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Background: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice., Patients and Methods: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment., Results: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01)., Conclusion: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib., Competing Interests: Disclosure J.M. reports research funding paid to institution from AbbVie, BMS, CTI BioPharm, Geron, Incyte, Kartos, Novartis, PharmaEssentia, and Roche; consulting fees from AbbVie, BMS, CTI BioPharm, Galecto, Geron, GSK, Incyte, Kartos, Karyopharm, MorphoSys, Novartis, PharmaEssentia, Roche, and Sierra Oncology. C.H. reports research funding from BMS/Celgene, Constellation Pharmaceuticals, a MorphoSys Company, and Novartis; and advisory role and speaker funding from Abbvie, AOP Orphan Pharmaceuticals, BMS/Celgene, CTI BioPharma, Galacteo, Geron, Gilead, Janssen, Keros, Novartis, Promedior, Roche, and Shire. T.A.S., D.L., M.G., and T.A.M. report employment with Cardinal Health. S.M. and A.M. report employment with BMS. D.T. and I.S.D. report employment with and stock ownership in BMS. P.A. reports no conflicts of interest. J.K. reports employment with and stock ownership in Cardinal Health at the time this study was conducted. B.A.F. reports research funding from BMS; and stock ownership in and employment with Cardinal Health. A.T.G. reports consulting for AbbVie, BMS/Celgene, CTI BioPharma, Constellation Pharmaceuticals, a MorphoSys Company, GSK/Sierra Oncology, Incyte, Kartos, Novartis, and PharmaEssentia., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Talazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting., Patients and Methods: Characteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics., Results: Among 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of ≥2 and 19.0% had brain metastasis. Mutations in gBRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS ≥2 at talazoparib initiation were associated with treatment failure and progression or mortality., Conclusion: Overall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA., (© The Author(s) 2023. Published by Oxford University Press.)

Objectives: Recent advances have created options for first-line (1L) treatment of advanced/metastatic non-small cell lung cancer (aNSCLC). The study objectives were to describe the utilization of 3 classes of 1L treatment-chemotherapy (CT), immunotherapy (IO), and chemoimmunotherapy (IO+CT)-and the total, third-party payer, direct health care costs., Study Design: Retrospective, administrative claims database analysis of patients with aNSCLC who initiated 1L treatment between January 1, 2017, and May 31, 2019, with IO, CT, or IO+CT., Methods: Microcosting enumerated health care resource utilization, including antineoplastic drug costs, using standardized costs. Generalized linear models estimated per-patient per-month (PPPM) costs during 1L treatment, and adjusted cost differences in 1L among treatment cohorts were calculated using recycled predictions., Results: A total of 1317 IO-, 5315 CT-, and 1522 IO+CT-treated patients were identified. Utilization of CT declined from 72.3% to 47.6% between 2017 and 2019, replaced by use of IO+CT, which increased from 1.8% to 29.8%. Total PPPM costs in 1L were highest with IO+CT at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT vs IO cohort (P < .001) and IO costs were $1024 (95% CI, $67-$1980) lower than CT (P = .04)., Conclusions: IO+CT accounts for almost one-third of 1L aNSCLC treatment modalities, coinciding with a reduction in treatment with CT. Costs for patients treated with IO were lower than those for patients treated with both IO+CT and CT alone, driven primarily by antineoplastic drug and associated medical costs.

Purpose: Most patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with a complement protein 5 (C5) inhibitor achieve full control of terminal complement activity and intravascular hemolysis. The minority remains anemic and transfusion dependent despite this control. Etiology for ongoing anemia is multifactorial and includes bone marrow failure, breakthrough hemolysis, extravascular hemolysis (EVH) and nutritional deficiencies., Patients and Methods: To evaluate the potential etiologies of hemoglobin levels <10 g/dL despite receiving C5 inhibitor therapy, we performed a retrospective US chart review of adult patients with PNH and treated for at least 12 months with eculizumab (n=53), ravulizumab (n=32), or eculizumab followed by ravulizumab (n=15). Clinically evident EVH was defined as at least one transfusion, reticulocyte count ≥120×10 9 /L and hemoglobin level ≤9.5 g/dL. Safety data were not collected. Mean treatment duration was 26.5±17.2 months., Results: Treatment with C5 inhibitors significantly improved hemoglobin, lactate dehydrogenase, and number of transfusions versus baseline. Among the patients with hemoglobin <10 g/dL during the last 6 months of treatment (n=38), one patient (eculizumab) had clinically evident EVH, and 10 patients had active concomitant bone marrow failure. Bone marrow failure was a major contributor to hemoglobin <10 g/dL and transfusion dependence; clinically evident EVH was uncommon., Conclusion: A range of hematologic causes need to be considered when evaluating anemia in the presence of treatment with a C5 inhibitor., Competing Interests: JS has received research support from Alexion, AstraZeneca Rare Disease, BMS, CTI, Novartis, Kartos Pharma and Stemline Therapeutics;  consulting fees from Novartis; has been a speaker for Incyte, Alexion, BMS and Sanofi. She also owns stocks from Abbvie, chairs the Data and Safety Monitoring Board (DSMB) for NS Pharma and is a member of the DSMB for Apellis. AG and JK are employees of Cardinal Health Inc. YP, IT, AH and JRS are employees and shareholders of Alexion, AstraZeneca Rare Disease. DA provides consulting to Alexion, AstraZeneca Rare Disease. The authors report no other conflicts of interest in this work., (© 2022 Shammo et al.)

Aim: To demonstrate the efficacy of pomalidomide for relapsed/refractory multiple myeloma (RRMM) following treatment in real-world, community practice using retrospective database analysis. Materials & methods: US-based community oncologists identified patients with RRMM treated with or without pomalidomide following first-line lenalidomide. Disease response (≥ very good partial response) and progression-free survival were compared. Results: Disease response was 78.6 and 51.7% for pomalidomide (n = 126) and nonpomalidomide cohorts (n = 174), respectively (p < 0.0001). Multivariate adjusted odds of response were 4.5-times greater for pomalidomide cohort (p < 0.0001). Median progression-free survival was not reached for pomalidomide cohort and 16.7 months for nonpomalidomide cohort (log-rank p < 0.01). Conclusion: Following lenalidomide induction in RRMM, pomalidomide is an effective treatment.

Background: Treatment for recurrent or advanced/metastatic non-small cell lung cancer (aNSCLC) has advanced in the past 5 years with immunotherapy (IO). This study sought to describe first-line (1L) aNSCLC treatment patterns and clinical outcomes., Methods: In this retrospective, multisite cohort study, community oncologists reported data for randomly selected stage IIIB/IV, EGFR-/ALK wild-type aNSCLC patients who initiated 1L systemic therapy from 01/01/2016 to 12/31/2019. Follow-up was through November 2020. Demographics, clinical characteristics, treatment patterns, disease response, progression, and death/last follow-up date were described. Overall response rate (ORR) was calculated using tumor measurements applying RECIST v1.1 guidelines. Progression-free survival (PFS) and overall survival (OS) were calculated from 1L initiation by Kaplan-Meier method., Results: 497 patients from 46 sites were included. The most common 1L regimens (%) were platinum-doublet chemotherapy plus IO (PDC+IO) (40.6%), PDC (29.4%), IO monotherapy (20.7%), and PDC+bevacizumab (6.2%). From 2016 to 2019, 1L PDC declined from 63% to 10%, whereas 1L PDC+IO increased from 14% to 58%. The ORRs were 64.9%, 32.9%, 60.2%, and 61.3% for 1L PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab, respectively. Median 1L PFS/OS (months) was 15.6/26.5, 5.3/13.7, 17.8/not reached, 10.8/18.6, respectively, for PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab. Among patients who received only 1L treatment (n = 299), 41.5% had no further therapy and were deceased., Conclusions: Although the 1L treatment paradigm has recently shifted to IO-based regimens, 41.5% did not survive past 1L. Median 1L PFS did not exceed 1.5 years and median OS remained limited across all 1L treatment groups, illustrating continued unmet aNSCLC therapeutic needs., Competing Interests: Declaration of Competing Interest LB receives consulting fees from Jannsen, Novartis, Boehringer Ingelheim, BMS, Merk, Regeneron, Genentech, Daichi, Sankyo, Bluprint, Takeda, Astra Zeneca, Bayer, Beyondsping, G1, Therapeutics, and Abbvie, and participates on an advisory board with Neuvogen and ORIC, owns stock or stock options; JK is an employee of Cardinal Health; BC is an employee of Novartis, receives salary, and is a stockholder of Novartis; NC is an employee of Novartis and is a stockholder of Novartis Pharmaceuticals; BF is an employee and a stockholder of Cardinal Health., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: Antiviral treatments for early intervention in patients with mild-to-moderate COVID-19 are needed as a complement to vaccination. We sought to estimate the impact on COVID-19 cases, deaths, and direct healthcare costs over 12 months following introduction of a novel, antiviral treatment, RD-X19, a light-based, at-home intervention designed for the treatment of mild-to-moderate COVID-19 infection., Methods: A time-dependent, state transition (semi-Markov) cohort model was developed to simulate infection progression in individuals with COVID-19 in 3 US states with varying levels of vaccine uptake (Alabama, North Carolina, and Massachusetts) and at the national level between 1 June 2020 and 31 May 2021. The hypothetical cohort of patients entering the model progressed through subsequent health states after infection. Costs were assigned to each health state. Number of infections/vaccinations per day were incorporated into the model. Simulations were run to estimate outcomes (cases by severity, deaths, and direct healthcare costs) at various levels of adoption of RD-X19 (5%, 10%, 25%) in eligible infected individuals at the state and national levels and across three levels of clinical benefit based on the results from an early feasibility study of RD-X19. The clinical benefit reflects a decline in the duration of symptomatic disease by 1.2, 2.4 (base case), and 3.6 days., Results: In the base case analysis with 10% adoption, simulated infections/deaths/direct healthcare costs were reduced by 10,059/275/$69 million in Alabama, 21,092/545/$135 million in North Carolina, and 16,670/415/$102 million in Massachusetts over 12 months. At the national level, 10% adoption reduced total infections/deaths/direct healthcare costs by 686,722/17,748/$4.41 billion., Conclusion: At-home, antiviral treatment with RD-X19 or other interventions with similar efficacy that decrease both symptomatic days and transmission probabilities can be used in concert with vaccines to reduce COVID-19 cases, deaths, and direct healthcare costs.

Purpose: For patients with advanced cancer, timely referral to palliative care (PC) services can ensure that end-of-life care aligns with their preferences and goals. Overestimation of life expectancy may result in underutilization of PC services, counterproductive treatment measures, and reduced quality of life for patients. We assessed the impact of a commercially available augmented intelligence (AI) tool to predict 30-day mortality risk on PC service utilization in a real-world setting., Methods: Patients within a large hematology-oncology practice were scored weekly between June 2018 and October 2019 with an AI tool to generate insights into short-term mortality risk. Patients identified by the tool as being at high or medium risk were assessed for a supportive care visit and further referred as appropriate. Average monthly rates of PC and hospice referrals were calculated 5 months predeployment and 17 months postdeployment of the tool in the practice., Results: The mean rate of PC consults increased from 17.3 to 29.1 per 1,000 patients per month (PPM) pre- and postdeployment, whereas the mean rate of hospice referrals increased from 0.2 to 1.6 per 1,000 PPM. Eliminating the first 6 months following deployment to account for user learning curve, the mean rate of PC consults nearly doubled over baseline to 33.0 and hospice referrals increased 12-fold to 2.4 PPM., Conclusion: Deployment of an AI tool at a hematology-oncology practice was found to be feasible for identifying patients at high or medium risk for short-term mortality. Insights generated by the tool drove clinical practice changes, resulting in significant increases in PC and hospice referrals.

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57-391, OPEN) and 110 (37-148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54-553) and 166 (108-262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy., (The Author(s). Published by S. Karger AG, Basel.)

Introduction: Approximately one-quarter of patients with polycythemia vera become resistant to and/or intolerant of hydroxyurea. This analysis characterizes reasons patients were switched from hydroxyurea to ruxolitinib and describes ruxolitinib dosing patterns and outcomes in real-world clinical practice., Patients and Methods: This medical chart review of United States community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network included patients with polycythemia vera who were ≥18 years old, received hydroxyurea for ≥3 months, started ruxolitinib between January 1, 2015 and December 31, 2016, and had ≥2 visits during the subsequent 6 months. Clinical data were collected at predefined intervals from diagnosis to last provider visit., Results: Providers identified 249 patients for inclusion. jcauses of hydroxyurea discontinuation were resistance (78%; frequently for hematocrit ≥45% [79%]) and intolerance (28%; frequently for nausea/vomiting [50%]). Initial ruxolitinib dosing was 10 mg twice daily (recommended dose) in 131 patients (53%). Among these patients, median treatment duration was 29.2 months, 35 (27%) had dose modification (increase, n = 24; decrease, n = 11) and 4 had interruptions within 6 months. The most common reason for dose increase was continued need for phlebotomy (46%); 6 patients had dose reductions owing to reduced platelets. Hematocrit control at initiation and during the first 6 months of ruxolitinib treatment was 15% and 63%, respectively., Conclusion: Most patients initiated ruxolitinib upon hydroxyurea resistance. Approximately half initiated ruxolitinib at the recommended dose, 27% of whom experienced dosing modifications within the first 6 months. After switching to ruxolitinib, most patients achieved hematocrit control and continued treatment for extended time frames., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ErbB family blocker, afatinib, is approved for patients with squamous cell carcinoma (SqCC) of the lung following platinum-doublet chemotherapy but has not been explored following immunochemotherapy. Here, we assessed the characteristics and outcomes of patients with SqCC of the lung who received second-line afatinib or chemotherapy after first-line pembrolizumab plus chemotherapy in a "real-world" setting., Methods: In this retrospective, multisite cohort study, community oncologists identified eligible patients and extracted data from electronic health records. Primary outcome measures were patient demographics and clinical characteristics, time on treatment, and incidence of severe immune-related adverse events (irAEs)., Results: Two hundred patients were included: 99 received second-line afatinib and 101 received second-line chemotherapy. Median age was 68 and 66 years, respectively; 35% and 3% of patients had mixed histology tumors, and 39% and 5% of tumors were epidermal growth factor receptor (EGFR) mutation-positive (EGFRm + ). Median time on treatment was 7.3 months with afatinib (mixed histology/SqCC tumors: 8.1/5.8 months; EGFRm + /EGFRm - tumors: 7.4/5.9 months) and 4.2 months with chemotherapy. Grade 3/4 irAEs were observed in 6 patients in the afatinib cohort (all had a prior grade 3/4 irAE during first-line therapy) and no patients in the chemotherapy cohort. The most common adverse drug reactions with afatinib were diarrhea (26%), rash (6%), stomatitis, fatigue, and nausea (5% each)., Conclusion: Encouraging time on treatment, and absence of newly diagnosed irAEs, indicate that afatinib is a treatment option following immunochemotherapy in patients with SqCC of the lung, and is currently the only approved oral agent in this setting., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Eribulin was approved in the United States (US) in 2010 for patients with metastatic breast cancer (MBC) who previously received at least two chemotherapeutic regimens, including anthracycline and taxane in the adjuvant or metastatic setting. With significant changes to the treatment landscape over the past decade, assessment of the real-world effectiveness of eribulin in clinical practice when used according to the approved US indication is valuable., Methods: Patients with MBC were identified by community oncologists through a retrospective, multi-site patient chart review; de-identified data were abstracted into electronic case report forms. Eligible patients initiated eribulin consistent with approved US indication between 1 January 2011 and 31 December 2017. Clinical outcomes assessed included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in all patients and those with triple negative breast cancer (TNBC)., Results: The analysis included 513 patients (median 59.0 years; 38.8% with Eastern Cooperative Oncology Group status ≥ 2). Eribulin was third-line therapy for 78.0% of patients, and fourth-line or later for the remainder. ORR was 54.4%, median PFS was 6.1 months (95% CI: 5.8, 6.6), and median OS was 10.6 months (95% CI 9.9, 11.7) in all patients. Among the 49.9% of patients with TNBC, ORR was 55.1%, median PFS was 5.8 months (95% CI 5.1, 6.4), and median OS was 9.8 months (95% CI 8.6, 11.0)., Conclusion: The current retrospective chart review study reinforces the clinical effectiveness of eribulin in patients with MBC, including those with TNBC, when used according to the approved US indication in real-world clinical practice.

Importance: In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research., Objective: To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice., Design, Setting, and Participants: This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020., Exposures: Undergoing treatment with immunotherapy or targeted therapy., Main Outcomes and Measures: Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports., Results: Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST-based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P < .001). Among 609 patients in the metastatic melanoma population, complete responses were reported in 112 physician-recorded responses (18.4%) vs 44 real-world RECIST-based responses (7.2%) (P < .001), compared with 11 of 247 responses (4.5%) to 31 of 192 responses (16.1%) across pivotal trials of the same melanoma therapies., Conclusions and Relevance: These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm with a prevalence of 4 to 6 per 100,000 people in the USA. Treatment recommendations are risk-adapted. This study was conducted to evaluate how physicians risk-stratify patients at the time of MF diagnosis, the accuracy of the risk stratification, and its effect on treatment selection. Medical charts were reviewed at US community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network; patient clinical characteristics, risk stratification, and treatment data were collected. Physician-assigned risk categorizations were compared with data-derived risk categorizations based on the International Prognostic Scoring System, the system recommended at diagnosis. A total of 491 patients diagnosed with MF between 2012 and 2016 (mean [SD] age at diagnosis, 65.4 [11.8] years; 54.8% male, 69.2% with primary MF) were included. Risk categorization was not assigned for 30.1% of patients. Of the patients with a physician-assigned risk categorization (n = 343), a scoring system was used in 49.9%. Compared with data-derived risk categorizations, 42.9% of physician-assigned risk categorizations were incorrect; 85.0% of incorrect physician-assigned risk categorizations were underestimations. Notably, 38.5% of patients with data-derived intermediate- or high-risk categorizations did not initiate treatment within 120 days of diagnosis. Among patients with data-derived intermediate risk, those with an underestimated physician-assigned risk categorization were significantly less likely to receive treatment within 120 days of diagnosis (51.6% with correct physician-assigned categorization vs 18.5% with underestimated risk categorization; P = 0.0023). These results highlight the gap in risk assessment and the importance of accurate risk stratification at diagnosis.

Aim: Guidelines list atezolizumab with nab-paclitaxel (ANP) as the preferred first-line (1L) therapy for metastatic triple-negative breast cancer (mTNBC) with PD-L1 expression ≥1%, but which clinical attributes impact ANP prescribing? Materials & methods: Medical oncologists participated in a discrete choice experiment (DCE) with four hypothetical mTNBC clinical scenarios to assess influences of: PD-L1 expression, menopausal status, prior adjuvant therapy and bulky liver metastases. Results:  A total of 47% chose ANP in 1L irrespective of menopausal status, prior adjuvant therapy or tumor bulk. PD-L1 expression was the only attribute with a significant impact on ANP preference, with 69% choosing ANP for those with ≥1% expression versus only 26% for those with <1% (p < 0.00001). Conclusion: ANP choice for 1L mTNBC deviated from guidelines.

Objectives: Real-world evidence (RWE) has gained increased attention in recent years as a complement to traditional clinical trials. The use of RWE to establish the efficacy of oncology drugs for Food and Drug Administration (FDA) approval has not been described. In this paper, we review 5 recent examples where RWE was submitted in support of the FDA approvals of original or supplementary indications for oncology drugs., Methods: To identify cases where RWE was used, we reviewed drug approval packages available at Drugs@FDA for oncology drugs approved between 2017 and 2019. Five cases were selected to present a broad overview of different types of RWE, different circumstances under which RWE has been used for regulatory approvals, and how FDA evaluated the data in each case. The type of RWE submitted, the indication, limitations identified by FDA reviewers, and the outcome of the submission are discussed., Results: RWE, particularly historical controls for rare or orphan indications, has been used to support both original and supplementary oncology drug approvals. Types of RWE included data from electronic health records, claims, post-marketing safety reports, retrospective medical record reviews, and expanded access studies. Small sample sizes, data quality, and methodological issues were among concerns cited by FDA reviewers., Conclusion: By bridging the gap between the constraints of the trial setting and the realities of clinical practice, RWE can add value to a regulatory submission. These early examples provide insight into how regulators evaluated RWE submitted as evidence of efficacy for oncology drugs., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the perceptions of US community-based hematologists/oncologists regarding approved CAR-T therapies in relapsed/refractory large B-cell lymphoma and barriers to their adoption in practice. Materials & methods: In February and November 2019, US physicians with diverse geographic representation submitted responses via a web-based survey prior to or via an audience response system at the live meetings. Results: In February and November, 46 and 29% of physicians indicated that they had not referred any patients for CAR-T therapy, respectively. Cumbersome logistics, high cost and toxicity were defined as major barriers to prescribing CAR-T therapy. Conclusions: These findings highlight a need to improve processes, and address costs, to ensure timely access to this potentially curative therapy for relapsed/refractory large B-cell lymphoma patients.

Introduction: Lenvatinib has become the most commonly prescribed first-line (1L) agent for the treatment of radioactive iodine-refractory differentiated thyroid cancer (RAI-r DTC) since its approval in 2015. With no real-world studies describing clinical outcomes of 1L lenvatinib and subsequent therapy, the current study aimed to assess treatment sequencing and related clinical outcomes in patients treated with 1L lenvatinib in the USA METHODS: We conducted a multisite, retrospective chart review of US patients with a diagnosis of RAI-r DTC who had initiated 1L therapy with lenvatinib from January 1, 2016 through May 31, 2017 with follow-up through October 17, 2018. Physicians completed electronic case report forms for two patient cohorts: patients still receiving 1L lenvatinib (cohort 1) and those who had initiated second-line (2L) therapy prior to data cutoff (cohort 2). Real-world objective response rate (ORR) was assessed for both cohorts. Progression-free survival (PFS) and overall survival (OS) were assessed for cohort 2., Results: A total of 252 patients met the study criteria with 71 in cohort 1 and 181 in cohort 2. Patients were predominantly female, had papillary DTC, and had lung metastases. The ORR was 64.8% for cohort 1 and 53.6% for cohort 2. In cohort 2, median PFS from 1L lenvatinib initiation was 14.0 months (95% CI 12.7-15.0). Second-line treatments included sorafenib (49.7%), cabozantinib (19.3%), and other targeted/chemotherapy/immuno-oncology agents. The ORR in 2L therapy was 15.5%. For cohort 2, the 12-, 18-, and 24-month OS from initiation of 1L lenvatinib was 92.8%, 81.5%, and 66.9%, respectively., Conclusions: In this first real-world examination of clinical effectiveness of 1L lenvatinib and subsequent therapy among patients in the US, the results demonstrated that treatment with 1L lenvatinib followed by another 2L therapy may deliver a clinical benefit, thus allowing a number of potential 2L options following 1L lenvatinib for patients with RAI-r DTC.

Background: In the absence of randomized controlled trials, real-world evidence may aid practitioners in optimizing the selection of therapy for patients with cancer. The study's aim was to determine real-word use, as well as compare effectiveness, of single-agent and combination chemotherapy as palliative treatment for female patients with metastatic breast cancer (mBC)., Materials and Methods: Using administrative claims data from the Symphony Health's Integrated Oncology Dataverse, female patients with mBC treated with at least one chemotherapy-only treatment (COT) between January 1, 2013, and December 31, 2017 were selected. The frequency of use of single-agent versus combination chemotherapy overall and by line of therapy (LOT) was calculated whereas effectiveness was measured using time to next treatment (TNT)., Results: A total of 12,381 patients with mBC were identified, and 3,777 (31%) received at least one line of COT. Of the 5,586 observed LOTs among the 3,777 patients, 66.5% were single-agent and 33.5% combination chemotherapy. Combination chemotherapy was most frequently used in first-line (45%) and least frequently in fifth-line (16%). Across all LOTs, median TNT was significantly longer for single-agent versus combination chemotherapy (5.3 months vs. 4.1 months, p < .0001). Comparison of median TNT by LOT showed significance in third-line and greater but not in first-line or second-line. Among single agents, the median TNT for patients receiving capecitabine was longest in comparison to all other single agents., Conclusions: The frequency of combination COT use, particularly in first-line, warrants further research given published guideline recommendations. The observed TNT difference favoring single-agent treatment in later lines supports guideline recommendations. Variance between single-agent preference and observed TNT was noteworthy., Implications for Practice: Although published data from evidence- and consensus-based guidelines recommend single-agent over combination chemotherapy, the extensive list of agents available for use and a gap in the comparative effectiveness research of these agents have resulted in significant variances in patterns of care. The aim of this study was to assess real-world treatment patterns and their effectiveness during palliative therapy of metastatic breast cancer. The objective was to understand when and how chemotherapy-only treatment is used in metastatic breast cancer and whether comparative effectiveness analysis supports the observed patterns of care., (© 2020 Cardinal Health. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Aims: In 2016, nivolumab and pembrolizumab were approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) following progression after initial platinum-based therapy. We sought to explore the uptake, effectiveness, and impact on healthcare resource utilization (HRU) and total costs of care pre and post introduction of immuno-oncology (IO) agents. Materials and Methods: Recurrent/metastatic SCCHN patients were identified from a healthcare claims clearinghouse by selecting patients with a claim for distant metastases or who initiated systemic therapy at least 120 days following discontinuation of platinum-based therapy. Two cohorts were created according to the date of post-platinum therapy (PPT) initiation: pre-IO = 08/01/2014-07/31/2015; post-IO = 08/01/2016-07/31/2017. Treatment patterns and effectiveness (duration of treatment, time to next treatment) during first-line (1 L) PPT, HRU, and costs were compared between propensity-score matched patients from each cohort. Results: Of 716 patients identified (pre-IO = 265, post-IO = 451) 46.3% of post-IO patients received IO post-platinum. In 229 matched patients 20.0% of the post-IO compared to 10.7% of the pre-IO ( p =.02) had at least a 6 month duration of 1 L PPT. Inpatient admissions during 1 L PPT: 34.1% post-IO versus 48.0% pre-IO ( p = <.01). PPPM total costs of care in 1 L PPT were significantly greater post-IO ($11,535) compared to pre-IO ($9,054, p =.002). Time to next treatment (from 1 L PPT start) was 6.1 months pre-IO versus 7.4 months post-IO ( p =.046). Limitations: Recurrent SCCHN patients were identified using a validated claims-based algorithm but misclassification may occur. Requiring patients to have received 1 L PPT the pre-IO cohort may be systematically different that the post-IO cohort as pre-IO patients were more likely to have not received further treatment beyond 1 L PPT. Conclusions: The significant uptake of IO therapy resulted in longer durations of therapy, lower rates of hospitalizations although higher treatment costs. The results suggest IO treatment provides additional clinical benefits to recurrent/metastatic SCCHN patients.

Aim: To estimate the real-world incidence and timing of radiation pneumonitis following chemoradiotherapy for Stage III non-small-cell lung cancer and compare costs between patients with and without radiation pneumonitis. Methods: Retrospective analysis using the Symphony Health Integrated Dataverse. Results: Pneumonitis incidence was 12.4% with a 177-day mean time to onset. Patients with versus without pneumonitis were more frequently admitted to the hospital (33.8 vs 19.2%, p < 0.0001) and seen in the emergency room (51.9 vs 35.8%, p < 0.0001) and had higher mean total healthcare costs (US$4251 vs US$3969 per-patient per-month; p = 0.0163). Conclusion: Although pneumonitis significantly increased healthcare resource utilization and costs in chemoradiotherapy-treated Stage III non-small-cell lung cancer, the per-patient per-month differential was <10%. Such financial assessments are critical for cost-benefit analysis.

Aim: To examine the effectiveness of eribulin mesylate for metastatic breast cancer post cyclin-dependent kinase inhibitor (CDKi) 4/6 therapy. Materials & methods: US community oncologists reviewed charts of patients who had received eribulin from 3 February 2015 to 31 December 2017 after prior CDKi 4/6 therapy and detailed their clinical/treatment history, clinical outcomes (lesion measurements, progression, death) and toxicity. Results: Four patient cohorts were created according to eribulin line of therapy: second line, third line, per US label and fourth line with objective response rates/clinical benefit rates of 42.2%/58.7%, 26.1%/42.3%, 26.7%/54.1% and 17.9%/46.4%, respectively. Median progression-free survival/6-month progression-free survival (79.5% of all patients censored) by cohort was: 9.7 months/77.3%, 10.3 months/71.3%, not reached/70.4% and 4.0 months/0.0%, respectively. Overall occurrence of neutropenia = 23.5%, febrile neutropenia = 1.3%, peripheral neuropathy = 10.1% and diarrhea = 11.1%. Conclusion: Clinical outcome and adverse event rates were similar to those in clinical trials and other observational studies. Longer follow-up is required to confirm these findings.

Aim: Targeted therapy (TT) and immuno-oncology (IO) drugs are approved for patients with BRAF mutant metastatic melanoma (MM). We compared real-world outcomes for first-line (1L) TT versus 1L IO to evaluate optimal sequencing. Materials & methods: Physicians-identified BRAF mutant MM patients initiating 1L TT or IO therapies and extracted treatment, disease and clinical outcomes including disease response which were compared between TT and IO and individual regimens. Results: 440 MM patients (TT = 283, IO = 157) were identified. A higher proportion of TT patients had liver metastases (46.3 vs 35.0%) and abnormal lactate dehydrogenase (61.1 vs 42.7%). IO-treated had a RECIST-determined response rate of 45.9 versus 60.1% for TT and time on treatment of 7.2 versus 11.4 months, respectively. There was no survival difference between cohorts. Conclusion: Despite higher risk patients, 1L TT resulted in higher response rate and longer treatment duration suggesting a preferred 1L sequence.

Aim: To evaluate real-world effectiveness of guideline-recommended palonosetron-containing antiemetic regimens in patients receiving highly (HEC) or moderately emetogenic (MEC) chemotherapy. Patients & methods: This retrospective analysis used records of adults receiving first-line chemotherapy and a three-drug palonosetron-containing antiemetic regimen for HEC or palonosetron-containing antiemetic regimen for MEC (carboplatin). Results: A total of 1587 records were evaluated. For HEC and MEC, respectively, chemotherapy-induced nausea and vomiting (CINV) occurred in 40 versus 44% of patient cycles (p = 0.01), and unscheduled iv. antiemetics in 41 versus 35% (p < 0.05). A total of 48% of HEC patients versus 42% of MEC patients had CINV-related clinic visits (p = 0.05). Conclusion: Palonosetron-containing antiemetic regimens may provide insufficient CINV control. Alternative regimens may improve patient quality of life and reduce healthcare resource utilization.

Does the rapid integration of both targeted and immuno-oncology drugs into treatment guidelines across solid tumors and hematologic malignancies herald the beginning of the end of chemotherapy as a foundational element in systemic cancer treatment? We respond to similar assertions posited after the 2018 American Society of Clinical Oncology Annual Meeting with an analysis of past, current, and future treatment of breast cancer-a tumor central to the evolution of modern cancer treatment principles. Our conclusions assert that reports of the demise of chemotherapy are greatly exaggerated and, as chemotherapy is likely to remain foundational for years to come, research is warranted to improve its patient-centricity.

Treatment options for patients with acute myeloid leukemia (AML), who are unfit for induction chemotherapy are unsatisfactory. Overall survival (OS) superiority has not been demonstrated in randomized controlled trials (RCT) in this population, challenging the value of available therapies. We sought to assess the relative value of approved therapies using value-assessment tools. Clinical, safety, quality-of-life (QOL), supportive care, and resource utilization outcomes data were abstracted from RCTs and examined using value-assessment frameworks. Three RCTs, one each of azacitidine, decitabine, and low-dose cytarabine were identified. OS was not statistically significant and secondary outcomes including response rates, rates of transfusion independence, the frequency of hospitalizations and changes in QOL were reported differently across trials. Value-assessment tools considered OS as the primary efficacy endpoint without consideration to response rates. The NCCN Evidence Blocks TM were most successful in considering secondary endpoints. With the move toward value-based care, understanding how these value tools apply to AML patients is critical.

This study assesses resource utilization and total direct medical cost among patients in the United States starting systemic antineoplastic therapy (ST) pre- and postapproval of immuno-oncology (IO) agents for advanced non-small cell lung cancer. Adults diagnosed with lung cancer initiating first-line ST within 6 months of diagnosis during either the pre- (March 2013-March 2014) or post-IO (March 2015-December 2016) approval period were identified in a US-based multipayer administrative claims database. Excluded were patients with small cell lung cancer, secondary malignancies, less than 1 month follow-up, and those in clinical trials. Total cost (TC) was calculated from the date of initiation of treatment until the last follow-up. Propensity score matching was adjusted for differences in patient cohorts, including follow-up time. Binary multiple logistic regression assessed predictors of high TC (above mean) pre- and post IO. Mean TC per patient was higher pre-IO versus post IO in both unmatched ($165,548 vs $95,715) and matched analyses($129,977 vs $113,177). Hospitalization and emergency department (ED) visit rates were higher pre-IO versus postapproval. Predictors of high TC pre-IO included use of first-line combination therapy, radiation, targeted therapy, maintenance therapy, biomarker testing, more comorbidities, longer follow-up, first-line hospitalization, first-line cost above mean, and age 65 years and older. In the post-IO period, additional predictors of higher TC included use of IO, having mild liver disease or hemiplegia, and longer time to ST initiation. Early data show lower ED visit and hospitalization rates and associated lower TC in the post-IO era.

Introduction: Real-world data are critical to demonstrate the consistency of evidence and external generalizability of randomized controlled trials (RCTs). This study examined characteristics and outcomes of metastatic triple-negative breast cancer (mTNBC) patients treated with eribulin mesylate at community oncology practices in the United States., Methods: Physicians identified mTNBC patients initiating eribulin between 1 January 2011 and 1 January 2014 and abstracted data into an electronic case report form (eCRF). Eribulin treatment in the metastatic setting was categorized as early use (EU, first-/second-line) and late use (LU, third-line or later). Patient characteristics, overall survival (OS), disease response (per treating physician), and adverse events (AEs) rates in each group, respectively, are reported., Results: Overall 252 eCRFs were completed: 125 (49.6%) EU and 127 (50.4%) LU. The median age at metastatic diagnosis was 53 years and 42.1% were stage IV at their initial diagnosis. The median duration of follow-up from the initiation of first-line treatment was 24 months. Rates of disease response (complete or partial per treating physician) were 69.9% in the EU group and 48.8% in the LU group. The five most commonly reported adverse events during eribulin were as follows: fatigue (65.1%), weakness (40.1%), decreased appetite (32.5%), neutropenia (31.0%), and leukopenia (27.4%). Discontinuation of eribulin due to AE was observed in 4.0% of patients. Median OS from initiation of eribulin was 23.0 months (95% CI: 18.7-27.3) among EU and 14.7 (95% CI: 12.6-16.9) among LU., Conclusion: In the real-world eribulin-treated mTNBC, patients have more sites of metastatic disease and exposure to greater numbers of prior therapies compared to RCTs. The median OS of 14.7 months among LU patients is consistent with, and slightly longer than the 13.1 months and 14.4 months reported in the EMBRACE and Study 301 clinical trials, respectively., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Haitian women have the highest incidence of cervical cancer within the Western hemisphere. Intravaginal hygiene practices have been linked with human papilloma virus (HPV) infection and cervical dysplasia. These practices, known as 'twalet deba' in Haitian Creole, are common among Haitian women and are performed with various natural and synthetic agents. As part of a community-based participatory research initiative aimed at reducing cervical cancer disparities in rural Haiti, we explored the use of intravaginal agents and their associations with high-risk HPV infection., Design: Community Health Workers recruited 416 women for cervical self-sampling from two neighborhoods within Thomonde, Haiti. Participants were interviewed regarding intravaginal hygiene practices and completed a cervical self-sampling procedure. Cervical samples were analyzed for the presence of high-risk HPV infection. Associations between each intravaginal agent and high-risk HPV infection were examined via univariate logistic regression analyses, as well as via multivariate analyses controlling for sociodemographic factors and concurrent agent use., Results: Nearly all women (97.1%) performed twalet deba, using a variety of herbal and commercially produced intravaginal agents. Approximately 11% of the participants tested positive for high-risk HPV. Pigeon pea and lime juice were the only agents found to be associated with high-risk HPV in the univariate analyses, with women who used these agents being approximately twice as likely to have high-risk HPV as those who did not. Only pigeon pea remained significantly associated with high-risk HPV after controlling for sociodemographic factors and concurrent agent use., Conclusion: Two agents, pigeon pea and lime juice, may contribute to risk for HPV infection in this population. Results suggest that in addition to cervical cancer screening interventions, future preventive initiatives should focus on minimizing risk by advocating for the use of less-toxic twalet deba alternatives.

Purpose: To determine if differences in screening and vaccination patterns across the population may accentuate ethnic and geographic variation in future burden of disease., Methods: Using Cancer in North America data provided by the North American Association of Central Cancer Registries, county cervical cancer incidence trends from 1995 to 2009 were modeled for the entire United States using ecologic covariates. Rates for health service areas were also modeled by ethnicity. State-level incidence was mapped together with Papanicolaou (Pap) screening, past 3 years (women ≥ 18 years old), and three-dose human papillomavirus (HPV) vaccine coverage (girls 13 to 17 years old) to identify potential priority areas for preventive services., Results: US cervical cancer incidence decreased more during the periods 1995 to 1999 and 2000 to 2004 than during the period 2005 to 2009. During these 15 years, the most affected areas became increasingly confined to Appalachia, the lower Mississippi Valley, the Deep South, Texas, and Florida. Hispanic and black women experienced a higher incidence of cervical cancer than both white and Asian and Pacific Islander women during each period. Women in 10 of 17 states/districts with a high incidence (≥ 8.14/100,000) reported low Pap testing (< 78.5%), HPV vaccine coverage (< 33.9%), or both prevention technologies., Conclusion: The decline in cervical cancer incidence has slowed in recent years. Access to HPV vaccination, targeted screening, and treatment in affected populations is needed to reduce cervical cancer disparities in the future., Competing Interests: AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Jonathan K. Kish Employment: Cardinal Health Consulting or Advisory Role: Cardinal Health (Inst) Travel, Accommodations, Expenses: Cardinal Health Alicia I. Rolin No relationship to disclose Zhaohui Zou No relationship to disclose James E. Cucinelli No relationship to disclose Zaria Tatalovich No relationship to disclose Mona Saraiya No relationship to disclose Sean F. Altekruse No relationship to disclose

Background: Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course., Objective: To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model., Methods: Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs., Results: In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost < $0.01 per member per month. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment., Conclusions: Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money., Disclosures: Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speaker's bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

Purpose: The development of skeletal-related events (SREs) (pathologic fracture, need for surgery and/or radiation to bone, spinal cord compression, and hypercalcemia of malignancy) in metastatic prostate cancer (MPC) is associated with worsened pain and compromised quality of life. Opioids are frequently used throughout the course of SRE treatment. This study describes the treatment patterns and incremental use of opioids in MPC patients diagnosed with SREs., Methods: PC patients with bone metastases newly diagnosed with an SRE between January 1, 2005, and September 30, 2014, were identified using MarketScan Commercial and Medicare databases. Included patients were aged ≥40 years, had medical/pharmacy benefits for ≥12 months before (preindex) and ≥6 months after (postindex) diagnosis, and were without evidence of other primary cancers. Patients were categorized as nonusers of opioids (<10 days), short-term users (≥10 and <60 days), or long-term users (≥60 days) and further by SRE type. Opioid type, proportion of time on opioids, morphine-equivalent dose, adjuvant medications, and radiation use before and after SRE diagnosis were evaluated., Findings: A total of 1071 eligible patients were identified (mean age, 71 years; 10.8% had chronic pain at baseline). The most common SRE types present were radiation (60.2%), radiation and bone surgery (15.0%), pathologic fracture (7.2%), and bone surgery (6.5%). Opioid use increased from 49.9% preindex to 53.3% postindex (P < 0.0001). The proportion of time on opioids doubled after SRE (pre, 0.3 vs post, 0.6; P < 0.0001). A greater percentage of patients used only opioids after an SRE (pre, 11.0%; post, 46.1% [P < 0.0001]), while a lesser percentage of patients used only radiation after an SRE (pre, 36.0%; post, 4.7% [P < 0.0001]). An increase was observed in patients using neither radiation nor opioids (pre, 14.5%; post, 42.0% [P < 0.0001]). An increase of ~50% was noted in long-term opioid users (from 22.1% to 32.1%). The use of monotherapy with a short-acting opioid decreased (pre, 35.1%; post, 32.5% [P < 0.0001]), while use of mixed opioids increased (pre, 13.7%; post, 19.1% [P < 0.0001]). Mean morphine-equivalent dose increased from pre- to post-SRE (9.1 vs 13.1 mg). Bisphosphonate and NSAID users decreased from before to after an SRE diagnosis (bisphosphonates, 40.2% vs 8.6%; NSAIDs, 26.7% vs 17.5% [both, P < 0.0001])., Implications: Long-term opioid use and dose were significantly increased after SRE development in MPC. The high percentage of patients not treated with an opioid or radiation potentially supports the need for additional treatment options for controlling pain if medically necessary and/or to prevent SREs., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)

Background: Evidence supporting optimal treatment sequencing in relapsed/refractory multiple myeloma (RRMM) patients requiring multiple therapy lines is lacking., Methods: Using retrospective chart data, this study describes real-world RRMM treatment patterns and related progression-free survival (PFS) in US community oncology clinics., Results: Bortezomib ± a non-immunomodulatory drug (IMiD), lenalidomide ± a non-proteasome inhibitor (PI), bortezomib + an IMiD were the most commonly used regimens in early lines of therapy. Median PFS was similar in 1(st) (11.1 months) and 2(nd) line (10.5) and decreased in lines 3 through 5 (3(rd): 7.9; 4(th): 7.2, 5(th): 5.4). Longest PFS (12.5 months) in first line was with bortezomib + ImiD; longest PFS in second line was with lenalidomide ± a non-PI was (13.2 months)., Conclusions: Re-treatment with bortezomib was common; novel agents were reserved for later therapy lines. Overall, the observed PFS associated with real-world treatment sequences were shorter than those reported in clinical trials.

Background: Liver resection is a key therapeutic strategy to improve survival in patients with colorectal cancer liver metastases. Underutilization may negatively affect outcomes. Using a Web-based survey and standardized imaging scenarios, this study assessed medical oncologists' (MOs) perceptions of resectability, preferences for chemotherapy sequencing, and referral for surgical consultation in a static patient profile of good performance status and no extrahepatic spread but varying bulk and distribution of disease., Methods: A total of 190 US-based MOs were surveyed. A single patient profile was created and combined with 10 different sets of liver computed tomographic images displaying a broad spectrum of metastases. Assessments of resectability and ranking were compared with the results obtained from an expert panel of 3 hepatic surgeons., Results: The expert hepatic surgeons designated 8 scans resectable, 1 borderline resectable/convertible, and 1 unresectable. In the 8 resectable cases, 34.4 % of MOS perceived the case to be initially resectable, 41.7 % potentially resectable after chemotherapy response, and 23.9 % unresectable. Increasing number of lesions, larger tumor diameter, and bilateral disease were associated with lower resectability perception (P < 0.01). Among those cases considered resectable by MOs, they preferred initial resection (54.2 %) over neoadjuvant chemotherapy (38.4 %). Initial referral for surgical consultation was generally favored only for cases considered initially resectable by MOs., Conclusions: This study confirms both potential discrepancies between MOs' and hepatic surgeons' perception of resectability and underutilization of early surgical consultation for patients with potentially resectable colorectal cancer liver metastases and underscores the importance of an evaluation that includes an experienced hepatic surgeon.

Background: Multiple myeloma is a progressive cancer for which there is no cure. Despite treatment, almost all patients eventually experience periods of disease relapse and remission. With the increasing use of novel therapies, including bortezomib, lenalidomide, carfilzomib, pomalidomide, and panobinostat, benchmarks for assessing the value of these therapies in treating patients with relapsed or refractory multiple myeloma (RRMM) are needed for physicians and payers alike., Objectives: To develop a model framework and to calculate an annual estimate of the total costs per patient for the treatment of patients with RRMM using 7 common treatment regimens, including bortezomib plus dexamethasone; panobinostat, bortezomib, and dexamethasone; lenalidomide plus dexamethasone; lenalidomide, bortezomib, and dexamethasone; carfilzomib; carfilzomib, lenalidomide, and dexamethasone; and pomalidomide plus dexamethasone., Methods: The expenditures for drugs and their administration, for prophylaxis and adverse event monitoring, and for the treatment of grade 3 or 4 adverse events were included in the calculations of the total pharmacy and medical costs. The drug costs were based on published pricing and labeled dosing schedules; the adverse event prophylaxis and monitoring costs were obtained from peer-reviewed publications; and the adverse event incidence rates were obtained from each regimen's prescribing information and from clinical trials. All the costs were summed over the duration of therapy for which the drugs were administered and were calculated separately for commercial and Medicare plans. The duration of therapy for each regimen was the time for which a patient had to be receiving the regimen to obtain 12 months of progression-free survival based on the duration-of-therapy to progression-free survival ratio observed from published clinical trials and/or the drug's labeling., Results: The pharmacy costs were highest for pomalidomide plus dexamethasone, whereas the medical costs were highest for the combination of carfilzomib, lenalidomide, and dexamethasone. The total cost associated with available treatments for RRMM was highest for regimens that included lenalidomide (approximate range, $126,000-$256,000). Only bortezomib plus dexamethasone and the combination of panobinostat, bortezomib, and dexamethasone had total costs that were lower than $125,000 per patient., Conclusion: This study represents the first model developed to comprehensively estimate the costs of managing RRMM with all currently approved and guideline-recommended regimens in the United States. As such, it provides the framework and basis for further budget impact analyses and for cost-effectiveness comparisons with these regimens.

Introduction: Reducing cancer disparities is a major public health objective. Disparities often are discussed in terms of either race and ethnicity or socioeconomic status (SES), without examining interactions between these variables., Methods: Surveillance, Epidemiology, and End Results (SEER)-18 data, excluding Alaska Native and Louisiana registries, from 2002 to 2008, were used to estimate five-year, cause-specific survival by race/ethnicity and census tract SES. Differences in survival between groups were used to assess absolute disparities. Hazard ratios were examined as a measure of relative disparity. Interactions between race/ethnicity and neighborhood SES were evaluated using proportional hazard models., Results: Survival increased with higher SES for all racial/ethnic groups and generally was higher among non-Hispanic white and Asian/Pacific Islander (API) than non-Hispanic black and Hispanic cases. Absolute disparity in breast cancer survival among non-Hispanic black vs non-Hispanic white cases was slightly larger in low-SES areas than in high-SES areas (7.1% and 6.8%, respectively). In contrast, after adjusting for stage, age, and treatment, risk of mortality among non-Hispanic black cases compared with non-Hispanic white cases was 21% higher in low-SES areas and 64% higher in high-SES areas. Similarly, patterns of absolute and relative disparity compared with non-Hispanic whites differed by SES for Hispanic breast cancer, non-Hispanic black colorectal cancer, and prostate cancer cases. Statistically significant interactions existed between race/ethnicity and SES for colorectal and female breast cancers., Discussion: In health disparities research, both relative and absolute measures provide context. A better understanding of the interactions between race/ethnicity and SES may be useful in directing screening and treatment resources toward at-risk populations., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Unlabelled: The purpose of the study was to assess the use of curative therapies for hepatocellular carcinoma (HCC) in the population. HCC treatment patterns were examined in Surveillance, Epidemiology, and End Results (SEER) 18 registries (28% of U.S.). Joinpoint regression analyses were performed to assess 2000-2010 incidence trends by tumor size, count, and receipt of potentially curative treatments (transplantation, resection, and ablation). SEER-Medicare data enabled evaluation of treatment patterns including receipt of sorafenib or transarterial chemoembolization (TACE) by HCC-associated comorbidities. Diagnoses of tumors≤5.0 cm in diameter significantly increased during 2000-2010, surpassing diagnosis of larger tumors. Overall, 23% of cases received potentially curative treatment. Joinpoint models indicated incidence rates of treatment with curative intent increased 17.6% per year during 2000-2005, then declined by -2.9% per year during 2005-2010 (P<0.001). Among HCC cases with a single tumor≤5.0 cm and no extension beyond the liver, use of ablative therapy significantly increased during 2000-2010. Use of invasive surgery for single tumors, regardless of size, significantly increased during the initial years of the decade, then plateaued. The group most likely to receive curative treatment in the SEER-Medicare cases was patients with one, small tumor confined to the liver (657 of 1,597 cases, 41%), with no difference in treatment by hepatic comorbidity status (P=0.24). A higher proportion of cases with reported liver-associated comorbidities were, however, diagnosed with tumors≤5.0 cm in diameter (1,745 0f 2,464, 71%) compared to patients with no reported comorbidities (996 of 2,596, 38%, P<0.001)., Conclusion: Although more HCC patients were diagnosed with early disease over time, the use of curative treatments in this patient group has recently plateaued. Efforts to identify and treat more eligible candidates for curative therapy could be beneficial., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: Post-transplant metabolic syndrome (PTMS) is associated with important causes of morbidity and mortality in solid organ transplant recipients. Our aim was to investigate predictors of PTMS in liver transplant (LT) recipients., Methods: We randomly selected 343 adults (>18 years of age) from a large cohort of 1,262 ethnically diverse patients who received LTs during 2000-2010., Results: Of 343 patients included, 68.2 % were male, with a mean age of 54 ± 10 years, 87 % White, and 31 % Hispanic. Prior to LTs, 6.2 % were on lipid-lowering agents and 24.5 % had BMI ≥ 30 (mean 26.9 ± 5 kg/m(2)). More Hispanics had diabetes before LTs compared to non-Hispanics (p = 0.037). Among those with follow-up of >6 months (n = 304) after LTs, the proportion of patients with diabetes and hypertension increased from 21.9 to 27 % (p < 0.0001), and from 11.5 to 51.6 % (p < 0.0001), respectively. Cholesterol levels increased from 150 ± 115 to 167 ± 70 (p < 0.0001). BMI remained unchanged. PTMS developed in 41 (13.5 %) and cardiovascular events in 31 (10.2 %) patients. Hispanics had higher risk of developing PTMS compared to non-Hispanics (OR 2.30, 95 % CI 1.18-4.49). Survival was not affected by PTMS (p = 0.3), ethnicity (p = 0.52), or nonalcoholic steatohepatitis as the etiology of liver disease (p = 0.50)., Conclusions: More Hispanics had diabetes before LTs (29 to 18 %, p < 0.05) and were more prone to developing PTMS after LTs compared to non-Hispanics.

Reports of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) detected in marine environments have occurred since the early 1990 s. This investigation sought to isolate and characterize S. aureus from marine waters and sand at a subtropical recreational beach, with and without bathers present, in order to investigate possible sources and to identify the risks to bathers of exposure to these organisms. During 40 days over 17 months, 1,001 water and 36 intertidal sand samples were collected by either bathers or investigators at a subtropical recreational beach. Methicillin-sensitive S. aureus (MSSA) and MRSA were isolated and identified using selective growth media and an organism-specific molecular marker. Antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) pattern, multi-locus sequence type (MLST), and staphylococcal protein A (spa) type were characterized for all MRSA. S. aureus was isolated from 248 (37 %) bather nearby water samples at a concentration range of <2-780 colony forming units per ml, 102 (31 %) ambient water samples at a concentration range of <2-260 colony forming units per ml, and 9 (25 %) sand samples. Within the sand environment, S. aureus was isolated more often from above the intertidal zone than from intermittently wet or inundated sand. A total of 1334 MSSA were isolated from 37 sampling days and 22 MRSA were isolated from ten sampling days. Seventeen of the 22 MRSA were identified by PFGE as the community-associated MRSA USA300. MRSA isolates were all SCCmec type IVa, encompassed five spa types (t008, t064, t622, t688, and t723), two MLST types (ST8 and ST5), and 21 of 22 isolates carried the genes for Panton-Valentine leukocidin. There was a correlation (r = 0.45; p = 0.05) between the daily average number of bathers and S. aureus in the water; however, no association between exposure to S. aureus in these waters and reported illness was found. This report supports the concept that humans are a potential direct source for S. aureus in marine waters.

In January 2010, a massive earthquake struck Haiti resulting in unprecedented damage. Little attention, however, has focused on the earthquake's mental health impact in the Haitian diaspora community. As part of an established community-based participatory research initiative in Little Haiti, the predominately Haitian neighborhood in Miami, FL, USA, community health workers conducted surveys with neighborhood residents about earthquake-related losses, coping strategies, and depressive/traumatic symptomology. Findings reveal the earthquake strongly impacted the diaspora community and highlights prominent coping strategies. Following the earthquake, only a small percentage of participants self-reported engaging in any negative health behaviors. Instead, a majority relied on their social networks for support. This study contributes to the discourse on designing culturally-responsive mental health initiatives for the Haitian diaspora and the ability of existing community-academic partnerships to rapidly adapt to community needs.

Background. Haitian immigrant women residing in Little Haiti, a large ethnic enclave in Miami-Dade County, experience the highest cervical cancer incidence rates in South Florida. While this disparity primarily reflects lack of access to screening with cervical cytology, the burden of human papillomavirus (HPV) which causes virtually all cases of cervical cancer worldwide, varies by population and may contribute to excess rate of disease. Our study examined the prevalence of oncogenic and nononcogenic HPV types and risk factors for HPV infection in Little Haiti. Methods. As part of an ongoing community-based participatory research initiative, community health workers recruited study participants between 2007 and 2008, instructed women on self-collecting cervicovaginal specimens, and collected sociodemographic and healthcare access data. Results. Of the 242 women who contributed adequate specimens, the overall prevalence of HPV was 20.7%, with oncogenic HPV infections (13.2% of women) outnumbering nononcogenic infections (7.4%). Age-specific prevalence of oncogenic HPV was highest in women 18-30 years (38.9%) although the prevalence of oncogenic HPV does not appear to be elevated relative to the general U.S. population. The high prevalence of oncogenic types in women over 60 years may indicate a substantial number of persistent infections at high risk of progression to precancer.

Studies evaluating the relationship between microbes and human health at non-point source beaches are necessary for establishing criteria which would protect public health while minimizing economic burdens. The objective of this study was to evaluate water quality and daily cumulative health effects (gastrointestinal, skin, and respiratory illnesses) for bathers at a non-point source subtropical marine recreational beach in order to better understand the inter-relationships between these factors and hence improve monitoring and pollution prevention techniques. Daily composite samples were collected, during the Oceans and Human Health Beach Exposure Assessment and Characterization Health Epidemiologic Study conducted in Miami (Florida, USA) at a non-point source beach, and analyzed for several pathogens, microbial source tracking markers, indicator microbes, and environmental parameters. Analysis demonstrated that rainfall and tide were more influential, when compared to other environmental factors and source tracking markers, in determining the presence of both indicator microbes and pathogens. Antecedent rainfall and F+ coliphage detection in water should be further assessed to confirm their possible association with skin and gastrointestinal (GI) illness outcomes, respectively. The results of this research illustrate the potential complexity of beach systems characterized by non-point sources, and how more novel and comprehensive approaches are needed to assess beach water quality for the purpose of protecting bather health.

Background: Staphylococcus aureus including methicillin resistant S. aureus, MRSA, are human colonizing bacteria that commonly cause opportunistic infections primarily involving the skin in otherwise healthy individuals. These infections have been linked to close contact and sharing of common facilities such as locker rooms, schools and prisons Waterborne exposure and transmission routes have not been traditionally associated with S. aureus infections. Coastal marine waters and beaches used for recreation are potential locations for the combination of high numbers of people with close contact and therefore could contribute to the exposure to and infection by these organisms. The primary aim of this study was to evaluate the amount and characteristics of the shedding of methicillin sensitive S. aureus, MSSA and MRSA by human bathers in marine waters., Results: Nasal cultures were collected from bathers, and water samples were collected from two sets of pools designed to isolate and quantify MSSA and MRSA shed by adults and toddlers during exposure to marine water. A combination of selective growth media and biochemical and polymerase chain reaction analysis was used to identify and perform limited characterization of the S. aureus isolated from the water and the participants. Twelve of 15 MRSA isolates collected from the water had identical genetic characteristics as the organisms isolated from the participants exposed to that water while the remaining 3 MRSA were without matching nasal isolates from participants. The amount of S. aureus shed per person corresponded to 105 to 106 CFU per person per 15-minute bathing period, with 15 to 20% of this quantity testing positive for MRSA., Conclusions: This is the first report of a comparison of human colonizing organisms with bacteria from human exposed marine water attempting to confirm that participants shed their own colonizing MSSA and MRSA into their bathing milieu. These findings clearly demonstrate that adults and toddlers shed their colonizing organisms into marine waters and therefore can be sources of potentially pathogenic S. aureus and MRSA in recreational marine waters. Additional research is needed to evaluate recreational beaches and marine waters as potential exposure and transmission pathways for MRSA.

The objectives of this work were to compare enterococci (ENT) measurements based on the membrane filter, ENT(MF) with alternatives that can provide faster results including alternative enterococci methods (e.g., chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)), and results from regression models based upon environmental parameters that can be measured in real-time. ENT(MF) were also compared to source tracking markers (Staphylococcus aureus, Bacteroidales human and dog markers, and Catellicoccus gull marker) in an effort to interpret the variability of the signal. Results showed that concentrations of enterococci based upon MF (<2 to 3320 CFU/100 mL) were significantly different from the CS and qPCR methods (p < 0.01). The correlations between MF and CS (r = 0.58, p < 0.01) were stronger than between MF and qPCR (r ≤ 0.36, p < 0.01). Enterococci levels by MF, CS, and qPCR methods were positively correlated with turbidity and tidal height. Enterococci by MF and CS were also inversely correlated with solar radiation but enterococci by qPCR was not. The regression model based on environmental variables provided fair qualitative predictions of enterococci by MF in real-time, for daily geometric mean levels, but not for individual samples. Overall, ENT(MF) was not significantly correlated with source tracking markers with the exception of samples collected during one storm event. The inability of the regression model to predict ENT(MF) levels for individual samples is likely due to the different sources of ENT impacting the beach at any given time, making it particularly difficult to to predict short-term variability of ENT(MF) for environmental parameters.

Background: Microbial water-quality indicators, in high concentrations in sewage, are used to determine whether water is safe for recreational purposes. Recently, the use of these indicators to regulate recreational water bodies, particularly in sub/tropical recreational marine waters without known sources of sewage, has been questioned. The objectives of this study were to evaluate the risk to humans from exposure to subtropical recreational marine waters with no known point source, and the possible relationship between microbe densities and reported symptoms in human subjects with random-exposure assignment and intensive individual microbial monitoring in this environment., Methods: A total of 1303 adult regular bathers were randomly assigned to bather and non-bather groups, with subsequent follow-up for reported illness, in conjunction with extensive environmental sampling of indicator organisms (enterococci)., Results: Bathers were 1.76 times more likely to report gastrointestinal illness [95% confidence interval (CI) 0.94-3.30; P = 0.07]; 4.46 times more likely to report acute febrile respiratory illness (95% CI 0.99-20.90; P = 0.051) and 5.91 times more likely to report a skin illness (95% CI 2.76-12.63; P < 0.0001) relative to non-bathers. Evidence of a dose-response relationship was found between skin illnesses and increasing enterococci exposure among bathers [1.46 times (95% CI 0.97-2.21; P = 0.07) per increasing log(10) unit of enterococci exposure], but not for gastrointestinal or respiratory illnesses., Conclusions: This study indicated that bathers may be at increased risk of several illnesses relative to non-bathers, even in the absence of any known source of domestic sewage impacting the recreational marine waters. There was no dose-response relationship between gastroenteritis and increasing exposure to enterococci, even though many current water-monitoring standards use gastroenteritis as the major outcome illness.

The use of enterococci as the primary fecal indicator bacteria (FIB) for the determination of recreational water safety has been questioned, particularly in sub/tropical marine waters without known point sources of sewage. Alternative FIB (such as the Bacteroidales group) and alternative measurement methods (such as rapid molecular testing) have been proposed to supplement or replace current marine water quality testing methods which require culturing enterococci. Moreover, environmental parameters have also been proposed to supplement current monitoring programs. The objective of this study was to evaluate the health risks to humans from exposure to subtropical recreational marine waters with no known point source. The study reported symptoms between one set of human subjects randomly assigned to marine water exposure with intensive environmental monitoring compared with other subjects who did not have exposure. In addition, illness outcomes among the exposed bathers were compared to levels of traditional and alternative FIB (as measured by culture-based and molecular-based methods), and compared to easily measured environmental parameters. Results demonstrated an increase in self-reported gastrointestinal, respiratory and skin illnesses among bathers vs. non-bathers. Among the bathers, a dose-response relationship by logistic regression modeling was observed for skin illness, where illness was positively related to enterococci enumeration by membrane filtration (odds ratio = 1.46 [95% confidence interval = 0.97-2.21] per increasing log10 unit of enterococci exposure) and positively related to 24 h antecedent rain fall (1.04 [1.01-1.07] per increasing millimeters of rain). Acute febrile respiratory illness was inversely related to water temperature (0.74 [0.56-0.98] per increasing degree of water temperature). There were no significant dose-response relationships between report of human illness and any of the other FIB or environmental measures. Therefore, for non-point source subtropical recreational marine waters, this study suggests that humans may be at increased risk of reported illness, and that the currently recommended and investigational FIB may not track gastrointestinal illness under these conditions; the relationship between other human illness and environmental measures is less clear., (Published by Elsevier Ltd.)

Due to global climate change, the world will, on average, experience a higher number of heat waves, and the intensity and length of these heat waves is projected to increase. Knowledge about the implications of heat exposure to human health is growing, with excess mortality and illness occurring during hot weather in diverse regions. Certain groups, including the elderly, the urban poor, and those with chronic health conditions, are at higher risk. Preventive actions include: establishing heat wave warning systems; making cool environments available (through air conditioning or other means); public education; planting trees and other vegetation; and modifying the built environment to provide proper ventilation and use materials and colors that reduce heat build-up and optimize thermal comfort. However, to inspire local prevention activities, easily understood information about the strategies' benefits needs to be incorporated into decision tools. Integrating heat health information into a comprehensive adaptation planning process can alert local decision-makers to extreme heat risks and provide information necessary to choose strategies that yield the largest health improvements and cost savings. Tools to enable this include web-based programs that illustrate effective methods for including heat health in comprehensive local-level adaptation planning; calculate costs and benefits of several activities; maps showing zones of high potential heat exposure and vulnerable populations in a local area; and public awareness materials and training for implementing preventive activities. A new computer-based decision tool will enable local estimates of heat-related health effects and potential savings from implementing a range of prevention strategies.

Traditionally, the use of enterococci has been recommended as the fecal indicator bacteria of choice for testing marine recreational water quality, and prior studies have shown that bathers shed large numbers of enterococci into the water. The current study expands upon prior research by evaluating shedding from both toddlers and adults, and by the expansion of measurements to include enterococci shedding via three different methods (membrane filter (MF), chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)) and shedding of alternative fecal indicator bacteria (Bacteroidales human markers UCD and HF8 via qPCR). Two sets of experiments were conducted. The first experiment consisted of two groups of 10 adults who bathed together in a large pool. The second study consisted of 14 toddlers who bathed individually in a small pool which allowed for sand recovery. Sand recovery was used to estimate the amount of sand transported on the bodies of toddlers and to estimate the number of fecal indicator bacteria released from this sand. The numbers of estimated enterococci shed per adult ranged from 1.8 x 10(4) to 2.8 x 10(6) CFU, from 1.9 x 10(3) to 4.5 x 10(6) MPN, and from 3.8 x 10(5) to 5.5 x 10(6) GEU based on the MF, CS, and qPCR methods, respectively. The estimated numbers of Bacteroidales human markers ranged from 1.8 x 10(4) to 1.3 x 10(6) for UCD, and ranged from the below detection limit to 1.6 x 10(5) for HF8. The estimated amount of sand transported per toddler (n=14) into the water column after sand exposure was 8+/-6g on average. When normalizing the numbers of enterococci shed from toddlers via sand by the 3.9 body surface area ratio, the differences between toddlers and adults were insignificant. Contributions of sands to the total enterococci (MF) shed per toddler was 3.7+/-4.4% on average. Although shedding via beach sand may contribute a small fraction of the microbial load during initial bathing, it may have a significant role if bathers go to water repetitively after sand exposure.