Lack of racial differences in clinical outcomes of breast cancer patients receiving neoadjuvant chemotherapy: a single academic center study.

PURPOSE: To examine the association between race and clinical outcomes (pathological complete response [pCR]; recurrence-free survival [RFS], and overall survival [OS]) in patients diagnosed with triple-negative (TNBC) or HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: Patients who self-identified as non-Hispanic white (NHW) or non-Hispanic Black (NHB) and were diagnosed with Stage I-III TNBC (n = 171 including 124 NHW and 47 NHB) and HER2-positive (n = 161 including 136 NHW and 25 NHB) breast cancer who received NAC from 2000 to 2018 at Roswell Park Comprehensive Cancer Center were included. Associations of race with pCR and survival outcomes were evaluated using logistic and Cox regression models, respectively. RESULTS: There was no statistically significant difference in pCR between NHB and NHW patients with TNBC (31.9 vs 29.8%; OR: 1.11, 95% CI 0.54-2.29) or HER2-positive breast cancer (36.0 vs 39.7%; OR: 0.87, 95% CI 0.36-3.11). After controlling for potential confounders, including age, stage, treatment regimens, insurance status, and comorbidities, no statistically significant difference in OS or RFS was observed between NHB and NHW patients within either subtype. CONCLUSION: TNBC or HER2-positive breast cancer patients treated at a single academic center in Buffalo, NY, showed similar outcomes independent of patients' race. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography, and clinical outcomes are warranted.

Community-engaged asset mapping with Latinx immigrant families of youth with disabilities.

Asset mapping is a participatory methodology that engages community members in identifying services and settings that promote health and well-being. This study aimed to identify community assets from the perspective of Latinx immigrant families with youth with disabilities. Latinx immigrant families (n = 21) participated in the mapping, followed by a reflection session and an open forum (n = 30). The findings revealed that families identified faith-based organizations and social service agencies as some of the main assets in their communities, while they identified mental health services as the most needed. The results also showed that participants preferred to utilize services and resources that are within walking distance of their homes, provide safe spaces, treat them well, offer bilingual services, do not require documentation, and are affordable. This study has important implications for community scholars and practitioners interested in implementing asset-based methodologies that focus on participants as experts of their own realities and agents of change and that promote advocacy and empowerment actions.

Latinx Parents' Perceptions of Neighborhood Walking Safety for Their Youth With Intellectual Disabilities: A Mixed-Methods Investigation.

Increased walking distance and frequency has been linked to positive health outcomes. Neighborhood walkability disproportionately impacts youth with intellectual and developmental disabilities (IDD). We investigated concerns of Latinx parents of youth with IDD about walkability and their impact on families' walking behavior. We surveyed Latinx parents of youth with IDD (n = 21) and compared results with the general population. Results were triangulated with a focus group (n = 5). Survey data were analyzed using a Mann-Whitney U test, and focus group data via thematic analysis. We found a significant difference (P < .05) between parents of youth with IDD and the general population on perceived aesthetics, opportunity to participate, and satisfaction. Latinx parents and their youth with IDD experience disparities in the safety and pleasantness of their communities for walking, which may contribute to decreased community participation, poorer health outcomes, and lower levels of neighborhood satisfaction among this already vulnerable population.

Barriers to and facilitators of community participation among Latinx migrants with disabilities in the United States and Latinx migrant workers in Canada: An ecological analysis.

Individuals migrate to improve their wellbeing and quality of life, and often experience adverse situations, both during the process of migration and once within the host country. The purpose of this paper is to unpack the barriers to and facilitators of community participation, among Latinx immigrants with disabilities in the United States and Latinx migrant workers in Canada, following the Social Ecological Model. The authors draw from an appraisal of existing literature and their own participatory research with Latinx immigrants. Based on this integrative literature review, Latinx experience individual issues such as language barriers and lack of knowledge of the services available to them. At the community level they experience discrimination, limited opportunities for community participation, and lack of opportunities for meaningful employment. At the systemic and policy level in the United States, the antimigrant political environment keeps Latinx immigrants with disabilities from participating in their communities due to fear of deportation. In Canada, Latinx workers experience the paradox of migration and discrimination. The discussion of barriers and facilitators is followed by recommendations for community research and action.

Treatment recommendations to cancer patients in the context of FDA guidance for next generation sequencing.

BACKGROUND: Regulatory approval of next generation sequencing (NGS) by the FDA is advancing the use of genomic-based precision medicine for the therapeutic management of cancer as standard care. Recent FDA guidance for the classification of genomic variants based on clinical evidence to aid clinicians in understanding the actionability of identified variants provided by comprehensive NGS panels has also been set forth. In this retrospective analysis, we interpreted and applied the FDA variant classification guidance to comprehensive NGS testing performed for advanced cancer patients and assessed oncologist agreement with NGS test treatment recommendations. METHODS: NGS comprehensive genomic profiling was performed in a CLIA certified lab (657 completed tests for 646 patients treated at Roswell Park Comprehensive Cancer Center) between June 2016 and June 2017. Physician treatment recommendations made within 120 days post-test were gathered from tested patients' medical records and classified as targeted therapy, precision medicine clinical trial, immunotherapy, hormonal therapy, chemotherapy/radiation, surgery, transplant, or non-therapeutic (hospice, surveillance, or palliative care). Agreement between NGS test report targeted therapy recommendations based on the FDA variant classification and physician targeted therapy treatment recommendations were evaluated. RESULTS: Excluding variants contraindicating targeted therapy (i.e., KRAS or NRAS mutations), at least one variant with FDA level 1 companion diagnostic supporting evidence as the most actionable was identified in 14% of tests, with physicians most frequently recommending targeted therapy (48%) for patients with these results. This stands in contrast to physicians recommending targeted therapy based on test results with FDA level 2 (practice guideline) or FDA level 3 (clinical trial or off label) evidence as the most actionable result (11 and 4%, respectively). CONCLUSIONS: We found an appropriate "dose-response" relationship between the strength of clinical evidence supporting biomarker-directed targeted therapy based on application of FDA guidance for NGS test variant classification, and subsequent treatment recommendations made by treating physicians. In view of recent changes at FDA, it is paramount to define regulatory grounds and medical policy coverage for NGS testing based on this guidance.

Patients' Preferences for Adjuvant Osimertinib in Non-Small-Cell Lung Cancer After Complete Surgical Resection: What Makes It Worth It to Patients?

BACKGROUND: The ADAURA trial confirmed adjuvant Osimertinib's efficacy in EGFR-mutated Non-small-cell lung cancer (NSCLC), yet the limited mature overall survival (OS) data at approval poses a challenge. This study explores patient preferences in the absence of complete OS information, hypothesizing that disease-free survival (DFS) benefit alone may influence adjuvant Osimertinib pursuit. METHODS: At Roswell Park Comprehensive Cancer Center (Jan-Dec 2021), patients assessed for adjuvant therapy received a survey probing OS and DFS preferences. Scenarios were (a) minimum OS justifying Osimertinib, (b) minimum DFS improvement justifying 3-years of adjuvant Osimertinib, (c) minimum 5-year DFS percent change, and (d) minimum OS justifying copay changes. Results were analyzed. RESULTS: Of 524 NSCLC patients, 51 participated. Scenario 1 saw 56% requiring a 12-month OS benefit for Osimertinib justification. In scenario 2, 72% deemed a 12-month DFS benefit sufficient. Scenario 3 revealed 31% opting out despite a 10% OS increase. Scenario 4 showed varied willingness to pay, with 33% unwilling to any shoulder copayment even with a 10-year OS benefit. CONCLUSION: This study explores patient preferences without complete OS data, revealing diverse thresholds. Factors include employment, education, and willingness to pay. Findings underscore shared decision-making importance. Limitations include sample size, potential biases, and regional focus; larger cohorts are needed for validation.

Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx.

BACKGROUND: Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs. METHODS: Six evaluable patients (33-69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m2; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks. The predetermined primary endpoint was the intratumoral change in the expression of CTL marker, CD8α, in the post-CKM versus pre-CKM tumor biopsies. Patients received follow-up pembrolizumab (200 mg, intravenously, every 3 weeks), starting 3-8 days after completion of CKM. RESULTS: Post-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8+ T cells and their CXCR3+ subset showed transient decreases in blood. One clinical response (breast tumor autoamputation) and three stable diseases were observed. The patient with clinical response remains disease free, with a follow-up of 46 months as of data cut-off. CONCLUSIONS: Short-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes.

Real world outcomes with alpelisib in metastatic hormone receptor-positive breast cancer patients: A single institution experience.

Background: It is critically important to study the real-world data of FDA-approved medications to understand the response rates and toxicities observed in the real-world population not represented in the clinical trials. Methods: We reviewed charts of patients diagnosed with metastatic, hormone receptor-positive, human epidermal growth factor receptor 2 negative, PIK3CA-mutated breast cancer treated with alpelisib from May 2019 to January 2022. Clinical characteristics and treatment outcomes were collected. The association of clinical characteristics with responses and adverse events (AEs) was evaluated using the logistic regression model. Results: 27 patients were included. Median age at alpelisib initiation 67 years (range: 44, 77 years). Majority of patients had excellent performance status at time of alpelisib initiation. Most patients had chronic comorbidities, notably; 2 patients had controlled type 2 diabetes mellitus at time of alpelisib initiation. Majority had a median of three lines of therapy (range: 1, 7) before alpelisib. Clinical responses were determined using RECIST v1.1. 3/27 (11.11%) patients discontinued therapy before response assessment due to grade 3 AEs. Overall response rate was 12.5% (3/24), with all partial responses (PR). The median duration of response was 5.77 months (range: 5.54, 8.98). 14/27 (51.9%) of patients required dose interruption/reduction. Overall, 23/27 (85.19%) patients discontinued alpelisib of which 11 (47.83%) discontinued alpelisib due to AEs. Median duration of treatment was 2 months in patients who had grade 3 AEs (range: <1.00, 8.30) and 6.28 (1.15, 10.43) in those who did not. Any grade AEs were reported in 24/27 (88.9%) patients, namely, hyperglycemia 16/27 (59.3%), nausea 11/27 (40.7%), diarrhea 10/27 (37.0%), fatigue 7/27 (25.9%) and rash 6/27 (22.2%). Grade 3 AEs were reported in 13/27 patients (50%), namely, hyperglycemia in 7/27 (53.8%) patients followed by skin rash 4/27 (30.8%), GI side effects 3/27 (23.1%). Those with progressive disease as best response to alpelisib, had more non-metabolic comorbidities, higher number of liver metastases, PIK3CA E545K mutations, and shorter duration on therapy compared to those with PR and stable disease. Conclusion: Patients should be counseled about the toxicity and modest benefit observed with alpelisib in real-world clinical practice when used in later lines of therapy.

Survival outcomes of alternate dosing schedule of pemetrexed as maintenance therapy in NSCLC: Single institution experience.

BACKGROUND: Maintenance therapy with pemetrexed has shown survival benefit in patients with advanced stage non-small cell lung cancer (NSCLC). The recommended dose schedule is 500 mg/m 2 in 21-day cycles. Prolonged treatment with maintenance pemetrexed can result in cumulative toxicities. We sought to compare treatment outcomes in patients receiving an alternate maintenance schedule in realworld practice. METHODS: This single-center, retrospective study investigated patients with advanced stage (IIIB and IV) NSCLC receiving at least two doses of maintenance pemetrexed from May 1, 2011 to June 30, 2016. The objective was to compare time on treatment with maintenance pemetrexed therapy initiated at a standard schedule (q3 weeks) versus an alternate schedule (q4 weeks or longer). Also evaluated were progressionfree survival (PFS) and overall survival (OS) differences between the two groups. RESULTS: 129 patients were included, of whom 40 started the alternate schedule no later than cycle 3 of treatment (29 of 40 patients initiated maintenance treatment on the alternate schedule). Average time on maintenance treatment for patients appeared to be longer in the patients who received the alternate schedule regimen (195 vs 263 days, p =0.008). OS trended towards better survival among patients receiving the alternate schedule regimen (11.9 vs 18.1 months, p =0.3). Limiting the analysis to ALK wildtype, the patients showed a similar trend, with median PFS (7.6 vs 11.5 months, p =0.46) and OS (11.9 vs 17.6 months, p =0.38), still favoring the alternate schedule. CONCLUSIONS: The alternate dosing schedule of maintenance pemetrexed (q4 weeks or longer) is feasible and not detrimental to OS. Future investigations evaluating the optimal administration schedule of maintenance pemetrexed is warranted.

Current overview of the management of urogenital atrophy in women with breast cancer.

Systemic treatments for women with breast cancer frequently induce urogenital symptoms that can negatively impact a women's quality of life. Urogenital atrophy is frequently undiagnosed and untreated, particularly in breast cancer survivors. Symptoms of urogenital atrophy can usually be relieved with vaginal estrogen preparations, but risk of recurrence and safety is undefined in women with a history of breast cancer. Treatment with nonhormonal modalities including vaginal moisturizers or lubricants and lifestyle modification are the first lines of management. Low-dose vaginal 17 ß-estradiol (vaginal estradiol tablets 10 µg or vaginal estradiol ring) can be considered for the treatment of symptomatic urogenital atrophy in women with a history of breast cancer after appropriate disclosure to the patient. While effective in treating the urogenital symptoms, the safety of such therapy remains uncertain. The decision to offer vaginal estrogen therapy needs to be individualized and should be made jointly with the oncologist.

Breast Cancer and Secondary Cancer Recurrences After Autologous Tissue Reconstruction.

BACKGROUND: The medical literature defining breast cancer recurrence and secondary cancers after autologous tissue reconstruction for breast cancer is sparse. We sought to identify and analyze occurrences at our institution. PATIENTS AND METHODS: A 20-year retrospective review of cancer recurrences and atypical breast neoplasms after autologous tissue breast reconstruction at Roswell Park Comprehensive Cancer Center was conducted after being granted a waiver from the institutional review board. RESULTS: Eighteen locoregional recurrences among 337 cases were identified and analyzed. Overall recurrence rate was 5.3%. Four secondary cancers (1.2%) were radiation-induced angiosarcoma, undifferentiated pleomorphic sarcoma, and metaplastic carcinoma. One case of flat epithelial atypia was identified. CONCLUSION: Our retrospective review found incidence and survival after treatment of breast cancer concordant with reports in the literature. We also identified and analyzed secondary neoplasms, including a unique case of undifferentiated pleomorphic sarcoma and metachronous recurrence of breast carcinoma. A case of recurrence as metaplastic carcinoma was identified.

CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin.

BACKGROUND: The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. OBJECTIVES: This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. METHODS: We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson's biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). RESULTS: Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. CONCLUSIONS: CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

Walkability Safety and Walkability Participation: A Health Concern.

Walking is correlated with both improved physical and emotional health. However, walking behavior is often heavily influenced by environmental conditions. The goal of this study was to examine actual and perceived walkability safety and the relationship between perceived walkability safety and self-rated levels of walkability participation, defined as the number of places one walks within the community on a regular basis. Researchers used a mixed-methods approach, combining direct observations of traffic safety and in-person surveys within a specific Chicago neighborhood from 2015 to 2016 and from 2016 to 2017, respectively. We conducted behavioral assessments on 25 intersections and 48 sidewalks and surveyed 96 pedestrians on perceived walkability safety and walkability participation. Findings showed 68% and 81% of vehicles in 2015 and 2016, respectively did not obey street signs, placing pedestrians at significant risk. Pedestrians expressed concerns about the safety of walking in their neighborhood yet walked to a median of eight places weekly. The results indicated a marginally significant positive relationship between self-reported community participation and walking habits, as well as relationships between various factors of perceived walkability and age, gender, or language of survey completion. It is clear from the results of this study that walkability in this community is not a safe activity. However, walking habits may also be influenced by community satisfaction and SES factors. Communities need to engage in safe driving campaigns and educate walkers on how to protect themselves from distracted drivers. Local governments should implement policy initiatives such as police enforcement and drivers' education campaigns.

Evaluation of Public Health Messages Promoting Early Detection of Dementia Among Adult Latinos With a Living Older Adult Parental Figure.

INTRODUCTION: We aimed to evaluate the resonance of public health messages promoting early detection of dementia in adult Latinos with a living older adult loved one. METHOD: We conducted a mixed-methods study with focus groups and surveys to evaluate eight messages encouraging Latino adults to accompany their older loved one for cognitive assessment. Qualitative data were transcribed and coded, and thematic analysis was conducted. We used descriptive statistics for quantitative data. RESULTS: Participants suggested that messages need to be translated into Spanish and images need to be more natural, present balance between positive and serious facial expressions, show more ethnic/racial diversity, and show family members other than the parents. Five major sociocultural themes affected how the messages were received: stigma, gender roles, the importance of the mother figure, guilt, and family togetherness. CONCLUSION: Public health messages targeting cultural values are needed to effectively encourage early dementia detection in Latinos. Findings can be used to adapt culturally appropriate public health messages encouraging early dementia detection in Latinos.

Outcome of Everolimus-Based Therapy in Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression on Palbociclib.

BACKGROUND: Despite the approval of mTOR inhibitor everolimus and CDK4/6 inhibitors in the management of hormone-receptor-positive HER2 non-amplified metastatic breast cancer (HR+ HER2-MBC), the optimal sequence of therapy is unclear. There are no clinical data on efficacy of everolimus in HR+ HER2-MBC after cancer progresses on CDK4/6 inhibitors. OBJECTIVE: The objective of this study is to find the efficacy of everolimus in HR+ HER2-MBC after they progress on a CDK4/6 inhibitor palbociclib. METHODS: This is a retrospective, 2-institute review of HR+ HER2-MBC from Jan 2015 to March 2018 treated with everolimus after progression on palbociclib. Primary end point was median progression-free survival (PFS), secondary end points objective response rate (ORR), clinical benefit ratio (CBR), and overall survival (OS). RESULTS: Out of 41 women with median age 61 years (33, 87) enrolled, 66% had received adjuvant systemic therapy, 61% had visceral disease, and 95% had prior nonsteroidal aromatase inhibitors. About 83% women had 3 or more chemotherapy or hormonal therapies prior to everolimus. Kaplan-Meier estimates showed a median PFS of 4.2 months (95% confidence interval [CI]: 3.2-6.2). The median OS was 18.7 months (95% CI 9.5 to not reached). Objective response rate and CBR were both 17.1%. CONCLUSION: Everolimus was associated with modest PFS and ORR in HR+ HER2-MBCs postprogression on palbociclib.

The occupational therapy practitioner's role in health promotion, injury prevention, and role participation for the older worker.

As the population of individuals aged sixty-five and older continues to grow, the number of older individuals participating in the workforce rises alongside, with projections estimating as many as 72 million older workers by 2030. Due to this rapid increase in the number of older workers, new challenges to worker health and to health-related productivity will arise in the coming years. Occupational therapy practitioners are uniquely suited to address many of these challenges given their background in activity analysis, assessment and modification of job demands, health promotion and successful aging. However, there is need for continued research in this area to expand the role of the occupational therapy practitioner in prevention and return-to-work interventions focused on the older worker, and to advocate for the value occupational therapy practitioners can contribute to this field.

Oncologist uptake of comprehensive genomic profile guided targeted therapy.

We describe the extent to which comprehensive genomic profiling (CGP) results were used by oncologists to guide targeted therapy selection in a cohort of solid tumor patients tested as part of standard care at Roswell Park Comprehensive Cancer Center June 2016-June 2017, with adequate follow up through September 2018 (n = 620). Overall, 28.4% of CGP tests advised physicians about targeted therapy use supported by companion diagnostic or practice guideline evidence. Post-test targeted therapy uptake was highest for patients in active treatment at the time of order (86% versus 76% of treatment naïve patients), but also took longer to initiate (median 50 days versus 7 days for treatment naïve patients), with few patients (2.6%) receiving targeted agents prior to testing. 100% of patients with resistance variants did not receive targeted agents. Treatment naïve patients received immunotherapy as the most common alternative. When targeted therapy given off-label or in a trial was the best CGP option, (7%) of patients received it. Our data illustrate the appropriate and heterogeneous use of CGP by oncologists as a longitudinal treatment decision tool based on patient history and treatment needs, and that some patients may benefit from testing prior to initiation of other standard treatments.

Proliferative potential and resistance to immune checkpoint blockade in lung cancer patients.

BACKGROUND: Resistance to immune checkpoint inhibitors (ICIs) has been linked to local immunosuppression independent of major ICI targets (e.g., PD-1). Clinical experience with response prediction based on PD-L1 expression suggests that other factors influence sensitivity to ICIs in non-small cell lung cancer (NSCLC) patients. METHODS: Tumor specimens from 120 NSCLC patients from 10 institutions were evaluated for PD-L1 expression by immunohistochemistry, and global proliferative profile by targeted RNA-seq. RESULTS: Cell proliferation, derived from the mean expression of 10 proliferation-associated genes (namely BUB1, CCNB2, CDK1, CDKN3, FOXM1, KIAA0101, MAD2L1, MELK, MKI67, and TOP2A), was identified as a marker of response to ICIs in NSCLC. Poorly, moderately, and highly proliferative tumors were somewhat equally represented in NSCLC, with tumors with the highest PD-L1 expression being more frequently moderately proliferative as compared to lesser levels of PD-L1 expression. Proliferation status had an impact on survival in patients with both PD-L1 positive and negative tumors. There was a significant survival advantage for moderately proliferative tumors compared to their combined highly/poorly counterparts (p = 0.021). Moderately proliferative PD-L1 positive tumors had a median survival of 14.6 months that was almost twice that of PD-L1 negative highly/poorly proliferative at 7.6 months (p = 0.028). Median survival in moderately proliferative PD-L1 negative tumors at 12.6 months was comparable to that of highly/poorly proliferative PD-L1 positive tumors at 11.5 months, but in both instances less than that of moderately proliferative PD-L1 positive tumors. Similar to survival, proliferation status has impact on disease control (DC) in patients with both PD-L1 positive and negative tumors. Patients with moderately versus those with poorly or highly proliferative tumors have a superior DC rate when combined with any classification schema used to score PD-L1 as a positive result (i.e., TPS ≥ 50% or ≥ 1%), and best displayed by a DC rate for moderately proliferative tumors of no less than 40% for any classification of PD-L1 as a negative result. While there is an over representation of moderately proliferative tumors as PD-L1 expression increases this does not account for the improved survival or higher disease control rates seen in PD-L1 negative tumors. CONCLUSIONS: Cell proliferation is potentially a new biomarker of response to ICIs in NSCLC and is applicable to PD-L1 negative tumors.

Community-based participatory research to promote healthy lifestyles among Latino immigrant families with youth with disabilities.

BACKGROUND/AIMS: Community-based participatory research (CBPR) is an optimal approach that brings together community stakeholders, researchers and practitioners in an effort to understand and address social issues and health disparities experienced by vulnerable populations. Latino immigrant families in the United States with youth and young families with disabilities have experienced a number of barriers in gaining positive health outcomes. These families face challenges in maintaining a healthy lifestyle, placing them at high risk for obesity, diabetes, and other chronic health conditions. The purpose of this study was to develop a healthy lifestyles intervention in collaboration with Latino immigrant families with youth and young adults with disabilities using a CBPR approach, and to examine the impact of the intervention from participants' perspectives. METHODS: Grounded in the principles of CBPR, we developed a partnership with community stakeholders to create a healthy lifestyles intervention aimed at meeting the needs of Latino families in the United States. During and following implementation of the intervention, we conducted focus groups with 12 intervention participants to examine the impact of the intervention. RESULTS: Participants identified the intervention program as meeting a need in the community and reported specific positive aspects related to health behaviors, social learning, inclusion, community participation, and peer advocacy. DISCUSSION: CBPR healthy lifestyle interventions are relevant to the needs of Latino immigrant families with youth and young adults with disabilities. Health professionals should involve community residents in the design of healthy lifestyles programming to ensure strategies for change are relevant and relatable.

Efficacy of Palbociclib Combinations in Hormone Receptor-Positive Metastatic Breast Cancer Patients After Prior Everolimus Treatment.

PURPOSE: Outcome data on hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2-) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+HER2- MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+HER2- MBC with prior exposure to everolimus while receiving palbociclib-based therapy. PATIENTS AND METHODS: A retrospective, single-institute review was conducted of HR+HER2- MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks. RESULTS: Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively. CONCLUSION: There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings.