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11دورية أكاديمية
المؤلفون: Frederick M. Howard, James Dolezal, Sara Kochanny, Jefree Schulte, Heather Chen, Lara Heij, Dezheng Huo, Rita Nanda, Olufunmilayo I. Olopade, Jakob N. Kather, Nicole Cipriani, Robert L. Grossman, Alexander T. Pearson
المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
مصطلحات موضوعية: Science
الوصف: Deep learning models have been trained on The Cancer Genome Atlas to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. Here, the authors demonstrate that site-specific histologic signatures can lead to biased estimates of accuracy for such models, and propose a method to minimize such bias.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2041-1723Test
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12دورية أكاديمية
المؤلفون: Linda T. Vahdat, Peter Schmid, Andres Forero-Torres, Kimberly Blackwell, Melinda L. Telli, Michelle Melisko, Volker Möbus, Javier Cortes, Alberto J. Montero, Cynthia Ma, Rita Nanda, Gail S. Wright, Yi He, Thomas Hawthorne, Rebecca G. Bagley, Abdel-Baset Halim, Christopher D. Turner, Denise A. Yardley
المصدر: npj Breast Cancer, Vol 7, Iss 1, Pp 1-10 (2021)
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract The METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2374-4677Test
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13دورية أكاديمية
المؤلفون: Christos Vaklavas, Brian S. Roberts, Katherine E. Varley, Nancy U. Lin, Minetta C. Liu, Hope S. Rugo, Shannon Puhalla, Rita Nanda, Anna Maria Storniolo, Lisa A. Carey, Mansoor N. Saleh, Yufeng Li, Jennifer F. Delossantos, William E. Grizzle, Albert F. LoBuglio, Richard M. Myers, Andres Forero-Torres, on behalf of the Translational Breast Cancer Research Consortium (TBCRC)
المصدر: Breast Cancer Research, Vol 22, Iss 1, Pp 1-15 (2020)
مصطلحات موضوعية: Preoperative therapy, Bevacizumab, Letrozole, Breast cancer, Hormone receptor-positive breast cancer, Luminal breast cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background In preclinical studies, the expression of vascular endothelial growth factor (VEGF) in hormone receptor-positive breast cancer is associated with estrogen-independent tumor growth and resistance to endocrine therapies. This study investigated whether the addition of bevacizumab, a monoclonal antibody against VEGF, to letrozole enhanced the antitumor activity of the letrozole in the preoperative setting. Methods Postmenopausal women with newly diagnosed stage 2 or 3 estrogen and/or progesterone receptor-positive, HER2-negative breast cancer were randomly assigned (2:1) between letrozole 2.5 mg PO daily plus bevacizumab 15 mg/kg IV every 3 weeks (Let/Bev) and letrozole 2.5 mg PO daily (Let) for 24 weeks prior to definitive surgery. Primary objective was within-arm pathologic complete remission (pCR) rate. Secondary objectives were safety, objective response, and downstaging rate. Results Seventy-five patients were randomized (Let/Bev n = 50, Let n = 25). Of the 45 patients evaluable for pathological response in the Let/Bev arm, 5 (11%; 95% CI, 3.7–24.1%) achieved pCR and 4 (9%; 95% CI, 2.5–21.2%) had microscopic residual disease; no pCRs or microscopic residual disease was seen in the Let arm (0%; 95% CI, 0–14.2%). The rates of downstaging were 44.4% (95% CI, 29.6–60.0%) and 37.5% (95% CI, 18.8–59.4%) in the Let/Bev and Let arms, respectively. Adverse events typically associated with letrozole (hot flashes, arthralgias, fatigue, myalgias) occurred in similar frequencies in the two arms. Hypertension, headache, and proteinuria were seen exclusively in the Let/Bev arm. The rates of grade 3 and 4 adverse events and discontinuation due to adverse events were 18% vs 8% and 16% vs none in the Let/Bev and Let arms, respectively. A small RNA-based classifier predictive of response to preoperative Let/Bev was developed and confirmed on an independent cohort. Conclusion In the preoperative setting, the addition of bevacizumab to letrozole was associated with a pCR rate of 11%; no pCR was seen with letrozole alone. There was additive toxicity with the incorporation of bevacizumab. Responses to Let/Bev can be predicted from the levels of 5 small RNAs in a pretreatment biopsy. Trial registration This trial is registered with ClinicalTrials.gov (Identifier: NCT00161291 ), first posted on September 12, 2005, and is completed.
وصف الملف: electronic resource
العلاقة: http://link.springer.com/article/10.1186/s13058-020-01258-xTest; https://doaj.org/toc/1465-542XTest
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14دورية أكاديمية
المؤلفون: Sara M Tolaney, Leisha A Emens, Mary L Disis, David B Page, Heather L McArthur, Ashley Cimino-Mathews, Sylvia Adams, Elizabeth A Mittendorf, Rita Nanda, Hope S Rugo, Margaret E Gatti-Mays, Krista M Rubin, Alice Y Ho, Kevin Kalinsky, Hatem Soliman, Patricia A Spears, Jennifer K Litton
المصدر: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 8 (2021)
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Breast cancer has historically been a disease for which immunotherapy was largely unavailable. Recently, the use of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for the treatment of advanced/metastatic triple-negative breast cancer (TNBC) has demonstrated efficacy, including longer progression-free survival and increased overall survival in subsets of patients. Based on clinical benefit in randomized trials, ICIs in combination with chemotherapy for the treatment of some patients with advanced/metastatic TNBC have been approved by the United States (US) Food and Drug Administration (FDA), expanding options for patients. Ongoing questions remain, however, about the optimal chemotherapy backbone for immunotherapy, appropriate biomarker-based selection of patients for treatment, the optimal strategy for immunotherapy treatment in earlier stage disease, and potential use in histological subtypes other than TNBC. To provide guidance to the oncology community on these and other important concerns, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew upon the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for breast cancer, including diagnostic testing, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence-based and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with breast cancer.
وصف الملف: electronic resource
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15دورية أكاديمية
المؤلفون: Wen Li, Nu N. Le, Natsuko Onishi, David C. Newitt, Lisa J. Wilmes, Jessica E. Gibbs, Julia Carmona-Bozo, Jiachao Liang, Savannah C. Partridge, Elissa R. Price, Bonnie N. Joe, John Kornak, Mark Jesus M. Magbanua, Rita Nanda, Barbara LeStage, Laura J. Esserman, I-SPY Imaging Working Group, I-SPY Investigator Network, Laura J. van’t Veer, Nola M. Hylton
المصدر: Cancers, Vol 14, Iss 18, p 4436 (2022)
مصطلحات موضوعية: diffusion-weighted MRI, breast cancer, immunotherapy, pathologic complete response, neoadjuvant therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy.
وصف الملف: electronic resource
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16دورية أكاديمية
المؤلفون: Natalie Reizine, Everett E. Vokes, Ping Liu, Tien M. Truong, Rita Nanda, Gini F. Fleming, Daniel V.T. Catenacci, Alexander T. Pearson, Sandeep Parsad, Keith Danahey, Xander M. R. van Wijk, Kiang-Teck J. Yeo, Mark J. Ratain, Peter H. O’Donnell
المصدر: Therapeutic Advances in Medical Oncology, Vol 12 (2020)
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes. Methods: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD . For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx. Discussion: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1758-8359Test
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17دورية أكاديمية
المؤلفون: Paolo A. Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
المصدر: Journal of Translational Medicine, Vol 15, Iss 1, Pp 1-21 (2017)
مصطلحات موضوعية: Immunotherapy, Melanoma, Solid tumors, Medicine
الوصف: Abstract The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies. Monotherapy in pre-treated NSCLC is studied and the use of nivolumab, pembrolizumab and atezolizumab as second-line of advanced NSCLC is demonstrated as well as first line monotherapy and combination therapy in metastatic NSCLC studied. Patients with HNSCC have immunotherapeutic promises as well: the FDA recently approved moAbs targeting immune checkpoint receptors. Nivolumab in combination with ipilumumab showed acceptable safety and encouraging antitumor activity in metastatic renal carcinoma. HCCs have significant amounts of genomic heterogeneity and multiple oncogenic pathways can be activated: the best therapeutic targets identification is ongoing. The treatment of advanced/relapsed EOC remain clearly an unmet need: a better understanding of the relevant immuno-oncologic pathways and their corresponding biomarkers are required. UC is an immunotherapy-responsive disease: after atezolizumab, three other PD-L1/PD-L1 inhibitors (nivolumab, durvalumab, and avelumab) were approved for treatment of platinum-refractory metastatic urothelial carcinoma. Anti-PD-1/PD-L1 monotherapy is associated with a modest response rate in metastatic breast cancer; the addition of chemotherapy is associated with higher response rates. Immunotherapy safety profile is advantageous, although, in contrast to conventional chemotherapy: boosting the immune system leads to a unique constellation of inflammatory toxicities known as immune-related Adverse Events (irAEs) that may warrant the discontinuation of therapy and/or the administration of immunosuppressive agents. Research should explore better combination with less side effects, the right duration of treatments, combination or sequencing treatments with target therapies. At present, treatment decision is based on patient’s characteristics.
وصف الملف: electronic resource
العلاقة: http://link.springer.com/article/10.1186/s12967-017-1309-2Test; https://doaj.org/toc/1479-5876Test
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18دورية أكاديمية
المؤلفون: Poornima Saha, Rita Nanda
المصدر: Therapeutic Advances in Medical Oncology, Vol 8 (2016)
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Triple-negative breast cancer (TNBC) is a heterogeneous disease in which tumors are defined by lack of expression of the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) receptor. No targeted therapies are available for the treatment of TNBC, and chemotherapy remains the standard of care. Gene expression profiling has identified six distinct molecular subtypes of TNBC. The identification of novel targets, coupled with the development of therapies for different subsets of TNBC, holds great promise for the future treatment of this aggressive form of breast cancer. This review focuses on novel therapies in development for the treatment of TNBC.
وصف الملف: electronic resource
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19دورية أكاديمية
المؤلفون: Kathy S. Albain, Christina Yau, Emanuel F. Petricoin, Denise M. Wolf, Julie E. Lang, A. Jo Chien, Tufia Haddad, Andres Forero-Torres, Anne M. Wallace, Henry Kaplan, Lajos Pusztai, David Euhus, Rita Nanda, Anthony D. Elias, Amy S. Clark, Constantine Godellas, Judy C. Boughey, Claudine Isaacs, Debu Tripathy, Janice Lu, Rachel L. Yung, Rosa I. Gallagher, Julia D. Wulfkuhle, Lamorna Brown-Swigart, Gregor Krings, Yunn Yi Chen, David A. Potter, Erica Stringer-Reasor, Sarah Blair, Smita M. Asare, Amy Wilson, Gillian L. Hirst, Ruby Singhrao, Meredith Buxton, Julia L. Clennell, Ashish Sanil, Scott Berry, Adam L. Asare, Jeffrey B. Matthews, Angela M. DeMichele, Nola M. Hylton, Michelle Melisko, Jane Perlmutter, Hope S. Rugo, W. Fraser Symmans, Laura J. van't Veer, Douglas Yee, Donald A. Berry, Laura J. Esserman
مصطلحات موضوعية: Cancer, Therapeutic Research and Development, Clinical Research and Trials, Breast Cancer, Clinical Trial Results, Phase II clinical trials, Precision Medicine, Translational Research
الوصف: Estimated pCR rates
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20دورية أكاديمية
المؤلفون: Kathy S. Albain, Christina Yau, Emanuel F. Petricoin, Denise M. Wolf, Julie E. Lang, A. Jo Chien, Tufia Haddad, Andres Forero-Torres, Anne M. Wallace, Henry Kaplan, Lajos Pusztai, David Euhus, Rita Nanda, Anthony D. Elias, Amy S. Clark, Constantine Godellas, Judy C. Boughey, Claudine Isaacs, Debu Tripathy, Janice Lu, Rachel L. Yung, Rosa I. Gallagher, Julia D. Wulfkuhle, Lamorna Brown-Swigart, Gregor Krings, Yunn Yi Chen, David A. Potter, Erica Stringer-Reasor, Sarah Blair, Smita M. Asare, Amy Wilson, Gillian L. Hirst, Ruby Singhrao, Meredith Buxton, Julia L. Clennell, Ashish Sanil, Scott Berry, Adam L. Asare, Jeffrey B. Matthews, Angela M. DeMichele, Nola M. Hylton, Michelle Melisko, Jane Perlmutter, Hope S. Rugo, W. Fraser Symmans, Laura J. van't Veer, Douglas Yee, Donald A. Berry, Laura J. Esserman
مصطلحات موضوعية: Cancer, Therapeutic Research and Development, Clinical Research and Trials, Breast Cancer, Clinical Trial Results, Phase II clinical trials, Precision Medicine, Translational Research
الوصف: Using Contemporary Controls and Adjusting for Time Trends in I-SPY2: The Time Machine
النص الكامل