Health-related social needs, medical financial hardship, and mortality risk among cancer survivors.

BACKGROUND: Cancer survivors may face challenges affording food, housing, and other living necessities, which are known as health-related social needs (HRSNs). However, little is known about the associations of HRSNs and mortality risk among adult cancer survivors. METHODS: Adult cancer survivors were identified from the 2013-2018 National Health Interview Survey (NHIS) and linked with the NHIS Mortality File with vital status through December 31, 2019. HRSNs, measured by food insecurity, and nonmedical financial worries (e.g., housing costs), was categorized as severe, moderate, and minor/none. Medical financial hardship, including material, psychological, and behavioral domains, was categorized as 2-3, 1, or 0 domains. Using age as the time scale, the associations of HRSNs and medical financial hardship and mortality risk were assessed with weighted adjusted Cox proportional hazards models. RESULTS: Among cancer survivors 18-64 years old (n = 5855), 25.5% and 18.3% reported moderate and severe levels of HRSNs, respectively; among survivors 65-79 years old (n = 5918), 15.6% and 6.6% reported moderate and severe levels of HRSNs, respectively. Among cancer survivors 18-64 years old, severe HRSNs was associated with increased mortality risk (hazards ratio [HR], 2.00; 95% confidence interval [CI], 1.36-2.93, p < .001; reference = minor/none) in adjusted analyses. Among cancer survivors 65-79 years old, 2-3 domains of medical financial hardship was associated with increased mortality risk (HR, 1.58; 95% CI, 1.13-2.20, p = .007; reference = 0 domain). CONCLUSIONS: HSRNs and financial hardship are associated with increased mortality risk among cancer survivors; comprehensive assessment of HRSN and financial hardship connecting patients with relevant services can inform efforts to mitigate adverse consequences of cancer.

Associations of Medical Debt With Health Status, Premature Death, and Mortality in the US.

Importance: Medical debt is increasingly common in the US. Little is known regarding its association with population health. Objective: To examine the associations of medical debt with health status, premature death, and mortality at the county level in the US. Design, Setting, and Participants: This cross-sectional study was conducted at the US county level using 2018 medical debt data from the Urban Institute Debt in America project linked with 2018 data on self-reported health status and premature death from the County Health Rankings & Roadmaps and with 2015 to 2019 mortality data from the National Center for Health Statistics. Data analysis was performed from August 2022 to May 2023. Exposure: Share of population with any medical debt in collections and median amount of medical debt. Main Outcomes and Measures: Health status was measured as (1) the mean number of physically and mentally unhealthy days in the past 30 days per 1000 people, (2) the mean number of premature deaths measured as years of life lost before age 75 years per 1000 people, and (3) age-adjusted all-cause and 18 cause-specific mortality rates (eg, malignant cancers, heart disease, and suicide) per 100 000 person-years. Multivariable linear models were fitted to estimate the associations between medical debt and health outcomes. Results: A total of 2943 counties were included in this analysis. The median percentage of the county population aged 65 years or older was 18.3% (IQR, 15.8%-20.9%). Across counties, a median 3.0% (IQR, 1.2%-11.9%) of the population were Black residents, 4.3% (IQR, 2.3%-9.7%) were Hispanic residents, and 84.5% (IQR, 65.7%-93.3%) were White residents. On average, 19.8% (range, 0%-53.6%) of the population had medical debt. After adjusting for county-level sociodemographic characteristics, a 1-percentage point increase in the population with medical debt was associated with 18.3 (95% CI, 16.3-20.2) more physically unhealthy days and 17.9 (95% CI, 16.1-19.8) more mentally unhealthy days per 1000 people during the past month, 1.12 (95% CI, 1.03-1.21) years of life lost per 1000 people, and an increase of 7.51 (95% CI, 6.99-8.04) per 100 000 person-years in age-adjusted all-cause mortality rate. Associations of medical debt and elevated mortality rates were consistent for all leading causes of death, including cancer (1.12 [95% CI, 1.02-1.22]), heart disease (1.39 [95% CI, 1.21-1.57]), and suicide (0.09 [95% CI, 0.06-0.11]) per 100 000 person-years. Similar patterns were observed for associations between the median amount of medical debt and the aforementioned health outcomes. Conclusions and Relevance: These findings suggest that medical debt is associated with worse health status, more premature deaths, and higher mortality rates at the county level in the US. Therefore, policies increasing access to affordable health care, such as expanding health insurance coverage, may improve population health.

US Medicare Hospice and Palliative Medicine Physician Workforce and Service Delivery in 2008-2020.

CONTEXT: Despite clinical benefits of early palliative care, little is known about Medicare physician workforce specialized in Hospice and Palliative Medicine (HPM) and their service delivery settings. OBJECTIVES: To examine changes in Medicare HPM physician workforce and their service delivery settings in 2008-2020. METHODS: Using the Medicare Data on Provider Practice and Specialty from 2008 to 2020, we identified 2375 unique Medicare Fee-For-Service (FFS) physicians (15,565 physician-year observations) with self-reported specialty in "Palliative Care and Hospice". We examined changes in the annual number of HPM physicians, average number of Medicare services overall and by care setting, total number of Medicare FFS beneficiaries, and total Medicare allowed charges billed by the physician. RESULTS: The number of Medicare HPM physicians increased 2.32 times from 771 in 2008 to 1790 in 2020. The percent of HPM physicians practicing in metropolitan areas increased from 90% to 96% in 2008-2020. Faster growth was also observed in female physicians (52.4% to 60.1%). Between 2008 and 2020, we observed decreased average annual Medicare FFS beneficiaries (170 to 123), number of FFS services (467 to 335), and Medicare allowed charges billed by the physician ($47,230 to $37,323). The share of palliative care delivered in inpatient settings increased from 47% to 68% in 2008-2020; whereas the share of services delivered in outpatient settings decreased from 37% to 19%. CONCLUSION: Despite growth in Medicare HPM physician workforce, access is disproportionately concentrated in metropolitan and inpatient settings. This may limit receipt of early outpatient specialized palliative care, especially in nonmetropolitan areas.

Importance of Patient Health Insurance Coverage and Out-of-Pocket Costs for Genomic Testing in Oncologists' Treatment Decisions.

PURPOSE: Use of genomic testing, especially multimarker panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Little is known about oncologists' treatment decisions with respect to patient insurance coverage and OOP costs for genomic testing. METHODS: We identified 1,049 oncologists who used multimarker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regressions examined associations of oncologist-, practice-, and area-level characteristics and oncologists' ratings of importance (very, somewhat, or a little/not important) of insurance coverage and OOP costs for genomic testing in treatment decisions, adjusting for oncologist years of experience, sex, race and ethnicity, specialty, use of next-generation sequencing (NGS) tests, region, tumor boards, patient insurance mix, and area-level socioeconomic characteristics. RESULTS: Among oncologists, 47.3%, 32.7%, and 20.0% reported that patient insurance coverage for genomic testing was very, somewhat, or a little/not important, respectively, in treatment decisions. In addition, 56.9%, 28.0%, and 15.2% reported that OOP costs for testing were very, somewhat, or a little/not important, respectively. In adjusted analyses, oncologists who used NGS tests were more likely to report patient insurance and OOP costs as important (odds ratio [OR], 2.00 [95% CI, 1.16 to 3.45] and OR, 2.12 [95% CI, 1.22 to 3.68], respectively) in treatment decisions compared with oncologists who did not use these tests, as were oncologists who treated solid tumors, rather than only hematological cancers. More years of experience and higher percentages of Medicaid or self-paid/uninsured patients in the practice were associated with reporting insurance coverage (OR, 1.43 [95% CI, 1.09 to 1.89]) and OOP costs (OR, 1.51 [95% CI, 1.13 to 2.01]) as important. Oncologists in practices with molecular tumor boards for genomic tests were less likely to report coverage (OR, 0.63 [95% CI, 0.47 to 0.85]) and OOP costs (OR, 0.72 [95% CI, 0.53 to 0.97]) as important than their counterparts in practices without these tumor boards. CONCLUSION: Most oncologists rate patient health insurance and OOP costs for genomic tests as important considerations in subsequent treatment recommendations. Modifiable factors associated with these ratings can inform interventions to support patient-physician decision making about care.

Assessment of Changes in Cancer Treatment During the First Year of the COVID-19 Pandemic in the US.

Importance: The COVID-19 pandemic led to disruptions in access to health care, including cancer care. The extent of changes in receipt of cancer treatment is unclear. Objective: To evaluate changes in the absolute number, proportion, and cancer treatment modalities provided to patients with newly diagnosed cancer during 2020, the first year of the pandemic. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older diagnosed with any solid tumor between January 1, 2018, and December 31, 2020, were identified using the National Cancer Database. Data analysis was conducted from September 19, 2022, to July 28, 2023. Exposure: First year of the COVID-19 pandemic. Main Outcomes and Measures: The expected number of procedures for each treatment modality (surgery, radiotherapy, chemotherapy, immunotherapy, and hormonal therapy) in 2020 were calculated using historical data (January 1, 2018, to December 31, 2019) with the vector autoregressive method. The difference between expected and observed numbers was evaluated using a generalized estimating equation under assumptions of the Poisson distribution for count data. Changes in the proportion of different types of cancer treatments initiated in 2020 were evaluated using the additive outlier method. Results: A total of 3 504 342 patients (1 214 918 in 2018, mean [SD] age, 64.6 [13.6] years; 1 235 584 in 2019, mean [SD] age, 64.8 [13.6] years; and 1 053 840 in 2020, mean [SD] age, 64.9 [13.6] years) were included. Compared with expected treatment from previous years' trends, there were approximately 98 000 fewer curative intent surgical procedures performed, 38 800 fewer chemotherapy regimens, 55 500 fewer radiotherapy regimens, 6800 fewer immunotherapy regimens, and 32 000 fewer hormonal therapies initiated in 2020. For most cancer sites and stages evaluated, there was no statistically significant change in the type of cancer treatment provided during the first year of the pandemic, the exception being a statistically significant decrease in the proportion of patients receiving breast-conserving surgery and radiotherapy with a simultaneous statistically significant increase in the proportion of patients undergoing mastectomy for treatment of stage I breast cancer during the first months of the pandemic. Conclusions and Relevance: In this large national cohort study, a significant deficit was noted in the number of cancer treatments provided in the first year of the COVID-19 pandemic. Data indicated that this deficit in the number of cancer treatments provided was associated with decreases in the number of cancer diagnoses, not changes in treatment strategies.

Health-related quality of life among prostate cancer survivors with metastatic disease and non-metastatic disease and men without a cancer history in the USA.

BACKGROUND: Few studies have comprehensively compared health-related quality of life (HRQoL) between metastatic prostate cancer survivors, survivors with non-metastatic disease, and men without a cancer history. METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) data linkage to identify men aged ≥ 65 years enrolled in Medicare Advantage (MA) plans. Prostate cancer survivors were diagnosed between 1988 and 2017 and completed MHOS surveys between 1998 and 2019. We analyzed data from 752 metastatic prostate cancer survivors (1040 survey records), 19,583 localized or regional prostate cancer survivors (non-metastatic; 30,121 survey records), and 784,305 men aged ≥ 65 years without a cancer history in the same SEER regions (1.15 million survey records). We used clustered linear regressions to compare HRQoL measures at the person-level using the Veterans RAND 12 Item Health Survey (VR-12) T-scores for general health and physical and mental component summaries. RESULTS: Compared to men without a cancer history, prostate cancer survivors were older, more likely to be married, and had higher socioeconomic status. Compared to men without a cancer history, metastatic prostate cancer survivors reported lower general health (T-score differences [95% confidence interval]: - 6.26, [- 7.14, - 5.38], p < .001), physical health (- 4.33, [- 5.18, - 3.48], p < .001), and mental health (- 2.64, [- 3.40, - 1.88], p < .001) component summaries. Results were similar for other VR-12 T-scores. In contrast, non-metastatic prostate cancer survivors reported similar VR-12 T-scores as men without a cancer history. Further analyses comparing metastatic and non-metastatic prostate cancer survivors support these findings. CONCLUSION: Interventions to improve health-related quality of life for men diagnosed with metastatic prostate cancer merit additional investigation. IMPLICATIONS FOR CANCER SURVIVORS: Interventions to improve health-related quality of life for metastatic prostate cancer survivors merit additional investigation.

Medicaid expansion is associated with treatment receipt, timeliness, and outcomes among young adults with breast cancer.

Female breast cancer is a common cancer in young adults, an age group with the highest uninsured rate. Among 51 675 young adult women (ages 18-39 years) diagnosed with breast cancer between 2011 and 2018 in the National Cancer Database, we estimated changes in guideline-concordant treatment receipt, treatment timeliness, and survival associated with the Affordable Care Act Medicaid expansion. Of young adults with stage I-III estrogen receptor-positive or progesterone receptor-positive breast cancer, Medicaid expansion was associated with a net increase of 2.42 percentage points (95% confidence interval [CI] = 0.56 to 4.28 percentage points) in the percentage receiving endocrine therapy. Among all young adults with stage I-III breast cancer, Medicaid expansion was associated with a net reduction of 1.65 percentage points (95% CI = 0.08 to 3.22 percentage points) in treatment delays defined as treatment initiation of at least 60 days after diagnosis and a net increase of 1.00 percentage points (95% CI = 0.21 to 1.79 percentage points) in 2-year overall survival. Our study provides evidence of benefit in cancer care and outcomes from Medicaid expansion among the young adult population.

Changes in cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic in the USA: a cross-sectional nationwide assessment.

BACKGROUND: The emergence of COVID-19 disrupted health care, with consequences for cancer diagnoses and outcomes, especially for early stage diagnoses, which generally have favourable prognoses. We aimed to examine nationwide changes in adult cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic by cancer type and key sociodemographic factors in the USA. METHODS: In this cross-sectional study, adults (aged ≥18 years) newly diagnosed with a first primary malignant cancer between Jan 1, 2018, and Dec 31, 2020, were identified from the US National Cancer Database. We included individuals across 50 US states and the District of Columbia who were treated in hospitals that were Commission on Cancer-accredited during the study period. Individuals whose cancer stage was 0 (except for bladder cancer), occult, or without an applicable American Joint Committee on Cancer staging scheme were excluded. Our primary outcomes were the change in the number and the change in the stage distribution of new cancer diagnoses between 2019 (Jan 1 to Dec 31) and 2020 (Jan 1 to Dec 31). Monthly counts and stage distributions were calculated for all cancers combined and for major cancer types. We also calculated annual change in stage distribution from 2019 to 2020 and adjusted odds ratios (aORs) using multivariable logistic regression, adjusted for age group, sex, race and ethnicity, health insurance status, comorbidity score, US state, zip code-level social deprivation index, and county-level age-adjusted COVID-19 mortality in 2020. Separate models were stratified by sociodemographic and clinical factors. FINDINGS: We identified 2 404 050 adults who were newly diagnosed with cancer during the study period (830 528 in 2018, 849 290 in 2019, and 724 232 in 2020). Mean age was 63·5 years (SD 13·5) and 1 287 049 (53·5%) individuals were women, 1 117 001 (46·5%) were men, and 1 814 082 (75·5%) were non-Hispanic White. The monthly number of new cancer diagnoses (all stages) decreased substantially after the start of the COVID-19 pandemic in March, 2020, although monthly counts returned to near pre-pandemic levels by the end of 2020. The decrease in diagnoses was largest for stage I disease, leading to lower odds of being diagnosed with stage I disease in 2020 than in 2019 (aOR 0·946 [95% CI 0·939-0·952] for stage I vs stage II-IV); whereas, the odds of being diagnosed with stage IV disease were higher in 2020 than in 2019 (1·074 [1·066-1·083] for stage IV vs stage I-III). This pattern was observed in most cancer types and sociodemographic groups, although was most prominent among Hispanic individuals (0·922 [0·899-0·946] for stage I; 1·110 [1·077-1·144] for stage IV), Asian American and Pacific Islander individuals (0·924 [0·892-0·956] for stage I; 1·096 [1·052-1·142] for stage IV), uninsured individuals (0·917 [0·875-0·961] for stage I; 1·102 [1·055-1·152] for stage IV), Medicare-insured adults younger than 65 years (0·909 [0·882-0·937] for stage I; 1·105 [1·068-1·144] for stage IV), and individuals living in the most socioeconomically deprived areas (0·931 [0·917-0·946] for stage I; 1·106 [1·087-1·125] for stage IV). INTERPRETATION: Substantial cancer underdiagnosis and decreases in the proportion of early stage diagnoses occurred during 2020 in the USA, particularly among medically underserved individuals. Monitoring the long-term effects of the pandemic on morbidity, survival, and mortality is warranted. FUNDING: None.

Medicaid Expansion Associated With Increase In Palliative Care For People With Advanced-Stage Cancers.

Clinical guidelines have endorsed early palliative care for patients with advanced malignancies, but receipt remains low in the US. This study examined the association between Medicaid expansion under the Affordable Care Act and receipt of palliative care among patients newly diagnosed with advanced-stage cancers. Using the National Cancer Database, we found that the percentage of eligible patients who received palliative care as part of first-course treatment increased from 17.0 percent preexpansion to 18.9 percent postexpansion in Medicaid expansion states and from 15.7 percent to 16.7 percent, respectively, in nonexpansion states, resulting in a net increase of 1.3 percentage points in expansion states in adjusted analyses. Increases in receipt of palliative care associated with Medicaid expansion were largest for patients with advanced pancreatic, colorectal, lung, and oral cavity and pharynx cancers and non-Hodgkin lymphoma. Our findings suggest that increasing Medicaid coverage facilitates access to guideline-based palliative care for advanced cancer, and they provide additional evidence of benefit in cancer care from states' expansion of income eligibility for Medicaid.

Interpretable Machine Learning for Fall Prediction Among Older Adults in China.

INTRODUCTION: Falls in older adults are potentially devastating, whereas an accurate fall risk prediction model for community-dwelling older Chinese is still lacking. The objective of this study was to build prediction models for falls and fall-related injuries among community-dwelling older adults in China. METHODS: This study used data (Waves 2015 and 2018) from 5,818 participants from the China Health and Retirement Longitudinal Study. A total of 107 input variables at the baseline level were regarded as candidate features. Five machine learning algorithms were used to build the 3-year fall and fall-related injury risk prediction models. SHapley Additive exPlanations was used for the prediction model explanation. Analyses were conducted in 2022. RESULTS: The logistic regression model achieved the best performance among fall and fall-related injury prediction models with an area under the receiver operating characteristic curve of 0.739 and 0.757, respectively. Experience of falling was the most important feature in both models. Other important features included basic activity of daily living, instrumental activity of daily living, depressive symptoms, house tidiness, grip strength, and sleep duration. The important features unique to the fall model were house temperature, sex, and flush toilets, whereas lung function, smoking, and Internet access were exclusively related to the fall-related injury model. CONCLUSIONS: This study suggests that the optimal models hold promise for screening out older adults at high risk for falls in facilitated targeted interventions. Fall prevention strategies should specifically focus on fall history, physical functions, psychological factors, and home environment.

Survival in Young Adults With Cancer Is Associated With Medicaid Expansion Through the Affordable Care Act.

PURPOSE: Medicaid expansion through the Affordable Care Act (ACA) has been shown to improve insurance coverage and early diagnosis of cancer in young adults (YAs); whether these improvements translate to survival benefits remains unknown. We examined the association between Medicaid expansion under the ACA and 2-year overall survival among YAs with cancer. METHODS: Using the National Cancer Database, we identified 345,413 YAs (age 18-39 years) diagnosed with cancer in 2010-2017. We applied the difference-in-differences (DD) method to estimate changes in 2-year overall survival after versus before Medicaid expansion in expansion versus nonexpansion states. RESULTS: Among all YAs, 2-year overall survival increased more in expansion states (90.39% pre-expansion to 91.85% postexpansion) than in nonexpansion states (88.98% pre-expansion to 90.07% postexpansion), resulting in a net increase of 0.55 percentage points (ppt; 95% CI, 0.13 to 0.96). The expansion-associated survival benefit was concentrated in patients with female breast cancer (DD, 1.20 ppt; 95%CI, 0.27 to 2.12) when stratifying by cancer type and in patients with stage IV disease (DD, 2.56; 95%CI, 0.36 to 4.77) when stratifying by stage. In addition, greater survival benefit associated with Medicaid expansion was observed among racial and ethnic minoritized groups (DD, 1.01 ppt; 95% CI, 0.14 to 1.87) as compared with non-Hispanic White peers (DD, 0.41 ppt; 95% CI, -0.06 to 0.87) and among patients with a Charlson comorbidity score of ≥ 2 (DD, 6.48 ppt; 95% CI, 0.81 to 12.16) than those with a comorbidity score of 0 (DD, 0.44 ppt; 95% CI, 0.005 to 0.87). CONCLUSION: Medicaid expansion under the ACA was associated with an improvement in overall survival among YAs with cancer, with survival benefits most pronounced among patients of under-represented race and ethnicity and patients with high-risk diseases.

Access to Care Among Adults with Limited English Proficiency.

BACKGROUND: There are approximately 25.6 million individuals with limited English proficiency (LEP) in the USA, and this number is increasing. OBJECTIVE: Investigate associations between LEP and access to care in adults. DESIGN: Cross-sectional nationally representative survey. PARTICIPANTS: Adults with (n = 18,908) and without (n = 98,060) LEP aged ≥ 18 years identified from the 2014-2018 Medical Expenditure Panel Survey MAIN MEASURES: Associations between LEP and access to healthcare and preventive services were evaluated with multivariable logistic regression models, stratified by age group (18-64 and ≥ 65 years). The official government definition of LEP (answers "not at all/not well/well" to the question "How well do you speak English?") was used. Access to care included having a usual source of care (and if so, distance from usual source of care, difficulty contacting usual source of care, and provision of extended hours), visiting a medical provider in the past 12 months, having to forego or delay care, and having trouble paying for medical bills. Preventive services included blood pressure and cholesterol check, flu vaccination, and cancer screening. KEY RESULTS: Adults aged 18-64 years with LEP were significantly more likely to lack a usual source of care (adjusted odds ratios [aOR] = 2.48; 95% confidence interval [CI] = 2.27-2.70), not have visited a medical provider (aOR = 2.02; CI = 1.89-2.16), and to be overdue for receipt of preventive services, including blood pressure check (aOR = 2.00; CI = 1.79-2.23), cholesterol check (aOR = 1.22; CI = 1.03-1.44), and colorectal cancer screening (aOR = 1.58; CI = 1.37-1.83) than adults without LEP. Results were similar among adults aged ≥ 65 years. CONCLUSIONS: Adults with LEP had consistently worse access to care than adults without LEP. System-level interventions, such as expanding access to health insurance coverage, providing language services, improving provider training in cultural competence, and increasing diversity in the medical workforce may minimize barriers and improve equity in access to care.

Postoperative day 1 serum cystatin C level predicts postoperative delayed graft function after kidney transplantation.

Background: Delayed graft function (DGF) commonly occurs after kidney transplantation, but no clinical predictors for guiding post-transplant management are available. Materials and methods: Data including demographics, surgery, anesthesia, postoperative day 1 serum cystatin C (S-CysC) level, kidney functions, and postoperative complications in 603 kidney transplant recipients who met the enrollment criteria from January 2017 to December 2018 were collected and analyzed to form the Intention-To-Treat (ITT) set. All perioperative data were screened using the least absolute shrinkage and selection operator. The discrimination, calibration, and clinical effectiveness of the predictor were verified with area under curve (AUC), calibration plot, clinical decision curve, and impact curve. The predictor was trained in Per-Protocol set, validated in the ITT set, and its stability was further tested in the bootstrap resample data. Result: Patients with DGF had significantly higher postoperative day 1 S-CysC level (4.2 ± 1.2 vs. 2.8 ± 0.9 mg/L; P < 0.001), serum creatinine level (821.1 ± 301.7 vs. 554.3 ± 223.2 µmol/L; P < 0.001) and dialysis postoperative (74 [82.2%] vs. 25 [5.9%]; P < 0.001) compared with patients without DGF. Among 41 potential predictors, S-CysC was the most effective in the parsimonious model, and its diagnostic cut-off value was 3.80 mg/L with the risk score (OR, 13.45; 95% CI, 8.02-22.57; P < 0.001). Its specificity and sensitivity indicated by AUC was 0.832 (95% CI, 0.779-0.884; P < 0.001) with well fit calibration. S-CysC yielded up to 50% of clinical benefit rate with 1:4 of cost/benefit ratio. Conclusion: The postoperative day 1 S-CysC level predicts DGF and may be used as a predictor of DGF but warrants further study.

Targeting the Mitochondria with Pseudo-Stealthy Nanotaxanes to Impair Mitochondrial Biogenesis for Effective Cancer Treatment.

The clinical success of anticancer therapy is usually limited by drug resistance and the metastatic dissemination of cancer cells. Mitochondria are essential generators of cellular energy and play a crucial role in sustaining cell survival and metastatic escape. Selective drug strategies targeting mitochondria are able to rewire mitochondrial metabolism and may provide an alternative paradigm to treat many aggressive cancers with high efficiency and low toxicity. Here, we present a pseudo-stealthy mitochondria-targeted pro-nanotaxane and test it against recurrent and metastatic tumor xenografts. The nanoparticle encapsulates a mitochondria-targetable pro-taxane agent, which can be converted into the chemically unmodified cabazitaxel drug, with further surface cloaking with a low-density lipophilic triphenylphosphonium cation. The resultant nanotaxane could be effectively taken up by cells and consequently specifically localized to the mitochondria. The in situ activated cabazitaxel causes mitochondrial dysfunction and ultimately results in potent cell apoptosis. After intravenous administration to animals, pro-nanotaxane mimics the stealthy behavior of polyethylene glycol-cloaked nanoparticles to provide a long circulation time. The antitumor efficacy of this mitochondria-targeted system was validated in multiple preclinical drug-resistant tumor models. Notably, in a patient-derived metastatic melanoma model that was initially pretreated with cabazitaxel, nanotaxane administration not only produced durable tumor reduction but also substantially suppressed metastatic recurrence. Taken together, these results demonstrate that this combination of a pseudo-stealthy platform with a rationally designed pro-drug is an attractive approach to target mitochondria and enhance drug efficacy.

Cancer Groundshot: Building a Robust Cancer Control Platform in Addition To Launching the Cancer Moonshot.

Cancer Groundshot is a philosophy that calls for prioritization of strategies in global cancer control. The underlying principle of Cancer Groundshot is that one must ensure access to interventions that are already proven to work before focusing on the development of new interventions. In this article, we discuss the philosophy of Cancer Groundshot as it pertains to priorities in cancer care and research in low- and middle-income countries and the utility of technology in addressing global cancer disparities; we also address disparities seen in high-income countries. The oncology community needs to realign our priorities and focus on improving access to high-value cancer control strategies, rather than allocating resources primarily to the development of technologies that provide only marginal gains at a high cost. There are several "low-hanging fruit" actions that will improve access to quality cancer care in low- and middle-income countries and in high-income countries. Worldwide, cancer morbidity and mortality can be averted by implementing highly effective, low-cost interventions that are already known to work, rather than investing in the development of resource-intensive interventions to which most patients will not have access (i.e., we can use Cancer Groundshot to first save more lives before we focus on the "moonshots").

Trends in Cancer Treatment Service Availability Across Critical Access Hospitals and Prospective Payment System Hospitals.

BACKGROUND: Rural residents experience worse cancer prognosis and access to cancer care providers than their urban counterparts. Critical access hospitals (CAHs) represent over half of all rural community hospitals. However, research on cancer services provided within CAHs is limited. OBJECTIVE: The objective of this study was to investigate trends in cancer services availability in urban and rural Prospective Payment System (PPS) hospitals and CAHs. DESIGN: Retrospective, time-series analysis using data from 2008 to 2017 American Hospital Association Annual Surveys. Multivariable logistic regressions were used to examine differential trends in cancer services between urban PPS, rural PPS, and CAHs, overall and among small (<25 beds) hospitals. SUBJECTS: All US acute care and cancer hospitals (4752 in 2008 to 4722 in 2017). MEASURES: Primary outcomes include whether a hospital provided comprehensive oncology services, chemotherapy, and radiation therapy each year. RESULTS: In 2008, CAHs were less likely to provide all cancer services, especially chemotherapy (30.4%) and radiation therapy (2.9%), compared with urban (64.4% and 43.8%, respectively) and rural PPS hospitals (42.0% and 23.3%, respectively). During 2008-2017, compared with similarly sized PPS hospitals, CAHs were more likely to provide oncology services and chemotherapy, but with decreasing trends. Radiation therapy availability between small PPS hospitals and CAHs did not differ. CONCLUSIONS: Compared with all PPS hospitals, CAHs offered fewer cancer treatment services and experienced a decline in service capability over time. These differences in chemotherapy services were mainly driven by hospital size, as small urban and rural PPS hospitals had lower rates of chemotherapy than CAHs. Still, the lower rates of radiotherapy in CAHs highlight disproportionate challenges facing CAHs for some specialty services.

Nanodelivery of a self-assembling prodrug with exceptionally high drug loading potentiates chemotherapy efficacy.

Nanomedicines have achieved several successful clinical applications for cancer therapy over the past decades. To date, numerous nanomedicine formats and design rationales have been proposed to improve pharmaceutical delivery and treatment efficacy. Despite these advances, the achievement of high drug loading and loading efficiencies of drug payloads in nanocarriers remains a technical challenge. In addition, study of the correlation between therapeutic potential and drug loading has been ignored. Here, using a self-assembling dimeric cabazitaxel prodrug, we show that the prodrug can be quantitatively entrapped within clinically approved polymer matrices for intravenous injection and that the drug loading in the nanoparticles (NPs) is tunable. The engineered NPs (NPs1-4) with different drug loading values exhibit dissimilar morphologies, release kinetics, in vitro cytotoxic activity, pharmacokinetic properties, tissue distribution, and in vivo anticancer efficacy and safety profiles. Furthermore, the effect of drug loading on the treatment outcomes was explored through detailed in vitro and in vivo studies. Intriguingly, among the constructed NPs, those comprising poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PLA) copolymers showed substantially prolonged pharmacokinetic properties in the blood circulation, which further promoted their intratumoral delivery and accumulation. Furthermore, the PEG-PLA-composed NPs with high drug loading (~50%) demonstrated favorable efficacy and safety profile in animal models. These data provide convincing evidence that the in vivo performance of a given self-assembling drug is not compromised by high drug loading in nanoplatforms, which may potentially reduce concerns over excipient-associated side effects and immunotoxicities. Overall, our study provides new insight into the rationale for designing more effective and less toxic delivery systems.

The Intersection of Rural Residence and Minority Race/Ethnicity in Cancer Disparities in the United States.

One in every twenty-five persons in America is a racial/ethnic minority who lives in a rural area. Our objective was to summarize how racism and, subsequently, the social determinants of health disproportionately affect rural racial/ethnic minority populations, provide a review of the cancer disparities experienced by rural racial/ethnic minority groups, and recommend policy, research, and intervention approaches to reduce these disparities. We found that rural Black and American Indian/Alaska Native populations experience greater poverty and lack of access to care, which expose them to greater risk of developing cancer and experiencing poorer cancer outcomes in treatment and ultimately survival. There is a critical need for additional research to understand the disparities experienced by all rural racial/ethnic minority populations. We propose that policies aim to increase access to care and healthcare resources for these communities. Further, that observational and interventional research should more effectively address the intersections of rurality and race/ethnicity through reduced structural and interpersonal biases in cancer care, increased data access, more research on newer cancer screening and treatment modalities, and continued intervention and implementation research to understand how evidence-based practices can most effectively reduce disparities among these populations.

Testicular tumors: discriminative value of conventional MRI and diffusion weighted imaging.

ABSTRACT: To explore the feasibility of using conventional MRI features combined with apparent diffusion coefficient (ADC) values for the differential diagnosis of testicular tumors.A total of 63 patients with pathologically confirmed testicular tumors were enrolled in this study. In particular, there were 46 cases of malignant lesions and 17 cases of benign lesions. All patients underwent conventional magnetic resonance imaging (MRI) and diffusion weighted imaging. Multivariate logistic regression models and receiver operating characteristic curves were constructed to assess diagnostic accuracies.T2-homogeneity, intratumoral septa, and peritumoral infiltration were more common in the malignant group, and capsule sign was more common in the benign group (P < .05 for all). The mean ADC value of the malignant group was lower than that of the benign group (P < .05). When the ADC value ≤ 0.90 × 10-3 mm2/s, the diagnosis tended to be malignancy. The conventional MRI model could achieve better diagnostic accuracy than ADC values alone (P < .05). Compared with the conventional MRI model, the specificity and accuracy of the full model (ADC and conventional MRI model) increased by 9.8% and 3.2%, respectively. T2-homogeneity and T2-hypointensity were more common in seminoma and lymphoma, cystic changes were more common in nonseminomatous germ cell tumor (NSGCT), and intratumoral septa was more common in seminoma (P < .05 for all). The ADC value of NSGCT was larger than seminoma, and lymphoma was the smallest (P < .05 for all). Cystic changes, T2-hypointensity, intratumoral septa, and ADC value were independent factors for differentiating the seminoma, NSGCT, and lymphoma subgroups.A combination of conventional MRI features and ADC values can improve the diagnostic efficiency for differentiating benign and malignant testicular tumors, and can additionally distinguish different subtypes of malignant testicular tumors.

Diagnostic value of hepatic artery perfusion fraction combined with TGF-ß in patients with hepatocellular carcinoma.

Diagnostic value of hepatic artery perfusion fraction (HAF) combined with transforming growth factor-ß (TGF-ß) in the diagnosis of primary liver carcinoma (PLC) was evaluated. The clinical data of 128 PLC patients undergoing radical hepatectomy in Affiliated Hospital of Jining Medical University were regarded as the study group. Seventy-four healthy volunteers examined in Affiliated Hospital of Jining Medical University were collected as the control group. Double-antibody sandwich enzyme-linked immunosorbent assay was used to detect the expression level of serum TGF-ß. The upper abdomen of the subjects was scanned by a 64-slice spiral CT, and the perfusion parameters were analyzed and calculated. According to the HAF and the expression level of TGF-ß in the two groups, single and combined detection of TGF-ß and HAF parameters were detected, respectively, by ROC curve. The expression of TGF-ß in serum of the study group was higher than that of the control group (P<0.05). The expression level of serum TGF-ß was closely related to total bilirubin, ascites, TNM stage, prothrombin time and tumor diameter. Blood flow (BF), blood volume (BV), permeability surface (PS), HAF and other perfusion parameters in the study group were higher than those in the control group (P<0.05). The specificity and sensitivity of TGF-ß expression level in diagnosing PLC were 73 and 93%, respectively; the specificity and sensitivity of HAF parameter in diagnosing PLC were 73 and 100%, respectively; the specificity and sensitivity of HAF parameter combined with TGF-ß expression level were 84 and 100%, respectively. TGF-ß is highly expressed in serum of PLC patients; HAF parameter combined with TGF-ß expression level can improve the specificity and has an important value in the diagnosis of PLC, which is worthy of clinical promotion.