Treatment Regimens Research Articles

Sleep in hospitalized children with cancer: relationship with psychiatric disorders and hospital conditions

Background. Children with cancer often undergo prolonged and recurrent hospitalization, which leads to an increased incidence of sleep disruptions and psychiatric disorders. This study aimed to objectively quantify the prevalence of sleep disruptions in hospitalized pediatric oncology patients and to determine the effects of psychiatric disorders, treatment regimens, and hospital conditions on sleep patterns. Method. This cross-sectional study included 39 children who were undergoing treatment and monitoring in the pediatric oncology inpatient service. Parents completed questionnaires providing information about their child’s sleep patterns, quality of life, and hospital conditions. The children were monitored for five days using actigraphy to record sleep parameters. They were evaluated with a semi-structured interview form (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version-DSM 5-Turkish Adaptation) for psychiatric diagnoses. Results. Sleep disruptions were identified in 27 (69.2%) children with cancer. In addition to adjustment disorder and anxiety disorder psychiatric diagnoses, behavioral problems and emotional symptoms were more common in the group with sleep disruptions. Actigraphy measurements indicated that poor sleep was associated with younger age, recent cancer diagnosis, specific phobias, depression, daytime napping, and frequent vital sign assessments. Conclusion. Sleep problems in hospitalized children with cancer are linked to psychiatric comorbidities, treatment routines, and hospital conditions. By recognizing psychiatric symptoms and optimizing hospital conditions that affect sleep, healthcare providers can enhance the quality of sleep for these children.

Abstract B020: A blood-based multi-omics test for early evaluation of lymphoma treatment effectiveness

Abstract Introduction: The standard clinical assessment for treatment response of lymphoma currently relies on periodic functional imaging examinations. In this prospective study, we utilized a blood-based multi-omics test, SeekInClarity, to evaluate treatment response and predict patient outcomes in the major types of lymphoma. Methods: 116 patients with various lymphoma subtypes were recruited from two clinical centers: The First Affiliated Hospital of Zhengzhou University and Sun Yat-sen University Cancer Center. Blood samples were collected at pre- treatment (baseline) and after two cycles of treatment (landmark) for SeekInClarity analysis, which integrated shallow whole-genome sequencing (sWGS) data of circulating-free DNA (cfDNA), including copy number aberrations (CNA) and fragment size (FS), with seven protein markers. The molecular tumor burden (MTB) score was calculated with SeekInClarity to assess the therapeutic efficacy of patients. Results: At 95.2% specificity, cancer signals were detected in 74.1% (86/116) of patients at baseline. Higher MTB scores were associated with advanced tumor stages, with MTB+ ratios of 31.8%, 63.6%, 84.6%, and 91.2% for stage I, II, III, and IV, respectively. After two cycles of treatment, patients with MTB+ status exhibited significantly poorer progression-free survival (PFS) (HR: 0.13, 95% CI, 0.05-0.33, P < 0.001) and overall survival (OS) (HR: 0.24, 95% CI, 0.06-0.97, P < 0.05) compared to MTB- patients. These trends were consistent across stages, subtypes, and treatment regimens. Traditional biomarkers, lactate dehydrogenase (LDH) and β2-microglobulin (B2M), showed no OS difference between high and low expression groups. The disease progression (PD) rate was 5.2 times higher in the MTB+ group (41.5%) than in the MTB- group (8.0%, P < 0.001), outperforming LDH (1.1 times, 20.7% vs 18.1%, P = 0.15) and B2M (3.1 times, 43.8% vs 14.0%, P = 0.02). All 116 patients, except four with stable disease, were classified as partial or complete response based on imaging at the landmark analysis. However, 13 patients experienced disease progression within six months after treatment. Notably, six (46.2%) were identified earlier through MTB reduction at the landmark. Greater MTB reduction at landmark associated with better OS (P<0.05). Multivariate Cox regression analysis confirmed MTB reduction at landmark as an independent prognostic indicator for PFS, with low reduction indicating a significant increase in disease progression (HR: 0.11, 95% CI: 0.03-0.42, P < 0.001), while other clinical parameters were not significant. Conclusions: This study confirms the clinical utility of SeekInClarity in evaluating lymphoma treatment responses. Reductions in MTB during treatment are associated with patient survival and can predict therapeutic outcomes. Furthermore, post-treatment MTB status after two cycles is an independent prognostic indicator for both PFS and OS. Citation Format: Mao Mao, Wang Xin hua, Li Zhi ming, Chang Yu, Li Shi yong, Wu Wei, Chang Fang yuan, Chang Yin yin, Zhu Dan dan, Zhang Ming zhi. A blood-based multi-omics test for early evaluation of lymphoma treatment effectiveness [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B020.

Cost-effectiveness analysis of trifluridine/tipiracil combined with bevacizumab vs. monotherapy for third-line treatment of colorectal cancer

BackgroundThe combination of trifluridine/tipiracil (FTD/TPI) and bevacizumab has demonstrated promising efficacy and safety in the treatment of colorectal cancer (CRC). This study aims to evaluate the cost-effectiveness of trifluridine/tipiracil combined with bevacizumab vs. trifluridine/tipiracil monotherapy as a third-line treatment regimen for colorectal cancer within the Chinese healthcare system, providing an economic basis for clinical application.MethodsBased on data from the SUNLIGHT Phase III clinical trial, a dynamic Markov model was constructed with a cycle length of 4 weeks and a simulation duration of 10 years. Direct medical costs and quality-adjusted life years (QALYs) were calculated. The incremental cost-effectiveness ratio (ICER) was compared with the willingness-to-pay threshold (WTP = ¥268,200.00/QALY) to assess the economic viability of the treatment regimen. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to verify the robustness of the model results.ResultsThe cost of trifluridine/tipiracil combined with bevacizumab treatment (¥838,492.74) was higher than that of trifluridine/tipiracil monotherapy (¥357,396.97), with greater health benefits (2.45 QALYs vs. 1.54 QALYs). The ICER was ¥527,577.36/QALY, exceeding the willingness-to-pay threshold. One-way sensitivity analysis indicated that drug costs and utility values during the progression-free period significantly impacted model outputs. Probabilistic sensitivity analysis further confirmed the robustness of the results, showing that at a willingness-to-pay threshold of ¥494,000.00, the probability of the combined treatment being cost-effective was 50%.ConclusionTrifluridine/tipiracil combined with bevacizumab, as a third-line treatment for colorectal cancer, does not have a cost-effectiveness advantage compared to trifluridine/tipiracil monotherapy in economic evaluations.

Abstract B050: Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities

Abstract We have developed a version of our "methylation DETection of Circulating Tumour" DNA (mDETECT) assay that is able to sensitively and quantitatively monitor Non-Small Cell Lung Cancer (NSCLC). We used this assay to frequently assess the tumour burden of a small cohort (17 individuals) of patients undergoing first line monotherapy with pembrolizumab for metastatic disease. Patients were tested weekly or biweekly in the period immediately after initiation of treatment with radiological assessment being done at approximately 3 months. Radiologically non-responding patients showed constant or increased mDETECT levels over the 3 month time frame. Responding patients showed 2 different patterns, with some showing dramatically increasing mDETECT levels for a short period of time followed by a rapid decrease. Other responders showed an immediate decrease within the first few week of treatment. In both responder groups these decreases were associated with a longer term response. Continued monitoring did reveal eventual progression in some of these patients with increasing mDETECT levels being seen 4 to 6 months before radiological changes. In some non-responding patients complex responses were seen, with mDETECT levels varying significantly over time. In one non-responding patient the addition of carboplatin to their treatment regime did produce a temporary improvement in their mDETECT levels. Frequent assessment of tumour burden by a liquid biopsy such as mDETECT offers the opportunity to rapidly determine a patient's response to therapy and potentially modify treatments to improve responses. Citation Format: Christopher R Mueller, Keira Parr, Mihaela Mates, Andrew Robinson, Harriet Feilotter, Keira Frosst. Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B050.

HPB SO17 - A rare case of Goblet cell adenocarcinoma of appendix presenting as primary ampullary tumour

Abstract Background Goblet cell adenocarcinoma (GCA), formerly known as goblet cell carcinoid,is a rare appendiceal tumour with amphicrine differentiation that has distinct morphologic and clinical features compared to carcinomas seen elsewhere in the gastrointestinal tract. The tumour histologically resembles both carcinoids and adenocarcinomas. It is found in 0.3–0.9 % of appendectomy specimens; hence, ampullary GCAs are exceptionally uncommon. Method A 57-year-old Caucasian male presented with a two-month history of weight loss, pruritus, and dark urine. His blood tests revealed deranged liver enzymes. His past medical history was unremarkable. Abdominal CT identified a double duct sign, no detectable mass. Endoscopic ultrasound (EUS) revealed a dilated biliary system terminating in a slightly enlarged ampulla (15mm) without any obvious mass lesions. Endoscopic retrograde cholangiopancreatography (ERCP) was performed showing a distal common bile duct (CBD) stricture. Cytology samples were negative for malignancy, and stents were placed in the CBD and pancreatic duct (PD). Pancreaticoduodenectomy was advised given the high risk of malignancy. Results Histopathology report showed clusters of goblet-like mucinous cells in an infiltrative pattern, in addition to classic neuroendocrine tumor morphology, reminiscent of goblet cell adenocarcinoma of the appendix, staged as pT3pN1M0. This is consistent with primary ampullary GCA given the normal appendix on preoprative CT imaging. Conclusion To our knowledge, this is the fourth case of ampullary GCA report in medical literature. There is no consensus on adjunct chemotherapy regimen for systemic treatment. Chicago consensus group (2018) recommends following the colorectal cancer pathway for goblet cell adenocarcinoma. In our experience, given the anatomical location of the tumour and the normal appendix, FOLFIRINOX was offered in line with ampullary adenocarcinoma cancer pathway.

OGC SO15 - Utility of radiological re-staging following neo-adjuvant chemotherapy and its impact on oncological outcomes in resectable gastric adenocarcinoma

Abstract Background The current perioperative chemotherapy regimen that comprises the multimodal treatment strategy for gastric cancer consists of Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel. Despite improvement in outcomes at a population level, real-world data suggests that ≤40% of patients show a poor/no response to the neoadjuvant phase of treatment. Identification of these poor/non-responders may facilitate a re-evaluation of their treatment strategy and prevent potentially futile surgery. Radiological re-staging following neoadjuvant treatment is routinely performed despite its debatable accuracy and benefits. This study aimed to define the accuracy of radiological re-staging and its impact on survival following neoadjuvant treatment for resectable GC. Method Patients with resectable gastric cancer who completed 4 cycles of neoadjuvant FLOT and underwent resectional surgery with curative intent between 2018 and 2022 were retrospectively identified. All patients were clinically staged with gastroscopy, CT and staging laparoscopy. The index radiological/clinical stage at diagnosis was compared to the radiological re-staging following neoadjuvant treatment. Patient were re-staged with either a CT or PET-CT. Both were then compared with the final pathological stage to assess for correlation between the radiological and pathological stage. A survival analysis was then performed to evaluate the impact of radiological-pathological staging discrepancy on overall survival Results A total of 65 consecutive patients met the inclusion criteria of this study. On comparison of the index clinical stage with the radiological re-stage post-neoadjuvant treatment, 71% had concordant stages, 25% were downstaged, and 4% were upstaged. On comparison of the index clinical stage with the final pathological stage, 35% had concordant stages, 38% were upstaged and 27% were down staged (Cohen kappa = -0.224, 95% CI -0.390, -0.058). Discrepancy between clinical stage and radiological re-stage did not influence survival. However, discrepancy between clinical and pathological stage highlighted survival differences where upstaged patients had reduced survival (p = 0.018). Conclusion The accuracy of clinical staging compared to final pathological staging in the setting of aggressive tumour biology remains undefined. Radiological re-staging following neoadjuvant treatment proves to be an unreliable tool for assessing treatment response and does not predict long-term survival outcomes. These findings highlight the importance of accurate staging and the need for more precise methods of evaluating treatment response. This may enhance decision-making, individualise treatment regimens, and improve patient outcomes.

Metabolic dysfunction-associated steatotic liver disease: a key factor in hepatocellular carcinoma therapy response

The conceptual evolution of non-alcoholic fatty liver disease (NAFLD) to what, since 2023, is called metabolic dysfunction-associated steatotic liver disease (MASLD) not only represents a change in the classification and definition of the disease but also reflects a broader understanding of this heterogeneous condition, which still with many aspects to refine. Although the definition of NAFLD can be interchanged to a high percentage with the new MASLD concept in different aspects, MASLD has been proposed as a relevant factor that influences the response to new immunotherapeutic treatments in the management of MASLD-related hepatocellular carcinoma (HCC), compared to HCC of other etiologies. This indicates that the etiology of HCC plays a relevant role in the prognosis, highlighting the urgency of evaluating treatment regimens for this subgroup of patients in upcoming clinical trials. A better understanding of the pathophysiology of MASLD generates strategies that not only aid in its management but also provide strategies to directly intervene in the carcinogenesis of HCC.

Real-world analysis of the incidence and risk factors of pneumonitis in non-small cell lung cancer patients treated with combined thoracic radiotherapy and immunotherapy

Abstract Objectives Combining radiotherapy with immune checkpoint inhibitor (ICI) treatment has emerged as an important therapeutic regimen. However, this combined treatment may increase the risk of pneumonitis. The aim of this study is to analyze the incidence and risk factors for pneumonitis in non-small cell lung cancer (NSCLC) patients receiving combined thoracic radiotherapy and ICI (RT + ICI) treatment in the real-world clinical setting, offering a reference and guidance for clinical physicians. Methods This study identified 447 patients with pathologically confirmed NSCLC at West China Hospital of Sichuan University from 2016 to 2021. Clinical characteristics, treatment regimens, immune-related adverse events (irAEs), and hematological data were collected and analyzed. Results Patients receiving combined RT + ICI treatment had a higher risk of developing pneumonitis than those receiving ICI treatment alone (26.9 vs. 6.7 %, p<0.001). The multivariate logistic analysis identified the following independent risk factors for pneumonitis in patients undergoing combined RT + ICI treatment: history of lung disease (p=0.032), first-line ICI treatment (p=0.001), anti-PD-L1 instead of anti-PD-1 treatment (p=0.035), and the development of immunotherapy-related thyroid dysfunction (p=0.019). The independent risk factors were incorporated into a nomogram to predict the incidence of pneumonitis. The area under the receiver operating characteristic curve is 0.727, suggesting an acceptable predictive efficacy. Conclusions Compared to ICI monotherapy, NSCLC patients receiving the combination of thoracic radiotherapy and ICI treatment are at higher risk of developing pneumonitis. The nomogram holds promise for facilitating the risk assessment and early identification of pneumonitis in NSCLC patients receiving combined RT + ICI treatment.

The Potential Health Risks and Benefits of Progesterone in the Transgender Woman Population—A Narrative Review

Introduction: Currently, progesterone is notably absent from conventional feminizing hormone therapies for transgender women. Anecdotal reports indicate the potential for health advantages following the incorporation of progesterone into treatment regimens. The primarily female hormone, progesterone naturally surges in women during the menstrual luteal phase. When administered exogenously, it may expedite bodily changes that are pivotal for gender transition. Progesterone holds promise as a potential remedy for various health conditions prevalent in the transgender woman population. Methods: This narrative review synthesizes existing literature and presents a comprehensive account of the administration of exogenous progesterone in transgender women. A literature search was conducted using the PubMed, Embase, ScienceDirect, and ResearchGate databases. The following keywords were used in the search: progesterone, transgender, breast neoplasms, lactation, prostate, testicular neoplasms, and thrombosis. These terms were combined using Boolean operators. The results of the initial search were screened by three independent reviewers based on their relevance to the topic under study. Results: A total of 104 studies were initially identified as meeting the criteria for inclusion. Following an assessment based on the contents of the title, abstract, and full text, 39 studies were deemed eligible for inclusion. A critical examination of health outcomes was conducted across key sections, including breast development, mental health, lactation, cancer risk (breast and prostate), thrombosis, and nervous and other systems. Discussion: The use of progesterone in the transgender woman population is a topic that has yet to be sufficiently researched. The limited sample size, short follow-up periods, and lack of randomization restrict the potential for achieving a robust scientific evidence base. In order to gain a fuller understanding of this topic, findings from studies on contraception, hormone replacement therapy, and animal models were considered. Conclusions: Progesterone may have a beneficial effect on the bodies of transgender women without significant adverse health effects. Further investigation through well-designed studies is recommended. Randomized controlled trials that include various dosages, broad and long-term effects, and precise demographics are needed. There is an immediate need for more knowledge to create appropriate patent and clinical practice guidelines.

Angiosarcoma of the Breast: Case Report

Angiosarcoma is a rare and aggressive tumor of the breast arising from endothelial cells. It is usually associated with chronic lymphedema or radiation therapy. The diagnosis is made by biopsy and there is no specific finding on mammography. In this study, we report a 59-year-old woman with a history of radiotherapy for invasive ductal carcinoma who subsequently developed primary angiosarcoma of the breast. Angiosarcoma of the breast was first documented in 1887 and is classified as primary and secondary. While surgical R0 resection is recommended for the treatment of these tumors with unclear etiology, the significance of axillary lymph node dissection remains uncertain. Adjuvant radiotherapy has been shown to reduce the local recurrence rate, but adjuvant chemotherapy and radiotherapy have no significant effect on 5-year survival. Although there is no consensus on treatment regimens, it is concluded that more comprehensive studies should be conducted in a larger sample.

Clinical diagnosis and treatment of lung cancer combined with interstitial lung disease

Lung cancer and interstitial lung disease have similar risk factors and pathogenesis. The incidence of lung cancer associated with interstitial lung disease is increasing, and the problem of comorbidity has gradually attracted attention. Early diagnosis of lung cancer associated with interstitial lung disease is difficult, there are many factors influencing treatment, and the prognosis is poor. Interstitial lung disease affects the treatment options for lung cancer in comorbid patients, and lung cancer treatment will increase the risk of acute exacerbation of interstitial lung disease in comorbid patients. For patients with early-stage lung cancer complicated with interstitial lung disease who have surgical indications, the surgical method and extend of resection should be determined on the basis of MDT according to tumor stage and lung function. For patients with early-stage lung cancer combined with interstitial lung disease who are not suitable for surgery, the benefits and risks of complications of the radiotherapy should be weighed, and the appropriate radiotherapy regimen and dose should be selected. Chemotherapy is an effective treatment for patients with advanced lung cancer complicated with interstitial lung disease. Some chemotherapy regimens cause acute progression of interstitial lung disease, and the choice of chemotherapy regimen is particularly important. For lung cancer patients with interstitial lung disease who are positive for driver gene mutations, targeted drugs with low pulmonary toxicity should be selected. Patients with lung cancer combined with interstitial lung disease may benefit from immunotherapy, but the risk of immune-related pneumonia is increased. The occurrence of adverse reactions should be closely monitored during immunotherapy. In the future, more prospective clinical trials are needed to formulate reasonable and effective treatment regimens for lung cancer combined with interstitial lung disease to achieve a better prognosis.

Abstract 4139191: ETX-258 - A GalOmic™ siRNA for the Treatment of Heart Failure Following Myocardial Infarction

Introduction: Heart failure with reduced ejection fraction (HFrEF) remains a significant clinical challenge, evidenced by high hospitalization rates and five-year mortality. Current treatments are limited by side effects, poor patient compliance, and the necessity for gradual drug titration. These challenges highlight the need for new therapies that are both safe and effective in targeting the structural remodeling pivotal to disease progression post-myocardial infarction (MI). e-therapeutics (ETX) uniquely combines computation and RNAi to discover life-transforming medicines. ETX’s RNAi platform, GalOmic™, enables generation of specific, potent, and long-acting siRNA therapies that effectively silence novel gene targets in hepatocytes. This highly specific mechanism of action limits unwanted side effects, positioning it as a promising approach to HFrEF treatment. Methods: Potent siRNAs against a hepatic target with cardioprotective potential were designed in silico. Candidate siRNAs were screened in vitro in HEK293 cells and in vivo in C57BL/6J mice to select the lead GalOmic™ siRNA, ETX-258. MI was induced by ligation of the left anterior descending artery in C57BL/6J mice after which ETX-258 was injected subcutaneously weekly for 6 weeks. Eplerenone, a mineralocorticoid receptor antagonist which is part of the current treatment regimen for HFrEF, was used as a comparator. Cardiac function was assessed by echocardiography at 2-, 4- and 6-weeks post-MI. Cardiac damage and structural remodeling were evaluated using circulating biomarkers of cardiac function and histological assessment. Results: ETX-258 was selected as a highly active siRNA for the treatment of heart failure with a long duration of action. Post-MI treatment with ETX-258 significantly improved key echocardiographic parameters of cardiac function, including ejection fraction and total cardiac output, achieving results comparable to eplerenone. Additionally, both structural cardiac parameters and markers of damage and remodeling showed significant improvements, reaching similar levels in both ETX-258 and eplerenone-treated mice. Conclusions: High unmet need remains for HFrEF patients despite existing therapies. These results highlight the potential of ETX-258 to improve cardiac function and pathogenic structural remodeling post-MI. This, paired with the long duration of action and favorable safety profile of GalOmic™ siRNAs, makes ETX-258 a promising candidate for further clinical development.

Differential Replication and Oncolytic Effects of Zika Virus in Aggressive CNS Tumor Cells: Insights from Organoid and Tumoroid Models

Central nervous system (CNS) cancers are responsible for high rates of morbidity and mortality worldwide. Malignant CNS tumors such as adult Glioblastoma (GBM) and pediatric embryonal CNS tumors such as medulloblastoma (MED) and atypical teratoid rhabdoid tumors (ATRT) present relevant therapeutic challenges due to the lack of response to classic treatment regimens with radio and chemotherapy. Recent findings on the Zika virus’ (ZIKV) ability to infect and kill CNS neoplastic cells draw attention to the virus’ oncolytic potential. Studies demonstrating the safety of using ZIKV for treating malignant CNS tumors, enabling the translation of this approach to clinical trials, are scarce in the literature. Here we developed a co-culture model of mature human cerebral organoids assembled with GBM, MED or ATRT tumor cells and used these assembloids to test ZIKV oncolytic effect, replication potential and preferential targeting between normal and cancer cells. Our hybrid co-culture models allowed the tracking of tumor cell growth and invasion in cerebral organoids. ZIKV replication and ensuing accumulation in the culture medium was higher in organoids co-cultured with tumor cells than in isolated control organoids without tumor cells. ZIKV infection led to a significant reduction in tumor cell proportion in organoids with GBM and MED cells, but not with ATRT. Tumoroids (3D cultures of tumor cells alone) were efficiently infected by ZIKV. Interestingly, ZIKV rapidly replicated in GBM, MED, and ATRT tumoroids reaching significantly higher viral RNA accumulation levels than co-cultures. Moreover, ZIKV infection reduced viable cells number in MED and ATRT tumoroids but not in GBM tumoroids. Altogether, our findings indicate that ZIKV has greater replication rates in aggressive CNS tumor cells than in normal human cells comprising cerebral organoids. However, such higher ZIKV replication in tumor cells does not necessarily parallels oncolytic effects, suggesting cellular intrinsic and extrinsic factors mediating tumor cell death by ZIKV.

An approach to reduce inhaler errors using Donabedian's triad

Inhaler errors inversely affect the outcome of respiratory diseases. Inhaler devices, such as the metered-dose inhalers (MDI) and dry powder inhalers (DPI), are commonly used in treating respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD), and incorrect use of these devices can result in suboptimal treatment outcomes, increased probabilities of hospitalizations or admissions, and poorer quality of life. Patient related factors to inhaler errors include age, cognitive and physical abilities, education, language barriers, and preferences. Device-related factors such as inhaler design and operational complexity can also lead to errors. Finally, factors related to healthcare professionals (HCP) such as competency, level of knowledge in disease and inhaler device and availability to educate patients, can play a role in inhaler error. Quality management is a potential solution to this problem. Quality improvement strategies towards addressing inhaler misuse can increase patient satisfaction and improve patient outcomes. Donabedian's triad, which includes structure, process, and outcome can be utilized in developing a framework for reducing inhaler errors. Institutional solutions are more towards the structural and process changes in the triad, such as HCP training, checklists on training efficacy, provision of action plans, and availability of staff to educate and train patients. Patient-centered solutions focus more on process and outcome domains, such as improvement in lung functions, patient education, re-assessment and re-education of inhaler techniques, and adherence to treatment regimen. By focusing on structural and process domains, the quality of care can be enhanced, resulting in improved outcomes.

CTNI-49. PRECISION MEDICINE CLINICAL TRIAL FOR ADULT PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract Salvage therapies for recurrent glioblastoma (rGBM) have limited efficacy, with median overall survival of 9 months (OS-9) and 6-month progression-free survival (PFS-6) of 10-25%. Given GBM’s molecular heterogeneity, targeting a single molecular abnormality in isolation has consistently failed as a strategy, and precision combination approaches are needed. An initial 15-patient cohort evaluated the feasibility and safety of treating patients with rGBM with an individualized treatment regimen; we added a second 15-patient expansion cohort to improve the power of preliminary efficacy assessment. Patients underwent clinically indicated surgery with genomic profiling using the UCSF500 targeted DNA sequencing panel. Each personalized treatment regimen combined up to 4 FDA-approved drugs, including one cytotoxic agent, as determined by consensus discussion at an individualized molecular tumor board for each patient. Bevacizumab was not utilized in these combinations. The primary objective of the combined 30-patient cohort was efficacy of individualized treatment regimens by OS-9; secondary objectives included safety and additional efficacy measures including PFS-6. Median age was 53 years (range 32-71). Of 30 patients, 18 were male, 23 were enrolled at first recurrence, 29 had IDH-wildtype glioblastoma, 1 had IDH-mutant astrocytoma, and 10 had MGMT promoter methylation. A total of 12 FDA-approved drugs were used in 18 combinations; the most common regimen prescribed was lomustine, afatinib, and abemaciclib (7; 23%,); second-most common was temozolomide, olaparib, and afatinib (4; 13%). OS-9 of the combined cohort was 70% (95% CI 0.55 – 0.89) and PFS-6 was 27% (95% CI 0.15 – 0.48), with median OS of 11.6 months (95% CI 9.7 – 16.7) and median PFS of 3.7 months (95% CI 2.0 – 5.5).While overall efficacy was modest, implementation of individualized treatment regimens in a timely fashion was safe and feasible for patients with surgically resectable rGBM. Analysis is ongoing to assess whether specific genomic profiles or treatment regimens were particularly efficacious.

Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis

Background. The main approach in the treatment of patients with uterine leiomyosarcoma is surgery followed by chemotherapy, which is the basis of treatment. Febrile neutropenia (FN) is a life-threatening condition, so the use of granulocyte colony-stimulating factor (G-CSF) after each cycle of chemotherapy in this category of patients remains an integral part. Aim. To evaluate the pharmacoeconomic efficacy of the use of short and long-acting G-CSF forms in a round-the-clock inpatient facility (RIF). Materials and methods. A retrospective analysis of economic expenditures was performed at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine in the RIF setting for the period from January 2018 to December 2023 for the treatment of 62 patients with high-grade uterine leiomyosarcomas of stage IB–IVA according to the classification of the International Federation of Gynecology and Obstetrics (2009). All patients underwent surgical treatment, complete hysterectomy with appendages, followed by antitumor drug therapy with a high risk of FN. In the economic cost analysis, the treatment regimens gemcitabine 900 mg/m2 on day 1 and day 8 + docetaxel 100 mg/m2 + empegfilgrastim (regimen code sh1207.1) and gemcitabine 900 mg/m2 on day 1 and day 8 + docetaxel 100 mg/m2 + filgrastim (regimen code sh1070) were compared. The costs of clinical blood tests and staying in RIF were also considered. Results. The stay in the RIF was 9 bed days with a long-acting G-CSF regimen and 15 days with a short-acting G-CSF regimen. When using a treatment regimen with filgrastim in 6 patients, the number of bed days increased to 18 due to persistent neutropenia. No FN events were reported. The calculations consisted of the cost of a bed day in the RIF (1,660 rubles) and purchasing of short- and long-acting G-CSF, without the cost of the main therapy. The costs of treating patients with short-acting G-CSF were comparable to those with long-acting G-CSF. Conclusion. The regimen with long-acting G-CSF is effective, easy to use, and cost-effective in RIF settings.

Impact of Persistent Alopecia on Quality of Life in Childhood Cancer and Transplant Survivors

ABSTRACTBackgroundWhile alopecia associated with chemotherapy, radiation, or hematopoietic stem‐cell transplant (C/R/HSCT) is transient in most children, prior reports indicate nearly one in seven childhood cancer survivors suffer from persistent alopecia after their treatment is completed. The objective of our study was to better characterize the impact of C/R/HSCT‐associated persistent alopecia on patient quality of life.ProcedureA cross‐sectional cohort study of patients with a history of C/R/HSCT who were seen at Dana Farber Cancer Institute/Boston Children's Hospital Dermatology from August 2023 to February 2024 for any indication was conducted. Patients who completed their C/R/HSCT treatment regimen >6 months prior to visit were invited to fill out a survey on patient experience with persistent alopecia, including a modified Children's Dermatology Life Quality Index (CDLQI). Participants also underwent a full scalp examination.ResultsTwenty one out of 47 (44.7%) patients in our cohort self‐reported persistent alopecia. For nine additional patients, alopecia was not self‐reported but noted by a dermatologist on exam. Median self‐reported alopecia severity was 3 (interquartile range [IQR] 2–5.25) on a visual analog scale of 1–10. The most common pattern of alopecia was diffuse thinning. Median CDLQI score was 5 (IQR 2–7) for those with persistent alopecia, indicating a small negative effect of disease on patient quality of life. Fifteen (31.9%) patients report receiving information about persistent alopecia prior to their C/R/HSCT.ConclusionsNearly half of childhood cancer and transplant survivors evaluated by dermatology suffered from persistent alopecia, which negatively impacted their quality of life. Better counseling on persistent alopecia should be provided to childhood cancer patients.

THE IMPACT OF ANTICOAGULANTS ON COAGULATION PARAMETERS IN THE TREATMENT OF PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA ASSOCIATED WITH COVID-19

The aim of the study was to evaluate the effect of anticoagulants on coagulation parameters in the treatment of patients with community-acquired pneumonia associated with coronavirus infection. Materials and methods. An open, prospective, observational study was conducted to achieve the research objectives. Between January 2021 and February 2022, 256 patients aged 40 to 65 years with community-acquired pneumonia were examined at the outpatient clinic of the Kherson City Clinical Hospital named after Athanasius and Olga Tropin of the Kherson City Council. Of these, 177 cases were associated with SARS-CoV-2, while 79 patients tested negative for coronavirus infection. Additionally, thirty-five healthy individuals were examined on an outpatient basis. After randomization, 143 hospitalized patients with severe community-acquired pneumonia associated with COVID-19 were divided into subgroups based on the anticoagulant used in their treatment regimen. The first subgroup consisted of 71 patients who received standard heparin infusions, while the second subgroup included 72 patients treated with enoxaparin. Results. The prothrombin time in the group of healthy volunteers was 12.60 [11.80; 13.30] seconds, and the median value was significantly higher by 13.5% compared to both the group of patients with community-acquired pneumonia associated with COVID-19 and the group without COVID-19 (p < 0.05). The median fibrinogen level in patients with COVID-19 and community-acquired pneumonia was 4.80 [4.50; 5.40] g/L, which did not significantly differ from the 4.60 [4.30; 5.40] g/L in the non-COVID-19 pneumonia group (p > 0.05). However, a significant difference was observed when compared to the healthy volunteer group, which had a fibrinogen level of 3.30 [2.50; 3.80] g/L (p < 0.05). After 72 hours of treatment, prothrombin time was significantly higher in the first subgroup (12.00 [11.00; 13.00] seconds) compared to the second subgroup (11.30 [10.00; 12.30] seconds) (p < 0.05). There was also a statistically significant difference in the international normalized ratio (INR) levels between the subgroups after 72 hours of treatment, with the first subgroup showing an INR of 1.20 [1.10; 1.30] U, versus 1.10 [1.00; 1.30] U in the second subgroup (p < 0.05). After 14 days of treatment, fibrinogen levels showed a statistically significant difference: 4.30 [4.10; 4.60] g/L in the first subgroup compared to 4.50 [4.30; 4.90] g/L in the second subgroup (p < 0.05). Conclusion. In patients with community-acquired pneumonia, blood coagulation parameters are disturbed, characterised by a decrease in prothrombin time and activated partial thromboplastin time, as well as an increase in total fibrinogen levels. After 72 hours, heparin demonstrated a more effective effect on prothrombin time and international normalised ratio compared to enoxaparin. When assessing the dynamics of coagulation parameters after 14 days, heparin was found as was more effective in reducing the level of total fibrinogen compared to enoxaparin.

CTNI-71. RELA FUSION-POSITIVE EPENDYMOMA, DIFFUSE MIDLINE GLIOMA AND GRADE 4 IDH MUTANT ASTROCYTOMA TREATED WITH VAL-083 UNDER EXPANDED ACCESS: CASE REPORTS

Abstract RELA fusion-positive ependymoma is associated with supratentorial location, higher WHO grade and poor prognosis. Diffuse Midline Glioma (DMG) is a relatively rare CNS tumor, originating in the midline location of the brain. Surgical intervention is restricted to biopsy and radiation. Grade-4 astrocytoma, is highly aggressive with rapid progression. Standard treatment includes surgery and radiation therapy, with limited systemic options other than clinical trials for recurrent disease. VAL-083 is a DNA-targeting agent which rapidly induces inter-strand DNA cross-links at O6- and N7-guanine inducing double-strand breaks causing cell death and acts independent of MGMT DNA repair in high-grade gliomas. We report on 4 patients who had recent disease progression and unmethylated MGMT promoter status treated with VAL-083 under an expanded access program: Case #1: a 47-yo male diagnosed with IDHwt, RELA fusion-positive ependymoma. Case #2: an 18-yo male diagnosed with IDHwt, MAP2K1 and RELA fusion-positive ependymoma. Case #3: a 25-yo male diagnosed with IDHmut Grade 4 astrocytoma, with ATRX, INPP4A, RET and TP53 mutations. Case #4: a 21 yo male diagnosed with IDHwt DMG of the brain stem. All patients had multiple recurrences, received radiation and multiple systemic treatment regimens. They received VAL-083 (30 mg/m2 for 3 days every 21 days) under an expanded access program. Patients with ependymoma received 6 and 5 cycles of VAL-083, (case 1 and 2, respectively), while the patients with IDHmut Gr 4. astrocytoma and DMG received 5 and 18 cycles of VAL-083, respectively. No adverse events were reported and no dose reductions were required. These cases highlight that VAL-83 may be a treatment option for recurrent RELA fusion-positive ependymoma, Gr4. IDHmut astrocytoma, and DMG refractory to other treatment regimens. Additional outcomes related to these cases will be presented at the meeting. Clinicaltrials.gov Identifier: NCT03138629. The treatment plans for the EA patients were approved by MD Anderson Cancer Center IRB

TMET-24. MULTI-OMIC CHARACTERIZATION OF THE TEMPORAL METABOLIC ADAPTATIONS UNDERPINNING THERAPY RESISTANCE AND TUMOR RECURRENCE IN GLIOBLASTOMA

Abstract Therapy resistance and tumor recurrence are barriers to achieving long-term survival in cancer patients, particularly evident in glioblastoma (GBM), known for its dismal 5-year survival rate below 10%. Despite aggressive treatment regimens, including maximal resection, alkylating chemotherapy, and radiation, the majority of GBM patients experience relapse within 7-9 months post-initial intervention. Recurrent GBM poses surgical challenges and resists subsequent treatments, leading to an almost universally fatal outcome and an average survival of 12-18 months. Metabolic networks can serve as ancient stress-protection mechanisms that operate independently of genomic changes, offering an initial line of defense against exogenous pressures. Although the role of metabolism in cancer has gained prominence, our understanding of the metabolic adaptations following chemoradiotherapy and their contributions to therapy resistance and tumor recurrence in highly aggressive GBM tumors remains incomplete. We postulate that metabolic adaptations play a pivotal role in facilitating therapy resistance and GBM recurrence. Exploring the metabolic dependencies of these persistent cells may unveil vulnerabilities for therapeutic exploitation to counteract chemoradiotherapy resistance. We established clinically relevant patient-derived in vitro and in vivo models mirroring the standard GBM treatment protocol. Using state-of-the-art single-cell and bulk multi-omics technologies, we profiled the temporal transcriptomic and metabolomic adaptations from therapy-naïve primary GBM to chemoradiotherapy-resistant recurrent tumors. Our findings revealed unique metabolic transitions that occurred during chemoradiotherapy treatment in GBM cells that were conserved in vitro and in vivo across ten genetically diverse GBM patients. In a pre-clinical animal trial, a novel metabolism-targeting combinatorial treatment regimen prevented the emergence of recurrent tumors and significantly prolonged survival compared to chemoradiotherapy alone. Altogether, our results uncover distinct metabolic adaptations mediating therapy resistance and tumor recurrence in GBM. These findings emphasize the need to consider metabolic flexibility and dependencies for effective therapeutic strategies, offering potential avenues to overcome chemoresistance in recurrent GBM tumors.