Patient-reported Quality Of Life Research Articles

Integrating Palliative Care and Hematologic Malignancies: Bridging the Gaps for Our Patients and Their Caregivers.

Patients with hematologic malignancies (HMs) struggle with immense physical and psychological symptom burden, which negatively affect their quality of life (QOL) throughout the continuum of illness. These patients are often faced with substantial prognostic uncertainty as they navigate their illness course, which further complicates their medical decision making, especially at the end of life (EOL). Consequently, patients with HM often endure intensive medical care at the EOL, including frequent hospitalization and intensive care unit admissions, and they often die in the hospital. Our EOL health care delivery models are not well suited to meet the unique needs of patients with HMs. Although studies have established the role of specialty palliative care for improving QOL and EOL outcomes in patients with solid tumors, numerous disease-, clinician-, and system-based barriers prevail, limiting the integration of palliative care for patients with HMs. Nonetheless, multiple studies have emerged over the past decade identifying the role of palliative care integration in patients with various HMs, resulting in improvements in patient-reported QOL, symptom burden, and psychological distress, as well as EOL care. Importantly, these studies have also identified active components of specialty palliative care interventions, including strategies to promote adaptive coping especially in the face of prognostic uncertainty. Future work can leverage the knowledge gained from specialty palliative care integration to develop and test primary palliative care interventions by training clinicians caring for patients with HMs to incorporate these strategies into their clinical practice.

Accelerating Fleur-de-lis Panniculectomy with the Absorbable Dermal Stapler-A Study of Efficiency, Aesthetics, and Quality-of-life.

Fleur-de-lis panniculectomy (FDL), a contouring technique involving vertical and horizontal tissue resections, often involves longer operative times and potential complications. This study assessed operative time, postoperative outcomes, and patient-reported quality of life (PRO) with Insorb® Absorbable Subcuticular Skin Stapler versus traditional sutures during FDL. A retrospective review from 2015 to 2022 of FDL patients excluded those with complex concomitant procedures. Demographics, operative details, and surgical outcomes were compared between patients using the dermal stapler and those with suture-only closures. Forty subjects were identified, with 25 (62.5%) in the dermal stapler cohort. The dermal stapler significantly reduced total procedure time (66.76 vs. 125.33 min, p < 0.05). There were no significant differences in surgical site occurrences, aesthetic outcomes, readmissions, or reoperations. Multivariate regression analysis further highlighted the choice of closure technique as an independent predictor of operative time, with traditional sutures indicating a significantly increased operative time compared to using the dermal stapler (AOR 76.53, CI 38.11-114.95, p < 0.001). Regarding PROs, both groups saw improvements across multiple BODY-Q domains, but the dermal stapler group reported greater enhancements (six out of nine domains vs. three for sutures). The absorbable dermal stapler significantly reduces FDL operative time without increasing wound healing or aesthetic dissatisfaction incidents and maintains comparable quality-of-life improvements to standard suture closure. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

Abstract PO1-19-06: Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: the randomized Neo-ACT trial

Abstract Introduction In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. Method The Neo-ACT trial is an international prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes two weekly 60-min exercise sessions plus at least 150 min of moderate to vigorous physical activity per week. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). Statistical methods Patients will be randomized in a 1:1 fashion. It is anticipated that the rate of the primary endpoint pCR will be approximately 30% in the control arm (all subtypes). We aim to increase the rate of pCR in the experimental arm to 40%, i.e. a 10 percentage points increase, which is regarded clinically relevant since it would translate into improved disease-related outcomes. With a power of 80% and an alpha of 5%, a total of 712 patients have to be included; 356 in each arm. Accounting for a drop-out of 10%, we aim to include 790 patients. Stratification at the moment of computerized randomization is based on site of treatment (hospital) and biological tumour subtype (ER+HER2-, ER+HER2+, ER-HER2+, ER-HER2-). All outcomes will primarily be analysed using an intention-to-treat approach, i.e. all study subjects will belong to the treatment group (exercise intervention or control) they were assigned to, disregarding compliance. As sensitivity analysis, all outcomes will also be analysed using a per-protocol approach, meaning that participants in the intervention group who comply with less than 65% of the prescribed physical exercise program, and participants who complete less than 40% of the planned neoadjuvant systemic therapy (around two 3-weekly courses) will be excluded from analysis. Present accrual The Neo-ACT trial has started enrolment at the first site in December 2022 and since then initiated a further five Swedish and one Finnish site. Until June 15, 2023, 26 participants had been randomized in the trial. A feasibility questionnaire is distributed via the EUBREAST network which officially supports this trial and has added the designation EUBREAST12-R. Further participating sites can be accommodated depending on volume, competing trials and language requirements for the mobile application. Contact: jana.de-boniface@ki.se Citation Format: Jana de Boniface, Cecilia Haddad Ringborg, Renske Altena, Yvonne Wengström. Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: the randomized Neo-ACT trial [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 PO1-19-06.

Abstract PO1-20-04: STX-478-101: A phase 1/2, first-in-human study of STX-478 monotherapy or in combination with fulvestrant in patients with breast cancer or other advanced solid tumors (trial in progress)

Abstract Background: The phosphoinositide 3-kinase-alpha (PI3Kα)/AKT/mTOR pathway is one of the major pathways in oncogenesis. PI3Kα alterations are especially prevalent in breast, gynecological, and head and neck squamous cell carcinomas. PI3Kα oncogenic mutations are highly enriched for kinase (H1047X) and helical (E542K, E545K) domain hotspots. The therapeutic potential of isoform-selective PI3Kα inhibition in PI3Kα-mutant cancers was established with alpelisib, which shows equipotent activity against both wild-type (WT) and mutant PI3Kα. However, alpelisib use is limited by toxicities induced by WT PI3Kα inhibition, e.g. hyperglycemia and mucositis. This suggests that mutant-selective PI3Kα inhibitors have the potential to improve efficacy while sparing WT-related toxicity. STX-478 is an investigational allosteric, mutant-selective PI3Kα inhibitor. Preclinical testing in human breast cancer xenografts bearing helical- or kinase-domain mutant PI3Kα demonstrated that STX-478 monotherapy and combinations with fulvestrant and/or CDK4/6 inhibitors provided robust efficacy without the metabolic dysfunction observed with alpelisib. Trial Design: This first-in-human, multicenter, phase 1/2 study (NCT05768139) evaluates the optimal dosing, safety, and preliminary efficacy of STX-478 as monotherapy in patients with locally-advanced or metastatic HR+/HER2− breast cancer or other solid tumor types with PI3Kα H1047X mutations, other kinase domain mutations, or helical domain mutations (Part 1), and STX-478 in combination with fulvestrant in patients with locally-advanced or metastatic HR+/HER2− breast cancer with PI3Kα H1047X or other kinase domain mutations (Part 2). Part 1 comprises 2 subparts (Table 1) to define the optimally biologically active dose (OBD) and maximum tolerated dose (MTD) in Part 1.1, and recommended phase 2 dose (RP2D) of STX-478 monotherapy in Part 1.2. At the conclusion of each dose-level in Part 1.1 (3 + 3 design), a backfill cohort will be initiated in patients with HR+/HER2− breast cancer with PI3Kα H1047X mutations or other kinase domain mutations, who will receive STX-478 at the determined safe dose. Part 2 comprises two subparts (Table 2) to define RP2D and assess the initial efficacy of STX-478 in combination with fulvestrant in patients with HR+/HER2− breast cancer expressing PI3Kα H1047X or other kinase domain mutations. Key Eligibility Criteria: Adults with a PI3Kα-mutant advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable, ECOG performance status score of 0–1, and no prior PI3K/AKT/mTOR inhibitor(s) use (except with prior intolerance) are eligible. Individuals with diabetes mellitus type 1 or uncontrolled diabetes mellitus type 2 are excluded. Cohort-specific eligibility criteria are provided in Tables 1 and 2. Endpoints: Efficacy, safety, pharmacokinetics, pharmacodynamics, patient-reported quality of life, and biomarkers (e.g., glucose metabolism, circulating tumor DNA) will be assessed. Trial Status: Recruitment opened April 2023 in the US and is ongoing, with potential for ex-US site expansion. Contact clinicaltrials@scorpiontx.com for additional information. Table 1. Part 1 Dose Escalation, RP2D Selection, and RP2D Expansion (STX-478 Monotherapy) Table 2. Part 2 RP2D Selection and Expansion (STX-478 + Fulvestrant Combination Therapy) Citation Format: Alberto Montero, Douglas Orr, Pamela Munster, Patricia LoRusso, Komal Jhaveri, Timothy Pluard, Ira Winer, Michael Streit, Monica Patterson, Simon Roberts, Stefani Corsi-Travali, Courtney Ewert, Dejan Juric. STX-478-101: A phase 1/2, first-in-human study of STX-478 monotherapy or in combination with fulvestrant in patients with breast cancer or other advanced solid tumors (trial in progress) [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 PO1-20-04.

A tailored intervention for improving diabetes self-care among people with visual impairment: A pilot study

The aim of this study is to develop and evaluate a tailored intervention for improving diabetes self-care among people with visual impairment (TID-VI) in South Korea. The TID-VI program was designed around the barriers, resources, and perceptual factors to promote diabetes self-care in those with visual impairment (VI). A single-arm pilot study was conducted to evaluate the feasibility and preliminary effects of the intervention. Diabetes self-efficacy, self-care behaviors, depression, health-related quality of life, and clinical outcomes (fasting blood glucose, A1C, lipids, and blood pressure) were measured before, and up to 2-months after the 12-week intervention. All 14 participants completed TID-VI. Diabetes self-efficacy, self-care behaviors, depression, and health-related quality of life showed improvement from baseline that was sustained at 2 months. While HDL and LDL were also improved, there were no differences in blood glucose, A1C, total cholesterol, or blood pressure at 2 months. A theory-driven, tailored intervention specific to the needs of adults with VI can produce substantial improvements in patient-reported quality of life and health status outcomes, though the benefits are yet to be confirmed in a controlled study.

Continuous subcutaneous insulin infusion versus multiple daily injection therapy in pregnant women with type 1 diabetes.

The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH). This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life. Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m2 at conception and 26.32 kg/m2 at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH. Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.

Quality-of-Life Assessment in Pediatric Advanced Cancer: Development of the Patient-Reported Outcome Measure Advance QoL.

A recent measure was developed to assess the Quality of Life (QoL) of young people with advanced cancer and is available for parents and professionals (Advance QoL). The present study aimed to elaborate self-reported versions for children and adolescents with advanced cancer. We adopted a four-phase research plan: (1) to elaborate the Advance QoL questionnaire for youth (8-12 and 13-18 years old) with a team of young research partners; (2) to evaluate the understandability of these versions in a sample of 12 young patients from the target population using cognitive interviews; (3) to assess social validity in the same group using a questionnaire and the content validity index (CVI); and (4) to refine the questionnaires according to these results. Four major themes were identified: (1) issues affecting the understanding of the tool; (2) issues that did not affect the understanding of the tool; (3) modifications to improve the tool; and (4) positive features of the tool. Advance QoL was well received, and feedback was positive. Adjustments were made according to young people's comments and two self-reported versions are now available. It is essential to measure the key domains of QoL in advanced cancer. Advance QoL self-report versions will help target the specific needs of young people with this condition and their families.

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.

Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma

Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. ClinicalTrials.gov Identifier: NCT04638465.

Patient-reported Quality of Life and Survival Outcomes in Prostate Cancer: Analysis of the ECOG-ACRIN E3805 Chemohormonal Androgen Ablation Randomized Trial (CHAARTED)

BackgroundChemohormonal therapy with androgen deprivation therapy and docetaxel (ADT + D) improves overall survival (OS) and quality of life (QOL) at 12 mo versus androgen deprivation therapy (ADT) alone in men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the prognostic role of QOL is unknown in this population. ObjectiveTo study the relationship between QOL, disease characteristics, and OS in men with mHSPC. Design, setting, and participantsIn this exploratory post hoc analysis, 790 patients with mHSPC completed the QOL instruments Functional Assessment of Cancer Therapy—Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F), and Brief Pain Inventory (BPI). Outcome measurements and statistical analysisLog-rank test and Cox proportional hazard models tested the association between QOL and OS by clinical and disease characteristics. Results and limitationsBaseline higher FACT-P trended toward improved survival after accounting for clinical variables (hazard ratio [HR] 0.80 [0.62, 1.04], p = 0.09), while higher 3-mo FACT-P was independently associated with better survival (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the poorest QOL (bottom quartile) at baseline and 3 mo had longer survival if they received ADT + D rather than ADT alone (median OS 45.2 vs 34.4 mo, HR 0.75 [0.53, 1.05], p = 0.09, and 48.3 vs 29.3 mo, HR 0.69 [0.48, 0.99], p = 0.05 respectively). In contrast, patients with the best QOL (top quartile) at baseline and 3 mo had comparable survival irrespective of whether or not docetaxel was added (median OS 72.1 vs 51.7 mo, HR 0.92 [0.63, 1.36], p = 0.69, and 69.9 vs 68.9 mo, HR 1.11 [0.73, 1.67], p = 0.63, respectively). Survival was linked with baseline FACIT-F (HR 0.76 [0.57, 1.0], p = 0.05), but not BPI (HR 0.98 [0.75, 1.28], p = 0.90). ConclusionsThree-month QOL had a stronger independent association with survival. The most symptomatic patients had longer survival with the addition of docetaxel; conversely, the least symptomatic patients did not appear to benefit. Consideration of QOL may enhance decision-making and patient selection when choosing chemohormonal treatment in mHSPC. Patient summaryQuality of life independently forecasted the survival of men with metastatic hormone-sensitive prostate cancer in the CHAARTED study. Close tracking of quality of life could help patients and clinicians make decisions about the appropriate treatment in this setting.

Association of Insomnia and Obstructive Sleep Apnea with Worse Oral Mucositis and Quality of Life in Head and Neck Cancer Patients Undergoing Radiation Therapy.

Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL). Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM. Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (p = 0.005), fatigue (p = 0.01), insomnia (p < 0.001), and sticky saliva (p = 0.002). Patients screening positive for OSA had worse physical function (p = 0.01), sticky saliva (p = 0.02), fatigue (p = 0.007), insomnia (p = 0.009), and pain (p = 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (p = 0.01) and positive OSA screen (p = 0.002) were associated with worse OM. Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.

Clinical Efficacy and Patient Reported Impacts of Roflumilast Foam 0.3% in Seborrheic Dermatitis: An Analysis of STRATUM Data for Patients Unresponsive or Intolerant to Topical Corticosteroids

Objective. Roflumilast foam 0.3% has demonstrated efficacy and tolerability in a Phase 3 clinical trial of moderate-to-severe seborrheic dermatitis (SD) patients (STRATUM). The aim of this subgroup analysis is to assess the efficacy and patient-reported quality of life (QOL) effects of roflumilast vs vehicle in patients with an inadequate response, intolerance, or contraindication to topical corticosteroids (TCS).&#x0D; Methods: Patients 9 years or older with at least moderate seborrheic dermatitis (Investigator Global Assessment [IGA] ≥ 3) were randomized 2:1 to roflumilast or vehicle for 8 weeks. Patients reporting a history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCS) were included in this subgroup analysis. The primary efficacy endpoint was IGA success (Clear or Almost Clear with at least a 2-grade improvement) at Week 8. QOL was assessed using the Dermatology Life Quality Index (DLQI) for patients aged ≥17 years. QOL endpoints included percentage change from baseline in DLQI score, achievement of a minimal important difference (MID; defined as at least a 4-point reduction in DLQI score), and patients achieving a DLQI score of 0 or 1 by treatment group at weeks 2, 4, and 8. Differences in change from baseline DLQI scores were assessed using the Kruskal-Wallis rank sum test. The Cochran–Mantel–Haenzel test was used to assess differences in the proportion of patients achieving binary endpoints between treatments.&#x0D; Results: 189 patients (129 roflumilast, 60 vehicle) were included in the subgroup analysis. At Week 8, 78.8% of roflumilast patients achieved IGA success vs. 48.3% of vehicle patients (odds ratio [OR] 3.45; 95% confidence interval [CI]: 1.62, 7.36; p&lt;0.001). At each time point, percentage change from baseline in DLQI score was significantly larger for roflumilast-treated patients relative to vehicle (p≤0.001). Treatment with roflumilast significantly increased the odds of achieving an MID in DLQI across all time points (OR: 6.97; 95% confidence interval [CI]: 3.97, 12.24; p&lt;0.001) and achieving a DLQI score of 0 or 1 (OR: 2.46; 95% CI: 1.58, 3.81; p&lt;0.001).&#x0D; Conclusions: Roflumilast foam 0.3% provided significant and meaningful efficacy with improved QOL in patients with moderate-to-severe SD who had a prior history of an inadequate response, intolerance, or contraindication to TCS. Clinical improvement aligned with patient-reported outcomes at all key assessment periods.

Fractional flow reserve and instantaneous wave-free ratio in coronary artery bypass grafting: a meta-analysis and practice review.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive methods to assess the functional significance of intermediate severity coronary lesions. Both indexes have been extensively validated in clinical trials in guiding revascularisation in patients with stable ischaemic heart disease undergoing percutaneous coronary intervention (PCI) with improved clinical outcomes. However, the role of these tools in coronary artery bypass grafting (CABG) is less clear. A meta-analysis of randomised trials and observational studies was carried out to help in determining the optimal strategy for assessing lesion severity and selecting graft targets in patients undergoing CABG. Electronic searches were carried out on Embase, MEDLINE, and Web of Science. A group of four authors independently screened and then assessed the retrieved records. Cochrane's Risk of Bias and Robins-I tools were used for bias assessment. A survey was conducted among surgeons and cardiologists to describe current attitudes towards the preoperative use of functional coronary investigations in practice. Clinical outcomes including mortality at 30 days, perioperative myocardial infarction, number of grafts, incidence of stroke, rate of further need for revascularisation, and patient-reported quality of life did not differ in CABG guided by functional testing from those guided by traditional angiography.The survey revealed that in half of the surgical and cardiology units functional assessment is performed in CABG patients; there is a general perception that functional testing has improved patient care and its use would clarify the role of moderate coronary lesions that often need multidisciplinary rediscussions; moderate stenosis are felt to be clinically relevant; and anatomical considerations need to be taken into account together with functional assessment. At present, the evidence to support the routine use of functional testing in intermediate lesions for planning CABG is currently insufficient. The pooled data currently available do not show an increased risk in mortality, myocardial injury, and stroke in the FFR/iFR-guided group. Further trials with highly selected populations are needed to clarify the best strategy. ClinicalTrials.gov, identifier (CRD42023414604).

Abstract A106: Associations between active cytomegalovirus infection and patient-reported quality of life, fatigue and cognitive functioning among ovarian cancer survivors

Abstract A106: Associations between active cytomegalovirus infection and patient-reported quality of life, fatigue and cognitive functioning among ovarian cancer survivors

Outcomes of complex abdominal wall reconstruction in patients with connective tissue disorders: a single center experience.

Individuals diagnosed with connective tissue disorders (CTD) are known to be predisposed to incisional hernia formation. However, there is a scarcity of data on outcomes for these patients undergoing hernia repair. We sought to describe our outcomes in performing abdominal wall reconstructions in these complex patients. Adult patients with CTD undergoing open, elective, posterior component separation with permanent synthetic mesh at our institution from January 2018 to October 2022 were queried from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term hernia recurrence, and patient-reported quality of life. Twelve patients were identified. Connective tissue disorders included Marfan's n = 7 (58.3%), Loeys-Dietz syndrome n = 2 (16.7%), Systemic Lupus Erythematosus n = 2 (16.7%), and Scleroderma n = 1 (8.3%). Prior incisions included three midline laparotomies and nine thoracoabdominal, mean hernia width measured 14cm, and 9 were recurrent hernias. Surgical site occurrences (SSOs) were observed in 25% of cases, and 16.7% necessitated procedural intervention. All twelve patients were available for long-term follow-up, with a mean of 34 (12-62) months. There were no instances of reoperation or mesh excision related to the TAR procedure. One patient developed a recurrence after having his mesh violated for repair of a new visceral aneurysm. Mean HerQLes scores at 1year were 70 and 89 at ≥ 2years; Mean scaled PROMIS scores were 30.7 at 1year and 36.3 at ≥ 2years. Ventral hernia repair with TAR is feasible in patients with connective tissue disorder and can be a suitable alternative in patients with large complex hernias.

Abstract B011: Phase 2, multicenter, open-label basket trial of nab-sirolimus for malignant solid tumors harboring pathogenic inactivating alterations in TSC1 and TSC2 (PRECISION I)

Abstract Introduction/objective: PRECISION I (NCT05103358) is an ongoing trial of nab-sirolimus in advanced cancers harboring pathogenic inactivating alterations in TSC1 or TSC2. TSC1 and TSC2 alterations have been observed in patients with various cancers, including the most common cancer of the female reproductive organs, endometrial cancer, where ~3% contain TSC1 and/or TSC2 alterations. nab-Sirolimus, approved in the USA for patients with advanced malignant perivascular epithelioid cell tumor (PEComa), is an albumin-bound mTOR inhibitor (mTORi) that inhibits the mTOR pathway via suppression of the mTORC1 complex. When TSC1 or TSC2 is inactivated via mutation or loss, the mTOR pathway may be aberrantly activated. In an exploratory analysis of AMPECT (NCT02494570), a pivotal trial of nab-sirolimus in advanced malignant PEComa, 64.3% (9/14) of patients with pathogenic inactivating TSC2 or TSC1 alterations had a confirmed response. Most treatment-related adverse events in AMPECT were grade 1/2 (none were grade ≥4) and were consistent with mTORi-class adverse events. Based on the clinical observations from AMPECT and the underlying mechanism of action of nab-sirolimus, the PRECISION I trial was designed to assess the safety and efficacy of nab-sirolimus in a tumor-agnostic study of patients with advanced cancers with TSC1 or TSC2 inactivating alterations. Patients with endometrial cancer are expected to be enrolled based on the frequency of TSC1 and TSC2 inactivating alterations. Methods: Eligible patients are ≥12 years old and mTORi-naïve, possess advanced or metastatic malignant solid tumors with TSC1 or TSC2 inactivating alterations identified using next-generation sequencing (NGS) in tumor tissue or liquid biopsy (confirmed by central review of NGS reports), and have received appropriate standard treatments, per investigator. nab-Sirolimus 100 mg/m2 is given intravenously over 30 min on days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate per independent radiographic review (IRR) using Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints include duration of response, time to response, progression-free survival by IRR, overall survival, patient-reported quality of life, and safety. Trial Status: Enrollment began in March 2022 and is expedited through collaboration with leading NGS providers; ongoing study access is facilitated through a just-in-time approach to trial location activation. Citation Format: Debra L. Richardson, Gopa Iyer, Li Ding, Anita N. Schmid, Willis Navarro, David Kwiatkowski, Jordi Rodon Ahnert. Phase 2, multicenter, open-label basket trial of nab-sirolimus for malignant solid tumors harboring pathogenic inactivating alterations in TSC1 and TSC2 (PRECISION I) [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B011.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial

PurposeThe POP-RT phase III randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT) for high/very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. Materials/MethodsLate urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65Gy, V68Gy) in the approved radiotherapy plans was compared for urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. ResultsComplete combined data for late urinary symptoms and dosimetry was available for 193/224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for WPRT and PORT (5.2% vs 4.1%, p=0.49), while grade 2 toxicity was 31.3% vs 22.7% respectively (p=0.12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior TURP, grade 2+ acute urinary toxicity, low bladder dose (V10Gy) and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. ConclusionOver long term follow up, whole pelvic radiotherapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiotherapy. The long term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Patient-Reported Quality of Life 6 Years After Breast Cancer

This cohort study assesses quality-of-life trajectories up to 6 years after breast cancer diagnosis among individuals in France.