Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have ...non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.
We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University.
285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size.
We present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic ...HER2(+) breast cancer. It kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance the activity of ADCC effectors, including NK cells, may improve the efficacy of trastuzumab. Here, we have shown that upon encountering trastuzumab-coated, HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. CD137 activation, which was dependent on NK cell expression of the FcγRIII receptor, occurred both in vitro and in the peripheral blood of women with HER2-expressing breast cancer after trastuzumab treatment. Stimulation of trastuzumab-activated human NK cells with an agonistic mAb specific for CD137 killed breast cancer cells (including an intrinsically trastuzumab-resistant cell line) more efficiently both in vitro and in vivo in xenotransplant models of human breast cancer, including one using a human primary breast tumor. The enhanced cytotoxicity was restricted to antibody-coated tumor cells. This sequential antibody strategy, combining a tumor-targeting antibody with a second antibody that activates the host innate immune system, may improve the therapeutic effects of antibodies against breast cancer and other HER2-expressing tumors.
Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and ...approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.
Multicancer screening is a promising approach to improve the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.
: Breast cancer is the most common cause of cancer‐related death among women worldwide, with case fatality rates highest in low‐resource countries. Despite significant scientific advances in its ...management, most of the world faces resource constraints that limit the capacity to improve early detection, diagnosis, and treatment of the disease. The Breast Health Global Initiative (BHGI) strives to develop evidence‐based, economically feasible, and culturally appropriate guidelines that can be used in nations with limited health care resources to improve breast cancer outcomes. Using an evidence‐based consensus panel process, four BHGI expert panels addressed the areas of early detection and access to care, diagnosis and pathology, treatment and resource allocation, and health care systems and public policy as they relate to breast health care in limited‐resource settings. To update and expand on the BHGI Guidelines published in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health care improvement using a tiered system of resource allotment into four levels—basic, limited, enhanced, and maximal—based on the contribution of each resource toward improving clinical outcomes. Early breast cancer detection improves outcome in a cost‐effective fashion assuming treatment is available, but requires public education to foster active patient participation in diagnosis and treatment. Clinical breast examination combined with diagnostic breast imaging (ultrasound ± diagnostic mammography) can facilitate cost‐effective tissue sampling techniques for cytologic or histologic diagnosis. Breast‐conserving treatment with partial mastectomy and radiation therapy requires more health care resources and infrastructure than mastectomy, but can be provided in a thoughtfully designed limited‐resource setting. The availability and administration of systemic therapies are critical to improving breast cancer survival. Estrogen receptor testing allows patient selection for hormonal treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some allocation of resources and infrastructure, is needed to treat node‐positive, locally advanced breast cancers, which represent the most common clinical presentation of disease in low‐resource countries. When chemotherapy is not available, patients with locally advanced, hormone receptor‐negative cancers can only receive palliative therapy. Future research is needed to better determine how these guidelines can best be implemented in limited‐resource settings.
Acts of Medical Kindness for People with Autism Wisner-Carlson, Robert W; Pekrul, Scott R; Flis, Thomas ...
The Psychiatric clinics of North America,
03/2021, Letnik:
44, Številka:
1
Journal Article
Abstract
Advances in cancer care have led to improved survival, which, coupled with demographic trends, have contributed to rapid growth in the number of patients needing cancer care services. ...However, with increasing caseload, care complexity, and administrative burden, the current workforce is ill equipped to meet these burgeoning new demands. These trends have contributed to clinician burnout, compounding a widening workforce shortage. Moreover, family caregivers, who have unique knowledge of patient preferences, symptoms, and goals of care, are infrequently appreciated and supported as integral members of the oncology “careforce.” A crisis is looming, which will hinder access to timely, high-quality cancer care if left unchecked. Stemming from the proceedings of a 2019 workshop convened by the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine, this commentary characterizes the factors contributing to an increasingly strained oncology careforce and presents multilevel strategies to improve its efficiency, effectiveness, and resilience. Together, these will enable today’s oncology careforce to provide high-quality care to more patients while improving the patient, caregiver, and clinician experience.
Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in ...any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative RAW_REF_TEXT Correction /RAW_REF_TEXT RAW_REF_TEXT Open Access /RAW_REF_TEXT RAW_REF_TEXT Published:24 October 2022 /RAW_REF_TEXT Correction: Novel trends of genome evolution in highly complex tropical sponge microbiomes RAW_REF_TEXT Joseph B. Kelly 1,2, /RAW_REF_TEXT RAW_REF_TEXT David E. Carlson2, /RAW_REF_TEXT RAW_REF_TEXT Jun Siong Low3,4,5 & /RAW_REF_TEXT RAW_REF_TEXT … /RAW_REF_TEXT RAW_REF_TEXT Robert W. Thacker2,6 /RAW_REF_TEXT Show authors Microbiome volume 10, Article number: 182 (2022) Cite this article RAW_REF_TEXT 234 Accesses /RAW_REF_TEXT RAW_REF_TEXT 1 Altmetric /RAW_REF_TEXT RAW_REF_TEXT Metrics details /RAW_REF_TEXT The Original Article was published on 04 October 2022 Correction: Microbiome 10, 164 (2022) https://doi.org/10.1186/s40168-022-01359-z Following the publication of the original article 1, the author reported that the affiliations were incorrectly assigned. Robert W. Thacker2,6 /RAW_REF_TEXT Show authors Microbiome volume 10, Article number: 182 (2022) Cite this article RAW_REF_TEXT 234 Accesses 1 Altmetric Metrics details
Multidisciplinary management tumor boards are now conducted worldwide for the management of patients with cancer. Studies evaluating their influence on decision making and patient outcome are ...limited; however, single-center studies have reported significant changes in diagnosis and treatment plans. A survey from Arabic countries showed widespread use and reliance on tumor boards for decision making. A recent multi-institutional survey of veteran affairs (VA) hospitals in the United States found limited association between the presence of tumor boards and care and outcomes. The Cancer Care Outcomes Research and Surveillance Consortium looked at the association between tumor board features and measures of quality of care. Results of overall survival among the patients of these physicians participating in tumor boards is ongoing, but preliminary results are outlined along with a recent ASCO survey of international members on the presence, utilization, and influence of tumor boards in this article. Tumor boards allow for implementation of clinical practice guidelines and may help capture cases for clinical trials. Efforts to improve preparations, structure, and conduct of tumor boards, research methods to monitor their performance, teamwork, and outcomes are outlined also in this article. The concept of mini-tumor boards and more efficient methods for MDM in countries with limited resources are also discussed. In suboptimal settings, such as small community hospitals, rural areas, and areas with limited resources, boundaries in diagnosis and management can be overcome, or at least improved, with tumor boards, especially with the use of video-conferencing facilities. Studies from the United Kingdom showed that special training of multidisciplinary teams (MDT) led to better team dynamics and communication, improved patient satisfaction, and improved clinical outcome. The weight of the benefits versus the time and effort spent to improve efficiency, patient care, and better time management in the United States and in the international oncology community is also reviewed in this article.
The phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is commonly dysregulated in breast cancer. In preclinical studies, hyperactivation of the PI3K pathway has been ...linked to resistance to both endocrine therapy and trastuzumab (Herceptin). Rapalogs, agents that primarily inhibit mTOR-raptor complex 1, have been studied in combination with endocrine therapy to overcome endocrine resistance.Trials of combination endocrine therapy and rapalogs in metastatic hormone receptor-positive breast cancer have demonstrated variable results. However, two independent trials have recently shown that combination everolimus (Afinitor) and tamoxifen or combination everolimus and exemestane (Aromasin) is more effective than either endocrine agent alone. These trials selected patients with cancer refractory to endocrine therapy, which may be important in sensitizing tumors to inhibition of this pathway. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the early clinical data with combinations of PI3K/mTOR inhibitors and anti-HER2 therapies are encouraging. Efforts to identify clinical biomarkers of response or resistance to mTOR inhibitors are ongoing. This review will summarize results of preclinical and clinical studies aswell as ongoing clinical trials with mTOR or dual PI3K/mTOR inhibitors.
The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in >30,000 fly strains ...were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7140 lines. It now includes individual lines predicted to disrupt 5362 of the 13,666 currently annotated Drosophila genes (39%). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene misexpression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.
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