Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The aim of this article was to systematically review the efficacy and safety of various antiemetics in prophylaxis of radiation-induced nausea and vomiting (RINV). METHODS: A literature search of Ovid MEDLINE, EMBASE and Cochrane CENTRAL was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy of prophylaxis for RINV in patients receiving radiotherapy to abdomen/pelvis, including total body irradiation (TBI). Primary endpoints were complete control of nausea and complete control of vomiting during acute and delayed phases. Secondary endpoints included use of rescue medication, quality of life (QoL) and incidence of adverse events. RESULTS: Seventeen RCTs were identified. Among patients receiving radiotherapy to abdomen/pelvis, our meta-analysis showed that prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA) was significantly more efficacious than placebo and dopamine receptor antagonists in both complete control of vomiting [OR 0.49; 95% confidence interval (CI): 0.33-0.72 and OR 0.17; 95% CI: 0.05-0.58 respectively] and complete control of nausea (OR 0.43; 95% CI: 0.26-0.70 and OR 0.46; 95% CI: 0.24-0.88 respectively). 5HT3 RAs were also more efficacious than rescue therapy and dopamine receptor antagonists plus dexamethasone. The addition of dexamethasone to 5HT3 RA compared to 5HT3 RA alone provides a modest improvement in prophylaxis of RINV. Among patients receiving TBI, 5HT3 RA was more effective than other agents (placebo, combination of metoclopramide, dexamethasone and lorazepam). CONCLUSIONS: 5HT3 RAs are more effective than other antiemetics for prophylaxis of RINV in patients receiving radiotherapy to abdomen/pelvis and TBI. Future RCTs should investigate the efficacy of newer agents such as substance P neurokinin 1 receptor antagonists in addition to 5HT3 RAs in prophylaxis of RINV during both acute and delayed phases.

Quality of life with Brain Symptom and Impact Questionnaire in patients with brain metastases.

BACKGROUND: To examine the baseline characteristics of patients who underwent different treatments for brain metastases. METHODS: Allocated into group A [whole brain radiation therapy (WBRT) alone], or group B [stereotactic radiosurgery (SRS) or neurosurgery with or without WBRT], brain metastases patients with assigned treatment completed the Brain Symptom and Impact Questionnaire (BASIQ). Items of BASIQ were arranged as a symptom score or function score. RESULTS: Lung, breast, melanoma and renal cancer were the most prevalent primary cancer site among the study population, with 91 (53%), 25 (15%), 17 (10%) and 15 (9%) patients, respectively. Baseline BASIQ results were obtained before patients were treated with WBRT, neurosurgery, or SRS. Seventy-six (44%) and 96 patients (56%) were grouped to A and B, respectively. Group A reported lower quality of life (QOL) in all function scores (P<0.0001) and all symptom scores (P values from <0.0001 to 0.005) with the exception of energy (P=0.1). CONCLUSIONS: Baseline QOL in patients assigned WBRT alone was statistically worse as compared to patients assigned SRS, neurosurgery with or without WBRT.

Solitary brain metastasis from prostate cancer: a case report.

Brain metastases arising from prostate cancer are exceedingly rare and typically occur late in the course of the disease. Most patients have widespread metastatic disease before developing brain metastases from prostate cancer. We report the case of a 67-year-old male with prostate cancer presenting with an isolated symptomatic brain metastasis. Aggressive treatment of the metastatic site included tumor resection and adjuvant stereotactic radiation treatment (RT) to the surgical bed, resulting in a favorable outcome.

Comparison of the FACT-C, EORTC QLQ-CR38, and QLQ-CR29 quality of life questionnaires for patients with colorectal cancer: a literature review.

PURPOSE: The purpose of this review was to compare the development, characteristics, validity, and reliability of three widely used quality of life (QOL) assessment tools used in colorectal cancer (CRC) patients: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), the European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Quality of Life Questionnaire Colorectal Cancer Module (QLQ-CR38) and its successor, the QLQ-CR29. METHODS: A literature search was conducted using Ovid EMBASE and EMBASE Classic (1996-2015 Week 39), Ovid MEDLINE and OLDMEDLINE (1996 September Week 4 2015), and the Cochrane Central Register of Controlled Trials (up to August 2015) to identify studies that discussed the FACT-C, EORTC QLQ-CR38, and QLQ-CR29 including, but not limited to, their development, characteristics, validity, and reliability. RESULTS: The FACT-C consists of 36 items, presented on a 5-point Likert scale, in four domains of well-being (physical, emotional, social, and functional), and the Colorectal Cancer Subscale (CCS). The physical and social well-being scales showed reasonable internal consistency (Cronbach's alpha coefficient > 60) in all studied populations. The EORTC QLQ-CR38 (38 items) and the QLQ-CR29 (29 items) are implemented in conjunction with the core QLQ-C30 (30 items); all are presented in 4-point Likert scales. Seven scales in the QLQ-CR38 demonstrated good internal consistency (Cronbach's alpha coefficient > 0.70). In the QLQ-CR29, three scales had a Cronbach's alpha coefficient of less than 0.70. CONCLUSION: The FACT-C, QLQ-CR38, and QLQ-CR29 have been extensively validated. However, analysis of their characteristics, validity, and reliability suggest differing suitability in assessing QOL in specific clinical situations.

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.

Inter-rater reliability in performance status assessment among health care professionals: a systematic review.

BACKGROUND: Studies have reported that performance status (PS) is a good prognostic indicator in patients with advanced cancer. However, different health care professionals (HCPs) could grade PS differently. The purpose of this review is to investigate the PS scores evaluated by different HCPs as reported in the literature. METHODS: A literature search was conducted in Ovid MEDLINE and OLDMEDLINE from 1946 to Present (July 5, 2015), Embase Classic and Embase from 1947 to 2015 Week 26, and Cochrane Central Register of Controlled Trials up to May 2015. Information of interest was whether there was a difference of PS assessment between HCPs. Other statistical information provided to assess the agreement in ratings, such as Cohen's kappa coefficient, Krippendorff's alpha coefficient, Spearman Rank Coefficient, and Kendall's correlation, was noted. RESULTS: Of the fifteen articles, eleven compared PS assessments between HCPs of different disciplines, one between the attending and resident physician, two between similarly-specialized physicians, and one between two unspecified-specialty physicians. Three studies reported a lack of agreement (kappa =0.19-0.26; Krippendorff's alpha =0.61-0.63), four reported moderate inter-rater reliability (kappa =0.31-0.72), two reported mixed reliability, and six reported strong reliability (kappa =0.91-0.92; Spearman rank correlation =0.6-1.0; Kendall's correlation =0.75-0.82). Four studies reported that Karnofsky performance status (KPS) had better inter-rater reliability than both the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the palliative performance scale (PPS). CONCLUSIONS: The existing literature cites both good and bad inter-rater reliability of PS scores. It is difficult to conclude which HCPs' PS assessments are more accurate.

Urinary cytokines/chemokines pattern in patients with painful bone metastases undergoing external beam radiotherapy experiencing pain flare.

BACKGROUND: External beam radiotherapy (EBRT) is a mainstay for treatment of painful bone metastases. Transient worsening of pain ("pain flare") occurs in 40% of patients. We investigated the pathophysiology of pain flare through assessment of changes in urinary cytokines/chemokines in patients receiving EBRT for painful bone metastases. METHODS: Urine samples were collected from patients receiving a single 8 Gy fraction for painful bone metastases preparation, day 1 or 2 and on an additional day between days 3 to 5 post radiation. Patients completed a standardized pain and analgesic use diary daily for 10 days following radiation. Patients were deemed to have pain flare if they had a two-point increase from baseline worst pain on 0-10 scale and no decrease in analgesic intake or a 25% increase in analgesic intake with no decrease in worst pain. The Millipore Milliplex 42-Plex Cyto-kine/Chemokine Kit™ was used to measure urinary levels of a panel of cytokines/chemokines. RESULTS: Forty-six patients consented to the study of which 28 were evaluable (complete urine and diary data), and 83/84 urine samples were available for analysis. Pain flare was experienced by 11 patients (39%). The following cytokines/chemokines were detectable in at least 50% of the patients: EGF, fractalkine, GRO, IL-4, IL-8, interferon gamma induced protein 10 (IP-10), MCP-1, macrophage derived chemokine (MDC), PDGF-AA, sIL-2Ra, TGF-Alpha, VEGF. Comparing patients with or without pain flare EGF, fractalkine, GRO, IL-8, IP-10, MCP-1, MDC, sIL-2Ra, and TGF-alpha increased following radiation in both groups. Patients with pain flare have significant lower levels on IL-8, IP-10, and MDC over time. No specific time trend was noticed. CONCLUSIONS: Patients who experience pain flare appear to have a different pattern in urinary cytokine/chemokine levels than patients without pain flare. A larger study is required to confirm the possible role of cytokines/chemokines in predisposition to and/or the cause of pain flare following radiation to painful bone metastases.

A case report of bone metastases from appendiceal adenocarcinoma and a review of literature.

Appendiceal adenocarcinoma (AA) is a rare cancer, accounting for less than 0.5% of all gastrointestinal cancers. As such, there is still debate surrounding both the nature of the disease and the roles of different treatment modalities in the care of this patient population. Metastases of AA, particularly distant metastases, have not been explored extensively in literature. As survival in optimally treated cases of AA continues to improve, clinicians may encounter previously unrealized complications of this disease or unlikely metastases at a higher frequency. We reported the rare case of a 50-year-old male with recurrent mucinous AA who developed painful pelvic bone metastases. To palliate his symptoms, the patient underwent 30 Gy of external beam radiation treatment (EBRT) in 10 fractions to the pelvis. The patient achieved a good pain response after completion of EBRT, with elimination of analgesic use one month post-treatment. This case demonstrates successful palliative management of bone metastases from a primary mucinous AA. Although there is a lack of evidence-based guidelines specific to the treatment of AA, there are a variety of therapies available [e.g., chemotherapy, cytoreductive surgery (CRS), radiation, etc.]. The use of these treatments is largely determined by prognostic factors.

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.

Do patients with brain metastases selected for whole brain radiotherapy have worse baseline quality of life as compared to those for radiosurgery or neurosurgery (with or without whole brain radiotherapy)?

BACKGROUND: The purpose was to examine the baseline characteristics, symptoms and quality of life (QOL) in patients who receive different treatments for brain metastases. METHODS: Eligible patients were divided and analysed based on their treatment: whole brain radiotherapy (WBRT) alone versus stereotactic radiosurgery (SRS) or neurosurgery with or without WBRT. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) items were grouped according to different domains for summary scores. The domains used for summary scores were physical, social/family, emotional, functional well-being (FWB) and additional concerns. RESULTS: A total of 120 patients were enrolled, with 37 treated with WBRT alone and 83 with SRS or neurosurgery with or without WBRT. Of the 50 baseline FACT-Br items, only five items (I feel ill; I get support from my friends; I worry about dying; I have difficulty expressing my thoughts, I am able to put my thoughts into action) were statistically worse in patients treated with WBRT alone (P<0.05). Patients who received SRS or surgery with or without WBRT had statistically (P<0.05) higher scores for the FWB domain, additional concerns domain, and FACT-G total scores, indicating better QOL. CONCLUSIONS: Patients selected for WBRT alone reported statistically different baseline QOL as compared to patients who were treated with SRS or neurosurgery (with or without WBRT).

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.

Enteral and parenteral nutrition in cancer patients: a systematic review and meta-analysis.

BACKGROUND: In cancer patients, weight loss is an ominous sign suggesting disease progression and shortened survival time. As a result, providing nutrition support for cancer patients has been proposed as a logical approach for improving clinical outcomes. Nutrition support can be given to patients through enteral nutrition (EN) or parenteral nutrition (PN). The purpose of the review was to compare the outcomes of PN and EN in cancer patients. METHODS: A literature search was conducted in Ovid MEDLINE and OLDMEDLINE, Embase Classic and Embase, and Cochrane Central Register of Controlled Trials. Studies were included if over half of the patient population had cancer and reported on any of the following endpoints: the percentage of patients that experienced no infection, nutrition support complications, major complications or mortality. Risk ratios (RR) and 95% confidence intervals (CIs) using Review Manager Version 5.3 were calculated. Primary endpoints were stratified according to type of EN for subgroup analysis, grouping studies into either tube feeding (TF) or standard care (SC). Additionally, another subgroup analysis was conducted comparing studies with protein-energy malnutrition (PEM) patients and studies without PEM patients. RESULTS: The literature search yielded 674 articles of which 36 were included for the meta-analysis. There were no difference in the endpoints between the two study interventions except that PN resulted in more infection when compared with EN (RR =1.09, 95% CI: 1.01-1.18; P=0.03). CONCLUSIONS: Other than increased incidence of infection, PN has not resulted in prolonging the survival, increasing nutrition support complications, or major complications when compared with EN in cancer patients.

Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis.

PURPOSE: Olanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV. METHODS: A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases. RESULTS: Ten RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis. CONCLUSION: Olanzapine is more efficacious than other standard antiemetics for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

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.

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.

Survival of patients with multiple brain metastases treated with whole-brain radiotherapy.

AIM: To report the survival outcomes of patients with multiple brain metastases treated with whole-brain radiotherapy. PATIENTS & METHODS: From 2004 to 2012, patients with brain metastases treated with whole-brain radiotherapy were included. Overall survival (OS) was calculated from the start of radiation treatment. Univariate and multivariate proportional hazard model of OS was conducted. Generalized R(2) statistic (ranged from 0 to 1) was calculated to determine the association with the outcome. RESULTS: Nine-hundred-ninety-one patients were included. The actuarial median OS time was 2.7 months (95% CI: 2.5-2.9). Patients of older age (>65 years), lower Karnofsky performance status, not postoperative and patients with gastrointestinal, genitourinary or lung as opposed to breast cancer were more likely to have a shorter survival. CONCLUSION: Short median survival of 2.7 months may reflect poorer prognosis of patients referred due to large amount of referrals for radiosurgery. Prognostic factors for survival should be considered at consultation.