Health-related Quality Of Life Analysis Research Articles

A Phase 3 Study of Pembrolizumab versus Placebo for Previously Treated Patients from Asia with Hepatocellular Carcinoma: Health-Related Quality of Life Analysis from KEYNOTE-394

Introduction: KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods: HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results: The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, −8.4; 95% CI: −11.7 to −5.1) versus pembrolizumab (−4.0; 95% CI: −6.4 to −1.6; difference vs. placebo: 4.4; 95% CI: 0.5–8.4; nominal p = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (−6.9; 95% CI: −9.4 to −4.5) versus pembrolizumab (−2.7; 95% CI: −4.5 to −1.0; difference vs. placebo: 4.2; 95% CI: 1.2–7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58–1.25; nominal p = 0.1993). Conclusion: Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.

Health-Related Quality of Life Analysis in Patients with Non-Functioning Pituitary Macroadenomas Treated with Transsphenoidal Surgery with or without Radiation Therapy

The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to assess patient-reported QoL in our institutional experience using a cross-sectional survey. We identified 488 patients with NFPMA treated at our institution from 1980-2010 who underwent transsphenoidal surgery (TSS) with or without adjuvant salvage therapy with radiation therapy (RT) and/or surgery. The following validated patient-reported outcome measures were collected: the RAND Short Form-36 Health Survey (SF-36), the Multidimensional Fatigue Inventory (MFI-20), and the Cognitive Failures Questionnaire (CFQ). Clinical characteristics of patients who did and did not receive RT were compared using Wilcoxon rank-sum test or Fisher's exact test. We used multivariable linear regression and reported mean score differences between comparison groups. The response rate to survey invitation was 47% (229 patients). Median age at the time of initial TSS was 55 years (18-85 years). 35% of patients were female. 25% of participants received RT a median of 2.0 years (0.1-22.5) after initial TSS, and 15% of patients had >1 additional surgery after initial TSS. The patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28 mm v 22 mm, p < 0.0001) and were more likely to have visual symptoms (65% v 34%, p = 0.0002 and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients completed QoL questionnaires a median of 7.7 years (1.3-29.9) after initial TSS, at which point patients with hypopituitarism reported worse energy and fatigue (SF-36 Energy/Fatigue: -7.95, p = 0.026) and cognitive function (CFQ: 5.35, p = 0.026). Patients who received RT reported significantly worse general health (SF-36 General Health Perceptions subscale: -8.44, p = 0.032), physical health (SF-36 Physical Health Composite: -4.07, p = 0.042), physical fatigue (MFI-20 Physical Fatigue subscale: 11.68, p = 0.024) and cognitive functioning (CFQ: 6.64, p = 0.0298). The largest QoL differences were seen in patients who experienced a financial stressor after treatment, independent of treatment type. These patients reported significantly worse QoL for most outcomes, including emotional well-being, physical and mental health, social functioning, energy level, and motivation. RT was associated with self-reported unstable/insecure or very dire financial circumstances (28% v 7%, p < 0.0001). Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with decreased QoL in several domains, and these factors may identify patients who can benefit most from early multidisciplinary care, including financial counseling and additional psychosocial support.

Health-related quality of life analyses in nonfunctioning pituitary macroadenoma patients identifies at-risk populations.

The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to investigate associations between patient factors, clinical data, and patient-reported QoL in patients with NFPMA. Patients with treated NFPMA and > 1 year of follow up after transsphenoidal surgery (TSS) and with no evidence of progressive disease were evaluated utilizing the following patient-reported outcome measures: RAND-36-Item Health Survey, Multidimensional Fatigue Inventory, Cognitive Failures Questionnaire. 229 eligible patients completed QoL questionnaires a median of 7.7 years after initial transsphenoidal surgery (TSS). 25% of participants received radiation therapy (RT) a median of 2.0 years (0.1-22.5) after initial TSS. Patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28mm v 22mm, p < 0.0001), were more likely to have visual symptoms (65% v 34%, p = 0.0002), and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients with hypopituitarism reported worse energy and fatigue and cognitive function (p < 0.03). Patients who received RT reported significantly worse general health, physical health, physical fatigue and cognitive functioning (p < 0.05). The largest QoL differences were in patients who experienced a financial stressor, independent of treatment type. Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with more impaired QoL in patients with NFPMA. Awareness of these factors can better guide use and timing of radiation therapy in addition to identifying patients who can benefit from multidisciplinary surveillance.

Longitudinal health-related quality of life analysis in childhood cancer survivors after proton beam therapy.

Whilst proton beam therapy (PBT) for children with cancer is expected to reduce their comorbidities, to date only a limited number of studies have been published. To analyze the long-term comorbidity and health-related quality of life (HRQoL) of childhood cancer survivors (CCSs) after PBT, we conducted a questionnaire-based study. Questionnaires were sent to CCSs who underwent PBT at the University of Tsukuba Hospital during the period from 1984 to 2020. Scores from 41 CCSs who did not undergo PBT (noPBT-CCSs) and from the general population were used for comparison. In total, 110 individuals who underwent PBT participated in the study. Among them, 40 individuals were longitudinally analyzed. The range of change in the scores was significantly greater in the CCSs whose initial scores were low. Although the comorbidity levels were more severe, HRQoL tended to be better in the PBT-CCSs than in the noPBT-CCSs with central nervous system (CNS) or solid tumors, respectively. When compared with the general population, the psychosocial health summary scores and its components were not different in the noPBT-CNS-CCSs. On the other hand, the psychosocial health summary scores and/or at least one of the scores of emotional, social, and school functioning were significantly higher in the other CCSs groups. The HRQoL scores of CCSs with low initial scores can be greatly changed over time. Appropriate psychosocial support for this population is warranted. PBT may avoid reduction in HRQoL in terms of the psychosocial functioning of CCSs with CNS tumors.

Health-related quality of life analysis in ovarian cancer clinical trials involving PARP inhibitors: a critical methodological perspective.

The poly (ADP-ribose) polymerase inhibitors (PARPi) have yielded significant clinical benefits as maintenance therapy in women with newly diagnosed and relapsed platinum-sensitive advanced ovarian cancer. These drugs were approved based on progression-free survival, the primary endpoint of their respective pivotal trials. Health-related quality of life (HRQoL) and/or patient-reported outcomes were included in these trials as a secondary exploratory endpoint. Nevertheless, many weaknesses in the analysis of HRQoL across these trials can be noticed. Heterogeneity and suboptimal HRQoL analysis in oncology trials contribute to misconceptions about this endpoint among oncologists and prevent quality of life as being an endpoint used for approvals. In this article, we discuss these HRQoL results from a methodological perspective and propose some solutions for improvement that could be used by regulatory and academic institutions running ovarian cancers trials. Notably, we suggest to measure and analyze HRQoL data after disease progression, to focus dedicated papers on the statistical analyses of HRQoL recommended by the SISAQOL consortium (linear mixed model for repeated measures and time-to-event approaches) and to communicate on available guidelines to ensure compliance with best international practices regarding the measurement and analysis of HRQoL.

Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma

BackgroundIn the phase 3 KEYNOTE-426 (NCT02853331) trial, pembrolizumab + axitinib demonstrated improvement in overall survival, progression-free survival, and objective response rate over sunitinib monotherapy for advanced renal cell carcinoma (RCC). ObjectiveTo evaluate health-related quality of life (HRQoL) in KEYNOTE-426. Design, setting, and participantsA total of 861 patients were randomly assigned to receive pembrolizumab + axitinib (n = 432) or sunitinib (n = 429). HRQoL data were available for 429 patients treated with pembrolizumab + axitinib and 423 patients treated with sunitinib. Outcome measurements and statistical analysisHRQoL end points were measured using the European Organisation for the Research and Treatment of Cancer Core (EORTC) Quality of Life Questionnaire (QLQ-C30), EQ-5D visual analog rating scale (VAS), and Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index—Disease-Related Symptoms (FKSI-DRS) questionnaires. Results and limitationsBetter or not different overall improvement rates from baseline between pembrolizumab + axitinib and sunitinib were observed for the FKSI-DRS (–0.79% improvement vs sunitinib; 95% confidence interval [CI] –7.2 to 5.6), QLQ-C30 (7.5% improvement vs sunitinib; 95% CI 1.0–14), and EQ-5D VAS (9.9% improvement vs sunitinib; 95% CI 3.2–17). For time to confirmed deterioration (TTcD) and time to first deterioration (TTfD), no differences were observed between arms for the QLQ-C30 (TTcD hazard ratio [HR] 1.0; 95% CI 0.82–1.3; TTfD HR 0.82; 95% CI 0.69–0.97) and EQ-5D VAS (TTcD HR 1.1; 95% CI 0.87–1.3; TTfD HR 0.98; 95% CI 0.83–1.2). TTfD was not different between treatment arms (HR 1.1; 95% CI 0.95–1.3) for the FKSI-DRS, but TTcD favored sunitinib (HR 1.4; 95% CI 1.1–1.7). Patients were assessed during the off-treatment period for sunitinib, which may have underestimated the negative impact of sunitinib on HRQoL. ConclusionsOverall, patient-reported outcome scales showed that results between the pembrolizumab + axitinib and sunitinib arms were not different, with the exception of TTcD by the FKSI-DRS. Patient summaryCompared with sunitinib, pembrolizumab + axitinib delays disease progression and extends survival, while HRQoL outcomes were not different between groups.

Health-Related Quality of Life Analysis Supports the Recommendation for HeartMate3 Implantation without Concomitant Mitral Valve Surgery

<h3>Purpose</h3> Functional mitral valve regurgitation (MR) is common in patients with end-stage heart failure awaiting left ventricular assist device (LVAD) implantation. The resolution of functional MR in LVAD patients has been detected for different LVAD types and across all grades of MR severity. However, it should be proven if the health-related quality of life (HRQoL) after LVAD implantation is comparable in patients with different preoperative MR grades. <h3>Methods</h3> We performed a single-center HRQoL analysis including 34 patients with HeartMate 3 (HM3) implantation using the SF12 Health Survey and the Hospital Anxiety and Depression Score (HADS) at least 1 year after LVAD implantation. The study groups were classified according to echocardiographically defined grade of MR. The group without severe MR (none, mild or moderate MR) comprised 24 patients; the group with severe MR comprised 10 patients. Clinical characteristics including the six-minute walk test (6MWT) were documented. <h3>Results</h3> Age, gender, history of prior heart valve surgery as well as the rate of heart transplantation, ECMO and RVAD implantation, right heart failure, ventricular arrhythmias, stroke, suction events, LVAD thrombosis, and bleeding events were comparable between LVAD patients with severe and not severe MR (p < 0.05). The 6MWT was comparable in the postoperative period (p = 0.13) and one year after LVAD implantation (p = 0.57). No significant differences were apparent in the SF-12-determined physical health (severe MR: 36.6 ± 8.4; not severe MR: 40.1 ± 9.3; p = 0.32) and mental health (severe MR: 49.5 ± 9.7; not severe MR: 54.3 ± 10.5; p = 0.22) as well as in the HADS-determined anxiety (severe MR: 5.6 ± 3.6; not severe MR: 4.9 ± 3.3; p = 0.58) and depression grade (severe MR: 6.3 ± 3.7; not severe MR: 4.6 ± 4.1; p = 0.28). <h3>Conclusion</h3> Physical and mental health as well as anxiety and the depression grade that were measured with standardized questionnaires are comparable in LVAD patients with preoperative severe and not severe MR. The results of this HRQoL pilot study support the recommendation of the International Society for Heart and Lung Transplantation for a HM3 implantation without concomitant MV repair and replacement.

Health-Related Quality of Life Analysis in Metastatic Colorectal Cancer Patients Treated by Second-Line Chemotherapy, Associated With Either Cetuximab or Bevacizumab: The PRODIGE 18 Randomized Phase II Study

Background and ObjectivesWe have previously showed that for patients with wild-type RAS metastatic colorectal cancer (mCRC) progressing after bevacizumab plus chemotherapy, bevacizumab continuation plus a switch of chemotherapy is the most appropriate option (PRODIGE 18 phase II study). Here we aimed to determine treatment impact in patient's Health-Related Quality Of Life (HRQoL) in PRODIGE18 study. MethodsHRQoL was evaluated in 2 arms bevacizumab or cetuximab—combined with chemotherapy (modified FOLFOX6 [mFOLFOX6] or FOLFIRI) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline, first and third tumor evaluation and at the end of the study. The temporal evolution of quality of life scores was investigated using longitudinal linear mixed models of variance. The time until definitive deterioration (TUDD) was estimated using the Kaplan-Meier method and the long-rank test. A univariate Cox model was used to calculate HR with 95% CI. A multivariate Cox model was applied to determine association of TUDD with age and gender. Safety was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events. ResultsHRQoL QLQ-C30 questionnaire compliance was high at baseline (>90%) and declined over time (∼70% in tumor evaluation 1 and ∼ 60% in tumor evaluation 3), but remained similar in both treatment arms. Patient reported mean diarrhea QLQ-C30 score is significantly higher in bevacizumab treatment arm. Clinician reported mild diarrhea was more frequently declared in bevacizumab treatment arm. Cox multivariate analyses showed no statistically significant differences in TUDD for all QLQ-C30 scales between treatments. TUDD of appetite loss was significantly associated to age. ConclusionsOur study shows that no relevant impairment of patients HRQoL between the 2 treatment arms. So, the analysis of the HRQoL with equal effectiveness does not make it possible to favor one treatment over another.

Implementation of Percutaneous Transforaminal Endoscopic Discectomy in Competitive Elite Athletes With Lumbar Disc Herniation: Original Study and Review of the Literature

Background: Lumbar disc herniation (LDH) represents a frequent clinical entity in athletes. Surgical treatment of LDH with endoscopic spine surgical techniques has been proposed as a feasible alternative in these patients. Purpose: To study the particular outcomes of percutaneous transforaminal endoscopic discectomy (PTED) in competitive elite athletes with surgically treatable LDH. Study Design: Case series; Level of evidence, 4. Methods: A total of 55 competitive elite athletes with diagnosed LDH based on clinical and radiologic criteria were enrolled in this prospectively designed study. All patients underwent successful PTED. Clinical evaluation was conducted with the well-established visual analog scale for lower limb and low back pain separately. The 36-Item Short Form Health Survey (SF-36) was implemented for health-related quality of life analysis. Patients were assessed preoperatively and at regular postoperative intervals: 6 weeks and 3, 6, and 12 months, as well as 2 years. Results: Operated levels were L3-L4 (5.5%), L4-L5 (69.1%), and L5-S1 (25.4%). No major perioperative complications were observed. All patients successfully reached the end of follow-up at 2 years. Both visual analog scale scores (lower limb and low back pain) showed clinically and statistically significant improvement at 6 weeks postoperatively, with subsequent minor improvement and stabilization. All recorded SF-36 parameters demonstrated major clinical amelioration at 6 weeks, with subsequent minor but constant statistically significant improvement until the end of follow-up. Comparative evaluation of the SF-36 revealed that the physical function, bodily pain, role-emotional, and mental health parameters showed quantitatively greater improvement in comparison with rest indices. Conclusion: PTED constitutes a feasible and effective technique for surgical management of LDH in athletes, providing favorable outcomes in terms of postoperative pain and health-related quality of life. Proper performance of technique for specific cases of L5-S1 LDH may be more challenging, and these cases should be evaluated selectively for suitability for this procedure.

TCL-389: Health-Related Quality of Life Effect of Mogamulizumab by Patient Blood Involvement

Context Cutaneous T-cell lymphomas (CTCLs) are rare non-Hodgkin lymphomas that present in skin and include mycosis fungoides (MF) and Sezary syndrome (SS) subsets. Leukemic involvement is an independent prognostic factor affecting overall and disease-specific survival and increasing the risk of disease progression (Agar 2010, Am Soc J Clin Oncol). CTCL has serious negative effects on patient quality of life (QoL). Therefore, treatment goals include reducing the burden of disease, delaying progression, and improving or preserving QoL. Objective This post hoc analysis of MAVORIC trial data sought to determine whether baseline blood tumor burden affected treatment effects on patient QoL. Design The Phase 3 MAVORIC trial (NCT01728805) compared vorinostat 400 mg daily PO to mogamulizumab 1.0 mg/kg weekly for the first 28-day cycle, then on days 1 and 15 of subsequent cycles. Patient-reported outcome (PRO) analysis of health-related QoL (HRQoL) was performed using the validated Skindex-29 and FACT-G (Functional Assessment of Cancer Therapy-General) instruments. Pruritus was assessed using ItchyQoL and Pruritus Likert scales. All PROs were administered at baseline; Skindex-29 and FACT-G were then administered at every other treatment visit (Cycle 1, 3, 5, …), and ItchyQoL and Pruritus Likert scales were administered every 4 weeks at each cycle. Results Overall, no statistically significant differences between mogamulizumab and vorinostat were seen for patients without blood involvement. Statistically significant differences were seen for patients with blood involvement, with mogamulizumab-treated patients seeing statistically significant improvement in Skindex-29 for treatment Cycles 3–11 in all domains (emotional, functional, symptoms) and in the functional domain of ItchyQoL at most time points. In mogamulizumab-treated patients with blood involvement, the Pruritus Likert Scale score showed a reduction in itch from Cycle 1 and a trend toward reducing levels of itch over 12 cycles. The FACT-G Total Score showed the greatest improvement from baseline for mogamulizumab-treated patients with blood involvement compared to those without blood involvement and all vorinostat-treated patients. Conclusions Mogamulizumab patients with blood involvement saw greater HRQoL improvement than those without blood involvement. Mogamulizumab offers QoL benefit, assessed across a number of PROs, especially to patients with blood involvement (B1 or B2). Supported by Kyowa Kirin, Inc.

Prospective Longitudinal Health-related Quality of Life Analysis of the Finnish Arm of the PRIAS Active Surveillance Cohort: 11 Years of Follow-up

BackgroundLiving with an untreated cancer may alter quality of life (QoL) in the long term. ObjectiveTo prospectively study long-term changes in general, mental, and physical QoL in a contemporary active surveillance (AS) patient cohort with low-risk prostate cancer (PCa). Design, setting, and participantsThe study population consisted of patients enrolled in the PRIAS trial in Helsinki University Hospital (n = 348). The RAND-36 questionnaire was used to assess general QoL at the start of AS and at 1, 3, 5, 7, 9, and 11 years during follow-up. Patients who had undergone robot-assisted laparoscopic prostatectomy (RALP; n = 88) also received the questionnaire after treatment. Outcome measurements and statistical analysisChanges over time were analysed using multilevel mixed-effects regression models, and reported as the mean and95% confidence interval. A rule of 0.5 × standard deviation was used to estimate changes of clinical importance. Results and limitationsMedian follow-up until the end of AS or last follow-up was 7.2 (range 0.3−12.7) yr. A decrease was observed in six of eight QoL subdomains at 7 yr. However, all scores were above age-stratified reference values. There was no difference between the group who continued AS throughout the study period and the group who discontinued AS and underwent RALP. More than half of the study cohort discontinued AS (n = 198; 57%), 135 men (68%) because of events specified in the protocol and only seven (3.5%) because of anxiety. Metastatic disease developed in six patients (1.7%), and two cases (0.6%) of PCa-related death were recorded among 348 patients in more than 12 yr of overall follow-up. The lack of a randomised control population is a limitation of the study. ConclusionsContemporary protocolised AS does not impair general QoL. Men undergoing a treatment change (RALP) did not experience a decrease in QoL before or after their treatment change. Patient summaryActive surveillance is a safe treatment option for men with low-risk prostate cancer. We show that this follow-up strategy does not cause a decline in patients’ general quality of life.

Health-related quality of life analysis in differentiated thyroid carcinoma patients after thyroidectomy

Although differentiated thyroid carcinoma (DTC) has a good prognosis and survival rate, long-term medication and recurrence monitoring might be needed. The factors that affect postoperative health-related quality of life (HRQoL) in patients with DTC in different regions remain unclear or conflicting. The purpose of this study was to assess the factors that influence the HRQoL of DTC patients after surgery. This study selected 174 patients with DTC who underwent thyroidectomy. Additionally, 174 participants who were matched by age, gender, and socioeconomic status were recruited from the population as the control group. Both the DTC and control population groups were invited to answer the HRQoL questionnaire SF-36. Scores on seven domains of the HRQoL including role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH), were significantly lower for DTC patients than for the control population. The patients with no comorbidities had much higher scores on the 8 domains of the SF-36 than DTC patients with two or more comorbidities (all P < 0.05). Hypertension, diabetes and depression were the predictive factors of a poor Physical Component Summary (PCS) score and diabetes and depression were predictive factors of the Mental Component Summary (MCS) score at one year of follow-up (all P < 0.05). HRQoL is significantly influenced by many sociodemographic and clinical factors. Hypertension, diabetes and depression had a negative impact on HRQoL in DTC patients. More attention and targeted intervention should be given to DTC patients after surgery to improve quality of life.

Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care. To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources. Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen. Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity. In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m2) (HR 0.93, 95% CI 0.83 to 1.04; I2 = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I2 = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I2 = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I2 = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I2 = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured. Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.

Health-related quality of life analysis in stage III melanoma patients treated with adjuvant dendritic cell therapy

BackgroundHealth-related quality of life (HRQoL) is an important issue in the rapidly evolving field of adjuvant treatment for stage III melanoma. Dendritic cell vaccination is one of the adjuvant forms of therapy currently investigated.MethodsWe enrolled adults with stage III melanoma to receive adjuvant dendritic cell vaccination after a complete radical lymph node dissection. HRQoL assessment was one of the secondary endpoints of this trial and investigated with the EORTC-QLQ-C30 questionnaire at baseline and week 26.ResultsFifteen patients with a median age of 50 years were included in the study, with twelve evaluable patients on study at time of the second questionnaire. Global health status and role functioning improved clinically relevant with a mean difference of 15 (p = 0.010) and 26 points (p = 0.005), respectively.DiscussionDespite the small number of patients, we found a clinically relevant improved global health status. Besides, compared to the other investigated therapies, toxicity of dendritic cell vaccination is low, which supports our finding.ConclusionThis is the first description of HRQoL in melanoma patients receiving dendritic cell vaccination. We show the expected improvement in global health status after surgical treatment of stage III melanoma. Thus, adjuvant dendritic cell vaccination does not seem to hamper this improvement, as shown in our small explorative study.

Utility analysis and calibration of QOL assessment in disease management

ABSTRACTIn clinical trials, the assessment of health-related quality of life (QOL) (or patient-reported outcome [PRO] measure) has become very popular especially for clinical studies conducted for evaluating clinical benefits of patients with chronic, severe, and/or life threatening diseases. Health-related QOL information and PRO measures are useful for disease management for achieving best clinical practice. In this article, we will focus on health-related QOL assessment. The concept, design, and analysis of health-related QOL in clinical trials are reviewed. Validation of the use of health-related QOL instrument in terms of some key performance characteristics such as accuracy, reliability, sensitivity, and responsibility for assuring quality, integrity, and validity of collected QOL data are discussed. The concept of utility analysis and calibration (e.g., with respect to life events) for achieving the optimization of disease management are proposed. The change of the QOL could be translated into different life events for effective disease management. These translations could evaluate the treatment effect by more directly displaying the change of the QOL.

Longitudinal health-related quality of life analysis in oncology with time to event approaches, the STATA command qlqc30_TTD

Background and objectiveHealth-related quality of life (HRQoL) has become one relevant and available alternative endpoint of clinical trials in cancer research to evaluate efficiency of care both for the patient and health system. HRQoL in oncology is mainly assessed using the 30-item European Organisation for Research and Treatment of Cancer Quality of Life—Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 questionnaire is usually assessed at different times along the clinical trials in order to analyze the kinetics of HRQoL evolution and to fully assess the impact of the treatment on the patient's HRQoL level. In this perspective, the realization of a longitudinal HRQoL analysis is essential and the time to HRQoL score deterioration approach is a method which is more and more used in clinical trials. MethodUsing the Stata software, we developed a QLQ-C30 specific command, qlqc30_TTD, which implements longitudinal strategies based on the time to event methods by considering the time to HRQoL score deterioration. This user-written command providing automatic execution of the Time To Deterioration (TTD) and Time Until Definitive Deterioration (TUDD) methods. ResultThe program implements all published definitions and provides the Kaplan–Meier curves for each dimension (by group) and a table with the Hazard Ratio and Log-Rank test. ConclusionThe longitudinal analysis of HRQoL data in cancer clinical trials remains complex with only few programs like ours computed. This program will be of great help and will allow a more systematic and quicker analysis of the HRQoL data in clinical trials in oncology.

A double blind, placebo-controlled, randomized clinical trial that breast milk derived-Lactobacillus gasseri BNR17 mitigated diarrhea-dominant irritable bowel syndrome.

The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.

Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors.

People with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrate, are suggested as alternative therapies to factor VIII (haemophilia A) or IX (haemophilia B) for individuals who no longer respond to these treatments because they develop inhibitory antibodies. The ultimate goal of treatment is to preserve the individual's joints, otherwise destroyed by recurrent bleeds. To assess the effects of bypassing agent prophylaxis to prevent bleeding in people with hemophilia A or B and inhibitors. We searched for relevant studies from the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries (16 February 2017) and bibliographic references of retrieved studies were reviewed for potential articles to be included in the review.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register: 12 December 2016. We included randomized and quasi-randomized controlled studies (cross-over or parallel design) evaluating the effect of prophylaxis treatment with bypassing agents compared with on-demand treatment, or studies evaluating the effects of high-dose compared with low-dose prophylaxis in males of any age with hemophilia with inhibitors. Two authors independently selected studies and extracted data and assessed the risk of bias according to standard Cochrane criteria. They assessed the quality of the evidence using the GRADE criteria. We included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias.Two studies compared on-demand treatment to prophylaxis with bypassing agents. In one study (34 males) prophylaxis significantly reduced mean overall bleeding rates, MD - 7.27 (95% CI -9.92 to -4.62) (low quality evidence), mean number of overall bleeding events per month, MD -1.10 (95% CI -1.54 to -0.66), mean number of hemarthrosis, MD -6.60 (95% CI -9.32 to -3.88) (low quality evidence) and mean number of joints that had hemarthrosis, MD -0.90 (95% CI -1.36 to -0.44). The meta-analysis did not conclusively demonstrate significant benefit of prophylaxis on health-related quality of life as measured by Haem-A-QoL score, EQ-5D total score and utility score, EQ-5D VAS and SF-36 physical summary and mental summary score (low quality evidence for all health-related quality of life analyses).The remaining two studies compared dose regimens. The results from one study (22 males) did not conclusively demonstrate benefit or harm of high-dose versus low-dose recombinant activated factor VIIa (rFVIIa) as a prophylaxis for overall bleeding rate, MD -0.82 (95% CI -2.27 to 0.63) (moderate quality evidence), target joint bleeding rate, MD -3.20 (95% CI -7.23 to 0.83) (moderate quality evidence) and serious adverse events, RR 9.00 (95% CI, 0.54 to 149.50) (moderate quality evidence).The overall quality of evidence was moderate to low due to imprecision from limited information provided by studies with small sample sizes and incomplete outcome data in one study. The evidence suggests that prophylaxis with bypassing agents may be effective in reducing bleeding in males with hemophilia with inhibitors. However, there is a lack of evidence for the superiority of one agent over the other or for the optimum dosage regimen. Further studies are needed to evaluate the benefits and harms of prophylaxis treatment on health-related quality of life, as well as the effects of dose of bypassing agents on the outcomes.

Abstract P1-10-04: Accelerated partial breast irradiation versus whole breast irradiation: Health-related quality of life analysis from a phase 3 trial

Abstract Background. Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC); potential advantages of APBI include shorter treatment time, improved safety profile, and a cost reduction compared with standard fractionation. We reported the final analysis of quality of life (QOL) results from a phase 3 randomized trial comparing standard adjuvant radiotherapy (50 Gy in 25 fractions, plus 10 Gy boost) to APBI using IMRT technique (30 Gy in 5 daily fractions). The 5-year results have been recently published showing equivalence in terms of local control (ClinicalTrials.gov, NCT02104895). Methods. Overall 205 patients (105 APBI and 100 WBI) fully completed the given questionnaires at time 0 (RT start), time 1 (RT end), and time 2 (2-year follow up). Patients were asked to compile two specific questionnaires on QOL, the EORTC QLQ-C30 as a reliable and valid measure of the QOL of cancer patients in multicultural clinical research settings, and the BR23 module as a supplementary questionnaire for assessing QOL issues relevant to patients with BC. The statistical software SPSS (SPSS Inc, Chicago, IL, USA) for Windows (version 22), and STATA (StataCorp LP, College Station TX77845, USA) for Windows (version 12) were used. Chi-squared test or Mann Whitney U test were used to compare the individual characteristics of the patients between two arms. Mean and standard deviations (SD) were calculated for all QOL domains, and all scores were compared between APBI and WBI arms using the Mann Whitney test due to non-parametric distribution of data. The Kruskal-Wallis test was used to compare the scores between age groups. Results. Mean values (and SD) of QLQ-C30 scores according to arm in the series of 205 BC patients at time 2 (time 0 vs time 2), showed significant improvement in favor of APBI in terms of global health status (mean 75.5 vs 59.5, SD range 13.3-22.0; p&amp;lt;0.0001), main functional (p&amp;lt;0.01), and symptom scales (p&amp;lt;0.01). Concerning the BR23 module, APBI showed significantly better outcome in terms of body image perception (mean 89 vs 72.1, SD 13.2-26.6; p&amp;lt;0.0001) and future perspective (84.8 vs 57, SD 23.1-28.5; p&amp;lt;0.0001) among functional scales; breast (6.1 vs 18.9, SD 6.6-18.2; p&amp;lt;0.0001) and arm symptoms (11.7 vs 19.6, SD 13.4-19; p=0.002) among symptom scales. Conclusions. Women treated with APBI reported a significantly better QOL outcome as compared with women treated using WBI. QOL improvement was evidenced in terms of functional, symptoms, and global health status/QOL scales, both at the end of radiation and at a 2-year follow-up time. Citation Format: Meattini I, Saieva C, Desideri I, Miccinesi G, Francolini G, Meacci F, Muntoni C, Scotti V, De Luca Cardillo C, Marrazzo L, Simontacchi G, Pallotta S, Sanchez L, Casella D, Bernini M, Orzalesi L, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation versus whole breast irradiation: Health-related quality of life analysis from a phase 3 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-04.

Health-related quality of life analysis from the accelerated partial breast irradiation IMRT-Florence phase 3 trial: Impact of age and scores trend over time

Health-related quality of life analysis from the accelerated partial breast irradiation IMRT-Florence phase 3 trial: Impact of age and scores trend over time