Healthcare-resource utilization associated with radiation to bone across eight European countries: Results from a retrospective study.

BACKGROUND: Bone metastases and lytic lesions due to multiple myeloma are common in advanced cancer and can lead to debilitating complications (skeletal-related events [SREs]), including requirement for radiation to bone. Despite the high frequency of radiation to bone in patients with metastatic bone disease, our knowledge of associated healthcare resource utilization (HRU) is limited. METHODS: This retrospective study estimated HRU following radiation to bone in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland. Eligible patients were ≥ 20 years old, had bone metastases secondary to breast, lung or prostate cancer, or bone lesions associated with multiple myeloma, and had received radiation to bone between 1 July 2004 and 1 July 2009. HRU data were extracted from hospital patient charts from 3.5 months before the index SRE (radiation to bone preceded by a SRE-free period of ≥ 6.5 months) until 3 months after the last SRE that the patient experienced during the study period. RESULTS: In total, 482 patients were included. The number of inpatient stays increased from baseline by a mean of 0.52 (standard deviation [SD] 1.17) stays per radiation to bone event and the duration of stays increased by a mean of 7.8 (SD 14.8) days. Outpatient visits increased by a mean of 4.24 (SD 6.57) visits and procedures by a mean of 8.51 (SD 7.46) procedures. CONCLUSION: HRU increased following radiation to bone across all countries studied. Agents that prevent severe pain and delay the need for radiation have the potential to reduce the burden imposed on healthcare resources and patients.

Disclosing the Uncertainty Associated with Prognostic Estimates in Breast Cancer.

BACKGROUND: Treatment decision making is often guided by evidence-based probabilities, which may be presented to patients during consultations. These probabilities are intrinsically imperfect and embody 2 types of uncertainties: aleatory uncertainty arising from the unpredictability of future events and epistemic uncertainty arising from limitations in the reliability and accuracy of probability estimates. Risk communication experts have recommended disclosing uncertainty. We examined whether uncertainty was discussed during cancer consultations and whether and how patients perceived uncertainty. METHODS: Consecutive patient consultations with medical oncologists discussing adjuvant treatment in early-stage breast cancer were audiotaped, transcribed, and coded. Patients were interviewed after the consultation to gain insight into their perceptions of uncertainty. RESULTS: In total, 198 patients were included by 27 oncologists. Uncertainty was disclosed in 49% (97/197) of consultations. In those 97 consultations, 23 allusions to epistemic uncertainty were made and 84 allusions to aleatory uncertainty. Overall, the allusions to the precision of the probabilities were somewhat ambiguous. Interviewed patients mainly referred to aleatory uncertainty if not prompted about epistemic uncertainty. Even when specifically asked about epistemic uncertainty, 1 in 4 utterances referred to aleatory uncertainty. When talking about epistemic uncertainty, many patients contradicted themselves. In addition, 1 in 10 patients seemed not to realize that the probabilities communicated during the consultation are imperfect. CONCLUSIONS: Uncertainty is conveyed in only half of patient consultations. When uncertainty is communicated, oncologists mainly refer to aleatory uncertainty. This is also the type of uncertainty that most patients perceive and seem comfortable discussing. Given that it is increasingly common for clinicians to discuss outcome probabilities with their patients, guidance on whether and how to best communicate uncertainty is urgently needed.

Pathologic fracture and healthcare resource utilisation: A retrospective study in eight European countries.

BACKGROUND: Skeletal-related events (SREs; pathologic fracture [PF], spinal cord compression and radiation or surgery to bone) are common complications of bone metastases or bone lesions and can impose a considerable burden on patients and healthcare systems. In this study, the healthcare resource utilisation (HRU) associated with PFs in patients with bone metastases or lesions secondary to solid tumours or multiple myeloma was estimated in eight European countries. METHODS: Eligible patients were identified in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland. HRU data were extracted from hospital charts from 3.5 months before the index PF (defined as a PF preceded by a 6.5-month period without a SRE) until 3 months after the last SRE during the study period. Changes from baseline in the number and duration of inpatient stays, number of outpatient visits and number of procedures provided were recorded. RESULTS: Overall, 118 patients with PFs of long bones (those longer than they are wide, e.g. the femur) and 241 patients with PFs of other bones were included. Overall, HRU was greater in patients with long bone PFs than in those with PFs of other bones. A higher proportion of patients with long bone PFs had multiple SREs (79.7%), and more of their SREs were considered to be linked (73.4%) compared with patients with PFs of other bones (51.0% and 47.2%, respectively). CONCLUSION: The increased number and duration of inpatient stays for PFs of long bones compared with those for PFs of other bones may be due in part to the requirement for complicated and lengthy rehabilitation in patients with long bone PFs. Implementing strategies to delay or reduce the number of PFs experienced by patients with bone metastases or lesions may therefore reduce the associated HRU and patient burden.

Health resource utilization associated with skeletal-related events: results from a retrospective European study.

BACKGROUND: Bone complications, also known as skeletal-related events (SREs), are common in patients with bone metastases secondary to advanced cancers. OBJECTIVE: To provide a detailed estimate of the health resource utilization (HRU) burden associated with SREs across eight European countries. METHODS: Eligible patients from centers in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden, and Switzerland with bone metastases or lesions secondary to breast cancer, prostate, or lung cancer or multiple myeloma who had experienced at least one SRE (defined as radiation to bone, long-bone pathologic fracture, other bone pathologic fracture, surgery to bone or spinal cord compression) were entered into this study. HRU data were extracted retrospectively from the patients' charts from 3.5 months before the index SRE until 3 months after the index SRE (defined as an SRE preceded by an SRE-free period of at least 6.5 months). RESULTS: Overall, the mean number of inpatient stays per SRE increased from baseline by approximately 0.5-1.5 stays, with increases in the total duration of inpatient stays of approximately 6-37 days per event. All SREs were associated with substantial increases from baseline in the frequency of procedures and the number of outpatient and day-care visits. CONCLUSIONS: SREs are associated with substantial HRU owing to considerable increases in the number and duration of inpatient stays, and in the number of procedures, outpatient visits, and day-care visits. These data collectively provide a valuable summary of the real-world SRE burden on European healthcare systems.

Immediate Administration of Zoledronic Acid Reduces Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women With Early Breast Cancer: 12-month analysis of the E-ZO-FAST trial.

BACKGROUND: Letrozole is a proven and effective adjuvant therapy in postmenopausal women with hormone receptor-positive (HR(+)) early breast cancer (EBC). As with other aromatase inhibitors (AIs), long-term letrozole administration is associated with decreased bone mineral density (BMD) and increased fracture risk. This study compared potential bone-protecting effects of immediate vs. delayed administration of zoledronic acid (ZOL) in patients with EBC receiving adjuvant letrozole. PATIENTS AND METHODS: Patients with HR(+) EBC in whom adjuvant letrozole treatment was initiated (2.5 mg/day for 5 years) were randomized to immediate ZOL treatment (immediate ZOL) or delayed ZOL treatment (delayed ZOL) (both at 4 mg every 6 months). Patients in the delayed ZOL group received ZOL only for a BMD T-score that decreased to < -2.0 (lumbar spine [LS] or total hip [TH]) or for fracture. The primary endpoint was percentage change in the LS BMD at month 12. Patients were stratified by established or recent postmenopausal status, baseline T-scores, and adjuvant chemotherapy history. RESULTS: At 12 months, the LS BMD increased in the immediate ZOL group (+2.72%) but decreased in the delayed ZOL group (-2.71%); the absolute difference between groups was significant (5.43%; P < .0001). Across all subgroups, patients receiving immediate ZOL had significantly increased LS and TH BMD vs. those who received delayed ZOL (P < .0001). Differences in fracture incidence or disease recurrence could not be ascertained because of early data cutoff and low incidence of events. Adverse events were generally mild, transient, and consistent with the known safety profiles of both agents. CONCLUSION: Immediate ZOL administration effectively prevented BMD loss and increased BMD in postmenopausal women with HR(+) EBC receiving adjuvant letrozole, regardless of BMD status at baseline.

Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma.

PURPOSE: This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. PATIENTS AND METHODS: Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). RESULTS: Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. CONCLUSION: Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.

[Antitumour effects of bisphosphonates in breast cancer]. / Antitumoreffect van bisfosfonaten bij mammacarcinoom.

Pre-clinical and clinical studies increasingly suggest that the most potent nitrogen-containing bisphosphonates have antitumour effects. Bisphosphonates inhibit osteoclast-mediated bone resorption, and can thus delay the spread of skeletal metastases. Bisphosphonates might also inhibit tumour growth outside the skeleton by inducing apoptosis and inhibiting proliferation, adhesion, invasion, and angiogenesis of tumour cells. Recent trials suggest a possible synergistic antitumour effect between bisphosphonates and chemotherapy. A mechanism of action for bisphosphonates that could explain their possible antitumour effect and their synergy with chemotherapy is speculative and demands further investigation. The role of bisphosphonates in primary neoadjuvant treatment of breast cancer is promising, but must be further investigated.

[When peripheral drips fail: favourable experience with peripherally-inserted central venous catheters]. / Wanneer perifere infusen falen: goede ervaringen met perifeer ingebrachte centraalveneuze katheters.

OBJECTIVE: Evaluation of the technical success rate, insertion complications and patient survival when peripherally-inserted central venous catheters (PICCs) are used in oncologic patients and patients with severe infections in whom it was not possible to place a peripheral drip. DESIGN: Retrospective cohort study. METHOD: Patient records and the radiological computer system RADOS were searched and analysed for data regarding patients, variables at the time of PICC insertion, indwelling time and the reasons for PICC removal. RESULTS: During the period 1 September 2000 - 30 June 2007, 68 patients underwent 101 attempts for PICC placement. Ninety-one (91%) procedures were successful in 64 patients. There were 2 (2%) periprocedural complications; local haematoma (n=1) and palpitations (n=1). At the time of data analysis 14 (15%) PICCs were still in situ. Forty-five (50%) had been removed electively after a mean period of 114 (range: 10-446) days. Thirty-two (35%) PICCs had been removed prematurely after a mean period of 67 (range: 7-266) days. Reasons for premature removal were infection (n=14, 15%), migration (n=10, 11%), dislocation (n=4, 4%), clinical thromboses (n=2, 2%) and occlusion (n=2, 2%). CONCLUSION: PICCs appear to be a good alternative in oncologic patients and patients with infections in whom peripheral drip insertion is not possible. The technical success rate of PICCs was high and was associated with a low periprocedural complication rate. The percentage of prematurely removed catheters seems acceptable, in part because these catheters were removed after a mean period of 2 months.

Fungal disease of the Western hemisphere: a patient with coccidioidomycosis.

We report the case of a 58 year old male patient with nonproductive coughing, fever, vomiting and loss of appetite, beginning at the moment that he returned back home from a 2 week holiday in California. His symptoms were accompanied by increased inflammatory markers in his blood (leucocytosis, high CRP) and pulmonary sequelae, becoming more prominent shortly after admission. Eventually, the final diagnosis of coccidioidomycosis was made by histopathology and confirmed by serology. Coccidioidomycosis is a rare infectious disease. However, the incidence in the endemic areas of this fungal infection is increasing and the population travelling towards its specific endemic regions in the United States and Southern America is considerably growing. Clinicians facing patients with pulmonary infection with the appropriate travel history and persistent pulmonary or systemic infection (with or without eosinophilia) should be alert to the possibility of coccidioidomycosis. Therefore, we present an up to date overview of the epidemiology, microbiology, clinical features, diagnosis and treatment of patients with coccidioidomycosis.

Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.

PURPOSE: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months. RESULTS: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001). CONCLUSION: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.