Follicular lymphoma treatment patterns between 2000 and 2014: a SEER-Medicare analysis of elderly patients.

Aim: Characterize follicular lymphoma (FL) treatment patterns among elderly patients using a dataset with longer follow-up time. Materials & methods: Using the linked Surveillance, Epidemiology and End Results-Medicare data, we identified patients diagnosed with FL between 2000 and 2013 with claims data until 2014. We investigated the treatments received and assigned them to lines of treatment. Results: We identified 10,238 elderly patients. Over a 4.7-year median follow-up, 78% of the patients received at least first-line treatment. Fewer individuals received second-line (47%) and third-line (30%) treatments. RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), RCVP (rituximab, cyclophosphamide, vincristine and prednisolone) and rituximab monotherapy were the most common treatment regimens. Conclusion: One in five elderly patients did not receive FL-directed therapy. The most common treatment regimens were limited to RCHOP, RCVP and rituximab monotherapy.

Modification of existing patient-reported outcome measures: qualitative development of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome (PRO) measure of symptom burden, the combined impact of disease-related and treatment-related symptoms on functioning. Validated PRO measures may require modification for use in specific study populations. We sought to modify the MDASI for patients with MPM and create a fit-for-purpose symptom-burden measure for use in a clinical trial, according to US Food and Drug Administration guidance on PRO utilization to support labeling claims. METHODS: A literature review for MPM symptoms was conducted. Patients with MPM were qualitatively interviewed about experiences of disease and treatment. Descriptive analysis identified symptoms and interference with functioning to define MPM-related symptom burden. An expert panel rated the relevance of identified symptoms to patients with MPM. Patients who received the investigational drug in a previous Phase I study were interviewed for drug-specific symptoms. RESULTS: Literature review and interviews of 20 patients identified 31 MPM-related symptoms. A conceptual model of MPM-related symptom burden was developed. After expert-panel relevance review, five MPM-specific items and the 13 core MDASI symptoms met criteria for inclusion in a provisional MDASI-MPM for psychometric testing. Interviews with six patients identified six drug-specific symptoms; three were mentioned by multiple patients. Of these three, one was not in the core MDASI. CONCLUSIONS: The MDASI-MPM has established content validity and, with the addition of one symptom item, is ready for psychometric testing as fit-for-purpose for a clinical trial of an investigational agent.

The Hand-Foot Skin Reaction and Quality of Life Questionnaire: An Assessment Tool for Oncology.

BACKGROUND: Skin toxicity (hand-foot syndrome/hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice, with potentially large impacts on health-related quality of life (HRQL). MATERIALS AND METHODS: A patient-reported questionnaire, the hand-foot skin reaction and quality of life (HF-QoL) questionnaire was developed to measure the HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL questionnaire was tested in a randomized trial of capecitabine with sorafenib/placebo in 223 patients with locally advanced/metastatic breast cancer. Other measures completed included patient ratings of condition severity, the Functional Assessment of Cancer Therapy-Breast cancer (FACT-B), and the clinician-rated National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0, hand-foot skin reaction grade. The psychometric properties of the HF-QoL tested included structural validity, internal consistency, construct validity, discriminant validity, and responsiveness. Finally, the minimal clinically important difference (MCID) was estimated. RESULTS: The HF-QoL instrument comprises a 20-item symptom scale and an 18-item daily activity scale. Each scale demonstrated excellent measurement properties and discriminated between NCI-CTCAE grade and patient-rated condition severity with large effect sizes. The daily activity scale had excellent internal consistency and correlated with the FACT-B and HF-QoL symptom scores. Both HF-QoL scale scores increased linearly with increasing patient-rated condition severity. The MCIDs were estimated as 5 units for daily activities and 8 units for symptoms mean scores. CONCLUSION: The HF-QoL was sensitive to symptoms and HRQL issues associated with HFS/R among participants treated with capecitabine with and without sorafenib. The HF-QoL appears suitable for assessing the HRQL impairment associated with HFS/R to cancer therapies. IMPLICATIONS FOR PRACTICE: Skin toxicity related to anticancer therapies is a significant issue in oncology practice. Several newer agents, as well as older therapies, are associated with the skin toxicity known as hand-foot skin reaction (HFSR) or hand-foot syndrome (HFS). This study describes the development and validation of a brief, patient-reported questionnaire (the hand-foot skin reaction and quality of life questionnaire) supporting its suitability for use in clinical research to aid in early recognition of symptoms, to evaluate the effectiveness of agents for HFS/R treatment within clinical trials, and to evaluate the impact of these treatments on HFS/R-associated patients' health-related quality of life.

Developing a fit-for-purpose composite symptom score as a symptom burden endpoint for clinical trials in patients with malignant pleural mesothelioma.

We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma (0.79-0.87) at each co-administration of the scales. The CSS also had good sensitivity to worsening disease and global quality-of-life ratings. The MDASI-MPM CSS can be used as an outcome in MPM clinical trials, including in responder analyses and at the individual patient level. It is brief enough to administer frequently, including electronically, to better capture symptom trajectories during and after a trial and in clinical practice. As a single score, the CSS addresses multiplicity issues that can arise when several symptoms increase due to worsening disease. Our process can be adapted to produce a CSS for other advanced-cancer trials.

Survival benefit associated with treating follicular lymphoma in patients 80 years or older.

OBJECTIVES: To evaluate the overall survival benefit associated with follicular lymphoma (FL)-directed therapy among patients diagnosed with FL at 80+ years. PATIENTS AND METHODS: This retrospective cohort study utilized the linked Surveillance, Epidemiology and End Results-Medicare dataset to identify patients 80+ years, diagnosed with FL between 2000 and 2013. We identified FL-directed treatments based on published guidelines. We utilized a propensity-score matched sample to compare treated and untreated groups who had similar observed characteristics. We reported the median overall survival time and the 3-year restricted mean survival time (RMST) of the study groups as well as the hazard ratio (HR) of death associated with treatment receipt. RESULTS: We identified 3705 older patients with FL (mean [SD] age, 84 [3.6] years). Over a median follow-up of 2.9 years, 68% of the sample received FL-directed therapy and the most common regimen was rituximab monotherapy (N = 768, 21%). The matched sample included 2306 patients. The median overall survival for the treated group was 4.31 years (95% confidence interval [CI], 4.00-4.61) compared to 2.86 years (95% CI, 2.59-3.16) for the untreated group. The 3-year RMST for the treated group was 2.36 years (95% CI, 2.30-2.41), while it was 2.05 years (95% CI, 1.98-2.11) for the untreated group. Treatment was associated with a 23% reduction in the hazards of death (HR: 0.77, 95% CI: 0.70-0.85; p < .001). CONCLUSION: FL-directed therapy was associated with improved survival among patients diagnosed with FL at 80+ years. These findings can support treatment decision-making for individuals diagnosed with FL at older ages.

Costs associated with follicular lymphoma among individuals diagnosed with non-Hodgkin lymphoma: a longitudinal analysis using SEER-Medicare data.

There is limited information on the cost burden associated with follicular lymphoma (FL) and how it compares to other non-Hodgkin lymphoma (NHL) subtypes. We examined the direct medical costs associated with FL and estimated the incremental 3-year cost of FL compared to other NHL subtypes. Using the linked Surveillance, Epidemiology and End Results-Medicare dataset, we identified 16,691 NHL patients aged 66 years or older who were diagnosed with NHL between 2007 and 2013. The mean 3-year cost among the full NHL sample was $120,120 (standard error (SE) 839). The mean 3-year cost per patient was $114,443 (SE 1738) for FL and $121,402 (SE 950) for non-FL subtypes. The incremental 3-year cost of FL compared to non-FL was US$-5458 (95% confidence interval: US$-9325 to US$-1590). Longitudinally, FL was less costly than other NHL subtypes in the first year only, and became more expensive in the second and third years.

Search for evidence-based approaches for the prevention and palliation of hand-foot skin reaction (HFSR) caused by the multikinase inhibitors (MKIs).

BACKGROUND: The anticancer multikinase inhibitors (MKIs) are associated with cutaneous adverse events, including hand-foot skin reaction (HFSR), a condition affecting 20%-40% of patients. Symptoms are usually mild, but can evolve into a painful condition that limits function and impacts quality of life (QoL), resulting in shortened cancer treatment duration or intensity. The goal of this study was to systematically review the literature on the prevention and palliation of MKI-associated HFSR, to identify areas for further clinical study, and to provide a foundation for evidence-based guidelines for HFSR management. METHODS: Systematic searches of the National Library of Medicine's PubMed database, Cochrane Reviews, BIOSIS, CancerLit, and the American Society of Clinical Oncology website were conducted using search terms for cutaneous toxicities associated with chemotherapeutic agents. Articles were categorized (C) based on type of agent and cutaneous reaction as: C1 (MKI and HFSR); C2 (MKI and other cutaneous toxicity); C3 (other antineoplastic agents and HFSR); and C4, other. RESULTS: Of the 2,069 abstracts screened, 350 (17%) met the criteria for C1-C4, with 56 (16%) coded as C1 with details of HFSR histology, pathogenesis, clinical outcome, QoL impact, and/or prevention and treatment approaches in MKI-treated patients. No randomized, controlled trials (RCTs) on prevention/palliation of HFSR were identified. Anecdotal evidence or expert opinion advocated protective measures, preventive and therapeutic skin care, systemic analgesics for pain, vitamin B(6), and MKI dose modification. CONCLUSION: No articles containing evidence from RCTs on preventive/palliative approaches to MKI-associated HFSR have been published. Systematic study of optimal treatment strategies for HFSR is needed to advance development of evidence-based treatment guidelines.

Evaluation of the psychometric properties and minimally important difference of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

BACKGROUND: Symptom assessment requires psychometrically validated questionnaires that are easy to use, relevant to the disease, and quick to administer. The MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM) was adapted from the general (core) MDASI to assess the severity of cancer-related and treatment-related symptoms specific to patients with this condition. The MDASI-MPM includes the 13 core MDASI symptoms, which are experienced by most cancer patients, and 6 MPM-specific items developed via qualitative interviewing, a method favored by the US Food and Drug Administration for instrument item generation and development. Qualitative interviewing that summarizes the item generation and development for the MDASI-MPM is detailed in a separate report. The psychometric study reported here was the next step in developing the validation dossier for the MDASI-MPM. RESULTS: In this secondary analysis of data from a Phase II trial, 248 patients provided MDASI-MPM data at multiple timepoints during therapy. Over time, fatigue, pain, shortness of breath, feeling of malaise, and muscle weakness were consistently the worst symptoms reported; symptoms interfered most with work and general activity and least with relations with others. Cronbach coefficient alpha values for all MDASI-MPM subscales were at least 0.88 at baseline and 0.91 during treatment, indicating good internal consistency reliability. Intraclass correlations of at least 0.86 for all MDASI-MPM subscales administered a cycle apart (n = 82) were indicative of good test-retest reliability. Correlations between MDASI-MPM subscales and LCSS-Meso scores were at least 0.70 (P < 0.001 for all comparisons). Patients with good performance status had significantly lower scores than did patients with poor performance status (all P < 0.05), supporting evidence for known-group validity and sensitivity. Effect-size differences were 0.69 and higher, indicating medium-to-large effects. The minimally important difference in the MDASI-MPM subscales ranged from 1.0 to 1.5 points on a 0-10 scale. CONCLUSIONS: Symptoms specific to a particular cancer, treatment method, or treatment site can be added to the core MDASI to create a tailored, "fit for purpose" instrument. We found the MDASI-MPM to be a valid, reliable, and responsive (sensitive) instrument for assessing the severity of symptoms of patients with MPM and their interference in patients' daily functioning.

Moxifloxacin versus levofloxacin for treatment of acute rhinosinusitis: a retrospective database analysis of treatment duration, outcomes, and charges.

OBJECTIVE: Antibiotics are clinically indicated for acute bacterial rhinosinusitis, but they may be prescribed inappropriately. This retrospective study examined how labeled recommendations for duration of moxifloxacin and levofloxacin treatment of acute bacterial rhinosinusitis compare with real-world practice, and compared the failure and recurrence rates, and associated charges. METHODS AND MAIN OUTCOME MEASURES: The PharMetrics Patient-Centric claims database was searched over a 3-year period for episodes of acute rhinosinusitis treated within 5 days with moxifloxacin or levofloxacin. The duration of antibiotic treatment prescribed was compared with the labeled recommendation. Failure rates (a second antibiotic claim to treat acute rhinosinusitis within 30 days of the first claim), recurrence rates (subsequent antibiotic claims to treat any rhinosinusitis more than 30 days after the original or second [in the case of failure] claim), and treatment charges from the perspective of the payer (health insurer) were also compared using multivariate analysis. RESULTS: The initial duration prescribed of moxifloxacin was shorter than for levofloxacin (-1.65 days, p < 0.0001), reflecting the shorter labeled recommendation (10 days versus 10-14 days). The durations of monotherapy (-2.06 days, p < 0.0001) and of all antibiotic treatment (-1.97 days, p < 0.0001) were also significantly shorter for episodes treated initially with moxifloxacin. The odds ratio for treatment failure (0.718; 95% confidence interval = 0.598-0.863; p = 0.0004) and the hazard ratio for recurrence (0.652; p = 0.0005) were both significantly lower for moxifloxacin than for levofloxacin, and resulted in lower total treatment charges (-$37.94 +/- 13.65; p = 0.0055). CONCLUSION: The shorter treatment durations seen for moxifloxacin in this database of real-world care reflect the label-recommended duration for acute rhinosinusitis. Despite this shorter duration of therapy, moxifloxacin resulted in better outcomes than levofloxacin in terms of the risk of treatment failure and recurrence. In addition, the total charges were lower for patients treated with moxifloxacin.

Fluoroquinolone therapy for uncomplicated skin and skin structure infections : a retrospective database comparison of treatment duration, failures and charges.

OBJECTIVE: Uncomplicated skin and skin structure infections (uSSSIs) are highly prevalent and costly. With the rising prevalence of bacterial resistance to older antibacterials, there has been an increase in the use of fluoroquinolones for the treatment of uSSSIs creating the need for comparative information. The objective of this study was to compare, under real-world conditions, the treatment duration, failure rates and treatment charges associated with initiation of outpatient treatment for uSSSIs with moxifloxacin versus levofloxacin. METHODS: This retrospective study was conducted using claims data (April 1999 through March 2002) from the PharMetrics Patient-Centric Database. A cohort was created of patients who had treatment for a uSSSI that was initiated with either moxifloxacin or levofloxacin. The endpoints evaluated were: treatment duration, treatment failure and total charges. Logistic and ordinary least-squares regression analyses were used to test for differences among treatment groups whilst controlling for demographic and clinical characteristics. RESULTS: 506 patients were identified, representing 517 uSSSI treatment episodes. The mean durations of monotherapy and all antibacterial prescription therapy were significantly shorter for the moxifloxacin than the levofloxacin group (differences of 1.97 days [p = 0.015] and 1.60 days [p = 0.036], respectively). The original prescription duration, treatment failure rate and treatment charges were lower for the moxifloxacin group than the levofloxacin group, but differences were not statistically significant (p = 0.241, 0.395 and 0.199, respectively). CONCLUSION: In general, patients who initiated therapy for a uSSSI with moxifloxacin had a shorter duration of antibacterial therapy than those who initiated treatment with levofloxacin, with comparable treatment failure and cost outcomes. When a fluoroquinolone is required for the treatment of a uSSSI, moxi- floxacin (which is approved for 7-day therapy) provides comparable outcomes to levofloxacin under real-world conditions.

Psychometric evaluation of the Sinonasal Outcome Test-16 and activity impairment assessment in acute bacterial sinusitis.

OBJECTIVE: To validate the Sinonasal Outcome Test-16 and Activity Impairment Assessment in patients with acute bacterial sinusitis. STUDY DESIGN: Data were used from a phase III clinical trial designed to evaluate the efficacy and safety of moxifloxacin 400 mg once daily for 5 consecutive days in the treatment of acute bacterial sinusitis. The psychometric properties and factor structure of the 2 measures were assessed. SETTING: Participants were given the measures to self-complete using either a telephone voice response system or a paper-and-pencil format. SUBJECTS AND METHODS: Three hundred seventy-four patients with acute bacterial sinusitis were used in the analysis. Patients received either a placebo or 400 mg moxifloxacin once daily. Patients were then reviewed at test of cure and follow-up. All analyses were conducted on a combined sample of placebo and active treatment patients. RESULTS: The Sinonasal Outcome Test-16 was associated with minimal missing data at baseline but a higher proportion by test of cure. There was no evidence of floor or ceiling effects and no significant skew. The Activity Impairment Assessment also had low missing data at baseline and no obvious floor or ceiling effects, but the data were not normally distributed. Both measures had good internal consistency. Convergent and divergent validity as well as sensitivity and the minimally important difference are also reported. CONCLUSION: The measures both have good psychometric properties and are suitable for use with patients with acute bacterial sinusitis. Both instruments are sensitive. The minimal important difference estimates for the Sinonasal Outcome Test-16 are quite high but are similar to estimates reported previously.

Economic burden of uncomplicated urinary tract infections: direct, indirect and intangible costs.

A better understanding of how antimicrobial therapies affect the total cost of lower uncomplicated urinary tract infection, including direct (e.g., doctor visits), indirect (e.g., productivity) and intangible (e.g., pain) costs would facilitate selection of an optimal therapeutic approach. The results of this literature review indicate that the there is a considerable societal burden from uncomplicated urinary tract infection, with approximately USD 1 billion in indirect and over USD 600 million in direct costs in 1995. However, no single identified study incorporated all three cost components, there are gaps in the knowledge concerning the current extent of these costs, and there are no comparative assessments based on total cost. Research is needed to provide current insights on the burden of uncomplicated urinary tract infection in terms of direct, indirect and intangible costs.

Educating patients with uncomplicated UTIs: the effect of an educational brochure on patient knowledge.

We evaluated the effectiveness of an educational brochure designed to increase patient knowledge about uncomplicated urinary tract infections (uUTIs). Participants were adult female outpatients (average age, 45 years) with a clinical diagnosis of uUTI. The 1,972 study sites (primary care physicians' offices and urology clinics) were randomized to receive patient enrollment kits with or without educational brochures. Pre- and post-treatment uUTI knowledge was assessed by questionnaire in 6,922 women who either received an educational brochure (n=3,431) or did not (n=3,491). Among those who received a brochure, the mean uUTI knowledge score increased by 0.59 from pre- to post-test. In contrast, the mean score of those who did not receive a brochure increased by only 0.23. The brochure group had a 0.37 improvement in mean scores compared with the non-brochure group, a statistically significant difference (P less than 0.0001). Affected patients who received the brochure showed greater improvement in a test on UTI-related knowledge compared with patients who did not.

A 'gap' between physician and patient assessment of symptom severity in acute cystitis?: a multicenter trial of women treated with extended-release ciprofloxacin.

The current trial assessed differences in physician and patient symptom-severity perceptions in ambulatory outpatient females with uncomplicated urinary tract infections (uUTIs). We also investigated the efficacy and safety profile of once-daily ciprofloxacin in a 500-mg PO extended-release formulation for 3 days to treat acute cystitis. This prospective, open-label, multicenter (1,972 sites), phase 4 clinical trial enrolled 7,614 adult women with a clinical diagnosis of an acute uUTI. After assessing the patient's cystitis symptoms, physicians rated each cystitis-related symptom on a 4-point severity scale. Patients independently completed a pretreatment survey including a self-assessment of these same symptoms. Clinical outcomes were assessed at the end-of-study visit (2 to 7 days post-therapy). Exact agreement on symptom severity between physician and patient was between 54% and 57% for symptoms. The discrepancies between assessments were significant in the marginal homogeneity tests (P less than 0.00001). Clinical cure following this regimen was 91.3% of efficacy-valid women. Women who had 2 or more UTI episodes in the previous 12 months tended to have lower rates of clinical cure than those who had 1 or no episodes in that time.