Cost savings and enhanced hospice enrollment with a home-based palliative care program implemented as a hospice-private payer partnership.

BACKGROUND: In the United States, 5% of the population is responsible for nearly half of all health care expenditures, with a large concentration of spending driven by individuals with expensive chronic conditions in their last year of life. Outpatient palliative care under the Medicare Hospice Benefit excludes a large proportion of the chronically ill and there is widespread recognition that innovative strategies must be developed to meet the needs of the seriously ill while reducing costs. OBJECTIVE: This study aimed to evaluate the impact of a home-based palliative care program, implemented through a hospice-private payer partnership, on health care costs and utilization. METHODS: This was a prospective, observational database study where insurance enrollment and claims data were analyzed. The study population consisted of Home Connections (HC) program patients enrolled between January 1, 2010 and December 31, 2012 who subsequently expired (n=149) and who were also Independent Health members. A control group (n=537) was derived using propensity-score matching. The primary outcome variable was overall costs within the last year of life. Costs were also examined at six months, three months, one month, and two weeks. Inpatient, outpatient, ancillary, professional, and pharmacy costs were compared between the two groups. Medical service utilization and hospice enrollment and length of stay were also evaluated. RESULTS: Cost savings were apparent in the last three months of life­$6,804 per member per month (PMPM) cost for palliative care participants versus $10,712 for usual care. During the last two weeks of life, total allowed PMPM was $6,674 versus $13,846 for usual care. Enhanced hospice entry (70% versus 25%) and longer length of stay in hospice (median 34 versus 9 days) were observed. CONCLUSIONS: Palliative care programs partnered with community hospice providers may achieve cost savings while helping provide care across the continuum.

Outcome of adolescents and young adults with acute myeloid leukemia treated on COG trials compared to CALGB and SWOG trials.

BACKGROUND: A retrospective meta-analysis of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) was performed to determine if differences in outcome exist following treatment on pediatric versus adult oncology treatment regimens. METHODS: Outcomes were compared of 517 AYAs with AML aged 16 to 21 years who were treated on Children's Oncology Group (COG), Cancer and Leukemia Group B (CALGB), and Southwest Oncology Group (SWOG) frontline AML trials from 1986 to 2008. RESULTS: There was a significant age difference between AYA cohorts in the COG, CALGB, and SWOG trials (median, 17.2 versus 20.1 versus 19.8 years, P < .001). The 10-year event-free survival of the COG cohort was superior to the combined adult cohorts (38% ± 6% versus 23% ± 6%, log-rank P = .006) as was overall survival (45% ± 6% versus 34% ± 7%), with a 10-year estimate comparison of P = .026. However, the younger age of the COG cohort is confounding, with all patients aged 16 to 18 years doing better than those aged 19 to 21 years. Although the 10-year relapse rate was lower for the COG patients (29% ± 6% versus 57% ± 8%, Gray's P < .001), this was offset by a higher postremission treatment-related mortality of 26% ± 6% versus 12% ± 6% (Gray's P < .001). Significant improvements in 10-year event-free survival and overall survival were observed for the entire cohort in later studies. CONCLUSIONS: Patients treated on pediatric trials had better outcomes than those treated on adult trials, but age is a major confounding variable, making it difficult to compare outcomes by cooperative group.

Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101.

PURPOSE: To determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Patients (n = 102) received fludarabine 25 mg/m(2) intravenously days 1 to 5 and rituximab 50 mg/m(2) day 1, 325 mg/m(2) day 3, and 375 mg/m(2) day 5 of cycle 1 and then 375 mg/m(2) day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks. RESULTS: Overall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab. CONCLUSION: Alemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.

Cancer surveillance behaviors and psychosocial factors among long-term survivors of breast cancer. Cancer and Leukemia Group B 79804.

BACKGROUND: Little is known about cancer surveillance (mammography, clinical breast examination, and pelvic examination) behaviors in long-term (9-16 years) breast cancer survivors. This report describes the relation of these behaviors to demographic and clinical characteristics, psychological symptoms, body satisfaction, and social support. METHODS: Survivors who had participated in Cancer and Leukemia Group B treatment Trial 8541 completed a survey that included questions on breast cancer surveillance and pelvic examination, psychological well being, body satisfaction, and social support. RESULTS: The participation rate was 78% and included 245 breast cancer survivors. Survivors (n = 107; 44%) reported completing breast cancer surveillance (mammography and clinical breast examination) and completing pelvic examination (n = 162; 68%) within recommended guidelines. There were no significant associations between breast cancer surveillance and breast cancer anxiety, depression, stressful life events, body satisfaction, social support, or demographic characteristics. Survivors within recommended guidelines for pelvic examinations were younger (P = .05), married (P = .003), had health insurance (P = .004), and had lower depression scores (P = .005) than survivors who underused or overused pelvic examination. In addition, survivors within recommended pelvic examination guidelines had significantly lower levels of breast cancer anxiety (P = .03) compared with survivors who underused pelvic examination. CONCLUSIONS: Many long-term breast cancer survivors were not within recommended cancer surveillance guidelines. Private health insurance was associated with following recommendations for pelvic examinations, although such a relation did not exist for breast cancer surveillance. The results of this study have implications for the development of educational programs to improve cancer surveillance among the growing population of long-term breast cancer survivors.

A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804.

BACKGROUND: Both homoharringtonine (HHT), an alkaloid derivative from the Chinese yew tree that inhibits protein synthesis, and low-dose cytarabine have independent activity in CML and have been used in combination after failure of interferon therapy. PATIENTS AND METHODS: The CALGB performed a phase II trial of HHT (2.5 mg/m(2) per day) plus cytarabine (7.5 mg/m(2) per day), given together via continuous intravenous infusion for 7 days in previously untreated patients with Ph chromosome positive chronic phase CML. HHT/cytarabine cycles were repeated every 28 days if the blood counts were adequate. The primary endpoint was the major cytogenetic response rate after 9 months. RESULTS: Forty of the 44 enrolled patients required reduction in the infusion duration during at least one cycle. Myelosuppression was common; 66% developed neutrophil count <500/microl, but grade 3 infections occurred in only 7%. Thirty-six of 44 patients (82%) achieved a complete hematologic remission; the median duration has not been reached. Only 4 of the 23 patients (17%) having adequate cytogenetic response assessment achieved a major response within nine cycles. CONCLUSIONS: Although HHT/cytarabine was generally well tolerated, the cytogenetic response rate did not exceed the level previously seen in patients with interferon-refractory CML and was not nearly as high as associated with imatinib in newly diagnosed patients.

Feasibility of administering oblimersen (G3139; Genasense) with imatinib mesylate in patients with imatinib resistant chronic myeloid leukemia--Cancer and leukemia group B study 10107.

The CALGB studied the feasibility and effectiveness of adding oblimersen (G3139; Genasense) to imatinib mesylate (IM) in imatinib-resistant chronic phase chronic myeloid leukemia (CML) patients. We hypothesised that IM resistant CML cells are no longer being driven to proliferate by Bcr/Abl activity alone. Instead, the anti-apoptotic protein Bcl-2 would regulate one of the pathways controlling growth and/or viability. Thus, blocking both Bcr/Abl and Bcl-2 simultaneously would result in hematologic and cytogenetic improvement. Oblimersen was administered via continuous intravenous infusion over 10 days every 21 days, along with daily IM. Doses of both drugs were escalated in 3 cohorts; the initial dose of IM was 600 mg/day. Response was defined as a decrease by >30% in the percentage of t(9;22) metaphase cells. Twelve patients had primary and nine had secondary imatinib resistance. Ten patients received 4 mg/kg/day oblimersen/600 mg IM, six patients received 7 mg/kg/day oblimersen/600 mg IM and five patients received 7 mg/kg/day oblimersen/800 mg IM. Only two (9.5%) patients achieved a decrease by >30% in the percentage of t(9;22) metaphase cells. Although the combination of oblimersen and IM is safe and feasible, we did not observe clinical benefit in these patients with imatinib-resistant CML using these doses and schedule.

Long-term outcome of stage I seminoma.

PURPOSE: To report on long-term outcomes among patients with stage I seminoma treated by orchiectomy with or without adjuvant radiation. MATERIALS AND METHODS: A retrospective review of medical records of patients treated between 1974 and 2002 was undertaken to identify factors associated with patient outcomes. RESULTS: With a median follow-up of 7.7 years, 80% (4 of 5) of the surveillance group experienced a disease relapse, while only 3% (2 of 70) in the radiation therapy group had disease relapse. This difference in relapse rates was statistically significant, but there was no significant difference in overall survival between the 2 groups. There was a significant relationship between patient age and disease relapse, whereby all of the relapses were seen in patients younger than 36 years at diagnosis (P = 0.03). Of the total 75 patients, 7 (9%) developed second primary tumors. Six of them (6 of 7) were treated with adjuvant radiation, and 1 patient (1 of 7) was on surveillance. CONCLUSION: In this study, risk of relapse was significantly associated with surveillance and in patients younger than 36 years at diagnosis. These results suggest that surveillance can only be safely adopted for patients who can be followed up closely. We consider adjuvant radiation a very effective choice despite the low risk of associated secondary malignancies.

Arsenic trioxide affects signal transducer and activator of transcription proteins through alteration of protein tyrosine kinase phosphorylation.

PURPOSE: Arsenic trioxide decreases proliferation of acute myeloid leukemia (AML) cells, but its precise mechanism of action is unknown. EXPERIMENTAL DESIGN: We studied the effect of arsenic trioxide on patient samples and the AML cell line HEL, which, like leukemic blasts from 50% of AML cases, has constitutively activated signal transducer and activator of transcription (STAT) proteins. RESULTS: Arsenic trioxide induced mitotic arrest starting at 24 hours and significant cell death at 48 hours. These events were preceded by an arsenic trioxide dose-dependent down-regulation of activated STAT proteins starting at 6 hours. We hypothesized that arsenic trioxide inhibits protein tyrosine kinases (PTK), which, among others, phosphorylate and activate STATs. We therefore studied arsenic trioxide effects on Janus kinases and on three oncogenic PTKs that are known to activate STATs [FLT3, ZNF198/fibroblast growth factor receptor 1 (FGFR1), and BCR/ABL]. Arsenic trioxide reduced STAT3 activation by Janus kinases, altered phosphorylation and electrophoretic mobility of ZNF198/fibroblast growth factor receptor 1, reduced kinase protein level, and decreased STAT3 protein phosphorylation. Arsenic trioxide also reduced the phosphorylation of BCR/ABL and FLT3 with corresponding decreased STAT5 phosphorylation. CONCLUSIONS: These results suggest a selective activity of arsenic trioxide on PTKs and will assist in developing clinical trials in AML.

T-Cell activation by t(9;22) acute lymphoblastic leukemia-derived dendritic-like cells is associated with increased tapasin expression.

Dendritic-like cells from t(9;22) acute lymphoblastic leukemia (ALL) blasts can activate T cells, while the original unmodified leukemic blasts cannot. To determine whether these functional differences were associated with differences in antigen-processing machinery (APM) component expression, we have measured the level of APM component expression in unmodified blasts and ALL-derived dendritic-like cells. Seven t(9;22) ALL patient samples and one cell line were studied for APM component expression utilizing a unique panel of recently developed monoclonal antibodies and a recently developed intracellular staining technique. In addition, the HLA class I antigen cell surface expression was measured. HLA class I antigens were similarly expressed on the unmodified blasts and on the autologous dendritic-like cells. Intracellular HLA class I antigen and tapasin expression (P=0.03 for both) were upregulated in all t(9;22) ALL-derived dendritic-like cells, in comparison to the unmodified blasts. These results provide a potential mechanism for the ability of t(9;22) ALL-derived dendritic-like cells to induce T-cell activation and, suggest that tapasin upregulation may serve as a marker to standardize and monitor the quality of the dendritic-like cells used in immunotherapy.

Misrepresentation of publications among radiation oncology residency applicants.

INTRODUCTION: Authorship misrepresentations have been described for residency and fellowship applications for various medical specialties. This study assessed the prevalence of misrepresented publications in radiation oncology residency applications. MATERIALS AND METHODS: The authors reviewed 117 applications to their residency program for a single 2004 position offered through the National Resident Matching Program. Publications listed on the applications were verified for accuracy, with the results and applicants' demographic information recorded. RESULTS: A total of 49 applicants (42%) claimed authorship of published research citations. The number of published citations averaged 3.6 per applicant (range, 1-23). Of the applicants reporting citations, 22% (11 of 49) listed inaccurate citation information. Overall, 9% of the citations (15 of 174) were considered misrepresentations, with 9% of the total number of applicants (11 of 117) responsible for inaccurate bibliographies. There was a significant relationship of United States Medical Licensing Examination score with publication misrepresentation, in which those with scores of 235 or greater who listed publications were more than 7 times more likely to have inaccurately listed citations (odds ratio, 7.67; 95% confidence interval, 1.12-52.31; P = .04). CONCLUSION: The misrepresentation of bibliographic citations does exist among radiation oncology residency applicants. Using a comprehensive search, the authors found that 22% of those who had listed at least 1 article had misrepresented publications on their applications.

Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival.

Signal transducer and activator of transcription (STAT) proteins are involved in hematopoietic cytokine receptor signaling pathways that regulate cell proliferation, differentiation, and survival. STATs are dysregulated in acute myeloid leukemia (AML); mechanisms of dysregulation include constitutive activation and truncation of the C-terminal transactivation domain; the latter results in a beta isoform that has a trans-dominant negative effect on gene induction mediated by the full-length STAT alpha form. It was hypothesized that constitutive STAT activity might correlate with unfavorable treatment outcome in AML. Pretreatment bone marrow samples from 63 adult patients with AML were analyzed by electrophoretic mobility shift assay for the presence of STAT DNA-binding activity. Isoforms and relative levels of STAT proteins were determined by immunoblotting. Constitutive STAT3 activity was detected in samples from 28 (44%) patients. Pretreatment clinical characteristics, expression of STAT alpha/beta isoforms, and treatment regimens did not differ significantly between patients with and without constitutive STAT3 activity. Disease-free survival (DFS) was significantly shorter in patients with than in patients without constitutive STAT3 activity (median 8.7 vs 20.6 months; P =.01). Overall survival did not differ significantly. The subgroup of patients with constitutive STAT3 activity and the STAT3 beta isoform had the shortest DFS (P =.006) and shorter overall survival (P =.049) than all other patients. Whether adverse treatment outcome is attributable to constitutive STAT activity itself or to a process that leads to constitutive STAT activity remains to be determined. This is the first demonstration of a prognostic significance for STAT proteins in a malignancy.