Clinical outcomes and transfusion management following intracranial hemorrhage in patients with acute leukemia.

BACKGROUND: There is little evidence to guide management of patients with acute leukemia and intracranial hemorrhage (ICH). Predictors of long-term outcome following ICH are unknown. STUDY DESIGN AND METHODS: This study included adult patients with acute leukemia and ICH over an 8-year period. The primary outcome was data regarding 90-day mortality. Secondary outcomes included data related to the proportion of patients receiving post-remission therapy and predictors of 90-day mortality. RESULTS: ICH occurred in 101 patients; 12 patients died within 72 hours. For the 89 others, 90-day mortality was 40%. Of 43 patients who received induction, 30 achieved remission and 26 received post-remission therapy. Older age (p = 0.03) and higher white count (p = 0.02) at the time of ICH were predictive of inferior survival. During 90-day follow-up, median platelet count was 37 x 109 /L (0-1526 x 109 /L). Lower platelet count during follow-up was predictive of 90-day mortality (p = <0.01). Twenty-one percent of platelet transfusions were provided when the platelet count was less than 10 x 109 /L, 54% between 10 and 29 x 109 /L, and 25% greater than 30 x 109 /L. New or progressive ICH occurred in 23 patients. There was no difference in the median platelet transfusion trigger between patients who had new or progressive ICH and those who did not. CONCLUSION: In patients with acute leukemia, survival following ICH is poor. Older age and higher white count is associated with increased mortality, perhaps reflecting higher risk disease. Following ICH in acute leukemia platelet transfusions do not appear to alter the risk of progressive bleeding or mortality.

Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a retrospective study.

BACKGROUND: While the efficacy of olanzapine in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) has been documented, the literature on the use of olanzapine as a rescue medication for breakthrough CINV has been scarce. The following study retrospectively evaluated the safety and efficacy of olanzapine for the treatment of breakthrough CINV. The efficacy and safety of olanzapine in the prophylactic setting was also examined in a smaller cohort. METHODS: Electronic medical records of adult patients aged >17 years receiving a prescription for olanzapine from the Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 and June 2015 were reviewed retrospectively. Inclusion criteria required receiving one or more doses of olanzapine for the rescue or prophylaxis of CINV and documentation of the outcome. RESULTS: A total of 154 patients and 193 treatment cycles were included in the breakthrough setting, while a total of 16 patients and 20 treatment cycles were included in the prophylaxis setting. In the breakthrough setting, 88% of cases experienced improved nausea, while 21% of cases reported improved vomiting. In the prophylactic setting, 100% of cases experienced improved nausea, while 65% achieved improved vomiting. A total of 43% of cases in the breakthrough setting and 65% of cases in the prophylactic setting experienced sedation. CONCLUSIONS: Olanzapine is effective in improving CINV in both the prophylactic and breakthrough settings. The safety, efficacy, and appropriate dosage of olanzapine for the rescue of breakthrough CINV should be prospectively evaluated in a randomized controlled trial (RCT).

The incidence of neuropathic pain in bone metastases patients referred for palliative radiotherapy.

BACKGROUND AND PURPOSE: To estimate the prevalence of neuropathic pain in patients with symptomatic bone metastases referred for palliative radiotherapy. MATERIAL AND METHODS: A prospective study of patients with symptomatic bone metastases was conducted. Patients referred for palliative radiotherapy completed the Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire to assess for neuropathic pain. Patient demographics, medication use, and radiotherapy prescribed were collected. Statistical approaches to identify relationships between the presence of neuropathic and other patient factors were conducted. RESULTS: 62 patients completed the S-LANSS and 16 (25.8%) patients had a score suggesting neuropathic pain. Fifty-nine (95.2%) patients received radiotherapy with total of 81 sites treated, the most common sites were spine and pelvis. No statistically significant difference in fractionation was found between patients with and without neuropathic pain. Of the 16 patients with neuropathic pain, only 2 were receiving a neuropathic specific analgesic. No significant difference between demographic factors or radiation treatments between patients with and without neuropathic pain was found. There was no significant difference in worst pain score between these two groups. CONCLUSIONS: Pain with neuropathic features remains prevalent in a population of patients referred for palliative radiotherapy. More frequent prescription of pain medications targeting neuropathic pain may be warranted in this patient population.

Comparison of the EORTC STO-22 and the FACT-Ga quality of life questionnaires for patients with gastric cancer.

This review compares the development, characteristics, validity, and reliability of two well-known quality of life (QOL) assessment tools used in patients with gastric cancer: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach (EORTC QLQ-STO22) and the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). A literature search was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL (inception to April 2015) to identify studies that discussed the development, characteristics, validity and reliability of the EORTC QLQ-STO22 or the FACT-Ga. The QLQ-STO22 was developed with collaboration with patients, healthcare professionals and literature review and was mainly field tested in European countries. Conversely, items on the FACT-Ga were generated from interviews with patients and healthcare professionals concurrently in North America and Asia. While both modules involve a 7-day recall period and use Likert scales, the QLQ-STO22 and FACT-Ga differ in terms of QOL domain focus, quantity and presentation of items, response options, and scoring. However, both tools show good internal consistency, test-retest reliability, sensitivity to change and construct validity. In addition, both questionnaires have been internationally validated within a large sample of patients undergoing a variety of treatments, thus demonstrating their cross-cultural applicability. The EORTC QLQ-STO22 and FACT-Ga are both valid and reliable tools with unique strengths and weaknesses. Selection between instruments should consider specific patient characteristics and goals of the study.

The accuracy of clinicians' predictions of survival in advanced cancer: a review.

The process of formulating an accurate survival prediction is often difficult but important, as it influences the decisions of clinicians, patients, and their families. The current article aims to review the accuracy of clinicians' predictions of survival (CPS) in advanced cancer patients. A literature search of Cochrane CENTRAL, EMBASE, and MEDLINE was conducted to identify studies that reported clinicians' prediction of survival in advanced cancer patients. Studies were included if the subjects consisted of advanced cancer patients and the data reported on the ability of clinicians to predict survival, with both estimated and observed survival data present. Studies reporting on the ability of biological and molecular markers to predict survival were excluded. Fifteen studies that met the inclusion and exclusion criteria were identified. Clinicians in five studies underestimated patients' survival (estimated to observed survival ratio between 0.5 and 0.92). In contrast, 12 studies reported clinicians' overestimation of survival (ratio between 1.06 and 6). CPS in advanced cancer patients is often inaccurate and overestimated. Given these findings, clinicians should be aware of their tendency to be overoptimistic. Further investigation of predictive patient and clinician characteristics is warranted to improve clinicians' ability to predict survival.

Latest advances in the management of radiation-induced pain flare, nausea and vomiting.

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

The Brain Symptom and Impact Questionnaire in brain metastases patients: a prospective long-term follow-up study.

AIMS: To assess the ability of the Brain Metastases Symptom and Impact Questionnaire (BASIQ) in evaluating symptoms and impact on daily life. PATIENTS & METHODS: Patients with brain metastases completed BASIQ, Functional Assessment of Cancer Therapy-General, FACT-Brain at baseline and at 1, 2 and 3 months follow-ups. RESULTS: Thirty-six patients completed all follow-ups. BASIQ correlated well (r ≥ 0.40) with FACT subscales, except for social/family and emotional wellbeing. Linear regression analysis found no significant changes in quality of life (QOL) over time in both the BASIQ and FACT scales. Therefore, the two questionnaires coincide as both detected nonchanges. CONCLUSION: The ability of the BASIQ in evaluating symptoms and impact on over longer assessment periods was supported by the FACT questionnaires.

Cut points for mild, moderate, and severe pain among cancer and non-cancer patients: a literature review.

Defining cut points (CPs) for varying levels of pain intensity is important for assessing changes in patient's functional status, and guiding the development and evaluation of treatment options. We aimed to summarize CPs identified in the literature for mild, moderate, and severe pain on the numeric rating scale (NRS), and recommend optimal CPs for cancer and non-cancer patients. We searched MEDLINE and EMBASE (inception to May 2015) for studies that used CPs to classify pain intensity on the NRS among patients with cancer or non-cancer conditions leading to acute or chronic pain. A CP was defined as the upper bound of a mild or moderate pain category. Of 1,556 identified articles, 27 were included for review. Among patients with cancer pain, mild-moderate pain CPs ranged from 1 to 4 (mean, 3.5±1.08), with CP4 being the most recommended CP (80%). For moderate-severe pain, CPs ranged from 4 to 7 (mean, 6.2±0.92), and CP6 (50%) was the optimal CPs. Among patients with non-cancer pain, mild-moderate pain CPs ranged from 2 to 5 (mean, 3.62±0.78), and CP4 was the most frequently used CP (52.9%). For moderate-severe non-cancer pain, CPs ranged from 4 to 8 (mean, 6.5±0.99), and CP6 (41.2%) was the most frequently recommended CP. A wide range of CPs for mild, moderate, and severe pain categories were identified in the literature among both cancer and non-cancer patient populations. Further studies are needed to delineate more accurate and precise CPs for pain intensity.

Re-irradiation for painful bone metastases: evidence-based approach.

The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non-responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions.

Incorporation of life expectancy estimates in the treatment of palliative care patients receiving radiotherapy: treatment approaches in light of incomplete prognostic models.

Physician estimates of patients' survival times have historically been inaccurate. In particular, physicians have often been overly optimistic in their predictions. Our review begins by documenting some of the literature addressing these concerns and proceeds to a discussion of prognostic models that have been created to aid physicians in providing more accurate estimates. We then discuss new findings showing survival to be influenced by particular treatment factors. Given such findings, currently existing prognostic models are now incomplete. However, with the abundance of evidence-based treatment options in a wide variety of patient populations, we propose that radiation oncologists need no longer rely so heavily on the precise prognostic capacity of survival models. Patients of different age demographics and survival prognoses benefit from palliative radiation treatment. More specifically, our report documents studies which show that for uncomplicated bone metastases, a single 8 Gy fraction of radiation is an equally effective tool for palliation regardless of whether a patient will have a short or long duration of survival. In addition we discuss evidence-based treatment options for patients with complicated bone metastases, lung and brain metastases. Further research is required to incorporate treatment factors in future survival prediction models.

Psychometric validation of the Brain Symptom and Impact Questionnaire (BASIQ) version 1.0 to assess quality of life in patients with brain metastases.

OBJECTIVE: To test the reliability, clinical and psychometric validity of the Brain Symptom and Impact Questionnaire (BASIQ) in patients with brain metastases. METHODS: Brain metastases patients were interviewed using the BASIQ, Functional Assessment of Cancer-Brain (FACT-Br) and FACT-General (FACT-G) at baseline, with a follow-up assessment at 1 month. RESULTS: Forty patients had complete one data and the median age was 64 years. Patients with higher KPS, ECOG of 2, primary breast cancer, or >3 brain metastases, scored higher on the symptom scale of the BASIQ. All subscales showed no significant change in patient symptoms from baseline to follow-up. CONCLUSION: This study supports that the reliability, clinical and psychometric validity of BASIQ to be used in brain metastases patients.

Student Accomplishments in the Rapid Response Radiotherapy Program: A 10-Year Review.

In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid Response Radiotherapy Program (RRRP). The objective of this clinic is to consult, simulate, plan, and treat patients with palliative radiotherapy on the same day. In 2004, the RRRP initiated a program to provide clinical and research experience to undergraduate students interested in health sciences. The purpose of this study is to review the 10-year (2004-2013) experience of the RRRP and to examine whether the goals of the student program have been met. Students who worked in the RRRP from 2004 to 2013 were contacted to complete a short survey regarding their overall experience with the program and their current endeavors. Student accomplishments were collected from an internal database as well as PubMed. Descriptive statistics were used to analyze results. A total of 54 students from ten postsecondary institutions have worked in the RRRP; 29 were from the University of Waterloo undergraduate co-op program. In total, 214 articles with first authorship from students were published, 93 (43%) of which can be found on PubMed. Other accomplishments include 40 book chapters, 58 invited presentations, and 99 awards cumulatively. Qualitative data regarding student perspectives of their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP has achieved its goal of providing quality medical and research experience to students interested in the health sciences. Using the responses of past and present students, we hope to continue to shape our program and provide unique opportunities to future students.

The effects of denosumab on calcium profiles in advanced cancer patients with bone metastases.

OBJECTIVE: To retrospectively examine the incidence and management of hypocalcemia for patients with bone metastases treated with denosumab. METHODS: Patients who had a record of filling a prescription of denosumab for treatment of bone metastases at the outpatient pharmacy at the Odette Cancer Centre from May 2011 to February 2013 were included in the analysis. Demographic information, previous bisphosphonate usage, calcium and albumin values, and adverse events were obtained using the Sunnybrook Electronic Patient Record system (EPR) and the Oncology Symptom Control and Information Resource (OSCIR). Hypocalcemia was defined as a calcium value below 2.0 mmol/L within a 28-day±7-day window after the last injection of denosumab based on the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 hypocalcemia. RESULTS: A total of 55 patients had record of a prescription for denosumab filled with an average age of 62 years (range 40 to 93 years), 18 (32.7%) were males and 37 (67.3%) were females. Twenty-nine (52.7%) patients had primary breast cancer, 12 (21.8%) prostate, 10 (18.2%) lung, and 4 (7.3%) with other types. Using CTCAE grading of hypocalcemia, 17 (32.7%) patients experienced grade 1, 4 (7.7%) patients grade 2, 4 (7.7%) patients grade 3, and 1 (1.9%) patient grade 4. The number of injections before the incident of hypocalcemia was a median of one injection (range 1 to 14). Time from the first hypocalcemia lab value to normocalcemia was a median of 33 days. CONCLUSIONS: This study found that 9 of 52 (17.3%) patients had at least one incidence of hypocalcemia of grade 2 or higher after receiving denosumab. Cautionary measures should be taken to avoid hypocalcemia in patients receiving denosumab.

Fatigue scores in patients with brain metastases receiving whole brain radiotherapy.

PURPOSE: Whole brain radiotherapy (WBRT) is a treatment strategy used commonly to relieve burdensome symptoms and improve quality of life (QOL) in patients with multiple brain metastases. The purpose of this study is to determine changes in fatigue score following WBRT as it is a common symptom experienced in this population. METHODS: Fatigue and overall QOL scores were collected prospectively in patients for up to 3 months post-WBRT by several questionnaires at different times including the following: Edmonton Symptom Assessment System (ESAS), Brain Symptom and Impact Questionnaire (BASIQ), Spitzer Questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC brain module (EORTC QLQ-BN20+2), EORTC QLQ-C15-PAL, and Functional Assessment of Cancer Therapy-General (FACT-G). Questionnaires were grouped for analysis by Wilcoxon Signed Rank test according to the scale of ranking into 0-10, 1-4, and 0-4. RESULTS: Thirty-six patients were interviewed with the ESAS or BASIQ. The median age was 65 years old, and median Karnofsky Performance Status (KPS) was 70. There was a significant increase in fatigue score from baseline to month 1 (p=0.02), and months 2 and 3 had no significant change. There was a significant correlation between fatigue and overall QOL score at baseline and month 1 (p=0.01, p<0.0001), respectively. Two hundred and twenty-eight patients were surveyed with Spitzer, C15-PAL, BN20+2, QLQ-C30, or FACT-G. Median age was 64 years old and median KPS was 80. Compared to baseline, fatigue score was significantly higher at month 1 (p<0.0001) and month 2 (p=0.001), with no significant change at month 3. Significant correlation was found between fatigue and overall QOL at baseline, months 1, 2 (p<0.0001), and 3 (p=0.0009). For all groups, there was no significant change in fatigue score between patients with or without dexamethasone (Dx), except for the fatigue changed score of the group with scale 0-4. CONCLUSIONS: Fatigue was significantly increased from baseline to month 1 in all patients, and most patients experienced no difference in fatigue if they were receiving Dx. Increased fatigue was significantly related with decreased overall QOL.

Review of international patterns of practice for the treatment of painful bone metastases with palliative radiotherapy from 1993 to 2013.

BACKGROUND AND PURPOSE: Numerous randomized controlled trials and meta-analyses have affirmed that single and multiple fractions of radiotherapy provide equally efficacious outcomes in the palliation of painful, uncomplicated bone metastases (UBM). We aim to determine geographic, temporal and ancillary factors that influence the global patterns of practice in this setting. MATERIALS AND METHODS: A literature search was conducted on Ovid MEDLINE and EMBASE. Studies were included if they disclosed prescription patterns of single fraction radiotherapy, either through hypothetical cases or actual patient data. Weighted analysis of variance was conducted for binary predictors while weighted linear regression analysis was performed for continuous parameters. RESULTS: Nine hypothetical case studies and thirteen actual patterns of practice articles were included from 301 search results. Radiation oncologists prescribed dose fractionations ranging from 3Gy×1 to 2Gy×30, with a median of 3Gy×10, for the palliation of UBM. Actual data demonstrated a weak, non-significant, negative linear relationship between the use of single fraction radiotherapy and the year of treatment. Geographical location of treatment was a key predictor of prescription patterns. CONCLUSION: In the last twenty years, there was an overall global reluctance to practice evidence-based medicine by employing single fractions for UBM.