Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study.

BACKGROUND: Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years. METHODS: 14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities. RESULTS: 276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia. CONCLUSION: Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.

Comparison of impedance cardiography and cardiac magnetic resonance imaging for the evaluation of cardiac function in early-stage breast cancer patients.

Objective.Breast cancer treatment can negatively impact cardiac function in some breast cancer patients. Current methods (MUGA, echocardiography) used in clinical practice to detect abnormal cardiac changes as a result of treatment suffer from important limitations. Use of alternative techniques that would offer safe, inexpensive and non-invasive cardiac function assessment in this population would be highly advantageous. The aim of this study was to examine the agreement between impedance cardiography (ICG) and cardiac magnetic resonance imaging (CMR) in quantifying stroke volume (SV), cardiac output (CO) and end-diastolic volume (EDV) in this population.Approach.Sixteen breast cancer patients underwent ICG and CMR assessments at three time-points (before treatment, immediately after chemotherapy, and four months after chemotherapy). Bland-Altman analysis was used to quantify the accuracy and precision of ICG (relative to CMR) in estimating absolute values of SV, CO and EDV. Four methods (concordance rate, polar concordance rate, clinical concordance rate and trend interchangeability rate) were also used to assess ICG performance in tracking changes in these variables.Main results.Bland-Altman analysis showed that the accuracy of ICG relative to CMR was -3.1 ml (SV), 0.2 l·min-1(CO) and -26.0 ml (EDV) and precision was 13.2 ml (SV), 1.1 l·min-1(CO) and 20.1 ml (EDV), respectively. Trending ability assessment showed that (1) the concordance rate was 87% (SV), 73% (CO) and 73% (EDV), (2) the polar concordance rate was 67% (SV), 53% (CO) and 33% (EDV), (3) the clinical concordance rate was 33% (SV), 40% (CO) and 20% (EDV) and (4) the trend interchangeability rate was 29% (SV), 43% (CO) and 17% (EDV), respectively.Significance.Our findings show that, although ICG showed good accuracy for absolute SV and CO measurements and for CO and EDV changes, precision was poor for all variables in terms of both absolute measurements and trend tracking performance. This suggests that ICG cannot be used interchangeably with CMR in breast cancer patients.

A micro-computed tomographic evaluation of root canal filling with a single gutta-percha cone and calcium silicate sealer.

OBJECTIVES: The purpose of this study was to evaluate the void of root canal filling over time when a calcium silicate sealer was used in the single gutta-percha cone technique. MATERIALS AND METHODS: Twenty-four J-shaped simulated root canals and twenty-four palatal root canals from extracted human maxillary molars were instrumented with ProFile Ni-Ti rotary instruments up to size 35/0.06 or size 40/0.06, respectively. Half of the canals were filled with Endoseal MTA and the other half were with AH Plus Jet using the single gutta-percha cone technique. Immediately after and 4 weeks after the root canal filling, the samples were scanned using micro-computed tomography at a resolution of 12.8 µm. The scanned images were reconstructed using the NRecon software and the void percentages were calculated using the CTan software, and statistically analyzed by 1-way analysis of variance, paired t-test and Tukey post hoc test. RESULTS: After 4 weeks, there were no significant changes in the void percentages at all levels in both material groups (p > 0.05), except at the apical level of the AH Plus Jet group (p < 0.05) in the simulated root canal showing more void percentage compared to other groups. Immediately after filling the extracted human root canals, the Endoseal MTA group showed significantly less void percentage compared to the AH Plus Jet group (p < 0.05). CONCLUSIONS: Under the limitations of this study, the Endoseal MTA does not seem to reduce the voids over time.

Incidental pulmonary embolism in oncology patients with current macroscopic malignancy: incidence in different tumour type and impact of delayed treatment on survival outcome.

OBJECTIVES: To evaluate the incidence and outcome of incidental pulmonary embolism (iPE) in patients with current macroscopic malignancy and delayed anticoagulation due to late reporting of CT scan. METHODS: Reports of CT thorax with i.v. contrast done on oncology patients between 1 January 2015 and 31 December 2015 in two district general hospitals in UK were reviewed. Electronic patient records of iPE patients were reviewed for demographic and treatment information. RESULTS: 26 iPEs were reported in 1,604 scans (731 patients), incidence 1.6%; female = 15; median age = 66 (range 32-90); main artery = 10; lobar artery = 8; segmental = 7; subsegmental = 1; median time (range) from scan to reporting = 1 day (0-60); scan to anticoagulation = 5 days (0-61) (three had no treatment); scan to death = 7 months (1-22+) with nine still alive and two lost to follow up. All had metastatic disease. There was no sudden death. None of the patients whose anticoagulation started more than 5 days after the iPE CT scan died within 3 months. iPE was absent in all repeat staging CT scans (done average 3.4 months after the anticoagulation) in 16 patients, without any anticoagulation in one patient with segmental iPE. CONCLUSION: Incidence of iPE in patients with current macroscopic malignancy is low-1.6%-mostly seen in lung, breast and colorectal cancer probably due to frequency of imaging. A few days' delay in anticoagulation does not appear to have an impact on the risk of sudden cardiac death. Advances in knowledge: This study tells us that iPE is infrequent, that it can be treated appropriately with anticoagulation, but this does not necessarily need to begin on the same day of diagnosis.

Root Canal Shaping Effect of Instruments with Offset Mass of Rotation in the Mandibular First Molar: A Micro-computed Tomographic Study.

INTRODUCTION: The aim of this study was to evaluate the root canal shaping effect of 2 nickel-titanium rotary instruments with offset mass of rotation compared with an instrument with a conventional centered mass of rotation. METHODS: Thirty-six extracted human mandibular first molars with 2 independent mesial canals and 1 oval distal canal were selected and divided equally into 3 groups for instrumentation with ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland), Revo-S (RS; Micro-Mega, Besançon, France), and ProTaper Universal (PTU, Dentsply Maillefer) systems (n = 12). For apical preparation, PTN X2 (#25/0.06), RS SU (#25/0.06), and PTU F2 (#25/0.08) were used in the mesial canals and PTN X3 (#30/0.07), RS AS30 (#30/0.06), and PTU F3 (#30/0.09) were used in the distal canals. Specimens were scanned before and after instrumentation using a SkyScan 1272 scanner (Bruker micro-CT, Kontich, Belgium) at 10-µm isotropic resolution. Changes in the canal area, volume, structure model index (SMI), and untouched canal area were evaluated. Canal transportation and centering ratio were measured at 1, 3, 5, and 7 mm from the apical foramen. Data were statistically analyzed using 1-way analysis of variance with the Tukey post hoc test. RESULTS: The PTN and RS systems showed significantly less transportation and better centering ability compared with the PTU system at 1 mm from the apical foramen (P < .05). All instrumentation increased the canal area, volume, and SMI values without significant differences among the 3 groups (P > .05). CONCLUSIONS: Regardless of the differences in the cross-sectional design, alloy type, and taper variation, instruments with offset mass of rotation showed better root canal shaping ability compared with an instrument with a centered mass of rotation.

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.

Experience with trabectedin in an advanced sarcoma patient on peritoneal dialysis for end-stage renal failure.

BACKGROUND: We wanted to evaluate the impact of peritoneal dialysis on trabectedin therapy in terms of side effects, response and levels in the blood and dialysate of a patient on peritoneal dialysis for end-stage renal failure caused by previous ifosfamide therapy. This has not yet been reported in the medical literature. METHODS: We measured the levels of trabectedin in the blood and peritoneal dialysate at different time points before and after the administration of a 3rd cycle of trabectedin (1.5 mg/m(2) over 24 h). Toxicity from the treatment was recorded and the response status was evaluated on a CT scan after the 3rd and 6th cycles. RESULTS: Serum creatinine clearance (Cockcroft-Gault formula) was 8.31 ml/min. The patient had a World Health Organization performance status score of '0' and did not suffer any significant side effects except for grade 2 anaemia. There was no difference in the plasma level of trabectedin just before and after a 3-hour session of peritoneal dialysis. The amount of trabectedin in the peritoneal dialysates was undetectable (limit of quantification: 25.9 pg/ml). The patient achieved stable disease after 3 cycles, and progressive disease was observed after 6 cycles on CT scan. CONCLUSION: Our patient did not suffer undue side effects from trabectedin, and peritoneal dialysis did not appear to have an impact on the clearance of the drug.

Curve progression in idiopathic scoliosis: follow-up study to skeletal maturity.

STUDY DESIGN: This is a follow-up study to skeletal maturity on a cohort of students screened for a 1-year prospective epidemiological prevalence study for scoliosis. OBJECTIVES: This study aims to identify the prognostic factors for curve progression to a magnitude of 30 degrees at skeletal maturity in skeletally immature patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The natural history of idiopathic scoliosis is not well understood. Previous reports have focused on the characteristics of curve progression where progression has been predefined at specific angles of 5 degrees to 6 degrees. However, the absolute curve magnitude at skeletal maturity is more predictive of long-term curve behavior rather than curve progression of a defined magnitude over shorter periods of skeletal growth. It is generally agreed that curves less than 30 degrees are highly unlikely to progress after skeletal maturity. Hence, defining the factors that influence curve progression to an absolute magnitude of more than 30 degrees at skeletal maturity would more significantly aid clinical practice. METHODS: One hundred eighty-six patients who fulfilled the study criteria were selected from an initial 279 patients with idiopathic scoliosis detected by school screening, and who were followed-up till skeletal maturity. The initial age, gender, pubertal status, and initial curve magnitude were used as risk factors to predict the probability of curve progression to more than 30 degrees at skeletal maturity. RESULTS: Curve magnitude at first presentation was the most important predictive factor for curve progression to a magnitude of more than 30 degrees at skeletal maturity. An initial Cobb angle of 25 degrees had the best receiver-operating characteristic of 0.80 with a positive predictive value of 68.4% and a negative predictive value of 91.9% for curve progression to 30 degrees or more at skeletal maturity. CONCLUSION: Initial Cobb angle magnitude is the most important predictor of long-term curve progression and behavior past skeletal maturity. We suggest an initial Cobb angle of 25 degrees as an important threshold magnitude for long-term curve progression. Initial age, gender, and pubertal status were less important prognostic factors in our study.