Search

Decompressive craniectomy is an increasingly implemented intervention for relief of intracranial hypertension refractory to medical therapy. Despite its therapeutic benefit, a myriad of short and long-term complications may arise when the once fixed-volume cranial vault remains decompressed. The authors present a case of recurrent Syndrome of the Trephined in a patient undergoing repeated craniectomy and cranioplasty.A 70-year old male with history significant for smoking and chronic obstructive pulmonary disease presented with frontoparietal subdural hematoma with midline shift following a ground level fall necessitating craniotomy and hematoma evacuation. Three months postoperatively, the patient developed an infection of his craniotomy bone flap necessitating craniectomy without cranioplasty. Six weeks post-craniectomy the patient began demonstrating right sided sensorimotor deficits with word finding difficulties. Alloplastic cranioplasty was performed following resolution of infection, with resolution of neurologic symptoms 6 weeks post cranioplasty. Due to recurrent cranioplasty infections, multiple alloplastic cranioplasties were performed, each with reliable re-demonstration of neurologic symptoms with craniectomy, and subsequent resolution following each cranioplasty. Final cranioplasty was successfully performed using a new alloplastic implant in combination with latissimus muscle flap, with subsequent return of neurologic function.Decompressive craniectomy is a life-saving procedure, but carries many short- and long-term complications, including the Syndrome of the Trephined. Our case is the first published report, to our knowledge, to demonstrate recurrent Syndrome of the Trephined as a complication of craniectomy, with reliable resolution of the syndrome with restoration of the cranial vault.

Decompressive craniectomy is an increasingly implemented intervention for relief of intracranial hypertension refractory to medical therapy. Despite its therapeutic benefit, a myriad of short and long-term complications may arise when the once fixed-volume cranial vault remains decompressed. The authors present a case of recurrent Syndrome of the Trephined in a patient undergoing repeated craniectomy and cranioplasty.A 70-year old male with history significant for smoking and chronic obstructive pulmonary disease presented with frontoparietal subdural hematoma with midline shift following a ground level fall necessitating craniotomy and hematoma evacuation. Three months postoperatively, the patient developed an infection of his craniotomy bone flap necessitating craniectomy without cranioplasty. Six weeks post-craniectomy the patient began demonstrating right sided sensorimotor deficits with word finding difficulties. Alloplastic cranioplasty was performed following resolution of infection, with resolution of neurologic symptoms 6 weeks post cranioplasty. Due to recurrent cranioplasty infections, multiple alloplastic cranioplasties were performed, each with reliable re-demonstration of neurologic symptoms with craniectomy, and subsequent resolution following each cranioplasty. Final cranioplasty was successfully performed using a new alloplastic implant in combination with latissimus muscle flap, with subsequent return of neurologic function.Decompressive craniectomy is a life-saving procedure, but carries many short- and long-term complications, including the Syndrome of the Trephined. Our case is the first published report, to our knowledge, to demonstrate recurrent Syndrome of the Trephined as a complication of craniectomy, with reliable resolution of the syndrome with restoration of the cranial vault.

Background Psoriatic arthritis (PsA) patients may experience disease manifestations across multiple domains and impaired functioning in daily activities at home and work. The phase 3b ACTIVE study is evaluating the efficacy of apremilast (APR) monotherapy in biologic-naive subjects with active PsA who may have had exposure to 1 prior conventional DMARD. Objectives To assess work productivity through Week 104. Methods Subjects were randomised (1:1) to receive APR 30 mg BID or placebo (PBO). Subjects who did not improve by ≥10% in swollen and tender joint counts at Week 16 were eligible for early escape. At Week 24, all remaining PBO subjects were switched to APR. Work productivity and activity impairment were assessed at baseline (BL) and Week 16 using the 6-item, self-administered Work Productivity and Activity Impairment Questionnaire: Psoriatic Arthritis (WPAI:PsA). WPAI:PsA includes 4 subscale scores (Absenteeism, Presenteeism, Work Productivity Loss, and Activity Impairment), each ranging from 0% to 100%; higher scores indicate greater impairment. Work-related subscales were evaluated only among employed subjects, while activity impairment was evaluated among all subjects, regardless of employment. Correlations were examined at Week 16 between WPAI:PsA subscale scores and the SF-36v2 domain scores for Physical Functioning (PF), Bodily Pain (Pain), and Vitality (VIT), as well as associations with ACR20 response. Improvement in work productivity was assessed through Week 104. Results BL characteristics were similar between APR and PBO subjects with WPAI:PsA scores included in this analysis. At Week 16, APR significantly improved work productivity and the ability to carry out daily activities vs PBO, with significantly greater mean improvements observed in the overall Work Productivity Loss (p=0.001) and Activity Impairment (p Results are from an analysis of covariance model, adjusted with BL WPAI: PsA subscale score, BL prednisone use (yes/no), and previous DMARD use (yes/no). LS mean is estimated using the observed margins of the covariates. WPAI: PsA scores were evaluated for subjects with values at both BL and Week 16. Absenteeism, Presenteeism, and Work Productivity Loss were evaluated only among employed subjects. Activity Impairment scores were evaluated among all randomised subjects with scores at BL and Week 16, regardless of employment status. CI=confidence interval; LS=least square. Conclusions In biologic-naive subjects with PsA, APR monotherapy contributed to an overall improvement in work productivity at Week 16, which correlated with SF-36v2 PF, Pain, and VIT scores and was associated with ACR20 response; improvements in WPAI:PsA subscale scores were generally maintained to Week 104. Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, and UCB, E. Davenport: None declared, X. Zhou: None declared, B. Guerette Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, S. Kaura Employee of: Celgene Corporation, P. Nash Grant/research support from: Celgene Corporation

Background: \ud \ud Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting.\ud \ud Methods: \ud \ud The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training—including information provision, joint goal setting, carer training, and task-specific training—that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3–6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707).\ud \ud Findings: \ud \ud Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78–1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80).\ud Interpretation: \ud \ud Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care.\ud \ud Funding: \ud \ud The National Health and Medical Research Council of Australia.

In recent times, the subject of dark matter has engaged the public thanks to reports in popular scientific journals and newspapers. In a first course in physics, we frequently encounter questions regarding reasons for belief in dark matter. Related questions regarding the composition and density of dark matter are also raised. In this article, we address the issue of the density distribution of dark matter.

Background Intravenous zoledronic acid (ZOL) is the standard of care for the prevention of SREs in advanced breast cancer. However, monthly subcutaneous denosumab (Dmab) was recently approved in the US, as an alternative to ZOL based on the results of a large randomized trial which demonstrated a prolongation in median time to first SRE (HR = 0.82, p = 0.01) and a 5.8% (p = 0.01) absolute reduction in SREs in favour of Dmab over the 34 month study period. The challenge for clinicians and payers is how to reconcile the modest benefits of Dmab with the cost, which is approximately twice that of ZOL. NNT represents the number of patients that need to be treated with a new intervention in order to avoid one additional event, and is a widely accepted approach used to make sense of numerical results from clinical trials. In this analysis, the NNT approach was used to assess the incremental benefit of Dmab over ZOL for the prevention of SREs in advanced breast cancer. Methods: The pivotal randomized trial for Dmab vs. ZOL in breast cancer (Stopeck, JCO 2010 & US PI 2010) was reviewed. As an alternative to ZOL, the NNT with Dmab to avoid any SRE at 12 and 34 months (trial end) was determined. NNT by type of SRE was also estimated. These consisted of pathologic fractures, radiation to bone, spinal cord compressions and surgery to bone. The calculated NNT represents the incremental benefit provided by Dmab above and beyond Zometa therapy. Results: To avoid a single SRE after 12 months of treatment of continuous therapy with Dmab, approximately 36 patients need to be treated. To avoid a single fracture and radiation to bone, approximately 39 and 27 patients need to be treated with Dmab over a 34 month period. Dmab was unable to offer any incremental benefit over ZOL in terms of avoiding spinal cord compressions or surgery to bone after 34 months of treatment. Discussion: The NNT approach is a simple and effective method to express the findings in a clinically meaningful way. In this analysis, the incremental benefit of Dmab would only be realized when a minimum of 36 patients are treated for 12 months. For the more severe skeletal-related events, in terms of clinical and economic burden to patients and society, such as spinal cord compression and surgery to bone, Dmab did not offer any incremental benefit over ZOL in terms of SRE avoidance. This marginal incremental benefit needs to be considered alongside the high cost of Dmab. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-14.

Kinematic models are often very useful. The back and forth throw of a ball between two ice skaters may help us appreciate the meson exchange theory of Yukawa. If the skaters throw the balls at each other, they move backward, which is equivalent to a repulsive force between them. On the other hand, if they snatch the ball from each other, the result will be akin to an equivalent attractive force between them. Such illustrative models may help us understand advanced concepts.

Objective The purpose of this study was to determine the role of nitric oxide (NO) in the pathogenesis of mucoid otitis media (OM) in lipopolysaccharide (LPS)-induced OM. Methods OM was induced in chinchillas by injecting S-nitroso-N-acetylpenicillamine (SNAP), LPS, and LPS + SNAP into the superior bullae. Auditory brainstem response thresholds were measured every 24 hours. Samples of middle ear fluid were collected and analyzed for mucin by the periodic acid–Schiff method. At the end of each experiment, temporal bones were harvested for histopathologic study. Results Mucin concentration was greatest in the LPS + the SNAP group and least in the SNAP-alone group. Auditory brainstem response threshold was highest in the LPS group and lowest in the SNAP group, although not significantly. Histopathology showed the greatest mucosal thickening and inflammation in the LPS + SNAP group. Conclusion The addition of NO in LPS-induced OM increased the mucin concentration in middle ear fluid and increased mucosal thickness and inflammation in middle ear mucosa. Significance In the OM disease process, NO may contribute to the pathogenesis of mucoid OM.

Angiotensin-converting enzyme (ACE) is used as a marker for sarcoid disease activity. We present an observational study of four African-American patients all of whom demonstrated improvement in their sarcoidosis after treatment with ACE inhibitors for hypertension.

Background: Aromatase inhibitors are used as adjuvant therapy for breast cancer (BC) and are associated with accelerated bone loss. Zoledronic acid (ZOL) prevents aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with BC. This analysis assessed the cost-effectiveness of ZOL for prevention of fractures in postmenopausal women with BC. Materials and methods: A Markov model was developed to project lifetime incidence of fractures, quality-adjusted life years (QALY), and costs as a function of bone mineral density (BMD) for women with early-stage BC receiving letrozole alone or with ZOL. Two strategies of ZOL therapy were compared with no treatment: starting ZOL treatment only when BMD levels decreased (‘delayed ZOL’) and starting ZOL simultaneously with letrozole therapy (‘upfront ZOL’). Results: Delayed ZOL therapy was estimated to cost £16 069 per QALY, when compared with not administering bisphosphonates for AIBL prevention. The corresponding cost per QALY gained for upfront ZOL versus no treatment was estimated at £21 973. The cost-effectiveness ratio for upfront versus delayed therapy was estimated at £24 868 per QALY gained. Conclusion: Both delayed and upfront therapy with ZOL for the prevention of AIBL and fractures in BC patients in the UK appear to result in highly acceptable cost-effectiveness ratios.

Angiotensin-converting enzyme is used as a marker for sarcoid activity. We describe a case of remission of cutaneous and lymphatic sarcoidosis in a patient treated with an ACE inhibitor for congestive heart failure and hypertension; the remission has continued over 4 years of follow-up. Because this is a report of only one case, there is a possibility of sampling error. Whether the patient's remission in this case was a serendipitous spontaneous remission that happened to occur during ACE inhibitor therapy or whether ACE inhibitor therapy can play a role in the treatment of sarcoidosis needs to be determined in a large clinical trial.

Background: Breakthrough innovation in oncology is commonly considered to be a substantial increase in overall survival (OS) above specific thresholds. However, this growing emphasis on significant OS gain, undervalues new products and may not capture aspects of treatment that are important to patients, including quality of life (QoL), delayed progression or improvements in side-effect profiles. We argue that progressive innovation in clinical and non-clinical domains needs to be considered and valued in regulatory andhealth technology assessment (HTA) decisions.Methods: We conducted a targeted literature search for definitions of innovation in academic and gray literature, covering regulatory, HTA, and industry bodies. Current/proposed OS thresholds were applied to standard of care therapies in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) and assessed in the light of the actual HTA decision made. Results: Regulators andHTA agencies do not provide clear, consistent definitions of innovation, but absoluteOSgain consistently emerges askey frompolicy (e.g., England’s Cancer Drugs Fund) and clinical (e.g., American Society of Clinical Oncology [ASCO]) perspectives. The emphasis is increasingly on “clinically meaningful” change expressed as minimum thresholds: OS gain >2.5 months, HR >0.8; PFS gain >3 months, HR>0.5. OS thresholds published by the ASCOCommittee (Ellis et al., 2014) were applied toCRCandNSCLC.Onlyoneof sixCRCdrugs approved since 2000 met the threshold, but survival doubled in that time. Since 2005 no NSCLC products have met this OS threshold, yet survival for first-line patients with advanced disease increased twofold. Conclusions: Innovation should be judged in relation to the value provided to patients and health systems, not restricted to one-time large survival gains. Smaller sequential clinical gains and improved QoL, safety, convenience, and system efficiency should be considered in assessing value and innovation. Progressive innovation provides opportunities for immediate benefit, including survival until the next therapy is available, and uncovering new clinical pathways with significant cumulative benefit over time. Recognition of this “option value” for future health and research advances is needed. Regulatory and HTA agencies should balance clinical and economic gains, and societal and patient preferences when evaluating innovation in a new therapy.

Aim Invasive procedures including venepuncture and venous cannulation are distressing experiences for ill children. Painful past experiences and needle phobia can cause the procedure to be more traumatic for the child and more difficult for healthcare professionals. Devices using near infra-red spectroscopy can aid the accurate location of superficial veins thus reducing the number of attempts and time taken to undertake these procedures, and aim to reduce the stress for all involved. The purpose of this study was to evaluate the usefulness and acceptability of a commercially available portable vein illuminator in two acute paediatric departments. Methods A range of health professionals used the device for venepuncture and venous cannulation in children presenting with acute or chronic illness to the departments. A structured questionnaire was completed by the user once the procedure was completed. Results 40 patients were enrolled in this study (males = 23, females = 17, mean age 4.8 years). Thirty six children underwent venepuncture and 4 underwent venous cannulation. The procedure was completed by registrar in 4 children, by a senior house officer in 24 children and by a nurse in 12 children. Sixty five per cent found the visibility of the veins improved, 5% found the visibility worse, and 30% were neutral. The device was found to be very acceptable or acceptable to parents and children in 92.5% and was graded very useful or useful in 65% and not useful in 35%. Conclusion The device was found to be useful and acceptable and did aid with phlebotomy within the departments. The best results were seen in younger children whose superficial veins were not visible to the naked eye. Further studies are required with a larger sample size including a wide range of ethnic groups, and ideally with a comparison group.

Nitric oxide (NO), a free radical, has been found to be important in the development of middle ear effusions. However, the effect of NO in the middle ear effusion on cochlear function and on perilymph concentrations of NO has not been reported. We placed S-nitroso-N-acetylpenicillamine (SNAP), a NO donor compound, on the round window membrane (RWM) of adult chinchillas. Auditory brainstem response (ABR) thresholds were measured before and after the placement of SNAP on the RWM and hourly for 8 h after SNAP placement. Samples of perilymph were collected 2 h after application of SNAP and were assayed for total nitrate and nitrite, the end products of NO. Experimental ears demonstrated significant ABR threshold elevations after 5 h and elevated nitrate/nitrite in the perilymph. These findings suggest that NO present in the middle ear passes through the RWM into the inner ear and can cause significant hearing loss.

4679 Background: Zoledronic acid (ZOL) is the only bisphosphonate indicated for the prevention of skeletal related events (SREs) in patients with bone metastases secondary to prostate cancer. This ...

e19518 Background: For cancer pts with BM, skeletal complications (SC) are common. Skeletal complications such as fracture may increase morbidity and mortality and reduce quality of life. Zoledroni...

e16519 Background: Letrozole (LET) and anastrozole (ANA) are more effective than tamoxifen (TAM) in preventing disease recurrence in postmenopausal women with early stage breast cancer. Recent data...

656 Background: The latest update of the BIG 1-98 study (74 months) applied IPCW to estimate treatment effect in the presence of selective crossover (25% of TAM pts). The IPCW hazard ratio for over...

Background: Following a diagnosis of early breast cancer (BC), there are a variety of treatment options open to physicians. However, with the development of alternative therapies and rapidly changing clinical guidelines, there are limited data available evaluating current patterns of care. This study investigated current treatment patterns following an initial diagnosis of early BC and examined demographic and clinical differences among patients receiving tamoxifen versus aromatase inhibitors (AI) as a preliminary analysis to inform a more in-depth study assessing early BC recurrence rates between therapy groups.Methods: In a retrospective cohort analysis among enrollees in managed care health plans, we identified female patients aged 55 years or older from 2004 to 2008 who were newly diagnosed with BC and had no evidence of prior BC surgery, chemotherapy, radiotherapy, or hormone therapy. Patients were followed from the date of first BC diagnosis until evidence of first (“index”) treatment with tamoxifen or an AI (anastrozole or letrozole). Outcomes of interest included differences between hormone therapy cohorts in patient characteristics (age, payer type) and clinical characteristics (risk group, Charlson comorbidity index [CCI]). Risk group was defined by treatments identified between the time of first BC diagnosis and index hormone therapy and included low (surgery only), medium (surgery and radiotherapy), higher (surgery then chemotherapy), and highest (neoadjuvant chemotherapy or combination surgery, radiotherapy, and chemotherapy). Unadjusted comparisons between cohorts were performed, with a p-value Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2060.

Background: Aromatase inhibitors (AIs) are increasingly used as adjuvant therapy in early-stage breast cancer (EBC) and are associated with accelerated bone-loss. Adjuvant therapy with zoledronic acid (ZOL) has been shown to prevent aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women (PMW) with EBC. This analysis assessed, via a model projecting lifetime incidence of osteoporotic fractures as a function of BMD, the cost-effectiveness of adjuvant ZOL for the prevention of fractures in PMW with hormone receptor positive breast cancer (stage I-IIIa) who receive adjuvant letrozole 2.5 mg daily for 5 years and who had a baseline bone mineral density (BMD) T score of ≥-2. Methods: A Markov model was developed to project the lifetime incidence of osteoporotic fractures, quality-adjusted life years (QALY), and healthcare costs as a function of BMD for women with EBC (aged 60 years) receiving adjuvant AIs (for up to 5 years) alone or with ZOL upfront or delayed. Two strategies of adjuvant ZOL therapy compared to no treatment were modelled: starting ZOL treatment only when BMD levels decreased (“delayed ZOL”) and starting ZOL 4mg i.v. q 6mo simultaneously with AI therapy (“upfront ZOL”). ZOL efficacy was derived from the ZO-FAST study (N=1,060) which reported a 5.41% (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1111.

581 Background: Adjuvant CT is an accepted treatment for N+ BC. The addition of taxanes to anthracycline based adjuvant CT has been demonstrated to improve overall survival (OS) in all but one study as in table below. BIG 1–98 has reported a survival gain with the aromatase inhibitor LET compared to tamoxifen (TAM). NNT (the reciprocal of absolute benefit) is the number of pts that need to be treated with a new intervention to avoid 1 additional event over the benefit provided by standard therapy. For multiple numerical outcomes from randomized trials, NNT is an effective method to express results in a clinically meaningful way. To evaluate the degree of benefit of LET over TAM in women with early stage N+ BC in BIG 1–98, we compared the NNT for survival benefit from LET to that needed to see benefit from the addition of a taxane to anthracycline based CT based on clinical trial data in BC pts with N+ disease. Methods: 5-yr survival data were taken from the pivotal randomized controlled trial (RCT) for LET (N+ pts from BIG 1–98, TAM arm censored for crossover to LET) and from 4 RCTs of adjuvant CT trials, AC-T, FEC-D, and DAC. NNT was calculated with respect to OS at 5 yrs; outcome is presented as the NNT to save a life (see Table). Results: The NNT to save a life for adjuvant LET vs TAM is comparable to the NNT for the addition of a taxane to anthracycline based CT in women with N+ BC. Conclusions: The magnitude of survival benefit of LET over TAM in terms of NNT is comparable to that needed to see a survival benefit from paradigm- changing modern adjuvant CT regimens. F= fluorouracil, E = epirubicin, C = cyclophosphamide, D = docetaxel, T = paclitaxel, A = doxorubicin [Table: see text] [Table: see text]

9518 Background: For cancer pts with malignant bone lesions (BM), SREs including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and radiotherapy and/or surgery to bone are associated with significant morbidity and mortality and reduced quality of life. ZOL is an IV bisphosphonate (BP) proven to reduce and delay incidence of SREs in several tumor types. This study was designed to assess the benefit of long-term ZOL use in a real-life setting. Methods: Claims-based analysis of commercial and Medicare data from a large US managed care plan and a 45 health-plan database was used to evaluate mortality rates, SRE rates, and time from BM to SREs in pts treated with ZOL, pamidronate (PAM), or no IV BP therapy. Pts older than 18 years with solid tumors (breast, prostate, lung, bladder, or renal cell cancers) or MM and BM diagnosed between Jan 2001 and Dec 2006 were included. Continuous enrollment in the health plan for 6 months before the index date and no prior evidence of BM or IV BP use were required. Pts were followed until they left the care plan, switched therapy, or completed the study period. SRE and mortality rates were assessed. Results: The study sample included 28,415 pts with a mean age of 62.5 ± 12.24 years; approx. 25% were treated with ZOL, 8% with PAM, and 67% with no IV BP. Incidences of first and subsequent SREs were higher in the no IV BP group (incidence rate ratio [IRR] = 2.27; 95% CI = 2.03, 2.53 and IRR = 1.3; 95% CI = 1.24, 1.37, respectively) vs the ZOL/PAM groups. Time to first SRE was delayed by approx. 153 days for ZOL vs no IV BP pts. Overall, pts who had greater persistency with ZOL had lower risks of first SRE compared with no IV BP, the greatest risk reduction being observed in the 12- to 18-month persistency cohort, which experienced > 5-fold risk reduction (IRR = 0.19; 95% CI = 0.11, 0.31). The same persistency cohort also had a 27% lower risk of developing a second SRE (IRR = 0.73; 95% CI = 0.62, 0.86) compared with no IV BP. Conclusions: This study showed that in cancer pts with BM, persistence with ZOL resulted in reduced risk of developing first and subsequent SREs. Pts with longer persistence with ZOL achieved better outcomes. [Table: see text]

5106 Background: Zoledronic acid (ZOL) significantly reduces the risk of new skeletal-related events (SREs) in patients (pts) with bone metastases from RCC. This study assessed and compared the cost-effectiveness of ZOL in pts with RCC from French, German, and United Kingdom (UK) societal perspectives. Methods: This analysis was based on a retrospective analysis of RCC pts with bone metastases who were enrolled in a 9-mo trial of ZOL or placebo (PBO) plus concomitant antineoplastic therapy. A model was developed to simulate costs and quality-adjusted life-years (QALYs) experienced by study pts. The model included data and assumptions regarding SRE incidence, mortality, drug and administration costs, SRE costs, reduced quality of life (QOL) because of SREs and bone pain, and therapy duration. SRE costs were estimated using diagnosis-related group tariff information and published literature. Consistent with similar economic analyses, it was assumed that QOL decreased 20% to 80% (depending on SRE type) for 1 mo after each SRE experienced. Sensitivity analyses were performed to test the effects of alternate assumptions, with < 30,000/QALY considered cost-effective. Results: Compared with PBO-treated pts (n = 19), ZOL-treated pts (n = 27) experienced 1.07 fewer SREs/pt and gained discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among pts treated with ZOL vs PBO (-4,196 in France, -3,880 in Germany, and -3,355 in the UK). After including drug therapy costs, ZOL saved 1,358, 1,223, and 719 per pt in France, Germany, and the UK, respectively. In multivariate sensitivity analyses, ZOL saved costs in 67% to 77% of cases, depending on the country. ZOL resulted in a cost per QALY gained < 30,000 in approximately 93% of cases. Conclusions: Treatment with ZOL reduces SREs, improves QOL, and lowers health-related costs compared with PBO in French, German, and UK pts with bone metastases from RCC. Use of ZOL in these populations therefore provides health-related cost savings and is a cost-effective use of healthcare resources. [Table: see text]

6566 Background: The latest update of the BIG 1–98 study reports a hazard ratio for overall survival (OS) of 0.81 (95% CI 0.69 = 0.94) (censoring TAM patients who crossed over to LET). Previous economic analyses of the aromatase inhibitors extrapolated observed differences in time to recurrence. This study uses observed differences in OS to estimate the incremental cost per life year (LY), and per quality adjusted LY (QALY) gained of 5 years LET versus 5 years TAM in ER+ postmenopausal women, from a UK NHS perspective. Methods: Annual survival probabilities over the first 7 years post-surgery were extracted from updated BIG 1–98 results. Survival was extrapolated to 20 years using data reported by the Early Breast Cancer Trialists’ Group for women receiving 5 years TAM. Equivalent annual survival probabilities were assumed for the LET and TAM groups post-7 years (likely to be a conservative assumption given diverging OS between 5 and 7 years). Costs included those of the interventions and and a wide range of adverse events (AEs). Published five year costs for locoregional recurrence (LR) and metastases (METS) were applied to reported recurrence rates over 9 years. A Markov model applied published utility weights for DFS with AEs, LR, and METS. All costs and health benefits were discounted at 3.5% annually. Results: The reference case results show that over a 20 year period, the discounted additional treatment costs of LET'are £4,427, and AEs incur an additional £88 per patient, while the reduced frequency decreases the cost difference by £807. The total cost difference between LET and TAM is £3,707. The discounted gain in LYs is 0.286. The incremental cost per LY gained for LET over TAM is £12,970. The Markov model estimated a difference in discounted QALYs of 0.297, with an incremental cost per QALY gained of £12,500. Conclusions: The economic analysis of 5 years LET compared to 5 years TAM based on observed differences in OS produces similar results to earlier modelled extrapolations based on differences in time to recurrence. However, the 20 year time horizon used in this analysis is shorter than previous analyses, and so the results may be considered conservative, i.e. LET may be more cost-effective than previously estimated. [Table: see text]

17547 Background: The ATAC and BIG 1–98 clinical trials demonstrated that anastrozole (ANA) and letrozole (LET) were more effective than tamoxifen (TAM) in preventing disease relapse in postmenopau...

596 Background: The BIG 1–98 and ATAC randomized controlled trials demonstrated that, in postmenopausal women with hormone receptor-positive (HR+) early breast cancer, initial adjuvant therapy for 5 years with the aromatase inhibitors (AIs) letrozole (LET) or anastrozole (ANA) is superior to tamoxifen (TAM). The table shows the difference in early effects of the 2 AIs. This study shows the cost-effectiveness of 5 years of initial adjuvant therapy with LET or ANA versus 5 years TAM in a postmenopausal HR+ population. Methods: Clinical trial data from BIG-198 and ATAC populated a Markov model to estimate the incremental cost per quality-adjusted life year (QALY) gained of the AIs compared to TAM. Variable annual hazard ratios for time to recurrence over the 5 year treatment period were applied to a pooled set of variable annual hazard rates for TAM. Probabilities of breast cancer event type and adverse events (AEs) (end. cancer, fractures, stroke, VTEs, and bleeding) were based on published results of the c...

1141 Background: Breast cancer is associated with considerable health care resource utilization and patients who experience recurrent breast cancer require more costly care than patients who do not develop recurrent disease. Research has also shown that the cost associated with a distant recurrence is significantly greater than the cost associated with a contralateral or local-regional recurrence. Distant metastasis has also been shown to account for the greatest number of breast cancer recurrence events early in the course of the disease (2–3 years after surgery). In this study we evaluated the cost associated with breast cancer recurrence in postmenopausal women diagnosed with breast cancer between 1995 and 2005. Methods: Using data from the Henry Ford Health System, patients who were at least 45 year old at the time of diagnosis without a stage IV or unknown tumor were identified and included in the study. Patients had at least one year of continuous enrollment and received at least one of the followin...