Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations.

Breast and ovarian cancers pose significant therapeutic challenges. We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. HDACi, PARPi, and decitabine combinations had synergistic cytotoxicity (assessed by MTT and clonogenic assays) in all cell lines (combination index < 1). Clonogenic assays confirmed the sensitivity of breast and ovarian cancer cell lines to the three-drug combinations (panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine; vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine). Cell proliferation was inhibited by 48-70%, and Annexin V positivity was 42-59% in all cell lines exposed to the three-drug combinations. Western blot analysis showed protein PARylation inhibition, caspase 3 and PARP1 cleavage, and c-MYC down-regulation. The three-drug combinations induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs, impaired the DNA repair pathways, and altered the epigenetic regulation of gene expression. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.

Psychological distress and mental health care utilization among lesbian, gay, and bisexual survivors of adolescent and young adult cancer.

PURPOSE: Survivors of adolescent and young adult (AYA) cancer face significant psychological distress and encounter barriers accessing mental health care. However, limited research exists on psychological health among lesbian, gay, and bisexual (LGB) survivors of AYA cancer, particularly in comparison with heterosexual survivors and LGB individuals without a history of cancer. METHODS: Using the National Health Interview Survey (2013-2018), we identified LGB survivors of AYA cancer, LGB individuals without a history of cancer, and heterosexual survivors of AYA cancer. Sociodemographic, chronic health conditions, modifiable factors (such as smoking and alcohol use), and psychological outcomes were assessed using chi-square tests. Logistic regression models, adjusted for survey weights, evaluated the odds of psychological distress by cancer status after accounting for covariates. Interactions between variables and cancer status were explored. RESULTS: The study comprised 145 LGB survivors, 1450 LGB individuals without a history of cancer, and 1450 heterosexual survivors. Compared to heterosexual survivors, LGB survivors were more likely to report severe distress (aOR = 2.26, p = 0.021) and had higher odds of reporting a mental health care visit (aOR = 1.98, p = 0.003). Odds of severe distress (aOR = 1.36, p = 0.36) and reporting a mental health care visit (aOR = 1.27, p = 0.29) were similar between LGB survivors and LGB individuals without a history of cancer. While 47.8% of LGB survivors reported moderate/severe distress, only 29.7% reported a mental health care visit. CONCLUSION: A history of cancer during the AYA years is associated higher odds of severe psychological distress among LGB survivors compared to heterosexual survivors. However, many LGB survivors with psychological distress have not accessed mental health care.

Synergistic cytotoxicity of histone deacetylase and poly-ADP ribose polymerase inhibitors and decitabine in pancreatic cancer cells: Implications for novel therapy.

Histone deacetylase inhibitors (HDACi) can modulate the acetylation status of proteins, influencing the genomic instability exhibited by cancer cells. Poly (ADP ribose) polymerase (PARP) inhibitors (PARPi) have a direct effect on protein poly (ADP-ribosyl)ation, which is important for DNA repair. Decitabine is a nucleoside cytidine analogue, which when phosphorylated gets incorporated into the growing DNA strand, inhibiting methylation and inducing DNA damage by inactivating and trapping DNA methyltransferase on the DNA, thereby activating transcriptionally silenced DNA loci. We explored various combinations of HDACi and PARPi +/- decitabine (hypomethylating agent) in pancreatic cancer cell lines BxPC-3 and PL45 (wild-type BRCA1 and BRCA2) and Capan-1 (mutated BRCA2). The combination of HDACi (panobinostat or vorinostat) with PARPi (talazoparib or olaparib) resulted in synergistic cytotoxicity in all cell lines tested. The addition of decitabine further increased the synergistic cytotoxicity noted with HDACi and PARPi, triggering apoptosis (evidenced by increased cleavage of caspase 3 and PARP1). The 3-drug combination treatments (vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine; panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine) induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs and impaired the DNA repair pathways (decreased levels of ATM, BRCA1, and ATRX proteins). The 3-drug combinations also altered the epigenetic regulation of gene expression (NuRD complex subunits, reduced levels). This is the first study to demonstrate synergistic interactions between the aforementioned agents in pancreatic cancer cell lines and provides preclinical data to design individualized therapeutic approaches with the potential to improve pancreatic cancer treatment outcomes.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Psychological distress and mental health care utilization among Black survivors of adolescent and young adult cancer.

BACKGROUND: Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population. METHODS: National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ2 tests. Logistic regression models, adjusted for survey weights, were used to evaluate the odds of psychological distress by cancer status after adjusting for covariates. Interactions between variables and cancer status were investigated. RESULTS: The study included 334 Black survivors of AYA cancer and 3340 Black controls. Compared to controls, survivors were more likely to report moderate/severe distress (odds ratio [OR], 1.64; p < .001), use mental health care (OR, 1.53; p = .027), report an inability to afford mental health care (OR, 3.82; p < .001), and use medication for anxiety and/or depression (OR, 2.16; p = .001). Forty-one percent of survivors reported moderate/severe distress, and only 15% used mental health care. Among survivors, ages 18-39 years (vs. 40-64 years) and current smoking (vs. never smoking) were associated with the presence of moderate/severe distress. Among survivors with distress, high poverty status was associated with reduced utilization of mental health care. CONCLUSIONS: A cancer diagnosis for a Black AYA is associated with greater psychological distress within an already vulnerable population.

Impact of patient demographics and neighborhood socioeconomic variables on clinical trial participation patterns for NHL.

ABSTRACT: Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with non-Hodgkin lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance, and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition, and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive adult patients with NHL seen between January 2017 and December 2020. The study cohort was predominantly male and non-Hispanic White (NHW). The most common insurance types were private insurance and Medicare; only 1.1% of patients had Medicaid. There was a high overall participation rate of 30.5%, with 20.9% enrolled in therapeutic trials. In univariate analyses, lower participation rates were associated with lower nSES including higher poverty rates and living in crowded households. Racial composition of CT was not associated with differences in trial participation. In multivariable analysis, trial participation varied significantly by histology, and participation declined nonlinearly with age in the overall, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) models. In the DLBCL subset, Hispanic patients had lower odds of participation than White patients (odds ratio, 0.36; 95% confidence interval, 0.21-0.62; P = .001). In our large academic cohort, race, sex, insurance type, and nSES were not associated with trial participation, whereas age and diagnosis were.

Cardiovascular Disease in Childhood, Adolescent, and Young Adult Cancer Survivors: The Impact of Family History of Premature Heart Disease.

Purpose: Childhood, adolescent, and young adult (CAYA) cancer survivors (age 0-39 years at diagnosis) are at increased risk of cardiovascular disease (CVD). Family history of early heart disease increases the risk of CVD in the general population; however, it is unknown whether this association is seen in CAYA cancer survivors. Methods: Self-report data from the National Health and Nutrition Examination Survey (2005-2018) were used to identify CAYA survivors (>5 years post-diagnosis). The risk of CVD based on family history status (parent or sibling with a diagnosis of heart attack or angina before age 50 years), personal sociodemographic factors, personal medical history factors, and personal behavioral risk factors was determined using logistic regression models. Results: Included were 95 CAYA survivors with CVD and 491 CAYA survivors without CVD. The odds of CVD were significantly higher in survivors with a first-degree family history of early heart disease (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.14-3.74). A history of diabetes (OR: 2.61, 95% CI: 1.41-4.84), hypertension (OR: 1.81, 95% CI: 1.04-3.16), and any smoking (OR: 2.19, 95% CI: 1.19-4.02) was also associated with higher odds of CVD in CAYA survivors. Reporting any physical activity in the past month was associated with lower odds (OR: 0.54, 95% CI: 0.30-0.97) of CVD. Conclusions: Family history of early heart disease was associated with increased odds of CVD in CAYA cancer survivors. Obtaining complete and accurate family history information is important both at time of diagnosis and throughout follow-up.

Factors contributing to financial distress in young adults with cancer: Material resources, health, and workplace.

BACKGROUND: Financial distress is a primary concern for young adults with cancer. OBJECTIVE: The aim of this study was to identify material resources, physical and psychological health, and workplace variables that are associated with financial distress in young adult cancer survivors. METHODS: A cross-sectional study was conducted using the Cancer Survivor Employment Needs Survey. Participants were young adults (18-39 years of age) who lived in the United States and had a cancer diagnosis. Multivariable linear regression was used to model relations between financial distress and material resources, physical and psychological health, and workplace variables. RESULTS: Participants (N = 214) were mostly non-Hispanic White (78%), female (79%), and had a mean age of 31 years and 4.6 years post-diagnosis. Material resources, physical and psychological health, and workplace variables were all identified as contributing to study participants' financial distress. Among the young adults surveyed, financial distress was prevalent, and an array of problems were associated with financial distress. CONCLUSION: Oncology and rehabilitation providers should openly discuss finances with YAs with cancer and guide them to resources that can address their financial, benefits, and vocational needs to ultimately improve quality of life.

Socioeconomic Status and Chronic Health Conditions in Asian Survivors of Adolescent and Young Adult Cancers.

Purpose: While there are known disparities in socioeconomic status (SES) and health outcomes among racially and ethnically minoritized adolescent and young adult (AYA; ages 15-39 years at diagnosis) cancer survivors compared with White survivors, outcomes in the Asian survivor population are understudied. To better understand the association of an AYA cancer diagnosis with SES and health outcomes within a minoritized population, the current study makes comparisons between individuals of the same race or ethnicity with and without a history of AYA cancer. Methods: Non-Hispanic, Asian AYA cancer survivors and non-Hispanic, Asian age- and sex-matched controls were identified from self-reported data in the National Health Interview Survey (2009-2020). Prevalence of chronic health conditions and socioeconomic factors were compared between groups using chi-square tests. Odds of chronic conditions by SES factors were determined within and between survivors and controls using logistic regression methods. Results: One hundred and thirty-one survivors and 1310 controls were included. Survivors were less likely to be married compared with controls; however, there were no differences in other SES factors examined. Survivors had higher odds of at least one chronic condition diagnosis (odds ratio = 4.17, p < 0.001) compared with controls. Of the chronic conditions assessed, survivors had higher odds of arthritis, pulmonary disease, and hypertension compared with controls. Conclusions: Asian AYA cancer survivors are at increased risk of chronic health conditions compared with Asian individuals without a cancer history. Culturally adapted targeted interventions are needed to improve health outcomes for this population.

Risk of chronic health conditions in lesbian, gay, and bisexual survivors of adolescent and young adult cancers.

BACKGROUND: In the general population, individuals with minoritized sexual orientation and gender identity have a higher burden of chronic health conditions than heterosexual individuals. However, the extent to which sexual orientation is associated with excess burden of chronic conditions in adolescent and young adult cancer survivors (AYACS) is unknown. METHODS: Lesbian, gay, and bisexual (LGB) AYACSs, LGB individuals without a history of cancer, and heterosexual AYACSs were identified by self-reported data from the cross-sectional National Health Interview Survey (2013-2020). Socioeconomic factors and the prevalence of chronic health conditions were compared between groups using χ2 tests. Logistic regression methods were used to determine the odds of chronic conditions by socioeconomic factors within and between survivor and comparison groups. RESULTS: One hundred seventy LGB cancer survivors, 1700 LGB individuals without a history of cancer, and 1700 heterosexual cancer survivors were included. Compared with heterosexual survivors, LGB survivors were less likely to be married (p = .001) and more likely to have never been married (p < .001). LGB survivors were more likely to have incomes between 100% and 200% of the federal poverty level than LGB individuals without a history of cancer (p = .012) and heterosexual survivors (p = .021) and were less likely to report incomes >200% the federal poverty level. LGB survivors had higher odds of chronic health conditions than LGB individuals without a history of cancer (odds ratio, 2.45; p < .001) and heterosexual survivors (odds ratio, 2.16; p = .003). CONCLUSIONS: LGB AYACSs are at increased risk of having chronic health conditions compared with both LGB individuals without a history of cancer and heterosexual AYACSs.

Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada.

OBJECTIVES: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist. METHODS: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants. RESULTS: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013). SIGNIFICANCE OF RESULTS: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

The impact of a multidisciplinary goals-of-care program on unplanned readmission rates at a comprehensive cancer center.

PURPOSE: This study examined the 30-day unplanned readmission rate in the medical oncology population before and after the implementation of an institution-wide multicomponent interdisciplinary goals of care (myGOC) program. METHODS: This retrospective study compared the 30-day unplanned readmission rates in consecutive medical patients during the pre-implementation period (May 1, 2019, to December 31, 2019) and the post-implementation period (May 1, 2020, to December 31, 2020). Secondary outcomes included 7-day unplanned readmission rates, inpatient do-not-resuscitate (DNR) orders, and palliative care consults. We randomly selected a hospitalization encounter for each unique patient during each study period for statistical analysis. A multivariate analysis model was used to examine the association between 30-day unplanned readmission rates and implementation of the myGOC program. RESULTS: There were 7028 and 5982 unique medical patients during the pre- and post-implementation period, respectively. The overall 30-day unplanned readmission rate decreased from 24.0 to 21.3% after implementation of the myGOC program. After adjusting for covariates, the myGOC program implementation remained significantly associated with a reduction in 30-day unplanned readmission rates (OR [95% CI] 0.85 [0.77, 0.95], p = 0.003). Other factors significantly associated with a decreased likelihood of a 30-day unplanned readmission were an inpatient DNR order, advanced care planning documentation, and an emergent admission type. We also observed a significant decrease in 7-day unplanned readmission rates (OR [95% CI] 0.75 [0.64, 0.89]) after implementation of the myGOC program. CONCLUSION: The 30-day and 7-day unplanned readmission rates decreased in our hospital after implementation of a system-wide multicomponent GOC intervention.

Dose and gender dependence of chlorine inhalation in a conscious ovine model.

Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl2 concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl2 premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO2/FiO2 ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO2/FiO2 ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO2/FiO2 ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl2 significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl2 concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl2 concentrations. No significant sex-dependent differences were found in measured endpoint variables.

Psychological distress and mental health care utilization among Hispanic/Latino survivors of adolescent and young adult cancer.

PURPOSE: Survivors of adolescent and young adult (AYA) cancer experience psychological distress and insufficient access to mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes in this population. This study compared psychological distress, mental health care use, and inability to afford mental health care between Hispanic/Latino survivors of AYA cancer and Hispanic/Latino controls. METHODS: The National Health Interview Survey data (2010-2018) were analyzed to identify Hispanic/Latino survivors of AYA cancer and Hispanic/Latino age- and sex-matched non-cancer controls. Sociodemographic, chronic health, modifiable factors, and psychological outcomes were compared using chi-square tests. Logistic regression models with survey weights were used to assess the log-odds of psychological distress in relation to covariates, along with the cancer group. Interactions were evaluated between each variable and cancer group. RESULTS: The study included 370 Hispanic/Latino survivors of AYA cancer (mean time since diagnosis = 12.34 years) and 3700 Hispanic/Latino controls. Compared to controls, survivors were more likely to report moderate/severe distress (OR = 2.23, p < 0.001), use of mental health care (OR = 2.11, p < 0.001) and inability to afford mental health care (OR = 3.05, p < 0.001). Forty-one percent of survivors reported moderate/severe distress and only 16% utilized mental health care. Among survivors, having more than two chronic health conditions and public insurance (compared to private insurance) were associated with the presence of moderate/severe distress. Among survivors experiencing moderate/severe distress, lack of insurance was associated with decreased utilization of mental health care. CONCLUSIONS: Having cancer as an AYA may exacerbate disparities in psychological health within the Hispanic/Latino population.

I Read, Therefore I Am: Examining Nonmedical Reading and Its Relationship to Empathy in Anesthesia Training.

Background: High levels of empathy among resident physicians are associated with improved patient outcomes. Empathy may be learned and practiced when reading nonmedical writing through narrative transportation, a process by which readers identify with characters and become emotionally involved in the plot. We hypothesized that residents and fellows who reported more nonmedical reading would have higher empathy levels and that empathy would decrease during training. Methods: An emailed survey was sent to program directors of Accreditation Council on Graduate Medical Education-accredited anesthesiology residency and fellowship programs, with a request to distribute the survey to trainees. The Toronto Empathy Questionnaire, reading volume, and demographics were included in the survey. Response data were analyzed using a multiple variable regression model. Results: Of 136 responses, 119 were included for data analysis. Seventeen partially completed surveys were excluded. Higher empathy scores were reported among women (P < .0001) and residents who worked 60 to 80 hours per week (P = .039). Age, postgraduate year of training, relationship status, time spent with family, and avid reading were not significantly associated with increased empathy. Conclusion: In this study, we examined whether nonmedical fiction reading would increase empathy in medical trainees. Our study was not able to find any significant association with time spent reading and increased empathy; however, we found that trainees who worked more hours, specifically 60 to 80 hours, had higher empathy scores. Limitations for this study included a smaller sample size. Further research should be done in this field to determine if there are other intangible factors that affect empathy in trainees.

Excess risk of chronic health conditions in Black adolescent and young adult cancer survivors.

BACKGROUND: The US population of adolescent and young adult (age 15-39 years at diagnosis) cancer survivors is growing. Previous studies have identified racial and ethnic disparities in survival and health outcomes in racially minoritized survivors, including Black survivors, compared with White survivors. However, comparisons should be made between those of the same race or ethnicity with and without a history of AYA cancer to fully understand the association of a cancer diagnosis with socioeconomic status (SES) and health outcomes within a minoritized population. METHODS: Non-Hispanic Black AYA cancer survivors and non-Hispanic Black age- and sex-matched controls were identified from self-reported data from the National Health Interview Survey (2009-2018). SES factors and chronic health conditions prevalence were compared between survivors and controls using chi-square tests. Survey-weighted logistic regression models were used to determine odds of chronic conditions by SES factors within and between survivors and controls. Interactions between each variable and cancer group were assessed. RESULTS: A total of 445 survivors and 4450 controls were included. Survivors were less likely than controls to be married, have family income >45K/year, have completed a bachelor's degree or higher, and have private insurance. Survivors had higher odds than controls of having at least one (odds ratio (OR): 7.02, p<0.001) and ≥3 (OR: 4.44, p<0.001) chronic conditions. Survivors had higher odds of each chronic condition assessed including cardiovascular disease, diabetes, and hypertension. Survivors had higher odds of having chronic health conditions compared with controls across all SES variables. CONCLUSIONS: A cancer diagnosis during adolescence and young adulthood is associated with poor SES outcomes and increased odds of comorbidities within the Black population, thus further exacerbating existing disparities. IMPLICATIONS FOR CANCER SURVIVORS: Black AYA cancer survivors have a very high risk of developing chronic health conditions after cancer treatment and interventions are needed to improve long-term health outcomes for this population.

Effects of nebulized adipose-derived mesenchymal stem cells on acute lung injury following smoke inhalation in sheep.

INTRODUCTION: Treatment of ARDS caused by smoke inhalation is challenging with no specific therapies available. The aim of this study was to test the efficacy of nebulized adipose-derived mesenchymal stem cells (ASCs) in a well-characterized, clinically relevant ovine model of smoke inhalation injury. MATERIAL AND METHODS: Fourteen female Merino sheep were surgically instrumented 5-7 days prior to study. After induction of acute lung injury (ALI) by cooled cotton smoke insufflation into the lungs (under anesthesia and analgesia), sheep were placed on a mechanical ventilator for 48 hrs and monitored for cardiopulmonary hemodynamics in a conscious state. ASCs were isolated from ovine adipose tissue. Sheep were randomly allocated to two groups after smoke injury: 1) ASCs group (n = 6): 10 million ASCs were nebulized into the airway at 1 hr post-injury; and 2) Control group (n = 8): Nebulized with saline into the airways at 1 hr post-injury. ASCs were labeled with green fluorescent protein (GFP) to trace cells within the lung. ASCs viability was determined in bronchoalveolar lavage fluid (BALF). RESULTS: PaO2/FiO2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO2/PaO2) was significantly lower in the ASCs group at 36 hr (p = 0.003). Pulmonary shunt fraction tended to be lower in the ASCs group as compared to the control group. GFP-labelled ASCs were found on the surface of trachea epithelium 48 hrs after injury. The viability of ASCs in BALF was significantly lower than those exposed to the control vehicle solution. CONCLUSION: Nebulized ASCs moderately improved pulmonary function and delayed the onset of ARDS.

External validation of a novel electronic risk score for cancer-associated thrombosis in a comprehensive cancer center.

Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value of 94.8%). The median follow-up for 21 142 cancer patients was 8.1 months. There were 1067 (5.7%) VTE within 6 months after systemic therapy. The distribution of the novel score for 0-, 1, 2, 3, 4, 5+ was 5661, 3558, 3462, 3489, 2918, and 2054; while the corresponding 6-month VTE incidence was 1.3%, 3.1%, 5.4%, 7.3%, 9.3%, and 13.8%, respectively (c statistic 0.71 [95% CI 0.69-0.72] with excellent calibration). In comparison, the Khorana score had a c statistic of 0.64 [95% CI 0.62-0.65]. The two risk scores had 80% concordance; the novel score reclassified 20% of Khorana score (3530 low-to-high with 9.0% VTE; 734 high-to-low with 3.4% VTE) and led to a 25% increment in VTEs captured in the high-risk group. In conclusion, the novel score demonstrated consistent discrimination and calibration across cohorts with heterogenous demographics. It could become a new standard to select high-risk populations for clinical trials and VTE monitoring.

Differential Impact of a Multicomponent Goals-of-Care Program in Patients with Hematologic and Solid Malignancies.

We recently reported that an interdisciplinary multicomponent goals-of-care (myGOC) program was associated with an improvement in goals-of-care (GOC) documentation and hospital outcomes; however, it is unclear if the benefit was uniform between patients with hematologic malignancies and solid tumors. In this retrospective cohort study, we compared the change in hospital outcomes and GOC documentation before and after myGOC program implementation between patients with hematologic malignancies and solid tumors. We examined the change in outcomes in consecutive medical inpatients before (May 2019-December 2019) and after (May 2020-December 2020) implementation of the myGOC program. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included GOC documentation. In total, 5036 (43.4%) patients with hematologic malignancies and 6563 (56.6%) with solid tumors were included. Patients with hematologic malignancies had no significant change in ICU mortality between 2019 and 2020 (26.4% vs. 28.3%), while patients with solid tumors had a significant reduction (32.6% vs. 18.8%) with a significant between-group difference (OR 2.29, 95% CI 1.35, 3.88; p = 0.004). GOC documentation improved significantly in both groups, with greater changes observed in the hematologic group. Despite greater GOC documentation in the hematologic group, ICU mortality only improved in patients with solid tumors.

Excess risk of chronic health conditions in Hispanic survivors of adolescent and young adult cancers.

PURPOSE: There is a growing population of survivors of adolescent and young adult (AYA) cancers (age 15-39 years at diagnosis). Studies in AYA cancer survivors have identified racial and ethnic disparities in long-term outcomes. To understand the extent to which a cancer diagnosis exacerbates pre-existent health disparities within a minoritized population, comparisons should be made to those of the same race or ethnicity without a cancer history. METHODS: Self-reported data from the National Health Interview Survey (2009-2018) were used to identify Hispanic AYA cancer survivors and Hispanic age- and sex-matched controls. SES factors (marital status, income, education, insurance) and prevalence of chronic health conditions were compared between groups using chi-square tests. The log-odds of chronic conditions were modeled by survey-weighted logistic regression with relation to age at survey, sex, marital status, education, family income, and cancer group (control versus cancer), together with interactions between each variable and cancer group (survivors vs. controls). RESULTS: Five hundred thirty-nine survivors and 5390 controls were included. Compared with controls, survivors were less likely to be married and have family income > 45 K/year, and more likely to be insured and have completed some college. Survivors had higher odds than controls of chronic health conditions (odds ratio (OR): 7.39, p < 0.001 for at least 1 and OR: 4.78, p < 0.001 for 3 or more) including cardiovascular disease, diabetes, and hypertension. Female sex, higher educational attainment, and public insurance were each associated with increased odds of chronic conditions in Hispanic AYA survivors. CONCLUSIONS: An AYA cancer diagnosis is associated with poor SES outcomes and increased odds of comorbidities within the Hispanic population. IMPLICATIONS FOR CANCER SURVIVORS: Cancer history can exacerbate underlying health disparities. Screening for chronic conditions is especially important in minoritized populations.