Changes in Physical Activity, Functional Capacity, and Cardiac Function during Breast Cancer Therapy.

PURPOSE: Functional capacity and cardiac function can decline during breast cancer (BC) therapy. In non-cancer populations, higher physical activity (PA) is associated with better physical function and cardiac health. This study compared baseline PA, functional capacity, and cardiac function between women with and without BC and tested if greater PA participation was related to higher functional capacity and/or better heart function after three months of BC therapy. METHODS: Data was collected in 104 women without BC (82% Caucasian, baseline only) and 110 women with stage I-III BC (82% Caucasian) before therapy and after three months of treatment. Participants self-reported PA and underwent six-minute walk distance (6MWD) testing to measure functional capacity and cardiovascular magnetic resonance to assess left ventricular ejection fraction (LVEF). Analyses were adjusted for age, race, body mass index (BMI), and medication use. RESULTS: The BC group was older (56.2 ± 10.7 vs 52.1 ± 14.7 yrs, P=0.02) with a higher average BMI than the non-cancer group (30.3 ± 6.8 vs 27.7 ± 6.2 kg/m2, P<0.01). Pre-treatment, BC participants reported lower PA scores (27.9 ± 2.8 vs 34.9 ± 2.8, P=0.04) with similar 6MWD and LVEF relative to those without cancer (485 ± 11 vs 496 ± 11 m, P=0.4 and 59.7 ± 0.7 vs 58.9 ± 0.8%, P=0.37, respectively). After three months of BC therapy, declines were observed for PA scores (27.9 ± 2.8 vs 18.3 ± 2.5, P=0.02), 6MWD (485 ± 11 vs 428 ± 10 m, P<0.001), and LVEF (59.7 ± 0.7 vs 56.1 ± 0.7%, P<0.001). Compared to BC participants who reported no PA at three months (n=24, 22%), BC women who reported any PA (n=78, 86%) had higher 6MWD (442 ± 11 vs 389 ± 17 m, P=0.006) but similar LVEF (56.5 ± 0.9 vs 55.3 ± 1.5%, p=0.5). Women who reported any PA were less likely to exhibit an LVEF below normal (<50%) or decline in LVEF of 'â•10 points compared to inactive women (BMI-adjusted, OR [95% CI]: 0.27 [0.09, 0.85]). CONCLUSIONS: These preliminary results indicate that self-reported PA, LVEF and 6MWD decline in the first three months of BC treatment, but PA participation during BC treatment may mitigate declines in functional capacity and cardiac function. Further research is needed to identify barriers and facilitators of PA participation during BC therapy. FUNDING: Data collection was funded by the Wake Forest NCORP Research Base grant 2UG1CA189824 with support of the NCI Community Oncology Research Program (NCORP). Additional funding for this study was provided by grants from the National Institutes of Health, National Cancer Institute (1R01CA199167 and 5T32CA093423). CLINICAL TRIAL ID: NCT02791581 for WF97415 UPBEAT.

Ethics of rural health care.

One quarter of the US population live in areas designated as rural. Delivery of rural health care can be difficult with unique challenges including limited access to specialists such as oncologists. The Rural Cancer Outreach Program is an alliance between an academic medical center and five rural hospitals. Due to the presence of this program, the appropriate use of narcotics for chronic pain has increased, the number of breast conserving surgeries has more than doubled and accrual to clinical trials has gone from zero to nine over the survey period. An increase in adjuvant chemotherapy has been noted. The rural hospitals and the academic center have seen a positive financial impact. The most prominent ethical issues focus on justice, especially access to health care, privacy, confidentiality, medical competency, and the blurring of personal and profession boundaries in small communities. As medical care has become more complex with an increasing number of ethical issues intertwined, the rural hospitals have begun to develop mechanisms to provide help in difficult situations. The academic center has provided expertise and continued education for staff, both individually and within groups, regarding ethical dilemmas.

Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation.

PURPOSE: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. METHODS AND MATERIALS: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. RESULTS: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for complete responders was 68%. This is in contrast to the 14% 5-year overall survival observed with incomplete responders. The 5-year actuarial disease-free survival and overall survival for the entire patient cohort was 11% and 33%, respectively. All patients tolerated irradiation with limited acute effects, of which all were managed conservatively. CONCLUSION: Our experience demonstrates that induction chemotherapy, accelerated superfractionated radiotherapy, and the selected use of mastectomy results in excellent locoregional control rates, is well tolerated, and optimizes breast preservation. Based on our present results, we recommend that a patient's response to induction chemotherapy guide the treatment approach used for locoregional disease, such that mastectomy be reserved for incomplete responders and avoided in those achieving a complete response.

Bone marrow changes associated with recombinant granulocyte-macrophage and granulocyte colony-stimulating factors. Discrimination of granulocytic regeneration.

The hematopoietic growth factors recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human granulocyte colony-stimulating factor are associated with changes of the bone marrow. To evaluate the morphologic features and to differentiate them from leukemia, bone marrow specimens from 12 patients who had been treated with one of these agents were evaluated. The bone marrow displayed marked promyelocytic hyperplasia and a less striking increased percentage of myeloblasts. In each of the 11 patients without leukemia at the time of bone marrow biopsy, the percentage of promyelocytes in the bone marrow was greater than that of myeloblasts. Cytologic features of stimulated regeneration included diffuse cytoplasmic hypergranulation of immature neutrophilic precursors that had prominent perinuclear spherical clear areas representing the Golgi zones. With consideration of bone marrow composition and careful attention to cytologic detail, the distinction of bone marrow regeneration from acute leukemia can be made in most patients who are being treated with recombinant hematopoietic growth factors.

How long does it take to get a "do not resuscitate" order?

UNLABELLED: Less than 50% of physicians know the resuscitation wishes of their patients and only a small fraction of patients have completed "do not resuscitate" (DNR) orders before death. One of the common reasons given by physicians is that the process of "getting a DNR" takes too long, and some authorities have suggested that additional reimbursement is needed. The purpose of this study is to assess how long the DNR education and consent process actually takes in practice. Our study group was a convenience sample of consecutive patients seen by experienced oncologists in a community and academic practice setting. Physicians were asked to record the time spent in DNR discussions with patients, the outcomes, and their comments. DNR orders were obtained on 16 of 22 patients with a single interview lasting a mean time of 16 minutes. Additional DNR orders were obtained on two more patients after a second interview of 6 patients, mean time 17.5 minutes. After a third interview of 4 patients, mean time 23 minutes, only 2 of 22 patients would not allow DNR orders. Of these two, one died intubated in the intensive care unit and the other underwent continued unsuccessful induction therapy for acute leukemia before dying. CONCLUSION: DNR orders can be obtained on nearly all patients within the time frame of an inpatient or outpatient visit. Time is not the main obstacle to DNR discussions, and additional reimbursement for additional time is not necessary. A small subset of patients continue to refuse DNR orders. Physician and patient reluctance to broach the subject may be a bigger impediment than time.

Percutaneous liver biopsy in adult haemophiliacs with hepatitis C virus: safety of outpatient procedure and impact of human immunodeficiency virus coinfection on the spectrum of liver disease.

Both HCV and HIV are common in haemophiliacs previously treated with non-viral-inactivated clotting factor concentrates. Because of increased bleeding risks, little data are available on the safety of percutaneous outpatient liver biopsy (LBx) and impact of HIV coinfection in this population. This study aims at reporting our experience with percutaneous LBx in a cohort of haemophiliacs infected with HCV and describe the spectrum of disease and impact of HIV coinfection. A retrospective review of consecutive patients with haemophilia and HCV who underwent percutaneous LBx was performed. All patients were positive for HCV RNA by commercial assay and received factor concentrate prior to biopsy. A total of 29 male patients (mean age 36, 24 haemophilia A, five haemophilia B, and 44% coinfected with HIV) underwent successful outpatient percutaneous LBx without bleeding complication. Histologic activity index was 6.44 with advanced fibrosis (bridging fibrosis/cirrhosis) in 31%. When patients were stratified by HIV positive (n = 13) vs. HIV negative (n = 16), coinfected patients had higher fibrosis scores and higher proportion advanced fibrosis (54% vs. 12%; P = 0.0167) with no differences in age, demographic or other laboratory parameters. Multivariate logistic regression found that HIV positivity was independently associated with advanced fibrosis (OR = 3.7; 95% CI: 1.17-11.8; P = 0.026). Outpatient percutaneous LBx can be safely performed in patients with haemophilia. Despite similar age, HIV coinfection was an independent predictor of advanced fibrosis. These data support the hypothesis that HIV accelerates fibrosis progression in those coinfected with HCV and highlights the importance of liver histology in this population.