Treatment Decisions Research Articles

Patient Preferences for Attributes of Androgen Deprivation Therapies in Prostate Cancer: A Discrete Choice Experiment with Latent Class Analysis.

Medical androgen deprivation therapy (ADT) options have expanded for patients with advanced prostate cancer (PC). Historically, ADT was primarily available in long-acting injectable formulations. In 2020, the first oral formulation was US Food and Drug Administration-approved for adults with advanced PC. This study's aim was to assess patient preferences for attributes of medical ADT, including mode of administration, side effects, impact on sexual interest, and out-of-pocket (OOP) costs, and to segment respondents into distinct groups based on their treatment choice patterns. A cross-sectional survey was conducted among US residents aged > 40years with PC, employing a discrete choice experiment to assess preferences for ADT attributes. For each choice task, respondents were asked to select the hypothetical treatment profile that they preferred out of two presented. Latent class analysis (LCA) was conducted to estimate attribute-level preference weights and calculate attribute relative importance for groups of respondents with similar treatment preferences. A total of 304 respondents completed the survey (mean age 64.4years). LCA identified four preference groups, named according to the attribute each group considered most important: Sexual interest, Cost-sensitive, Favors daily pill, and Favors injection. Most respondents in the Sexual interest group were < 65years, while the Cost-sensitive group was mostly ≥ 65years. Favors daily pill had the highest proportion of ADT-naïve individuals. On average, respondents in these groups preferred an oral medication. Favors injection, which had the highest proportion of ADT-experienced individuals, preferred infrequent intramuscular injections, lower chance of post-ADT testosterone recovery, and lower OOP cost. Respondents differed in their preferences regarding ADT attributes, highlighting the need for patient involvement in their treatment decisions. Effective communication between healthcare providers and patients about the benefits and risks of available therapies should be encouraged to ensure that patients receive the PC treatment that best meets their needs.

CANVAR: A Tool for Clinical Annotation of Variants Using ClinVar Databases.

Genomic medicine has transformed clinical genetics by utilizing high-throughput sequencing technologies to analyze genetic variants associated with diseases. Accurate variant classification is crucial for diagnosis and treatment decisions, and various tools and software such as the Ion Reporter Software and the Illumina Nirvana Software often used in a clinical setting utilize information from the ClinVar database/archive to aid in variant interpretation. However, these existing annotation tools may lack access to the latest ClinVar data, necessitating manual variant inspection. To address this gap in developing a tool providing the latest ClinVar data for variant annotation in clinical and research settings. We introduce CANVAR, a Python-based script that efficiently annotates variants identified from next-generation sequencing in a clinical or research context, offering comprehensive information from the latest ClinVar database. CANVAR provides accurate, up-to-date variant annotations, streamlining variant analysis. The rise in genomic data requires accurate variant annotation for clinical decision-making. Misclassification poses risks, and current tools may not always access the latest data, challenging variant interpretation. CANVAR contributes to enhancing variant annotation by offering comprehensive information from the latest ClinVar database for genetic variants identified through next-generation sequencing.

Impact of Bacille Calmette-Guérin vaccination on the therapeutic schedule of infantile epileptic spasms syndrome: A 25-year Japanese single-center survey

Adrenocorticotropic hormone (ACTH) therapy is effective for infantile epileptic spasms syndrome (IESS) but can induce immunosuppression. In Japan, Bacille Calmette-Guérin (BCG) vaccination, modified in 2013 to reduce osteitis/osteomyelitis risk, coincides with the peak onset age of IESS. This raises concerns about infection risks when administering ACTH therapy post-vaccination. To evaluate the impact of BCG vaccination timing on treatment decisions, we retrospectively reviewed the medical records of 86 IESS patients at our hospital (1996–2020). Infants who received ACTH therapy within eight weeks of BCG vaccination experienced no serious adverse events. Four patients deferred or opted out of ACTH therapy, with seizure remission taking 2-15 weeks. The overlap between IESS onset and BCG vaccination period presents clinical challenges in determining the appropriate timing for ACTH therapy. Further epidemiological and immunological research is needed to clarify the relationship between ACTH therapy and BCG-associated adverse events and to optimize treatment strategies and vaccination schedules.

Prescription predicament: Unveiling the financial fallout of drug shortages.

1 Background: Managing drug shortages has become a part of care delivery in oncology. Shortages have been reported to result in missed/delayed treatment, substitution of alternative therapy, increased costs, and significant administrative burden. A national shortage of cisplatin caused by manufacturing disruptions was reported by the Food and Drug Administration in the United States from February until August 2023 (shortage period). We assessed the effects of cisplatin shortage on the treatment of head and neck cancer (HNC) at practices in The US Oncology Network (The Network). Methods: Using drug administration data from medical records and claims for 26 practices in The Network prior to (July 2022 to January 2023), during, and after (September 2023 to March 2024) the shortage period, we assessed the utilization trends and financial impact (using Medicare average sale price (ASP)) of cisplatin and other anti-cancer drugs for HNC patients. Results: During the shortage period, cisplatin utilization for HNC decreased by 15% compared to pre-shortage levels. The lowest utilization occurred in June and July 2023, with a 60% decrease. Practices initially obtained supplies through an allocation model and fair-share utilization guidance from The Network Pharmacy &amp; Therapeutics Committee. During the shortage period, alternative chemotherapy drugs for HNC saw increased use: carboplatin by 40%, paclitaxel by 24%, 5-fluorouracil by 5.3%, and cetuximab by 15%. The increased use of alternative drugs corresponded to the decrease in cisplatin usage, with new starts shifting to carboplatin (with or without paclitaxel), cetuximab and 5-fluorouracil. Ten percent of existing cisplatin recipients were shifted to an alternative drug during the shortage period. Interestingly, 5-fluorouracil was also in short supply, albeit less acutely than cisplatin. After the shortage, cisplatin volumes rebounded by 8% of pre-shortage use, while carboplatin use dropped below pre-shortage levels. Cetuximab use remained consistently 12% higher. The average cost per administration was $18 for cisplatin, $14 for carboplatin, $16 for paclitaxel, $22 for 5-fluorouracil, and $2,607 for cetuximab, based on the ASP. The increased use of cetuximab instead of cisplatin resulted in a 16% total cost increase, leading to a 144-fold increase in costs at the administration level, impacting payer costs and patient cost-sharing amounts. Conclusions: Cisplatin shortage led to a shift in utilization to alternative therapies for HNC, resulting in significant cost increases for both payers and patients. These consequences may not be limited to specific cancer types or drugs and may have other undesirable effects. Even temporary shortages of drugs can lead to lasting utilization changes and have long-term financial implications. The impacts of drug shortages on treatment decisions, guideline concordance, costs, and patient outcomes are apt for further investigation.

The impact of ePRO presentation during MDTB on clinician discussion of patient fitness and preferences: The INSPIRE intervention pilot.

251 Background: Treatment of pancreatic cancer often entails multiple modalities (e.g., chemotherapy, surgery, radiation) that vary in intensity, timing, and toxicity. While some options are only recommended for ‘fit’ patients regardless of age, formal fitness measures (such as the geriatric assessment [GA]) and patient preferences are seldom utilized during treatment decision-making. Methods: The INtegrating Systematic PatIent-Reported Evaluations into Multi-Disciplinary Tumor Board (INSPIRE-MDTB) intervention involves the presentation of GA and treatment preferences during MDTB discussions of patients with stage I-IV pancreatic adenocarcinoma. This qualitative study inductively analyzed, recorded and transcribed historical (November 2021 - February 2022) and intervention (September 2022 - June 2023) MDTBs using NVivo software. A constant comparative method was used to establish a grounded scheme representative of clinicians’ characterization of patients’ fitness and preferences during decision-making. Results: Recordings of the MDTB of 31 historical and 49 intervention patients with similar gender (52%; 53% female), age (m=68.1; 72.3), race (65%; 59% White), and cancer stage (26%; 22% stage IV) were included. The GA was not utilized in any historical case but was presented in 94% of intervention cases. Compared to historical controls, INSPIRE patients had more frequent discussions of (1) Cancer-Related Factors (e.g. size, location, progression speed; 35% vs. 43%), (2) Individual Risk Factors (e.g. age, comorbidities, tolerance; 90% vs 98%), and (3) Psychosocial Factors (e.g. health literacy, social support, substance use; 19% vs 33%) (Table 1). Preference domains were discussed in 39% of historical and 80% of intervention patients, with notable increases in patients’ concerns regarding physical (0%; 35%) and mental/emotional (0%; 20%) side effects, ability to work (0%; 10%), and the logistics and convenience of treatment (6%; 14%). Conclusions: INSPIRE-enhanced MDTB discussion of patient fitness and preferences represents a promising approach to providing a venue for consistent and systematic presentation and discussion of ePROs. Clinicians’ characterization of patients’ fitness during MDTB. Factors Impacting Fitness Baseline Intervention Cancer Related 11 (35%) 21 (43%) High Risk (size, location) 8 (26%) 16 (33%) Rapid Progression 0 (0%) 3 (6%) Prior or Concurrent Cancer 3 (10%) 3 (6%) Individual Risk Factor 28 (90%) 48 (98%) Age 19 (61%) 26 (53%) Comorbidities 24 (77%) 43 (88%) Weight Loss 11 (35%) 5 (10%) Tolerance 7 (23%) 9 (18%) Psychosocial Factor 6 (19%) 16 (33%) Insurance 2 (6%) 0 (0%) Language Barrier 0 (0%) 1 (2%) Health Literacy 0 (0%) 6 (12%) Social Support 3 (10%) 12 (24%) Substance use 1 (3%) 2 (4%)

The Encounter of Two Worlds: Divided Narratives of Decision-Making on Cancer Treatment Between Physicians and Patients.

Divided narratives pose long-standing difficulties in physician and patient communication. In decision-making on cancer treatment, divided narratives between physicians and patients hinder mutual understanding and agreement over the illness and its treatment. For effective decision-making on treatments, it is necessary to investigate the similarities and differences in these divided narratives. This study adopted a qualitative research design of narrative inquiry to examine the data, which included interviews with 32 cancer patients and 16 paired physicians in two hospitals in China. Data analysis was conducted using grounded theory to generate findings. Both physicians and patients were concerned about goals and obstacles to their decision-making on cancer treatment. Four common aspects of goal setting were identified from the divided narratives: decision pools, treatment goals, identity practice and preferred identity. Four common obstacles were identified: pains and trust, communication gap, financial issues and complex family. However, the meanings attached to these eight aspects differed between physicians and patients. Cancer treatment decision-making is an encounter of the scientific world and lifeworld. A divided narrative approach can identify the similarities and differences in the decision-making on cancer treatment between physicians and patients. Physicians generally adopt a rational decision-making approach, whereas patients generally adopt a relational decision-making approach. Despite the common concerns in their goals and obstacles, physicians and patients differed in their contextualized interpretations, which demonstrates the physicians' and the patients' pursuit of preferred identities in decision-making. The results of this study provide a new perspective to treatment decision-making, emphasizing the importance of narrative integration in reaching mutual agreement. The findings were shared with 15 cancer patients and caregivers for feedback and advice in June 2024. This study was also presented at the international conferences of COMET (International and Interdisciplinary Conference on Communication, Medicine, and Ethics) and ICCH (International Conference on Communication in Healthcare) 2023 for continuous feedback and comments.

Automatic Echocardiographic Assessment of Left Atrial Function for Prediction of Low-Voltage Areas in Non-Valvular Atrial Fibrillation.

Left atrial low-voltage areas (LA-LVAs) identified by 3D-electroanatomical mapping are crucial for determining treatment strategies and prognosis in patients with atrial fibrillation (AF). However, convenient and accurate prediction of LA-LVAs remains challenging. This study aimed to assess the viability of utilizing automatically obtained echocardiographic parameters to predict the presence of LA-LVAs in patients with non-valvular atrial fibrillation (NVAF). This retrospective study included 190 NVAF patients who underwent initial catheter ablation. Before ablation, echocardiographic data were obtained, left atrial volume and strain were automatically calculated using advanced software (Dynamic-HeartModel and AutoStrain). Electroanatomic mapping (EAM) was also performed. Results were compared between patients with LA-LVAs ≥5% (LVAs group) and <5% (non-LVAs group). LA-LVAs were observed in 81 patients (42.6%), with a significantly higher incidence in those with persistent AF than paroxysmal AF (55.6% vs 19.3%, P <0.001). Compared with the non-LVAs group, the LVAs group included significantly older patients, lower left ventricular ejection fraction, higher heart rate, and higher E/e' ratio (P <0.05). The LVAs group exhibited higher left atrial volumemax index (LAVimax) and lower left atrial reservoir strain (LASr) (P <0.001). In multivariate analysis, both LAVimax and LASr emerged as independent indicators of LVAs (OR 0.85; 95% CI 0.80-0.90, P<0.001) and (OR 1.15, 95% CI 1.02-1.29, P =0.021). ROC analysis demonstrated good predictive capacity for LA-LVAs, with an AUC of 0.733 (95% CI 0.650-0.794, P <0.001) for LAVimax and 0.839 (95% CI 0.779-0.898, P <0.001) for LASr. Automatic assessment of LAVimax and LASr presents a promising non-invasive modality for predicting the presence of LA-LVAs and evaluating significant atrial remodeling in NVAF patients. This approach holds potential for aiding in risk stratification and treatment decision-making, ultimately improving clinical outcomes in patients.

Pre-operative prediction of BCR-free survival with mRNA variables in prostate cancer.

Technological innovation yielded opportunities to obtain mRNA expression data for prostate cancer (PCa) patients even prior to biopsy, which can be used in a precision medicine approach to treatment decision-making. This can apply in particular to predict the risk of, and time to biochemical recurrence (BCR). Most mRNA-based models currently proposed to this end are designed for risk classification and post-operative prediction. Effective pre-operative prediction would facilitate early treatment decision-making, in particular by indicating more appropriate therapeutic pathways for patient profiles who would likely not benefit from a systematic prostatectomy regime. The aim of this study is to investigate the possibility to leverage mRNA information pre-operatively for BCR-free survival prediction. To do this, we considered time-to-event machine learning (ML) methodologies, rather than classification models at a specific survival horizon. We retrospectively analysed a cohort of 135 patients with clinical follow-up data and mRNA information comprising over 26,000 features (data accessible at NCBI GEO database, accession GSE21032). The performance of ML models including random survival forest, boosted and regularised Cox models were assessed, in terms of model discrimination, calibration, and predictive accuracy for overall, 3-year and 5-year survival, aligning with common clinical endpoints. Results showed that the inclusion of mRNA information could yield a gain in performance for pre-operative BCR prediction. ML-based time-to-event models significantly outperformed reference nomograms that used only routine clinical information with respect to all metrics considered. We believe this is the first study proposing pre-operative transcriptomics models for BCR prediction in PCa. External validation of these findings, including confirmation of the mRNA variables identified as potential key predictors in this study, could pave the way for pre-operative precision nomograms to facilitate timely personalised clinical decision-making.

Patient needs in women of childbearing age with psoriasis: retrospective analysis from the German PsoBest registry.

Women of childbearing age (WoCBA) with psoriasis face additional burden related to contraindications of systemic treatments during pregnancy/lactation and to the physical and psychosocial impact of psoriasis on their intimate/sexual relationships. Within a people-centered health care model, this study aimed to identify specific patient needs and their correlates in WoCBA (18-45 years), in comparison to same-age men and women above 45 years. Baseline data from the German PsoBest registry, including patients with moderate/severe plaque-type psoriasis with the indication for systemic therapy, were retrospectively analyzed. Psoriasis severity was assessed with the Psoriasis Area and Severity Index and patient-reported outcomes included EuroQoL Visual Analogue Scale, Dermatology Life Quality Index (DLQI), and Patient Needs Questionnaire. The participants were 2308 WoCBA, 3634 men between 18 and 45 years of age, and 3401 women older than 45 years. In comparison to both control groups, WoCBA reported more DLQI impairments and higher needs to reduce social impairments (eg, "to be able to lead a normal working life"; "to be less burdened in your partnership"; "to be able to have a normal sex life"). These patient needs were associated with having psoriasis arthritis, previous systemic therapy, worse general health, and more DLQI impairments. Retrospective analysis of an established dataset limited the examination of specific developmental, sexual, and reproductive variables. The specific needs of WoCBA with psoriasis were particularly related to the work context/financial stability and intimate relationships, which are crucial aspects in family planning. These results claim for a sex/age-sensitive approach in the psoriasis health care, by considering these needs as qualifiers in the clinical decision for systemic treatment.

155P The experience of parents as they make treatment decisions for their child with spinal muscular atrophy and the factors that influence these decisions: a narrative review

155P The experience of parents as they make treatment decisions for their child with spinal muscular atrophy and the factors that influence these decisions: a narrative review

Adaptation du plan thérapeutique en fonction de l’âge

Lung cancer is a very common disease of the elderly. Its incidence is expected to increase in Western countries because of the ageing of the population and the increase of cancer incidence with age. The purpose of this article is to synthesize the published data available to manage elderly patients with lung cancer at various stages: early-stage, locally advanced inoperable and metastatic. We will describe the indications of surgery and radiotherapy. We will also discuss, for each of the stage of the disease, the respective contributions of systemic therapies as chemotherapy, targeted therapies and immunotherapy and their use as sole therapy or in combination with local treatments. International recommendations have been published but they are difficult to apply because of the lack of consensual definition of frailties relevant to make treatment decision and to adapt it. We will also discuss data about the usefulness of geriatric assessment.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Barriers, facilitators, and recommendations to increase the use of a clinical decision support tool for managing chronic pain in primary care

Background and ObjectivePrimary care providers (PCPs) use poorly organized patient information in electronic health records (EHR) within a limited time when treating patients with chronic pain. Clinical decision support (CDS) tools assist PCPs by synthesizing patient information and prompting guideline-concordant treatment decisions. A CDS tool- Chronic Pain OneSheet was developed through a user-centered design process to support PCP’s decision-making for patients with chronic noncancer pain. OneSheet aggregates relevant patient information in one place in the EHR. OneSheet also guides PCPs in completing guideline-recommended opioid risk management tasks, tracking patient treatments, and documenting pain-related symptoms. Our objective was to identify barriers, facilitators, and recommendations to increase OneSheet use for chronic noncancer pain management in primary care. MethodsWe conducted 19 qualitative interviews with PCPs from two academic health systems who had access to OneSheet in their EHR. Interview transcripts were coded to identify common themes using a modified thematic approach. ResultsPCPs identified several barriers to using OneSheet, including limited time to address patient needs associated with multiple chronic conditions, resistance to changing established workflows, and complex OneSheet display. PCPs reported several facilitators to using OneSheet, such as OneSheet’s ability to serve as a hub for chronic pain data, easy access to features that facilitate completing mandatory tasks and improved planning for certain patient visits. PCPs recommended prioritizing access to commonly used features, adding display customization capabilities, and expanding access to patients and other team members to increase OneSheet use. ConclusionOur findings highlight the importance of acknowledging the PCP workflow and task load when designing CDS tools. Future CDS tools should balance the extent of information provided with assisting PCPs to fulfill mandatory tasks. Expanding CDS tools to multiple care team members and patients can also lead to higher use by facilitating data entry, leading to more streamlined care delivery.

Exploring the meaning of “a good day” for individuals living with advanced cancer: A qualitative interview study.

249 Background: More people are living longer with stage IV cancer due to advances in cancer treatments. However, individuals living with advanced cancer must navigate dynamic treatment schedules, side effects, fear of progression, and uncertainty, resulting in unique day-to-day experiences that may be poorly understood by their health care team. The goal of this project was to better understand the activities, behaviors, and experiences that characterize a “good day” versus a “bad day” among individuals living with advanced cancer. Methods: Twenty participants with stage IV cancer were enrolled (mean 63 years old, range 41-75; 65% female; 65% White and 35% Black; mean 1.5 years since Stage IV diagnosis, range 9 days to 7.5 years). Participants completed semi-structured interviews which involved rating the quality of their day yesterday from 1-5 (1 = very bad and 5 = very good) and characterizing their experiences and activities during the day. Participants were also asked to describe a theoretical ‘very good day’ versus a ‘very bad day’ for them personally, as well as advice they would give to another patient with advanced cancer about how to make a day better. Interview transcripts were reviewed to identify common themes across participants. Results: Interviews revealed that “good days” were associated with feeling like oneself (feeling symptom-free, in control, like pre-cancer self), bringing oneself to engage in activities that bring personal wellness, feeling connected to others (spending quality time with others, helping others, feeling supported and understood by others), feeling accomplished (getting things done, reaching goals), and practicing positive thought patterns (gratitude, reframing success, letting go). On the other hand, loss of control, uncertainty/unpredictability, disruptive physical symptoms, negative experiences with health care, and inability to reach one’s goals were common on “bad days.” When asked what they felt most grateful for yesterday, some participants cited their support system, kids, and grandkids, but the majority of participants reported feeling most grateful for simply living another day, good or bad. Conclusions: Preliminary findings suggest that days on which individuals with advanced cancer are able to engage in activities that give them a sense of normalcy, control, self-identity, and connection to others are better than days without these activities. Findings also suggest that what defines a “good day” looks different between individuals with stage IV cancer. Understanding these individuals’ values and priorities may help care teams support people with advanced cancer to optimize their quality of life and functioning and navigate treatment decisions.

Dynamics of minimal residual disease and its clinical implications in multiple myeloma: A retrospective real-life analysis

BackgroundMinimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic natures of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications. MethodsWe retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD test at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration, and loss) on clinical outcomes was analysed. ResultsIn a cohort of 220 patients with newly diagnosed MM, attainment of MRD− offered favourable outcomes (P < 0.0001 for both PFS and OS), regardless of baseline risk factors. Notably, the MRD− duration ≥12 months was associated with an 83% (95% CI, 0.09−0.34; P < 0.0001) or 69% (95% CI, 0.13−0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD− was sustained, the better the outcome was. Loss of MRD− led to poor PFS (HR 0.01, 95% CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95% CI 0-0.24, P = 0.0008). Most patients (70%) who lost the MRD− status carried high-risk cytogenetic abnormalities (HRCAs). While MRD− was temporally inconsistent with conventional therapeutic responses (e.g., ≥CR or VGPR), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of the baseline risk factors (e.g., HRCA, ISS, or R-ISS staging). ConclusionsLongitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.

PSMA PET/CT for treatment response evaluation at predefined time points is superior to PSA response for predicting survival in metastatic castration-resistant prostate cancer patients

BackgroundIn metastatic castration-resistant prostate cancer (mCRPC), using serum prostate-specific antigen (PSA) levels to evaluate treatment response is not always accurate. This study aimed to assess the efficacy of PSMA PET/CT at specific time points for evaluating treatment response and predicting survival in mCRPC patients, compared to PSA. MethodsSixty mCRPC patients underwent [18F]PSMA-1007 PET/CT at baseline and for treatment response evaluation of either androgen receptor-targeted agents (after 3 months) or chemotherapy (after completion), and were retrospectively analysed. Visual assessment categorised overall response and response of the worst responding lesion as partial response, stable disease, or progressive disease, using the EAU/EANM criteria. Additionally, percentage changes in SUVmax, total tumour volume and total lesion uptake (tumour volume * SUVmean) were calculated. PSA response was defined according to the PCWG3 criteria. Cox regression analysis identified predictors of overall survival. ResultsPSMA PET/CT and PSA response were discordant in 47 % of patients, and PSMA PET/CT response was worse in 89 % of these cases. Overall response on PSMA PET/CT independently predicted overall survival (progression versus non-progression: HR = 4.05, p < 0.001), outperforming PSA response (progression versus non-progression: HR = 2.53, p = 0.010) and other PSMA PET/CT parameters. Among patients with a PSA decline of > 50 %, 31 % showed progressive disease on PSMA PET/CT, correlating with higher mortality risk (progression versus non-progression: HR = 4.38, p = 0.008). No flare in PSMA uptake was observed in this cohort. ConclusionsPSMA PET/CT for assessing treatment response at predefined time points was superior to PSA-based response for predicting overall survival in mCRPC patients treated with androgen receptor-targeted agents and chemotherapy. PSMA PET/CT showed the ability to detect disease progression earlier than PSA levels, which can affect treatment decisions and has the potential to improve patient outcomes. We recommend further research to validate these findings in larger patient cohorts, to extend the number of treatments, and to evaluate cost-effectiveness and impact on patient outcomes.

Utilization of genomic tumor testing (GTT) among community oncologists participating in SWOG S2108CD.

320 Background: As targeted therapy options increase in oncology, GTT use is also increasing; however, the strategies and barriers to ordering GTT can vary across clinics. S2108CD is a cluster randomized trial comparing an educationally enhanced genomic tumor board intervention to usual practice to increase evidence-based genome-informed therapy based on GTT results. This analysis seeks to understand the utilization of GTT by physicians in rural and community oncology clinics. Methods: Physicians at sites enrolled on S2108CD completed baseline questionnaires collecting demographics, practice characteristics, and physicians’ experience with and use of GTT in practice. We also conducted semi-structured interviews at baseline and mid-study with select physicians in both arms to understand how and when physicians are ordering GTT and how it guides treatment decision making. Descriptive statistics were generated for survey data. Interviews were analyzed using conventional content analysis to identify recurring themes. Results: Surveys were completed by 117 physicians across 18 Recruitment Centers, with 57 from the usual practice and 60 from the intervention arm. Interviews were conducted with 10 physicians at baseline and 10 within 12-18 months of start of the study. Physicians reported feeling confident in determining whether GTT is clinically appropriate for a patient (42% moderately confident, 50% very confident). Some physicians utilize GTT from multiple vendors, with the following vendors used most frequently: Tempus (50% of physicians), Caris Life Sciences (61%), Foundation Medicine (62%) and Guardant Health (69%). Over two-thirds of physicians reported that professional guidelines were “very important” in the decision to utilize GTT. Reasons for not ordering GTT included “not relevant for the patient” (36%) and “difficulty in obtaining sufficient tissue” (20%) as “often” reasons. Notably, lack of access and cost/insurance coverage were “never” or “rarely” a reason for not ordering GTT in 80% physicians. Long waits to receive GTT results reportedly caused a delay in making patient care decisions (47% sometimes and 26% often). Physicians rely on the following sources to learn about new GTT panels: scientific meetings (91%), peer-reviewed literature (92%), and professional societies (90%). Interview data confirmed that physicians are generally confident ordering GTT but there is variability in the processes for ordering GTT and receipt of GTT results amongst clinics. Conclusions: Physicians enrolled on S2108CD self-reported high genomic confidence in ordering GTT. Access to GTT and coverage of GTT do not appear to be barriers to utilization. However, physicians did report delays in decision-making due to result turn-around times, which were sometimes attributed to length of time to tissue sendout and receipt of results into health record. Funding : NIH/NCI/NCORP grant UG1CA189974. Clinical trial information: NCT05455606 .

Advancing quality of care using a knowledge transfer approach to foster the use of single-fraction radiation therapy.

288 Background: There are significant barriers between the publication of scientific evidence and its adoption in clinical practice. Research in bone metastasis has demonstrated the effectiveness of single-fraction radiation therapy for uncomplicated cases. A persistent reluctance to adopt this approach in favor of multi-treatment courses remain. The aim of this project was to advocate for a better treatment method by employing a knowledge transfer approach to disseminate information, gather clinician feedback, and change practices. Methods: Initially, experts were invited to share best practices and raise awareness about the issue. Quality measures were developed with help from a consortium-wide working group and were introduced in 2020. The performance metric was steadily increased from 20% to a consortium-wide rate of ≥45% in 2023. The knowledge transfer project involved using video presentations to educate clinicians on the benefits of single-fraction treatment, a post-session survey to assess the impact of the information provided, and a 30-minute virtual discussion that followed days after the presentation. The 30-minute recorded video presentation by a radiation oncologist with expertise in palliative care presented evidence in support of the treatment and dispelled myths surrounding single-fraction treatment. This was first piloted at four sites before being rolled out consortium wide. Results: The project was effective. Physicians at 22 radiation oncology centers reported an increased awareness of single-fraction treatment and a willingness to try it. The table shows: 100% reported the topic was relevant, 94% were prompted to reflect on their current practice, 63% reported their thoughts about fractionation changed and 84% acknowledged an increase in their knowledge of the evidence supporting single-fraction treatment. Annual rates of single-fraction use increased over time. The consortium wide target promoting the use of single fraction for uncomplicated patients was met in 2023– single fraction was used 46% of the time for the treatment of uncomplicated bone metastases patients as compared to about 37% in 2021. Conclusions: Patient care can be enhanced by supporting providers who make health care decisions daily. Quality care can be encouraged by conveying evidence-based knowledge to providers, who are responsible for making healthcare treatment decisions. This project illustrates that sustained efforts in knowledge transfer can effectively change clinical practice patterns to align with evidence-based recommendations. Knowledge transfer project. Physician participation vs. those invited to participate 22/24 (91.67%) Survey Responses: a. Relevant to Practice 100% b. Usefulness to practice and reflection on current practice 94% c. Thoughts changed about fractionation treatment 63% d. Knowledge of evidence supporting treatment increased 84%

Analytical and clinical validation of a NGS panel in detecting targetable variants from ctDNA of metastatic NSCLC patients.

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive cancer diagnostics, particularly in the context of metastatic non-small-cell lung cancer (NSCLC). Detecting targetable variants through ctDNA analysis offers the potential to guide treatment decisions, especially in cases where tissue samples are insufficient or unavailable. In this study, we developed and validated a next-generation sequencing panel targeting 101 cancer-related genes (101-test) to detect somatic variants in ctDNA from a large cohort of Chinese patients with metastatic NSCLC. The performance of the 101-test was assessed by evaluating its limit of detection (LOD), accuracy, and precision in identifying molecular variants. Additionally, the concordance between ctDNA and tissue samples for detecting targetable variants was analyzed in 904 patients. The 101-test demonstrated a LOD of 0.38% for single-nucleotide variants (SNVs), 0.33% for insertions and deletions (InDels), and 0.33% for fusions. Sensitivity was 98.3% for SNVs, 100% for InDels, and 100% for fusions when compared to digital droplet PCR (ddPCR)/breakpoint PCR reference methods. The by-variant sensitivity for somatic variants was 97.5%, with a specificity of 99.9% between tumor-only and tumor-normal analyses. In a real-world cohort, the concordance between ctDNA and tissue samples for identifying targetable variants was 72.2% (457/633). Notably, the EGFR S768I variant, recently recommended by clinical guidelines, achieved an 80% concordance rate. Furthermore, 4.3% of patients (27/633) with targetable variants were identified exclusively through ctDNA testing. The ctDNA-based 101-test is a highly sensitive and specific tool for detecting targetable variants in metastatic NSCLC, particularly in cases with insufficient tissue samples. The findings support the use of ctDNA testing as a reliable and complementary method to traditional tissue-based molecular analysis, enhancing the precision of treatment strategies for NSCLC patients.

Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

IntroductionNon-small cell lung cancer (NSCLC) is the most common type of lung neoplasm. Despite surgical resection, it has a high relapse rate, accounting for 30–55% of all cases. Next-generation sequencing (NGS) based on a customized gene panel and the analysis of circulating tumor cells (CTCs) can help identify heterogeneity, stratify high-risk patients, and guide treatment decisions. In this descriptive study involving a small prospective cohort, we focus on the phenotypic characterization of CTCs, particularly concerning EZH2 expression (a member of the Polycomb Repression Complex 2), as well as on the mutation profiles of the tissue using a customized gene panel and their association with poor outcomes in NSCLC. MethodsIsolation and characterization of EZH2 on CTCs were evaluated before surgical resection (CTC1) and one month after surgery (CTC2) in resectable NSCLC patients. Targeted NGS was performed using a customized 50-gene panel on tissue samples from a subset of patients. Results76 patients with resectable NSCLC were recruited. The top mutated genes in the cohort included TP53, FLT1, MUC5AC, EGFR, and NLRP3. Pair of genes that had mutually exclusive mutations was TP53-RIN3, and pairs of genes with co-occurring mutations were CD163-TLR4, FGF10-FOXP2, ADAMTSL3-FLT1, ADAMTSL3-MUC5AC and MUC5AC-NLRP3. CTCs decreased significantly between the two time points CTC1 and CTC2 (p<0.0001), and CTCs+ patients with high EZH2 expression had an 87% increased risk of death (p=0.018). ConclusionsIntegrating molecular profiling of tumors and CTC characterization can provide valuable insights into tumor heterogeneity and improve patient stratification for resectable NSCLC.

Acknowledgement and use of advance care directives and goals of care by emergency department staff: a mixed method post intervention study

Abstract Introduction Advance Care Planning (ACP) refers to a process that includes Advance Care Directives (ACD) and Goals of Care (GOC), a practice widely used for over three decades. Following the findings of an audit and a cross-sectional study in 2019 and 2021 respectively, we implemented several educational and other interventional strategies aimed at enhancing staff awareness and emphasizing the importance of recognizing and documenting of ACD/GOC. The aim of this study was to evaluate the acknowledgement and use of ACD and GOC by Emergency Department (ED) staff following these interventions. Method We used a mixed methods approach, incorporating both observational and cross-sectional designs with reflexive thematic analysis. Data extraction for the observational study took place between 1st April and 30th June 2023 focusing on a target population of randomly sampled adults aged ≥ 65 years. Demographics and other ACD and GOC related patients’ clinical data were collected. Data collection for the cross-sectional study occurred between 19th July and 13th September 2023 targeting all ED staff. Information gathered included demographics, awareness about ACD and GOC, including storage location and implementation, as well as knowledge of Medical Treatment decision Makers (MTDM), a jurisdictional term identifying a person legally appointed to make healthcare decisions on behalf of someone who lacks decision-making capacity and other Victorian State legislative requirements were collected. Results In the observational period, 22,335 patients attended the ED and 19% (n = 6546) qualified for inclusion from which a sample of 308 patients were randomly extracted. We found ACD documents were noted in the medical records of 6.5% of the sample, fewer than 8% identified in our previous study. There was no correlation between ACD record availability and age (p = 0.054; CI ranging from − 0.065 to 7.768). The response rate for the cross-sectional survey was 12% (n = 340) in contrast to earlier study with 28% (n = 476) respondents. Staff knowledge and familiarity with ACD was 25% and GOC 45%. Conclusion After implementing interventions in staff education and ACP awareness, we found that ACD documentation did not improve. However, GOC documentation increased in the context of heightened institutional awareness and integration into the Electronic Medical Records (EMR).