Efficacy of conventional immunosuppressants in relapsing or refractory eosinophilic granulomatosis with polyangiitis: evidence from a Canadian single-centre cohort.

OBJECTIVES: To describe the efficacy of conventional immunosuppressants in disease control of relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) compared to recently published mepolizumab and rituximab studies. METHODS: A retrospective analysis from the Toronto Vasculitis Clinic was conducted. Patients with relapsing or refractory EGPA with similar entry criteria as the main mepolizumab (MIRRA) or rituximab (case-series) studies, who were started on conventional immunosuppressants, were assessed for remission at 24- and 52-weeks. Remission was defined as a Birmingham Vasculitis Activity Score of 0 and a prednisone dose of ≤4mg/day, ≤7.5mg/day, corresponding to the mepolizumab trial, or any prednisone dose per day, as in the rituximab study. RESULTS: Among 110 cohort patients, 24 with relapsing or refractory EGPA met eligibility criteria. Conventional immunosuppressants used were methotrexate (n=15), azathioprine (n=8) or leflunomide (n=1). Remission rates at 24-weeks were 8.3% with prednisone ≤4mg/day (vs. 28.0% in the mepolizumab trial); 41.6% with prednisone ≤7.5mg/day (vs. 45% in the mepolizumab trial) and 62.5% with any prednisone dose (vs. 34% in the rituximab study). Remission at 52-weeks was 50.0% with any prednisone dose (vs. 49% in the rituximab study), whereas sustained remission at week 52 (as of week 24) was 4.2% with prednisone ≤4mg/day (vs. 19% in the mepolizumab trial), and 33.3% with prednisone ≤7.5mg/day (vs. 24% in the mepolizumab trial). CONCLUSIONS: Though our study was small and retrospective, rates of remission observed with conventional immunosuppressants were substantial. This should be kept in mind when interpreting results of placebo-controlled or retrospective studies on biologics in EGPA.

Quality of life (QOL) and symptom burden (SB) in patients with breast cancer.

PURPOSE: The purpose of this study was to determine the quality of life (QOL) and symptom burden (SB) among breast cancer patients. METHODS: Patients with DCIS, early stage, locally advanced, or metastatic breast cancer completed the Edmonton Symptom Assessment System (ESAS) and the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). Patients were divided into subsequent cohorts based on their last day of treatment, age at enrollment, radiation, chemotherapy, and hormone therapy. RESULTS: A total of 1513 patients were enrolled. Metastatic patients had a lower QOL and greatest SB compared to all other patient groups. Patients ≤50 years old with early stage or locally advanced breast cancer had a lower QOL and greater SB for fatigue, depression, and anxiety compared to all other age cohorts. Patients with early stage breast cancer who received chemotherapy had a lower QOL and greater SB. Patients taking selective estrogen receptor modulator (SERM) had greater SB for depression and lower QOL compared to those not on SERM. Patients 2-10 years post-treatment had a lower QOL compared to patients ≥10 years post-treatment. CONCLUSION: Patients ≤50 years old, 2-10 years post-treatment, treated with chemotherapy or SERM had increased SB and decreased QOL. Individualized interventions and programs can be developed to tailor to physical, educational, and psychosocial needs identified across the breast cancer continuum.

Inadequate pain management in cancer patients attending an outpatient palliative radiotherapy clinic.

PURPOSE: The aim of this study is to assess the prevalence of undertreated cancer pain in an outpatient palliative radiotherapy clinic using the Pain Management Index (PMI). METHODS: A retrospective analysis of a prospective database to assess pain management was done on patients with cancer pain enrolled from January 2009 to March 2015 using recorded pain intensity (0-10) and baseline pain medications. The pain intensities were categorized into no pain (0), mild pain (1), moderate pain (2), and severe pain (3), and an analgesic score was assigned to the most potent pain medication the patient was taking during the time of data collection. "0" was assigned to no analgesics, "1" to non-opioids, "2" to weak opioids, and "3" for strong opioids based on the WHO guidelines. The PMI was calculated for each patient by subtracting the pain score from the analgesic score. A negative value indicated undertreatment, and a value of 0 or greater corresponded to adequate pain management. RESULTS: Three hundred fifty-four patients were included in the study. The incidence of inadequate pain management was 33.3 %, similar to that reported in our previous studies. Additionally, 106 patients were taking strong opioids and reporting severe pain despite being the PMI reporting adequately treated. CONCLUSION: The rate of undertreatment is similar to that reported in past studies; however, the rates have shown a slight increase in our palliative radiotherapy clinic since the last assessment. Inadequate management of cancer pain continues to be a problem.

A novel prospective descriptive analysis of nausea and vomiting among patients receiving gastrointestinal radiation therapy.

PURPOSE: Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients' quality of life (QOL). This study described the subjective experience of patients with radiation-induced nausea and vomiting (RINV) and its relation to QOL. METHODS: Forty-eight patients treated with abdominal radiotherapy alone or with concomitant chemoradiotherapy were followed in a prospective study. All episodes of nausea, vomiting, and antiemetic use were recorded daily for the treatment period and the week following completion of therapy. QOL was assessed weekly using the Functional Living Index-Emesis QOL Tool (FLIE) and the EORTC QLQ-C30 core questionnaire (C30). RESULTS: In total, 351 episodes of nausea severity, duration, onset time, and 154 outcomes of vomiting onset times and contents were documented. The median nausea severity experienced per episode was 5 (on a scale from 1 to 10), and the most common durations of nausea were 30 min or less and constant nausea all day and night. The most common location of nausea was the abdomen. Longer nausea duration, great nausea severities, and the location of nausea experienced had significant adverse relationships to multiple QOL items on both the FLIE and the C30. In addition, the onset timing and number of vomiting episodes were related to the majority of all FLIE and QOL scores. CONCLUSION: Patient's subjective experiences of RINV directly correlated to the worsening of QOL outcomes. The identification and amelioration of these RINV experiences could improve QOL.

Quality of life and symptom burden in patients with breast cancer treated with mastectomy and lumpectomy.

INTRODUCTION: Mastectomy (MAS) and lumpectomy (LUMP) are the two common local surgical treatments for early breast cancer. There has been a debate whether MAS or LUMP results in better quality of life (QOL). The purpose of this study was to examine the symptom burden (SB) and QOL of both MAS and LUMP patients. METHODS: Patients at the Louise Temerty Breast Cancer Centre in Toronto, Canada, were approached to complete two self-administered questionnaires, the Edmonton Symptom Assessment Score (ESAS) and the Functional Assessment of Cancer Therapy-Breast (FACT-B) cancer edition. Additionally, patient demographics were recorded from medical records. Patients were divided into two cohorts depending on their surgical treatment: MAS and LUMP. The QOL and SB, assessed by FACT-B and ESAS, respectively, of MAS and LUMP patients were compared. The analysis was repeated excluding patients with metastases. RESULTS: From January to August 2014, 614 MAS and 801 LUMP patients were accrued. The MAS patients reported a lower QOL in all categories, except social well-being. There was however no statistical difference in ESAS scores for MAS and LUMP patients with non-metastatic breast cancer. CONCLUSION: This study supports existing literature that SB of MAS and LUMP patients without metastases are similar. QOL of MAS patients including those with metastases was lower than that of LUMP patients.

Quality of life and symptom burden in patients with metastatic breast cancer.

PURPOSE: The goal of this study was to examine the symptom burden (SB) and quality of life (QOL) in patients with metastatic breast cancer. METHODS: Breast cancer patients with metastases were asked to complete the Edmonton Symptom Assessment System (ESAS) and FACT-B questionnaires. Statistical analysis was performed to identify (1) any differences in SB and QOL between patients with bone metastases only and patients with visceral +/- bone metastases and (2) any associations between SB and/or QOL and various clinical factors, including treatment with bisphosphonates, participation in a clinical trial and presence of brain metastases. RESULTS: A total of 174 patients were enrolled. Treatment with bisphosphonates was significantly associated with lower ESAS well-being scores (less symptoms) in patients with bone metastases only. In this same group, receiving treatment prior to diagnosis of metastases was significantly associated with increased fatigue, anxiety and dyspnoea. The presence of brain metastases was associated with higher physical well-being scores (increased QOL). Participation in clinical trials was associated with better QOL. CONCLUSION: Breast cancer patients with metastases have different SB and QOL in relation to the type of the metastases, treatment interventions and participation in clinical trials.

Validation of the long-term quality of life breast cancer scale (LTQOL-BC) by health care professionals.

INTRODUCTION: Quality of life has become an important measure of treatment success and is currently being explored not only for patients on active treatment, but also for long-term breast cancer survivors. The long-term quality of life breast cancer scale (LTQOL-BC) is a tool to assess QOL in breast cancer survivors. This study aimed to validate the tool with health care professionals (HCPs). METHODS: Six HCPs with extensive experience working with breast cancer survivors were selected. HCPs completed the LTQOL-BC and were asked to assess the relevance of each included item to the disease-free breast cancer population. They were also instructed to identify items that could be upsetting for patients, irrelevant to this population, and to assess the tool's breadth of coverage. RESULTS: Feedback indicated that some items such as the body image and sexual functioning questions were potentially upsetting to patients and should be rephrased or removed. The overall breadth of coverage of the tool was inadequate, with employment status, economic situation, ability to meet needs of family, health care insurance coverage, and overall sense of well-being not being addressed by the LTQOL-BC. HCPs also identified that certain items should be edited including those specifying pain in the lower body and the item containing the term "homemaker". CONCLUSION: The LTQOL-BC may need to be modified to take into the recommendations provided by HCPs.

Fatigue scores in patients receiving palliative radiotherapy for painful bone metastases.

INTRODUCTION: The purpose of this study was to examine changes in fatigue scores for patients receiving radiation therapy for bone metastases and its impact on quality of life (QOL). METHODS: Fatigue and QOL scores were prospectively collected in patients for up to 3 months following radiation therapy for bone metastases using three questionnaires: group 1, Edmonton Symptom Assessment System (ESAS) (0-10); group 2, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30); and Core 15 Palliative (EORTC QLQ-C15-PAL) (1-4). RESULTS: Average fatigue score in group 1 (399 patients) was 4.72 at baseline, 5.08 at month 1, 5.01 at month 2, and 4.95 at month 3, and was 2.40, 2.39, 2.56, and 2.70 in group 2 (482 patients), respectively. Thirty-five percent of patients in group 1 had fatigue score increase ≥2 points at month 1, 36% at month 2, and 36% at month 3. Twenty-one percent of patients in group 2 had fatigue score increase ≥1 at month 1, 27% at month 2, and 40% at month 3. There was a statistically significant increase in fatigue score from baseline to all 3 months in group 1 only. In both groups, there was a highly significant negative correlation between fatigue and overall QOL scores at baseline and any follow-up month. CONCLUSIONS: There was a statistically significant worsening in fatigue in group 1 only. Up to one third had increased fatigue of clinical significance. Patients with less fatigue symptoms reported better overall QOL.

Minimal clinically important differences in the EORTC QLQ-BN20 in patients with brain metastases.

INTRODUCTION: Quality of life (QOL) is an important treatment endpoint in advanced cancer patients with brain metastases. In clinical trials, statistically significant changes can be reached in a large enough population; however, these changes may not be clinically relevant. OBJECTIVE: The objective of this study was to determine the minimal clinically important difference (MCID) for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire brain module (EORTC QLQ-BN20) in patients with brain metastases. METHODS: Patients undergoing radiotherapy for brain metastases completed the EORTC QLQ-BN20 and QLQ-C30/C15-PAL at baseline and 1-month follow-up. MCIDs were calculated for both improvement and deterioration using anchor- and distribution-based approaches. The anchor of overall QOL (as assessed by question 30 or question 15 on the QLQ-C30 and QLQ-C15-PAL, respectively) was used to determine meaningful change. RESULTS: A total of 99 patients were included. The average age was 61 years, and the most common primary cancer sites were the lung and breast. Statistically significant meaningful differences were seen on two scales. A decrease of 6.1 (95 % confidence interval (CI) 0.8 to 11.4) units and 13.8 (0.2 to 27.4) units was required to represent clinically relevant deterioration of seizures and weakness of legs, respectively. Distribution-based MCID estimates tended to be closer to 0.5 SD on the EORTC QLQ-BN20. CONCLUSION: Understanding MCIDs allows physicians to determine the impact of treatment on patients' QOL and allows for determination of sample sizes for clinical trials. Future studies should be conducted to validate our findings in a larger population of patients with brain metastases.

Symptom clusters of gastrointestinal cancer patients undergoing radiotherapy using the Functional Living Index-Emesis (FLIE) quality-of-life tool.

OBJECTIVE: The Functional Living Index-Emesis (FLIE) instrument is a validated nausea and vomiting specific quality of life (QOL) tool originally created as a 3-day test of the impact of chemotherapy-induced nausea and vomiting on cancer patients' daily life. The primary objective of the present study was to retrospectively explore the use of the FLIE from data obtained in a previously published study of patients with gastrointestinal radiation-induced nausea and vomiting (RINV) and compare the extracted symptom clusters on a weekly basis for the entirety of gastrointestinal cancer patients' radiotherapy treatments. METHODS: QOL was assessed on a weekly basis using the 18-item FLIE questionnaire for patients' radiotherapy treatments. A principal component analysis with varimax rotation was performed at each visit. The internal consistency and reliability of the derived clusters was assessed with Cronbach's alpha. Robust relationship and correlation among symptoms was displayed with biplot graphics. RESULTS: A total of 460 FLIE assessments were completed for the 86 gastrointestinal patients who underwent radiotherapy. Two components were consistently identified except for week 5 where only one component was identified. Component 1 contained the items "Q10-Q18" which included all vomiting items. Component 2 included all nausea items from "Q1 to Q9". All the variables were well accounted for by two components for most weeks of treatment with excellent internal consistency. Biplots indicate that the two symptom clusters were evident at each week, with the exception of the first week of treatment. Strong correlations were seen between the effect of nausea on patients' ability to make meals, patients' ability to do tasks within the home, and patients' willingness to spend time with family and friends. CONCLUSION: The high internal consistency at all timepoints indicates that the FLIE QOL instrument is useful for the RINV population.

Inadequacy of Palliative Training in the Medical School Curriculum.

This report examines the literature on palliative training in the current medical school curriculum. A literature search was conducted to identify relevant articles. Physicians and medical students both report feeling that their training in end-of-life care and in palliative issues is lacking. The literature expresses concerns about the varied and non-uniform approach to palliative care training across medical schools. The authors recommend the development of more palliative training assessment tools in order to aid in the standardization of curriculum involving end-of-life care. In addition, increased exposure to dying patients will aid students in building comfort with palliative care issues. Such a goal may be accomplished through required clerkships or other similar programs.

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.

Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT(3)RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT(3)RAs in CINV prophylaxis. METHODS: A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT(3)RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT(3)RA-related adverse events. RESULTS: Sixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT(3)RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints. CONCLUSIONS: Palonosetron is safer and more efficacious than other 5-HT(3)RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.

A prospective study of gastrointestinal radiation therapy-induced nausea and vomiting.

OBJECTIVE: Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients' quality of life (QOL). A prospective study among patients with GI cancers was conducted to document the timing, incidence and risk factors of radiation therapy-induced nausea and vomiting (RINV). METHODS: Forty-eight patients planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemoradiotherapy were followed prospectively. All episodes of nausea, vomiting, retching and antiemetic use were recorded daily for the entire treatment period and for the week following completion of therapy. QOL was assessed weekly using the Functional Living Index--Emesis Quality of Life Tool and the EORTC QLQ-C30 core questionnaire. RESULTS: Nausea occurred in 83 % of patients and emesis in 54 %. Pancreatic cancer was significantly correlated to higher proportions of nausea and emesis (p = 0.002 and p = 0.0003) compared to other primary sites. There were no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for nausea and emesis. Patients had significantly greater proportions of RINV during the first, second and fifth weeks of treatment and during the first week following treatment. Vomiting was found to impair patients' usual recreation or leisure activities and enjoyment of their meals. Worse physical, role and social functioning and greater fatigue and appetite loss over the course of treatment correlated directly with the timing of RINV symptoms. CONCLUSION: RINV worsened QOL and was experienced even after treatment was completed; physicians should therefore be cognizant and monitor patients in the week following radiotherapy. Concomitant chemoradiotherapy should potentially be included in the moderate emetogenic risk category.

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.

Comparison of the EORTC QLQ-BN20 and the FACT-Br quality of life questionnaires for patients with primary brain cancers: a literature review.

PURPOSE: This review compares and contrasts the development, validity, and characteristics of two quality of life (QOL) assessment tools used in patients with primary brain cancers: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain Cancer Module (EORTC QLQ-BN20) and the Functional Assessment of Cancer Therapy-Brain (FACT-Br). METHODS: A literature search was conducted using the Cochrane Central Register of Controlled Trials (June 2013), Ovid EMBASE (1947 to 2013, week 27), and Ovid MEDLINE (1946 to July 2013, week 1) to identify studies that discussed the development, characteristics, validity, and reliability of the EORTC QLQ-BN20 or the FACT-Br. RESULTS: The EORTC QLQ-BN20 consists of 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = "not at all" to 4 = "very much." Reliability and validity testing of the QLQ-BN20 revealed a Cronbach's alpha coefficient that ranged from 0.71 to 0.90. The FACT-Br consists of 23 items that assess general well-being and brain cancer-specific concerns that include concentration, memory, seizures, eyesight, hearing, speech, personality, expression of thoughts, weakness, coordination, and headaches. These items are presented as statements on a scale ranging from 0 = "not applicable" to 4 = "extremely relevant." The FACT-Br underwent validity as well as test-retest reliability testing with 101 and 46 patients, respectively. Validity testing found low to moderate correlation with the FACT-G questionnaire, while reliability testing for the brain subscale revealed an acceptable correlation coefficient (r = 0.66; p < 0.001). CONCLUSIONS: The QLQ-BN20 and the FACT-Br are both valid and reliable tools that have been used extensively in the primary brain cancer population. Choice between the two tools should consider each instrument's individual strengths and weaknesses.

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.

Management of radiation-induced nausea and vomiting with palonosetron in patients with pre-existing emesis: a pilot study.

BACKGROUND: Approved almost 15 years ago for use in the chemotherapy setting, palonosetron, a 2nd generation 5-hydroxtryptamine 3 receptor antagonist (5-HT3 RA), has demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting. However, its utility in the prophylaxis and treatment of radiation-induced nausea and vomiting (RINV) has yet to be evaluated. In this pilot study, we investigated the rates of control in RINV in patients with pre-existing emesis. METHODS: Patients with pre-existing emesis undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). Prophylaxis and rescue (PR) was defined as a decrease in anti-emetic use, or episodes of nausea and/or vomiting from baseline. Complete prophylaxis (CP) was defined as no increase in anti-emetic use, or episodes of nausea and/or vomiting. Secondary endpoints included control of nausea and quality of life (QOL), as assessed with the Functional Living Index-Emesis and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15 Palliative. RESULTS: Fourteen patients were enrolled. Rates of control were higher in the acute phase (n=14) for nausea (PR =42.9%, CP =42.9%) and vomiting (PR =21.4%, CP =71.4%) compared to the delayed phase (n=13) for nausea (PR =42.9%, CP =7.7%) and vomiting (PR =15.4%, CP =53.8%). CONCLUSIONS: Palonosetron appears to be safe and patients with pre-existing emesis receiving palliative radiotherapy. More studies are needed to investigate its efficacy in this patient population.

A pilot study with palonosetron in the prophylaxis of radiation-induced nausea and vomiting.

BACKGROUND: Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the present study was to investigate the efficacy and safety of palonosetron in the prophylaxis of radiation-induced nausea and vomiting (RINV). METHODS: Patients without existing nausea and vomiting undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg orally before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). The primary endpoint was control of vomiting. Complete control was defined as no use of rescue medication and no episodes of nausea or vomiting. Secondary endpoints included control of nausea and quality of life (QOL). QOL was assessed with the Functional Living Index-Emesis and the European Organisation for Research and Treatment of Cancer QOL Questionnaire-Core 15 Palliative (C15-PAL). RESULTS: In all evaluable patients (n=75), complete control of vomiting was 93.3% in the acute phase and 93.2% in the delayed phase. Complete control of nausea was 74.7% in the acute phase and 74.0% in the delayed phase. CONCLUSIONS: Results suggest improved control in RINV compared to historical reports with first generation serotonin receptor antagonists (RA). A randomized study will be needed to confirm this finding.

Estimating prognosis at the time of repeat whole brain radiation therapy for multiple brain metastases: The reirradiation score.

PURPOSE: Whole brain radiation therapy (WBRT) remains the standard of care for patients with multiple brain metastases, but more than half of treated patients will develop intracranial progression. Because there is no clear consensus on the optimal therapeutic approach, a prognostic index would be helpful to guide treatment options at progression. We explored whether the recursive partitioning analysis (RPA) score prior to repeat WBRT is predictive of survival. METHODS AND MATERIALS: This multi-institutional pooled analysis included patients with 2 or more brain metastases from any solid primary tumor that was treated with 2 courses of WBRT. Information on demographics, disease characteristics, and intervals between courses was collected. RPA class was abstracted or retrospectively assigned, and descriptive statistics calculated. Median survival (MS) was determined using the Kaplan-Meier method and compared using log rank tests. Univariate and multivariate analyses were performed via Cox regression analysis. RESULTS: For 205 patients, the median age was 55 years (range, 25-83 years), 68% were female, 40.5% had non-small cell lung cancer, and 31.2% had small cell lung cancer. Prior to the second WBRT, 4.9% of patients were RPA class 1, 36.6% were RPA2, and 58.5% were RPA3, with an MS of 7.5 months (95% confidence interval [CI], 4.7-10.3), 5.2 months (95% CI, 3.7-6.7 months), and 2.9 months (95% CI, 2.2-2.9 months), respectively (P = .001). On univariate and multivariate analyses, a Karnofsky Performance Status of <80, extracranial metastases, interval between courses <9 months, small cell lung cancer histology, and uncontrolled primary significantly correlated with shorter MS. By assigning a score of 1 to each of these factors, a new prognostic index was created, the reirradiation (ReRT) score. Survival on the basis of ReRT score grouping ranged from 2.2 to 7.2 months and demonstrated significant differences in MS. CONCLUSIONS: In the largest reported cohort to receive repeat WBRT, application of the RPA score was not predictive of MS. The new ReRT score is a simple tool based on readily available clinical information.