Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with HR+, HER2+ advanced breast cancer: plain language summary of the monarcHER study.

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the results of a study called monarcHER. The study included participants with a certain type of aggressive breast cancer called HR+, HER2+ advanced breast cancer (ABC) that had their disease worsen or return after multiple previous therapies. This summary intends to help you understand the impact of a non-chemotherapy treatment called abemaciclib in people with HR+, HER2+ ABC. When the study was planned, HER2-targeted therapy (ie trastuzumab) was standard treatment and was typically combined with chemotherapy and endocrine therapy (ie fulvestrant). However drug resistance can develop when HER2+ targeted therapy is used for a long time, making it less effective and allowing cancer to grow or spread to other parts of the body. When this happens, few chemotherapy-free options are available. Because of the chemotherapy side effects, this is not desirable. There is an urgent need to develop new, effective, safe, and tolerable treatment options for patients with HR+, HER2+ ABC. The monarcHER study compared the effects of abemaciclib plus trastuzumab with or without fulvestrant compared to the standard of care treatment. WHAT WERE THE RESULTS?: Participants were randomly assigned to 1 of 3 groups: Group A (abemaciclib, trastuzumab and fulvestrant), Group B (abemaciclib and trastuzumab), or Group C (trastuzumab and standard of care chemotherapy). The study compared the length of time patients took study treatments without worsening or dying from their breast cancer. This is called the progression free survival (PFS). Participants in Group A had a longer median PFS than those in groups B and C (8.3 months, 5.7 months and 5.7 months respectively). There was no notable difference in PFS between participants in Groups B and C. Additionally, the study looked at the side effects with each treatment group. The most common side effect which is considered severe or lifethreatening was neutropenia, defined as decreased white blood cell levels. Neutropenia may lead to an increased risk of getting infections. However, the percentage of patients experiencing neutropenia was similar in all groups A, B and C (27%, 22% and 26%, respectively). Patients in groups A (79%) and B (78%) who received abemaciclib experienced similar rates of diarrhea. WHAT DO THE RESULTS MEAN?: The data from the monarcHER study suggest that the combination of abemaciclib, trastuzumab, and fulvestrant may offer a chemotherapy-free option for patients with HR+, HER2+ ABC who have experienced worsening of disease despite multiple prior therapies.

Lobar versus sublobar resection for atypical lung carcinoid: An analysis from the National Cancer Database.

BACKGROUND: There is a knowledge gap regarding lobar versus sublobar resection for atypical carcinoid (AC) of the lung. As such, the authors sought to understand and analyze the outcomes of sublobar resection versus lobectomy in this patient population. METHODS: A retrospective analysis using the National Cancer Database was performed to compare overall survival (OS) between patients treated with lobectomy and patients treated with sublobar resection for AC of the lung between the years 2004 and 2016. Patient characteristics were compared with χ2 tests. The Kaplan-Meier method was used to estimate OS distributions, and the log-rank test was used to compare distributions by treatment strategy. A multivariable Cox regression model was used to assess associations between the treatment strategy and OS. A propensity score matching method was also implemented to further eliminate treatment selection bias in the study sample. RESULTS: The database identified 669 patients with T1-T4 and N0-N3 lung ACs that were surgically resected. Unadjusted Kaplan-Meier survival curves did not demonstrate an OS difference between lobectomy and sublobar resection (p = .094). After propensity score matching, curves demonstrated a numerical improvement in OS with lobectomy; however, it was not statistically significant (p = .5). In a subgroup analysis, lobectomy and node-negative disease were associated with the best OS, whereas sublobar resection and node-positive disease were associated with the worst OS (p < .0001). Nodal involvement was associated with worse survival, regardless of surgical treatment (p < .0001). CONCLUSIONS: In patients with T1-T4 and N0-N3 ACs of the lung, lobectomy was not associated with an improvement in OS in comparison with sublobar resection.

Evaluating survival in subjects with astrocytic brain tumors by dynamic susceptibility-weighted perfusion MR imaging.

PURPOSE: Studies have evaluated the application of perfusion MR for predicting survival in patients with astrocytic brain tumors, but few of them statistically adjust their results to reflect the impact of the variability of treatment administered in the patients. Our aim was to analyze the association between the perfusion values and overall survival time, with adjustment for various clinical factors, including initial treatments and follow-up treatments. MATERIALS AND METHODS: This study consisted of 51 patients with astrocytic brain tumors who underwent perfusion-weighted MRI with MultiHance® at a dose of 0.1 mmol/kg prior to initial surgery. We measured the mean rCBV, the 5% & 10% maximum rCBV, and the variation of rCBV in the tumors. Comparisons were made between patients with and without 2-year survival using two-sample t-test or Wilcoxon rank-sum test for the continuous data, or chi-square and Fisher exact tests for categorical data. The multivariate cox-proportional hazard regression was fit to evaluate the association between rCBV and overall survival time, with adjustment for clinical factors. RESULTS: Patients who survived less than 2 years after diagnosis had a higher mean and maximum rCBV and a larger variation of rCBV. After adjusting for clinical factors including therapeutic measures, we found no significant association of overall survival time within 2 years with any of these rCBV values. CONCLUSIONS: Although patients who survived less than 2 years had a higher mean and maximum rCBV and a larger variation of rCBV, rCBV itself may not be used independently for predicting 2-year survival of patients with astrocytic brain tumors.

The impact of histology in the outcomes of patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) and adjuvant chemotherapy.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is the standard of care treatment for nonsurgical patients with early-stage non-small cell lung cancer (NSCLC). A recent report has indicated an improvement in overall survival (OS) with adjuvant chemotherapy in patients with tumors ≥ 4 cm treated with SBRT. We present a retrospective study evaluating the impact of histology in patients treated with SBRT and adjuvant chemotherapy. MATERIALS AND METHODS: Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 12,055). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup. We performed subgroup analysis for the three main NSCLC histologies (i.e., adenocarcinoma, squamous cell carcinoma (SCC), and large cell). RESULTS: In patients with adenocarcinoma, SCC and, large cell carcinoma; adjuvant chemotherapy was associated with worse OS in tumors < 4 cm (P<.0001, P<.0099, and P=.0082, respectively). In patients with adenocarcinoma and tumor ≥ 4 cm, adjuvant chemotherapy was not associated with improved OS (P=.262); however, in patients with SCC and large cell, adjuvant chemotherapy improved OS (P<.0001, and P=.0129, respectively). CONCLUSION: In patients with NSCLC ≥ 4 cm treated with SBRT, adjuvant chemotherapy was associated with improved OS in patients with SCC and large cell histologies.

Omega-3 Long-Chain Polyunsaturated Fatty Acids Intake by Ethnicity, Income, and Education Level in the United States: NHANES 2003-2014.

Although there are many recognized health benefits for the consumption of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA), intake in the United States remains below recommended amounts. This analysis was designed to provide an updated assessment of fish and n-3 LCPUFA intake (eicosapentaenoic (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States adult population, based on education, income, and race/ethnicity, using data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES) (n = 44,585). Over this survey period, participants with less education and lower income had significantly lower n-3 LCPUFA intakes and fish intakes (p < 0.001 for all between group comparisons). N-3 LCPUFA intake differed significantly according to ethnicity (p < 0.001), with the highest intake of n-3 LCPUFA and fish in individuals in the "Other" category (including Asian Americans). Supplement use increased EPA + DHA intake, but only 7.4% of individuals consistently took supplements. Overall, n-3 LCPUFA intake in this study population was low, but our findings indicate that individuals with lower educational attainment and income are at even higher risk of lower n-3 LCPUFA and fish intake.

Adjuvant chemotherapy following SBRT for early stage non-small cell lung cancer (NSCLC) in older patients.

Adjuvant chemotherapy improves overall survival (OS) following stereotactic body radiotherapy (SBRT) in patients with early stage non-small cell lung cancer and tumors ≥four cm. Here, we aim to evaluate its role following SBRT in older patients. Patients >70 years diagnosed with clinical stages I-II NSCLC, (N0 disease), who received SBRT, were identified using the National Cancer Database (n = 7042). The Kaplan-Meier method was used to estimate OS, and the log-rank test was used to compare distributions by treatment strategy overall and within clinical stages I and II. There were 3533 female patients (50.2%), and 6074 (86.3%) had stage I disease. Among stage I patients, 643 (10.6%) received adjuvant chemotherapy, compared to 372 stage II patients (38.4%). Median OS was better with SBRT in patients with stage I disease (25.4 vs. 20.3 months; p < .001); while patients with stage II NSCLC had better OS with SBRT + chemotherapy (20.2 vs. 14.2 months; p < .001). On multivariate analysis, patients with stage I NSCLC who received SBRT alone had better overall survival (HR: 0.79; 95% CI, 0.73, 0.87). SBRT alone was associated with an increased risk of death in patients with stage II disease (HR: 1.34; 95% CI, 1.15, 1.55). Patients with tumors ≥4 cm had better OS with SBRT + chemotherapy (18.5 vs. 15.5 months; p = .003), while patients with tumors <4 cm did better with SBRT (median OS of 24.1 vs. 20.3 months; p < .001). In >70 years old patients with tumors ≥4 cm, adjuvant chemotherapy following SBRT was associated with improved OS.

HPV Status and Survival in Non-Oropharyngeal Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND/AIM: HPV-mediated oropharyngeal squamous cell carcinoma is associated with an increased survival. The prognostic value of HPV status for other primary sites is unclear. We aimed to assess the effect of HPV status on overall survival in patients with non-oropharyngeal head and neck squamous cell carcinoma (non-OPSCC) using the National Cancer Database (NCDB). PATIENTS AND METHODS: Adults with non-OPSCC [gum, lip, floor of mouth, tongue (excluding base), hypopharynx, nasopharynx, other pharynx] and known HPV status were included in our study. Associations between HPV status, primary site, patient characteristics and overall survival (OS) were assessed. RESULTS: HPV positivity was associated with a better OS compared to HPV-negative patients (HR=0.83, 95%CI=0.74-0.93, p<0.001). Female gender, gum, lip, nasopharynx primaries, and private insurance predicted for improved OS. CONCLUSION: HPV positivity and female gender are good prognostic factors in non-OPSCC. Routine HPV testing should be considered for HPV positive non-OPSCC, as well as studies evaluating de-escalation of treatment if this association is confirmed.

n-3 Docosapentaenoic Acid Intake and Relationship with Plasma Long-Chain n-3 Fatty Acid Concentrations in the United States: NHANES 2003-2014.

The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250-500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003-2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20-55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (ß = 138.5; p < 0.001) and DHA (ß = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (ß = 13.15; p = 0.001 and ß = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.

Association Between Treatment Facility Volume, Therapy Types, and Overall Survival in Patients With Stage IIIA Non-Small Cell Lung Cancer.

BACKGROUND: There is significant heterogeneity in the treatment of stage IIIA non-small cell lung cancer (NSCLC). This study evaluated the therapeutic and survival disparities in patients with stage IIIA NSCLC based on the facility volume using the National Cancer Database. METHODS: Patients with stage IIIA NSCLC diagnosed from 2004 through 2015 were included. Facilities were classified by tertiles based on mean patients treated per year, with low-volume facilities treating ≤8 patients, intermediate-volume treating 9 to 14 patients, and high-volume treating ≥15 patients. Cox multivariate analysis was used to determine the volume-outcome relationship. RESULTS: Analysis included 83,673 patients treated at 1,319 facilities. Compared with patients treated at low-volume facilities, those treated at high-volume centers were more likely to be treated with surgical (25% vs 18%) and trimodality (12% vs 9%) therapies. In multivariate analysis, facility volume was independently associated with all-cause mortality (P<.0001). Median overall survival by facility volume was 15, 16, and 19 months for low-, intermediate-, and high-volume facilities, respectively (P<.001). Compared with patients treated at high-volume facilities, those treated at intermediate- and low-volume facilities had a significantly higher risk of death (hazard ratio, 1.09 [95% CI, 1.07-1.11] and 1.11 [95% CI, 1.09-1.13], respectively). CONCLUSIONS: Patients treated for stage IIIA NSCLC at high-volume facilities were more likely to receive surgical and trimodality therapies and had a significant improvement in survival.

Adjuvant Systemic Therapy in Patients With Early-Stage NSCLC Treated With Stereotactic Body Radiation Therapy.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting. METHODS: Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 11,836). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup. RESULTS: In patients with T2bN0, median OS in the SBRT alone and SBRT plus adjuvant chemotherapy groups were 16.5 months versus 24.2 months, respectively (95% confidence interval [CI]: 14.1-20.1 months and 18.8-33.3 months, respectively; p < .001); whereas for T3N0, median OS times were 13 months and 20.1 months, respectively (95% CI: 11.7-14.5 mohths and 17.7-21.9 months, respectively; p < .001). For tumors 4 cm or larger and node-negative disease, median OS was 15.9 months in the SBRT-alone group, and 19 months in the SBRT-plus-chemotherapy group (95% CI: 15.1-16.8 months and 17.9-20.8 months, respectively; p < .001). For patients with tumors less than 4 cm and node-negative disease, the median OS was 28.5 months in the SBRT-alone group and 24.3 months in the SBRT-plus-chemotherapy group (95% CI: 27.4-29.4 months and 22.8-26.1 months, respectively; p < .001). CONCLUSIONS: SBRT followed by adjuvant chemotherapy was associated with improved OS in comparison with SBRT alone in patients with T greater than or equal to 4 cm, similar to that seen after surgery.

Loss of Dnmt3a induces CLL and PTCL with distinct methylomes and transcriptomes in mice.

Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EµSRα-tTA;Teto-Cre;Dnmt3afl/fl; Rosa26LOXPEGFP/EGFP (Dnmt3aΔ/Δ) mice. The extent to which molecular changes overlap between these diseases is not clear. Using high resolution global methylation and expression analysis we show that whereas patterns of methylation and transcription in normal B-1a cells and CD8-positive T cells are similar, methylomes and transcriptomes in malignant B-1a and CD8+ T cells are remarkably distinct, suggesting a cell-type specific function for Dnmt3a in cellular transformation. Promoter hypomethylation in tumors was 10 times more frequent than hypermethylation, three times more frequent in CLL than PTCL and correlated better with gene expression than hypermethylation. Cross-species molecular comparison of mouse and human CLL and PTCL reveals significant overlaps and identifies putative oncogenic drivers of disease. Thus, Dnmt3aΔ/Δ mice can serve as a new mouse model to study CLL and PTCL in relevant physiological settings.