Chronic health conditions among long-term survivors of adolescent and young adult cancer: A comparison of outcomes in Israel and the United States.

BACKGROUND: There is a paucity of information on health outcomes of adolescent and young adult (AYA) cancer survivors living outside North America and Europe. This study compared outcomes in AYA cancer survivors in Israel with individuals without cancer and similar demographics and access to health care, and to AYA cancer survivors living in the United States. METHODS: This study included 12,674 2-year survivors of AYA (aged 15-39 years) cancer diagnosed between 2000 and 2018 at Clalit Health Services (CHS) in Israel. CHS participants without cancer (N = 50,696) were matched 4:1 to survivors on age, sex, ethnicity, and membership duration. Poisson regression was used to determine incidence rate ratios (IRRs) for chronic conditions. The US Kaiser Permanente Southern California AYA cohort (N = 6778) was used to estimate weighted (age, sex) standardized incidence ratios (SIRs) for CHS survivors. RESULTS: CHS AYA cancer survivors were more likely to have any chronic condition (IRR, 1.6 95% CI, 1.5-1.7), compared with participants without cancer. Survivors had an increased risk across nearly all conditions examined, with especially elevated risks for osteoporosis (IRR, 4.7; 95% CI, 4.1-5.5) and cardiomyopathy (IRR, 4.2 95% CI, 3.4-5.3). Compared with the Kaiser Permanente Southern California cohort, CHS survivors had an overall lower (SIR, 0.68; 95% CI, 0.65-0.72) incidence of developing any health condition, with noticeably lower incidence of hyperlipidemia (SIR, 0.7; 95% CI, 0.64-0.75). CONCLUSION: AYA cancer survivors in Israel are at increased risk for developing chronic conditions compared with individuals without cancer, but the overall incidence was lower than in US survivors. These findings may allow for refinement of surveillance recommendations for AYA survivors, taking into consideration regional differences in sociodemographic characteristics and cancer care. PLAIN LANGUAGE SUMMARY: The burden of chronic conditions was consistently greater in Israeli adolescent and young adult cancer survivors compared with individuals without cancer, with clear differences in risk of specific conditions by cancer diagnosis. However, the overall incidence of chronic conditions in Israeli survivors was generally lower than in US survivors.

Financial hardship differences by LGBTQ+ status among assigned female at birth adolescent and young adult cancer survivors: a mixed methods analysis.

BACKGROUND: Adolescent and young adult (AYA) cancer survivors are at an elevated risk of financial hardship. However, financial hardship among LGBTQ+ AYAs has not been widely explored. Thus, we used qualitative and quantitative survey data from the Horizon Study cohort to assess financial hardship of AYAs by LGBTQ+ status. METHODS: Multivariable logit models, predicted probabilities, average marginal effects or differences in predicted probabilities (AME) and 95% confidence intervals (CI) were used to assess the association of LGBTQ+ status and two components of financial hardship: material and psychological. Qualitative content analysis of an open-ended survey question about financial sacrifices was used to describe the third component of financial hardship, behavioral. RESULTS: Among 1,635 participants, 4.3% self-identified as LGBTQ+. Multivariable logit models controlling for demographic factors revealed that LGBTQ+ AYAs had an 18-percentage point higher probability of experiencing material financial hardship (95%CI 6-30%) and a 14-percentage point higher probability of experiencing psychological financial hardship (95%CI 2-26%) than non-LGBTQ+ AYAs. Controlling for economic factors attenuated the association of LGBTQ+ status with psychological financial hardship (AME = 11%; 95%CI - 1-23%), while the material financial hardship association remained statistically significant (AME = 14%; 95%CI 3-25%). In the qualitative analysis, LGBTQ+ AYAs frequently reported educational changes and costs (e.g., quitting school), unpaid bills and debt (e.g., medical debt, taking on credit card debt), as well as changes in housing and poor housing conditions (e.g., moving into less expensive house). CONCLUSIONS: LGBTQ + targeted and tailored interventions are needed to move toward equity for LGBTQ+ AYAs-an overlooked minority population.

Human papillomavirus vaccination history and diagnosis of cervical intraepithelial neoplasia grade ≥2 severe lesions among a cohort of women who underwent colposcopy in Kaiser Permanente Southern California.

BACKGROUND: The risk of a high-grade lesion in women undergoing colposcopy following an abnormal screening result may be different by human papillomavirus vaccination status, because women who are vaccinated are presumably less likely to harbor human papillomavirus types 16 and 18. OBJECTIVE: This study aimed to evaluate whether the risk of high-grade cervical lesion diagnosed through colposcopy is lower in women with human papillomavirus vaccination than in women without vaccination referred to colposcopy based on equal abnormal screening findings. STUDY DESIGN: Kaiser Permanente Orange County female patients between ages 21 and 38 years were included following an abnormal screening if they had ≥1 colposcopies between July 2017 and August 2018 and had at least 1 pathology diagnosis from the colposcopy visits. Data on demographic characteristics, clinical and sexual histories, and human papillomavirus vaccination were collected using a colposcopy registry smart form and from electronic medical records. Human papillomavirus genotyping was performed for tissues from confirmed cervical intraepithelial neoplasm grade 2+ diagnoses. A multilevel generalized linear model with a logic function was used to evaluate the association between human papillomavirus vaccination history and the outcome of a cervical intraepithelial neoplasm grade 2+ diagnosis and for human papillomavirus type 16- or 18-positive cervical intraepithelial neoplasm grade 2+ as an alternative outcome, adjusting for screening results and potential confounders. RESULTS: Of 730 women included in the study, 170 had a histologic diagnosis of cervical intraepithelial neoplasm grade 2+ (23.2%). Moreover, 68 cases (40.0%) were histologically human papillomavirus type 16 and/or 18 positive. Of the 730 women, 311 (43%) were vaccinated for the human papillomavirus before colposcopy. Most women (206 [66.2%]) with human papillomavirus vaccination received the vaccine between the ages 18 and 26 years. A history of human papillomavirus vaccination overall, before sexual debut, before the age of 18 years, or with complete dosing was not associated with lower odds of a cervical intraepithelial neoplasm grade 2+ diagnosis (odds ratio, 1.07 [95% confidence interval, 0.70-1.64]; odds ratio, 1.11 [95% confidence interval, 0.55-2.24]; odds ratio, 0.96 [95% confidence interval, 0.49-1.91]; and odds ratio, 0.84 [95% confidence interval, 0.53-1.35], respectively, in reference to no vaccination). Human papillomavirus vaccination history was not significantly associated with the odds of a human papillomavirus type 16- or 18-positive cervical intraepithelial neoplasm grade 2+ diagnosis (P=.45). Notably, 8 cases (4.8% of all cervical intraepithelial neoplasm grade 2+ cases) showed a human papillomavirus type 16 on a cervical intraepithelial neoplasm grade 2+ histologic polymerase chain reaction analysis despite reported or documented human papillomavirus vaccination before sexual debut, including 2 cases who started vaccination before the age of 13 years. CONCLUSION: Our study did not support modifying the colposcopy management guidelines for abnormal screening results for women with human papillomavirus vaccination, especially those vaccinated in the catch-up age range. Our findings on the 8 cases of human papillomavirus 16-positive cervical intraepithelial neoplasm grade 2+ vaccination before sexual debut suggested that lowering the recommended age for human papillomavirus vaccination may have additional benefits for preventing human papillomavirus infection that could occur early in life in some women.

Impact of COVID-19 on Cervical Cancer Screening Rates Among Women Aged 21-65 Years in a Large Integrated Health Care System - Southern California, January 1-September 30, 2019, and January 1-September 30, 2020.

On March 19, 2020, the governor of California issued a statewide stay-at-home order to contain the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* The order reduced accessibility to and patient attendance at outpatient medical visits,† including preventive services such as cervical cancer screening. In-person clinic visits increased when California reopened essential businesses on June 12, 2020.§ Electronic medical records of approximately 1.5 million women served by Kaiser Permanente Southern California (KPSC), a large integrated health care system, were examined to assess cervical cancer screening rates before, during, and after the stay-at-home order. KPSC policy is to screen women aged 21-29 years every 3 years with cervical cytology alone (Papanicolaou [Pap] test); those aged 30-65 years were screened every 5 years with human papillomavirus (HPV) testing and cytology (cotesting) through July 15, 2020, and after July 15, 2020, with HPV testing alone, consistent with the latest recommendations from U.S. Preventive Services Task Force.¶ Compared with the 2019 baseline, cervical cancer screening rates decreased substantially during the stay-at-home order. Among women aged 21-29 years, cervical cytology screening rates per 100 person-months declined 78%. Among women aged 30-65 years, HPV test screening rates per 100 person-months decreased 82%. After the stay-at-home order was lifted, screening rates returned to near baseline, which might have been aided by aspects of KPSC's integrated, organized screening program (e.g., reminder systems and tracking persons lost to follow-up). As the pandemic continues, groups at higher risk for developing cervical cancers and precancers should be evaluated first. Ensuring that women receive preventive services, including cancer screening and appropriate follow-up in a safe and timely manner, remains important.

Cause-specific mortality in survivors of adolescent and young adult cancer.

BACKGROUND: Few studies have adequately addressed long-term survival (>20 years from diagnosis) among survivors of adolescent and young adult (AYA) cancers. METHODS: In this retrospective, population-based cohort study in a US integrated health care system, the authors examined cause-specific mortality in 2-year survivors of AYA cancers (patients aged 15-39 years who were diagnosed between 1990 and 2012; N = 10,574) matched (by age, sex, and calendar year) to individuals without cancer (N = 136,683) to determine whether mortality rates changed over time. Incidence rate ratios (IRRs) for mortality were estimated using multivariable Poisson regression. A multivariable Cox model was used to examine predictors of cause-specific mortality among AYA cancer survivors. RESULTS: Through December 31, 2014, 1352 deaths were observed among AYA cancer survivors, yielding an overall survival rate of 78.5% at 25 years after diagnosis. Overall, AYA cancer survivors were at 10.4-fold increased risk for death (95% CI, 9.7-fold to 11.2-fold increased risk for death) compared with the matched noncancer cohort, and this risk remained elevated at >20 years after diagnosis (IRR, 2.9; 95% CI, 2.0-4.3). The absolute excess risk for death from any cause was 12.7 per 1000 person-years (95% CI, 11.9-13.4 per 1000 person-years). Starting at 15 years after diagnosis, the incidence of second cancer-related mortality exceeded the rate of recurrence-related mortality, and similar trends were observed for deaths from other health-related conditions. The 8-year cumulative incidence of mortality declined over time (before 2000, 12.6%; 2000-2006, 10.1%; after 2006, 7.3%; P < .001), largely because of declines in recurrence-related mortality. Age, sex, race/ethnicity, cancer stage at diagnosis, and cancer treatment predicted cause-specific mortality. CONCLUSIONS: The current data highlight the need for specialized, long-term follow-up care for AYA cancer survivors.

Long-term Health Outcomes in Survivors of Childhood Cancer Diagnosed Between 1990 and 2000 in a Large US Integrated Health Care System.

We evaluated the long-term health outcomes of childhood cancer survivors (CCS) using data from the Kaiser Permanente Southern California (KPSC) health plan, whose members have similar health care coverage. Five-year survivors of invasive cancer diagnosed at ages 0 to 18 years between 1990 and 2000 at KPSC were identified and followed to December 31, 2010. A group of KPSC members without history of cancer were 10:1 matched to each CCS for comparison. Health outcomes of interest included mortality, second cancer, and chronic comorbidities. Incidence rate ratio (IRR) was estimated using multivariable Poisson regression. Cumulative incidence of each health condition over time was calculated. A total of 652 CCS and 6520 noncancer subjects were included. Compared with the noncancer subjects, IRR was significantly elevated among CCS for mortality (IRR=14.1), second cancer (IRR=10.0), cerebrovascular disease (IRR=10.1), dyslipidemia (IRR=1.9), hearing/vision loss (IRR=5.1), heart disease (IRR=3.9), hypogonadism (IRR=4.2), renal failure (IRR=13.4), and thyroid disorder (IRR=6.4). Approximately 40% of CCS developed at least 1 chronic health condition within 15 years of cancer diagnosis. Cumulative incidence curves showed different risk trajectories of various comorbidities which may inform screening schedule. These data suggested that CCS treated in a more contemporary era continued to experience substantial disease burden in their adolescent and young adulthood.

Trends in anemia treatment among patients with five non-myeloid malignancies treated with chemotherapy in a large integrated health care delivery system in California, 2000-2013.

PURPOSE: The aim of this study is to examine treatment patterns for chemotherapy-induced anemia (CIA) between calendar periods when the changes in the US prescribing information, for erythropoiesis-stimulating agents (ESAs) took place. METHODS: Patients diagnosed with breast, lung, colorectal, ovarian, or gastric cancer (2000-2012) who developed grade 2+ CIA (hemoglobin (Hb) <10 g/dl) were identified from Kaiser Permanente Southern California Health Plan. We estimated the proportions of CIA episodes with ESA use, red blood cell (RBC) transfusion, or prescription nutritional supplements in three calendar periods: January 1, 2000-December 31, 2006 (P1), January 1, 2007-March 24, 2010 (P2), and March 25, 2010-June 30, 2013 (P3). Multivariable regressions were used to test the differences of CIA treatment approaches and Hb concentration prior to CIA treatment across these calendar periods. RESULTS: The proportions of CIA episodes with ESA use were 28 % in P1, 21 % in P2, and 3 % in P3. For RBC transfusion, they were 8 % in P1, 14 % in P2 and 16 % in P3. The trend of decreasing ESA use and increasing transfusion use were statistically significant. Relative to P1, the odds ratio (OR) was 0.69 (95% CI: 0.55, 0.86) for P2 and 0.08 (0.30, 0.88) for P3 for ESA use. For RBC transfusion, OR was 2.00 (1.56, 2.56) for P2 and 2.37 (1.88, 3.00) for P3. Use of prescription nutritional supplement was rare across calendar periods. There was a decreasing trend of Hb concentration prior to ESA use (p value <0.01), but no difference in Hb concentrations prior to transfusion. CONCLUSION: In the management of CIA, use of ESA has decreased over time, while use of RBC transfusion has increased.

The effect of chemotherapy-induced anemia on dose reduction and dose delay.

PURPOSE: To evaluate moderate (grade 2, hemoglobin <10 g/dl) and severe (grade 3+, hemoglobin <8 g/dl) anemia as potential risk factors for DDR in the first line course of chemotherapy. While chemotherapy-induced neutropenia has been shown to be associated with dose delay/reduction (DDR) in several studies, the effect of anemia is less well studied. METHODS: We identified 3955 Kaiser Permanente patients diagnosed with incident non-Hodgkin's lymphoma (n = 574), breast (n = 2043), lung (n = 463), gastric (n = 113), ovarian (n = 204), or colorectal cancers (n = 558) between 2010 and 2012. Generalized linear mixed effects models were used to study the effect of anemia in subsequent cycles, adjusting for demographics, comorbidities, chemotherapy cycle, neutropenia, thrombocytopenia, and liver and renal function. RESULTS: We found that moderate (grade 2) to severe (grade 3-4) anemia increased the risk of DDR in subsequent chemotherapy cycles [odds ratio (OR) = 1.46, 95 % CI (1.32, 1.62) and OR = 2.02 (1.41, 2.89)], respectively, compared to grade 1 or no anemia. Both stage I-III and IV patients with grade 2 or greater anemia were at higher risk for DDR than patients with grade 1 or no anemia [ORstage IV, grade 2 = 1.94 (1.58, 2.38); ORstage IV, grade 3/4 = 2.83 (1.42, 5.62) and ORstage I-III, grade 2 = 1.33 (1.18, 1.49); ORstage I-III, grade 3-4 = 1.81 (1.18, 2.76)]. CONCLUSIONS: These results provide insight into novel risk factors for chemotherapy dose modification that may inform clinicians on management strategies to optimize treatment outcomes.

Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care.

Concerns remain for an increased myocardial infarction (MI) risk among individuals infected with human immunodeficiency virus (HIV). We conducted a cohort study evaluating MI risk from 1996 to 2011 by HIV status. The adjusted MI rate ratio for HIV status declined over time, reaching 1.0 (95% confidence interval, .7-1.4) in 2010-2011, the most recent study period.

[Determination of six C-Glycoside flavones and antitumor activity of water-soluble total flavonoids from Isodon lophanthoides var. gerardianus].

This research established an HPLC method for determination of six C-Glycoside flavones of warer-soluble total flavonoids from Isodon lophanthoides var. gerardianus (Benth.) H. Hara, and studied the antitumor activity of the warer-soluble total flavonoids. The HPLC system consisted of Kromasil 100-5 C18 (4.6 mm x 250 mm, 5 microm) column and a solution system of methanol, acetonitrile and 0.5% formic acid gradient elution at a flow rate of 0. 8 mL x min(-1) and the wavelength of detector was at 334 nm. The column temperature was 25 degrees C. The antitumor activity of water-soluble flavonoids was assayed using HepG2 cell as the tested cell. The linear ranges of vicenin II, vicenin III, isoschaftoside, schaftoside, vitexin, 6, 8-di-C-a-L-arabinosylapigenin were 0.25-2.53, 0.12-1.20, 0.37-3.69, 0.16-1.63, 0.19-1.92, 0.14-1.42 microg, respectively. The average recoveries (n = 6) were 99.6% (RSD 0.87%), 100.2% (RSD 2.0%), 99.6% (RSD 1.8%), 97.9% (RSD 1.5%), 98.8% (RSD 1.2%), 98.6% (RSD 1.2%), respectively. After exposure in 24, 48, 72 h, the total flavonoids showed inhibitory effect on the proliferation of HepG2 cells with IC50 as the evaluation index, the IC50 values of 1.89, 1.71, 1.51 g x L(-1), respectively. The method is quick, simple and accurate with good re- producibility, and can be used for determination of vicenin II, vicenin III, isoschaftoside, schaftoside, vitexin, 6, 8-di-C-a-L-arabino- sylapigenin in the warer-soluble total flavonoids from L lophanthoides var. gerardianus. The warer-soluble total flavonoids from L lophanthoides have inhibitory effect on the proliferation of HepG2 cells.

Antitumor effects of naturally occurring oligomeric resveratrol derivatives.

This study was designed to evaluate and characterize the molecular basis of antitumor activity of naturally occurring resveratrol (RES; 3,5,4'-trihydroxy-trans-stilbene) derivatives. The compounds were isolated from plants in previous studies and characterized spectroscopically. The antitumor activities of 31 RES derivatives, including dimers, trimers, and tetramers of RES, were evaluated using cell-based assays and validated on a murine model. Several trimeric and a tetrameric stilbenoids induced tumor cell apoptosis or growth arrest of several tumor cell lines with IC50 values (2.8-19.7 µM), significantly lower than that of RES (IC50>70 µM). Using pauciflorol B (PauB) as an example, we showed that the compound induced apoptosis p53 dependently, inducing p53 accumulation and p53-modulated gene expression in cells with wild-type p53, but not in those with nonfunctional p53. Reexpression of p53 in p53-null cells rescued cell death response. In parallel, the MAPK/p38 was activated and critical for PauB-induced killing. Interestingly, activation of p38 in p53 deficient cells was sufficient to drive cells into senescence via the p16-pRb pathway. Finally, PauB dose-dependently inhibited tumor growth on nude mice. Naturally occurring trimeric and tetrameric stilbenoids are potent antitumor agents. Those compounds exert antitumor effect through p53-dependent induction of apoptosis or senescence.

Impact of the Coronavirus Disease 2019 pandemic on neoadjuvant chemotherapy use in patients diagnosed with epithelial type ovarian cancer.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic posed critical challenges in providing care to ovarian cancer (OC) patients, including delays in OC diagnosis and treatment initiation. To accommodate for delays in OC surgery, the Society of Gynecologic Oncology (SGO) recommended preferential use of neoadjuvant chemotherapy during the pandemic. The purpose of this study was to assess the association of the COVID-19 pandemic with neoadjuvant chemotherapy use in patients diagnosed with OC. Methods: This retrospective cohort study included patients diagnosed with stage II-IV ovarian cancer of epithelial subtype between 01/01/2017-06/30/2021 at Kaiser Permanente Southern California (KPSC), a large integrated healthcare system in the United States. Ovarian cancer patients diagnosed between 2017-2020 were identified from KPSC's Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry. Patients diagnosed in 2021 were identified from the electronic medical records (EMR) using ICD-10 diagnosis codes, followed by medical chart review to validate diagnosis and extract information on histology and stage at diagnosis. March 4, 2020 was used as the cut-off to define pre-pandemic and pandemic periods. Patients diagnosed with COVID-19 between OC diagnosis and treatment completion were excluded. Data on neoadjuvant chemotherapy use were extracted from the cancer registry and EMR, supplemented by chart review. Modified Poisson regression was used to evaluate the association of the pandemic with neoadjuvant chemotherapy use. Results: Of 566 OC patients, 160 (28.3%) were diagnosed in the pandemic period. Patients diagnosed in the pandemic period were slightly younger (mean age 62.7 vs 64.9 years, p=0.07) and had a higher burden of Charlson comorbidities (p=0.05) than patients diagnosed in pre-pandemic period. No differences in time to treatment initiation were observed by pandemic periods. Neoadjuvant chemotherapy use was documented in 58.7% patients during the pandemic period compared to 47.3% in pre-pandemic period (p=0.01). After adjusting for covariates, patients diagnosed in the pandemic period were 29% more likely to receive neoadjuvant chemotherapy than patients diagnosed in pre-pandemic period [RR(95%CI): 1.29(1.12-1.49)]. Discussions: Ovarian cancer patients diagnosed in the COVID-19 pandemic were more likely to receive neoadjuvant chemotherapy than patients diagnosed before the pandemic. Future research on patient outcomes and trends in the post-pandemic period are warranted.

Neighborhood factors associated with late effects among survivors of adolescent and young adult cancer.

PURPOSE: The purpose of this study is to evaluate the associations between neighborhood income, education, and neighborhood racial composition (measured as a low percentage of white residents) and risk of developing cardiovascular diseases (CVD), diabetes (DM), and severe depression among survivors of AYA cancer and matched non-cancer peers. METHODS: Two-year survivors of AYA cancers diagnosed at age 15-39 yrs at Kaiser Permanente Southern California (diagnosed 2000-2012) and individually matched (1:13) non-cancer subjects were included. The development of CVD, DM, and severe depression was ascertained via electronic health records. Neighborhood characteristics were obtained from census-based geocoded data. Cox regression evaluated associations between neighborhood characteristics and the health outcomes of interest among both the cancer survivors and the non-cancer comparison cohort and effect modification by cancer survivor status on these relationships. RESULTS: Among cancer survivors (n = 6774), living in mostly non-white neighborhoods, was associated with risk of CVD (hazard ratio (HR) = 1.54 (95% CI 1.00-2.36)), while lower education level (HR = 1.41 (95% CI 1.02-1.94)) was associated with risk of severe depression. None of the neighborhood characteristics were associated with risk of DM. Effect modification was found for neighborhood education and risk of DM and severe depression. CONCLUSION: When jointly considered, cancer survivors who resided in the most disadvantaged neighborhoods were at the highest risk of developing these health outcomes compared to other subgroups. IMPLICATIONS FOR CANCER SURVIVORS: Our findings may inform screening strategy and addressing social determinants of health among AYA cancer survivors.

Quality of End-of-Life Care Among Adolescents and Young Adults With Cancer.

Adolescents, young adults with cancer receive limited psychosocial and spiritual support near death.

Use of cancer-directed therapy at the end of life among adolescents and young adults.

BACKGROUND: Adolescents and young adults frequently receive chemotherapy near death. We know less about the use of targeted agents and immunotherapy or trends over time. METHODS: We conducted a retrospective cohort study of 1836 adolescents and young adults with cancer who died between 2009 and 2019 after receiving care at 1 of 3 sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs. RESULTS: Over the study period, 35% of adolescents and young adults received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Additionally, 56% received at least 1 form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of adolescents and young adults receiving targeted therapy (odds ratio [OR] = 1.05 per year of death, 95% confidence interval [CI] = 1.02 to 1.10; P = .006), immunotherapy (OR = 1.27, 95% CI = 1.18 to 1.38; P < .0001), and any cancer-directed therapy (OR = 1.04, 95% CI = 1.01 to 1.08; P = .01) in the last 90 days of life increased over time. CONCLUSIONS: More than half of adolescents and young adults receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy is increasing over time. Although some adolescents and young adults may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of adolescents and young adults approaching death.

Risk of adverse birth outcomes after adolescent and young adult cancer.

BACKGROUND: Many women diagnosed with cancer as adolescents and young adults (AYAs, age 15-39 years) want biological children after cancer but lack information on the potential impact of their cancer history on future reproductive outcomes. We investigated the risk of adverse birth outcomes among AYA cancer survivors. METHODS: We identified insured women diagnosed with AYA breast cancer, thyroid cancer, gynecologic cancers, lymphoma, or melanoma from 2003 to 2016 in the state of North Carolina or the Kaiser Permanente health care systems in northern and southern California. Post-diagnosis births to cancer survivors were each matched with up to 5 births to women without cancer. Risk ratios for preterm birth (<37 completed weeks), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and small for gestational age (SGA, <10th percentile of weight for gestational age) were estimated using modified Poisson regression. RESULTS: Analyses included 1648 births to 1268 AYA cancer survivors and 7879 births to 6066 women without cancer. Overall, risk of preterm birth, very preterm birth, low birth weight, and SGA did not significantly differ between births to women with and without cancer. However, births to women with gynecologic cancers had a significantly increased risk of low birth weight (risk ratio = 1.82; 95% confidence interval: 1.03 to 3.21) and suggested increased risk of preterm birth (risk ratio = 1.59; 95% confidence interval: 0.99 to 2.54). Chemotherapy exposure was not associated with increased risk of adverse birth outcomes. CONCLUSIONS: Women with gynecologic cancers, but not other cancers, had an increased risk of adverse birth outcomes compared to women without cancer.

Use of statins and prostate cancer recurrence among patients treated with radical prostatectomy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Statins have shown broad spectrum anti-cancer properties in laboratory studies. In epidemiological studies, use of statins has been associated with reduced risk of advanced prostate cancer. However, the effects of statins on prostate cancer disease progression following curative treatment have not been extensively studied, and previous studies reported conflicting results. This study found no clear association between overall statin use and risk of disease progression, as well as lack of a monotone dose-response relationship between the use of statins, whether it was use before or after prostatectomy, and prostate cancer disease progression. OBJECTIVE: To investigate whether use of HMG-CoA reductase inhibitors ('statins'), which have shown broad spectrum anti-cancer properties in laboratory studies, is associated with a reduced risk of recurrence in patients with prostate cancer who undergo radical prostatectomy. PATIENTS AND METHODS: All men with incident prostate cancer diagnosed between 2004 and 2005 who subsequently underwent radical prostatectomy by the end of 2005 in the Kaiser Permanente Southern California (KPSC) health plan were identified using KPSC's cancer registry. Subjects were followed for up to 5 years after prostatectomy for (i) biochemical recurrence, defined as a single PSA measurement >0.2 ng/mL, and (ii) clinical disease progression, defined as diagnosis of metastatic disease or prostate-cancer-related death. Information on statin use, demographics, comorbidities, patho-clinical factors and outcomes were ascertained from KPSC's electronic medical records. The effects of statin use prior to and after prostatectomy were both examined using bivariate and multivariate Cox models, adjusting for known prognostic factors. For postoperative statin exposure, a time-dependent Cox model was used. RESULTS: A total of 1200 men were included; 37% had preoperative and 56% had postoperative statin use. Neither preoperative nor postoperative statin use was associated with biochemical recurrence (hazard ratio [HR] = 1.00 [0.72-1.39] and 1.05 [0.76-1.46], respectively) or clinical disease progression (HR = 0.63 [0.31-1.27] and 1.20 [0.63-2.30], respectively). No clear dose-response relationship was found for duration of use. CONCLUSIONS: Statin use may not prevent prostate cancer progression following radical prostatectomy. These findings do not provide support for the pursuit of a prospective clinical trial of statin use as a secondary prevention among surgically treated patients with prostate cancer.

The accuracy and trends of smoking history documentation in electronic medical records in a large managed care organization.

The accuracy of smoking history documentation in the electronic medical records was examined at a large managed care organization among 36,494 male members who self-reported smoking history in mailed surveys. The sensitivity of electronic smoking history documentation for ever-smoking status was 0.19 in years 2003-2005 (using ICD-9/CPT code only), 0.80 in 2006-2008 and 0.84 in 2009-2010 (combination of ICD-9/CPT codes and risk factor module used after 2006). The positive predictive value was 0.96, 0.90, and 0.95 in these periods, respectively. Among self-reported ever-smokers, increased healthcare utilization and smoking intensity/duration were associated with higher likelihood of having electronic smoking history documentation, while Asian race and Spanish language preference were associated with lower likelihood. These data suggest that enhanced efforts may be needed to screen for and document smoking among racial/ethnic minorities.

Discussions About Goals of Care and Advance Care Planning Among Adolescents and Young Adults With Cancer Approaching the End of Life.

PURPOSE: Adolescents and young adults (AYAs) with cancer receive high rates of medically intensive measures at the end of life. This study aimed to characterize the prevalence and timing of conversations about goals of care and advance care planning among AYAs at the end of life as one potential influence on care received. METHODS: This was a review of electronic health data and medical records for 1,929 AYAs age 12-39 years who died after receiving care at one of three sites between 2003 and 2019, including documented conversations about goals of care and advance care planning, and care received. RESULTS: A majority of AYAs were female (54%) and White (61%); 12% were Asian, 8% Black, and 27% Hispanic. Most patients had documented discussions about prognosis (86%), goals of care (83%), palliative care (79%), hospice (79%), and preferred location of death (64%). When last documented goals of care were evaluated, 69% of patients wanted care focused on palliation; however, 29% of those with palliative goals spent time in the intensive care unit (ICU) in the last month of life, and 32% had multiple emergency room (ER) visits. When goals-of-care discussions happened earlier, >30 days before death, AYAs were less likely to receive chemotherapy in the last 14 days of life (P = .001), ICU care (P < .001), ER visits (P < .001), and hospitalizations in the last month (P < .001). CONCLUSION: High rates of medically intensive measures among AYAs near the end of life do not appear to be the result of a lack of discussions about goals of care and advance care planning. Although some interventions may be used to support palliative goals, earlier discussions have potential to reduce late-life intensive measures.

Topical bioequivalence of acyclovir creams using dermal microdialysis in pigs: a new model to evaluate bioequivalence for topical formulations.

The aim was to evaluate the bioequivalence of topically applied Acyclovir (ACV) creams using dermal microdialysis (DMD) in a pig model. Three ACV creams (3%), ACV1, ACV2 and ACV3, were topically administrated on the dorsum of pigs, and the DMD sampling technique was used to continuously collect microdialysate. The concentration of ACV in microdialysate was measured by HPLC and the concentration-time profiles were used to calculate pharmacokinetic parameters. The results showed that 90% confidence interval (CI) of the ratio of AUC(0-4 h) of ACV2 and ACV3 was between 88.2 and 105.7%, which was within the acceptance range (80-125%). Ninety percent CI of the ratio of C(max) of ACV2 and ACV3 was between 87.4 and 124.4%, which was within the acceptance range (80-125%). These data indicate that ACV2 and ACV3 used in this study were bioequivalent. This study demonstrates that the pig model coupled with DMD sampling can potentially provide a cost-effective strategy to evaluate topical drug delivery and its associated pharmacokinetic studies.