Quality Of Patient-reported Outcomes Research Articles

«Declared quality of life»: new perspectives for assessing patients’ quality of life in clinical medicine

In modern patient-oriented medical care, quality of life is an important criterion for a comprehensive assessment of the patient's health and evaluation of treatment effectiveness. This article is devoted to the current methodological issues of assessing quality of life and other patient-reported outcomes (PRO) and attempts to reveal the difficulties of interpreting PRO data obtained in real-world clinical practice. A new concept for identifying significant changes in the patient's general health condition in clinical practice is presented, and a new model of quality of life outcomes before and after treatment is considered. The concepts of “declared quality of life”, “index of achieved quality of life” and “declared clinical effect” have been declared. Assessment of the declared quality of life of the patient and determination of the index of the achieved quality of life can be used for practical purposes to implement the principle of patient-oriented care in clinical practice.

Patient-Reported Outcomes in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and can progress to serious complications, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Predisposing risk factors for MASH include obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. Patients with MASH often experience significant impairments in their health-related quality of life and other patient-reported outcomes (PROs), particularly in physical functioning domains, fatigue, and vitality. Incorporating PROs offers valuable insights into patients' perspectives on their symptoms, treatment efficacy, and overall well-being, thereby guiding more holistic and patient-centered care strategies. This review aims to investigate the utilization of patient-reported outcome measures (PROMs) in the context of MASLD and MASH care, identify which PROMs are employed, and summarize the outcomes reported.

Advancements in breast cancer management: a comprehensive review of ribociclib combined with endocrine therapy.

In this review, the complicated landscape of breast cancer management is explored with a focus on the promising synergies between ribociclib and endocrine therapy. Ribociclib mainly acts as a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, which disrupts cell cycle progression necessary for tumor growth. This, in combination with endocrine therapy, aims to produce hormone receptor-positive breast cancers, which is a very relevant subtype with challenging therapeutics. A comprehensive review was conducted using multiple databases, PubMed, Embase, Scopus, Cochrane Library, and Web of Science, covering the period from January 1990 to May 2024. Pharmacokinetic studies underscore the efficacy and tolerability of ribociclib, thus providing vital information for dose adjustments, particularly among patients with renal and hepatic impairments. Ribociclib's value in extending progression-free survival and improving overall survival has been shown by clinical trials such as the MONALEESA series. Quality of life considerations and patient-reported outcomes from these trials indicate that ribociclib has a broader effect on the well-being of the patients. However, despite the success experienced by this drug in clinical practice, it still has some side effects, including hematologic toxicity, hepatotoxicity, and thromboembolism associated with it. Ribociclib resistance mechanisms are multifaceted mixtures comprising genetic variations or mutations, compensatory signaling pathways, and epigenomic changes. While overcoming resistance remains challenging, ongoing research seeks to reconcile. Ribociclib combined with endocrine therapy represents a significant advancement in breast cancer treatment, albeit with challenges that necessitate ongoing research and holistic patient care approaches.

CTIM-32. PHASE I/II STUDY OF STEREOTACTIC RADIOSURGERY WITH CONCURRENT OLAPARIB FOLLOWED BY ADJUVANT DURVALUMAB AND PHYSICIAN’S CHOICE SYSTEMIC THERAPY IN SUBJECTS WITH BREAST CANCER BRAIN METASTASES (SOLARA)

Abstract BACKGROUND Despite progress in the treatment of brain metastasis for HER2+ breast cancer, outcomes for patients with HER2-negative breast cancer brain metastases remain poor. Preclinical studies show inhibitors of poly(ADP-ribose) polymerase (PARP) are effective in combination with radiation therapy as a DNA damage response inhibitor. Triple-negative breast cancer (TNBC) has higher rates of homologous recombination deficiency compared to other subtypes, and together with HER2-negative, BRCA-mutated breast cancer would be particularly sensitive to PARP inhibition. PARP inhibition has also demonstrated promising efficacy combined with immunotherapy in patients with germline BRCA-mutant and metastatic TNBC in clinical trials. In addition, immunotherapy with stereotactic radiosurgery (SRS) is associated with favorable intracranial control and survival in patients with brain metastases. We hypothesize that this biologically-driven combination will enhance local control of SRS-treated brain metastases through synergy with PARP inhibition, while controlling micrometastatic disease via potentiation of the immune response. METHODS We are conducting a multi-institution, Phase I/II trial of SRS plus olaparib, followed by durvalumab (with physician’s choice systemic therapy), for patients with TNBC (any BRCA status) or HER2-negative with BRCA-mutated (germline or somatic) breast cancer brain metastases [NCT04711824]. A total of 41 patients are planned for enrollment at 8 sites. The primary objectives are to evaluate safety and tolerability (Phase I) and determine intracranial disease control at 6 months (Phase II). Secondary objectives include assessing intracranial and global progression-free survival, overall survival, and intracranial and extracranial response rate. Exploratory objectives will assess potential biomarkers of treatment response, including changes in circulating tumor cells and DNA in blood and cerebrospinal fluid, germline and tumor mutations in DNA repair pathway genes, and PD-L1 expression, as well as quality of life and patient-reported outcomes. As of May 2024, phase I has been completed without dose-limiting toxicity, and phase II is currently enrolling. Funding/drug provision from AstraZeneca.

Peer support interventions improve disease self-management after coronary heart disease diagnosis: a systematic review and meta-analysis

Abstract Background Patients with coronary heart disease (CHD) diagnoses often experience impacts on patient-reported outcomes (quality of life, depression, disease self-management and self-efficacy) at a time when secondary prevention is required. Peer support has proven benefits for these issues in many chronic conditions but synthesis of the evidence in CHD populations has not been undertaken. Purpose In this systematic review and meta-analysis, we aimed to explore the impact of peer support interventions on health-related quality of life, depression, anxiety, self-management and self-efficacy in CHD. Methods Electronic databases were searched from inception to November 2023 (MEDLINE, Embase, PsycINFO, CINAHL, Scopus, PubMed [non-MEDLINE], Web of Science, and the Cochrane Central Register of Controlled Trials). Randomised controlled trials (RCTs) evaluating peer support interventions (that enable experience sharing and/or support by others with the same condition) in populations with diagnosed CHD were eligible for inclusion. Risk of bias was assessed using the Cochrane risk of bias tool. Meta-analyses were undertaken in RevMan Version: 7.4.0 using the inverse variance method and a random effects model. Results In total, 16 papers reporting 14 unique RCTs were included. The total sample (n=1793) was 65% male with a mean age of 54.5±13.0 years. The diagnosis of the samples varied between studies, including coronary artery bypass graft(s), first time or newly diagnosed myocardial infarction and percutaneous coronary intervention. By 6-months follow-up, peer support interventions demonstrated no statistically significant improvements in health-related quality of life (SMD -0.38, 95% CI -1.84, 1.08), depression (SMD -0.09, 95% CI -0.26, 0.08) and anxiety (SMD -0.85, 95% CI -1.83, 0.14). Whereas, improvements occurred in disease self-management (SMD 1.49, 95% CI 0.66, 2.32) and self-efficacy in both short term (by 6-months, SMD 0.57, 95% CI 0.37, 0.77) and longer term (6-12 months, SMD 0.67, 95% CI 0.29, 1.05). Peer support interventions varied widely in format and several studies were of poor quality. Conclusion Peer support interventions benefit patient-reported outcomes of disease self-management and self-efficacy up to 6 and 12 months, but not for other patient reported outcomes after CHD diagnosis. More exploration is needed of content, delivery and focus of peer support interventions to maximise effectiveness for CHD secondary prevention.

Reduced Sense of Smell in Patients with Severe Chronic Rhinosinusitis and its Implications for Diagnosis and Management: A Narrative Review.

Reduced sense of smell is a common symptom in patients with chronic rhinosinusitis (CRS). Although it is often under-diagnosed by healthcare providers, reduced sense of smell can have a substantial negative impact on patient's quality of life as measured by health-related quality of life (HRQoL) assessments and patient-reported outcomes. This narrative review describes current smell loss diagnosis and management guidelines in CRS, and the relationship between smell loss and CRS. Reduced sense of smell can be an indication of CRS disease severity in patients with (CRSwNP) and without nasal polyps (CRSsNP), and recovery of smell can be an indicator of successful CRS treatment. The current first-line therapeutic options for smell loss are intranasal corticosteroids and nasal irrigation, and second-line therapeutic options include systemic steroids and surgery. Shared decision-making between patient, caregiver, and healthcare provider is important when choosing the most appropriate CRS treatment option. Emerging biologic therapies that target type 2 inflammation signaling pathways, such as dupilumab, omalizumab, and mepolizumab, have been shown to improve smell and taste in randomized controlled trials of patients with CRSwNP.A graphical abstract and video abstract are available with this article.

Clinical Approach to STRIDE-II in Real-Life Settings: Analysis and Practical Recommendations.

We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles. This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs). Based on this, a survey was carried out among educational course participants. The experts discussed the literature review and survey results and proposed several statements and practical actions. A total of 55 gastroenterologists answered the survey. The reported difficulty level in reaching STRIDE-II treatment goals in clinical practice was high. Only 22% of participants performed clinical remission assessments using clinical indexes and PROs. Seventy percent of responders did not use fecal calprotectin cutoffs and considered changes from the previous levels instead. Mucosal healing as a long-term therapeutic goal was considered necessary to be individualized in specific patient subgroups (eg, elderly/fragile patients, multiple treatment failures, and last-line therapies). Other barriers, like the lack of access to imaging techniques or insufficient knowledge and skills among healthcare professionals, were detected. The experts suggested adding less stringent treatment goals and measurements, patient stratification, local adaptations, educational activities, and research. STRIDE-II recommendations face various implementation barriers needing careful evaluation in order to enhance their adoption in clinical practice, and ultimately improve outcomes in IBD patients.

Establishing minimal clinically important differences for the quality of life scale QLICD-SLE for patients with systemic lupus erythematosus based on ROC curve

The minimal clinically important difference (MCID) is an important concept with big appeal in a field struggling to interpret quality of life (QOL) and other patient-reported outcomes (PRO), is also a bridge between statistics and clinical medicine. This study uses the ROC curve to formulate the MCID value of the Quality of Life Instruments for Chronic Diseases of Systemic lupus erythematosus (QLICD-SLE V2.0) scale. Using the representative item “In general, would you say your health is” of the MOS item short form health survey(SF-36) as an anchor, the questionnaire of QLICD-SLE V2.0 and the anchor item were used to investigate the patients on the first day of hospitalization, and the day before the patient was discharged. 279 patients with lupus erythematosus were participated in this longitudinal follow-up study. The ROC curve was constructed by using the classification based on the anchor item as the gold standard and the difference score of the scale as the test variable. The cut-off point corresponding to the maximum value of the Youden index in the ROC curve is taken as the minimum clinical importance difference (MCID) value of the QLICD-SLE (V2.0) scale. The Results showed that the MCID of physical domain, psychological domain, social domain, general module, specific module and QLICD-SLE (V2.0) total scale are 8.3, 2.3, 2.5, 2.7, 9.2 and 3.2, respectively. Area under the ROC curve of QLICD-SLE (V2.0) is 0.898, P (Area = 0.5) < 0.001, the sensitivity is 100%, the specificity is 66.9%. It concluded that if the total scores after treatments changes at least 3.2 points positively, the treatment intervention can be considered as clinically significant. It is more convincing to use the corresponding cut-off point as the MCID for ROC curve method can visualize the sensitivity and specificity.

Health-Related Quality of Life of People Living with HIV: Contributions of Emotion Regulation and Self-Compassion

Living with chronic health conditions such as HIV has implications for health-related quality of life (HRQoL) and improving the HRQoL of people living with HIV (PLWH) is becoming increasingly important for researchers, policymakers, and health practitioners. However, there is limited research on factors that help to explain HRQoL among persons with HIV in sub-Saharan Africa. We examined the contributions of emotion regulation and self-compassion in the HRQoL of 187 PLWH (56.1% female) drawn from the HIV clinic in a specialist hospital in southeast Nigeria. They completed the Brief Version of the Difficulties in Emotion Regulation Scale (DERS-18), Self-compassion Scale, and Patient-Reported Outcome Quality of Life-HIV (PROQOL-HIV). While controlling for participants’ demographic variables, the regression results showed that self-compassion was positively associated with HRQoL. Higher difficulties in emotion regulation were not associated with HRQoL in the presence of self-compassion. The findings extend the outcomes of previous research in other parts of the world and support the notion that enhancing self-compassion interventions may shore up the HRQoL of people living with chronic health conditions. HRQoL interventions that embody culturally informed self-compassion strategies and developmental level approach are needed for the health system in sub-Saharan Africa.

The Landmark Series: Multimodal Management of Oligometastatic Sarcoma.

The concept of "oligometastatic" disease suggests the presence of intermediate states between localized disease and widespread metastases, which may be potentially treatable with curative therapeutic strategies. Metastases local therapy (MLT) can be accomplished through various techniques such as stereotactic ablative radiotherapy (SABR), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, or surgical metastasectomy. The incorporation of MLT in the multidisciplinary treatment of patients with metastatic sarcoma is complex. Retrospective studies support consideration of MLT for selected patients based on factors such as patient condition, disease biology, histologic type, and disease burden. Decisions regarding type and timing of MLT should be made after multidisciplinary discussion including radiation oncologists, surgical and orthopedic oncologists, medical oncologists, and interventional radiology to explore all options before treatment decsions. All MLT techniques have advantages and disadvantages and should be performed in centers specialized in the care of complex oncology patients where various options can be explored concurrently or sequentially for each patient. Future studies evaluating quality of life and patient-reported outcomes are necessary to adequately align patient goals and optimal outcomes. This article reviews the medical scenarios that may benefit the use of MLT, evaluates the distinct advantages and disadvantages associated with these various techniques, and analyzes the findings from pivotal series to provide a comprehensive understanding of its role in clinical practice.

Evaluating the feasibility of a Mobile Audio Companion (Elly) to reduce anxiety and to improve patient-reported outcomes among patients with cancer.

11120 Background: Anxiety is one of the most commonly reported symptoms among cancer patients, and is a known risk factor for reduced health-related quality of life and other negative patient-reported outcomes (PROs). Mobile health applications (apps) are tools that can be used flexibly in patients’ preferred environments with the potential to reduce anxiety and improve quality of life. The current study sought to examine the feasibility and preliminary efficacy of a mobile audio companion app, Elly, to improve anxiety and other critical PROs among cancer patients. Methods: This was a single-site, single-arm pilot study conducted over 6-months. Adults 18 years or older with a diagnosis of cancer of any type, received treatment within 6 months of consent, and had access to an iPhone were eligible. The primary outcome was change in mean anxiety t-scores (NIH PROMIS anxiety short form (8a)) administered electronically via REDCap at baseline, 1 (primary timepoint), 3, and 6 months. Secondary outcomes included changes in NIH PROMIS depression, loneliness, social support, and perceived stress scores from baseline to 6 months. Changes in NIH PROMIS T-scores at each time point were calculated and analyzed using paired t-tests. Results: Of 53 patients who consented for the study, 38 patients (72%) were included in the analysis ( Mage: 52.8 years, SD: 11.7, 84.2% female). Most participants reported a history of breast cancer (50%), followed by ovarian (16%), hematologic (11%), and other cancer types (24%) Phone incompatibility and technological challenges were the most common reasons for screen-fails (n=15). All participants downloaded and used the app at least once, with an average of 154 app usage events across participants recorded over the study period (median: 64, range 11-1186 times). The mean baseline anxiety T-score was 63.5 (SD: 2.1). Anxiety levels decreased among participants over time, with a mean difference in anxiety T-scores of -1.9 at 30 days, -3.3 at 90 days, and -3.0 at 6 months from baseline, which was statistically (p&lt;0.05) and clinically significant. Participants also reported improvements in perceived stress, depression symptomatology, social support, and loneliness, although statistical significance was not reached. Conclusions: Mobile apps, such as Elly, may feasibly be used to support patient-reported anxiety as well as other PROs, especially among those who present with high levels of anxiety at baseline. Efforts to increase access to mobile health apps and provide technical support for patients should be made increase equity across the cancer survivor population. Larger, multi-center randomized controlled trials are needed to build on these findings.

Patient-centered perspectives: Examining quality-of-life integration in phase III lung cancer trials (2019-2023).

e23181 Background: In the dynamic landscape of lung cancer treatment, marked by precision medicine advancements, addressing the persistent global health challenge of lung cancer requires nuanced evaluations beyond traditional endpoints like Overall Survival (OS). Aligned with the emphasis on patient-centered care, both the US FDA and ASCO advocate for consistent integration of Quality of Life (QoL) and Patient-Reported Outcomes (PRO). The FDA's 2021 guidance underscores standardized assessment strategies, and ASCO's conceptual framework highlights the pivotal role of QoL and PRO data in elucidating the genuine value of cancer treatment options. This investigation aims to illuminate the extent to which recent trials consider patients' subjective experiences without presupposing an impact on QoL. Methods: This systematic review analyzed PubMed for Phase III lung cancer clinical trials involving anticancer drugs conducted between 2019 and 2023 to assess if QoL was included as an endpoint. Subgroup analyses categorized trials by cancer subtype (e.g., non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC]). Analyses were also stratified by publication year to explore potential temporal trends. The total prevalence of QoL as an endpoint was calculated across all lung cancer subtypes for the entire 5-year period. Subanalyses included impact factor categories (≥ 10 and &lt; 10) and differentiation between superiority and noninferiority trials. Results: The systematic analysis identified 191 Phase III lung cancer clinical trials published between 2019 and 2023, meeting the criteria. QoL was included in 31.93% of trials across all subtypes. Subgroup analyses showed that 33.72% of NSCLC trials incorporated QoL, with variations observed in early-stage resectable disease (26.31%) and unresectable advanced and metastatic cases (34.66%). For SCLC, 19.04% of trials included QoL, with none in the limited stage and 22.22% in the extensive stage. Stratified by publication year, 2019 had 33.33%, 2020 had 39.02%, 2021 had 33.33%, 2022 had 23.33%, and 2023 had 28.94% trials with QoL assessments. Stratification based on impact factor (IF) and trial type revealed 29.4% in Journals ≥10 IF, 35.6% in Journals &lt; 10 IF, 35.5% in superiority trials, and 21.6% in non-inferiority trials. Conclusions: Our analysis reveals a significant shortfall in incorporating QoL as an endpoint. Across all subtypes and stages, a limited percentage of trials included PRO, highlighting a crucial gap in evaluating the comprehensive impact of interventions. The underrepresentation of QoL assessments signals a need for greater attention to the holistic patient experience in lung cancer research. Moving forward, a more standardized and comprehensive integration of QoL assessments in Phase III trials is essential to enhance our understanding of treatment impact and inform more patient-centered care decisions.

Precision oncology clinical trials: A systematic review of phase II clinical trials with biomarker-driven, adaptive design.

e23005 Background: Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. Methods: We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Results: Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Table. Precision Oncology Trials led to the FDA approval. Conclusions: Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape. [Table: see text]

The State of Patient-Reported Outcome Measures in Rheumatology.

We sought to evaluate the quality and timeliness of patient-reported outcome (PRO) measure reporting, which have not been previously studied. Clinical trials that informed new US Food and Drug Administration (FDA) approvals for the first rheumatological indication between 1995 and 2021 were identified. Data were recorded to determine whether collected PROs were published, met minimum clinically important difference (MCID) or statistical significance (P < 0.05) thresholds, and were consistent with Consolidated Standards of Reporting Trials (CONSORT)-PRO standards. Hazard ratios and Kaplan-Meier estimate were used to assess the time from FDA approval to PRO publication. Thirty-one FDA approvals corresponded with 110 pivotal trials and 262 reported PROs. Of the 90 included studies, 1 (1.1%) met all 5 recommended items, 10 (11.1%) met 4 items, 17 (18.9%) met 3 items, 21 (23.3%) met 2 items, 26 (28.9%) met 1 item, and 15 (16.7%) met none of the reporting standards. Most PROs met MCID thresholds (149/262; 56.9%) and were statistically significant (223/262; 85.1%). Of our subset analysis, one-third of PROs were not published upfront (70/212; 33%) and 1 of 9 (22/212; 10.4%) remained unpublished ≥ 4 years after initial trial reporting. Publication rates were highest for the Health Assessment Questionnaire-Disability Index (97.4%) and lowest for the 36-item Short Form Health Survey (81.8%). Less than half of these published PROs met MCID and statistical significance thresholds (94/212; 44.3%). One in 9 PROs remained unpublished for ≥ 4 years after initial trial reporting, and compliance with CONSORT-PRO reporting guidelines was poor. Efforts should be made to ensure PROs are adequately reported and expeditiously published.

Electronic health record-integrated questionnaires in colorectal surgery patients as a new standard: Could preoperative bowel function be used to predict postoperative patient-reported outcomes?

Patient-reported bowel function has been previously shown to correlate with quality of life and patient-reported outcomes (PROs) after colorectal surgery. We examined the relationship between preoperative patient-reported bowel function and postoperative symptom reporting using an electronic health record-integrated symptom management (eSyM). Patients who underwent major abdominal surgery for colorectal cancer at a single institution were included. Preoperative bowel function was assessed prospectively using the validated colorectal functional outcome (COREFO) questionnaire. Patients with electronic portal access received automated eSyM questionnaires after discharge. Logistic regression was used to analyze the association between COREFO scores and eSyM use. 169 patients underwent surgery between April 2020 and June 2022 (median age 64, 46.7% female). 148 completed COREFO questionnaires preoperatively; 54 (36.5%) had scores ≥15. Of the 108 patients with portal access, 67.6% used eSyM postoperatively. Among users, 72.3% (47/73) reported severe symptoms. Those with COREFO scores ≥15 were more likely to use eSyM (80.0% vs. 62.7%) though this difference was not significant (p = 0.079). We found that eSyM utilization regardless of preoperative baseline bowel function was high in this cohort of colorectal surgery patients. This suggests that electronically captured PROs is an effective way for patients to communicate symptoms to their care teams in a postsurgical setting.

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Abstract PO5-20-03: Phase I/II study of stereotactic radiosurgery with concurrent olaparib followed by adjuvant durvalumab and physician’s choice systemic therapy in subjects with breast cancer brain metastases

Abstract BACKGROUND: Despite progress in the treatment of brain metastasis for HER2+ breast cancer, outcomes for patients with HER2-negative breast cancer brain metastases remain poor. Current standard of care consists of local therapies, including surgery and radiotherapy, followed by systemic therapy. Preclinical studies show inhibitors of poly(ADP-ribose) polymerase (PARP) are effective in combination with radiation therapy as a DNA damage response inhibitor. Triple-negative breast cancer (TNBC) has higher rates of homologous recombination deficiency compared to other breast cancer subtypes, and together with HER2-negative, BRCA-mutated breast cancer would be particularly sensitive to PARP inhibition. PARP inhibition has also demonstrated promising efficacy combined with immunotherapy in patients with germline BRCA-mutant and metastatic TNBC in clinical trials (MEDIOLA, TOPACIO). In addition, immunotherapy with stereotactic radiosurgery (SRS) is associated with favorable intracranial control and survival in patients with brain metastases. We hypothesize that this biologically-driven combination will enhance local control of SRS-treated brain metastases through synergy with PARP inhibition, while controlling micrometastatic disease in the brain and extracranial sites via potentiation of the immune response. METHODS: We are conducting a multi-institution, Phase I/II trial of SRS plus olaparib, followed by durvalumab (with physician’s choice systemic therapy), for patients with TNBC (any BRCA status) or HER2-negative with BRCA-mutated (germline or somatic) breast cancer brain metastases [NCT04711824]. A total of 41 patients are planned for enrollment at 8 sites. The primary objectives are to evaluate safety and tolerability (Phase I) and determine intracranial disease control at 6 months (Phase II) of this treatment combination. Secondary objectives include determining clinical activity via intracranial and global progression-free survival, overall survival, and intracranial and extracranial response rate. Exploratory objectives will assess potential biomarkers of treatment response, including changes in circulating tumor cells and DNA in blood and cerebrospinal fluid, germline and tumor mutations in DNA repair pathway genes, and PD-L1 expression, as well as quality of life and patient-reported outcomes. A surgical sub-study (n=5) will evaluate olaparib concentration/distribution in resected brain metastases. As of June 2023, cohort 2 of phase I has been completed without dose-limiting toxicity. Citation Format: Colette Shen, Yara Abdou, Linda Chen, Xianming Tan, Gaorav Gupta, Mina Lobbous, Filipa Lynce, Erica Stringer-Reasor, Carey Anders. Phase I/II study of stereotactic radiosurgery with concurrent olaparib followed by adjuvant durvalumab and physician’s choice systemic therapy in subjects with breast cancer brain metastases [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 PO5-20-03.

Statistical Analysis Methods and Reporting of Patient-Reported Outcomes in Randomized Controlled Trials for Cancer Conducted in Japan: A Systematic Review.

The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative was established in 2016 to assess the quality and standardization of patient-reported outcomes (PRO) data analysis in randomized controlled trials (RCTs) on advanced breast cancer. The initiative identified deficiencies in PRO data reporting, including nonstandardized methods for handling missing data. This study evaluated the reporting of health-related quality of life (HRQOL) in Japanese cancer RCTs to provide insights into the state of PRO reporting in Japan. The study reviewed PubMed articles published from 2010 to 2018. Eligible studies included Japanese cancer RCTs with ≥50 adult patients (≥50% were Japanese) with solid tumors receiving anticancer treatments. The evaluation criteria included clarity of the HRQOL hypotheses, multiplicity testing, primary analysis methods, and reporting of clinically meaningful differences. Twenty-seven HRQOL trials were identified. Only 15% provided a clear HRQOL hypothesis, and 63% examined multiple HRQOL domains without adjusting for multiplicity. Model-based methods were the most common statistical methods for the primary HRQOL analysis. Only 22% of the trials explicitly reported clinically meaningful differences in HRQOL. Baseline assessments were reported in most trials, but only 26% reported comparisons between the treatment groups. HRQOL analysis was based on the intention-to-treat population in 19% of the trials, and 74% reported compliance at follow-up; however, 41% did not specify how missing values were handled. Although the rates of reporting clinical hypotheses and clinically meaningful differences were relatively low, the current state of HRQOL evaluation in the Japanese cancer RCT appears comparable to that of previous studies.

Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.

Minimal clinically important differences in health-related quality of life after treatment with direct-acting antivirals for chronic hepatitis C: ANRS CO22 HEPATHER cohort (PROQOL-HCV).

Patient Reported Outcomes Quality of Life survey for HCV (PROQOL-HCV) is a specific tool developed to assess health-related quality of life (HRQoL) in patients with chronic hepatitis C receiving direct-acting antivirals (DAA). Thresholds for clinically meaningful changes in PROQOL-HCV scores should be documented to improve the tool's use in clinical practice. This study aimed to estimate the minimal clinically important differences (MCIDs) in PROQOL-HCV scores before and after HCV cure by DAA among participants in the prospective cohort ANRS-CO22 HEPATHER. Data from 460 chronic HCV patients were collected at DAA initiation (baseline) and 24weeks after treatment end. MCIDs were estimated for the six HRQoL dimensions (Physical Health (PH), Emotional Health (EH), Future Uncertainty (FU), Intimate Relationships (IR), Social Health (SH), and Cognitive Functioning (CF)) using two approaches: anchor-based and score distribution-based. Each MCID was estimated for improvement/deterioration both globally and separately for patients with a baseline PRQoL-HCV score ≤ 50 (group1) and patients with a baseline PRQoL-HCV score > 50 (group2). The pooled MCIDs for improvement/deterioration globally, in group1, and in group2, respectively, were as follows: 8.8/-7.6, 9.7/-9.5, and 6.0/-6.9 for PH; 7.1/-4.6, 7.7/-9.6, and 6.6/-6.7 for EH; 6.7/-6.7, 8.2/-8.2, and 6.0/-6.0 for FU; 7.0/-7.0, 5.4/-5.4, and 6.2/-6.2 for IR; 7.7/-7.7, 8.6/-8.6, and 6.5/-6.5 for SH; 7.3/-5.6, 9.1/-8.0, and 6.5/-6.3 for CF. The overall MCID for the PROQOL-HCV scores ranged from 6.7 to 8.8 for improvement and from -7.7 to -4.6 for deterioration. The effect of DAA on PROQOL-HCV scores seemed particularly beneficial for patients with lower baseline scores. This subgroup could be motivated to take DAA if they are informed of the benefits for their HRQoL.