Antineoplastic Regimens Research Articles

Survival outcomes, multidimensional prediction and subsequent therapy in patients with hormone receptor-positive advanced breast cancer receiving palbociclib: a real-world analysis.

To date, the overall survival (OS) of hormone receptor-positive advanced breast cancer (ABC) treated with palbociclib has not been reported in Chinese patients. It still remains unclear what kind of patients may benefit in OS from palbociclib treatment and what the optimal sequential antineoplastic regimen is for those progressing on palbociclib. Therefore, we aimed to investigate the OS outcome of ABC patients receiving palbociclib, establish a predictive model to identify the potential candidates who may benefit from palbociclib and explore the ideal subsequent treatment strategy after palbociclib. This is a single-center ambispective real-world analysis of palbociclib in hormone receptor-positive ABC from April 2018 to August 2021. The patients were followed up via telephone or clinic visit. Progression-free survival (PFS), OS, overall response rate and time to second disease progression (PFS2) were evaluated as prognosis outcomes. Cyclin-dependent kinases 4/6 inhibitor (CDKI) score was established to predict OS benefit on the basis of tumor burden, line of palbociclib treatment and tumor marker. Fifty patients were included with the median PFS of 9.57 months and the median OS of 33.60 months. Age <65 years [hazard ratio (HR) 0.33, P=0.008], lung or liver involvement (HR 3.01, P=0.005) and > first line palbociclib therapy (HR 2.13, P=0.03) were independent unfavorable prognosticators for PFS. Positive estrogen receptor (ER) (HR 0.22, P=0.004), metastatic sites <3 (HR 3.59, P=0.02), absence of lung or liver involvement (HR 3.77, P=0.058) and PFS ≥12 months during palbociclib regimen (HR 0.14, P<0.001) could predict longer OS. CDKI score discriminated OS significantly (HR 4.41, P=0.009) and the CDKI score-based models were multidimensionally verified with satisfying performance, among which the area under the curve of receiver operating characteristic reached 0.835 and the C-index was 0.72. Moreover, chemo-free regimens saw improvement in time to second disease progression (HR 0.32, P=0.006) and OS (HR 0.32, P=0.049) for patients progressing on palbociclib compared with chemotherapy-based regimens. CDKI score is a practical and comprehensive tool in predicting OS benefit for ABC patients treated with palbociclib, which deserves further validation. Patients who progressed on palbociclib seem to keep benefiting from chemo-free antineoplastic treatments. These findings may help identify the candidates for CDK4/6 inhibitor and optimize the strategies for hormone receptor-positive ABC.

Severe toxicities in amazonian populations and the role of precision medicine in acute lymphoblastic leukemia treatment.

Corticosteroids, such as prednisone or dexamethasone, constitute integral components of antineoplastic regimens for Acute Lymphoblastic Leukemia (ALL) therapy, albeit accompanied by significant adverse effects. The multifactorial nature of interindividual variability in drug response, encompassing genetic polymorphisms, underscores the complexity of pharmacotherapy outcomes. However, pharmacogenetic investigations hitherto have predominantly focused on cohorts of European and North American descent, thus limiting the generalizability of findings to populations with minimal representation. Indigenous populations in Brazil, particularly those inhabiting the Amazon region, exhibit a distinctive genetic heritage, predominantly characterized by Native American ancestry. These populations frequently manifest suboptimal therapeutic responses and elevated mortality rates following ALL treatment. Therefore, delineating the molecular signatures of genes implicated in the corticosteroid pathway within these indigenous cohorts assumes paramount importance. This study identified novel variants within genes associated with the glucocorticoid pathway in indigenous Amazonian populations and conducted comparative analyses of variant frequencies across diverse global populations. The findings underscore the genetic uniqueness of indigenous groups and highlight the potential impact of genetic factors on adverse responses to ALL treatment. Precision medicine approaches tailored to the genetic peculiarities of indigenous populations emerge as imperative strategies for optimizing therapeutic efficacy and mitigating treatment-related toxicities in these communities.

Abstract 4117922: The Role of Combined Renin Angiotensin Aldosterone System Inhibitors (RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer. Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software. Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P &lt; 0.0001; I2 = 0%). Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.

Incidence, characteristics, and clinical impact of serious adverse events in patients with breast cancer receiving antineoplastic treatment in the ambulatory setting.

Patients with breast cancer experience various types of adverse events (AEs) during their treatment journey. We aimed to evaluate the incidence, characteristics, and impact of serious AEs in breast cancer patients receiving antineoplastic treatment in the ambulatory setting. A 4-month prospective observational study that included patients with breast cancer treated in the chemotherapy infusion clinics. Patients were assessed for serious AEs, defined as any AE that resulted in a visit to the emergency department (ED) with or without hospital admission, or required any clinical intervention, which were considered as the addition of supportive medications or modifications to the treatment protocol. Characteristics of the patients and antineoplastic regimens as well as the type of AEs were recorded. During the study period, 1168 patients received 2547 cycles. The mean age was 50 ± 11.6 (SD) years and patients had received a median (IQR) of 3 (1-5) treatment cycles prior to enrollment. Among the study cohort, 465 patients(40%) developed at least one serious AE. A total of 660 (26%) cycles were associated with 757 AEs, which required ED visits, addition of supportive medications, and modifications to the treatment protocol in 58%, 29%, and 17% of the cycles, respectively. Most common AEs were musculoskeletal (n = 132, 17%) and gastrointestinal (n = 125, 16.5%). Taxane-based regimens were associated with the most AEs (n = 286, 38%). In a cohort of patients with breast cancer treated in the ambulatory setting, 4 out of 10 patients developed at least one serious AE during the study period. Future research should identify measures to reduce the incidence and severity of such complications.

Effect of polypharmacy and potentially inappropriate medications on physical functional decline among older adults with advanced cancer receiving systemic treatment.

Polypharmacy and potentially inappropriate medications (PIM) are common among older adults with advanced cancer, but their association with physical functional outcomes is understudied. This study aimed to estimate the risk of physical functional decline associated with medication measures in older adults with advanced cancer starting a new line of systemic treatment. This secondary analysis of GAP 70+ Trial (PI: Mohile) enrolled patients aged 70+ with advanced cancer, had ≥ 1 geriatric assessment domain impairment and planned to start a new antineoplastic regimen with a high risk of toxicity. Polypharmacy (concurrent use of ≥ 8 medications (meds)) was assessed before initiation of treatment. PIM were categorized using Screening Tool of Older Person's Prescriptions (STOPP) criteria and 2019 Beers criteria. Physical functional outcomes were assessed within 3months of treatment initiation: (1) Activity of Daily Living (ADL) decline: 1-point decrease in ADL score between baseline and 3months; (2) Instrumental ADL (IADL) decline: 1-point decrease in IADL score between baseline and 3months; (3) Short physical performance battery (SPPB) decline, defined as 1-point decrease on SPPB; (4) ≥ 1 falls within 3months of treatment. Separate multivariable, cluster-weighted Generalized Estimating Equations models adjusted for relevant covariates (e.g., age, baseline function/comorbidities). Among 616 participants, mean number of meds was 6 (range 0-24); 28% received ≥ 8 meds. Polypharmacy was associated with increased risk of ADL decline (adjusted risk ratio [aRR], 1.31; 95% CI, 1.00-1.71). Taking ≥ 1 PIM per STOPP was associated with increased risk of IADL decline (aRR, 1.21; 95% CI, 1.04-1.40) and falls (aRR, 1.93; 95% CI, 1.49-2.51). In a large cohort of vulnerable older adults with advanced cancer receiving systemic treatment, polypharmacy and PIM were independently associated with an increased risk of physical functional decline. This emphasizes the need to develop interventions to optimize medication use, intending to improve outcomes in these patients. ClinicalTrials.gov Identifier: NCT02054741. Registered 01-31-2014.

Chemotherapy-induced oral mucositis: hierarchical analysis of recurrence factors.

This study aimed to analyze, through a hierarchical model, the risk factors associated with the recurrence of chemo-induced oral mucositis (OM) in children and adolescents. A retrospective cohort with 31 individuals of both sexes, aged 1-18years, who were undergoing chemotherapy, and presented OM lesions was conducted. Data collection included analysis of medical records, interviews, and intraoral examination. Information regarding patients' socioeconomic and demographic profile, underlying disease, antineoplastic regimen, hematological condition, and oral health status were collected. To assess the association of independent variables with the outcome, the Chi-square, Fisher's Exact, and Mann-Whitney tests were used, in addition to a binary logistic regression model, with a maximum error of 5% and a 95% confidence interval. Significant associations were observed between the history of OM and the diagnosis of the child/adolescent, neutrophil count, previous cancer treatments and the chemotherapy scheme in use (p < 0.05). Binary logistic regression revealed a 13.69 higher risk of developing OM recurrence in individuals who received high-dose methotrexate (MTX) therapy. Socioeconomic and demographic factors did not influence OM recurrence. However, clinical variables, such as neutropenia, diagnosis of leukemia, and high-dose MTX protocols increase the chance of OM new cases.

Neurolymphomatosis secondary to primary central nervous system lymphoma: illustrative case.

Neurolymphomatosis (NL) is a rare disease defined as an invasion of lymphoma into peripheral nerves, nerve roots, or nerve plexuses, including the cranial nerves. No clear treatment protocols have yet been defined for this pathology. A woman in her 40s had a primary central nervous system lymphoma diagnosed from an intracranial tumor biopsy and underwent chemotherapy and radiation therapy. After she complained of pain in the trunk and extremities, magnetic resonance imaging and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) performed 25 months after initial diagnosis revealed multiple lesions in the nerve ganglia, plexuses, and peripheral nerves from the cervical to the sacral spinal cord. Cerebrospinal fluid cytology revealed atypical lymphocytes and lymphoma dissemination in the spinal cavity. Based on these findings, NL was diagnosed. An intrathecal antineoplastic regimen temporarily reduced abnormal uptake of FDG, but the lesion recurred. After additional high-dose methotrexate therapy, FDG accumulation in the previously identified lesions disappeared. However, peripheral neuropathic pain and paraplegia remained. The patient died 9 months after the initial diagnosis of NL. The authors reported a case of NL following primary central nervous system lymphoma. In this case, FDG-PET proved useful for diagnosis, and high-dose methotrexate therapy was temporarily effective. https://thejns.org/doi/suppl/10.3171/CASE24107.

Membrane Lipid Replacement for reconstituting mitochondrial function and moderating cancer-related fatigue, pain and other symptoms while counteracting the adverse effects of cancer cytotoxic therapy.

Cancer-related fatigue, pain, gastrointestinal and other symptoms are among the most familiar complaints in practically every type and stage of cancer, especially metastatic cancers. Such symptoms are also related to cancer oxidative stress and the damage instigated by cancer cytotoxic therapies to cellular membranes, especially mitochondrial membranes. Cancer cytotoxic therapies (chemotherapy and radiotherapy) often cause adverse symptoms and induce patients to terminate their anti-neoplastic regimens. Cancer-related fatigue, pain and other symptoms and the adverse effects of cancer cytotoxic therapies can be safely moderated with oral Membrane Lipid Replacement (MLR) glycerolphospholipids and mitochondrial cofactors, such as coenzyme Q10. MLR provides essential membrane lipids and precursors to maintain mitochondrial and other cellular membrane functions and reduces fatigue, pain, gastrointestinal, inflammation and other symptoms. In addition, patients with a variety of chronic symptoms benefit from MLR supplements, and MLR also has the ability to enhance the bioavailability of nutrients and slowly remove toxic, hydrophobic molecules from cells and tissues.

Prevalence of recreational and medical cannabis products in Veterans and their interactions with cancer directed pharmacological treatment.

3089 Background: There is proliferation of literature about the medical uses of cannabis products in patients with malignancies. However, research is lacking as to how cannabis use is affecting the efficacy and toxicity of anti-neoplastic regimens It is known that cannabis is metabolized by the cytochrome p450 pathway, the same as many anti-neoplastic agents and thus there are concerns for potential interactions. Methods: We report an observational study to identify cannabis users in veterans receiving anti-neoplastic therapy in the Memphis VA health system, and to then analyzed for potential interactions between cannabis product and the antineoplastic agent/s they were receiving. Data was collected via voluntary surveys. We then reviewed their charts, recorded the anti- neoplastic medications they were receiving, and evaluated for potential interactions with cannabis, based on a literature review of potential interactions. Results: In this study, 132 veterans agreed to participate. 50 of them acknowledged recent use of cannabis products within the last 90 days. Thus, the prevalence of cannabis use amongst those who participated is 37.87%. Demographically, 10% of the cannabis users were female, and 90% were male, with the majority aged 60-65 (range 46-85). Predominantly, patients inhaled cannabis once daily (38%) as opposed to using a different formulation. The patients who admitted cannabis use were primarily on chemotherapy (42%), while 38% were on immunotherapy, 24% were on targeted therapy and 20% were on endocrine therapy. Some were on multiple drugs. Based on this data and a literature search for interactions, we found that a significant number of the patients in our Veteran’s oncology clinic have a potential increase in toxicity or decreased efficacy from their ant-neoplastic therapy due to CYP interactions with cannabis use. Conclusions: In this exploratory study, we discovered a notable prevalence of patients concurrently using cannabis products while on anti-neoplastic treatment. Given that many anti-neoplastic agents undergo metabolism via the CYP450 pathway, our data suggest that a moderate number of patients in our clinic risk less than optimal outcomes due to concurrent cannabis and anti-neoplastic therapy. To delve deeper, we intend to conduct a follow-up study, focusing on specific adverse effects, hospitalizations, and the subsequent need for 2nd and 3rd line treatments in patients using cannabis. A much larger multi-institutional study should be considered to provide statistically relevant data on true outcomes. [Table: see text]

2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis

BackgroundThe Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens.MethodsGuided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020.ResultsComprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated.ConclusionsThe primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

First-in-human phase 1/2 trial evaluating TAC01-CLDN18.2 autologous T cells in CLDN18.2-positive solid tumors.

TPS419 Background: CLDN18.2 is a tight junction protein expressed in differentiated gastric epithelial cells and is abnormally expressed in various solid tumor types, serving as a promising target for therapy. To date, there are no approved therapies directed against this target, but compelling data exist using monoclonal antibodies and conventional CAR T therapy. The T Cell Antigen Coupler (TAC) technology is an approach to modifying T cells ex vivo, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T cell receptor. The TAC technology has a safer profile than conventional CAR T therapies and is used to create an autologous TAC01-CLDN18.2 T cell product targeting CLDN18.2. Methods: This first in-human trial (NCT05862324) is designed to assess both the safety profile and preliminary antitumor activity of TAC01-CLDN18.2 in patients with CLDN18.2+/HER2- solid tumors after ≥ 2 lines of therapy. The phase 1 dose escalation segment employs a traditional 3+3 dose-escalation design to evaluate increasing doses of TAC01-CLDN18.2 with estimated enrollment numbers of 9 to 24 subjects. The subsequent phase 2 will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-CLDN18.2 dose. With 3 cohorts, Group A will enroll up to 57 subjects with gastric and esophageal adenocarcinoma, Group B aims to enroll 10 subjects with pancreatic ductal adenocarcinoma (PDAC) while Group C will examine up to 22 subjects with ovarian and non-small cell lung cancer (NSCLC). Groups A and C will leverage a Simon 2-stage design to assess whether the treatment achieves efficacy, while Group B will be exploratory with an opportunity for cohort enrichment based on clinical data. Prior to TAC01-CLDN18.2 infusion, subjects will undergo leukapheresis and may receive bridging anticancer therapy as appropriate during cell manufacturing. CLDN18.2 expression levels will be determined centrally using a clinical trial assay validated across relevant indications. Subjects will then undergo low intensity lymphodepletion chemotherapy. A second dose of TAC01-CLDN18.2 may be administered based on prespecified safety and clinical criteria. Evaluation of DLTs will take place within a 28-day window following the first infusion. In both phases, CLDN18.2+/HER2- solid tumor patients must have completed at least two prior therapy lines except for PDAC patients who may qualify after one prior antineoplastic regimen. For phase 2, up to four prior treatment lines is permissible and definitions of eligible CLDN18.2 expression levels will be based on retrospective analysis of data from Phase 1 in association with clinical efficacy. The trial is currently in the open-enrollment stage, awaiting the inclusion of the inaugural patient. No data analysis is available as of the submission deadline. Clinical trial information: NCT05862324 .

Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell lung cancer in Spain

IntroductionLung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC), and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years).The main treatment regimens used for first-line treatment of NSCLC are: cisplatin/pemetrexed (cis/pem), cisplatin/gemcita- bine/bevacizumab (cis/gem/bev), and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev). The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. MethodologyA cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. ResultsThe PFS obtained in clinical trials with cls/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19942€, 15594 € and 36095€, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cls/pem and cls/gem/bev was 19303€. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V.), due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

Drug-related problems among esophageal, gastric and colorectal cancer patients at the National and referral hospital in Kenya.

Cancer therapy has remarkable potential for drug-related problems due to the high cytotoxicity and narrow therapeutic index of most anti-neoplastic regimens. However, there is a lack of comprehensive studies on drug-related problems in patients with gastrointestinal cancer in Kenya. Therefore, the present study aimed to investigate the prevalence, types and predictors of drug-related problems among gastrointestinal cancer patients at Kenyatta National Hospital. A cross-sectional study was used to assess the prevalence of drug-related problems among a random sample of 160 esophageal, 103 gastric, and 96 colorectal cancer patients. Data were collected using a researcher-administered questionnaire and data abstraction tool after training the data collectors. Patient-specific details such as socio-demographic features, histological cancer types, cancer stage, comorbidity types, and treatment regimen were recorded after the review of medical records and patient interviews. The potential of drug-related problems was determined as per the standard guidelines. The data were entered and analysed using version 26.0 SPSS statistical software. Most esophageal (51.9%), gastric (59.2%), and colorectal (62.5%) cancer patients had a high prevalence of drug-related problems. The need for additional drug therapy and adverse drug reactions were the predominant categories of drug-related problems. Most adverse drug reactions identified had possible categories of causality score, mild severity levels, and definitely preventable types of adverse drug reactions among all gastrointestinal cancer patients. Comorbidity and advanced-stage disease were significant predictors of drug-related problems. Drug-related problems were prevalent among gastrointestinal cancer patients in our setting. Comorbidity and advanced stages of disease were significant predictors of drug-related problems.

Abstract P4-03-43: Disease characteristics and outcomes of people with metastatic breast cancer in a single center cohort study: The Dallas Metastatic Breast Cancer Study

Abstract Background: Breast cancer is the most common cancer in women, and metastatic disease accounts for most breast cancer related deaths. Identifying risk factors for the onset and progression of metastatic breast cancer (MBC) can help us understand how to address and improve morbidity and mortality due to MBC. Large national databases, such the Surveillance, Epidemiology, and End Results (SEER) Program are limited in their ability to capture granular details from patients’ cancer histories. The Dallas Metastatic Breast Cancer Study (DMBCS) is a clinical database established at a single academic medical system to track patient demographics, associated pathology, treatments, and other variables to improve outcomes for patients with MBC. Methods: The DMBCS database was generated from a registry of breast cancer patients submitted to the National Cancer Institute from 2010 to 2021. Patients were initially excluded if they were identified as non-metastatic from this list. Chart review was then done to identify MBC patients from this subsequent group. Demographics, clinical history, pathologic features, lines of treatment, and subsequent recurrences were collected for all patients. Clinical data was stored in REDCap, a secure data collection platform for entering and managing data. Results: 230 cases were included in this preliminary data set. Of the 230 cases, 185 cases were metastatic at time of diagnosis while 45 cases were metastatic recurrences of breast cancer. At diagnosis, 14.8% were less than 40 years of age, 17.3% were 40-49, 35.7% were 50-59, 18.7% were 60-69, and 13.5% were greater than 70 years of age. In terms of ethnicity, 63.5% were White, 27.4% were Black, and 21.7% identified as Hispanic. At time of diagnosis, 30.9% of patients had a BMI classified as overweight and 40.4% were considered obese. Medical comorbidities included hypertension in 43% of cases, diabetes (18.3%), hyperlipidemia (27.4%), and autoimmune disease (13.0%). Clinical subtype analysis revealed 57.8% of patients were hormone receptor positive, 24.8% HER2 positive, and 17.4% triple negative, at diagnosis. 14.8% of cases were diagnosed as inflammatory breast cancer. The most common site of metastasis at presentation was bone with 69.1% of cases, followed by lung (33.9%), liver (30.0%), and brain (15.2%). Over 90% of patients were treated with at least one antineoplastic regimen and 39.6% underwent at least 4 therapies. Calculated 1-year survival after diagnosis was 85.7%. Conclusions: The introduction of the DMBCS will allow continued investigation into clinical drivers of MBC. In this first cohort of patients, we characterized key, yet often underreported, variables and outcomes. Potential applications of this database include investigating the association between obesity and overall survival in patients with MBC, understanding how socioeconomic disparities affects outcomes of patients with MBC, and exploring correlations between autoimmune disease and the progression of MBC. Citation Format: Meng Cao, Mir Lim, Anna Moscowitz, Jonathan Ladner, Christine Hodgdon, Julia Maues, Sangeetha Reddy, Isaac Chan. Disease characteristics and outcomes of people with metastatic breast cancer in a single center cohort study: The Dallas Metastatic Breast Cancer Study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-43.

Which hematology/oncology patients are high priority for ambulatory clinical pharmacist review? A three-round Delphi survey by the National Comprehensive Cancer Network.

Prioritization and acuity tools have been leveraged to facilitate targeted and efficient clinical pharmacist interventions. However, there is a lack of established pharmacy-specific acuity factors in the ambulatory hematology/oncology setting. Therefore, National Comprehensive Cancer Network's Pharmacy Directors Forum conducted a survey to establish consensus on acuity factors associated with hematology/oncology patients that are high priority for ambulatory clinical pharmacist review. A three-round electronic Delphi survey was conducted. During the first round, respondents were asked an open-ended question to suggest acuity factors based on their expert opinion. Respondents were then asked in the second round to agree or disagree with the compiled acuity factors, in which those with ≥75% agreement were included in the third round. The final consensus was defined as a mean score ≥3.33 on a modified 4-point Likert scale (4 = strongly agree, 1 = strongly disagree) during the third round. A total of 124 hematology/oncology clinical pharmacists completed the first round of the Delphi survey (invitation response rate, 36.7%), of which 103 completed the second round (response rate, 83.1%) and 84 the third round (response rate, 67.7%). A final consensus was achieved for 18 acuity factors. Acuity factors were identified in the following themes: antineoplastic regimen characteristics, drug interactions, organ dysfunction, pharmacogenomics, recent discharge, laboratory parameters, and treatment-related toxicities. This Delphi panel of 124 clinical pharmacists achieved consensus on 18 acuity factors that would identify a hematology/oncology patient as a high priority for ambulatory clinical pharmacist review. The research team envisions incorporating these acuity factors into a pharmacy-specific electronic scoring tool.

Diagnosis and management of AL amyloidosis due to B-cell non-Hodgkin lymphoma.

Immunoglobulin light chain (AL) amyloidosis may be caused by a B-cell non-Hodgkin lymphoma (NHL) rather than a plasma cell neoplasm in rare cases, which presents unique diagnostic and management considerations. NHL associated with AL will often have an IgM paraprotein; thus, this disease is termed IgM-related AL amyloidosis (IgM AL). The clinical presentation of IgM AL is more likely to involve the lungs, peripheral nerves, and soft tissue; cardiac involvement is less common. Patients with IgM AL amyloidosis should undergo a lymphoma-directed work-up including evaluation for nodal and extranodal disease. Additionally, patients with an IgM paraproteinemia should be screened for AL amyloidosis through history and physical examination. Treatment regimens active against underlying lymphoma, rather than plasma cell-directed regimens, are recommended. Historical response rates in IgM AL have been poor; prospective studies of novel antineoplastic regimens may improve treatment outcomes.

Overexpression of miR-181a regulates the Warburg effect in triple-negative breast cancer

Objective Triple-negative breast cancer (TNBC) is highly aggressive and leads to a poor prognosis. microRNA-181a (miR-181a) exhibits strong antineoplastic effects in many types of cancer. In this study, we examine the responses of human miR-181a-transfected TNBC cells and explore the mechanisms underlying the observed effects. Methods A series of cellular assays were conducted using cells from the MDA-MB-231 TNBC line to assess the impact of miR-181a overexpression. The extracellular acidification rate, lactate production and glucose uptake were evaluated as a measure of aerobic glycolysis (i.e. the Warburg effect). The expressions of glycolysis-related gene were analyzed. Results Viability, migration and survival of miR-181a-transfected MDA-MB-231 cells were all significantly reduced. miR-181a inhibited glycolysis in TNBC cells by reducing the rates of glucose uptake and lactate production and a substantial downregulation of factors known to contribute to the Warburg effect, including the serine/threonine kinase, AKT3, hypoxia-inducible factor-1α (HIF-1α) and progesterone receptor membrane component 1 (PGRMC1). Conclusion Our results demonstrate that miR-181a may regulate glycolysis in MDA-MB-231 TNBC cells, potentially via interference with components of the AKT3–HIF-1α and PGRMC1 pathways. These results suggest that miR-181a might be developed as a therapeutic agent for use in antineoplastic regimens directed at TNBC and PGRMC1-overexpressing breast cancers.

Obinutuzumab Plus Chemotherapy As First Line Treatment in Patients with Follicular Lymphoma: Experience from a Community Hospital

Background The combination of Obinutuzumab plus chemotherapy (Obi-chemo) regimen is currently one of the standard first-line treatments available for patients diagnosed with follicular non-Hodgkin's lymphoma (FL). The aim of our study is to evaluate the efficacy and safety of the Obi-chemo regimen in a community hospital setting. Methods Retrospective analysis of patient's medical records admitted to our hospital with a confirmed pathologic diagnosis of FL that were treated with the regimen of Obi-chemo as first-line treatment. Between January 1, 2017 and January 5, 2022, a total of 10 consecutive patients met the criteria for evaluation. Results The baseline characteristics of the patients evaluated are as follows: The group consisted of 7 males and 3 females. Median age in years was 56 (range 43-80). 10% (n=1) patients had stage 2, and the remaining 90% (n=9) had stage III-IV. Bone marrow involvement was noted in 70% (n=7) and 40% (n=4) had bulky mass >7 cm at presentation. Of the total ten patients, 60% (n=6) received Obinutuzumab plus Bendamustine and the remaining 40% (n=4) received Obinutuzumab plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). All patients required G-CSF support. After completion of chemotherapy, 7 patients achieved a complete clinical and radiologic remission whereas 3 patients achieved a partial remission. Of these last 3 patients, two went on to achieve a complete remission during follow-up. Of the 7 patients who achieved an initial complete remission, one subsequently did relapse during follow-up. While on treatment, neutropenia and thrombocytopenia were documented in all 10 patients. 40% (n=4) of patients developed neutropenic fever, and 10% (n=1) developed grade 3 thrombocytopenia. 50% (n=5) of patients developed grade 1-2 infusion-related adverse events (nausea, hypertension, headache and skin rash). Two patients required chemotherapy de-escalation due to toxicity. No long-term toxicity or treatment-related deaths were reported. Conclusions Our study supports the findings of the pivotal clinical trials that led to the approval of the Obi-chemo antineoplastic regimen as first-line treatment for patients with FL by the regulatory agencies in Europe (EMA) and North America (FDA).

Radiation Recall Pneumonitis: A Rare Syndrome That Should Be Recognized.

Simple SummaryA combination of radiotherapy and systemic antineoplastic agents is a common treatment strategy for lung cancer. However, Radiation recall pneumonitis (RRP) is a rare disease which has been mainly detected in the previously irradiated lung of patients with cancer after the application of triggering agents, including, but not limited to, antineoplastic agents. Physicians should be aware of this rare reaction, as the occurrence of RRP could impact the outcome of anti-cancer treatment. Given that current studies on RRP are primarily case reports and retrospectively reviewed data, the aim of our article was to review the current understanding and evidence on RRP and define the characteristics of RRP.Radiation recall pneumonitis (RRP) is a rare but severe condition which has been mainly detected in the previously irradiated lung of patients with cancer after administering inciting agents, most commonly antineoplastic regimens including chemotherapy, targeted therapy, or immunotherapy. More recently, coronavirus disease vaccines were found to induce RRP. In addition to typical radiation pneumonitis (RP) or drug-induced interstitial lung disease, the management of RRP requires withholding inciting agents and steroid therapy. Thus, the occurrence of RRP could significantly impact cancer treatment, given that inciting agents are withheld temporarily and even discontinued permanently. In the present review, we discuss the current understanding and evidence on RRP and provide additional insights into this rare but severe disease.

Potential Ophthalmological Side Effects Induced by Anti-Neoplastic Regimens for the Treatment of Genitourinary Cancers: A Review.

The outcomes of patients with genitourinary (GU) cancers have been steadily improving in recent years. Novel therapies have entered our armamentarium, while several other regimens are currently being studied in clinical trials. This recent explosion of new agents has improved patient survival and the quality of life for patients, but has also significantly increased the frequency of several side effects. The current review will focus on the potential ocular adverse reactions of GU neoplastic treatments. The broad spectrum of manifestations of ocular toxicity underscores the uniqueness and complexity of the anatomic, physiologic, and metabolic features of the human eye. Most side effects are mild in severity and transient, but some can be severe, disabling, and irreversible. Clinicians should be aware of complications that might be vision threatening and impact the patient's quality of life. In this review, we focused on the ocular toxicity of the antineoplastic regimens that are currently used for the treatment of GU, including prostate cancer, bladder cancer, renal cell carcinoma, testicular cancer, pheochromocytoma, adrenocortical carcinoma, and penile cancer.