tbuckley/cabot-search huggingface dataset:
Everolimus and exemestane in hormone receptor-positive advanced breast cancer: A comprehensive cancer center’s experience.
Authors: Inês Moreira, Marta Ferreira, Ana Afonso, Ana Ferreira, Ana Rodrigues, Claudia Vieira, Cristina Oliveira, Joana Savva-Bordalo, João Dias, Maria Cassiano, Miguel Abreu, Sara Alves, Susana Sousa
Journal: Journal of Clinical Oncology (2021)

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.
Efficacy and safety of low-dose albumin-bound paclitaxel plus tislelizumab as second- or further lines treatment for elderly patients with metastatic non-small cell lung cancer.
Authors: Qian Geng, Dongqing Li, Wenyu Zhu, Haoliang Peng, Zhihui Jin, Hua Jiang
Journal: Journal of Clinical Oncology (2021)

e21066 Background: Lung cancer ranks first globally in morbidity and mortality rates among cancers. There are few studies focused on the different doses of chemotherapy drugs in combination with programmed cell death-1 (PD-1) inhibitors in non-small-cell lung cancer (NSCLC). Tislelizumab, a novel PD-1 monoclonal antibody, has been shown to improve antitumor activity when combined with chemotherapy as first-line treatment for patients with NSCLC. Elderly patients usually have poor physical conditions and many complications, resulted in higher risks of chemotherapy. This study aimed to preliminarily assess the efficacy and safety of low-dose chemotherapy plus tislelizumab for elderly patients with metastatic NSCLC. Methods: Eligible patients should be diagnosed as metastatic NSCLC, aged ≥65 years, and failed in one or more lines treatment. Patients with epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) inhibitor resistance could be enrolled in the study. Participants received albumin-bound paclitaxel (130mg/m 2 ) plus tislelizumab (200mg) every 3 weeks. Chemotherapy lasted for no more than 6 cycles. Once chemotherapy intolerance occurred or at end of 6 cycles, patients with objective response or stable disease would continue to receive tislelizumab until confirmed disease progression, death, and unacceptable toxicity. Primary endpoints were progression free survival (PFS) and safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), as well as overall survival (OS). Results: Total 23 patients were enrolled from May 2019 to March 2020: 43.5% (10/23) male, 39.1% (9/23) smokers, 26.1% (6/23) with squamous cell carcinoma and 56.5% (13/23) with ECOG 2. Median age was 71 yr (range: 65, 82). Patients had received 1 (47.8%) or ≥2 (52.2%) lines of therapy. 13 (56.5%) patients with EGFR/ALK TKI resistance participated in the study. As of data cut-off on December 1, 2020, the median PFS was 9.5 months (95% CI: 5.7–13.3 months). Nine patients achieved partial response (PR). The ORR was 39.1% (9/23) and DCR was 87.0% (20/23). Only 4 participants died in the study and the mOS was not reached. Sixteen (69.6%) patients had a decrease in tumor size as compared with baseline and the median change from baseline was −22%. 13 (56.5%) participants suffered at least one adverse event (grade 3 in 3 (13.0%) patients). The main adverse events were fatigue (17.4%), fever (17.4%), abnormal liver function (17.4%), rash (13.0%) and numbness (13.0%). No grade 4 adverse event was reported. Conclusions: Low-dose albumin-bound paclitaxel plus tislelizumab might be an optional choice for elderly patients with metastatic NSCLC after the failure of platinum-based chemotherapy or targeted therapy. Perspective clinical studies with large sample size are needed to validate our results.
Potential impact of HPV vaccine on incidence of high-grade vulvar, vaginal, and anal precancers among females and males aged 15 to 39 years, United States 2000 to 2017.
Authors: Mona Saraiya, Virginia Senkomago
Journal: Journal of Clinical Oncology (2021)

5594 Background: Since introduction of HPV vaccine, cervical precancers have decreased, but the vaccine’s impact on non-cervical anogenital precancers is unknown. These precancers are identified opportunistically and are not routinely collected in most cancer registries. Methods: We examined high-grade vulvar (VIN3), vaginal (VAIN3), and anal (AIN3) precancers among persons aged 15-39 years using 2000-2017 data from select cancer registries covering 27.8% of the U.S. population. Incidence trends were evaluated with Joinpoint regression. Results: VIN3 rates declined 21% per year post-HPV vaccination introduction among women. VAIN3 rates declined 19.1% per year among women aged 15-29 years, also post-HPV vaccination introduction. Compared to the pre-vaccination period when AIN3 rates were increasing, AIN3 rates were stable among women aged 15-29 years and among men aged 30-39 years. Conclusions: Decreases in rates of VIN3 and VAIN3 after HPV vaccine introduction among younger age groups were similar to declines observed in cervical precancers, suggesting HPV vaccine impact.
Immune Activation and Microbial Translocation as Prognostic Biomarkers for AIDS-Related Non-Hodgkin Lymphoma in the AMC-034 Study
Authors: Laura E. Martínez, Shelly Lensing, Di Chang, Larry I. Magpantay, Ronald Mitsuyasu, Richard F. Ambinder, Joseph A. Sparano, Otoniel Martínez-Maza, Marta Epeldegui
Journal: Clinical Cancer Research (2021)

Abstract Purpose: AIDS-related non-Hodgkin lymphoma (ARL) is the most common cancer in HIV-infected individuals in the United States and other countries in which HIV-positive persons have access to effective combination antiretroviral therapy (cART). Our prior work showed that pretreatment/postdiagnosis plasma levels of some cytokines, such as IL6, IL10, and CXCL13, have the potential to serve as indicators of clinical response to treatment and survival in ARL. The aims of this study were to identify novel prognostic biomarkers for response to treatment and/or survival in persons with ARL, including biomarkers of microbial translocation and inflammation. Experimental Design: We quantified plasma levels of several biomarkers (sCD14, LBP, FABP2, EndoCab IgM, IL18, CCL2/MCP-1, sCD163, IP-10/CXCL10, TARC/CCL17, TNFα, BAFF/BLyS, sTNFRII, sCD44, and sIL2Rα/sCD25) by multiplexed immunometric assays (Luminex) or ELISA in plasma specimens obtained from ARL patients enrolled in the AMC-034 trial, which compared infusional combination chemotherapy (EPOCH: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with concurrent or sequential rituximab. Plasma was collected prior to the initiation of therapy (n = 57) and after treatment initiation (n = 55). Results: We found that several biomarkers decreased significantly after treatment, including TNFα, sCD25, LBP, and TARC (CCL17). Moreover, pretreatment plasma levels of BAFF, sCD14, sTNFRII, and CCL2/MCP-1 were univariately associated with overall survival, and pretreatment levels of BAFF, sTNFRII, and CCL2/MCP-1 were also associated with progression-free survival. Conclusions: Our results suggest that patients with ARL who responded to therapy had lower pretreatment levels of inflammation and microbial translocation as compared with those who did not respond optimally.
Comparison of checkpoint inhibitor treatment-related cutaneous adverse events in racial and ethnic minority and Caucasian cohorts at Memorial Sloan Kettering Cancer Center.
Authors: Amaris Geisler, Dulce M. Barrios, Gregory Phillips, Rosa Nouvini, Mario E. Lacouture, Sarah Noor
Journal: Journal of Clinical Oncology (2021)

2632 Background: Immune-related cutaneous adverse events (irCAEs) are the most common and often the first toxicity of immune checkpoint inhibitors (CPIs). In the general population, irCAEs occur on average within 3.6 weeks of treatment initiation and most commonly manifest as maculopapular rash, lichenoid rash, and pruritus. Less is known about these irCAEs in racial and ethnic minority patients. The purpose of this study is to compare the irCAEs of cohorts of Caucasian and racial and ethnic minority patients at Memorial Sloan Kettering Cancer Center. Methods: Herein, we conducted a retrospective chart review of racial and ethnic minority patients treated with CPIs between 2012-2019 at Memorial Sloan Kettering Cancer Center. irCAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. These were compared to a Caucasian cohort matched by demographics and cancer therapy regimen. Results: One hundred ten racial and ethnic minority patients presented to dermatology for irCAEs. Our population consisted of 59 (53.6%) females and 51 (46.4%) males with a mean age of 59 (range 20-85). Of the patients who were seen by dermatology, 63/110 were Asian (57.3%) followed by 34/110 African American (30.9%), and 1 Native American. Twelve patients were of Hispanic ethnicity (10.9%), which included those of both African American and Caucasian race. The 110 patients that were evaluated by dermatology had 221 cutaneous adverse events. Rash (96, 43.4%), pruritus (40, 18.1%), and xerosis (23, 10.4%) were most frequently diagnosed (average time from treatment start to presentation was 125 days). Dermatology identified 87 (39.3%) grade 1, 103 (46.6%) grade 2, 30 (13.5%) grade 3, and 1 (0.4%) grade 4 events. There were 17 (15.5%) treatment interruptions, including 7 patients who required permanent discontinuation. In the Caucasian cohort, mean time to onset was 228 days (range 1-1500). Dermatology identified 48 (43.6%) grade 1, 44 (40.0%) grade 2, 18 (16.4%) grade 3, and 0 (0.0%) grade 4 events, with maculopapular rash (55, 50.0%) and pruritus (25, 22.7%) most frequently diagnosed. Conclusions: Our findings suggest that irCAEs occur frequently in cancer patients from racial and ethnic minority groups, with similar grade and morphology as Caucasian patients. When irCAEs develop in this population, the diagnosis occurred later than what has previously been reported, possibly due to these patients seeing MSK oncologists with an established dermatology consultation system and insight into how to manage these patients on their own. Prospective evaluation of underrepresented minorities receiving CPI therapy is warranted in order to identify risk factors and therapeutic strategies for these untoward events, so that optimal cancer care may be delivered.
Deep learning to predict subtypes of poorly differentiated lung cancer from biopsy whole slide images.
Authors: Gouji Toyokawa, Fahdi Kanavati, Seiya Momosaki, Kengo Tateishi, Hiroaki Takeoka, Masaki Okamoto, Koji Yamazaki, Sadanori Takeo, Osamu Iizuka, Masayuki Tsuneki
Journal: Journal of Clinical Oncology (2021)

8536 Background: Lung cancer is the leading cause of cancer-related death in many countries, and its prognosis remains unsatisfactory. Since treatment approaches differ substantially based on the subtype, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC) and small cell lung cancer (SCLC), an accurate histopathological diagnosis is of great importance. However, if the specimen is solely composed of poorly differentiated cancer cells, distinguishing between histological subtypes can be difficult. The present study developed a deep learning model to classify lung cancer subtypes from whole slide images (WSIs) of transbronchial lung biopsy (TBLB) specimens, in particular with the aim of using this model to evaluate a challenging test set of indeterminate cases. Methods: Our deep learning model consisted of two separately trained components: a convolutional neural network tile classifier and a recurrent neural network tile aggregator for the WSI diagnosis. We used a training set consisting of 638 WSIs of TBLB specimens to train a deep learning model to classify lung cancer subtypes (ADC, SCC and SCLC) and non-neoplastic lesions. The training set consisted of 593 WSIs for which the diagnosis had been determined by pathologists based on the visual inspection of Hematoxylin-Eosin (HE) slides and of 45 WSIs of indeterminate cases (64 ADCs and 19 SCCs). We then evaluated the models using five independent test sets. For each test set, we computed the receiver operator curve (ROC) area under the curve (AUC). Results: We applied the model to an indeterminate test set of WSIs obtained from TBLB specimens that pathologists had not been able to conclusively diagnose by examining the HE-stained specimens alone. Overall, the model achieved ROC AUCs of 0.993 (confidence interval [CI] 0.971-1.0) and 0.996 (0.981-1.0) for ADC and SCC, respectively. We further evaluated the model using five independent test sets consisting of both TBLB and surgically resected lung specimens (combined total of 2490 WSIs) and obtained highly promising results with ROC AUCs ranging from 0.94 to 0.99. Conclusions: In this study, we demonstrated that a deep learning model could be trained to predict lung cancer subtypes in indeterminate TBLB specimens. The extremely promising results obtained show that if deployed in clinical practice, a deep learning model that is capable of aiding pathologists in diagnosing indeterminate cases would be extremely beneficial as it would allow a diagnosis to be obtained sooner and reduce costs that would result from further investigations.
The effects of vitamin D (Vit D) replacement on pathological complete response (PCR) in breast cancer (BC) patients receiving neoadjuvant systemic chemotherapy (NAC).
Authors: Vahit Ozmen, Cetin Ordu, Ahmet Serkan Ilgun, Caglar Unal, Gursel Soybir, Zeynep Erdogan, Fatma Aktepe, Sitki Tuzlali, Alper Ozturk, Gul Alco, Tomris Duymaz, Tuba Kayan Tapan, Tolga Ozmen
Journal: Journal of Clinical Oncology (2021)

e12604 Background: Studies show that Vit D increases apoptosis by inhibiting the proliferation of BC cells. The aims of this study were to prospectively investigate the effects of Vit D replacement on PCR rates in patients receiving NAC. Methods: Breast cancer patients qualified for NAC between June 2019 and September 2020 and consent for the study were given weekly oral 50,000 IU Vit D (study group). The Control group consisted of patients who were given NAC between 2015-2020 and who did not receive Vit D replacement. Tumor characteristics and PCR compared between the study and control groups. Results: A total of 117 patients included in the study (55% in the study group). Both groups had similar patient, tumor, and treatment characteristics. PCR (ypT0/is ypN0 and ypT0/is) rates were significantly higher in the study group (28.1% vs 11.3%, p=0.025 and 37.5% vs 13.2%, p=0.003, respectively). In multivariate logistic regression analysis, estrogen receptor (ER) and HER 2 positivity, and Vit D3 replacement were identified as independent variables affecting PCR. Conclusions: Adding Vit D to NAC in breast cancer patients significantly increases PCR. This effect is more prominent in ER negative and HER2 positive breast cancer patients. Clinical trial information: NCT03986268. [Table: see text]
A retrospective study of anlotinib combined with adriamycin and ifosfamide in unresectable soft tissue sarcoma.
Authors: Zuoyao Long, Yajie Lu, Minghui Li, Guojing Chen, Jing Li, Zhanli Fu, Yunus Akbar, Hong-Mei Zhang, Zhen Wang
Journal: Journal of Clinical Oncology (2021)

e23542 Background: Soft tissue sarcoma (STS) is a group of malignant tumors with high heterogeneity that originates from mesenchymal tissue. Considering that the reliable anti-tumor efficiency of tyrosine kinase inhibitor (TKI), we attempted to combine the TKI and chemotherapy to observe the synergistic effect in STS. This study documented the result on the efficiency and safety of anlotinib+AI in 28 patients with unresectable STS. Methods: The key inclusion criteria of this retrospective study included: (a) age was 10-70 years; (b) histologically documented high-grade STS; (c) unresectable and sensitive to chemotherapy; (c) having measurable lesions according to RECIST 1.1; (d) haven’t received tyrosine kinase inhibitors; (e) adequate organ function and blood pressure. Patients were excluded when they had distal metastasis. Patients took 12mg of anlotinib once daily on a schedule of 2 weeks on and 1 week off, and received 20mg/m 2 /d of Adriamycin(A) and 3g/m 2 /d of ifosfamide(I) in the first three days. Four cycles after treatment, patients were evaluated to receive surgery or other therapies. The primary end points were objective response rate (ORR) and limb salvage rate, and other endpoints include PFS, disease control rate (DCR), rate of R0 resection and recurrence. Results: Finally, a total of 28 patients were eligible to analysis including 17 males. Mean age was 39.11±13.46. The pathological subtypes in the study were consist of fibrosarcoma (FS, n = 6), synovial sarcoma (SS, n = 6), myxoid liposarcoma (MLPS, n = 6), undifferentiated pleomorphic sarcoma (n = 4) and others (n = 6). Until the last follow-up, no CR or PD occurred. The best response of 8 patients (28.57%) were PR and others were SD (20/28, 71.43%). The ORR and DCR was 28.57% and 100.0% respectively. Additionally, the tumor regression of SS and MLPS were significantly than FS (p = 0.012，p = 0.042). Eventually, 24 patients received surgery including 19 of R0 resection, 3 of R2 resection and 2 of amputation. The rate of limb salvage and R0 resection was 91.67% (22/24) and 79.17% (19/24). The median PFS was 21 months (95%CI: 8.53-33.69 months). Only one patient had dead due to tumor progression with a OS of 10 months. All patients had experienced adverse events (AE, 100.0%). The most common grade 3-4 AE were leukopenia (57.14%), hypertension (14.29%) and hand-foot syndrome (7.14%). All AEs could be tolerated or relieved by expectant treatment. Conclusions: The results in our study revealed that anlotinib+AI could be an alternative strategy of unresectable soft tissue sarcoma.
COVID‐19 vaccines and the role of other potential allergenic components different from PEG. A reply to: “Other excipients than PEG might cause serious hypersensitivity reactions in COVID‐19 vaccines”
Authors: Beatriz Cabanillas, Cezmi A. Akdis, Natalija Novak
Journal: Allergy (2021)

CA reports grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne-Center for Allergy Research and Education, European Commission Horizon 2020 Framework Programme, Cure, Novartis Research Institutes, AstraZeneca, SciBase, advisory role for Sanofi/Regeneron, GlaxoSmithKline, SciBase, and Novartis, outside the submitted work. NN and BC declare no conflicts of interest.
Late-onset adverse events of anti-PD1 therapy in melanoma patients: An observational study from MELBASE, a nationwide prospective cohort
Authors: Clémentine Carlet, Stéphane Dalle, Marie-Thérèse Leccia, Laurent Mortier, Sophie Dalac-Rat, Caroline Dutriaux, Delphine Legoupil, Henri Montaudié, Olivier Dereure, Julie De Quatrebarbes, Florence Granel-Brocard, Myrtille Le-Bouar, Julie Charles, Florence Brunet-Possenti, Brigitte Dreno, Wendy Lefevre, Clara Allayous, Céleste Lebbe, Charlée Nardin
Journal: Journal of the American Academy of Dermatology (2021)
AI-Assisted Echocardiographic Prescreening of Heart Failure With Preserved Ejection Fraction on the Basis of Intrabeat Dynamics
Authors: Yu-An Chiou, Chung-Lieh Hung, Shien-Fong Lin
Journal: JACC. Cardiovascular imaging (2021)

The aim of this study was to establish a rapid prescreening tool for heart failure with preserved ejection fraction (HFpEF) by using artificial intelligence (AI) techniques to detect abnormal echocardiographic patterns in structure and function on the basis of intrabeat dynamic changes in the left ventricle and the left atrium.Although diagnostic criteria for HFpEF have been established, rapid and accurate assessment of HFpEF using echocardiography remains challenging and highly desirable.In total, 1,041 patients with HFpEF and 1,263 asymptomatic individuals were included in the study. The participants' 4-chamber view images were extracted from the echocardiographic files and randomly separated into training, validation, and internal testing data sets. An external testing data set comprising 150 patients with symptomatic chronic obstructive pulmonary disease and 315 patients with HFpEF from another hospital was used for further model validation. The intrabeat dynamics of the geometric measures were extracted frame by frame from the image sequence to train the AI models.The accuracy, sensitivity, and specificity of the best AI model for detecting HFpEF were 0.91, 0.96, and 0.85, respectively. The model was further validated using an external testing data set, and the accuracy, sensitivity, and specificity became 0.85, 0.79, and 0.89, respectively. The area under the receiver-operating characteristic curve was used to evaluate model classification ability. The highest area under the curve in the internal testing data set and external testing data set was 0.95.The AI system developed in this study, incorporating the novel concept of intrabeat dynamics, is a rapid, time-saving, and accurate prescreening method to facilitate HFpEF diagnosis. In addition to the classification of diagnostic outcomes, such an approach can automatically generate valuable quantitative metrics to assist clinicians in the diagnosis of HFpEF.