Laura Spring

Impact of pass/fail grading on medical students' well-being and academic outcomes.

Medical Education 2011:45: 867–877

Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Meta-analysis

Importance Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear. Objective To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer. Data Sources Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015. Study Selection Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion. Data Extraction and Synthesis Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. Results The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%). Conclusions and Relevance Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.

Clinical Management of Potential Toxicities and Drug Interactions Related to Cyclin‐Dependent Kinase 4/6 Inhibitors in Breast Cancer: Practical Considerations and Recommendations

This review article reports the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer, with a focus on palbociclib and ribociclib, and summarizes practical management strategies for the oncologist.

Risk Factors for Readmission after Allogeneic Hematopoietic Stem Cell Transplantation and Impact on Overall Survival

Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) are presumed to be at high risk for hospital readmission. The objective of this study was to identify the incidence and associated risk factors for readmissions in allogeneic HSCT patients and to evaluate the effect of readmissions on overall survival. In this retrospective review, we included 1141 HSCT patients (503 patients receiving a myeloablative [MAC] HSCT and 638 a reduced-intensity conditioning [RIC] HSCT). We measured rates of readmission at 30 days after discharge from HSCT and by day +100 after HSCT. Reasons for readmission, risk factors for readmission, and effect on overall survival were assessed. In the MAC group, 130 of 459 (28.3%) patients were readmitted within 30 days of discharge and 195 of 456 (42.8%) patients by day 100. In the RIC group, 105 of 600 (17.5%) patients were readmitted within 30 days of discharge and 185 of 595 (31.1%) patients by day 100. There were significantly more readmissions in the MAC group at both the 30-day (P < .001) and day +100 time points (P < .001). The most frequent reason for readmission was infection (28.2% in MAC group, 27.3% in RIC group). The occurrence of infection during the index admission was the only risk factor significant in both groups at both time points in the multivariable regression analysis. Readmission was significantly associated with decreased overall survival in both groups and at both time points. MAC patients are readmitted significantly more than RIC patients. Infection is the most common cause of readmission after HSCT and the occurrence of infection during the index transplantation admission is a significant risk factor for readmission. Readmission within 30 days of discharge and by day +100 after transplantation was a significant risk factor for a lower 5-year overall survival rate in both groups.

Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer

Background While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods We identified patients who had pre- and post-genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors. Genotyping was carried out in tumor tissue or blood collected before start of CDK 4/6 inhibitor and after disease progression on CDK 4/6 inhibitor, covering more than 90% of the coding region in RB1. Results We identified detectable acquired RB1 mutations in circulating tumor DNA (ctDNA) after exposure to CDK4/6 inhibitor (palbociclib, palbociclib, ribociclib) for 5, 8, and 13 months, respectively, in three patients. The RB1 mutations included substitution in donor splicing site of exon 8 of the RB1 gene in patient #1; substitution in donor splicing site of exon 22 of RB1 gene, exon 19 deletion, exon 3 insertion in patient #2; and RB1 exon 16 H483Y mutation in patient #3. None of these RB1 mutations were present in the pre-CDK 4/6 specimen highlighting these molecular alterations, which lead to functional loss of Rb1, likely emerged under selective pressure from the CDK4/6 inhibitor potentially confering therapeutic resistance. Conclusion This is the first clinical report to describe the emergence of somatic RB1 mutations after exposure to palbociclib or ribociclib, in patients with metastatic breast cancer. Further research is needed to validate these findings, identify how these mutations temporally emerge under selective pressure of CDK 4/6 inhibitor, and develop rational therapeutic strategies.

Pulmonary Clinicopathological Correlation after Allogeneic Hematopoietic Stem Cell Transplantation: An Autopsy Series

Pulmonary complications are a significant cause of morbidity, mortality, and resource utilization after hematopoietic stem cell transplantation (HSCT). The objective of this study was to compare antemortem clinical suspicion of pulmonary complications and postmortem findings in a modern HSCT cohort. All patients who underwent allogeneic HSCT at our institution (n = 1854) between January 1, 2000 and June 30, 2010 were reviewed and patients who died of any cause greater than 1 year after HSCT and had an unrestricted autopsy available for analysis were included. Presence of pulmonary graft-versus-host disease (GVHD) was assessed by a pathologist blinded to the autopsy report, as previously described by Yousem (1995). A total of 35 (1.9%) patients had autopsies available for review. Airway disease, vascular disease, and interstitial disease were all clinically under-recognized compared with the pathological findings on autopsy. Varying degrees of pathological changes were detected, including 10 (28.6%) patients having bronchiolitis obliterans (BO) and 12 (34.3%) patients having pulmonary veno-occlusive disease (PVOD). Pulmonary manifestations of chronic GVHD, particularly BO and PVOD, were clinically under-recognized in our cohort. Our results suggest that PVOD, which has traditionally been considered a rare complication, may be clinically and histologically under-recognized.

Mammography decision making: Trends and predictors of provider communication in the Health Information National Trends Survey, 2011 to 2014.

In 2009, the US Preventive Services Task Force recommended that the decision to initiate screening mammography before age 50 years should be individualized. Herein, the authors examined whether health care providers are communicating regarding mammography decision making with women and whether communication is associated with screening behavior.

Readmissions after Umbilical Cord Blood Transplantation and Impact on Overall Survival

Patients treated with allogeneic hematopoietic stem cell transplantation (SCT) have high rates of readmission, but the incidence after umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence and risk factors for readmission after UCBT and the impact of readmission on overall survival (OS). A retrospective review of patients receiving a UCBT at Dana-Farber/Brigham and Womens Hospital between January 1, 2004 and December 31, 2013 was performed. The readmission rates 30 days after discharge from the UCBT admission and at day +100 after the UCBT were examined. Reasons for readmission, as well as sociodemographic, disease-, and SCT-related variables were evaluated. Predictors of readmission and the impact of readmission on OS were identified using multivariate regression analysis. Of patients who received a UCBT, 42 of 126 patients (33.3%) were readmitted within 30 days of discharge and 57 of 123 patients (46.3%) were readmitted by day +100 after transplantation. The most common causes for readmission were infection (38.3%), fever without a source (14.8%), and graft-versus-host disease (8.6%). Infection during the index admission was the only significant risk factor for readmission at both time points in a univariate and multivariate regression analysis (OR, 11.66; 95% CI, 2.77 to 49.13; P < .01 and OR, 5.4; 96% CI, 1.87 to 15.58; P < .01). Prior radiation therapy was also associated with an increased risk of readmission at both time points in the multivariate regression model (OR, 20.6; 95% CI, 3.53 to 120.04; P ≤ .01 and OR, 5; 95% CI, 1.21 to 20.71; P = .03). The multivariate regression model also showed that black race and a median income of <60,000 in the patients home zip code increased the risk of readmission by day +100 (OR, 30.17; 95% CI, 1.33 to 684.48; P = .03 and OR, 2.88; 95% CI, 1.04 to 7.8; P = .04, respectively). After adjusting for age, disease type, and the disease status at transplant, OS was reduced for the patients who were readmitted by day +100 (HR, 2.44; 95% CI, 1.46 to 4.06; P < .01). There was also a trend toward decreased survival in patients readmitted 30 days after discharge (HR, 1.58; 95% CI, .96 to 2.6; P = .07). Readmissions are common after UCBT. Infections and fever without a source are the most common causes of readmission. Being readmitted by day +100 resulted in a lower 5-year OS rate as compared with patients who were not readmitted. Prior radiation and infection during the transplant admission resulted in increased risk of readmission by 30 days and day +100. Similarly, race and socioeconomic status predicted readmission by day +100. Further understanding of the mechanisms leading to readmissions in these groups may allow for identification of interventions that could reduce readmissions and thus improve mortality.

Readmissions following umbilical cord blood stem cell transplantation.

272 Background: Readmission within 30 days of discharge has been perceived by the Centers for Medicare and Medicaid Services to be an indicator of poor healthcare quality, however it is unclear how accurately this applies to oncology patients. Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of readmission, but the incidence following umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence, reasons, and risk factors for readmission following UCBT. METHODS A retrospective review of patients receiving an UCBT at Dana-Farber/Brigham and Womens Hospital between January 1, 2004 and December 31, 2013 was performed. The 30-day and the day +100, a traditional assessment point in transplantation, readmission rates were examined. Reasons for readmission, as well as sociodemographic and disease and stem cell transplant related variables were evaluated. Predictors of readmission were identified using multivariate regression analysis. RESULTS 33.6% (42/125) of patients were readmitted within 30 days of discharge. Of patients who survived until day +100, 46.7% (57/122) were readmitted within 100 days of UCBT. The most common cause for readmission was infection (38.3%), followed by fever without a source (14.8%) and graft vs. host disease (GVHD) (8.6%) (Table). A multivariate logistic regression model of the probability of being readmitted within 30 days and by day +100 suggested that infection during transplant admission was a significant risk factor for readmission (OR: 5.1, p=0.003 and OR: 2.9, p=0.014, respectively). CONCLUSIONS There is a high rate of readmission within 30 days and by day +100 following UCBT. The most common causes of readmission were infection and fever without a source. Infection during the transplant admission predicted a higher risk of readmission, suggesting a possible group to target for interventions aimed at reducing readmissions and improving quality of care. [Table: see text].

High-Content Biopsies Facilitate Molecular Analyses and Do Not Increase Complication Rates in Patients With Advanced Solid Tumors

PurposePrecision oncology relies on frequent pathologic, molecular, and genomic assessments of tumor tissue to guide treatment selection, evaluate pharmacodynamic effects of novel agents, and determine drug resistance mechanisms. Newer forms of analyses such as drug screens in cell lines and patient-derived xenografts demand increasing amounts of tissue material. It remains unknown how the need for serial biopsies with large numbers of tumor cores relates to tissue yields and biopsy complication rates.Materials and MethodsIn this study, we performed a retrospective analysis of 199 focal liver biopsies performed in 143 patients in the setting of oncologic research protocols (research biopsy group) over a 4-year period at a single-intervention oncology service. Practice patterns and complication rates were compared with those related to 1,522 consecutive biopsies performed in 1,154 patients in whom two cores were obtained for standard clinical management of patients (standard biopsy).ResultsIn the research ...