Robert Chapman

Activation of Nuclear Factor κB in Single Living Cells DEPENDENCE OF NUCLEAR TRANSLOCATION AND ANTI-APOPTOTIC FUNCTION ON EGFPRELA CONCENTRATION

We have studied the dynamics of nuclear translocation during nuclear factor κB activation by using a p65(RELA)-enhanced green fluorescent protein (EGFP) fusion construct. Quantitation of expression levels indicates that EGFPRELA can be detected at physiological concentrations of about 60,000 molecules per cell. Stimulation of transfected fibroblasts with interleukin (IL)-1β caused nuclear translocation of EGFPRELA, typically resulting in a 30-fold increase in nuclear protein at maximum induction and a concomitant 20% decrease in cytoplasmic levels. The response of individual cells to IL-1β was graded, and the kinetics of nuclear translocation were dependent on the dose of IL-1β and the level of EGFPRELA expression. The rate of nuclear uptake was saturable, and the time lag for uptake increased at higher EGFPRELA expression levels. Furthermore, nuclear translocation was reduced at less than saturating doses of IL-1β suggesting that the pathway is limited by incoming signals. The response to IL-1β was biphasic, demonstrating a decline in nuclear import rate at expression levels above three to four times endogenous. This correlated with the anti-apoptotic function of EGFPRELA which was more prominent at low expression levels and demonstrated successively less protection at higher levels. In comparison, transfection of p50 had no effect on the level of apoptosis and demonstrated some toxicity in combination with EGFPRELA.

Phase II trial of paclitaxel by 24-hour continuous infusion for relapsed non-Hodgkin's lymphomas: Southwest Oncology Group trial 9246.

PURPOSE The Southwest Oncology Group (SWOG) recently conducted a multiinstitutional phase II trial to determine the complete response (CR) and partial response (PR) rates, toxicities, and progression-free and overall survivals of patients with relapsed non-Hodgkins lymphomas (NHLs) treated with a 24-hour continuous infusion of paclitaxel at a dose of 175 mg/m2. PATIENTS AND METHODS Sixty-six patients with relapsed NHL who had received minimal prior therapy (one prior chemotherapy regimen for intermediate- to high-grade NHL [44 patients] or one or two prior regimens for low-grade NHL [22 patients]) were premedicated with dexamethasone, diphenhydramine, and cimetidine and then treated with continuous intravenous infusion paclitaxel over 24 hours every 21 days. RESULTS Eleven of 66 patients (17%) achieved rigorously documented objective remissions, including two CRs (3%) and nine PRs (14%). In addition, another five patients (8%) achieved apparent PRs on a single computed tomographic (CT) scan. Responses were brief, lasting a median of 3 months (5 months for indolent lymphomas and 3 months for intermediate- to high-grade lymphomas). Grade 4 or 5 granulocytopenia was the only common serious toxicity, and occurred in 42 of 66 patients (64%). CONCLUSION Paclitaxel is generally well tolerated when given as a continuous infusion of 175 mg/m2 over 24 hours, despite predictable granulocytopenia. However, single-agent paclitaxel has modest clinical efficacy compared with other available treatments for relapsed NHL.

An Analysis of Race-related Attitudes and Beliefs in Black Cancer Patients: Implications for Health Care Disparities.

Abstract:This research concerned relationships among Black cancer patients’ health care attitudes and behaviors (e.g., adherence, decisional control preferences,) and their race-related attitudes and beliefs shaped by (a) general life experiences (i.e., perceived discrimination, racial identity) and (b) experiences interacting with health care systems (i.e., physician mistrust, suspicion about medical care). Perceived discrimination, racial identity, and medical suspicion correlated weakly with one another; mistrust and suspicion correlated only moderately. Race-related attitudes and beliefs were associated with health care attitudes and behavior, but patterns of association varied. Physician mistrust and medical suspicion each independently correlated with adherence and decisional control preferences, but discrimination only correlated with control preferences. Associations among patients’ different racial attitudes/beliefs are more complex than previously assumed. Interventions that target patient attitudes/beliefs and health care disparities might be more productive if they focus on mistrust or suspicion specific to health care providers/systems and their correlates identified in this study.

Patient and oncologist discussions of treatment costs.

178 Background: Financial toxicity-the burden of treatment costs and its impact on well-being, treatment decisions, and outcomes-affects many cancer patients, especially racial minorities. Discussing cost during clinic visits may ease financial toxicity, but oncologists are often hesitant to discuss cost. A better understanding of cost discussions is needed to improve care and inform oncologist training interventions. We conducted an observational study of patient-oncologist treatment cost discussions during clinic visits. METHODS Data were video-recorded clinic visits of African American patients (114) and their medical oncologists (19) meeting for the first time to discuss treatment. Cost discussions were any verbal expression of a direct (paying for scans) or indirect (time off work) expense to the patient for treatment. Trained coders observed the videos and coded for presence, duration, initiation, topic, oncologist response, and patient reaction of cost discussions. RESULTS Cost discussions occurred in 44% (n = 50) of the visits with a range of 1-6 per visit for a total of 93 discussions (M = 35 seconds; SD = 28). Patients initiated (61%) more than oncologists (38%), and patients were more likely to initiate multiple times. Time off work was discussed most (48%), followed by insurance (26%), transportation (12%), paying for treatment (8%), and job loss (4%). Time off work was the most commonly patient initiated topic and insurance was the most commonly oncologist initiated topic. Oncologists typically addressed the issue (72%), and patients often reacted positively (81%) but passively. A few times (9%) the oncologist acknowledged the patients initiation but did not address it. Negative patient reactions were rare and only occurred when the oncologist responded to a patient initiation (5%). Younger patients were more likely discuss cost than older patients (p = .02) and retired patients were less likely to discuss cost (p = .05). CONCLUSIONS Findings suggest discussing indirect cost is important to patients, but oncologists infrequently initiate and do not always respond adequately when patients initiate. Further research and interventions are needed to address patient-oncologist cost discussions and the economic impact of cancer treatment.

Oncologists’ discussions of treatment goals and prognosis during clinic visits with African Americans with advanced cancer.

34 Background: The National Academy of Medicine recommends that cancer patients be informed of their prognosis to enable informed treatment decisions, but research shows few patients receive this information. This problem is greater for minorities, who experience poorer quality clinical communication and end-of-life care relative to white patients. This study describes patient-oncologist discussions about treatment goals/prognosis during clinic visits with African American patients. METHODS Data were from a larger study of communication between African Americans and medical oncologists at two cancer hospitals in Detroit, MI. The present study included video recordings/transcripts of clinic visits with patients with Stage III (n=20) or IV (n=6) cancer and their oncologists (n=9). Two investigators read the transcripts independently to determine whether treatment goals and/or prognosis were mentioned; disagreement was resolved through discussion. Discourse analysis was conducted to describe interactional strategies oncologists used to discuss or avoid discussing these topics. RESULTS Treatment goals were discussed during most visits (n=24; 92.3%); prognosis was discussed less frequently (n=19; 73.1%). Oncologists often used vague language to describe prognosis (e.g. prognosis is a bit worse in your case). Only one visit included a clear survival estimate. Oncologists used clear language when the goal was cure, but when describing other goals, they often used technical terms (e.g., reduce the risk of recurrence); imprecise terms (e.g., keep the cancer in check); and emphasized uncertainty (e.g., these lesions are suspicious). Oncologists missed opportunities to further explain or elicit patient questions or preferences by directing the discussion to the urgency and details of treatment. CONCLUSIONS Oncologists used ambiguous language to discuss treatment goals/prognosis and missed opportunities to discuss patient perspectives or other options, including palliative care. Interventions are needed to improve communication about these important topics, especially among minority patients with advanced cancer.

Assessing cancer clinic visit time as a marker of quality care.

95 Background: The uses of patient time and clinic space in outpatient cancer clinics can be indicators of efficiency and quality of cancer care. Inefficient use of these can have deleterious effects on clinic flow, patient satisfaction, physician/staff morale, and treatment adherence. We tested a unique method of assessing patient time and clinic space in cancer clinics as a measure of cancer care quality. METHODS We video recorded patient occupancy in exam rooms in two outpatient cancer clinics (n = 53) using an IRB-approved, custom-designed unobtrusive recording system (Albrecht et al. 2005) and analyzed use of time. Coders assessed: Patient Occupancy Time (total time in the exam room; POT); Patient Wait Time (time spent in the exam room prior to seeing the oncologist; PWT); and Physician-Patient Interaction Time (PPIT). POT was compared with Scheduled Occupancy Time (from clinic records; SOT) to obtain measures of Discrepancy in Occupancy Time (difference in scheduled exam room time and actual time the patient spent in the exam room; DiOT). RESULTS Mean POT across both clinics was 82.0 minutes (SD = 36.2), mean PWT was 24.8 minutes (SD = 26.0), and mean PPIT was 31.4 (SD = 14.9) minutes. SOT was only available for Clinic A in which case mean DiOT was 42.6 minutes with a range of 3.5 to 146.5 minutes. Only three cases used the room for less time than originally scheduled. SOT was unrelated to POT, PWT, and PPIT. DiOT was unrelated to PPIT. CONCLUSIONS This method of objectively measuring cancer clinic time can help inform interventions to improve clinic efficiency. We found wait times were lengthy, suggesting an inefficient use of time and space. Importantly, there was no consistent relationship between scheduled and actual time spent in the exam room, reflecting an inefficient use of resources and potential inaccuracy in using scheduled time as a valid measure of quality. [Table: see text].