Quality Of Life Endpoints Research Articles

Quality of life from the perspective of the patient with acute myeloid leukemia.

Although outcomes for acute myeloid leukemia (AML) have improved over time, they remain poor overall, and toxicity from both the disease and its treatment can affect quality of life (QOL). One barrier to including QOL endpoints in clinical trials is the lack of a disease-specific QOL instrument that can efficiently capture the major QOL deficits in this population. A cross-sectional study was performed to elicit concepts for inclusion in a new AML-specific QOL instrument called the AML-QOL. Eighty-two patients at various stages of disease were interviewed about sources of support (positive concepts) and problems and symptoms (negative concepts) experienced over the past week, and they were asked to grade how much each affected their QOL. In addition, patients were asked to complete 2 validated instruments: the Functional Assessment of Cancer Therapy with the leukemia and transplant modules and the 29-item Patient-Reported Outcomes Measurement Information System questionnaire. With data from the open-ended and questionnaire-based portions of the interview, 7 positive concepts and 64 negative concepts were elicited. From these, 5 positive concepts and 21 negative concepts were selected for inclusion in the preliminary AML-QOL on the basis of concept prevalence and the impact on QOL. These concepts will form the basis of a new QOL instrument specific to AML. Cancer 2018;124:145-52. © 2017 American Cancer Society.

Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC-A Possible Path Forward.

In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage ≥T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240 mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR = 0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.

A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial

BackgroundNutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone).MethodsIn this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery.ResultsIn total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed.ConclusionsProvision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated—potentially focusing on the more poorly EN-fed surgical ICU setting.Trial registrationNCT01206166

A phase III randomized study comparing perioperative nivolumab vs. observation in patients with localized renal cell carcinoma undergoing nephrectomy (PROSPER RCC).

TPS4596 Background: The anti-PD-1 antibody nivolumab (nivo) improves overall survival (OS) in metastatic treatment refractory RCC and is generally tolerable. In 2017, there is no standard adjuvant therapy proven to increase OS over surgery alone in non-metastatic (M0) disease. Mouse solid tumor models have revealed an OS benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivo in RCC patients (pts) have shown preliminary feasibility and safety with no surgical delays or complications. The PROSPER RCC trial will examine if the addition of perioperative nivo to radical or partial nephrectomy can improve clinical outcomes in pts with locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in M0 RCC, we propose a three-pronged, multidisciplinary approach of presurgical priming with nivo followed by resection and adjuvant PD-1 blockade. Methods: Tumorbiopsy prior to randomization is mandatory to ensure the correct diagnosis and will permit unparalleled correlative science in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. 766 pts with clinical stage ≥T2 or any node positive M0 RCC of any histology will be enrolled. The study arm will receive nivo 240mg IV for 2 doses prior to surgery followed by nivo adjuvantly for 9 months (q2 wks x 3 mo followed by q4 wks x 6 mo). The control arm will undergo the current standard of care: surgical resection followed by observation. Pts are stratified by clinical T stage, node positivity, and histology. There is 84.2% power to detect a 14.4% absolute increase in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 yrs (HR 0.70). The study is also powered to detect a significant OS benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the significance of the baseline immune milieu and changes after neoadjuvant priming and to identify predictive gene expression patterns. Additional collaborations are welcomed.

A pilot study of palbociclib in patients with HER2-positive breast cancer with brain metastasis.

TPS1110 Background: HER2+ breast cancers have the propensity to metastasize to the CNS. Most systemic therapy does not cross the blood-brain barrier (BBB) effectively, limiting treatment options. Palbociclib is a small molecule inhibitor of cyclin dependent kinases (CDK) 4 and 6, which has been studied in hormone positive breast cancers and found to have significant anti-tumor activity. Preclinical models demonstrate HER2+ tumors require cyclin D1 and CDK4 for progression and maintenance, and palbociclib has been found to have single agent activity in transgenic HER2+ models. Preclinical studies have also found that palbociclib crosses the BBB and exerts anti-cancer effects; indeed, clinical trials investigating its activity in primary brain tumors are ongoing. The summary of these data provide rationale for investigation of palbociclib in patients with HER2+ breast cancer and brain metastasis. Methods: A single arm study of palbociclib in patients with metastatic HER2+ breast cancer with brain metastasis was designed. The primary objective is to determine overall radiographic response rate in the CNS using modified RANO-BM criteria. Secondary objectives include PFS, OS, systemic response rates, safety, and tolerability. Exploratory objectives include assessment of mutational profiles in tissue and ctDNA, and quality of life endpoints using FACT-Cog and FACT-Br. Eligible patients must have metastatic HER2+ breast cancer with measurable brain metastasis (at least 1 lesion &gt; = 5mm). Patients with rapidly progressive symptoms or with leptomeningeal disease are excluded. Concurrent therapy with trastuzumab is allowed. Eligible patients are treated with palbociclib 125mg PO (21 days on, 7 days off) until progressive disease or unacceptable toxicity. Available archival tissue will be obtained, ctDNA/FACT-Cog/Br will be assessed at baseline, 2, and 4 months. A total of 20 patients will be enrolled. To detect a radiographic response rates increase from 23% to 40%, a Bayesian posterior probability will be calculated after the response status in 20 patients has been assessed. The goal is that there is at least an 80% probability that the response rate exceeds 40%. Clinical trial information: NCT02774681.

Drainage of malignant ascites: patient selection and perspectives.

Malignant ascites (MA) is a sign of advanced cancer and poor prognosis. MA can result in impairment in quality of life (QOL) and significant symptoms. As a supportive treatment, ascites can be drained by paracentesis (PC), percutaneously implanted catheters (tunneled, untunneled, central venous catheters), or peritoneal ports, or peritoneovenous shunts. The aim of this study was to evaluate the effectiveness, safety, and patient-reported outcomes (PRO) of different drainage methods for the management of MA. A systematic review of the literature was performed, and 32 original articles met the inclusion criteria. Patients selected for permanent drain insertion demonstrated symptoms related to MA and had undergone repeated PC. The primary focus of the reviewed articles was procedural safety issues. The rate of technical success of drainage device installation was 100%. Most patients experienced improvements in symptom control after ascites drainage. When analyzed together, 19.7% (255/1297) of patients experienced any complication and 6.2% (81/1297) experienced serious adverse events during MA drainage. Complications were reported for every drainage method; however, the least occurred after PC or central venous catheter, while the most serious occurred after peritoneovenous shunts. Adverse events were as follows: catheter obstruction: 4.4%, infection: 4.1%, leakage: 3.5%, catheter dislodgment: 2.3%, hypotension: 0.6%, injuries during device insertion: 0.6%, renal impairment: 0.5%, electrolyte imbalance: 0.2%, other: 3.6%. PRO and QOL endpoints were available for 12 studies. When PRO were measured using an interview, a significant improvement in symptom control and QOL was reported in almost all patients. Once standardized questionnaires were used, improvements in symptomatic scores and role functioning were observed. Deterioration was observed in cognitive and emotional subscales. MA drainage is a safe and effective method to control symptoms associated with ascites, and should be perceived as a supportive care, that can be applied for those who need it at any time of their cancer trajectory. Patient selection should be performed using a thorough assessment of symptoms and QOL, and should not be delayed.

Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial

A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT). The participants were randomized to yoga and no-yoga cohorts (1:1). Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT. Comparisons of standardized assessments were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction, urinary incontinence, and QOL before, during, and after RT. From October 2014 to January 2016, 68 eligible PCa patients underwent informed consent and agreed to participate in the study. Of the 68 patients, 18 withdrew early, mostly because of treatment schedule-related time constraints, resulting in 22 and 28 patients in the yoga and no-yoga groups, respectively. Throughout treatment, those in the yoga arm reported less fatigue than those in the control arm, with global fatigue, effect of fatigue, and severity of fatigue subscales showing statistically significant interactions (P<.0001). The sexual health scores (International Index of Erectile Function Questionnaire) also displayed a statistically significant interaction (P=.0333). The International Prostate Symptom Score revealed a statistically significant effect of time (P<.0001) but no significant effect of treatment (P=.1022). The QOL measures had mixed results, with yoga having a significant time by treatment effect on the emotional, physical, and social scores but not on functional scores. A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients.

The Effect of a Home Delivery Meal Service of Energy- and Protein-Rich Meals on Quality of Life in Malnourished Outpatients Suffering from Lung Cancer: A Randomized Controlled Trial

ABSTRACTUndernutrition is prevalent in cancer patients and associated with increased incidence of complications and mortality. We investigated the effects of a home delivery meal service, providing a selection of energy-dense, protein-rich meals, on quality of life (QoL) in malnourished lung cancer patients. Forty lung cancer patients with nutritional risk score ≥3 (NRS-2002) were randomized to control or intervention. The intervention group was offered energy- and protein-rich main meals and snacks, delivered 3 times per week. The control group continued their habitual diet. Primary endpoint, QoL, and secondary endpoints were assessed at baseline, and after 6 and 12 wk. Data on unplanned readmissions, length of hospital stay, and mortality were collected 3 and 6 mo post-intervention. Intervention group improved standard Chair Stand Test (30-s CST) after 6 and 12 wk (P < 0.01) compared to control. Intervention exerted a significant positive effect on performance score after 12 wk (P = 0.047). Increased energy and protein intakes were strongly associated with improved QoL, functional score, hand grip strength, symptom and performance scores. Food delivery service with energy- and protein-rich main meals and snacks can improve lower body strength and performance status in malnourished lung cancer patients.

Stereotactic ablative body radiotherapy (SAbR) for oligometastatic cancer.

The metastatic state of most solid cancers traditionally has been regarded as an incurable dissemination of disease, with treatment focused on delaying progression rather than eliminating all tumour burden. In this setting, local therapies including surgery and radiotherapy are directed at quality of life end points and not at improvement in survival. However, improvements in imaging and systemic therapy have highlighted populations of patients with lower burden of metastatic disease, termed "oligometastatic," who may present an exception. This condition is hypothesized to bridge the gap between incurable metastatic disease and locoregional disease, where miliary spread either has not occurred or remains eradicable. Consequently, elimination of such low-burden residual disease may "cure" some patients or delay further progression. Accordingly, use of local therapies with the intent of improving survival in oligometastatic disease has increased. Technological advances in radiation delivery with stereotactic ablative body radiotherapy (SAbR) in particular have provided a non-invasive and low-morbidity option. While observational studies have provided interesting preliminary data, significant work remains necessary to prove the merits of this treatment paradigm. This review discusses the data for the oligometastatic state and its treatment with SAbR, as well as challenges to its investigation.

The burden of amyloid light chain amyloidosis on health-related quality of life

BackgroundLight chain (AL) amyloidosis is a rare disease characterized by misfolded amyloid protein deposits in tissues and vital organs, and little is known about the burden of AL amyloidosis on health-related quality of life. This study aimed to quantify the burden of AL amyloidosis in terms of health-related quality of life in a diverse, community-based sample of AL amyloidosis patients.ResultsThe SF-36v2® Health Survey (SF-36v2), a widely used generic measure of health-related quality of life (using physical and mental summary scales and subscales assessing eight aspects of functioning and well-being), was administered as an online survey of AL amyloidosis patients with AL amyloidosis (ClinicalTrials.gov, NCT02574676; n = 341). Compared with adjusted general population sample norms, health-related quality of life of AL amyloidosis patients was significantly worse across all SF-36v2 scales and summary measures based on analysis of variance (p < 0.05 for all). The largest decrement in AL amyloidosis patients was related to General Health (Δ = 9.7; p < 0.001). With the exception of Bodily Pain and Mental Health, differences were also clinically meaningful based on established clinically minimal important differences. The burden of AL amyloidosis overall and in key subgroups tended to be greater on physical health than on mental health. Stratified analyses indicated additional burden among patients with recently diagnosed disease and those with cardiac involvement than among their respective counterparts.ConclusionUnderstanding the burden of AL amyloidosis highlights the unmet need for treatment, helps physicians identify ancillary treatments and services geared towards improving patients’ functioning, well-being, and overall health-related quality of life. These findings also help to support the use of health-related quality of life end points as important outcome measures in current and future treatment studies.Trial registrationClinicalTrials.gov, NCT02574676. Registered October 5, 2015.

Meta-Analysis of Prostatic Artery Embolization for Benign Prostatic Hyperplasia

PurposeTo perform meta-analysis of available data on prostatic artery embolization (PAE). Materials and MethodsMeta-analysis was conducted on articles published between November 2009 and December 2015. Peer-reviewed studies with > 5 patients and standard deviations and/or individual-level data on one or more of the following outcomes were included: prostate volume (PV), peak flow rate (Qmax), postvoid residual (PVR), International Prostate Symptom Score (IPSS), quality of life (QOL) score, International Index of Erectile Function (IIEF) score, and prostate-specific antigen (PSA) level. A random-effects meta-analysis was performed on the outcomes at 1, 3, 6, and 12 months after PAE compared with baseline values, with a P < .05 decision rule as the null hypothesis rejection criterion. ResultsNineteen of 268 studies were included in data collection, with 6 included in the meta-analysis. At 12 months, PV decreased by 31.31 cm3 (P < .001), PSA remained unchanged (P = .248), PVR decreased by 85.54 mL (P < .001), Qmax increased by 5.39 mL/s (P < .001), IPSS improved by 20.39 points (P < .001), QOL score improved by −2.49 points (P < .001), and IIEF was unchanged (P = 1.0). There were a total of 218 adverse events (AEs) among 662 patients (32.93%), with 216 being Society of Interventional Radiology class A/B (99%). The most common complications were rectalgia/dysuria (n = 60; 9.0%) and acute urinary retention (n = 52; 7.8%). No class D/E complications were reported. ConclusionsPAE provided improvement in Qmax, PVR, IPSS, and QOL endpoints at 12 months, with a low incidence of serious AEs (0.3%), although minor AEs were common (32.93%). There was no adverse effect on erectile function.

Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy.

BackgroundTo evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT).MethodsForty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation.ResultsIn a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus.ConclusionsProton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life endpoints.

A prospective analysis of high-dose-rate endobronchial brachytherapy in the palliation of obstructive symptoms in lung cancer patients: A single-institution experience.

Obstructive symptoms that affect quality of life (QOL) are commonly caused by endobronchial disease in many patients with locally advanced, inoperable lung cancer. High-dose-rate endobronchial brachytherapy (HDREBBT) has been used to palliate these symptoms, yet its role is not well defined in the literature. Ninety-eight patients with locally advanced, inoperable lung cancer received HDREBBT. They were prospectively followed for survival, QOL, and toxicity endpoints. QOL measures were captured using the Quality of Life Questionnaire-Lung Cancer 30 and -Lung Cancer13. At 1-year follow-up, no significant toxicities were seen. Overall survival was 13.4% at 12months (mean 192days). Performance status, additional treatment after HDREBBT and treatment intent affected overall survival on univariate analysis (p < 0.05). Mean hemoptysis-free survival for all patients was 232.3days, cough-free survival was 140.3days, and dyspnea-free survival was 173.5days. There was no impact of any treatment- or patient-related factors of these outcomes on multivariate analysis, including additional treatment modalities and HDREBBT dose. HDREBBT is a safe and effective way to palliate endobronchial symptoms. Additional external-beam radiation therapy, chemotherapy, or chemoradiation after HDREBBT improves survival, but does not affect QOL measures.

Die identifisering van ’n geskikte vraelys vir die bepaling van lewenskwaliteit by Suid-Afrikaanse vroue met servikskanker

Cervical cancer is one of the commonest cancers among South African women. In the absence of an adequate, preventative cervical cytology programme, the majority of women present with an advanced stage of disease. Despite treatment, the prognosis for these women is poor. Furthermore, HIV and AIDS impacts adversely on the treatment of cervical cancer, whereas cervical cancer and its treatment again affect the quality of life. Objective assessment of the quality of life can improve treatment and supportive care. The current study was done to identify the most appropriate questionnaire to assess the quality of life experienced by South African women with cervical cancer. The European Organisation for the Research and Treatment of Cancer (EORTC) and the Functional Assessment of Chronic Illness Therapy Measurement System (FACIT) questionnaires are the most commonly used for assessment of the quality of life patients with cancer have. The current study assessed the appropriateness of these questionnaires for use in South Africa on the following criteria: study structure (prospective or transverse), quality of life endpoint (primary or secondary), timing of assessment during disease process and the nationalities of the study populations. The EORTC questionnaire was identified as the most appropriate for application to South African women with cervical cancer.

Mesenchymal Stem Cells & Endothelial Function

Mesenchymal Stem Cells & Endothelial Function

New initiatives for Neuro-Oncology Practice-building on the success of the first year.

It has been one year since the launch of Neuro-Oncology Practice and its success is attributed to the dedication of the editorial board members, the incredible support from authors willing to contribute high-quality original work and relevant review articles, and the enthusiasm of the readership. In addition, the editorial staff at Oxford University Press has been invaluable in the timely production of the issues. The journal will continue to focus on practical issues for providers, and I am excited to announce some special features that will be introduced in 2015. The first of these will be series of articles focused on the design, conduct and interpretation of quality-of-life (QoL) research. QoL endpoints are being included in more studies than ever before, and it is essential to be aware of the special challenges in analyzing this type of data. In this issue, Linda Dirven, Terri Armstrong, and Martin Taphoorn present a valuable introductory overview of Clinical Outcomes Assessments in neuro-oncology research and ask important questions about how they can be combined with standard measures of survival and progression. This sets the stage for the topics that will be highlighted in future reviews. Other special features planned for the coming year include updated multidisciplinary case reviews (edited by Derek Johnson) and a series on biostatistics for the practicing clinician (edited by Annette Molinaro). These articles will hopefully be a great resource for the neuro-oncology community. PubMed citations of manuscripts are an important metric for academic advancement and many authors and potential contributors have inquired about the timeline for citation indexing in Medline/PubMed. Because it is a brand new journal, Neuro-Oncology Practice does not yet have a sufficient number of issues published to be assessed for indexing. In the next year this will no longer be the case, and it will be submitted for assessment. If it is accepted, all articles will be retroactively indexed. In the meantime, the journal is fully indexed by Google/Google Scholar and articles published in the journal are easily found. It is interesting to note that even for journals that are indexed by Medline, Google and GoogleScholar drive far more online usage – up to 50–60% of online usage comes via Google, compared with about 10% via Medline/PubMed. This reflects the readers' familiarity with Google and its ease of use through full-text searching, as opposed to Medline's quality thesaurus indexing. Articles in this first issue of the second volume of Neuro-Oncology Practice highlight topics that span many clinical aspects of the subspeciality. Steroids are perhaps the most universally prescribed medication for patients with brain tumors of all grades, and as new therapies are developed it is critical to know how they may interact with steroids. Roth et al. provide an excellent update on the mechanism of action, dosing, and side effects of corticosteroids as well as potential contraindications for newer therapies. Another familiar topic that is examined anew is the use of Karnofsky Performance Status scores for evaluating cognitive function. Martin et al. unfortunately find that high KPS scores do not always correlate with high capacity for medical decision-making, stressing the need for providers not to rely solely on KPS when determining whether or not patients are able to fully comprehend treatment choices. Neuropsychologist Karin Gehring and colleagues present data to support combining both subjective and objective tools for obtaining an accurate neuropsychological assessment. Subjective data can be very valuable for information on the patient's quality of life, but may not always be directly tied to neuropsychological deficit. Neuropsychological assessment for survivors of childhood brain tumors can be especially important for discovering long-term deficits that should be addressed by physicians. While administering regular assessments to every patient may not be feasible, Hardy et al. find that parent-reported attention surveys could be a simple and cost-effective way of identifying children that could be suffering from neuropsychological impairments. This issue also contains two articles that delve into the use of radiation therapy for extensive disease. The M.D. Anderson experience with Gamma Knife radiosurgery for brainstem metastases emphasizes its ability to provide local control of many of these lesions. Back et al. examine whether concomitant bevacizumab may reduce the morbidity that can be associated with large-volume irradiation for refractory high-grade glioma. I would like to thank my co-editors and the editorial board for their role in making the first year of Neuro-Oncology Practice such a success and am looking forward to collaborating with them on future issues.

Quality of life (QoL) during first-line treatment with FOLFOX4 with or without panitumumab (pmab) in RAS wild-type (WT) metastatic colorectal carcinoma (mCRC).

693 Background: The benefits of anti-cancer treatment must be balanced with the impact of adverse events on QoL. In the PRIME study, first-line pmab + FOLFOX4 significantly improved overall survival vs. FOLFOX4 in patients (pts) with RAS WT (KRAS/NRAS WT exons 2, 3 and 4) mCRC, but was associated with typical EGFR inhibitor adverse events. Here we report pre-specified tertiary QoL endpoints for pts with RAS WT mCRC. Methods: PRIME was a randomised open-label phase III study of first-line pmab 6.0 mg/kg Q2W + FOLFOX4 vs. FOLFOX4 in mCRC pts. QoL was assessed every 4 weeks until disease progression, and once at safety follow-up, using the EuroQoL 5-domain (EQ-5D) health state index (HSI) and overall health rating (OHR; 0–100 visual analogue scale). Differences were assessed from baseline to disease progression, and to discontinuation of first-line treatment, using analysis of covariance (ANCOVA) and a mixed-effect piecewise linear model. Analysis of QoL by skin toxicity severity is also planned. Results: 505 pts had RAS WT mCRC; overall compliance rates (evaluable vs. expected assessments) were 57% for both HSI and OHR. When analysed by ANCOVA there were no significant differences between the pmab + FOLFOX4 and FOLFOX4 arms from baseline to progression (Table) or to discontinuation. In the mixed-effect model, there were no significant differences between pmab + FOLFOX4 and FOLFOX4 in terms of HSI (overall test of difference between arms from baseline to discontinuation, p=0.2433; baseline to progression, p=0.5364) or OHR (p=0.1312 and 0.1290, respectively). Significant differences in favour of pmab + FOLFOX4 were reported in the baseline to discontinuation analysis at week 8 for HIS (p=0.0267) and OHR (0.0137) and week 12 for OHR (p=0.0187), and in the baseline to disease progression analysis at week 16 for OHR (p=0.0163) (Table). Conclusions: Addition of pmab to FOLFOX4 in first-line mCRC improves OS with no negative effect on overall QoL. Clinical trial information: NCT00364013. [Table: see text]

Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer anorexia-cachexia syndrome (CACS).

Patients with cancer anorexia-cachexia syndrome (CACS) suffer a significant symptom burden, impaired quality of life (QoL), and shorter survival. Measurement of QoL impairments related to CACS is thereby important both in clinical practice and in research. We aimed to further validate the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer population. We tested the performance of the FAACT and its anorexia-cachexia subscale (ACS) within a dataset of patients with advanced non-small cell lung cancer (aNSCLC), using standard statistical methods. We then compared the performance of commonly used QoL measures stratified by CACS status and by patient self-report of appetite and weight loss. The FAACT and its ACS demonstrate internal validity consistent with acceptable published ranges for other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation coefficients demonstrate moderate correlations in the expected directions between FAACT and ACS and scales that measure related constructs. Comparing patients with and without CACS, the ACS is more sensitive to change than other QoL instruments (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). In patients with aNSCLC, the FAACT and its ACS performed well compared with other instruments, further supporting their validity and value in clinical research. FAACT and ACS scores covaried with symptoms and other QoL changes that are typical hallmarks of CACS, lending further support to their use as QoL endpoints in clinical trials among patients with CACS.

Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial

BackgroundOpen radical cystectomy (ORC) and urinary diversion in patients with bladder cancer (BCa) are associated with significant perioperative complication risk. ObjectiveTo compare perioperative complications between robot-assisted radical cystectomy (RARC) and ORC techniques. Design, setting, and participantsA prospective randomized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy (RC), pelvic lymph node dissection (PLND), and urinary diversion. Patients were randomized to ORC/PLND or RARC/PLND, both with open urinary diversion. Patients were followed for 90 d postoperatively. InterventionStandard ORC or RARC with PLND; all urinary diversions were performed via an open approach. Outcome measurements and statistical analysisPrimary outcomes were overall 90-d grade 2–5 complications defined by a modified Clavien system. Secondary outcomes included comparison of high-grade complications, estimated blood loss, operative time, pathologic outcomes, 3- and 6-mo patient-reported quality-of-life (QOL) outcomes, and total operative room and inpatient costs. Differences in binary outcomes were assessed with the chi-square test, with differences in continuous outcomes assessed by analysis of covariance with randomization group as covariate and, for QOL end points, baseline score. Results and limitationsThe trial enrolled 124 patients, of whom 118 were randomized and underwent RC/PLND. Sixty were randomized to RARC and 58 to ORC. At 90 d, grade 2–5 complications were observed in 62% and 66% of RARC and ORC patients, respectively (95% confidence interval for difference, −21% to −13%; p=0.7). The similar rates of grade 2–5 complications at our mandated interim analysis met futility criteria; thus, early closure of the trial occurred. The RARC group had lower mean intraoperative blood loss (p=0.027) but significantly longer operative time than the ORC group (p<0.001). Pathologic variables including positive surgical margins and lymph node yields were similar. Mean hospital stay was 8 d in both arms (standard deviation, 3 and 5 d, respectively; p=0.5). Three- and 6-mo QOL outcomes were similar between arms. Cost analysis demonstrated an advantage to ORC compared with RARC. A limitation is the setting at a single high-volume, referral center; our findings may not be generalizable to all settings. ConclusionsThis trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing RC/PLND and urinary diversion. Similar 90-d complication rates, hospital stay, pathologic outcomes, and 3- and 6-mo QOL outcomes were observed regardless of surgical technique. Patient summaryOf 118 patients with bladder cancer who underwent radical cystectomy, pelvic lymph node dissection, and urinary diversion, half were randomized to open surgery and half to robot-assisted laparoscopic surgery. We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups. Trial RegistrationClinicalTrials.gov identifier NCT01076387, www.clinicaltrials.gov.

Quality of Life and Patient-Reported Outcomes in Endometrial Cancer Clinical Trials

There is increasing recognition that quality of life (QoL) and patient-reported outcomes (PROs) are of fundamental importance and particularly relevant given the relatively high likelihood of long-term survival in most women with endometrial cancer (EC). However, there has been relatively little research focused on this topic. Our objective was to analyze our current knowledge and identify research questions to be included in the design of next clinical trials. Analyze and critically assess reported clinical trials in EC that have included QoL and PROs as primary or secondary end points. Surgery has a significant impact on physical and functional domains of QoL particularly in the first 6 months after diagnosis. Minimally invasive surgery is associated with less acute morbidity than open procedures and this persists over time. Lymphadenectomy is associated with increased incidence of lymphedema, important late effect. Adjuvant external irradiation may cause gastrointestinal and genitourinary symptoms that impact on physical functioning and which can persist over time. In contrast, vaginal brachytherapy has less toxicity and fewer late effects than external irradiation. The impact of treatment on sexuality has been poorly evaluated in EC survivors. There are few published data on QoL and PROs in patients treated with chemotherapy and the long-term impact has not been addressed. There is no evidence that palliative chemotherapy reduces symptoms and improves QoL. There are very few longitudinal studies on survivorship that is an important concern in EC survivors. Although there have been some studies addressing QoL and PROs in EC, we have identified deficiencies and gaps in our knowledge. Careful consideration of QoL and PROs end points and how to include them in clinical trials will result in a better appreciation of how treatments can impact on patients QoL and lead to conduct interventions to reduce late effects.