Lisa W. Le

Phase II Study of an Outpatient Palliative Care Intervention in Patients With Metastatic Cancer

PURPOSE Although there is increasing advocacy for timely symptom control in patients with cancer, few studies have assessed outpatient palliative care clinics. This study assessed prospectively the efficacy of an Oncology Palliative Care Clinic (OPCC) in improving patient symptom distress and satisfaction. PATIENTS AND METHODS Eligible patients were new referrals to an OPCC, had metastatic cancer, were at least 18 years old, and were well enough and able to speak and read English sufficiently to provide informed consent and complete questionnaires. Patients received a consultation by a palliative care team. The primary end points of symptom control and patient satisfaction were assessed using the Edmonton Symptom Assessment Scale (ESAS) and patient-adapted Family Satisfaction with Advanced Cancer Care (FAMCARE) scale at baseline, 1 week, and 1 month. Initial and follow-up scores were compared using paired t tests. RESULTS Of 150 patients enrolled, 123 completed 1-week assessments, and 88 completed 4-week assessments. At baseline, the mean ESAS Distress Score (EDS) was 39.5. The mean improvement in EDS was 8.8 points (P < .0001) at 1 week and 7.0 points (P < .0001) at 1 month. Statistically significant improvements were observed for pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, dyspnea, insomnia, and constipation at 1 week (all P < or = .005) and 1 month (all P < or = .05). The mean improvement in FAMCARE score was 6.1 points (P < .0001) at 1 week and 5.0 points (P < .0001) at 1 month. CONCLUSION This phase II study demonstrates efficacy of an OPCC for improvement of symptom control and patient satisfaction with care. Randomized controlled trials are indicated to further evaluate the effectiveness of specialized outpatient palliative care.

Referral practices of oncologists to specialized palliative care.

PURPOSE To describe current referral practices of oncologists to specialized palliative care (SPC) and define demographic characteristics, practice situations, and opinions associated with referral. METHODS Physician members of the Canadian Association of Medical Oncologists, Canadian Association of Radiation Oncologists, and Canadian Society of Surgical Oncology were invited to participate in an anonymous survey assessing SPC referral practices. Participants received two e-mailed and two mailed invitations. RESULTS The response rate was 72% (603 of 839 physicians); 37% were medical oncologists/hematologists, 50% were radiation oncologists, and 12% were surgical oncologists. Ninety-four percent reported that SPC was available to them, but only 37% reported that these services accepted patients on chemotherapy. Eighty-four percent referred terminally ill patients usually/always, but generally for uncontrolled symptoms or discharge planning late in the disease course. One third would refer to SPC earlier if it was renamed supportive care. Predictors of higher referral frequency included comprehensiveness of available SPC services (P = .004), satisfaction with SPC availability (P < .001), SPC acceptance of patients receiving chemotherapy (P < .001), and oncologist ease with referring patients to a palliative care service before they were close to death (P < .001). Controlling for specialty, predictors of referral at diagnosis or during chemotherapy, rather than later, included satisfaction with SPC service availability (P < .001) and SPC service acceptance of patients on chemotherapy (P < .001). CONCLUSION Oncologists referred patients frequently to SPC, but generally late in the disease course for patients with uncontrolled symptoms. Availability of comprehensive SPC, especially for patients receiving chemotherapy, and persisting definitional issues seem to be the main barriers preventing timely referral.

Outcomes of Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal

BackgroundFor patients with anal canal cancer who fail combined modality treatment (CMT), salvage surgery (SS) offers the potential for long term survival. The literature regarding SS is limited by small patient numbers and/or heterogeneous treatment protocols. We report on a large series of patients initially treated with chemoradiation at a major referral center.MethodsWe identified 60 patients with persistent or recurrent anal cancer who had undergone SS; 20 were excluded. Overall and disease-free survival (OS, DFS) curves were constructed using the Kaplan Meier method. Univariate analysis was done using the Log-Rank test, and multivariable analysis using Cox proportional hazards.ResultsThe 40 patients (29 women, 11 men, median age 57) underwent curative intent resection. The initial procedure was multivisceral resection (n = 24), abdominoperineal resection alone (n = 14) or local excision (n = 2). Postoperative mortality was 5%. Postoperative complications were seen in 72%. Median follow-up was 18 months overall and 36 months in survivors. Median OS was 41 months; OS and disease free survival at 5 years were 39% and 30%, respectively. Recurrence was present in 21 patients at time of analysis. Failure was locoregional in 86% (18 of 21) and distant in 48% (10 of 21). Independent predictors of poor OS were male gender, Charlson Comorbidity Score and tumor size. Independent predictors of poor disease free survival were positive margins and lymphovascular invasion.ConclusionSS for anal canal cancer was associated with significant morbidity. Long-term survival was achieved in 39% of patients. Comorbidities should guide patient selection, and R0 resection should be the goal.

Treatment of Prostate Cancer With Intermittent Versus Continuous Androgen Deprivation: A Systematic Review of Randomized Trials

PURPOSE Uncertainty exists regarding benefits of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation (CAD) for treatment of prostate cancer. On the basis of a systematic review of evidence, our aim was to formulate a recommendation for either IAD or CAD to treat relapsing, locally advanced, or metastatic prostate cancer. METHODS We searched literature published up to September 2012 from MEDLINE, EMBASE, the Cochrane Library, and major conference proceedings. We included randomized controlled trials comparing IAD and CAD if they reported overall survival (OS) or biochemical/radiologic time to disease progression. RESULTS Nine studies with 5,508 patients met our criteria. There were no significant differences in time-to-event outcomes between the groups in any studies. The pooled hazard ratio (HR) for OS was 1.02 (95% CI, 0.94 to 1.11) for IAD compared with CAD, and the HR for progression-free survival was 0.96 (95% CI, 0.76 to 1.20). More prostate cancer-related deaths with IAD tended to be balanced by more deaths not related to prostate cancer with CAD. Superiority of IAD for sexual function, physical activity, and general well-being was observed in some trials. Median cost savings with IAD was estimated to be 48%. CONCLUSION There is fair evidence to recommend use of IAD instead of CAD for the treatment of men with relapsing, locally advanced, or metastatic prostate cancer who achieve a good initial response to androgen deprivation. This recommendation is based on evidence against superiority of either strategy for time-to-event outcomes and substantial decrease with IAD in exposure to androgen deprivation, resulting in less cost, inconvenience, and potential toxicity.

The Association of Physical and Psychological Symptom Burden with Time to Death Among Palliative Cancer Outpatients

Previous studies have reported on the symptom burden of cancer inpatients, but outpatient studies have been few and have not examined the association of symptoms with time to death (TTD). Cancer patients seen in an oncology palliative care clinic from January 2005 to June 2006 and who subsequently died were identified from a palliative care database. Data from the last outpatient Edmonton Symptom Assessment Scale (ESAS) score completed in clinic were analyzed among patients who were followed during the last four months of life. Multiple linear regression analyses with Bonferroni adjustment were used to determine the association of ESAS total symptom distress score (TSDS), physical subscore (PHS), psychological subscore (PSS), and individual symptom scores with demographic parameters, disease characteristics, and TTD. Data from 198 patients were analyzed. All had stage IV cancer, the median age was 65, and 55% were men. There was no significant association between symptom burden and age, gender, or cancer site. TTD was significantly associated with TSDS (P=0.001) and PHS (P=0.001) but not with PSS (P=1.0). Individual symptoms most strongly associated with TTD were lack of appetite (P=0.001), drowsiness (P=0.006), dyspnea (P=0.009), and fatigue (P=0.01). There was no significant association between TTD and anxiety (P=1.0) or depression (P=1.0). Lack of appetite, drowsiness, dyspnea and fatigue represent a cluster of symptoms that tend to intensify at the end of life. The lack of intensification of psychological symptoms in relation to time to death is striking and needs to be further investigated using specific validated measures for depression and anxiety.

Simple Prognostic Model for Patients With Advanced Cancer Based on Performance Status

PURPOSE Providing survival estimates is important for decision making in oncology care. The purpose of this study was to provide survival estimates for outpatients with advanced cancer, using the Eastern Cooperative Oncology Group (ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status (KPS) scales, and to compare their ability to predict survival. METHODS ECOG, PPS, and KPS were completed by physicians for each new patient attending the Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC) from April 2007 to February 2010. Survival analysis was performed using the Kaplan-Meier method. The log-rank test for trend was employed to test for differences in survival curves for each level of performance status (PS), and the concordance index (C-statistic) was used to test the predictive discriminatory ability of each PS measure. RESULTS Measures were completed for 1,655 patients. PS delineated survival well for all three scales according to the log-rank test for trend (P < .001). Survival was approximately halved for each worsening performance level. Median survival times, in days, for each ECOG level were: EGOG 0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to 70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C-statistic was similar for all three scales and ranged from 0.63 to 0.64. CONCLUSION We present a simple tool that uses PS alone to prognosticate in advanced cancer, and has similar discriminatory ability to more complex models.

Biomarker testing and time to treatment decision in patients with advanced nonsmall-cell lung cancer

BACKGROUND Testing for EGFR mutations and ALK rearrangement has become standard in managing advanced nonsmall-cell lung cancer (NSCLC). However, many institutions in Europe, North America and other world regions continue to face a common challenge of facilitating timely molecular testing with rapid result turnaround time. We assessed the prevalence of biomarker testing for advanced NSCLC patients and whether testing affected the timeliness of treatment decisions. METHODS We conducted a retrospective chart review of a random sample of one-quarter of all patients with advanced NSCLC referred to the Princess Margaret Cancer Centre from 1 April 2010 to 31 March 2013. RESULTS Of 300 patients reviewed, 175 seen by medical oncology had nonsquamous NSCLC, 72% of whom had biomarker testing carried out. Patients tested for biomarkers were more likely to be female (47% versus 21%, P = 0.002), Asian (27% versus 6%, P = 0.005) and never smokers (42% versus 8%, P < 0.0001). Only 21% of patients with biomarker testing had results available at their initial oncology consultation. This group had a shorter median time from consultation to treatment decision (0 versus 22 days, P = 0.0008) and time to treatment start (16 versus 29, P = 0.004). Thirteen percent underwent repeat biopsy for molecular testing after the initial consultation. Of those with positive EGFR or ALK results, 19% started chemotherapy before biomarker results became available. CONCLUSIONS Awaiting biomarker testing results can delay treatment decisions and treatment initiation for patients with advanced NSCLC. This may be avoided by incorporating reflex biomarker testing into diagnostic algorithms for NSCLC at the level of the pathologist, and further education of specialists involved in obtaining diagnostic cancer specimens to ensure they are sufficient for molecular testing.

Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

PURPOSE A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. METHODS AND MATERIALS From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. RESULTS Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus-positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were significantly better at 12 months than at baseline. Multiple dose-volume parameters correlated moderately with diarrhea, skin, and hematologic toxicity scores. CONCLUSION IMRT reduces acute grade 3 + hematologic and gastrointestinal toxicities compared with reports from non-IMRT series, without compromising locoregional control. The reported QOL scores most relevant to acute toxicities returned to baseline by 3 months after treatment.

Utilization of prophylactic cranial irradiation in patients with limited stage small cell lung carcinoma

This study reports the adoption of prophylactic cranial irradiation (PCI) in patients with limited stage small cell lung carcinoma (LS‐SCLC) at Princess Margaret Hospital (PMH) and the factors that impact PCI utilization.

Shifting Patterns in the Interpretation of Phase III Clinical Trial Outcomes in Advanced Non–Small-Cell Lung Cancer: The Bar Is Dropping

PURPOSE Despite multiple trials of new agents in advanced non-small-cell lung cancer (NSCLC), outcomes remain poor. This study explores how the design and interpretation of randomized trials in advanced NSCLC has changed over time. METHODS Phase III randomized controlled trials of systemic therapy for advanced NSCLC between 1980 and 2010 were identified, and their primary end point, outcome, statistical significance, and conclusions were recorded. RESULTS Of 245 trials identified, 203 were eligible for study inclusion. Although overall survival remains the most common primary end point of phase III trials, more trials from the last decade have used progression-free survival instead (none in 1980 to 1990, 13% in 2001 to 2010; P = .002). The percentage of trials meeting their primary statistical end points remained stable over time; however, the percentage of trials reporting a positive outcome without meeting that end point increased (30% in 1980 to 1990, 53% in 2001 to 2010; P < .001). A trend toward decreasing magnitude of survival gain in positive trials was seen over time (3.9 months in 1980 to 1990, 2.5 months in 2001 to 2010; P = .11), with a concomitant increase in the sample size of clinical trials over the same time period (median: 152 patients in 1980 to 1990, 413 in 2001 to 2010; P < .001). Only studies predating 1990 reported negative results as a result of insufficient magnitude of survival benefit despite statistical significance. CONCLUSION A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced NSCLC. The use of survival as the primary measure of benefit is declining, as is the magnitude of benefit deemed clinically relevant.