Most patients are eligible for an alternative to conventional whole breast irradiation for early‐stage breast cancer: A National Cancer Database Analysis

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery.     

Brain iron in patients with Parkinson disease: MR visualization using gradient modification

In patients with Parkinson disease, improved visualization of brain iron on a mid-field-strength magnet can be obtained with T2-weighted images and elimination of phase-encoding artifacts. A long echo delay time accentuates the loss of signal from brain iron. However, the long pulse sequence creates phase-encoding artifacts from CSF pulsations at the level of the basal ganglia. These artifacts are eliminated and resolving power increased with additional pulsing in the slice-selective and read gradients. Elimination of motion artifacts enhances visualization of brain iron in three ways: (1) extrapyramidal nuclei containing iron have better definition, (2) abnormalities are better identified, and (3) pseudolesions disappear. Our findings suggest there is significant improvement in the resolving power of brain iron on MR scans made with a mid-field-strength scanner when gradient modification is used.     

Reverse‐Phase Protein Array for Prediction of Patients at Low Risk of Developing Bone Metastasis From Breast Cancer

Background.

A biomarker that predicts bone metastasis based on a protein laboratory assay has not been demonstrated. Reverse-phase protein array (RPPA) enables quantification of total and phosphorylated proteins, providing information about their functional status. The aim of this study was to identify bone-metastasis-related markers in patients with primary breast cancer using RPPA analysis.

Patients and Methods.

Tumor samples were obtained from 169 patients with primary invasive breast carcinoma who underwent surgery. The patients were categorized by whether they developed breast cancer bone metastasis (BCBM) during follow-up. Clinical characteristics and protein expression by RPPA were compared and verified by leave-one-out cross-validation.

Results.

Lymph node status (p = .023) and expression level of 22 proteins by RPPA were significantly correlated with BCBM in logistic regression analysis. These variables were used to build a logistic regression model. After filtering the variables through a stepwise algorithm, the final model, consisting of 8 proteins and lymph node status, had sensitivity of 30.0%, specificity of 90.5%, positive predictive value of 30.0%, and negative predictive value of 90.5% in the cross-validation. Most of the identified proteins were associated with cell cycle or signal transduction (CDK2, CDKN1A, Rb1, Src, phosphorylated-ribosomal S6 kinase, HER2, BCL11A, and MYH11).

Conclusion.

Our validated model, in which the primary tumor is tested with RPPA, can predict patients who are at low risk of developing BCBM and thus who likely would not benefit from receiving a bisphosphonate in the adjuvant setting. Clinical trials excluding these patients have the potential to clarify the benefit of bisphosphonates in the adjuvant setting.     

Mucuna pruriens proves more effective than L-DOPA in Parkinson's disease animal model

Seeds of the Mucuna pruriens plant, now known to contain L -DOPA, have long been used for the treatment of Parkinson's disease patients in ancient Eastern Indian ethnotherapeutics. Following validation of the intrastraital 6-OHDA injection with amphetamine in the parkinsonian rat model, the animals were fed synthetic L -DOPA (125 or 250 mg/kg) or Mucuna pruriens endocarp (MPE, 2.5 or 5.0 g/kg) mixed with rat chow (n =6, for each dose and drug). Controls received no drug. An additional dose of L -DOPA or MPE in the same doses plus carbidopa (50 mg/kg) were administered via gavage (controls received only carbidopa 50 mg/kg) 1 h prior to testing with rotometer. Contralateral rotation (to the side of the 6-OHDA lesion) (CLR) was recorded for 240 min as a measure of antiparkinsonian activity. Results indicated that dose for dose, MPE showed twice the antiparkinsonian activity compared with synthetic L -DOPA in inducing CLR in the parkinsonian animal model. This study suggests that MPE may contain unidentified antiparkinsonian compounds in addition to L -DOPA, or it may have adjuvants that enhance the efficacy of L -DOPA. © 1997 John Wiley & Sons, Ltd.     

Bilateral striopallidodentate calcinosis: clinical characteristics of patients seen in a registry.

Clinical features in bilateral striopallidodentate calcinosis (BSPDC), popularly referred to as Fahr's disease (five autosomal dominant families and eight sporadic cases, n = 38), recruited through a registry, are reported. Applying uniform criteria, cases reported in the literature (n = 61) were combined for detailed analysis. The mean (+/- S.D.) age of Registry patients was 43 +/- 21 and that of literature was 38 +/- 17. In combined data set (n = 99), 67 were symptomatic and 32 were asymptomatic. Of the symptomatic, the incidence among men was higher compared with women (45:22). Movement disorders accounted for 55% of the total symptomatic patients. Of the movement disorders, parkinsonism accounted for 57%, chorea 19%, tremor 8%, dystonia 8%, athetosis 5%, and orofacial dyskinesia 3%. Overlap of signs referable to different areas of central nervous system (CNS) was common. Other neurologic manifestations included: cognitive impairment, cerebellar signs, speech disorder, pyramidal signs, psychiatric features, gait disorders, sensory changes, and pain. We measured the total volume of calcification using an Electronic Planimeter and Coordinate Digitizer. Results suggest a significantly greater amount of calcification in symptomatic patients compared to asymptomatic patients. This study suggests that movement disorders are the most common manifestations of BSPDC, and among movement disorders, parkinsonism outnumber others.     

A comparison of phonemic, semantic, and alternating word fluency in Parkinson's disease.

Word fluency in 45 medicated non-demented Parkinson's disease (PD) patients and 45 normal control subjects was studied with a Phonemic Word Fluency (PWF) task using the letters F, A, and S, a Semantic Word Fluency (SWF) task using the categories animals, boys' names, and states, and an Alternating Word Fluency (AWF) task requiring the person to alternate between colors and occupations, animals and states, and words beginning with C and P. The number of words generated did not differ for trials with F, A, S, or states, but PD patients generated significantly fewer animal names and boys' names. PD patients also generated significantly fewer words on each of the three AWF trials. The PD patients scored 21% lower than the normal control group on the total AWF score, but only 10% lower for the PWF and SWF scores. The greater impairment on the AWF task which requires the use of internal attentional control to rapidly shift mental set can be considered a type of executive functioning deficit. This is consistent with the growing literature suggesting frontal systems dysfunction in PD and with the view that dopaminergic treatment only incompletely restores functioning in the frontostriatal system.     

p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

The role of p53 family member, p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16^INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell–like DLBCL patients with wide-type TP53. The prognostic impact in germinal-center-B-cell–like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations.