Clinical Oncology Research Articles

Multi-Enzyme Nanoparticles as Efficient Pyroptosis and Immunogenic Cell Death Inducers for Cancer Immunotherapy.

Immunotherapy represents a widely employed modality in clinical oncology, leveraging the activation of the human immune system to target and eradicate cancer cells and tumor tissues via endogenous immune mechanisms. However, its efficacy remains constrained by inadequate immune responses within "cold" tumor microenvironment (TME). In this study, a multifunctional nanoscale pyroptosis inducer with cascade enzymatic activity (IMZF), comprising superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), is dissociated within the acidic and glutathione-rich TME. The vigorous enzymatic activity not only generates oxygen (O2) to alleviate hypoxia and promote M2 to M1 macrophage polarization but also yields reactive oxygen species (ROS) and depletes glutathione (GSH) within the TME. Functioning as an immunogenic cell death (ICD) activator and pyroptosis inducer, IMZF synergistically triggers dendritic cell maturation and inflammatory lymphocyte infiltration via ICD-associated pyroptosis, thereby reversing immune suppression within the TMEs. Consequently, it exerts inhibitory effects on both primary and distal tumors. This cascade enzymatic platform-based pyroptosis inducer offers an intelligent strategy for effectively overcoming immune suppression within "cold" tumors, thereby providing a promising avenue for advanced immunotherapeutic interventions.

Proof-of-concept study of a small language model chatbot for breast cancer decision support – a transparent, source-controlled, explainable and data-secure approach

PurposeLarge language models (LLM) show potential for decision support in breast cancer care. Their use in clinical care is currently prohibited by lack of control over sources used for decision-making, explainability of the decision-making process and health data security issues. Recent development of Small Language Models (SLM) is discussed to address these challenges. This preclinical proof-of-concept study tailors an open-source SLM to the German breast cancer guideline (BC-SLM) to evaluate initial clinical accuracy and technical functionality in a preclinical simulation.MethodsA multidisciplinary tumor board (MTB) is used as the gold-standard to assess the initial clinical accuracy in terms of concordance of the BC-SLM with MTB and comparing it to two publicly available LLM, ChatGPT3.5 and 4. The study includes 20 fictional patient profiles and recommendations for 5 treatment modalities, resulting in 100 binary treatment recommendations (recommended or not recommended). Statistical evaluation includes concordance with MTB in % including Cohen’s Kappa statistic (κ). Technical functionality is assessed qualitatively in terms of local hosting, adherence to the guideline and information retrieval.ResultsThe overall concordance amounts to 86% for BC-SLM (κ = 0.721, p < 0.001), 90% for ChatGPT4 (κ = 0.820, p < 0.001) and 83% for ChatGPT3.5 (κ = 0.661, p < 0.001). Specific concordance for each treatment modality ranges from 65 to 100% for BC-SLM, 85–100% for ChatGPT4, and 55–95% for ChatGPT3.5. The BC-SLM is locally functional, adheres to the standards of the German breast cancer guideline and provides referenced sections for its decision-making.ConclusionThe tailored BC-SLM shows initial clinical accuracy and technical functionality, with concordance to the MTB that is comparable to publicly-available LLMs like ChatGPT4 and 3.5. This serves as a proof-of-concept for adapting a SLM to an oncological disease and its guideline to address prevailing issues with LLM by ensuring decision transparency, explainability, source control, and data security, which represents a necessary step towards clinical validation and safe use of language models in clinical oncology.

Efficacité de 6 scénarios de décontamination de bras de fauteuils contaminés volontairement au cyclophosphamide

The arms of chairs in outpatient oncology clinics are frequently contaminated with cyclophosphamide. To evaluate the effectiveness of decontamination scenarios. This was a descriptive simulation-type study of 6 decontamination scenarios of a silicone fabric surface contaminated with 10 μg of cyclophosphamide. The decontamination products tested (quaternary ammonium, 0.5% hydrogen peroxide, 0.005% detergent, and sodium hypochlorite 0.5%) were applied with microfibre wipes. Residual contamination was measured using an ultra-performance liquid chromatography-tandem mass spectrometry system with identical cyclophosphamide detection and quantification limits (0.0006 ng/cm2). Among the 59 samples, 3 blanks were negative, 5 allowed measurement of the recovery rate (93.7% [standard deviation 4.6%]), and 51 were experimental. The average efficiency of the agents was greater than or equal to 99.79%. Regardless of the agent used, effectiveness was 99.30% (SD 1.20%) after 1 cleanse (n = 18), 99.90% (SD 0.15%) after 2 cleanses (n = 18), and 99.95% (SD 0.06%) after 3 cleanses (n = 15). The 6 decontamination scenarios were effective. Repeated cleaning marginally increased the effectiveness of decontamination.

Consideration of factors of low accrual and methods for setting appropriate accrual periods: Japan Clinical Oncology Group study

BackgroundPoor patient accrual can delay reporting of clinical trials and, consequently, the development of new treatments. For reducing the risk of additional resource requirements, a method for setting planned accrual periods with minimal deviation from the actual accrual periods is desirable. Risk factors for poor patient accrual and the appropriate method of estimating the required accrual period for timely completion of clinical trials were evaluated using the data of trials conducted by the Japan Clinical Oncology Group.MethodsThe study included 199 trials that started patient accrual between January 1, 1990, and June 30, 2021. The explanatory variables included factors that could be evaluated prior to trial commencement. We also evaluated whether the estimation methods for accrual pace could lead to completion within the planned accrual period.ResultsApproximately 23.6% of trials were completed within the planned accrual period. The risk factors for trial extension included planned accrual periods > 3 years (reference group: ≤ 3 years, odds ratio [OR] 0.37, 95% confidence interval [CI]: 0.15–0.92, P = 0.033) and stratified trial design (reference group: nonrandomized phase II trials, nonrandomized phase III trial [OR: 3.28, 95% CI: 0.99–10.9, P = 0.051], randomized phase II trial [OR: 3.91, 95% CI: 0.75–20.30, P = 0.105], and randomized phase III trial [OR: 9.29, 95% CI: 3.39–25.40, P < 0.001]). The method of estimating the accrual pace based on past clinical trials facilitated timely completion of the trial (OR: 3.51; 95% CI: 1.73–7.10, P < 0.001), unlike the estimation method based on survey evaluation of the accrual pace for participating institutions (OR: 1.12, 95% CI: 0.56–2.26, P = 0.751). Furthermore, the discrepancy between planned and actual accrual periods was minimal when using the methods of considering the accrual pace of past clinical trials.ConclusionsConsidering the accrual pace of past clinical trials is useful for estimating the required accrual period if data from past trials are available. When conducting a survey, it is necessary to be cautious of overestimating the cases at each facility.

Cancer survivors' adherence to the American cancer society and American institute of cancer research dietary guidelines in Lebanon.

Adequate diet and lifestyle practices are postulated to improve health and enhance wellbeing of cancer survivors. Despite the heavy cancer burden in Lebanon, little is known about the diet quality of survivors. This cross-sectional study assessed the compliance of survivors in remission with the American Cancer Society/American Institute Research Fund (ACS/AICR) diet and physical activity guidelines. Cancer survivors in remission for at least 3 months and attending oncology clinics in two referral centers in Beirut, Lebanon were recruited. Adherence to the ACS/AICR was assessed by examining the compliance to guidelines promoting fruits, vegetables and whole grain and discouraging elevated alcohol, meat and energy dense foods intake. Dietary data was assessed through food frequency and lifestyle questionnaires administered face to face and through phone interviews. Anthropometrics, food security and sociodemographic data was also collected. Univariate and bivariate descriptive and logistic regressions were used to determine predictors of adherence rates to the ACS/AICR score. A total of 268 participants were recruited (mean age = 59 ± 23 years, 83% females, 70% breast cancer). Mean time since remission was 3.2 ± 4 years and the majority (72%) had food insecurity. Low physical activity and overweight/obesity were present in 65% and 67% of the survivors, respectively. Median adherence score with the ACS/AICR score was 9.0 out of 15. The majority of survivors had complete adherence to the moderate meat and alcohol consumption guidelines. However, 98% were noncompliant with the whole grains' consumption guidelines. Cancer type, site of recruitment and education were the significant predictors of the ACS/AICR diet adherence score. This study highlights the elevated rates of overweight/obesity, physical inactivity and the alarmingly low adherence with the whole grains consumption guideline among cancer survivors in remission. Policy makers ought to use study findings to redirect government subsidization and educational interventions in the country and physicians should stress the importance of adherence to a healthy diet during remission through counseling and timely referral.

Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation.

Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

8016 Resolution of Refractory Hypoglycemia Following Pancreatic Solitary Fibrous Tumor Resection

Abstract Disclosure: M.E. Horowitz: None. S. Stefan: None. Introduction: Solitary fibrous tumors (SFT) are exceptionally rare mesenchymal tumors, accounting for only 3.7% of all cases of soft-tissue sarcoma with an incidence of 0.35 cases per 100,000 persons per year. SFT may arise in various anatomical locations, approximately 30% occuring in the abdomen. SFT can manifest with paraneoplastic syndromes, with the most commonly described being non-islet cell hypoglycemia. We present a case of refractory hypoglycemia which resolved following the resection of a large pancreatic SFT. Clinical Case: A 75-year-old male with a history of hypertension presented from oncology clinic with hypoglycemia. Two weeks prior, a 26cm mass of the pancreatic head was identified after he presented to the hospital for one month of abdominal pain and distention, and biopsy of the mass confirmed an SFT. The patient complained of nighttime weakness, confusion, nausea, vomiting, and urinary incontinence for two nights prior to arrival. During this time, the patient had multiple fingersticks showing hypoglycemia below 70 mg/dL, the lowest at 37 mg/dL. On arrival, fingerstick glucose was 38 mg/dL and serum glucose was 27 mg/dL, with a c-peptide level of 0.28 ng/mL (1.00-4.00 ng/mL). Despite hypoglycemia, he was asymptomatic at the time of presentation, indicating hypoglycemia unawareness. Investigation into the cause of hypoglycemia included normal morning cortisol levels, normal thyroid function tests, and normal liver and renal function tests. Further assessment for paraneoplastic disease was conducted, revealing an IGF1 level of 36 ng/dL (5-34 ng/dL) and IGF2 241 ng/dL (267-616 ng/dL), with a ratio of IGF2:IGF1 of 6.7:1. He underwent surgical removal of the large abdominal mass with distal gastrectomy and Billroth-I reconstruction. Pathology was consistent with a 34cm retroperitoneal SFT, STAT6 positivity, and negative margins. Following surgery, the patient did not experience any further hypoglycemia or related symptoms, and glucose ranged 78-135 mg/dL through discharge. Clinical Lessons: Refractory hypoglycemia resulting from a tumor's production of IGF2 is a rare paraneoplastic syndrome known as Doege-Potter Syndrome. This syndrome is observed in fewer than 5% of patients with SFT. The first documented case of hypoglycemia in a patient with "fibrous sarcoma" dates back to 1930. To establish a diagnosis, a ratio of IGF2:IGF1 exceeding 3:1 is suggestive of tumor-mediated production, while a ratio exceeding 10:1 is considered diagnostic. A positive immunohistochemical stain for STAT6 confirms the diagnosis. Patients with these tumors should be routinely monitored for hypoglycemia and related symptoms. Presentation: 6/3/2024

7839 Assess Management of Adrenal Insufficiency in Melanoma Patients Treated with Cancer Immunotherapy

Abstract Disclosure: W. Lin: None. L. Min: None. Despite high prevalent of adrenal insufficiency in melanoma patients treated with cancer immunotherapy, no study has examined the management of adrenal insufficiency in these patients. We performed this retrospective, longitudinal cohort study at Mass General Brigham, Boston, aims to characterize the management of adrenal insufficiency in melanoma patients. Patients were identified through our RPDR search tool, and medical record reviews were conducted. Three patient groups were analyzed: Melanoma with secondary adrenal insufficiency group (Mel_SAI, n=74), Melanoma matched control group (Mel_Con, n=69), and Pituitary macroadenoma-related adrenal insufficiency matched control group (Pit_Con, n=37). We compared self-perceived quality of life, glucocorticoid replacement dose, and clinic visit. Mel_SAI patients exhibited significantly higher incidences of anxiety (43.1%, 95%CI: 32.3-54.6), fatigue (73.6%, 95%CI: 62.4-82.4), pain (58.3%, 95%CI: 46.8-69.0), and insomnia (36.1%, 95%CI: 26.0-47.6), as compared to Pit_Con group (21.6%, 11.4-37.2; 24.3, 13.4-40.1; 29.7%, 17.5-45.8; 5.4%, 1.5-17.7, respectively). The initial hydrocortisone dose was higher for Mel_SAI (30mg qd, 95%CI: 20.5-25.1) compared to Pit_Con (15mg qd, 95%CI: 12.8-18.3). Additionally, the Mel_SAI group had fewer endocrinology clinic visits (3, 95%CI: 3.40-5.04) than the Pit_Con group (9, 95%CI: 7.35-10.9). Subgroup analysis indicated a higher mortality risk (HR 2.61, 95% CI 1.11-6.13) in Mel_SAI patients with fewer than three endocrinology visits over five years. Compared to the Mel_Con group, Mel_SAI patients also showed higher incidences of fatigue (71.6%, 95%CI: 60.5-80.6; Mel_Con: 55.1%, 95%CI: 43.4%-66.2%), but lower rates of depression (25.7%, 95%CI: 17.1-36.7; Mel_Con: 43.5%, 95%CI: 32.4-55.2) and appetite loss (24.3%, 95%CI: 16.0-35.2; Mel_Con: 47.8%, 95%CI: 36.4-59.4). No significant difference in other self-perspective symptoms. Furthermore, Mel-SAI patients had more oncological clinic visits (71, 95%CI: 74.0-109.2) than those in the Mel_Con group (41, 95%CI: 42.1-64.1). Our study suggests that most self-perceived quality of life in the Mel_SAI group is related to melanoma rather than adrenal insufficiency. Therefore, a higher initiating dose of hydrocortisone in melanoma patients with adrenal insufficiency may not be necessary. However, increasing endocrine clinic visits in cancer patients with cancer immunotherapy-related adrenal insufficiency may improve their survival outcomes. Presentation: 6/3/2024

Can We Offset Local Recurrence in Locally Advanced Non-Small Cell Lung Cancer? The Merry-Go-Round of Radiation Dose Escalation and Stubborn Outcomes.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Bibliometric Analysis of Research on Exercise Intervention for Cancer-Related Cognitive Impairments.

Introduction: Cancer treatments frequently lead to cognitive impairments, affecting a substantial global population. Among various approaches, exercise has emerged as a promising strategy for rehabilitation. However, a comprehensive bibliometric analysis of research in this field is lacking. Methods: We conducted a bibliometric analysis of 10,345 articles sourced from the Web of Science database using the R package "bibliometrix". Our analysis examined publication trends, leading countries, journals, authors, institutions, keywords, and prevalent themes. Results: Over the past two decades, research on exercise interventions for cancer-related cognitive impairments (CRCI) has advanced significantly. Nonetheless, challenges persist in elucidating underlying mechanisms, developing innovative strategies, and creating effective tools. Conclusions: The number of publications notably increased from 1998 to 2023, although there has been a recent decline in citations. The United States (US) leads in both publications and citations, while China is showing increasing influence. Using Lotka's Law in our bibliometric analysis, we identified 58 key authors in the field of exercise interventions for CRCI. Leading institutions such as the University of Toronto and Duke University are at the forefront of this research. Although the Journal of Clinical Oncology has fewer publications, it remains influential. Current research focuses on exercise interventions to enhance the quality of life for cancer patients, with particular emphasis on cognitive rehabilitation in breast cancer and the challenges faced by survivors. Future research should delve deeper into intervention mechanisms, behavioral strategies, telemedicine, and precise cognitive assessment tools.

Antitumour activity of oleanolic acid: A systematic review and meta‑analysis.

Oleanolic acid (OA), a compound known for its potent antitumour properties, has been the subject of investigations in both cell and animal models. Although OA has good biological activity, its low water solubility and bioavailability limit its therapeutic use, and therefore translating the potential of OA into the clinical oncology setting remains challenging. The present systematic review and meta-analysis utilized evidence from animal model studies to gain insights into the antitumour mechanisms of OA to address the gap in understanding, and to provide guidance for future research directions and potential clinical applications. The guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were applied in the present study and a comprehensive search was conducted across the PubMed/MEDLINE, Web of Science, Cochrane Library and Embase databases, with a cut-off date of June 30, 2023. The primary focus was on randomized controlled trials that used animal models to assess the antitumour effects of OA. The methodological quality appraisal was conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool, and tumour volume and weight served as the principal outcome measures. Data were analysed using the RevMan (version 5.3) and Stata SE11 software packages, with an assessment of heterogeneity conducted using the I2 statistical test, sensitivity analysis conducted using the leave-one-out approach, and evaluation of publication bias performed using Egger's test and funnel plot analysis. The present study demonstrated a significant inhibitory effect of OA intervention on tumour growth and a decrease in tumour weight in animal models. Despite the broad spectrum of antitumour effects exhibited by OA, further investigations are warranted to optimize the dosage and administration routes of OA to maximize its efficacy in clinical cancer treatment.

B-191 Genomic Profile of Circulating Tumor DNA in Advanced Lung Cancer: Comparison with Tissue DNA

Abstract Background The most common cancer in Korea is thyroid cancer, followed by lung cancer, and the most common cancer in men is lung cancer. The cancer with the highest mortality rate is lung cancer. Recently, the precision medical approach is becoming a major treatment strategy for lung cancer. For precision medical approach, the usefulness of next-generation sequencing (NGS) analysis targeting circulating tumor DNA (ctDNA) is being emphasized. Therefore, in this study, NGS analysis was performed on blood and tissues of advanced lung cancer patients to compare and analyze genetic mutation patterns to confirm the usefulness of ctDNA NGS assay. Methods A total of 101 patients with advanced lung cancer (stage 3 or 4) were recruited, and ctDNA NGS assays were performed on their plasma using a Pan100 panel (Dxome). Tissues from primary lung cancer, metastatic lymph nodes, or metastatic organs of 22 patients were analyzed using ONCOaccuPanel (NGeneBio). All variants were classified into four tiers based on the level of clinical significance, according to the standards and guidelines established by the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. Results In the ctDNA NGS assay of 101 patients, 70 (69.3%) harbored 154 tier 1 or 2 variants. Mutations in TP53 (45, 29.2%) and EGFR (23, 14.9%) were the most frequently detected, followed by mutations in RB1, CHEK2, ATM, JAK2, ATR, DNMT3A, and KRAS. Among the 22 patients whose tissue was examined, tier 1 or 2 variants were detected in both the plasma and tissue of 14 patients and only in the tissue of six patients. All genes for these variants were targeted using both methods. Identical variants were detected in the plasma and tissue of six of the 14 patients, and discordant results were observed in the remaining eight patients. Twenty copy number variations were detected in 13 of the 101 patients, with copy number gain of EGFR being the most common (6, 30%). Fusion genes were detected in five of the 101 patients, two of which were not detected in the tissue. Overall, 74 (73.3%) of the 101 patients had positive ctDNA NGS assay results. Conclusions Although the NGS assay with ctDNA is less sensitive than that with tissue DNA, some genetic alterations are detected only in ctDNA NGS assays; therefore, it is useful to apply the ctDNA NGS assay as a complement.

The relationship between serum interleukin-1β and circulating CD16+ neutrophils for assessing progression-free time in advanced ovarian cancer

BACKGROUND: Ovarian cancer is the most aggressive gynecological tumor with high mortality. The ambivalent, both helper and suppressive effects of neutrophils on the cells of innate and adaptive immunity determines their important immunoregulatory role in the development of malignant tumors. AIM: Evaluation of the effect of serum interleukin-1β and circulating neutrophils CD16+ on progression-free time in advanced ovarian cancer. MATERIAL AND METHODS: In 42 primary patients with serous ovarian adenocarcinoma (median age 54 years) with ascites and 15 patients with benign ovarian tumors (median age 60 years) admitted for examination and treatment to the Regional Clinical Oncology Dispensary before receiving neoadjuvant antitumor treatment (2015–2020), the level of interleukin-1β in the blood serum was determined using enzyme immunoassay, and the number of CD16+ neutrophils was determined by fluorescence microscopy using monoclonal antibodies. Statistical processing was performed using Statistica 13 and Jamovi 2.4.14 programs. Progression-free time analysis of patients was performed using the Cox and Kaplan–Meier regression methods. RESULTS: It was found that the number of circulating CD16+ neutrophils in advanced ovarian cancer with ascites was lower than in benign ovarian tumors [48.0; 95% confidence interval (CI) 46.59–48.12 versus 50.0; 95% CI 48.51–49.76; p=0.017]. At the same time, the level of interleukin-1β in the blood serum in advanced ovarian cancer with ascites was higher than in benign ovarian tumors [2.52 (95% CI 2.50–3.37) versus 1.26 (95% CI 0.97–1.55) (p=0.0001)]. In multivariate Cox analysis in patients with ascites (odds ratio 4.334; 95% CI 1.83–10.23; p=0.001), both the CD16+ neutrophil count (odds ratio 0.73; 95% CI 0.62–0.86; p=0.0001) and serum interleukin-1β levels (odds ratio 1.90; 95% CI 1.41–2.57; p=0.0001) had prognostic significance for assessing progression-free time. CONCLUSION: The number of circulating CD16+ neutrophils and serum interleukin-1β levels simultaneously affect progression-free time in advanced ovarian cancer.

Compassion fatigue in surgical oncologists: A scoping review.

343 Background: The practice of clinical oncology includes diverse and complex clinical, interpersonal and ethical challenges that can lead to physical and/or emotional distress, including burnout (BO), compassion fatigue (CF), secondary traumatic stress (STS) or moral distress (MDS), which potentially impacts patient care and provider well-being. Surgical oncology presents additional stressors and challenges, yet little is known about CF, STS, and MDS in this population, and the greater body of literature in oncology is heterogenous.The aim of this paper is to review current literature regarding CF, MDS, and STS in clinical oncologists, with a focus on surgical oncologists. Methods: Searches of OVID Medline and Embase databases were performed, as well as relevant bibliographies to identify articles related to CF, STS and MDS in clinical and surgical oncologists. Descriptive analysis was completed on relevant articles to address common definitions, themes, and potential aggravating/protective factors. Results: 619 articles were retrieved, of which 196 underwent data extraction. Of these, 48 articles were related to CF, MDS, or STS in oncologists and 5 included surgical oncologists. There was no data specific to surgical oncologists. Definitions of the terms were inconsistent across the literature. Potential contributing factors for CF/STS/MDS are related to the work environment, time pressures, and poor communication skills. In contrast, self-care, supportive colleagues/supervisors, and experience appear to be protective. Conclusions: This study highlights a need for standardized definitions to accurately capture and explore each of these phenomena. Further research is needed to provide insight into the challenges faced by surgical oncologists and how to support them.

A collaborator-engaged approach to tailoring strategies for implementing systematic health-related social needs assessment: Results from a cross-center study.

166 Background: Health-related social needs (HRSNs) exacerbate inequities in cancer incidence, morbidity and mortality. To improve health equity, policymakers recommend systematic HRSN screening in oncology clinics. In preliminary studies, we found low rates (&lt;10%) of HRSN screening in oncology. Building upon these findings and transdisciplinary expertise across four Implementation Science Centers in Cancer Control (ISC3), in the current study, we engaged oncology care teams in tailoring site-specific strategies to implement HRSN screening. Methods: Centers varied in collaborator engagement methods, including Context-Driven Co-Design (CD2), which aims to harmonize the intervention (i.e., HRSN screening), context (e.g., oncology clinic), and implementation strategies. First, site leads conducted semi-structured interviews with 8-10 care team members and clinic observations to identify current HRSN assessment processes and opportunities and barriers to systematic HRSN screening. Second, site leads engaged collaborators in one-on-one interviews or, when using CD2, in 3-4 iterative co-design workshops in which they used context assessment data and user-centered design activities (e.g., storyboarding) to prioritize contextual factors, identify necessary adaptations to HRSN screening, and co-design implementation strategies to address salient barriers. Centers met monthly to share knowledge and troubleshoot. Results: Most Centers’ oncology clinics had established informal HRSN screening approaches. Across Centers, collaborators (e.g., providers, nurses, medical assistants, patients) identified similar opportunities (e.g., desire for a standardized approach to HRSN screening; well-functioning clinical teams and physical space). Common challenges included limited familiarity with HRSN screening and documentation tools; lack of standardized screening protocol; and limited awareness of HRSN screening’s purpose. Implementation strategies included pencil-and-paper screening tools; clinic signage regarding HRSN screening’s purpose; training and creation of standardized screening protocol; and a centralized resource for responding to HRSN with adjustment, assistance, alignment, and/or advocacy. Conclusions: Four ISC3 Centers developed multicomponent implementation plans tailored to their oncology clinic. Centers’ varied approaches and timelines presented challenges and opportunities for cross-Center learning. Oncology clinics exhibited substantial overlap in opportunities and challenges in HRSN screening. Much of CD2’s benefits were related to its collaborator-driven approach to implementation strategy development. Next steps include deploying implementation plans and assessing their impact on equitable reach and adoption of HRSN screening and response to identified needs.

Improving flu vaccination rates among adult patients with cancer at Kaiser Permanente.

326 Background: Vaccines protect cancer patients from developing severe illness, hospitalization, and death. At Kaiser Permanente (KP) South Sacramento Medical Center (KPSSC), oncology patients on active chemotherapy had an overall flu vaccination rate of 13% between September 1, 2022, and December 1, 2022. Our aim was to increase this rate to 33% during the 2023 flu season. Methods: In conjunction with the ASCO Quality Training Program, we applied quality improvement initiatives to improve flu vaccination. Our population of interest included adult cancer patients on active chemotherapy at KPSCC. We evaluated the barriers to vaccination assessment by distributing surveys to infusion nurses. We performed three Plan-Do-Study-Act (PDSA) cycles for quality improvement and monitored flu vaccination rates. Cycle 1 (9/11/2023 to 11/5/2023): We distributed the ASCO flu vaccine handout at oncology clinic. We had medical assistants and infusion nurses administer flu vaccines during clinic visits and chemotherapy sessions. Cycle 2 (11/6/2023 to 11/21/2023): We added the vaccine handout in Chinese and Spanish and updated our receptionists’ script to strongly encourage patients to receive flu vaccine. Cycle 3 (11/22/2023 to 12/6/2023): KP flu clinic set up an onsite flu vaccine cart one half day per week in the oncology clinic. Results: Barriers to vaccination assessment in the clinic included lack of time (60%), difficulty remembering to ask (10%), and non-influenza season (10%). Our interventions resulted in an increased flu vaccination rate from 13% in 2022 to 36% in 2023. During cycle 1, 298 out of 615 patients received their vaccine (48.5%). During cycle 2, 16 out of 118 patients received their vaccine (13.6%). PDSA cycle 3 resulted in 14 out of 178 patients receiving their vaccine (7.9%). Conclusions: Promoting vaccine awareness via active engagement with nurses and medical assistants early on and having onsite vaccine availability in the oncology clinic were keys to improve the overall flu vaccination rate. While most vaccines were administered at the beginning of flu season, the addition of language-tailored vaccine handouts and having an onsite vaccine cart towards the end of the season did result in late season vaccinations. Our findings do support the importance of providing timely vaccine information in the oncology clinic. Our future goal is to expand these efforts to other KP Northern California oncology centers to establish stable onsite vaccine availability in clinics and include additional vaccine types.

Management of de novo Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) and the role of Radiation Therapy: A Consensus by the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Prostate cancer treatments paradigms are in continuous evolution, especially in metastatic setting. In this context, the Genito-Urinary (GU) Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO) aimed to create a Consensus on radiotherapy indication in de novo metastatic hormone sensitive prostate cancer both on primary tumour and metastatic sites. A panel of experts, involved in clinical management of prostate cancer, through the estimate-talk-estimate (ETE) method, developed a list of items and correspondent statements on the identified topic. Seven conclusive items were identified with 12 statements about the chosen topic, radiotherapy in metastatic hormone sensitive prostate cancer on primary tumour and metastatic sites. This consensus might help clinicians in prostate cancer managing in daily clinical practice.

Two decades of advances in clinical oncology - lessons learned and future directions.

Two decades of advances in clinical oncology - lessons learned and future directions.

The more you test, the more you find: Expansion of routine urine drug screening facilitated through an embedded palliative care clinic in thoracic oncology.

194 Background: Consensus guidelines strongly recommend urine drug screening (UDS) for all patients receiving opioids for cancer pain management. However, implementation of UDS in oncology clinics is underreported. The primary aim of this study was to evaluate incidence of unexpected UDS results among patients with lung cancer after implementation of confirmatory UDS in a thoracic oncology clinic. Methods: This is a single-institution retrospective study of UDS results among patients diagnosed with any stage thoracic malignancy before and after expansion of chromatography-based UDS facilitated by a palliative care provider embedded in a thoracic medical oncology clinic. Patients were included if their first UDS was collected during the year prior to (pre-intervention) or during the 12 months after (post-intervention) opening of the embedded Thoracic Onco-Palliative Clinic on September 5, 2018. In the pre-intervention period, UDS was routinely ordered for only patients referred to a standalone palliative care clinic. This 2-step UDS includes immunoassay and chromatography-based testing followed by interpretation of results by a specialty-trained palliative care clinical pharmacist. In the post-intervention period, UDS was expanded to include any patient seen by Thoracic Medical Oncology regardless of palliative care referral status. A Kaplan-Meier curve and log-rank test were used to compare time to first unexpected UDS between cohorts. Results: More patients had UDS testing in the post-intervention (n = 182) versus pre-intervention (n = 61) period. A higher volume and proportion of patients had unexpected UDS results in the post-cohort (25/182; 13.7%) compared to pre-cohort (6/61; 9.8%), although this difference was not statistically significant (p = 0.43). The number of UDS tests per patient was significantly higher (p &lt; 0.01) in the post-cohort (mean (SD): 2.4 (2.7)) vs. pre-cohort (1.5 (1.3)). A larger proportion of pre-cohort patients completed only one UDS during the study period (pre: 73.8% (45/61); post: 53.3% (97/182); p &lt; 0.01). In the post-cohort, 58 (31.9%) patients completed UDS ordered by oncology team prior to palliative care referral compared to 0 patients in the pre-cohort; 29 (21.4%) patients completed UDS without receiving outpatient palliative care compared to 0 patients in the pre-cohort. Kaplan-Meier curves for the pre- and post-cohorts were similar during the first 6 months of drug screening (p = 0.7) and diverged after 6 months, with a higher probability of detecting an unexplained UDS in the post cohort at 24 months (Pre: 15.0%; Post: 40.0%). Conclusions: Implementation of confirmatory UDS in a thoracic oncology clinic facilitates closer monitoring for nonprescribed substance use during opioid management and continued detection of unexpected UDS results up to 24 months.

Improving the detection and documentation of patients’ symptoms in an integrated gastrointestinal oncology and palliative care clinic.

336 Background: Patients with gastrointestinal (GI) malignancies experience a high burden of disease-related symptoms and treatment side effects. We established an integrated GI oncology and palliative care (PC) clinic in which a PC physician is co-located with the oncology team and can provide timely response to patient distress and facilitate communication with the interdisciplinary palliative care team. Yet, even in the integrated clinic, patient symptoms were unreliably assessed, leading to missed opportunities to address patient suffering. Between October 2023 and January 2024 for patients seen in-person in the integrated clinic for oncology or PC visits, the median rate of symptom documentation was 45%. Emotional, financial, and spiritual distress documentation rates were lowest. We hypothesized that by implementing a systematic, comprehensive patient-reported symptom assessment tool, we could increase the detection and documentation of symptoms, and in turn, improve communication around patient distress and timely response to symptoms. Methods: We measured the rate of symptom documentation (primary outcome) and the use of a patient-reported symptom assessment tool for adults with GI cancers seen in-person in the integrated clinic in Spring 2024. Based on the Edmonton Symptom Assessment Scale (ESAS) and expert consensus, we determined which symptoms were most important to identify. Documentation rates were assessed via manual chart review of visit notes and flowsheet data. Prospective post-intervention data (March to May 2024) were compared to retrospective pre-intervention baseline data (October 2023 to January 2024). Interventions included modification of the ESAS to include GI oncology-specific symptoms, implementation of the tool in paper format to encourage patient-clinician communication, frequent staff education and feedback sessions, creation and dissemination of a resource guide for clinicians to respond to identified distress, and patient satisfaction surveys. Results: 126 patients were included in the study (31 pre-intervention and 95 post-intervention). During the post-intervention period, the median rate of symptom documentation increased from 45% to 83% and the median rate of ESAS survey completion increased from 9% to 68%. Documentation of financial and spiritual distress increased from 13% to 71%, for both, and documentation of emotional distress increased from 35% to 72%. On satisfaction surveys (N=20), most patients reported the tool was helpful in sharing their symptoms (70%), was easy to read and understand (100%), and that their clinician was engaged in addressing their symptoms (67%). Conclusions: The implementation of a patient-reported symptom assessment tool in an integrated GI oncology/PC clinic increased documentation of important symptoms, potentially increasing clinician awareness of patient distress.