Factors associated with longer endocrine therapy use by South Carolina Medicaid-insured breast cancer survivors.

PURPOSE: The objective of this study is to determine demographic, clinical, and pharmaceutical factors that are associated with longer endocrine therapy usage duration. METHODS: South Carolina Central Cancer Registry incidence data linked with South Carolina Medicaid prescription claims and administrative data were used. The study included a sample (N = 1399) of female South Carolina Medicaid recipients with hormone receptor-positive breast cancer diagnosed between 2000 and 2012 who filled at least one ET prescription. A series of multiple regression models were built to explore the association of demographic, clinical, and pharmaceutical factors with the endocrine therapy usage duration. RESULTS: Multiple linear regression analysis showed that none of the demographic or clinical factors tested were significantly associated with the endocrine therapy usage duration. However, the type of endocrine therapy taken as well as receipt of the prescriptions that could have been used to alleviate side-effects (adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and vitamins) were significantly associated. CONCLUSION: Our study highlights the potential value of concurrent prescriptions for improving the endocrine therapy usage duration, with an optimal intervention point before 14 months post ET initiation. This work informs further research needed to test pharmacologic interventions that may significantly increase the endocrine therapy duration as well as other nonpharmacologic strategies for side-effect management.

Contemporary Assessment of Long-Term Survival Rates in Patients With Stage I Nonseminoma Germ-Cell Tumor of the Testis: Population-Based Comparison Between Surveillance and Active Treatment After Initial Orchiectomy.

BACKGROUND: Historical data demonstrated similar survival outcomes in patients with stage I nonseminoma germ-cell tumor of the testis (NSGCTT) subjected to either surveillance or active treatment (AT) after orchiectomy. However, data with long-term follow-up are unavailable. We tested contemporary treatment rates and their effect on cancer-specific mortality (CSM) and other-cause mortality (OCM) relative to surveillance, as well as after stratification between chemotherapy (CHT) versus retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: We identified patients with stage I NSGCTT with initial orchiectomy within the Surveillance, Epidemiology, and End Results (SEER) database (1988-2015). Subsequent surveillance versus CHT versus RPLND use rates were reported. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used after propensity score (PS) matching. These tests first compared surveillance versus AT (CHT vs. RPLND) and subsequently CHT versus RPLND. RESULTS: Of 5034 patients with stage I NSGCTT, 61.2%, 24.9%, and 13.9%, respectively, underwent surveillance, CHT, and RPLND. Between 1988 and 2015, surveillance (estimated annual percentage change [EAPC]: +1.1%, P < .001) and CHT (EAPC: +2.3%, P < .001) rates increased. RPLND rates decreased (EAPC: -5.7%; P < .001). After PS matching, CRR models failed to identify AT as an independent predictor of lower mortality relative to surveillance. However, after PS matching, CRR models identified RPLND as an independent predictor of lower CSM (hazard ratio, 0.26; P = .002) relative to CHT. No difference in OCM rates was recorded (hazard ratio, 1.25; P = .2). CONCLUSION: Surveillance and CHT use rates increased while RPLND decreased in the last two decades. Virtually the same outcomes were recorded between surveillance and AT. However, within AT, RPLND was associated with lower CSM than CHT.

Trends and appropriateness of perioperative chemotherapy for muscle-invasive bladder cancer.

INTRODUCTION: Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment. RESULTS: We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P < 0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P < 0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P < 0.05). CONCLUSION: From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Racial differences in long-term adjuvant endocrine therapy adherence and mortality among Medicaid-insured breast cancer patients in Texas: Findings from TCR-Medicaid linked data.

BACKGROUND: There are racial/ethnic disparities in breast cancer mortality may be attributed to differences in receipt of adjuvant cancer treatment. Our purpose was to determine whether the mortality disparities could be explained by racial/ethnic differences in long-term adherence to adjuvant endocrine therapy (AET). METHODS: We conducted a retrospective cohort study with the Texas Cancer Registry and Medicaid claims-linked dataset of women (20-64 years) diagnosed with local and regional breast cancer who filled a prescription for AET from 2000-2008. Adherence to AET was measured at three time points (1-, 3-, and 5-year adherence) using a value for the percentage of medication filled for each period divided by the total number of possible prescriptions prescribed (Medication Possession Ratio, MPR). We created a binary variable of adherence (MPR≥80%). We performed multivariable logistic regressions to assess racial differences for the odds of AET adherence and Cox proportional hazard models to determine the risk of mortality adjusting for potential confounding variables of SES, comorbidities, tumor prognostic factors, and other cancer treatment. RESULTS: Of the 1,497 women with breast cancer who initiated AET, 56.9%, 42.3%, and 33.3% were adherent for 1, 3, and 5-years, respectively. Hispanics compared to non-Hispanic whites did differ in the proportion that were adherent to 5-years of AET. In the adjusted analysis for long-term adherence to AET, Hispanics did not have a significantly increased risk of death compared to non-Hispanic white patients (HR: 1.13, 95% CI: 0.58-2.21). However, black compared to non-Hispanic white patients had significantly lower odds of three-year adherence (OR: 0.45, 95% CI: 0.28-0.73). After controlling for 5-year adherence to AET, the risk of death for black compared to non-Hispanic white patients was 12% lower (HR: 1.90; 95% CI: 1.03-3.51) and in the fully adjusted model, the disparity was reduced and no longer significant (OR: 1.86, 95% CI: 0.94-3.66). CONCLUSIONS: Long-term adherence in the Medicaid population is suboptimal and racial/ethnic differences in AET adherence may partially explain disparities in mortality. This study underscores the critical need to ensure long-term adherence to AET for all racial/ethnic groups to decrease disparities in mortality.

Utilization of perioperative systemic chemotherapy in upper tract urothelial carcinoma.

INTRODUCTION: Evidence for the use of perioperative chemotherapy (PC) in upper tract urothelial carcinoma (UTUC) is largely derived from level I evidence for invasive urothelial carcinoma of the bladder (UCB). There has been an increase in PC for urothelial carcinoma of the bladder, as it has disseminated into clinical practice. Therefore, we sought to not only analyze trends in the utilization of PC in UTUC, but also assess factors associated with its use in a large cancer registry database. METHODS: The National Cancer Database was queried for patients with UTUC who underwent extirpative surgery from 2004 to 2013. Predictors of receiving PC were identified using univariate and multivariate logistic regression. Temporal trends in the utilization of PC were also analyzed using a general analysis of variance linear model. RESULTS: From 2004 to 2013, there was significant increase in PC for UTUC from 9.6% to 13.8% (P = 0.0003). Neoadjuvant chemotherapy increased from 0.7% to 2.1% (P = 0.0018), whereas adjuvant chemotherapy remained relatively stable at 11.3%. Significant predictors of receiving PC on multivariate analysis were private insurance, ureter as the primary site, poorly differentiated and undifferentiated grade, lymphovascular invasion, positive margins, clinical T3 or T4 disease, nodal metastasis, and reporting from an academic research program. Patients who were≥70 years old,>50 miles to treatment center, had tumor in the kidney, or had an increased Charlson-Deyo Score were significantly less likely to receive PC. CONCLUSIONS: Over the time period studied, there has been an increase in the use of PC, primarily from increased administration of neoadjuvant chemotherapy. Its use is mostly associated with advanced pathologic characteristics. The study also highlights key demographic and socioeconomic differences that can help identify barriers to receiving PC and aid in making improvements in delivery of health care to patients with UTUC.

Improving survival and local control in rectal cancer in Catalonia (Spain) in the context of centralisation: A full cycle audit assessment.

BACKGROUND: Rectal cancer surgery in Catalonia has been involved in a process of centralisation. We assessed the impact of this health policy strategy on quality of care and clinical results. METHODS: We compared patterns of care and clinical outcomes of all rectal cancer patients receiving radical surgery for the first time in public hospitals in two time periods, before (2005 and 2007) and after (2011-2012) centralisation, analysing indicators of care quality according to the regional clinical practice guidelines. Clinical outcomes at two years were also assessed. RESULTS: A total of 3780 patients were included. From 2005 to 2012, the proportion of patients treated surgically for the first time in centres whose annual surgical caseload was more than 11 increased from 84.0% to 90.4%. The rate of locoregional recurrence at two years fell from 4.5 to 3.06/100 person-years (p = 0.005). The crude mortality rate at three months, one and two years was reduced by 55%, 40% and 34% (p < 0.001). CONCLUSION: Improvements in quality of care might be associated with the centralisation of surgery and with the selective focus effect derived from the process of auditing. Our results support the continuation of clinical auditing and surveillance of authorised centres.

Trends in the treatment of uterine leiomyosarcoma in the Medicare population.

OBJECTIVE: Uterine leiomyosarcoma (LMS) is a relatively rare malignancy that is associated with a poor prognosis. The rarity of LMS has led to a lack of consensus regarding appropriate treatment. The goal of this study was to identify the role that chemotherapy and radiotherapy have played in the treatment of uterine LMS in the United States as well as the effectiveness of adjuvant treatment. MATERIALS/METHODS: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare database to gather information on uterine LMS patients older than the age of 66 years diagnosed between 1992 and 2009. Basic demographic and clinical characteristics were collected. A logistic regression model analysis was performed to determine predictors of treatment. Cox proportional hazards models were used to identify clinical parameters and treatment strategies associated with survival differences. RESULTS: Our final study group included 230 patients. We found that the rate of use of chemotherapy and radiotherapy in the treatment of patients with uterine LMS increased over the period investigated. However, we identified no significant survival advantage associated with either mode of therapy. The strongest predictor of survival was stage at diagnosis. The logistic regression model analysis revealed that age at diagnosis, treatment year, stage, and underlying health status were all independent predictors of chemotherapy. Age at diagnosis was also a predictor of radiation therapy. CONCLUSIONS: The increasing rates of chemotherapy and radiotherapy use in this population seem to be unfounded given the lack of survival benefit. Further investigation into alternative treatment regimens is merited. The prognostic significance of stage at diagnosis indicates the importance of improving early detection of uterine LMS.

Trends in the use of perioperative chemotherapy for localized and locally advanced muscle-invasive bladder cancer: a sign of changing tides.

BACKGROUND: Despite the documented survival benefit conferred by neoadjuvant (NAC) and adjuvant chemotherapy (AC), there has been a slow adoption of guideline recommendations for the use of perioperative chemotherapy (POC) in patients with muscle-invasive bladder cancer (MIBC). OBJECTIVE: To evaluate temporal trends in POC utilization and identify factors influencing POC delivery in a representative cohort of patients with MIBC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study identifying factors associated with receipt of POC and evaluating temporal changes in NAC and AC utilization. We included patients from the National Cancer Data Base (NCDB) with no prior malignancy who ultimately underwent radical cystectomy for ≥ cT2/cN0/cM0 MIBC between 2006 and 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships between demographic and hospital factors and the likelihood of receiving POC were evaluated using Pearson chi-square and Wilcoxon rank-sum tests, and multivariable logistic regression. Temporal changes in NAC and AC use were detected using a linear test of trend. RESULTS AND LIMITATIONS: A total of 5692 patients met our inclusion criteria. POC use increased from 29.5% in 2006 to 39.8% in 2010 (p < 0.001). NAC use increased from 10.1% in 2006 to 20.8% in 2010 (p = 0.005); AC remained stable between 18.1% and 21.3% (p = 0.68). Multivariable modeling revealed advanced age, increasing comorbidity, lack of insurance, increased travel distance, geographic location outside the northeastern United States, and lower income as negatively associated with POC receipt (all p < 0.05). Limitations include retrospective design and potential sampling bias, excluding patients treated at non-NCDB facilities. CONCLUSIONS: POC use for MIBC increased from 2006 to 2010, with this increase disproportionately due to rising NAC utilization. Nonetheless, there is persistent variation in the likelihood of receiving POC secondary to nonclinical factors. PATIENT SUMMARY: When retrospectively analyzing a representative cohort of patients undergoing radical cystectomy for muscle-invasive bladder cancer between 2006 and 2010, we noted that preoperative chemotherapy rates increased steadily while use of chemotherapy after surgery remained stable. Factors related to access to care significantly influenced receipt of chemotherapy.

Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients - a large population-based study from 1990 to 2008.

BACKGROUND: Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. METHODS: All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. RESULTS: A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92-0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00-1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97-0.99; p < 0.001). CONCLUSIONS: The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups.

Predictors of IMRT and conformal radiotherapy use in head and neck squamous cell carcinoma: a SEER-Medicare analysis.

PURPOSE: The extent to which new techniques for the delivery of radiotherapy for head and neck squamous cell carcinoma (HNSCC) have diffused into clinical practice is unclear, including the use of 3-dimensional conformal RT (3D-RT) and intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 2,495 Medicare patients with Stage I-IVB HNSCC diagnosed at age 65 years or older between 2000 and 2005 and treated with either definitive (80%) or adjuvant (20%) radiotherapy. Our primary aim was to analyze the trends and predictors of IMRT use over this time, and the secondary aim was a similar description of the trends and predictors of conformal radiotherapy (CRT) use, defined as treatment with either 3D-RT or IMRT. RESULTS: Three hundred sixty-four (15%) patients were treated with IMRT, and 1,190 patients (48%) were treated with 3D-RT. Claims for IMRT and CRT rose from 0% to 33% and 39% to 86%, respectively, between 2000 and 2005. On multivariable analysis, IMRT use was associated with SEER region (West 18%; Northeast 11%; South 12%; Midwest 13%), advanced stage (advanced, 21%; early, 9%), non-larynx site (non-larynx, 23%; larynx, 7%), higher median census tract income (highest vs. lowest quartile, 18% vs. 10%), treatment year (2003-2005, 31%; 2000-2002, 6%), use of chemotherapy (26% with; 9% without), and higher radiation oncologist treatment volume (highest vs. lowest tertile, 23% vs. 8%). With CRT as the outcome, only SEER region, treatment year, use of chemotherapy, and increasing radiation oncologist HNSCC volume were significant on multivariable analysis. CONCLUSIONS: The use of IMRT and CRT by Medicare beneficiaries with HNSCC rose significantly between 2000 and 2005 and was associated with both clinical and non-clinical factors, with treatment era and radiation oncologist HNSCC treatment volume serving as the strongest predictors of IMRT use.

Lacosamide: an adjunctive agent for partial-onset seizures and potential therapy for neuropathic pain.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of lacosamide, a new agent for use as adjunctive treatment in partial-onset seizures and a potential agent for treatment of neuropathic pain. DATA SOURCES: A MEDLINE search (1966-July 2009) was conducted using the key words lacosamide, harkoseride, SPM-927, ADD-234037, epilepsy, anticonvulsant, and neuropathic pain. Bibliographies of all articles retrieved were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing lacosamide for the adjunctive treatment of partial-onset seizures and for treatment of neuropathic pain were reviewed. DATA SYNTHESIS: Lacosamide is a functionalized amino acid molecule that selectively enhances the slow inactivation of voltage-gated sodium channels and interacts with the collapsin-response mediator protein-2. With its bioavailability of approximately 100%, minimal protein binding, and few drug-drug interactions, lacosamide has a favorable pharmacokinetic profile. Recent data suggest that lacosamide may have a role as adjunctive treatment of partial-onset seizures. Open-label studies showed a 14-47% reduction in seizure frequency, while placebo-controlled trials demonstrated a 26-40% reduction in seizure frequency. The 50% responder rates ranged from 32.7% to 41.2% with varying doses of lacosamide. Although lacosamide use is not approved by the Food and Drug Administration for treatment of neuropathic pain, studies demonstrated reductions of 2.01-3.60 in pain scale scores. The most common adverse effects, occurring in greater than 10% of subjects in the clinical trials, include arthralgia, ataxia, blurred vision, diplopia, dizziness, fatigue, headache, injection site pain (only in intravenous studies), nausea, tremor, upper respiratory tract infection, and vomiting. CONCLUSIONS: Lacosamide is an effective agent for adjunctive treatment of refractory partial-onset seizures. Its exact role in the treatment of neuropathic pain needs to be determined.

Quality of life assessment in the International Breast Cancer Study Group: past, present, and future.

UNLABELLED: The past: Since 1986, the IBCSG has been accruing a comprehensive longitudinal health-related quality of life (QL) database in addition to biomedical data of patients with early breast cancer who are receiving or have received adjuvant treatment. Our aim is to establish QL as a complementary outcome in randomized clinical trials and to gain new insight in biopsychosocial interactions. In regard to methodology, the IBCSG has made major contributions to the field through the development of global indicators, cross-cultural validation, impact of timing of assessments and working on practical and statistical issues relating to missing data. The present: In two large-scale clinical trials (IBCSG VI and VII) adjuvant chemotherapy (CMF) had a measurable effect on health-related QL, but contrary to expectations this effect was transient and minor compared with the effect of patients' adjustment and coping after diagnosis and surgery. THE FUTURE: In addition to the assessment of health-related QL, the IBCSG is currently developing and applying a global indicator for a patient-derived adapted utility concept in order to better assess the cost-benefit ratio of adjuvant treatment. However, the real challenge for the immediate future is the question how patients' adjustment can be fostered within primary care.