A novel approach using sorafenib in alpha fetoprotein-producing hepatoid adenocarcinoma of the lung.

Hepatoid adenocarcinoma of the lung (HAL) is an extremely rare cancer without clear treatment guidance and with a poor prognosis. This report discusses a 64-year-old man who presented with complaints of hemoptysis and was found to have a right upper lobe (RUL) lung mass on chest CT with presence of a right hilar mass and retrocaval lymphadenopathy, and metastasis to the vertebral spine and rib. The patient was diagnosed with T2N2M1 (stage IV) unresectable disease. A biopsy of the RUL mass revealed hepatoid variant adenocarcinoma. Immunohistochemical stains showed tumor cells positive for CK7, AFP, Hep Par 1, napsin A, and cytoplasmic TTF-1 staining. In contrast, CK5, CK6, and CK20 were negative, and EGFR was wild-type. Serum alpha fetoprotein (AFP) level was elevated at 181 ng/mL. The patient was treated with platinum-based doublet chemotherapy and sorafenib, and his AFP level decreased to 25 ng/mL. This case report presents the novel use of sorafenib in combination with platinum-based doublet chemotherapy in EGFR wild-type HAL, which led to a partial response. Single-agent sorafenib led to stable disease overall, achieving a survival among the longest reported for unresectable stage IV, all while maintaining an ECOG performance status of 0 to 1.

Assessment of PSA responses and changes in the rate of tumor growth (g-rate) with immune checkpoint inhibitors in US Veterans with prostate cancer.

We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-world. We queried the VA corporate data warehouse (CDW) to identify Veterans with a diagnosis of PC who received ICI for any malignancy and had ≥1 PSA measurement while receiving ICI. To evaluate ICI monotherapy, we restricted analysis to Veterans who had not received LHRH agonists/antagonists, PC-directed medical therapy, or radiation/extirpative surgery of the bladder/prostate within and preceding the duration of ICI administration. For ICI combination analysis, we identified Veterans who received abiraterone or enzalutamide for PC while on ICI. We calculated rates of tumor (PSA) growth (g-rates), comparing them to a 1:2 matched reference cohort. We identified 787 Veterans with PC and ≥1 PSA measurement while receiving an ICI. Median duration of ICI therapy was 155 days. 223 Veterans received ICI monotherapy, with only 17(8%) having a reduction in PSA (median decline = 43%). 12 (5%) had PSA declines >30% (PSA30) which included 6 (3%) who had PSA reductions greater than 50% (PSA50). Median g-rates for ICI plus abiraterone (n = 20) or enzalutamide (n = 31) were 0.000689/d-1 and 0.002819/d-1, respectively, and were statistically insignificant compared to g-rates of matched cohorts receiving abiraterone (g = 0.000925/d-1, P = 0.73) or enzalutamide (g = 0.001929/d-1, P = 0.58) alone. Our data align with clinical trial data in PC, demonstrating limited benefit from ICI monotherapy and predicting no survival benefit from simultaneous abiraterone or enzalutamide with an ICI using g-rate.

Influence of Cancer on COVID-19 Incidence, Outcomes, and Vaccine Effectiveness: A Prospective Cohort Study of U.S. Veterans.

PURPOSE: Coronavirus disease 2019 (COVID-19) has been a constant health threat since its emergence. Amongst risk factors proposed, a diagnosis of cancer has been worrisome. We report the impact of cancer and other risk factors in US Veterans receiving care at Veterans Administration (VA) Hospitals, their adjusted odds ratio (aOR) for infection and death, and report on the impact of vaccines on the incidence and severity of COVID-19 infections in Veterans without/with cancer. METHODS: We conducted a cohort study of US Veterans without/with cancer by mining VA COVID-19 Shared Data Resource (CSDR) data using the VA Informatics and Computing Infrastructure (VINCI). Our observation period includes index dates from 14DEC2020 to 25JAN2022, encompassing both the delta and omicron waves in the US. RESULTS: We identified 915,928 Veterans, 24% of whom were African Americans who had undergone COVID testing-688,541 were and 227,387 were not vaccinated. 157,072 had a cancer diagnosis in the preceding two years. Age emerged as the major risk factor, with gender, BMI, and (Elixhauser) comorbidity contributing less. Among veterans with solid tumors other than lung cancer, risks of infection and death within 60 days were comparable to Veterans without cancer. However, those with hematologic malignancies fared worse. Vaccination was highly effective across all cancer cohorts; the respective rates of infection and death after infection were 8% and 5% among the vaccinated compared to 47% and 10% in the unvaccinated. Amongst vaccinated, increased risk of infection was noted in both, Veterans with hematologic malignancy treated with chemotherapy (HR, 2.993, P < 0.0001) or targeted therapies (HR, 1.781, P < 0.0001), and in solid tumors treated with either chemotherapy (HR 2.328, 95%CI 2.075-2.611, P < 0.0001) or targeted therapies (HR 1.328, P < 0.0001) when compared to those not on treatment. CONCLUSIONS: Risk for COVID-19 infection and death from infection vary based on cancer type and therapies administered. Importantly and encouragingly, the duration of protection from infection following vaccination in Veterans with a diagnosis of cancer was remarkably like those without a cancer diagnosis. Veterans with hematologic malignancies are especially vulnerable, with lower vaccine effectiveness (VE).

Positive attitudes toward clinical trials among military veterans leaves unanswered questions about poor trial accrual.

Participation in clinical trials is essential to bringing novel and innovative cancer treatments to the bedside but trials that specifically enroll Veterans are relatively few. Given the inherent differences between Veterans and the general United States population, we sought to investigate awareness of and attitudes toward clinical trials among Veterans diagnosed with cancer at a large, urban Veterans Administration Medical Center in Bronx, New York. The survey was administered in 2018-2019. Questions assessed sociodemographic characteristics, health literacy, and general attitudes about clinical trials. Based on key informant interviews, we also inquired about military-specific attitudes. Univariable analyses were conducted to evaluate differences in attitudes by age (<65 v ≥65 years) and race/ethnicity (non-Hispanic black v other). Of 115 Veterans approached, 67 (58.3%) completed the survey. Approximately 95% of participants were male, 59.7% were ≥65 years old, and 41.8% were non-Hispanic black. Only 58.2% reported knowing what a clinical trial is but 78.5% of Veterans stated that they trust doctors who do medical research and 87.5% reported they would strongly consider joining a trial if their VA primary care physician recommended it. Many stated that they would be part of a clinical trial if it would help fellow Veterans in the future (93.8%) and would help scientists learn how to treat other Veterans with the same disease (93.8%). Among non-Hispanic black participants, 62.5% agreed that the government has a history of using Veterans in experiments without their knowledge compared to 34.2% of Veterans of other race/ethnicity (P = 0.03). Clearly Veterans in our study were amenable to joining clinical trials. While many are aware of past misconduct in the treatment of military personnel in research, overall attitudes toward clinical trials were favorable and were especially positive when the possibility of improving cancer care for fellow Veterans was considered. In approaching Veterans regarding participation in a clinical trial we recommend education aligned with the literacy level of the Veteran, involvement of the VA primary care provider in clinical trial decisions, and awareness of a Veteran's altruism to help others.

Screening High-Risk Women Veterans for Breast Cancer.

BACKGROUND: Within the US Department of Veterans Affairs (VA), breast cancer prevalence has more than tripled from 1995 to 2012. Women veterans may be at an increased breast cancer risk based on service-related exposures and posttraumatic stress disorder (PTSD). METHODS: Women veterans aged ≥ 35 years with no personal history of breast cancer were enrolled at 2 urban VA medical centers. We surveyed women veterans for 5-year and lifetime risks of invasive breast cancer using the Gail Breast Cancer Risk Assessment Tool (BCRAT). Data regarding demographics, PTSD status, eligibility for chemoprevention, and genetic counseling were also collected. Descriptive statistics were used to determine results. RESULTS: A total of 99 women veterans participated, of which 60% were Black. In total, 35% were high risk with a 5-year BCRAT > 1.66%. Breast biopsies had been performed in 22% of our entire population; 57% had a family history positive for breast cancer. Comparatively, in our high-risk Black population, 33% had breast biopsies and 94% had a family history. High-risk patients were referred for chemoprevention; 5 accepted and 13 were referred for genetic counseling. PTSD was present in 31% of the high-risk subgroup. CONCLUSIONS: A high percentage of Black patients participated in this pilot study, which also showed an above average rate of PTSD among women veterans who are at high risk for developing breast cancer. Historically, breast cancer rates among Black women are lower than those found in the general population. High participation among Black women veterans in this pilot study uncovered the potential for further study of this population, which is otherwise underrepresented in research. Limitations included a small sample size, exclusively urban population, and self-selection for screening. Future directions include the evaluation of genetic and molecular mutations in high risk Black women veterans, possibly even a role for PTSD epigenetic changes.

Gemcitabine plus nab-paclitaxel versus FOLFIRINOX for unresected pancreatic cancer: Comparative effectiveness and evaluation of tumor growth in Veterans.

PURPOSE: Advanced, unresectable pancreatic cancer is often treated with either gemcitabine plus nab-paclitaxel (Gem/NabP) or FOLFIRINOX, although these regimens have never been compared in a head-to-head trial. In this study, we compared these two regimens using Veterans Administration (VA) data and evaluated the use of a novel tumor growth formula to predict outcomes. METHODS: We identified 670 Veterans from national VA data with unresected stage II-IV pancreatic adenocarcinoma diagnosed between 2003 and 2016 who were treated with either first-line Gem/NabP or FOLFIRINOX. We compared overall survival (OS) and adverse events by treatment using propensity scores (PS) to account for allocation bias. Using longitudinal CA19-9 biomarker information we then fit the data to a novel tumor growth equation, comparing growth with OS. RESULTS: We found no difference in PS-adjusted (hazard ratio [HR] 1.00; 95% confidence interval [95% CI] 0.84-1.20) or PS-matched (HR: 0.93; 95% CI: 0.76-1.13) OS between the two treatment groups. Tumor growth analysis revealed similar growth parameter values for Gem/NabP and FOLFIRINOX (P = .074 for difference). CONCLUSIONS: Gem/NabP appeared noninferior to FOLFIRINOX for survival outcomes for advanced pancreatic adenocarcinoma based on national VA data. Biomarker-based growth equations may be useful for monitoring treatment response and predicting prognosis for pancreatic cancer.

Breast Cancer Risk Assessment and Chemoprevention Use Among Veterans Affairs Primary Care Providers: A National Online Survey.

INTRODUCTION: Breast cancer is the most common cancer diagnosed among women and the second most common cause of cancer death among women. There are ways to reduce a woman's risk of breast cancer; however, most eligible women in the United States are neither offered personalized screening nor chemoprevention. Surveys have found that primary care providers are largely unaware of breast cancer risk assessment models or chemoprevention. This survey aims to investigate Veterans Health Administration primary care providers' comfort level, practice patterns, and knowledge of breast cancer risk assessment and chemoprevention. MATERIALS AND METHODS: An online, Research Electronic Data Capture-generated survey was distributed to VHA providers in internal medicine, family medicine, and obstetrics/gynecology. Survey domains were provider demographics, women's health experience, comfort level, practice patterns, barriers to using risk models and chemoprevention, and knowledge of chemoprevention. RESULTS: Of the 167 respondents, 33.1% used the Gail model monthly or more often and only 2.4% prescribed chemoprevention in the past 2 years. Most VHA primary care providers did not answer chemoprevention knowledge questions correctly. Designated women's health providers were more comfortable with risk assessment (P < 0.018) and chemoprevention (P < 0.011) and used both breast cancer risk models (P < 0.0045) and chemoprevention more often (P < 0.153). Reported barriers to chemoprevention were lack of education and provider time. CONCLUSIONS: VHA providers and women Veterans would benefit from a system to ensure that women at increased risk of breast cancer are identified with risk modeling and that risk reduction options, such as chemoprevention, are offered when appropriate. VHA providers requested risk reduction education, which could improve primary care provider comfort level with chemoprevention.

A novel approach to assess real-world efficacy of cancer therapy in metastatic prostate cancer. Analysis of national data on Veterans treated with abiraterone and enzalutamide.

BACKGROUND: With 1.3 million new cases in 2018 worldwide, prostate cancer remains a challenge. Development of novel therapies targeting the androgen pathway followed recognition of the continued importance of androgens in castrate-resistant prostate cancer. To assess abiraterone and enzalutamide efficacy we analyzed data from US Veterans Administration Medical Centers (VAMCs). METHODS: We used a novel method independent of assessment intervals and ideal for real-world analysis to estimate rates of tumor growth (g) and regression (d). FINDINGS: Using the VA Informatics and Computing Infrastructure, we collected data from 5,116 Veterans with castrate-resistant prostate cancer prescribed abiraterone, enzalutamide or both. We estimated values for g and d and demonstrated a correlation of g with overall survival (P < .0001). Abiraterone and enzalutamide slowed growth rates across age groups and across the entire VAMC system, although less so in Veterans previously treated with a taxane and those with Gleason grade group 5 tumors. Abiraterone and enzalutamide efficacy in first-line were comparable although abiraterone in first-line slowed growth rates significantly more in African Americans than in Caucasians; enzalutamide was a better salvage therapy. When abiraterone was first-line and g was low, switching to enzalutamide was associated with a faster g in 67%. INTERPRETATION: In the real-world g can be estimated using a novel analysis method indifferent to assessment intervals that correlates highly with OS. While we show excellent real-world outcomes with abiraterone and enzalutamide, 2 effective and tolerable therapies, our results in VAMCs suggest enzalutamide should follow abiraterone. Changing therapies may be detrimental and consideration should be given to continue monitoring of growth rates over time. Funding Support from the Prostate Cancer Foundation and the Blavatnik Family Foundation.

Cancer Care Collaborative Approach to Optimize Clinical Care.

A collaboration between clinicians and industrial engineers resulted in significant improvements in cancer screening, the development of toolkits, and more efficient care for hepatocellular carcinoma and breast, colorectal, lung, head and neck, and prostate cancers.