COMPOSITION OF CEREBROSPINAL FLUID IN CLINICALLY NORMAL GRIZZLY BEARS (URSUS ARCTOS HORRIBILIS).

Five cerebrospinal fluid (CSF) samples were collected from four clinically normal grizzly bears from the Washington State University Bear Research, Education, and Conservation Center. CSF samples were collected from the cerebellomedullary cisternal space. Samples were immediately processed and analyzed for microprotein content, red blood cells, white blood cells (WBCs), and differential cell count. Microprotein concentration (range 4.2-14.6 mg/dl; median, less than 6 mg/dl), total WBC count (range 0-2 cells/µl; median 2 cells/µl), and differential WBCs (predominance mononuclear cells) of the five CSF samples were comparable to previously published CSF analyses from clinically normal felines and canines. Providing documentation of CSF composition for clinically normal grizzly bears is important for neurologic disease diagnosis and treatment.

Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadjuvant pathologic tumor response in operable breast cancer patients.

BACKGROUND: To determine the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of clinical examination and breast imaging techniques in determining pathologic complete response in patients with locally advanced breast cancer after neoadjuvant therapy. METHODS: A retrospective review was performed of data collected from patients treated with either neoadjuvant hormonal or chemotherapy between January 2005 and September 2010. Patients were evaluated by one of three surgical breast oncologists before neoadjuvant therapy and within 1 month before surgery by clinical breast examination (CBE), digital mammogram, breast ultrasound, and/or magnetic resonance imaging (MRI). The accuracy, NPV, and PPV of each modality was calculated on the basis of the final pathologic report. Available data from the literature was synthesized. RESULTS: Sixty-two tumors in 61 patients with a mean age of 56 (range 34-87) years were evaluated. Overall accuracy ranged from 54% (CBE) to 80% (breast ultrasound). All modalities had a PPV greater than 75% for identifying the presence of residual disease. The PPV of each modality was generally higher in the younger patients. The NPV of all methods was less than 50%. The accuracy and NPV were compromised even further in younger patients. The combination of our own data with data available from the literature revealed MRI to be superior with regard to accuracy and PPV, but the NPV of MRIs remained poor at 65%. CONCLUSIONS: All measured tests are good at predicting the presence of disease on final pathology, but none are able to reliably predict a pathologic complete response.

The need for axillary dissection in patients with positive axillary sentinel lymph nodes.

The need for completion axillary dissection after a positive sentinel node biopsy continues to be challenged. In the 2 years since we last reviewed this subject, a number of authors have shared their experiences about micrometastatic disease and isolated tumor cells, opining both for and against axillary treatment. Data from the ACOSOG Z0011 trial and other small studies do not appear to support the use of completion axillary dissection even for macro-metastatic disease in patients with clinically node-negative (N0) disease. While existing guidelines still recommend axillary dissection for patients with clinically positive nodes, even when conversion to clinically negative disease following neoadjuvant chemotherapy has occurred, this concept is being questioned in ACOSOG Z1071 and in several other recent small trials. The surgical approach to the treatment of breast cancer continues to move away from the traditional Halstedian concept.

Representation of Women and Minorities in Clinical Trials for New Molecular Entities and Original Therapeutic Biologics Approved by FDA CDER from 2013 to 2015.

BACKGROUND: The U.S. Food and Drug Administration (FDA) has made efforts to encourage adequate assessment of women, racial/ethnic minorities, and geriatric participants in clinical trials through regulations and guidance documents. This study surveyed the demographics of clinical trial participants and the presence of efficacy and safety analyses by sex for new drugs approved between 2013 and 2015 by the FDA Center for Drug Evaluation and Research. METHODS: New drug marketing applications submitted to FDA were surveyed for demographic data (sex, race, ethnicity, and age) and the presence of sex-based analyses for efficacy and safety. The Ratio of the Proportion of women in clinical trials for the indicated disease population relative to the estimated Proportion of women in the disease population (PPR) was calculated for new drug indications. RESULTS: Of the 102 new drugs in this cohort (defined as new molecular entity drugs and original therapeutic biologics), sex was reported for >99.9% of trial participants, and women accounted for 40.4% of these participants. An estimated 77.2% of participants were White, 6.4% were Black/African American, and 29.1% were aged ≥65 years. Sex-based analyses for both efficacy and safety were conducted for 93.1% of applications. PPR was calculated for 82 new drugs for a total of 60 indications, of which 50 indications (83.3%) had a PPR ≥0.80. CONCLUSIONS: Sex data are now collected for almost all study participants, and this study shows appropriate sex participation for most new drugs when estimated disease prevalence by sex (PPR) is considered. Therapeutic area and disease indication are important considerations when assessing the sex of participants because variation occurs depending on the disease under study. Some racial minorities, especially Blacks/African Americans, are still not well represented in most drug development programs and remain an area where improvement is needed.

Sentinel lymph node biopsy and management of the axilla in ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) of the breast historically has been a disease detected by physical examination, diagnosed by open surgical biopsy, and treated by mastectomy and axillary dissection. It is now increasingly detected by screening mammography, diagnosed by needle core biopsy, and treated by lumpectomy, with axillary dissection having been abandoned and sentinel node biopsy being used in axillary staging. However, outcomes related to sentinel node biopsy in DCIS have not been validated in well-controlled clinical trials. Current guideline recommendations are to use sentinel node biopsy when needle core biopsy is highly suspicious for invasive cancer or where there is a high-risk DCIS when lumpectomy identifies invasive breast cancer with the DCIS, or when mastectomy is performed for extensive DCIS. Routine use of sentinel node biopsy for DCIS is not supported.

Axillary recurrences following positive sentinel lymph node biopsy with individual tumor cells or micrometastases and no axillary dissection.

The increased use of sentinel lymph node (SLN) excision for staging the axilla in women with breast cancer has benefited women by lowering morbidity and at the same time has raised issues related to the extent of treatment needed to the nodal basin. This is of particular concern when micrometastases or isolated tumor cells are found in the sentinel nodes on the final pathology. The probability of finding metastatic disease in non-sentinel lymph nodes (NSLN) ranges from 0 to 20% with only micrometastatic deposits in the SLN. Very low rates (0-3.7%) of axillary recurrence have been reported in selected patients with micrometastases tumor in sentinel nodes who have not had a completion axillary node dissection (ALND). Risk factors for additional positive NSLN include primary tumor size, the presence of lymphovascular invasion and the size of the SN metastatic deposit. Currently, the decision to not complete the ALND when micrometastic disease is found in the SLN should be made on a case-by-case basis. One should consider the tumor characteristics, findings within the SLN, and a multidisciplinary treatment plan. Clinical trial results may help to resolve the dilemma. There appears to be a low risk for axillary recurrence.