The Impact of Medicaid Expansion Under the Affordable Care Act on the Gap Between American Indians and Whites in Breast Cancer Management and Prognosis.

BACKGROUND: Breast cancer (BC) death rates in the USA have not significantly declined for American Indians (AIs) in comparison to Whites. Our objective was to determine whether Medicaid Expansion as part of the Affordable Care Act led to improved BC outcomes for AIs relative to Whites. PATIENTS AND METHODS: Using the National Cancer Database, we conducted a retrospective cohort study. Included were BC patients who were AI and White; 40 to 64 years of age; diagnosed in 2009 to 2016; lived in states that expanded Medicaid in January 2014, and states that did not expand Medicaid. Our outcomes were stage at diagnosis, insurance status, timely treatment, and 3-year mortality. RESULTS: There were 359,484 newly diagnosed BC patients, 99.49% White, 0.51% AI. Uninsured rates declined more in the expansion states than in the nonexpansion states (OR = 0.44, 95% CI: 0.15-0.97, P < 0.001). Lower rates of Stage I BC diagnosis was found in AIs compared to Whites (46.58% vs. 55.33%, P < .001); these differential rates did not change after Medicaid expansion. Rates of definitive treatment initiation within 30 days of diagnosis declined after Medicaid expansion (P < .001); there was a smaller decline in the expansion states (OR 1.118, 95% CI: 1.09, 1.15, P < .001). Three year mortality was not different between expansion and nonexpansion states post Medicaid expansion. CONCLUSIONS: In newly diagnosed BCs, uninsured rates declined more in the states that expanded Medicaid in January 2014. Timely treatment post Medicaid expansion declined less in states that expanded Medicaid. There was no differential benefit of Medicaid expansion in the 2 races.

Differences in Breast Cancers Among American Indian/Alaska Native and non-Hispanic Whites in the USA.

IMPORTANCE: Breast cancer (BC) death rates have not improved for American Indian/Alaska Native (AI/AN) women, whereas, it has significantly decreased for non-Hispanic White (White) women. OBJECTIVE: Delineate the differences in patient and tumor characteristics among AI/AN and Whites with BC, and its impact on age and stage at diagnosis as well as overall survival (OS). METHODS: Hospital-based, cohort study using the National Cancer Database to identify female AI/AN and Whites diagnosed with BC between the years 2004 and 2016. RESULTS: BC in 6866 AI/AN (0.3%) and 1,987,324 Whites (99.7%) were studied. The median age at diagnosis was 58 for AI/AN and 62 for Whites. AI BC patients traveled double the distance for treatment, lived in lower median income zip codes, had a higher percentage of uninsured, higher comorbidities, lower percentage of Stage 0/I, larger tumor size, greater number of positive lymph nodes, higher proportion of triple negative and HER2-positive BC than Whites. All the above comparisons were significant, p<0.001. Association between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AI/AN and Whites. Unadjusted OS was worse for AI/AN as compared to Whites (HR=1.07, 95% CI=1.01-1.14, p=0.023). After adjustment of all covariates, OS was not different (HR=1.038, 95%CI=0.902-1.195, p=0.601). CONCLUSION: There were significant differences in patient/tumor characteristics among AI/AN and White BC which adversely impacted OS in AI/AN. However, when adjusted for various covariates, the survival was similar, suggesting that the worse survival in AI/AN is mostly the impact of known biological, socio-economic, and environmental determinants of health.

Palbociclib in Patients With Non-Small-Cell Lung Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non-small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported. METHODS: Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon's two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting. CONCLUSION: Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.

Delivering Precision Oncology in a Community Cancer Program: Results From a Prospective Observational Study.

INTRODUCTION: Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care. MATERIALS AND METHODS: Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes. RESULTS: A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration-approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen. CONCLUSION: A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.

Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer.

OBJECTIVES: Patients with advanced squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options. Inhibition of histone deacetylases (HDACs) represents a novel therapeutic approach warranting additional investigation in solid tumors. METHODS: A phase II trial of single agent romidepsin, an HDAC inhibitor, was performed in 14 patients with SCCHN who provided consent for pre- and post-therapy samples of accessible tumor, blood and uninvolved oral mucosa. Romidepsin was administered at 13 mg/m(2) as a 4-h intravenous infusion on days 1, 8 and 15 of 28 day cycles, with response assessment by RECIST every 8 weeks. RESULTS: Objective responses were not observed, although 2 heavily pretreated patients had brief clinical disease stabilization. Observed toxicities were expected, including frequent severe fatigue. Immunohistochemical analysis of 7 pre- and post-treatment tumor pairs demonstrated induction of p21(Waf1/Cip1) characteristic of HDAC inhibition, as well as decreased Ki67 staining. Exploratory microarray analyses of mucosal and tumor samples detected changes in gene expression following romidepsin treatment that were most commonly associated with regulation of transcription, cell cycle control, signal transduction, and electron transport. Treatment with romidepsin did not alter the extent of DNA methylation of candidate gene loci (including CDH1 and hMLH1) in SCCHN tumors. CONCLUSIONS: Single agent romidepsin has limited activity for the treatment of SCCHN but can effectively achieve tumor-associated HDAC inhibition. Although tolerability of romidepsin in this setting may be limiting, further evaluation of other HDAC inhibitors in combination with active therapies may be justified.

Modulation of CDK2-AP1 (p12(DOC-1)) expression in human colorectal cancer.

We have previously demonstrated an association between microsatellite instability and decreased CDK2-AP1 (p12(DOC-1)) expression in human colorectal cancer (CRC) cell lines. In those same studies, induction of CDK2-AP1 expression promoted both cell cycle arrest and apoptosis. The goals of our present study were to better understand the mechanisms leading to reduced CDK2-AP1 expression in microsatellite unstable (MSI) CRC and to study further the effect of CDK2-AP1 modulation on cell proliferation and apoptosis utilizing RNA interference (RNAi) techniques. We used direct sequencing to screen for mutations of the poly (T)8 microsatellite-like region in the 3' end of the CDK2-AP1 gene in 24 CRC cell lines. We then utilized an in vitro human mismatch repair (MMR) recombinant system to assess for correction of the mutation and changes in CDK2-AP1 expression secondary to hMLH1 transfection. We also investigated the effect of CDK2-AP1 modulation in four settings: (1) native CDK2-AP1 absence, (2) endogenous CDK2-AP1 expression, (3) RNAi-induced CDK2-AP1 inhibition and (4) induced CDK2-AP1 over expression. The mutation - del T poly (T)8 - at the 3' end of the CDK2-AP1 gene was found in 3/12 (25%) of MSI CRC cell lines, but in none of the microsatellite stable samples (0/12). Interestingly, when wild-type MMR protein - MLH1 - was induced in an in vitro human recombinant system, the del T poly (T)8 mutation was reversed and CDK2-AP1 expression increased. RNAi-mediated CDK2-AP1 inhibition was associated with decreased apoptosis and increased cell proliferation in CDK2-AP1-non deficient CRC cell lines. We conclude that mutations in the microsatellite-like sequence of the CDK2-AP1 gene in MSI CRC are associated with decreased CDK2-AP1 expression. In addition, modulation of CDK2-AP1 expression in human CRC alters cell proliferation and apoptosis.

Metastatic carcinoma: an unusual cause of focal brain lesions in HIV infection.

The most common causes of focal brain lesions (FBLs) in patients with HIV infection are cerebral toxoplasmosis, primary central nervous system lymphoma (PCNSL), and progressive multifocal leukoencephalopathy. Neoplasms other than PCNSL are uncommon. We report a rare case of metastatic carcinoma causing an FBL in a patient with HIV infection. The diagnostic workup and further management of FBLs in HIV are outlined in this review. The standard approach includes a lumbar puncture and cerebrospinal fluid (CSF) analysis for cytology and Epstein-Barr virus (EBV) DNA testing by polymerase chain reaction. Empiric therapy for PCNSL is justifiable for patients with positive CSF EBV-DNA test results and a positive single-photon emission computed tomography (SPECT) scan, especially if there has been no response to antitoxoplasmosis therapy. Brain biopsy may be indicated, however, in select cases that do not meet these criteria in order to identify potentially treatable infections and PCNSL.