Institutional review of compliance with NCCN guidelines for breast cancer: lessons learned from real-time multidimensional synoptic reporting.

BACKGROUND: Variations exist in compliance with NCCN Guidelines. Prior reports of adherence to NCCN Guidelines contain limitations because of lack of contemporary review and incomplete listing of reasons for noncompliance. PURPOSE: To assess institutional compliance and assist national quality improvement strategies through identifying valid reasons for noncompliance. METHODS: Compliance with NCCN Guidelines was recorded prospectively using electronic synoptic templates for patients with newly diagnosed breast cancer treated at a single institution between January 2010 and December 2011. Compliance with NCCN Guidelines was recorded. The accuracy of real-time synoptic auditing methods compared with retrospective chart review and reasons for noncompliance was assessed. SAS 9.3 software was used for data analysis. RESULTS: Compliance with NCCN Guidelines among 395 patients was 94% for initial staging evaluation, 97% for surgery, 91% for chemotherapy, 89% for hormone therapy, 91% for radiation therapy, 85% for follow-up, and 100% for determination of estrogen receptor/progesterone receptor and HER2 status. Age, comorbidities, and stage influenced guideline compliance. The most common reasons for noncompliance were patient refusal, patient choice after shared decision-making, and overuse of testing. Synoptic templated reporting was accurate in 97% patients. CONCLUSIONS: High compliance with NCCN Guidelines was demonstrated. Reasons for noncompliance were identifiable. Compliance and nonadherence can be evaluated quickly with electronic synoptic reporting. This allows real-time action plans to address quality concerns and aids national risk adjustment for comparison and benchmarking.

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target.

CD43 is a transmembrane sialoglycoprotein. Normally the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signaling, apoptosis, migration and proliferation. Two CD43 antibodies were used to interrogate 66 cases of non-small cell lung cancer (NSCLC) and 24 cases of small cell lung cancer (SCLC). In addition, we engineered the CD43-positive lung cancer cell line A549 to stably express either non-targeted or CD43-targeted small-interfering RNA (siRNA). These lines were then subjected to in vitro assays of apoptosis, natural killer (NK) cell cytotoxicity, intercellular adhesion and transendothelial migration. A xenograft mouse model evaluated the ability of the lines to grow primary tumors in vivo. CD43 was found to be expressed in the majority of both SCLC and NSCLC. Inclusive of CD43-negative tumors, differential patterns of nuclear and cytoplasmic expression of CD43 define four molecular subcategories of lung cancer. Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells. Furthermore, targeting inhibited the growth of primary tumors in nude mice.

Core needle biopsy rate for new cancer diagnosis in an interdisciplinary breast center: evaluation of quality of care 2007-2008.

OBJECTIVE: The purpose of this study is to evaluate the rate of minimally invasive biopsy for diagnosis of breast cancer at an interdisciplinary breast center. BACKGROUND: Percutaneous core needle biopsy (CNB) is optimal for minimizing surgery for the diagnosis of benign and malignant lesions of the breast while preserving surgery for definitive resection. Core needle biopsy increases patient satisfaction and reduces the cost of diagnosis and treatment. Despite the endorsement of CNB by many professional organizations, the literature documents underutilization. METHODS: Institutional review board approval was obtained. An audit of a single institution's prospectively maintained cancer databases was performed for all breast cancers diagnosed in 2007 and 2008. Methods of diagnosis included image-guided and freehand-guided CNB, image-guided vacuum assisted needle biopsy, image-guided fine needle aspiration, punch biopsy, and open surgical biopsy. RESULTS: Three hundred sixty new breast cancers were diagnosed in 2007 and 2008. Malignancy was diagnosed by minimally invasive techniques in 350/360 (97%) cancers. CONCLUSION: A very high rate of accurate tissue diagnosis of breast cancer by minimally invasive techniques is achievable.

Perioperative quality metrics for one step breast cancer surgery: a patient-centered approach.

BACKGROUND AND OBJECTIVES: Patient-centered care is recommended by the Institute of Medicine to build a better healthcare system. The aim of this study was to audit patient-centered quality measures (QM) to create a breast center report card that could be provided to patients for education and informed consent. METHODS: An IRB approved retrospective review of 695 patients undergoing sentinel lymph node biopsy for breast cancer was conducted to audit the components of one step surgery and other QM. RESULTS: The intraoperative sensitivity to detect node positive patients was 25% (2/8), 27% (9/34), and 87% (68/78) for pN0(i+), pN1mi, pN1 patients, respectively. The re-excision lumpectomy rate was 15% (72/471) and the one step surgery success rate, which included lumpectomy and mastectomy patients, was 86% (598/695). Patient self-assessment of "very good to excellent" cosmesis and pain control were 77% (103/134) and 83% (60/72). Local recurrence rate was 2% (12/695) at a mean 3.1-year follow-up. CONCLUSIONS: The components of care that contribute to a patient-centered assessment of breast cancer surgery are measurable. "Bundling" of QM creates a perioperative report card that aids patients' informed consent and provides a framework for future comparative effectiveness studies.

Cardiovascular resistance to thrombosis in 13-lined ground squirrels.

13-lined ground squirrels (Ictidomys tridecemlineatus) enter hibernation as a survival strategy during extreme environmental conditions. Typical ground squirrel hibernation is characterized by prolonged periods of torpor with significantly reduced heart rate, blood pressure, and blood flow, interrupted every few weeks by brief interbout arousals (IBA) during which blood flow fluctuates dramatically. These physiological conditions should increase the risk of stasis-induced blood clots and myocardial ischemia. However, ground squirrels have adapted to survive repeated bouts of torpor and IBA without forming lethal blood clots or sustaining lethal ischemic myocardial damage. The purpose of this study was to determine if ground squirrels are resistant to thrombosis and myocardial ischemia during hibernation. Blood markers of coagulation, fibrinolysis, thrombosis, and ischemia, as well as histological markers of myocardial ischemia were measured throughout the annual hibernation cycle. Hibernating ground squirrels were also treated with isoprenaline to induce myocardial ischemia. Thrombin-antithrombin complex levels were significantly reduced (p < 0.05) during hibernation, while D-dimer level remained unchanged throughout the annual cycle, both consistent with an antithrombotic state. During torpor, the ground squirrels were in a hyperfibrinolytic state with an elevated ratio of tissue plasminogen activator complexed with plasminogen activator inhibitor to total plasminogen activator inhibitor (p < 0.05). Histological markers of myocardial ischemia were reversibly elevated during hibernation with no increase in markers of myocardial cell death in the blood. These data suggest that ground squirrels do not form major blood clots during hibernation through suppression of coagulation and a hyperfibrinolytic state. These animals also demonstrate myocardial resistance to ischemia.

Determining whether excision of all fibroepithelial lesions of the breast is needed to exclude phyllodes tumor: upgrade rate of fibroepithelial lesions of the breast to phyllodes tumor.

Fibroepithelial lesions (FELs) are a common histologic finding on core needle biopsy (CNB) of the breast. Fibroepithelial lesions include fibroadenoma and phyllodes tumor, which can be difficult to distinguish with an initial CNB. An institutional experience was reviewed from February 12, 2001, to January 4, 2007, to determine the safety of selective rather than routine excision of FELs and to determine the factors associated with upgrading diagnosis of FELs to phyllodes tumors without definitive phyllodes tumor diagnosis by CNB. Of 313 patients, 261 (83%) with FELs diagnosed by CNB received observation with long-term follow-up (mean, 8 years). Of the observed patients, 3 (1%) were diagnosed with phyllodes tumor on follow-up. Eighteen of 52 patients (35%) who received excision had an upgrade of diagnosis to phyllodes tumor. Sensitivity and specificity of the pathologist's comment of concern for phyllodes tumor on a CNB demonstrating FELs without definitive phyllodes tumor diagnosis were 82% and 93%, respectively. Our policy of selective excision of FELs without definitive phyllodes tumor diagnosis resulted in safe avoidance of many surgical procedures.

Local recurrence of invasive micropapillary breast cancer after MammoSite brachytherapy: a case report and literature review.

Controversy exists over the optimal patient selection criteria for accelerated partial-breast irradiation (APBI), which has been introduced as an alternative to whole-breast irradiation. The goal is to select patients with the lowest risk for tumor spread outside of the original lumpectomy bed targeted by the local internal radiation dose. Therefore, patients with more aggressive types of breast cancer might not be ideal candidates for partial breast irradiation. We discuss the case of a 67-year-old woman who presented with local recurrence of invasive micropapillary breast cancer, a rare aggressive tumor type, 5 years after MammoSite brachytherapy. The patient's primary tumor possessed all favorable indicators except for the histology of invasive micropapillary carcinoma. This is the first report of invasive micropapillary carcinoma recurring after APBI. Although this is a single case, it supports the hypothesis that more aggressive types of breast cancer have a higher risk of local recurrence after APBI. We propose that invasive micropapillary carcinoma be considered a potential exclusion criterion until it can be validated in prospective clinical trials. More aggressive treatment approaches including whole-breast irradiation and/or chemotherapy might be needed to reduce the risk of local recurrence for invasive micropapillary breast cancer.

Nuclear survivin predicts recurrence and poor survival in patients with resected nonsmall cell lung carcinoma.

BACKGROUND: Survivin, which is a member of the inhibitor of apoptosis protein gene family, regulates both programmed cell death and mitosis. It has been shown that survivin expression and its subcellular localization both have prognostic value for patients with malignant disease. In this study, the authors investigated whether nuclear or cytoplasmic staining of survivin was a prognostic marker for patients with lung carcinoma. METHODS: Paraffin-embedded tissue blocks from 144 patients with Stage I and II resected nonsmall cell lung carcinoma (NSCLC) were obtained for immunohistochemical staining. Three specimens from each patient were prepared and stained with a survivin-specific antibody. Nuclear and cytoplasmic staining was graded from 1 to 3 based on intensity. RESULTS: Patients who had nuclear staining for survivin had a significantly increased risk of disease recurrence (hazard ratio, 2.95; P = 0.0046) and death (hazard ratio, 2.74; P = 0.0086). CONCLUSIONS: The nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with resected Stage I and II NSCLC.

Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression.

Signaling through the phosphatidylinositol 3-kinase (PI3-kinase) pathway has been associated with lung tumorigenesis. We examined the association between gene copy number of the PI3-kinase catalytic subunit alpha (PIK3CA) and phosphorylated Akt expression in invasive and preinvasive lung cancers. We sought to determine at what stage of tumor development gene copy number increase or phosphorylated Akt overexpression might affect tumor development. We assessed PIK3CA gene copy number by fluorescence in situ hybridization and expression of phosphorylated Akt by immunohistochemistry in 242 invasive and 43 preinvasive lung cancers and correlated our findings with clinical outcome. The PIK3CA was amplified in 70% of squamous carcinomas, 38% of large cell carcinomas, 19% of adenocarcinomas, and 67% of small cell lung cancers. Phosphorylated Akt overexpression was frequently observed, and strongly so in 12 to 17% of lung cancers depending on nuclear or cytoplasmic localization. Neither PIK3CA gene copy number nor phosphorylated Akt protein expression had prognostic significance. In preinvasive lesions, amplification of the PIK3CA and overexpression of phosphorylated Akt were associated with severe dysplasia and each other. These observations suggest frequent and early involvement of the PI3-kinase pathway in lung cancer.