Quality Of Life Analysis Research Articles

CTNI-78. PNOC008: A PILOT TRIAL TESTING THE CLINICAL BENEFIT OF USING MOLECULAR PROFILING TO DETERMINE AN INDIVIDUALIZED TREATMENT PLAN IN CHILDREN AND YOUNG ADULTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (EXCLUDING DIFFUSE INTRINSIC PONTINE GLIOMA)

Abstract BACKGROUND Despite multiple clinical trials in young patients with newly diagnosed high grade gliomas (HGG), survival remains poor. PNOC008 is a single-arm, multi-center pilot trial, investigating the feasibility, toxicity, and efficacy of a molecularly guided individualized treatment approach following radiotherapy. METHODS Patients aged ≤21 years with newly diagnosed, localized, hemispheric HGG (Stratum A) or non DIPG, diffuse midline glioma (DMG) (Stratum B) were eligible. Comprehensive molecular profiling (targeted gene panel, whole exome, and whole transcriptome sequencing) was performed on primary tumor tissue. The molecular data was reviewed by a dedicated tumor board that recommended an individualized treatment plan combining up to four FDA approved drugs. Patients were followed for toxicity and efficacy. Circulating tumor DNA (ctDNA), imaging, and quality of life (QOL) measures were collected at multiple timepoints. RESULTS Fifty-five HGG patients enrolled between 2018 and 2023 (median age 11 years [range 2-20], n=31 female, n=29 Stratum A), including H3K27-altered (n=17), H3/IDH-wildtype diffuse pediatric-type (n=16), and H3G34-mutant diffuse hemispheric glioma (n=12). In 44 patients that followed the recommended treatment, median overall survival (OS) from time of study enrollment was 26.5 months in Stratum A (lower 95% CI: 18.5) and 23.6 months in Stratum B (lower 95% CI: 16.8), and 30 months in H3G34-mutant patients (n=10, lower 95% CI:24.6) with median follow-up of 34.5 months for all patients (lower 95% CI: 32.2). The treatment recommendations most commonly included alkylator with targeted therapy combinations. The often novel drug combinations were generally well tolerated with grade 3 or 4 treatment-related adverse events being mostly hematologic. Central imaging, ctDNA, and QOL analyses are underway. CONCLUSIONS A personalized treatment approach using comprehensive transcriptomic and genomic analysis is feasible and well tolerated with encouraging survival data in children and young adults with HGG. Further analyses of molecular subgroups and correlatives are ongoing.

Early Rituximab versus Escalating Therapy in Neuromyelitis Optica: A Cost and Quality of Life Analysis

Introduction: Rituximab, an anti-CD20 monoclonal antibody, has shown effectiveness in reducing disease relapses and disability accrual through relapses in patients with neuromyelitis optica spectrum disorders (NMOSD). However, its higher cost compared to oral immunosuppressants raises questions about its cost-effectiveness, particularly in low and middle-income countries. This study aimed to compare the cost-effectiveness of early rituximab treatment versus escalation treatment in NMOSD patients. Methods: We conducted a retrospective study of NMOSD patients treated with rituximab in the first five years of disease at a hospital in São Paulo, Brazil, from 2015 to 2019. The Early Group consisted of NMOSD patients who received rituximab as a first-line treatment. The Escalating Therapy Group included patients who were prescribed rituximab after experiencing disease activity while on oral immunosuppressants, primarily azathioprine. An economic model based on Expanded Disability Status Score (EDSS) transitions was used to assess cost-effectiveness. Cost and utility data were derived from previous studies, and sensitivity analyses for different willingness to pay (WTP) thresholds and percentage of patients upscaling from oral immunossupressants to rituximab were performed. Results: Thirty NMOSD patients were included. In the Early Group, the proportion of patients reaching the highest EDSS states (6.5 or more) decreased over five years compared to baseline. In contrast, the Escalating Therapy Group experienced an increase in this proportion over the same period. Cost-effectiveness was achieved for willingness to pay (WTP) of €20-80,000 in our main analysis, sustained in our sensitivity analysis. Conclusion: Early treatment with rituximab has the potential to lower healthcare costs and enhance quality of life for NMOSD patients, supporting its early prescription for preventive treatment.

Quality of life of patients with neurofibromatosis 1-Physical disability does not necessarily result in poor mental health.

Neurofibromatosis 1 (NF1) is a chronic neurocutaneous disease known to profoundly affect quality of life (QoL). We have performed an analysis of disease severity, mental and physical QoL and compare the different subclasses among patients with neurofibromatosis 1 (NF1). We conducted a prospective analysis of 89 NF1 patients between January 2016 and March 2018. Data sourced from local records including demographic information, employment status, education level, and marital status. All patients completed 36-Item Short Form Health Survey (SF-36) and additionally the numerical pain rating scale (NPS). Patients were stratified based on severity of NF1, visibility and disease severity. Among 89 patients, severity was classified as grade 4 was identified in 42 (47.2%), moderate in 17 (19.1%), mild in 23 (25.8%) and minimal in 7 (7.9%) cases. According to visibility scale, severe grade 3 was found in 28 (31.5%), moderate grade 2 in 26 (29.2%) and mild grade in 35 (39.3%) cases. SF-36 data, except for pain, showed significantly lower values, if compared to the standard German population (P < 0.001, physical component summary P = 0.045). Sex, marital status and education level did not significantly influence results. Employment was significantly associated with better mental and physical status (P = 0.028 and P = 0.01 respectively) and age >40 was linked to lower physical (P = 0.027) but not mental component scores (P = 0.362). The numerical pain rating scale indicated pain levels of 7-10 in 9 cases (10,1%), 5-6 in 10 patients (11.2%), 1-4 in 26 patients (29.2%) and no pain in 44 cases (49.4%). Physical component scores significantly differed across different NPS grades (P < 0.001) but not in mental component scores (P = 0.06). Finally, no significant differences were found in mental component scores across severity or visibility grades. Severity and visibility grades of patients with NF1 may not necessarily result in poor mental health. Symptomatic treatment should be considered even for severely disabled patients as they may have comparable QoL to less severely affected patients with NF1. Employment was linked to better quality of life outcomes in our findings.

Comparative analysis of Health-Related Quality of Life, anxiety and depression in patients with alopecia areata, atopic dermatitis and with association of these diseases

Introduction. Alopecia areata (AA) and atopic dermatitis (AtD) are associated with significant psychosocial burden, emphasizing the importance of quality of life (QoL) assessment due to potential psychological distress and treatment hindrance.Aim. To conduct a comparative analysis of QoL, anxiety and depression in patients with AA, AtD and their combination, according to diseases severity.Materials and methods. The study included 91 patients of both sexes (18–52 years old). All patients were divided into 3 groups: group 1 – 25% patients with AA, group 2 – 28% with AtD, group 3 – 47% patients with both diseases; the groups were subdivided by dermatoses severity. The DLQI, Skindex-29 and HADS questionnaires were used. Mann-Whitney U-test was conducted to compare the mean values of quantitative data (М ± n) (p &lt; 0.05).Results. Group 1 had moderately decreased QoL according to DLQI (6.5 ± 0.67); total Skindex-29 score was 23.55 ± 2.46 (low impact) with the highest value in the emotion domain. In group 2 DLQI score was 12.5 ± 1.51, total Skindex-29 score was48.41 ± 3.76; in group 3 DLQI was 11.5 ± 0.58, Skindex-29 – 50.46 ± 2.14. These values corresponded to very negative impact on QoL, increasing with diseases severity. There was a reliable difference in DLQI and Skindex-29 values between groups 1 and 2 and groups 1 and 3. Mean HADS scores in all groups were generally comparable and correlated with AtD and AA severity.Conclusion. Compared to AA, AtD has a greater impact on QoL, involving all areas of social health; AA predominantly affects emotional sphere. The presence of both diseases worsens QoL as well as AtD alone, especially in aspects “emotions” and “functions”.

The Effectiveness of Facial Neuromuscular Retraining on Patients with Facial Nerve Dysfunction: A Mental Health and Quality of Life Analysis.

Background: Facial muscle dysfunction can have drastic psychosocial effects. Objectives: To evaluate the impacts of customized neuromuscular retraining on mental health, quality of life (QoL), facial muscle function, and synkinesis. Methods: Thirty patients with facial nerve dysfunction completed a course of neuromuscular retraining. Patients' mental health, QoL, facial muscle function, and synkinesis were evaluated using Patient Health Questionnaire (PHQ-9), Facial Clinimetric Evaluation (FaCE) scale, electronic, clinician-graded facial function scale (eFACE), and Synkinesis Assessment Questionnaire (SAQ) at the initial and final visits. Scores were compared before and after treatment. Results: Patients (n = 30) included had a mean age of 59.4 ± 13.4 years (range 32.3-82.8) and were mostly female (22/30, 73.3%). The most common etiology was Iatrogenic facial nerve paralysis (11/20, 36.7%). Most patients had postfacial paralysis synkinesis (15/30, 50%), while 10 had complete flaccid paralysis. The median house-Brackmann score was 2 (range 1-6). The mean duration of facial palsy was 39.5 ± 106.9 (range 1-576 months). The duration of follow-up after the initial treatment session was 5.5 months, including 10 sessions. After neuromuscular retraining median PHQ-9 scores improved from 5 (range 0-25) to 3 (range 0-20) (p = 0.002). Mean FaCE PROM scores increased from 47.7 ± 11.5 to 56.5 ± 8.8 (p = 0.001). The mean eFACE score increased from 55.8 ± 15.1 to 71.7 ± 13.6 (p < 0.001). Median SAQ score was lower at the final visit (34.6 ± 13.4) compared to the initial visit (47.7 ± 17.8; p < 0.001). Conclusion: Customized neuromuscular retraining may improve patient-reported mental health, QoL, and facial muscle function and reduce synkinesis in facial nerve dysfunction.

Survivorship program including long-term toxicities and quality-of-life development over 10 years in a randomized trial in operable stage III non-small-cell lung cancer (ESPATUE).

Over 40% stage-III non-small-cell lung cancer (NSCLC) patients (pts) experience 5-year survival following multimodality treatment. Nevertheless, little is known about relevant late toxicities and quality-of-life (QoL) in the further long-term follow-up. Therefore, we invited pts from our randomized phase-III trial (Eberhardt et al., Journal of Clinical Oncology 2015) after 10 years from diagnosis to participate within a structured survivorship program (SSP) including follow-up imaging, laboratory parameters, cardio-pulmonary investigations, long-term toxicity evaluations and QoL questionnaires. Of 246 pts initially accrued, 161 were considered potentially resectable following the induction therapy and were randomized (80 to arm A: definitive chemoradiation; 81 to arm B: definitive surgery; 85 not randomized for different reasons; group C). 31 from 37 pts still alive after 10 years agreed to the SSP (13 in A; 12 in B; 6 in C). Clinically relevant long-term toxicities (grade 3 and 4) were rarely observed with no signal favoring any of the randomization arms. Furthermore, available data from the global QoL analysis did not show a signal favoring any definitive locoregional approach (Mean QoL in SSP A pts: 56.41/100, B pts: 64.39/100) and no late decline in comparison to baseline and early 1-year follow-up. This is the first comprehensive SSP of very late survival follow-up reported in stage-III NSCLC treated within a randomized multimodality trial and it may serve as important baseline information for physicians and pts deciding for a locoregional treatment option.

Nationwide cost-effectiveness and quality of life analysis of minimally invasive distal pancreatectomy

BackgroundThis study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP).MethodsConsecutive patients submitted to LDP or RDP from 2010 to 2020 in four high-volume Italian centers were included, with a minimum of 12 months of postoperative follow-up were included. QoL was evaluated using the EORTC QLQ-C30 and EQ-5D questionnaires, self-reported by patients. After a propensity score matching, which included BMI, gender, operation time, multiorgan and vascular resections, splenic preservation, and pancreatic stump management, the mean differential cost and Quality-Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane.ResultsThe study population consisted of 564 patients. Among these, 271 (49%) patients were submitted to LDP, while 293 (51%) patients to RDP. After propensity score matching, the study population was composed of 159 patients in each group, with a median follow-up of 59 months. As regards the QoL analysis, global health and emotional functioning domains showed better results in the RDP group (p = 0.037 and p = 0.026, respectively), whereas the other did not differ. As expected, the median crude costs analysis confirmed that RDP was more expensive than LDP (16,041 Euros vs. 10,335 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay more than 5697 Euros/QALY was accepted.ConclusionRDP was associated with better QoL as explored by specific domains. Crude costs were higher for RDP, and the cost-effectiveness threshold was set at 5697 euros/QALY.

Defining optimal left ventricular assist device short-term outcomes may provide insight into programmatic quality assessment

BackgroundPatients have substantial variability in perioperative outcomes after left ventricular assist device (LVAD) implant. A perioperative multidimensional tool integrating mortality, adverse events (AEs), and patient-reported outcomes to assist in quality improvement initiatives is needed. MethodsPatients undergoing HeartMate 3 LVAD implant (1/1/2017 and 1/31/2024) in the Society of Thoracic Surgeons’ Intermacs registry were studied. A Cox proportional hazard multivariable analysis incorporating AEs as time-varying covariates for mortality out to 180 days was used to generate the Intermacs Short-Term Composite Quality (INSITE) score, reflecting the adjusted hazard ratio (HR) for mortality contributed by each AE, applying global ranking methodology. In those alive and on support at 6 months, multivariable logistic regression (odds ratio, OR) was used to examine the impact of AEs on health-related quality of life (QOL) at 180 days, captured through the INSITE-QOL score. Failure to achieve ≥1 point increase in visual analog scale (VAS) from baseline was the event in the QOL analysis. ResultsOf 13,148 patients, 4,389 (33.4%) suffered at least one AE or death through 180 days. Stroke (survival: HR 13.1; QOL: HR 1.7), dialysis (survival: HR 31.4; QOL: HR 4.2), prolonged respiratory failure (survival: HR 5.7; QOL: HR 2.3), reoperation (Survival: HR 3.4; QOL: HR 1.6) and right heart failure (survival: 5.0; QOL: HR 1.4), contributed to both mortality and failure to improve QOL at 180 days (all p<0.05). The median INSITE and INSITE-QOL scores were 0.0 [0.0,1.6] and 0.0 [0.0,0.0], respectively. At 9.4% (n=17) of centers, a high INSITE score (≥13) was present in 15% of patients while the top 25% of centers had perfect INSITE-QOL scores in at least 75% of patients. ConclusionsAEs after LVAD confer differential impact on mortality and QOL, enabling development of global rank outcome scores. Given the high mortality hazard conferred by 180-day AEs, center-specific quality interventions aimed at reducing early complications provide the greatest opportunity to improve long-term survival and QOL.

Factors Associated with Quality of Life in Patients with Dementia with Lewy Bodies: Additional Analysis of a Cross-Sectional Study.

Quality of life (QOL) and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers are important factors to consider when developing treatment strategies. To investigate factors associated with QOL in patients with DLB, and to examine factors associated with activities of daily living (ADL) if ADL was associated with QOL. We previously conducted a questionnaire survey study to investigate the treatment needs of patients with DLB and their caregivers. This pre-specified additional analysis evaluated the Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form-8 for QOL, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II total score for ADL. In total, 231 patient- caregiver pairs and 38 physicians were included. Multivariable analysis of QOL showed that the MDS-UPDRS Part II total score (standard regression coefficient [β], - 0.432) was associated with the PCS, and presence of depression (β, - 0.330) was associated with the MCS. The severity of postural instability/gait disorder (PIGD) (β, 0.337) and rigidity (β, 0.266), presence of hallucinations (β, 0.165), male sex (β, 0.157), and use of "short stay" or "small-scale, multifunctional home care" (β, 0.156) were associated with worsened ADL. In patients with DLB, QOL was negatively impacted by severity of ADL disability and depression, and ADL was negatively impacted by severity of PIGD and rigidity, hallucinations, male sex, and use of "short stay" or "small-scale, multifunctional home care."

The analysis of quality of life of patients with glioblastoma after adjuvant radiation therapy

Background. Optimizing approaches to the treatment of patients with glioblastoma (GB) is an urgent task partly owing to the wider implementation of hypofractionated radiation therapy (HRT) regimens. At the same time, increasing survival without maintaining the patient’s quality of life (QoL) cannot be considered successful treatment. Purpose – to analyze QoL of patients with GB after adjuvant radiation treatment in the groups of standard and hypofractionated radiation regimens. Materials and methods. 159 patients with verified GB, who had undergone surgery in State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine» over the period from 2014 to 2020, were divided into two groups according to the regimen of RT: SRT group (n = 49) – standard regimen (total dose 60.0 Gy in 30 fractions over 6 weeks); HRT group (n = 110) – hypofractionated regimen (total dose 52.5 Gy in 15 fractions over 3 weeks). The patients were surveyed about QoL three times during their follow-up (3, 6 and 12 months after RT) according to the Global Health Status Scale (GHSS), domains of insomnia and fatigue of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30 version 3.0). Statistical analysis was performed separately for each group (SRT and HRT; intragroup analysis), as well as between SRT and HRT groups as comparison of independent groups with a different number of follow-up examinations for each period of the follow-up (intergroup analysis). Results. The H0 hypothesis about the absence of statistically significant difference between the results of three subsequent surveys according to the GHSS, domains of insomnia and fatigue in both SRT (p = 0.00003; p = 0.00002; p = 0.00002, respectively) and HRT (p = 0.00000; p = 0.00001; p = 0.00001, respectively) groups in the intragroup analysis according to the Friedman test was rejected. The pairwise comparison of the results of the second and the first survey (6 vs. 3 months) according to the Wilcoxon test showed a statistically significant decrease in QoL in the domain of insomnia (р = 0.000733) in SRT group and in the domain of fatigue (р = 0.016813) in HRT group. When comparing the results of the third and the second survey (12 vs. 6 months), the H0 hypothesis for all the studied parameters of QoL (GHS, insomnia, and fatigue) was rejected in both SRT and HRT groups (p ≤ 0.017 with the Bonferroni correction). When comparing the results of the third and the first survey (12 vs. 3 months), a statistically significant decrease in QoL in all studied parameters of QoL was observed: GHSS (р = 0.000078); fatigue (р = 0.000294); insomnia (р = 0.000318). The comparison of the results of these surveys in SRT group showed a statistically significant decrease of QoL in GHSS (р = 0.004650) and fatigue (p = 0.017938), with the level of statistical significance getting closer to the set critical value considering the Bonferroni correction. The intergroup analysis according to the Mann-Whitney U test showed a statistically significant advantage of HRT over SRT in all studied parameters of QoL in three subsequent surveys (p &lt; 0.05). The ρ-test confirmed these data: HRT group patients had better parameters of QoL than SRT group patients over the whole period of the follow-up. Conclusions. The analysis of QoL according to the results of three subsequent surveys 3, 6, and 12 months after RT according to the GHSS, domains of insomnia and fatigue of the EORTC QLQ-C30 demonstrated a decrease in QoL of patients in both SRT and HRT groups. At the same time, a statistically significant advantage of HRT group over SRT group in all studied parameters of SRT was observed when the results of three subsequent surveys were compared. The proposed regimen of HRT for patients with primarily diagnosed GB may be considered an acceptable alternative to SRT in view of impact on QoL.

Cost and Quality of Life of Disability Progression in Multiple Sclerosis Beyond EDSS: Impact of Cognition, Fatigue, and Limb Impairment.

Understanding the socioeconomic burden of multiple sclerosis (MS) is essential to inform policymakers and payers. Real-world studies have associated increasing costs and worsening quality of life (QoL) with disability progression. This study aims to further evaluate the impact of cognition, fatigue, upper and lower limb function (ULF, LLF) impairments, and disease progression per Expanded Disability Status Scale (EDSS) level, on costs and QoL. This was a cross-sectional cohort study including 20,988 patients from the German NeuroTransData MS registry from 2009 to 2019. QoL analyses were based on EQ-5D-5L. Cost analyses included indirect/direct medical and non-medical costs. Eight subgroups, ranging from 439 to 1812 patients were created based on presence of measures for disease progression (EDSS), cognition (Symbol Digit Modalities Test [SDMT]), fatigue (Modified Fatigue Impact 5-Item Scale [MFIS-5]), ULF (Nine-Hole Peg Test [9HPT]), and LLF (Timed 25-Foot Walk [T25FW]). Multivariable linear regression assessed the independent effect of each test's score on QoL and costs, while adjusting for EDSS and 12 other confounders. Lower QoL was associated with decreasing cognition (p<0.001), worsening ULF (p=0.025), and increasing fatigue (p<0.0001); however, the negative impact of LLF worsening on QoL was not statistically significant (p=0.54). Higher costs were associated with decreasing cognition (p<0.001), worsening of ULF (p=0.0058) and LLF (p=0.049), and increasing fatigue (p<0.0001). Each 1-scale-step worsening function of SDMT, MFIS-5, 9HPT, and T25FW scores resulted in €170, €790, €330, and €520 higher costs, respectively. Modeling disability progression based on SDMT, MFIS-5, 9HPT, and T25FW scores as an interaction with EDSS strata found associations with lower QoL and higher costs at variable EDSS ranges. Disease progression in MS measured by 9HPT, SDMT, and MFIS-5 had a significant negative impact on QoL and broad socioeconomic costs independent of EDSS. T25FW had a significant negative association with costs. Cognition, fatigue, ULF, and LLF have stronger impact on costs and QoL in patients with higher EDSS scores. Additional determinants of MS disability status, including SDMT, MFIS-5, 9HPT, and T25FW, should be considered for assessing cost effectiveness of novel therapeutics for MS.

HGG-32. PNOC008: A PILOT TRIAL TESTING THE CLINICAL BENEFIT OF USING MOLECULAR PROFILING TO DETERMINE AN INDIVIDUALIZED TREATMENT PLAN IN CHILDREN AND YOUNG ADULTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (EXCLUDING DIFFUSE INTRINSIC PONTINE GLIOMA)

Abstract BACKGROUND Children and young adults diagnosed with high-grade glioma (HGG) face extremely poor prognoses. Despite multiple clinical trials testing new treatments in this population, a survival advantage has yet to be achieved. Herein we assessed, in a single-arm, multi-center pilot trial, the feasibility of molecular profiling of primary HGG tumor tissue to create an individualized treatment plan with up to four FDA approved medications. METHODS Patients aged &amp;lt;21 years with newly diagnosed, localized, hemispheric HGG (Stratum A) or midline HGG (non-DIPG; Stratum B) were eligible. Tumor tissue underwent comprehensive molecular profiling (targeted gene panel, whole exome, and whole transcriptome sequencing). Based on detailed review of the molecular data by a dedicated tumor board, an individualized treatment plan that combined up to four FDA approved drugs was recommended. Circulating tumor DNA (ctDNA), imaging, and quality of life (QOL) measures were collected at multiple timepoints. RESULTS Fifty-five patients enrolled between 2018 and 2023 (median age 11 years [range 2-20], n=31 female, n=29 Stratum A). The most common integrated diagnoses included H3K27-altered diffuse midline glioma (n=17), H3/IDH-wildtype diffuse pediatric-type HGG (n=16), and H3G34-mutant diffuse hemispheric glioma (n=12). Median overall survival (OS) from the time of study enrollment was 26.5 months in Stratum A (lower 95% CI: 18.7) and 21.7 months in Stratum B (lower 95% CI: 16.8), with a median follow-up of 35.4 months for all patients (lower 95% CI: 32.5). The most common grade 3 or 4 treatment-related adverse events were decreased neutrophils (n=28), decreased platelets (n=22), and decreased white blood cells (n=16). As of December 2023, seven patients remain on therapy. Central imaging, ctDNA, and QOL analyses are underway. CONCLUSIONS A personalized treatment recommendation for children and young adults with HGG based on comprehensive transcriptomic and genomic analysis is feasible. Current survival data are encouraging, and molecular subgroup analyses are ongoing.

Health-related quality of life (QoL) in randomized phase III trials in oncology: Association between results of QoL, results of primary endpoint and drug approval.

11109 Background: scientific community and regulatory agencies have shown a growing interest on QoL, although the inclusion and reporting of QoL analysis in clinical trials is still suboptimal. Methods: we previously published a meta-research study of phase III randomized clinical trial (RCT) in patients with solid neoplasms treated with systemic therapy, published from 2012 to 2021 (BMJ Oncology 2023;2:e000021). For the present analysis, we selected the RCT conducted in the advanced setting, integrating the database with results of QoL and of primary endpoints, and with info about regulatory approval. The main outcome was the analysis of correlation of QoL results with study primary endpoint (EP1), namely overall survival (OS) or progression free survival (PFS). Among secondary outcomes, the availability of QoL results was reported for treatments approved by EMA/FDA, with description of time-trends. Results: 592phase III RCTpublished from 2012 to 2021 were included: 322 (54.4%) published in 2012-2016 and 270 (45.6%) in 2017-2021. 151 RCT (25.5%) were conducted in gastro-intestinal cancers, 138 (23.3%) in thoracic cancers, 71 (12%) in breast cancer, 79 (13.3%) in genito-urinary cancers. Experimental treatment was chemotherapy in 322 studies (54.4%), targeted therapies in 331 (55.9%), immunotherapy in 94 (15.9%) and hormone therapy in 52 (8.8%). OS was the EP1 in 298 clinical trials (50.3%) and PFS in 304 clinical trials (51.4%), with an overlap for 79 studies (13.3%) with multiple primary endpoints. 124 RCT (41.6%) with EP1 OS reported a positive result in EP1. Among these, QoL analysis was positive for experimental treatment in 62 studies (50%), without statistically significant difference or unfavourable in 30 (24.2%) and not available in 32 (25.8%). In the 182 studies (59.5%) with EP1 PFS and a positive result in EP1, QoL analysis was positive for experimental arm in 77 studies (42.3%), without statistically significant difference or unfavourable in 49 (26.9%) and not available in 56 (30.8%). FDA drug approvals were reported for 143 studies (24.2%). Among them, QoL results were positive for experimental arm in 101 studies (70.6%), negative in 19 (13.3%), absent in 23 (16.1%). Similarly, 142 studies (24%) were associated to EMA approval: positive QoL in 101 studies (71.1%), negative in 21 (14.8%) and absent in 20 (14.1%). The percentage of FDA and EMA approvals associated with the availability of positive QoL data increased from 2012-2016 to 2017-2021. Namely, the proportion of approvals with available QoL positive results increased from 56.5% to 81.5% (p&lt;0.001) among FDA approvals, and from 55.4% to 84.4% (p&lt;0.001) among EMA approvals. Conclusions: in many cases, a positivity in OS or PFS is not accompanied by the demonstration of QoL benefit. The temporal trend of positive QoL results among treatments approved by regulatory agencies is encouraging.

Physical activity (PA) impact on metabolome and immunity of oncogene addicted non-small cell lung cancer (NSCLC): The EXcellenT trial.

e20582 Background: Today patients (pts) with oncogene addicted advanced NSCLC receive molecular targeted therapies as first-line treatment ensuring high compliance to therapy, few side effects and long survival time. These pts are usually young and with a strong wish to regain the pre-diagnosis quality of life (QoL), including the ability to perform PA. It’s known that PA can impact significantly on metabolomic and immunity status, but to date only few studies on its role in NSCLC have been performed. The aim of the EXcellenT trial is to evaluate if a tailored PA program may have an impact on QoL and performances of this homogeneous subgroup of pts. An exploratory objective was to explore the complex interplay between PA and immune status and the influence of PA on metabolome. Methods: EXcellenT (Exercise in Extended oncogene addicted Lung Cancer in Active Treatment - NCT05306652) is an Italian monocentric prospective study enrolling 40 pts with oncogene-addicted advanced NSCLC in active treatment with tyrosine kinase inhibitors (TKI). Pts are randomized in 2 arms: an interventional arm of a personalized supervised PA program or a counselling group of home-based exercise. We explored peripheral variations of T cells subsets during TKI treatment combined with exercise training to better define the immuno-dependence of these tumors. Fatty acid composition (FA) of plasma has been carried out using gas chromatography-flame ionization detection (GC-FID) and liquid chromatography-mass spectrometry (LC-MS). Immature and mature neutrophils, monocytes, CD34+ cells and megakaryocytes (MK) precursors have been determined through flow cytometry analysis. Results: A preliminary exploratory analysis on the first patients enrolled with 3 complete time point (baseline; week 4 and 12) was performed. To date 23 out of 40 pts have been enrolled, 46% of them with pre-diagnosis leisure-time physical activity. The oncogene identified are: ALK 52%, EGFR 26%, BRAF 9%, RET 4%, ROS1 9%. 35% had stable brain metastasis (mts) and 39% bone mts not at risk of skeletal-related events. FA analysis (4 pts) showed significant increase of monounsaturated fatty acids (p = 0.0329) during the study. According to immunophenotype, we observed (3 pts) a significant reduction of CD34+ cancer stem cell (p 0.0112) and a consistent increase in mature CD66b+CD10+ neutrophils with a trend of decrease in CD66b+CD10- cells. Conclusions: The ExcellenT trial is showing that PA programs are feasible and well accepted by patients with oncogene-addicted NSCLC. The QoL analysis will be performed at the end of enrolment. The preliminary analysis on metabolomic and immunity status shows an improvement of fatty acid composition and an increase of mature cell precursors compared to immature counterpart suggesting a potential role of PA in hindering tumor immune escape strategies. Clinical trial information: NCT05306652 .

Deep endometriosis – diagnosis and impact on quality of life

Introduction. Deep infiltrating endometriosis (DIE) is considered the most painful form of endometriosis, responsible for reducing the women’s quality of life (QoL). Its management presents difficulties in medicine. The #Enzian classification reflects locations of DIE and simplifies its medical management. International guidelines recommend studies of QoL in women with endometriosis. Objective. To investigate the symptoms of DIE and determine its impact on QoL to optimize its diagnostics. Materials and methods. A cohort study was conducted over 2 years at the Gheorghe Paladi Municipal Clinical Hospital, including 190 patients with endometriosis, who were divided into groups: main group - 85 patients with DIE, control group - 105 other endometriosis forms. To objectify the pain, Visual Analog Scale and Biberoglu and Behrman (B&amp;B) were used. Endometriosis was staged with the #Enzian classification. For the analysis of QoL, three standardized questionnaires were used. Data were recorded in Excel and statistically calculated with the SPSS program. Results. Pelvic pain syndrome according to the Visual Analog Scale and B&amp;B scales in the main group was 3 times more pronounced than in the control group (p &lt; 0.01). Lesions of DIE according to the #Enzian statistically correlated with chronic pelvic pain, dysmenorrhea, dyspareunia, dysuria, dyschezia &gt;7 points (VAS), catamenial rectal tenesmus, defecation disorders, menometrorrhagia, hematuria, bladder tenesmus, hydronephrosis with ureteral stenting during pregnancy, catamenial cough and hemoptysis, chest pain and spontaneous pneumothorax, hemorrhagic scar, hiccups, and the frenicus symptom (p &lt; 0.05). According to the questionnaires of QoL, DIE significantly influences life determinants by 44.27%, compared to the control group at 3.64% (p &lt; 0.01), allowing realization of life determinants in a maximum of 58.54% vs. the control group’s 92.18% (p &lt; 0.01). Additionally, psychological well-being in patients with DIE is lower than that in the control group (44.29% vs. 81.38%, p &lt; 0.01). Conclusions. High-intensity pain syndrome and extragenital symptoms correlated with compartments of #Enzian will assist in the preoperative multidisciplinary diagnosis of DIE. The high influence on life determinants, the low realization of life potential, and the low psychological well-being confirm the significant impact of DIE on QoL, classifying it as a disability.

The Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Elderly Breast Cancer Patients: What Do We Know?

Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.

Quality of Life Analysis in Patients with Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a chronic progressive disease causing loss of visual acuity and ultimately blindness. This visual impairment can contribute to psychiatric comorbidity and worse overall quality of life (QOL). Our goal was to assess the relationship between the severity of disease for people with RP and QOL as it pertains to mental health, social support, disability resources, and financial factors. This was a survey study conducted from June 2021 to February 2022 including 38 people with RP. QOL was assessed through a survey questionnaire focusing specifically on demographics, visual function, family, employment, social support, and mental health/well-being. Statistical analysis was conducted using a χ2 test for significance. A best corrected visual acuity (BCVA) of less than 20/200 (p = 0.0285) and living alone (p = 0.0358) were both statistically significant independent risk factors for experiencing depressive symptoms. Highest education level attained and unemployment rate were not found to be related to the development of depressive symptoms. Subjects had a higher unemployment rate (64% vs. US rate of 3.6%) and a high likelihood of reporting depressive symptoms (47.4%). People with RP are more likely to be unemployed and to develop depressive symptoms when compared to the general population. Similar to previous studies' findings, those with a BCVA of less than 20/200 were statistically more likely to experience depressive symptoms; living alone is a novel risk factor that is also associated with the presence of depressive symptoms. Contrary to prior findings, highest education level and unemployment status were found not to be related to the development of depressive symptoms. These patients may benefit from regular depression screenings and optional establishment of care with a psychiatrist or psychologist if they live alone or their BCVA is 20/200 or worse.

Sacral neuromodulation in children and adolescents with defecation disorders.

Even if understanding of neuronal enteropathies, such as Hirschsprung's disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation. A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDLR). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency. Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung's disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity. SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation.

Abstract PO3-19-12: Evaluating the impact of ePRO-based follow-up system (Pink Ribbon Diary) on quality of life and treatment adherence in patients with breast cancer receiving CDK4/6 inhibitors: a single center, randomized controlled study (JPRO-B)

Abstract Background: Treatment-related toxicities (TRT) may decrease patient’s quality of life (QOL) and may result in a decrease of adherence to the therapy. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), such as palbociclib (PAL) and abemaciclib (ABM) improved patients’ outcomes with estrogen receptor-positive (ER+) HER2 negative (HER2-) advanced breast cancer (ABC), however, majority of patients who undergo CDK4/6i therapy experience ≥ Grade 2 TRTs, such as hematological abnormalities, gastrointestinal disorders or general fatigue. While prompt management of those TRTs is mandatory to prevent patients from discontinuing the therapy, real-time monitoring of TRTs has been warranted. Recently, efforts have been made to monitor symptoms using electronic patient-reported outcome (ePRO) to detect side effects as early as possible and to provide timely support. However, the efficacy of ePRO in daily clinical practice for those receiving CDK4/6is is still unclear. In addition, the researches in the field of ePRO to date have only focused on drugs administered intravenously in hospitals, where patients’ adherence has no clinical importance. Study design and eligibility criteria: This randomized, open-label, controlled phase 2 trial is designed to assess the efficacy of a new proprietary ePRO system, the Pink Ribbon Diary (PRD), compared with placebo (usual care without the ePRO system) in breast cancer patients with ER+HER2-ABC receiving oral CDK4/6i-based therapy aged ≥ 20 years. All eligible patients who complete training on how to use ePRO system are randomly allocated to either arm A using ePRO system or arm B receiving usual care (1:1). Participants in the arm A are required to record medication taken and physical condition every day for 3 months, and report adverse events using PRO-CTCAETM once a week. Patients in the arm B are also asked to answer to questions concerning adverse events using PRO-CTCAETM at monthly hospital visit for 3 months. All participants are asked to respond to the EORTC QLQ-C30 at their monthly visit and a questionnaire survey on adherence before the study and after completion of the study. Participants in the arm A and healthcare providers, will answer the questionnaire about the feeling of using the PRD. Primary endpoint is the change in global health status/QOL (EORTC QLQ-C30) at 3 months from baseline. Secondary endpoints are RDI (relative dose intensity), other domains of EORTC QLQ-C30, number of days missed medication, PDC (proportion of days covered), survey of medication compliance awareness using MMAS-8 (Morisky Medication Adherence Scale), questionnaire on use of PRD, and comparison between two groups of occurrence of adverse events and incidence of missed medication. Study objective: To assess the clinical efficacy of PRD in patients with ER+HER2-ABC undergoing CDK4/6i-based therapy. Statistical methods: For analysis of QOL, the primary endpoint, the differences in global health status/QOL (EORTC QLQ-C30) before and after the study will be compared between the two groups using the t-test. Present accrual and target accrual: The study was approved by institutional review board in December 2022, and is open for enrollment. The target sample size is 70. The study is on-going and 22 patients have been accrued to date. Trial registration numbers: Japan Registry of Clinical Trials (jRCT) jRCT1030220626 (https://jrct.niph.go.jp/re/reports/detail/30182). Citation Format: Rie Ozeki, Hideo Shimizu, Kotaro Iijima, Misato Okazaki, Junichiro Watanabe, Mitsue Saito. Evaluating the impact of ePRO-based follow-up system (Pink Ribbon Diary) on quality of life and treatment adherence in patients with breast cancer receiving CDK4/6 inhibitors: a single center, randomized controlled study (JPRO-B) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-12.

Long-term survival outcomes and quality of life of image-guided proton therapy for operable stage I non-small cell lung cancer: A phase 2 study

Background and purposeThis study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). Materials and methodsThis single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. ResultsWe enrolled 43 patients (median age: 68 years; range, 47–79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83–99), 95 % (82–99), and 86 % (72–94), respectively, at 3 years, and 83 % (66–92), 95 % (82–99), and 77 % (60–88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. ConclusionOur findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL.