Improved survival and decreased cancer deaths in young adults with cancer after passage of the Affordable Care Act Dependent Coverage Expansion.

BACKGROUND: The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited? METHODS: The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative survival data of patients who were diagnosed with cancer were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results regions representing 42%-44% of the country. RESULTS: Joinpoint analysis identified the DCE-eligible cohort as the only age group of the three groups evaluated that have had improvements in both cancer survival and death rate trends after ACA implementation and that 2010, the year the ACA was passed, was the inflection year for both survival and deaths. By 6 years, the relative survival after cancer diagnosis was 2.6 and 3.9 times greater in the DCE-eligible age group than in the younger and older control groups, respectively (both p < .001), and the cancer death rate in the DCE-eligible age group improved 2.1 and 1.5 times greater than in the younger and older control age groups, respectively (both p < .01). CONCLUSIONS: During the first decade of the ACA, eligible young adults with cancer have had significantly improved survival and mortality. Additional policies expanding insurance coverage and enabling earlier cancer diagnosis among young adults are needed. PLAIN LANGUAGE SUMMARY: The Patient Protection and Affordable Care Act (ACA) Dependent Care Expansion (DCE) that began in the United States in 2011 allowed young adults aged 19-25 years to remain on their parents' health insurance plans until age 26 years. The survival rate at 6 years in young adult patients diagnosed with cancer was 2.6 to 3.9 times greater in the DCE-eligible age group compared with the younger and older age groups, and the rate of deaths from cancer improved 1.5 to 2.1 times more. During the first decade of the ACA, young adults with cancer who were in the eligible group had significantly longer survival and reduced deaths from cancer. Additional policies that expand insurance coverage and allow the diagnosis of cancer sooner are needed in young adults.

Abatement of the Survival Cliff in Older Adolescents and Young Adults with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma in the United States.

Purpose: In 2018, a "survival cliff" in the United States was identified among older adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). This study reassessed the cliff and associated putative causes. Methods: Survival data were obtained using the U.S. Surveillance Research Program, National Cancer Institute (NCI) SEER 22 Registries. Accrual data on cancer treatment trials conducted by the NCI cooperative groups and NCI-designated cancer centers were obtained from the NCI Cancer Therapy Evaluation Program. Trend and average percent changes and statistical significances were identified with the NCI Joinpoint Regression Program. Results: A previous cliff-like decrement in the survival of 17- to 20-year-olds is no longer apparent, overall and in all racial and ethnic groups. The "survival cliff" age range was coincident with a clinical trial accrual cliff, and both diminished when more clinical trials were available to, and participated in by, young adult patients. Older AYA patients of ages 30-39 had minimal improvement in clinical trial accrual and least survival gain among the AYA age group. Conclusion: The survival cliff has abated, resulting in thousands of fewer premature deaths and tens of thousands of years of life saved-a remarkable achievement. The survival improvement may be attributed to improved clinical trial availability for and recruitment and participation of AYAs on treatment trials, application of pediatric-inspired ALL treatment regimens to AYAs, expanded national health insurance for -18 to 25 year olds, improved AYA cancer services, and a national focus on AYA oncology.

Fallacy of attributing the U.S. firearm mortality epidemic to mental health.

BACKGROUND: Annual global data on mental disorders prevalence and firearm death rates for 2000-2019, enables the U.S. to be compared with comparable counties for these metrics. METHODS: The Institute for Health Metrics and Evaluation (IHME) Global Health Burden data were used to compare the prevalence of mental disorders with overall, homicide and suicide firearm death rates including homicides and suicides, in high sociodemographic (SDI) countries. RESULTS: Overall and in none of the nine major categories of mental disorders did the U.S. have a statistically-significant higher rate than any of 40 other high SDI countries during 2019, the last year of available data. During the same year, the U.S. had a statistically-significant higher rate of all deaths, homicides, and suicides by firearm (all p<<0.001) than all other 40 high SDI countries. Suicides accounted for most of the firearm death rate differences between the U.S. and other high SDI countries, and yet the prevalence of mental health disorders associated with suicide were not significantly difference between the U.S. and other high SDI countries. CONCLUSION: Mental disorder prevalence in the U.S. is similar in all major categories to its 40 comparable sociodemographic countries, including mental health disorders primarily associated with suicide. It cannot therefore explain the country's strikingly higher firearm death rate, including suicide. Reducing firearm prevalence, which is correlated with the country's firearm death rate, is a logical solution that has been applied by other countries.

United States marijuana legalization and opioid mortality trends before and during the first year of the COVID-19 pandemic.

BACKGROUND: To determine if marijuana legalization was associated with reduced opioid mortality. STUDY DESIGN: The United States (US) opioid mortality trend during the 2010-2019 decade was compared in states and District of Columbia (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, the first year of the coronavirus disease 2019 (COVID-19) pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions. METHODS: Joinpoint methodology was applied to the Centers for Disease Control and Prevention WONDER data. Trends in legalizing jurisdictions were cumulative aggregates. RESULTS: The overall opioid and fentanyl death rates and the percentage of opioid deaths due to fentanyl increased more during 2010-2019 in jurisdictions that legalized marijuana than in those that did not (pairwise comparison p = 0.007, 0.05, and 0.006, respectively). By 2019, the all-opioid and fentanyl death rates were 44 and 50 percent greater in the legalizing than in the nonlegalizing jurisdictions, respectively. When the COVID-19 pandemic hit in 2020, jurisdictions that implemented recreational marijuana legalization before 2019 had significantly greater increases in both overall opioid and fentanyl death rates than jurisdictions with medicinal-only legalization. For all-opioids, the mean (95 percent confidence interval) 2019-to-2020 increases were 46.5 percent (36.6, 56.3 percent) and 29.1 percent (20.2, 37.9 percent), respectively (p = 0.02). For fentanyl, they were 115.6 percent (80.2, 151.6 percent) and 55.4 percent (31.6, 79.2 percent), respectively (p = 0.01). CONCLUSIONS: During the past decade, marijuana legalization in the US was associated at the jurisdiction level with a greater acceleration in opioid death rate. An even greater increase in opioid mortality occurred in recreational-legalizing jurisdictions with the onset of the COVID-19 pandemic. Marijuana legalization is correlated with worsening of the US opioid epidemic.

Prevention of cisplatin-induced hearing loss in children: achievements and challenges for evidence-based implementation of sodium Thiosulfate.

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly. The aim of this perspective paper is to explore the key safety issues and challenges important for pediatric oncologists and pharmacists when considering the clinical use of STS as an otoprotectant for children and adolescents receiving cisplatin. These include: the choice of the formulation; the timing, both that of the STS in relation to cisplatin as well as the timing of the cisplatin infusion itself; the dosing; the challenge left by the definition of localized versus disseminated disease and the difference in indication for STS, between cisplatin treated patients and those receiving another platinum chemotherapeutic agent, carboplatin.

Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature.

PURPOSE: Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN: A comprehensive narrative review is presented. RESULTS: Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION: Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.

Severe Methotrexate Toxicity Following a Capizzi Cycle in an Obese Adolescent With Acute Lymphoblastic Leukemia and Hepatic Steatosis.

Methotrexate is a major component of pediatric leukemia treatment. While toxicities are common after high-dose methotrexate, escalating dose methotrexate (Capizzi methotrexate) is typically well-tolerated. We report an adolescent Hispanic female with pre-B acute lymphoblastic leukemia, preexisting obesity and hepatic steatosis who developed severe multiorgan failure following an escalating dose of methotrexate with delayed methotrexate excretion of 11 days. We identified one similar report in an obese adult; however, this case is the first to our knowledge involving a pediatric patient. With the rising incidence of obesity and associated comorbidities among children and adolescents with leukemia, attention to potential risks for this population is warranted.

Retrospective evidence for pediatric benefit of U.S. assault weapons ban as rationale for implementing an even more effective ban.

BACKGROUND: With data available since 1981, firearm death rates in American children and adolescents can be evaluated for trends during the 13 years before, the decade of, and during 16 years since the United States (U.S.) 1994-2004 Federal Assault Weapons Ban (FAWB). METHODS: National and regional firearm mortality trends in the U.S. during 1981-2020 were assessed with joinpoint regression applied to Centers for Disease Control and Prevention data. RESULTS: After increasing exponentially before the FAWB, the national firearm death rate in 0-14 year-olds promptly reversed course and declined throughout the FAWB and then reversed again after the FAWB and resumed an exponential increase (all phases p<0.001). The reduction in firearm death rate occurred within 1-3 years of the start of the FAWB, in both sexes, in all four census regions of the U.S., and in all four major race/ethnicity subgroups, especially non-Hispanic blacks. No other form of violence in 0-14 year-olds had this temporal relationship with the FAWB. The firearm mortality reduction during the FAWB is strongly-highly correlated with the concomitant reduction in handgun manufacturing in 91 % of 24 sex, race/ethnicity and region subsets analyzed, These FAWB-related trends were also apparent in older adolescents and young adults and less so in older persons. CONCLUSIONS: Firearm death rates in 0-14 year-olds before, during, and after the FAWB, and no other type of injury, implicate the FAWB as having had a beneficial effect. Legislation to mitigate firearm mortality and injury inclusive of a FAWB should be especially beneficial to children and young adolescents, and regardless of sex, race/ethnicity or region in the U.S.

Increasing Cancer in Adolescents and Young Adults: Cancer Types and Causation Implications.

Purpose: This study aimed to identify cancer incidence trends in the United States and globally in adolescents and young adults (AYAs) 15-39 years of age, by sex, and to speculate on causes for trend changes. Methods: For the United States, SEER*Stat was used to obtain average annual percent change (AAPC) trends in cancer incidence during the period 2000-2019 among 395,163 AYAs. For global data, the source was the Institute of Health Metrics and Evaluation and its sociodemographic index (SDI) classification system. Results: In the United States, the invasive cancer incidence increased during the period 2000-2019 in both females (AAPC: 1.05, 95% CI: 0.90-1.20, p << 0.001) and males (AAPC: 0.56, 95% CI: 0.43-0.69, p << 0.001). A total of 25 and 20 types of cancers increased statistically significantly in female and male AYAs, respectively. Among potential causes for the increases, the obesity epidemic in the United States strongly correlates with the overall cancer increase in both its female (Pearson correlation coefficient R2 = 0.88, p = 0.0007) and male (R2 = 0.83, p = 0.003) AYAs, as does the most common malignancy in American AYAs, breast cancer (R2 = 0.83, p = 0.003). Worldwide, cancer incidence in the age group increased steadily during the period 2000-2019 among high-middle, middle, and low-middle SDI countries, but not in low SDI countries and with slowing of increase in high SDI countries. Conclusions: The increases and their age-dependent profiles implicate several causations that are preventable, including obesity, overdiagnosis, unnecessary diagnostic radiation, human papilloma virus infection, and cannabis avoidance. The United States is beginning to reverse the increasing incidence, and prevention efforts should be augmented accordingly.

Improved Survival of Young Adults with Cancer Following the Passage of the Affordable Care Act.

BACKGROUND: Compared with their ensured counterparts, uninsured adolescents and young adults (AYAs) with cancer are more likely to present with advanced disease and have poor prognoses. The Patient Protection and Affordable Care Act (ACA), enacted in 2010, provided health care coverage to millions of uninsured young adults by allowing them to remain on their parents' insurance until age 26 years (the Dependent Care Expansion, DCE). The impact of the expansion of insurance coverage on survival outcomes for young adults with cancer has not been assessed. PARTICIPANTS: Utilizing the Surveillance, Epidemiology, and End Results database, we identified all patients aged 12-16 (younger-AYAs), 19-23 (middle-AYAs), and 26-30 (older-AYAs) who were diagnosed with cancer between 2006-2008 (pre-ACA) and 2011-2013 (post-ACA). METHODS: In this population-based cohort study, we used an accelerated failure time model to assess changes in survival rates before and after the enactment of the ACA DCE. RESULTS: Middle-AYAs ages 19-23 (thus eligible to remain on their parents' insurance) experienced significantly increased 2-year survival after the enactment of the ACA DCE (survival time ratio 1.25, 95% confidence interval: 0.75-2.43, P = .029) and that did not occur in younger-AYAs (ages 12-16). Patients with sarcoma and acute myeloid leukemia accounted for the majority of improvement in survival. Middle-AYAs of hispanic ethnicity and those with low socioeconomic status experienced trends of improved survival after the ACA DCE was enacted. CONCLUSION: Survival outcomes improved for young adults with cancer following the expansion of health insurance coverage. Efforts are needed to expand coverage for the millions of young adults who do not have health insurance.

United States marijuana legalization and opioid mortality epidemic during 2010-2020 and pandemic implications.

BACKGROUND: The hypothesis that marijuana availability reduces opioid mortality merits more complete testing, especially in a country with the world's highest opioid death rate and 2nd highest cannabis-use-disorder prevalence. METHODS: The United States opioid mortality rate was compared in states and District of Columbia that had implemented marijuana legalization with states that had not, by applying joinpoint methodology to Centers for Disease Control and Prevention data. Variables included race/ethnicity and fentanyl-type opioids (fentanyls). RESULTS: After the same rates during 2010-2012, the opioid mortality rate increased more rapidly in marijuana-legalizing than non-legalizing jurisdictions (2010-2020 annual pairwise comparison p = 0.003 for all opioids and p = 0.0004 for fentanyls). During the past decade, all four major race/ethnicities in the U.S. had evidence for a statistically-significant greater increase in opioid mortality rates in legalizing than non-legalizing jurisdictions. Among legalizing jurisdictions, the greatest mortality rate increase for all opioids was in non-Hispanic blacks (27%/year, p = 0.0001) and for fentanyls in Hispanics (45%/year, p = 0.0000008). The greatest annual opioid mortality increase occurred in 2020, the first year of the COVID-19 pandemic, with non-Hispanic blacks having the greatest increase in legalizing vs. non-legalizing opioid-death-rate difference, from 32% higher in legalizing jurisdictions in 2019 to more than double in 2020. CONCLUSIONS: Instead of supporting the marijuana protection hypothesis, ecologic associations at the national level suggest that marijuana legalization has contributed to the U.S.'s opioid epidemic in all major races/ethnicities, and especially in blacks. If so, the increased use of marijuana during the 2020-2022 pandemic may thereby worsen the country's opioid crisis.

Current approaches to management of bone sarcoma in adolescent and young adult patients.

Bone tumors are a group of histologically diverse diseases that occur across all ages. Two of the commonest, osteosarcoma (OS) and Ewing sarcoma (ES), are regarded as characteristic adolescent and young adult (AYA) cancers with an incidence peak in AYAs. They are curable for some but associated with unacceptably high rates of treatment failure and morbidity. The introduction of effective new therapeutics for bone sarcomas is slow, and to date, complex biology has been insufficiently characterized to allow more rapid therapeutic exploitation. This review focuses on current standards of care, recent advances that have or may soon change that standard of care and challenges to the expert clinical research community that we suggest must be met.

Important factors improving outcome of young adults with acute lymphoblastic leukemia (ALL).

Four categories of important factors improving outcome of young adults and older adolescents with acute lymphoblastic leukemia (ALL) are biologic type, clinical trials, pediatric vs. adult treatment regimen, and psychosocial challenges. Overall, the outcome of ALL in the age group has improved and beginning to catch up with that in children, as exemplified by CALGB 10403, a pediatric treatment regimen. Each is dependent for optimum development, however, on progress in the others. Without adequate psychosocial support and improvement, progress in clinical trials, translational research, and pediatric regimen application is impaired. Without clinical trials, advances in translational research, optimal pediatric regimen application and adequate psychosocial research are restricted. Overall, we have improved the outcome and outlook of ALL in AYAs, as exemplified by CALGB 10403, but we and our current and future patients still have a long way to go.

Patterns of National Cancer Institute-Sponsored Clinical Trial Enrollment in Black Adolescents and Young Adults.

BACKGROUND: Both adolescent and young adult (AYA) and Black or African American (hereafter referred to as Black) cancer patients are historically under-enrolled in cancer treatment trials (CTT). The purpose of this study was to quantify enrollment of Black AYAs in National Cancer Institute (NCI)-sponsored CTTs overall and by age, sex, and cancer diagnosis during 2000-2015. METHODS: Utilizing data from NCI's Cancer Therapy Evaluation Program and the Surveillance, Epidemiology and End Results (SEER) Program, we assessed CTT enrollment in Black patients with cancer and measured changes in enrollment over time between the study periods 2000-2007 and 2008-2015. Enrollment patterns were compared across age groups (≤14 years [y], 15-19y, 20-29y, 30-39y and 40+ years), sex, and cancer diagnosis. RESULTS: From 2000 through 2015, <3% of Black AYAs (20-39y) enrolled on CTTs. While AYAs had significantly higher cancer incidence than children, 20.5% fewer Black AYAs enrolled on CTTs. Enrollment was lowest among Black males 20-29y, with a mean of 18 enrolling in CTTs annually. The proportion of AYA enrollees who were Black did not change significantly over time periods (2000-2007 vs 2008-2015). CONCLUSIONS: Few Black AYAs enroll in CTTs each year. Given known benefits of clinical trial participation and the well-documented racial and age-related differences in cancer outcomes, addressing barriers to enrollment in these patients may, in turn, reduce disparities. Targeted interventions aimed at increasing the CTT enrollment of Black cancer patients, particularly young Black men, are urgently needed. PRECIS: This study documents that compared with Black children, Black adolescent, and young adult (AYA) patients were less likely to enroll in NCI-sponsored CTTs from 2000 to 2015. Black AYA male enrollment decreased with increasing age, highlighting disparities among this specific population in CTT enrollment.

Increasing Rate of Unintentional Firearm Deaths in Youngest Americans: Firearm Prevalence and Covid-19 Pandemic Implication.

BACKGROUND: The United States has had, by far, the world's greatest civilian ownership of firearms. An even greater ownership occurred during the Covd-19 pandemic, mostly of handguns and including many new owners. The U.S. has also had the least progress of the 41 highest sociodemographic countries ranked by the Institute for Health Metrics and Evaluation in reducing the unintentional firearm mortality rate in young children. This study characterized the unintentional firearm mortality trends in American 1-4 year-olds by sex and race/ethnicity and evaluated the trends in the context of firearm prevalence in the U.S. METHODS: Mortality data for 1999-2018 were obtained from the U.S. Centers for Disease Control and Prevention and the Institute for Health Metrics and Evaluation, firearm injury and mortality data for 2016-2020 from Everytown for Gun Safety #NotAnAccident database, firearm background check data for 1999-2020 from the National Instant Criminal Background Check System, and civilian firearm prevalence for 2017 from the Small Arms Survey. RESULTS: In American 1-4 year-olds, the rate of unintentional firearm deaths during 1999-2018 increased exponentially at an average annual percent rate of 4.9 (p < 0.001) and was greatest in non-Hispanic black children. Unintentional firearm deaths had the most rapid increase of all evaluable causes of death in the age group. The unintentional firearm death rate increase was correlated with the concurrent rate of firearm background checks and handgun permits issued (each p < 0.001) and in non-Hispanic white children with handgun prevalence in their families (p = 0.03). Globally, the unintentional firearm death rate was also correlated with firearm prevalence (p = 0.02). CONCLUSIONS: An increase in fatal firearm accidents in the United States death rate among 1-4 year-olds is directly associated with the steadily increasing prevalence of firearms. The acceleration of firearm deaths and injuries among young Americans, especially among non-Hispanic black children, requires urgent solutions to address firearm prevalence and access. The problem is expected to become even more urgent as a result of the record high firearm sales that occurred in the United States during the 2020 coronavirus pandemic.

Breast Cancer in Adolescent and Young Adult Women Under the Age of 40 Years.

In the United States, one in 196 women is diagnosed with breast cancer under the age of 40 years. Adolescents and young adults (AYAs), of age 15-39 years at diagnosis, experience a number of unique challenges when confronting breast cancer. The incidence of invasive breast cancer has increased among AYA women in the United States since 2004, and most of this change is due to an increase in young women diagnosed with distant disease. AYAs are more likely than older women to present with aggressive subtypes and advanced disease, and they often require systemic staging at diagnosis. Clinical trials should be considered whenever possible, particularly in AYAs with locally advanced or metastatic disease at diagnosis and those with disease progression or recurrence. A significant proportion of AYAs carry germline cancer predisposition mutations, which necessitates prompt genetic testing for all AYAs at diagnosis and may influence choice of local therapy. Suppression of ovarian function, as an adjunct to chemotherapy, may improve breast cancer survival in AYAs. To provide optimal care for AYAs with breast cancer, clinicians should engage multidisciplinary teams that offer fertility preservation, genetic counseling, physical and occupational therapy, nutrition, and psychosocial support, along with medical expertise in tailoring cancer-directed therapy and symptom management toward young women.