with residual disease (RD). We examined the pCR in Black and White BC patients who received NACT and their OS after attaining pCR and RD. Methods: The National Cancer Database (NCDB) was queried for Black and White females with non-metastatic BC from the years 2010 – 2016 who received NACT. Logistic regression was used to analyze pCR/RD and Cox proportional hazards regression to analyze OS, with adjustment for age, race, stage, grade, body mass index, treatments received, insurance status and comorbidities. STATA/IC 16.0 was used for analysis and a two-sided p-value < 0.05 was considered significant. Results: A total of 101,014 White and Black BC patients were identified, including 24,852 (Whites - 74.43%, Black - 25.57%) triple negative breast cancer (TNBC), 51,043 (Whites - 84%, Blacks - 16%) hormone receptor positive HER2 negative (HR+HER2-) and 17,818 (Whites - 83%, Blacks - 17%) HER2 positive. Whites had a slightly higher odds of attaining pCR compared to Blacks (adjusted Odds Ratio (aOR) = 1.040, 95% Confidence Interval (CI) = 1.02 - 1.19, p = 0.02). The difference was largest in TNBC subtype (TNBC: aOR = 1.34, 95% CI = 1.20 - 1.56, p < 0.001; HR+HER2-: aOR = 1.1; 95% CI = 1.02 - 1.32, p = 0.038; HER2+: aOR = 1.13, 95% CI = 1.08 - 1.27, p < 0.001). Among those who attained pCR, Blacks had worse OS when compared to Whites in HER2+ subtype (adjusted Hazard Ratio (aHR) = 1.41, 95% CI = 1.04 - 1.93, p = 0.028) but not in TNBC or HR+HER2- subtypes. Among those with RD, Blacks had worse OS in the whole cohort compared to Whites (aHR = 1.43, 95% CI = 1.26 - 1.58, p < 0.001), and in all subtypes: TNBC (aHR = 1.17, 95% CI = 1.11 - 1.23, p < 0.001), HR+HER2- (aHR = 1.38, 95% CI = 1.31 - 1.45, p < 0.001) and HER2+ (aHR = 1.45, 95% CI = 1.32 - 1.59, p < 0.001). Conclusions: Black BC patients with TNBC were less likely to achieve pCR than Whites after NACT. When Black patients with HER2+ subtype did attain pCR, they still had worse OS than Whites. The same racial difference in OS was observed in all BC subtypes - TNBC, HR+HER2- and HER2+ among patients with RD. This highlights the importance to investigate novel personalized treatment strategies for Black patients.
State public welfare spending and racial/ethnic disparities in overall survival among adults with cancer.
Authors: Barnes Justin Michael , Johnston Kenton J , Osazuwa-Peters Nosayaba
Published: June 2022

6509

Background: State public welfare spending may partially address social determinants of health and mitigate structural racism. However, its association with racial and ethnic disparities and overall survival for newly diagnosed patients with cancer is unknown. Methods: Adults ages 18 and older with a new cancer diagnosis from 2007-2016 were queried from the Surveillance, Epidemiology, and End Results program. Annual state spending data were obtained from the US Census Bureau. We evaluated the association of 5-year overall survival (OS) and public welfare spending using cluster-robust regression. Analyses were conducted overall, by race and ethnicity, and by cancer site. To determine whether public welfare spending was associated with changes in racial and ethnic disparities in survival, we additionally assessed for interaction effects between public welfare spending and race and ethnicity. Analyses were adjusted for covariates including age, sex, metropolitan residence, state, county-level income and education, insurance status, cancer site, stage at diagnosis, and year of diagnosis. Sensitivity analyses were conducted also accounting for state Medicaid expansion effects and state spending on health care and hospitals. Results: A total of 2,925,550 individuals were identified in our cohort. 5-year OS was 10.6% lower in non-Hispanic Black vs. White patients. Public welfare spending was not associated with 5-year OS overall (0.25 % per 10% increase in spending, -1.47 to 1.96, p =.78) or for non-Hispanic White patients (0.52% per 10% increase in spending, 95% CI -1.30 to 2.33, p =.58). However, increased public welfare spending was associated with increased 5-year OS among non-Hispanic Black patients (2.02% per 10% increase in spending, 95% CI = 0.01 to 4.03, p =.049). There was a 4.46% (95% CI = 2.63 to 6.30, pinteraction<.001) narrowing of the 5-year OS disparity in non-Hispanic Black relative to White patients per 10% increase in spending, or a 42% closure of the 10.6% OS disparity. Specifically, increased public welfare spending was associated with a narrowed Black vs. White 5-year OS disparity for patients with breast (7.50% increase in 5-yr OS for non-Hispanic Black relative to White per 10% increasing in spending, corresponding to closing 42.1% of the disparity), cervical (12.2%, 45.9%), colorectal (3.37%, 44.9%), head and neck (8.23%, 35.7%), liver (4.54%, 44.8%), lung (1.76%, 63.3%), ovarian (6.43%, 35.9%), prostate (2.89%, 41.9%), bladder (7.62%, 42.9%), and uterine cancers (14.9%, 40.9%). Results were similar after accounting for state health care and hospital spending and state Medicaid expansion effects. Conclusions: State investment in public welfare was associated with improved 5-year OS for non-Hispanic Black individuals with cancer, decreasing racial disparities in cancer outcomes overall and for many cancer sites.
Racial and socioeconomic disparities in telemedicine use among US patients initiating cancer treatment during the COVID-19 pandemic.
Authors: Guadamuz Jenny , Wang Xiaoliang , Royce Trevor Joseph , Calip Gregory Sampang
Published: June 2022

6511

Background: The COVID-19 pandemic was associated with declines in in-person clinical visits. While telemedicine visits have increased, uptake has varied. Here we assess demographic and socioeconomic factors associated with telemedicine use among patients initiating treatment for 21 common cancers at community oncology clinics. Methods: This retrospective study uses the nationwide Flatiron Health electronic health record-derived de-identified database of patients with cancer. Patient characteristics were determined using structured and unstructured data curated via technology-enabled abstraction. We included patients (≥ 18 years) who initiated first-line cancer treatment between March 2020 and September 2021 (follow-up through December 2021). We focused on differences in telemedicine use (≥ 1 telemedicine visit within 90 days after treatment initiation) across race/ethnicity, insurance coverage, rurality (per Rural-Urban Commuting Areas), and socioeconomic status (SES). SES was defined using census block group data from the American Community Survey (2015-2019) (quintiles representing least to most affluent areas) based on patient addresses and measured using the Yost Index (incorporating income, home values, rental costs, poverty, blue-collar employment, unemployment, and education information). We used logistic regression models adjusted for clinical characteristics ( i.e., age, sex, performance status, and stage) to examine differences in telemedicine use. Results: This study included 24,164 patients (48.1% women, median age: 69 [interquartile range: 61-77] years), of whom 15.9% used telemedicine services. Black patients were less likely to use telemedicine services than White patients (11.4% vs. 15.6%, odds ratio [OR] 0.69 [95% confidence interval [CI]: 0.59-0.79], p<0.01). Telemedicine use was also lower among patients without documented insurance than well-insured (commercial and Medicare payers) patients (10.7% vs. 15.9%, OR 0.62 [95% CI: 0.54-0.72], p<0.01). Those in rural (9.8%, OR 0.51 [95% CI: 0.45-0.58], p<0.01) and suburban areas (13.1%, OR 0.71 [95%: 0.64-0.79], p<0.01) were less likely to use telemedicine services than patients in urban areas (17.6%). Finally, patients in the least affluent areas had lower telemedicine use than those in the most affluent areas (10.2% vs. 24.3%, OR 0.35 [95% CI: 0.31-0.40], p<0.01). Conclusions: During the COVID-19 pandemic, nearly one-fifth of patients initiating cancer treatment used telemedicine services. However, there were substantial disparities: Black, uninsured, non-urban, and less affluent patients are less likely to use telemedicine services. While telemedicine may expand access to specialty care, the proliferation of these services may widen cancer care disparities if vulnerable populations do not have equitable access.
Survival among patients with multiple myeloma in the U.S. military health system compared to the Surveillance, Epidemiology, and End Results (SEER) program.
Authors: Dew Alexander , Darmon Sarah , Lin Jie , Ware Jason , Roswarski Joseph Lee , Shriver Craig D , Zhu Kangmin , Chiu Alden Vincent
Published: June 2022

6524

Background: Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable despite therapeutic advances. The US Military Health System (MHS) provides universal healthcare to beneficiaries and has been associated with improved survival across multiple malignancies. It is unknown whether access to universal healthcare via the MHS translates to improved survival for MM patients. We sought to answer this question by comparing survival data from the Department of Defense’s Automated Central Tumor Registry (ACTUR) and the NCI’s SEER database. Methods: Patients 18 years and older diagnosed with histologically confirmed MM between 1987-2013 were identified in ACTUR (N=1,488) and SEER (N=2,976) databases. Two SEER patients were matched to an ACTUR patient by age group, sex, race, and diagnosis year group. Five and 10-year survival was compared between ACTUR and SEER patients using Kaplan-Meier curves and log-rank tests. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) adjusted for potential confounders of age at diagnosis, sex, race and diagnosis year. The proportional hazards assumption for the analysis was assessed with log-log survival curves. Results: Median survival in the ACTUR patients was 47.1 months (95% CI: 43.9-50.4) compared to 33.0 months (95% CI: 32.0-35.0) in the SEER group. Five and 10-year survival was superior in patients from the ACTUR group compared to the SEER group with an aHR of 0.74 (95% CI: 0.68-0.81) and 0.79 (95% CI: 0.74-0.85) after adjustment for potential confounders, respectively. The survival advantage of ACTUR patients was preserved when stratified by age, sex, race, and diagnosis year. Conclusions: Patients treated with MM in the MHS had superior 5 and 10-year overall survival when compared to the general population. This benefit remained despite age, sex, race, and diagnosis year. Our study findings suggest the benefits of universal healthcare provided by the MHS improve survival among MM patients. Further research is warranted to delineate factors which improve survival and reduce disparity in the treatment of MM patients.[Table: see text]
Saving TIME: Accuracy of a text intervention to minimize the time burden of cancer care.
Authors: Bange Erin Mary , Coughlin Kerry Q. , Brown Timothy J , Li Wenrui , Moriarty Elizabeth , Bange Tara E. , Rosin Roy , Josephs Michael , Smith David R. , Cohen Roger B. , Getz Kelly D. , Ragusano Daniel , Balar Eesha , Schuchter Lynn Mara , Balachandran Mohan , Long Qi , Shulman Lawrence N. , Guerra Carmen , Mamtani Ronac
Published: June 2022

6527

Background: Patients with cancer spend substantial time receiving cancer care. There is a need for innovative strategies to decrease the time burden of cancer therapy. The current care model consists largely of in-person visits to assess treatment toxicity. Most patients treated with immunotherapy, however, do not experience substantial toxicity. We designed and evaluated a text-based instrument to identify patients without symptoms of immunotherapy toxicity. This instrument has the potential to be combined with lab assessment to identify individuals who can safely proceed directly to treatment, lessening the need for in-person office visits. Methods: This cross-sectional study evaluated the performance characteristics of a text-based instrument to identify patient-reported immunotherapy toxicity, against the gold standard in-person provider assessment documented in the electronic medical record (EMR). Those eligible for inclusion spoke English, were receiving single agent immune checkpoint blockade for a solid tumor, and had access to a mobile device with text messaging capabilities. The instrument contained 16 questions adapted from the NCI Pro-CTCAE and was administered via text-message 96 hours prior to the patient’s scheduled infusion visit. Patient perspectives were quantified via a 13-item questionnaire. Results: Between October 1 and November 25, 2021, 50 patients enrolled in the study, and 45 patients completed the instrument (90% response). The median age was 68 (IQR 60-72), 31 (62%) were male, and 44 (88%) were white. Most patients received either pembrolizumab (n=27, 54%) or nivolumab (n=17, 34%) in the palliative setting (n=37, 74%) for genitourinary (n=15, 30%), lung (n=13, 26%), or skin (n=11, 22%) cancer. Patients who completed the instrument were younger (median age 67 vs 76) than those who did not complete the instrument. The prevalence of immune related toxicity documented in the EMR was 57.8%. The sensitivity and negative predictive value of the instrument was 100% (95% CI 0.87-1.00) and 100% (95% CI 0.664-1.00), respectively; other accuracy parameters are presented in the Table. The patient user questionnaire revealed that visual impairment, lack of access to a smart phone, and lack of recognition of the instrument were barriers to completion. Conclusions: A text-based platform is both feasible and effective at identifying patients who are not experiencing symptoms of immune toxicity, and when combined with lab assessment, can eliminate office visits for up to 47% of patients. A prospective clinical trial to assess this is underway (NCT05134636). [Table: see text]