Kristopher Dennis

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

PurposeThe aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients.MethodsA systematic review of the available literature was conducted. The body of evidence for the use of each agent, in each setting, was assigned a level of evidence. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible.ResultsA recommendation was developed in favor of patient-controlled analgesia with morphine in hematopoietic stem cell transplant (HSCT) patients. Suggestions were developed in favor of transdermal fentanyl in standard dose chemotherapy and HSCT patients and morphine mouth rinse and doxepin rinse in head and neck radiation therapy (H&N RT) patients. Recommendations were developed against the use of topical antimicrobial agents for the prevention of mucositis. These included recommendations against the use of iseganan for mucositis prevention in HSCT and H&N RT and against the use of antimicrobial lozenges (polymyxin–tobramycin–amphotericin B lozenges/paste and bacitracin–clotrimazole–gentamicin lozenges) for mucositis prevention in H&N RT. Recommendations were developed against the use of the mucosal coating agent sucralfate for the prevention or treatment of chemotherapy-induced or radiation-induced OM. No guidelines were possible for any other agent due to insufficient and/or conflicting evidence.ConclusionAdditional well-designed research is needed on prevention and management approaches for OM.

EORTC QLQ-C15-PAL quality of life scores in patients with advanced cancer referred for palliative radiotherapy

PurposeSymptom control and improved quality of life (QOL) are primary goals of treatment in palliative oncology. The present study assessed and compared patient demographics, baseline Karnofsky Performance Status (KPS) and QOL using the QLQ-C15-PAL questionnaire prior to palliative radiotherapy (RT) for bone, brain, or lung disease. Few studies have used this questionnaire, an abbreviated version that was developed by the European Organization for Research and Treatment of Cancer specifically for patients with advanced cancer to decrease the burden of completing the longer, more time-consuming QLQ-C30.MethodsPatients referred to an outpatient palliative RT clinic completed QLQ-C15-PAL questionnaires prior to palliative RT for bone, brain, or lung cancer sites. The associations between baseline QLQ-C15-PAL functional/symptom scales, patient demographics, and clinical variables including KPS were explored.ResultsWhen data from all 369 patients were analyzed, higher KPS scores correlated significantly with better overall QOL and higher physical and emotional functioning. The QLQ-C15-PAL provided more detailed information regarding how symptom burden varied depending on disease site. Patients with bone metastases had worse QLQ-C15-PAL scores for pain, while those with brain and lung disease had worse scores for fatigue. Other health-related QOL scores measured by the QLQ-C15-PAL varied as a function of age and gender.ConclusionAs the QLQ-C15-PAL provides detailed and often critical information regarding symptom burden, it may eventually be recognized as a universal core questionnaire to assess QOL in this patient population with advanced cancer while relieving the survey burden.

Fatigue in advanced cancer patients attending an outpatient palliative radiotherapy clinic as screened by the Edmonton Symptom Assessment System

IntroductionAdvanced cancer patients present with a variety of physical and psychological symptoms. Fatigue is one such symptom which reduces overall quality of life and is difficult to manage. The purpose of this study was to report the presence, severity, and correlating factors of fatigue in advanced cancer patients attending an outpatient palliative radiotherapy clinic.Materials/methodsPatients referred to the Rapid Response Radiotherapy Program between January 1999 and October 2009 completed the Edmonton Symptom Assessment System (ESAS) prior to consultation. Demographic information including age, Karnofsky Performance Status (KPS), gender, and primary cancer sites were collected. Ordinal logistic regression analysis was conducted to determine relationships between demographic information, other ESAS items, and levels of fatigue. Multivariate ordinal logistic regression analysis was used to determine the most significant predictors of fatigue. A p value of <0.05 was considered statistically significant.ResultsA total of 1,397 patients completed the ESAS prior to consultation. Median age was 68xa0years (range, 21–95), median KPS was 60 (range, 10–100), and slightly more males completed the ESAS (53.0%). Common primary cancers were of the lung (35.8%), breast (20.7%), and prostate (17.7%). Only 179 (12.8%) patients reported no fatigue; the majority of patients reported moderate (31.8%) or severe (34.4%) fatigue. A low KPS (pu2009<u20090.0001), being female (pu2009=u20090.0056), or being referred for bone metastases (pu2009=u20090.0185) significantly correlated with higher levels of fatigue. Patients with a genitourinary primary cancer (pu2009=u20090.0078) and/or referred for malignant spinal cord compression (pu2009=u20090.0004) reported less fatigue. All other ESAS items were significantly related to fatigue. The most significant predictors of fatigue were pain (pu2009<u20090.0001, odds ratio (OR)u2009=u20091.07), nausea (pu2009=u20090.0010, ORu2009=u20091.10), depression (pu2009<u20090.0001, ORu2009=u20091.10), drowsiness (pu2009<u20090.0001, ORu2009=u20091.33), dyspnea (pu2009=u20090.0003, ORu2009=u20091.08), and overall well-being (pu2009<u20090.0001, ORu2009=u20091.19).ConclusionModerate fatigue was reported in over 66% of our advanced cancer patients prior to radiotherapy. Since radiotherapy inherently causes fatigue, proactive and multidisciplinary management is required for these patients. Similar rates of fatigue severity, in lengthier, fatigue-specific tools, suggest that the ESAS may be a good tool for screening the advanced cancer population.

Prophylaxis of radiotherapy-induced nausea and vomiting in the palliative treatment of bone metastases

PurposeTo document the incidence and timing of radiotherapy-induced nausea and vomiting (RINV) in the treatment of bone metastases among patients receiving prophylaxis with a 5-HT3 receptor antagonist.MethodsPatients receiving single (SF) or multiple fraction (MF) palliative radiotherapy (RT) of moderate or low emetogenic risk for bone metastases were prescribed prophylactic Ondansetron. The frequency and duration of prophylaxis and the use of rescue antiemetics were left to the discretion of the treating physicians. Patients documented episodes of nausea (N) and vomiting (V) in daily diaries before and during RT, and until 10xa0days following RT completion. Rates of complete prophylaxis (CP) for N&V, respectively (CPu2009=u2009no event and no rescue medication), were calculated for the acute phase (the period from the start of RT to the first day following RT completion inclusive) and the delayed phase (the second to tenth days following RT completion inclusive).ResultsFifty-nine patients were enrolled, and 32 were evaluable. CP rates were as follows: moderate-risk SF group (nu2009=u200916), acute phase (CP for Nu2009=u200956%, CP for Vu2009=u200969%) and delayed phase (CP for Nu2009=u200931%, CP for Vu2009=u200944%); moderate-risk MF group (nu2009=u20097), acute phase (CP for Nu2009=u200971%, CP for Vu2009=u200957%) and delayed phase (CP for Nu2009=u200943%, CP for Vu2009=u200957%); low-risk SF group (nu2009=u20098), acute phase (CP for Nu2009=u200950%, CP for Vu2009=u2009100%) and delayed phase (CP for Nu2009=u200943%, CP for Vu2009=u200957%); and low-risk MF group (nu2009=u20091), acute phase (CP for Nu2009=u2009100%, CP for Vu2009=u2009100%) and delayed phase (CP for Nu2009=u2009100%, CP for Vu2009=u2009100%).ConclusionsDespite prophylaxis, RINV was common among patients receiving palliative radiotherapy for bone metastases, especially during the delayed phase.

Timing and duration of 5-HT3 receptor antagonist therapy for the prophylaxis of radiotherapy-induced nausea and vomiting: a systematic review of randomized and non-randomized studies

Introduction5-HT3 receptor antagonists (5-HT3RAs) are the most commonly recommended agents for the prophylaxis of radiotherapy-induced nausea and vomiting (RINV) within international antiemetic guidelines. However, the optimal timing and duration of their administration is unknown. We reviewed the relevant literature as a first step in addressing this important issue in supportive care.MethodsEMBASE and EMBASE Classic, Ovid MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched for articles reporting on patient cohorts receiving prophylactic therapy with a 5-HT3RA and being prospectively evaluated for RINV. Cohorts were grouped into high-, moderate-, and low-emetic-risk categories according to international guidelines.ResultsThe search identified 599 references, and 25 were included in the review. These contained 33 discrete patient cohorts (cumulative nu2009=u20091,067) that were prospectively evaluated for RINV while receiving prophylactic 5-HT3RA therapy. Of the 11 high-emetic-risk radiotherapy cohorts, two, eight, and one received 5-HT3RAs for durations longer than, equal to, or shorter than the duration of radiotherapy, respectively. Of the 22 moderate or low-emetic-risk radiotherapy cohorts, 5, 14, and 3 received 5-HT3RAs for durations longer than, equal to, or shorter than the duration of radiotherapy, respectively. Radiotherapy regimens and study endpoints were heterogeneous, precluding statistical comparisons of prophylaxis strategies.Conclusion5-HT3RAs were most commonly administered for the entire duration of a course of radiotherapy. Future studies should compare different timings and durations of therapy with common efficacy endpoints to develop effective and cost-efficient antiemetic strategies.

Do elderly patients with metastatic cancer have worse quality of life scores

PurposeThe purpose of this study is to compare self-reported quality of life (QOL) scores in old and young patients with metastatic cancer using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire.Materials and methodsPatients receiving palliative radiotherapy (RT) for bone metastases and brain metastases completed the QLQ-C15-PAL questionnaire prior to treatment. Using multiple linear regression analysis, a parametric test, the QLQ-C15-PAL scores were compared using 65 and 70xa0years as cutoff ages.ResultsA total of 340 patients were referred for palliative RT for bone metastases (nu2009=u2009190) or brain metastases (nu2009=u2009150). Physical functioning and appetite were worse in the older group using either 65 or 70xa0years as the cutoff age. Age-related differences in the QLQ-C15-PAL scores varied as a function of age cutoff used and location of metastatic site irradiated.ConclusionBased on the (EORTC) QLQ-C15-PAL, elderly advanced cancer patients have a different QOL profile. Similar observations have been reported with the (EORTC) QLQ-C30 questionnaire.

Comparing cost-effectiveness analyses of denosumab versus zoledronic acid for the treatment of bone metastases

BackgroundBone metastases from various cancers have been traditionally treated with bisphosphonates, such as zoledronic acid (ZA), to prevent future skeletal-related events (SREs). Denosumab (Dmab) has been shown to have more advantages in preventing SREs in clinical trials than ZA, but the cost to administer Dmab is significantly higher.MethodsA literature review was conducted to investigate the methodologies used to compare the cost-effectiveness of Dmab and ZA. MEDLINE® and EMBASE were searched systematically for all cost-effectiveness analyses published between January week 1, 2006 to August week 1, 2012. Search strategies were designed to retrieve articles analyzing the cost-effectiveness and cost utility of Dmab compared to ZA in patients with bone metastases. From 12 references obtained in the initial database search, eight satisfied the predetermined criteria for full article review. Articles were analyzed for incremental costs per skeletal-related event avoided or incremental cost per quality-adjusted life year gained.ResultsAll the studies identified received funding from Novartis Pharmaceuticals (the manufacturer of ZA) or Amgen Incorporated (the manufacturer of Dmab). The studies looked at the economic analysis using different associated costs and over various time periods, ranging from a 1-year to a lifetime time horizon.ConclusionIt is not clear whether the methods used across studies are consistent, which may account for the differences between estimated costs and effects. Future research is suggested to explore the cost-effectiveness between Dmab and ZA using a standardize time frame and endpoint.

Symptom clusters in patients with bone metastases—a reanalysis comparing different statistical methods

PurposeThe aims of this study were to determine whether symptom clusters in patients with bone metastases varied when derived using three different statistical methods and to compare the presentation of symptom clusters over time in responders and nonresponders to palliative radiation treatment (RT).MethodsSecondary analysis of a previously reported data set compiled using the brief pain inventory from 348 patients with bone metastases. Hierarchical cluster analysis (HCA) and exploratory factor analysis (EFA) were performed to identify symptom clusters at baseline, 1, 2, and 3xa0months following radiation treatment. Clusters derived were compared with the findings obtained using principal component analysis (PCA) in our previous study. The total patient sample was further separated into two subgroups: responders and nonresponders to RT. PCA, HCA, and EFA identified symptom clusters experienced by each subgroup at the same time points as before.ResultsLittle correlation was observed in the symptom cluster findings of PCA, EFA, and HCA in the total patient sample. Absolute consensus among all three statistical methods was never reached at any assessment time point in the present study. Varying patterns of symptom cluster presentation over time were observed in the responders versus nonresponders subgroups regardless of the analytical method employed. A core cluster of symptoms composed of worst pain, general activity, walking ability, normal work, and enjoyment of life frequently presented in the same cluster.ConclusionThe presence and composition of symptom clusters derived varied depending on which statistical analysis method was employed. A key step in attaining consistency in symptom cluster research necessitates the utilization of a common method.

Dexamethasone toxicity and quality of life in patients with brain metastases following palliative whole-brain radiotherapy

ObjectiveCorticosteroids are often one of the first treatments administered to relieve brain metastases symptoms; however, they are associated with unfavorable side effects with continued use. Whole-brain radiotherapy (WBRT) can relieve symptom burden due to the tumor as well as allow the patient to taper off of dexamethasone. The aim of this study was to prospectively assess the relationship between dexamethasone usage and symptoms and quality of life (QOL) in brain metastases patients undergoing palliative WBRT.Materials and methodsBrain metastases patients taking dexamethasone completed the Dexamethasone Symptom Questionnaire (DSQ) alongside the palliative core questionnaire, the EORTC QLQ-C15-PAL prior to palliative WBRT and at regular follow-up intervals thereafter until discontinuation of dexamethasone. Statistical analyses included general linear regression analysis, Fisher exact, and Kruskal–Wallis tests to assess relationships between dexamethasone dose/duration and the DSQ and QLQ-C15-PAL.ResultsSixty-eight patients were evaluable at baseline. Using the QLQ-C15-PAL, at weekxa02 post-WBRT patients on a higher dose of dexamethasone had worse physical (pu2009=u20090.0223) and emotional (pu2009=u20090.0082) functioning, and tended to score higher on fatigue (pu2009=u20090.0414) and dyspnea (pu2009=u20090.0117). When comparing dexamethasone dose with DSQ scores, a dose of ≥16xa0mg/day was significantly related to trouble getting to sleep (pu2009=u20090.009) at weekxa02 post-WBRT. Only less appetite loss on the QLQ-C15-PAL was significantly related to longer dexamethasone duration (pu2009=u20090.03) at baseline.ConclusionThis study is the first to use the DSQ and QLQ-C15-PAL to assess the impact of dexamethasone and WBRT on symptoms, functioning, and QOL in this patient group. Future investigations should determine the relationship between extended and high-dosage steroid use concurrently with WBRT and QOL in this patient group.

Management of bone metastases: recent advances and current status

This narrative review summarizes new and existing local and systemic management strategies for bone metastases from the fields of radiation oncology, medical oncology and orthopaedic surgery. Local management strategies are organized according to different clinical scenarios, with complicated bone metastases defined as those with associated pathological fractures, soft tissue components or those compressing the spinal cord or cauda equina, and uncomplicated lesions defined as those without these adverse features. The distinction applies for both sclerotic and lytic lesions. Systemic strategies are organized according to classes of therapeutic agents.