Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019.

BACKGROUND: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). FINDINGS: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration. CONCLUSIONS: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

Patient characteristics associated with delayed time to adjuvant chemotherapy among women treated for stage I-IIIA breast cancer.

For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression.

Number of Older Biological Siblings and Early-Onset Colorectal Cancer Risk.

Colorectal cancer (CRC) is the third most common cancer in the United States.1 Although CRC incidence has declined in individuals >50 years, incidence is rising in adults <50 years (early onset).1 By 2027, CRC is projected to become the leading cause of cancer mortality in US adults <50 years.2 To combat the rising incidence of early onset CRC (EOCRC), national guidelines recently lowered the screening age from 50 to 45 years for average-risk individuals.3 Understanding the risk profile of EOCRC can help combat the rising burden in young adults, especially in those ineligible for screening.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system.

PURPOSE: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. METHODS: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. RESULTS: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. CONCLUSION: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.

Validating a semi-quantitative food frequency questionnaire to assess regional diet in a study of cancer in South West Nigeria.

PURPOSE: Cancer burden is rising rapidly in Nigeria, the most populous country in sub-Saharan Africa; this trend may in part be attributable to diet. We developed and validated a semi-quantitative food frequency questionnaire (FFQ) to assess regional diet in Nigeria. METHODS: We recruited 68 adult participants from rural and urban settings in South West Nigeria. We developed an FFQ administered at baseline and assessed its validity using 3 dietary recalls (baseline, 7 days post baseline, 3 months post baseline). We calculated Spearman's rank correlation coefficients and energy-adjusted de-attenuated correlation coefficients for food items and macronutrients. We evaluated cross-classification using quartiles of macronutrient intake. RESULTS: Energy-adjusted de-attenuated food item correlations between the FFQ and dietary recalls ranged from -0.08 (smoked beef/goat) to 0.73 (fried snacks) for the average intake from the first 2 recalls (2DR) and from -0.05 (smoked beef/goat) to 0.75 (smoked fish) for the average of all 3 recalls (3DR). Macronutrient correlations ranged from 0.15 (fat) to 0.37 (fiber) for the 2DR and from 0.08 (fat) to 0.41 (carbohydrates) for the 3DR. The percent of participants classified in the same quartile ranged from 16.4% (fat) to 32.8% (fiber, protein) for the 2DR and from 25.6% (fat) to 34.9% (carbohydrates) for the 3DR. Agreement improved when including adjacent quartiles, from 65.5% (carbohydrates) to 70.5% (fat, fiber) for the 2DR and from 62.8% (protein) to 76.8% (carbohydrate) for the 3DR. CONCLUSION: Our semi-quantitative FFQ was reasonably valid for ranking intake of certain foods and macronutrients in adults in South West Nigeria.

Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Vitamin B12 Supplementation and Vitamin B12 Blood Serum Levels: Evaluation of Effect Modification by Gender and Smoking Status.

Research suggests that high intake of supplemental vitamin B12 may be associated with increased risk of cancer, with some evidence that this association may vary by gender and smoking status. This investigation evaluates if similar patterns in association are observed for data for 11,757 adults from the National Health and Nutrition Examination Survey (1999-2006). Survey-weighted multivariable-adjusted linear regression was used to evaluate the association between regular B12 supplement use and log-transformed serum B12 levels. Persons taking vitamin B12 through a multivitamin/multimineral (MVMM) had a median supplemental intake of 12 mcg/day (Q1: 6, Q3: 25), compared to 100 mcg/day (Q1: 22, Q3: 500) for persons reporting supplemental B12 intake through a MVMM-exclusive source. MVMM users had a geometric mean serum B12 26% (95% CI: 23%-30%) higher than nonusers, whereas MVMM-exclusive users' geometric mean was 61% (95% CI: 53%-70%) higher than nonusers (p-trend < 0.001). Although a positive trend (p-trend < 0.001) was observed for both men and women, the association was stronger among women (p-interaction < 0.001). No interaction was observed for smoking status (p-interaction = 0.45). B12 supplementation is associated with higher levels of serum B12, with significant interaction by gender but not smoking. Further work is needed to better understand the interplay of B12 and gender.

Clinical features of young onset colorectal cancer patients from a large cohort at a single cancer center.

PURPOSE: The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC. METHODS: A retrospective review of patients with CRC diagnosed between ages 20 and 49 years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis. Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record. RESULTS: We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4). CONCLUSION: Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening.

Association between fish oil supplements use and serum per- and polyfluoroalkyl substances (PFAS): Results from the National Health and Nutrition Examination Survey.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants and classified as potentially carcinogenic to humans. Although consumption of fish, seafood, and their byproducts is a known source of dietary PFAS exposure, little is known about the association between use of fish oil supplements and PFAS. Here, we examine associations between fish oil supplement use and serum PFAS concentrations. METHODS: This analysis includes adults, ages 25 years of age and older, surveyed as part of the National Health and Nutrition Examinations Survey (NHANES). Outcomes include five serum PFAS compounds: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulphonic acid (PFHxS) and perfluorodecanoic acid (PFDA). To determine the association between fish oil use and log-transformed PFAS concentrations, survey-weighted linear regression was used to estimate multivariate-adjusted ratios between supplement-users' and non-users' geometric mean serum PFAS concentrations. RESULTS: No association was observed between fish oil use and PFAS. While results did not vary substantially by age, gender, study cycle, there was some indication of a potential inverse association in subgroups of interest. Specifically, an inverse association was observed between fish oil supplement use and PFOS levels in older adults, females, and in early calendar years; an inverse association was also observed between fish oil and PFNA in females and early calendar years. CONCLUSIONS: While fish oil users did not experience increased serum PFAS, there was an unexpected inverse association in some population subgroups. Further research will be needed to better understand whether this pattern reflects true differences, chance, or bias.

Risk Factors Associated With Early-Onset Colorectal Cancer.

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) is increasing in individuals younger than 50 years, who do not usually undergo screening if they are of average risk. We sought to identify risk factors for CRC in this population. METHODS: We compared sociodemographic and medical characteristics of patients who received a diagnosis of CRC at an age of 18-49 years (early-onset) with patients who received a diagnosis of CRC at an age of 50 years or older (late-onset) and with age-matched, cancer-free individuals (controls) at a tertiary academic hospital. We collected data from all adult patients with a diagnosis of CRC from January 1, 2011 through April 3, 2017 from electronic health records. Associations with risk factors were assessed using univariable and multivariable logistic regression models. RESULTS: We identified 269 patients with early-onset CRC, 2802 with late-onset CRC, and 1122 controls. Compared with controls, patients with early-onset CRC were more likely to be male (odds ratio [OR], 1.87; 95% CI, 1.39-2.51), have inflammatory bowel disease (IBD) (3% vs 0.4% for controls; univariable P < .01), and have a family history of CRC (OR, 8.61; CI, 4.83-15.75). Prevalence values of well-established modifiable CRC risk factors, including obesity, smoking, and diabetes, were similar. Compared to patients with late-onset CRC, patients with early-onset CRC were more likely to be male (OR, 1.44; 95% CI, 1.11-1.87), black (OR, 1.73; 95% CI, 1.08-2.65) or Asian (OR, 2.60; 95% CI, 1.57-4.15), and have IBD (OR, 2.97; 95% CI, 1.16-6.63) or a family history of CRC (OR, 2.87; 95% CI, 1.89-4.25). Sensitivity analyses excluding IBD and family history of CRC showed comparable results. Early-onset CRC was more likely than late-onset disease to be detected in the left colon or rectum (75% vs 59%, P = .02) and at a late stage of tumor development (77% vs 62%, P = .01). CONCLUSIONS: In a retrospective study of patients with early-onset CRC vs late-onset CRC or no cancer, we identified non-modifiable risk factors, including sex, race, IBD, and family history of CRC, to be associated with early-onset CRC.

The effect of intravenous dexamethasone on postoperative nausea and vomiting after Cesarean delivery with intrathecal morphine: a randomized-controlled trial.

PURPOSE: Intrathecal morphine administered during spinal anesthesia for Cesarean delivery is associated with a high incidence of postoperative nausea and vomiting (PONV). Small studies performed to date provide conflicting evidence on the effectiveness of dexamethasone as prophylaxis in this setting, raising the possibility that efficacy may be linked to dose timing. This study hypothesized that intravenous dexamethasone given prior to intrathecal morphine during spinal anesthesia may reduce the incidence of PONV. METHODS: In this double-blind, placebo-controlled trial, 108 patients undergoing Cesarean delivery were randomized to receive 8 mg dexamethasone or placebo prior to spinal anesthesia that included 0.2 mg intrathecal morphine. Outcomes were assessed on postanesthesia care unit arrival, as well as at postoperative hours one, three, six, 24, and 48. The primary outcome was the total number of subjects experiencing PONV during the study period of 48 hr postpartum. Secondary outcomes included severity of pain via the numeric rating scale pain score, and the use of rescue antiemetics and analgesics. RESULTS: No significant difference in the number of patients experiencing PONV was found between the treatment (n = 44, 80.0%) and control groups (n = 45, 84.9%) (difference -4.9%; 95% confidence interval, -19.2 to 9.4; P = 0.50), nor for median numeric rating scale pain scores (P = 0.24), total consumption of rescue antiemetics (P = 0.40), or opioid analgesics (P = 0.26). CONCLUSIONS: This trial does not support the use of dexamethasone prior to intrathecal morphine for PONV prophylaxis in Cesarean delivery. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01734161); registered 27 November, 2012.

RéSUMé: OBJECTIF: La morphine intrathécale administrée au cours de la rachianesthésie pour un accouchement par césarienne est associée à une forte incidence de nausées et vomissements postopératoires (PONV). Les petites études menées à ce jour ont fourni des données probantes contradictoires sur l'efficacité de la prophylaxie par dexaméthasone dans ce contexte, soulevant la possibilité que son efficacité soit liée au moment de l'administration. Les auteurs de cette étude ont fait l'hypothèse que la dexaméthasone intraveineuse administrée avant la morphine intrathécale au cours d'une rachianesthésie pouvait réduire l'incidence des PONV. MéTHODES: Dans cette étude en double insu, contrôlée contre placebo, 108 patientes subissant un accouchement par césarienne ont été randomisées pour recevoir 8 mg de dexaméthasone ou un placebo avant une rachianesthésie qui incluait 0,2 mg de morphine intrathécale. Les résultats ont été évalués à l'arrivée dans l'unité de soins post anesthésie ainsi qu'à 1, 3, 6, 24 et 48 heures postopératoires. Le critère d'évaluation principal était le nombre de patientes éprouvant des PONV au cours de la période d'étude de 48 heures post-partum. Les critères d'évaluation secondaires étaient, notamment, la sévérité de la douleur établie par le score de douleur sur une échelle d'évaluation numérique, et le recours aux antiémétiques et analgésiques de secours. RéSULTATS: Aucune différence significative n'a été constatée sur le nombre de patientes éprouvant des PONV entre le groupe recevant le traitement (n = 44; 80,0 %) et le groupe contrôle (n = 45; 84,9 %) (différence -4,9 %; intervalle de confiance à 95 % : -19,2 % à 9,4%; P = 0,50). Il n'y a pas eu non plus de différences dans les scores de douleur avec l'échelle d'évaluation numérique (P = 0,24) et la consommation totale de médicaments de secours, antiémétiques (P = 0,40) ou narcotiques (P = 0,26). CONCLUSIONS: Cette étude ne soutient pas l'utilisation de dexaméthasone avant l'administration de morphine intrathécale pour la prophylaxie des PONV dans l'accouchement par césarienne. ENREGISTREMENT DE L'ESSAI CLINIQUE: www.clinicaltrials.gov (NCT01734161); enregistré le 27 novembre 2012.

Use of dietary supplements in relation to urinary phthalate metabolite concentrations: Results from the National Health and Nutrition Examination Survey.

BACKGROUND: Research suggests that dietary supplements may be a source of exposure to phthalates, given that diethyl phthalate (DEP) or di-n-butyl phthalate (DBP) can be components of coatings that facilitate extended release or encapsulate dietary supplements. METHODS: Using nationally representative data on a population of 12,281 adults ages 20 y + surveyed between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES), we evaluated the association between dietary supplement use in relation to urinary phthalate metabolites of DEP (monoethyl phthalate, MEP) and DBP (mono-n-butyl phthalate, MBP). We examined associations pertaining to regular use of multivitamin/multimineral (MVMM) supplements, as well as regular use of any other non-MVMM supplement products, the number of non-MVMM supplement products used, as well as individual supplements potentially containing phthalates (exclusive of MVMM). For each urinary phthalate metabolite, results are presented as the minimally-adjusted and multivariable-adjusted ratio, comparing the geometric mean among users to non-users. RESULTS: In multivariable models, we observed a significant positive association between regular use of MVMM use and MEP, with persons using MVMM supplements having 11% higher geometric mean MEP than non-users (Ratio: 1.11; 95% CI: 1.04-1.20); no association was observed for MVMM in relation to MBP. No other significant multivariable-adjusted associations were observed, although power was limited in analyses of individual supplements. Associations did not markedly vary by gender; however, the associations of garlic supplement use with MEP and MBP varied by calendar time, with statistically significant positive associations observed in later years. CONCLUSIONS: A modest significant association was observed between MVMM use and MEP. No other significant associations were observed in our overall multivariable models. Follow-up on the positive association observed between garlic and urinary phthalate metabolite concentrations observed in later years in a well-powered, prospective study would further clarify study findings.

A retrospective analysis of severe intraoperative respiratory compliance changes during ophthalmic arterial chemosurgery for retinoblastoma.

BACKGROUND AND OBJECTIVES: Ophthalmic arterial chemosurgery for retinoblastoma has been associated with intraoperative decreases in respiratory compliance. Through the analysis of data from computerized records, we objectively defined severe respiratory compliance events and correlated them with demographic and clinical information in patients undergoing this procedure. METHODS: Data were collected from ophthalmic arterial chemosurgery cases from 2006 to 2013. Intraoperative PIP, PEEP, TV, SpO2 , and EtCO2 were analyzed. Compliance changes, desaturations, decreases in EtCO2 , and clinical outcomes were assessed. RESULTS: Respiratory compliance decreases with a bimodal distribution. Severe events were defined as exhibiting a minimum compliance decrease of 40%. Seventy-eight of 122 children (64%) experienced a severe compliance event during at least one treatment, and it occurred in 137/468 cases (29%). A subset of 94 children had complete or at least the first three records. The incidence of a severe respiratory compliance event in this subgroup was 17/94 (18%) on the first and 84/261 (32%) on subsequent procedures. The probability of developing a severe respiratory compliance event on a subsequent procedure was 0.40 if the child developed it on the first procedure, 0.30 if he did not; this difference was not significant. The incidence of desaturation below 90% with severe respiratory compliance events was 0.20; the incidence of a 30% drop in EtCO2 was 0.34. No morbidity, no extended recovery, and no admissions were associated with intraoperative severe respiratory compliance events. We found no correlation between history, age, sex, weight or allergies, and intraoperative severe respiratory compliance events. CONCLUSIONS: Here, most patients experienced a severe respiratory compliance event during at least one of their procedures. Overall incidence was 29% and was more likely on subsequent procedures. A severe respiratory compliance event at the initial procedure was poorly predictive of its occurrence on subsequent procedures. No morbidity was associated with intraoperative severe respiratory compliance events.

Evaluation of Algorithms Using Automated Health Plan Data to Identify Breast Cancer Recurrences.

BACKGROUND: We updated algorithms to identify breast cancer recurrences from administrative data, extending previously developed methods. METHODS: In this validation study, we evaluated pairs of breast cancer recurrence algorithms (vs. individual algorithms) to identify recurrences. We generated algorithm combinations that categorized discordant algorithm results as no recurrence [High Specificity and PPV (positive predictive value) Combination] or recurrence (High Sensitivity Combination). We compared individual and combined algorithm results to manually abstracted recurrence outcomes from a sample of 600 people with incident stage I-IIIA breast cancer diagnosed between 2004 and 2015. We used Cox regression to evaluate risk factors associated with age- and stage-adjusted recurrence rates using different recurrence definitions, weighted by inverse sampling probabilities. RESULTS: Among 600 people, we identified 117 recurrences using the High Specificity and PPV Combination, 505 using the High Sensitivity Combination, and 118 using manual abstraction. The High Specificity and PPV Combination had good specificity [98%, 95% confidence interval (CI): 97-99] and PPV (72%, 95% CI: 63-80) but modest sensitivity (64%, 95% CI: 44-80). The High Sensitivity Combination had good sensitivity (80%, 95% CI: 49-94) and specificity (83%, 95% CI: 80-86) but low PPV (29%, 95% CI: 25-34). Recurrence rates using combined algorithms were similar in magnitude for most risk factors. CONCLUSIONS: By combining algorithms, we identified breast cancer recurrences with greater PPV than individual algorithms, without additional review of discordant records. IMPACT: Researchers should consider tradeoffs between accuracy and manual chart abstraction resources when using previously developed algorithms. We provided guidance for future studies that use breast cancer recurrence algorithms with or without supplemental manual chart abstraction.

Patient characteristics associated with intended non-guideline chemotherapy in women with stage I-IIIA breast cancer.

BACKGROUND: Guidelines informing chemotherapy regimen selection are based on clinical trials with participants who do not necessarily represent general populations with breast cancer. Understanding who receives non-guideline regimens is important to understanding real-world chemotherapy administration and how it relates to patient outcomes. METHODS: Using data from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) cohort study, based at Kaiser Permanente Northern California (2006-2019) and Kaiser Permanente Washington (2004-2015), we use logistic regression to examine the associations between patient characteristics and receipt of non-NCCN-guideline chemotherapy among 11,293 women with primary stage I-IIIA breast cancer receiving chemotherapy. RESULTS: Use of non-guideline regimens was strongly associated with several factors, including older age (OR≥80 vs 18-39: 5.25, 95%CI: 3.06-9.00)(p-trend=0.002) and human epidermal growth factor-2 status (ORHER2+ vs HER2-: 3.44; 95%CI: 3.06-3.87) and was less likely in women with larger tumor size (OR>5cm vs 0.1-≤0.5cm: 0.56; 95%CI: 0.36-0.87)(p-trend=0.01) and diagnosed in later years (OR2012-2019 vs 2005-2011: 0.80; 95%CI: 0.71-0.90). Factors associated varied by type of non-guideline regimen. For example, women with comorbidity and older age were more likely to receive non-guideline drug combinations in particular, while women with larger tumor size were less likely to receive non-guideline administration schedules. CONCLUSIONS: Non-guideline chemotherapy regimens are more likely in certain patient populations. IMPACT: These associations highlight that vulnerable patient populations may be less likely to receive guideline care and thus real-world studies are essential to understanding how the use of non-guideline regimens impacts patient outcomes in these groups.

Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer.

PURPOSE: Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. METHODS: In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015). RESULTS: In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status. CONCLUSION: We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.