暂无摘要（点击查看原文获取完整内容）
Article1 February 1966Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute LeukemiaGERALD P. BODEY, M.D., MONICA BUCKLEY, B.A., Y. S. SATHE, PH.D., EMIL J FREIREICH, M.D.GERALD P. BODEY, M.D., MONICA BUCKLEY, B.A., Y. S. SATHE, PH.D., EMIL J FREIREICH, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-2-328 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptInfection is currently the major fatal complication of acute leukemia (1). Previous studies have indicated a relationship between leukopenia and the presence of infection in patients with acute leukemia (2-4) and various types of agranulocytosis (5-7). Chemotherapeutic agents with bone marrow toxicity are being used with increasing frequency in malignant and other chronic diseases. Also, a high incidence of infection has accompanied the use of these agents as immunosuppressive therapy in patients receiving organ transplantation (8). The present study examines the quantitative relationships between the presence of infection and the degree and duration of leukopenia in patients with acute leukemia....References1. HERSHBODEYNIESFREIREICH EMGPBAEJ: The causes of death in acute leukemia. A study of 414 patients from 1954-1963. JAMA 193: 105, 1965. CrossrefMedlineGoogle Scholar2. MILLERSHANBROM SPE: Infectious syndromes of leukemias and lymphomas. Amer. J. Med. Sci. 246: 420, 1963. CrossrefMedlineGoogle Scholar3. SILVERBEALSCHNEIDERMANMCCULLOUGH RTGAMANB: The role of the mature neutrophil in bacterial infections in acute leukemia. Blood 12: 814, 1957. CrossrefMedlineGoogle Scholar4. BAKER RD: Leukopenia and therapy in leukemia as factors predisposing to fatal mycoses. Mucormycosis, aspergillosis, and cryptococcosis. Amer. J. Clin. Path. 37: 358, 1962. CrossrefMedlineGoogle Scholar5. BROWNEMARCUS EAAJ: Chronic idiopathic neutropenia. New Eng. J. Med. 262: 795, 1960. CrossrefMedlineGoogle Scholar6. KOSTMANN R: Infantile genetic agranulocytosis. Acta Paediat. (Stockholm) (Supplement 105) 45: 1, 1956. MedlineGoogle Scholar7. SPAETDAMESHEK THW: Chronic hypoplastic neutropenia. Amer. J. Med. 13: 35, 1952. CrossrefMedlineGoogle Scholar8. HILLROLLAROWLANDSRIFKIND JBDTD: Infectious pulmonary disease in patients receiving immunosuppressive therapy for organ transplantation. New Eng. J. Med. 271: 1021, 1964. CrossrefMedlineGoogle Scholar9. FREIKARONLEVINFREIREICHTAYLORHANANIANSELAWRYHOLLANDHOOGSTRATENWOLMANABIRSAWITSKYLEEMILLSBURGERTSPURRPATTERSONEBAUGHJAMESMOON EMRHEJRJJOJFBIJEASSDEOCLRBFGGWJH: Effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. In press. Google Scholar10. LEVINHENDERSONKARONFREIREICH RHEMEJ: Treatment of acute leukemia with methylglyoxal-bis-guanylhydrazone (Methyl GAG). Clin. Pharmacol. Ther. 6: 31, 1965. CrossrefMedlineGoogle Scholar11. RICHARBREAKELL WJES: Evaluation of an electronic particle counter for the counting of white blood cells. Amer. J. Clin. Path. 31: 384, 1959. CrossrefMedlineGoogle Scholar12. BISEL HF: Criteria for the evaluation of response to treatment in acute leukemia. Blood 11: 676, 1956. Google Scholar13. WINTROBE MM: Clinical Hematology, 5th ed. Lea & Febiger, Philadelphia, 1961, p. 254. Google Scholar14. MCFARLANDLEBRE WEP: Abnormal leukocyte response in alcoholism. Ann. Intern. Med. 59: 865, 1963. LinkGoogle Scholar15. BOGGSWINTROBECARTWRIGHT DRMGE: The acute leukemias. Analysis of 322 cases and review of the literature. Medicine (Balt.) 41: 163, 1962. CrossrefMedlineGoogle Scholar16. BOGGSFREI DRE: Clinical studies of fever and infection in cancer. Cancer 13: 1240, 1960. CrossrefGoogle Scholar17. HERSHCARBONEWONGFREIREICH EMPPVGEJ: Inhibition of the primary immune response in man by antimetabolites. Cancer Res. In press. Google Scholar18. JAFFE RH: Morphology of the inflammatory defense reactions in leukemia. Arch. Path. (Chicago) 14: 177, 1932. Google Scholar19. BRAUDEFELTESBROOKS AIJM: Differences between the activities of mature granulocytes in leukemic and normal blood. J. Clin. Invest. 33: 1036, 1954. CrossrefMedlineGoogle Scholar20. BOGGS DR: The cellular composition of inflammatory exudates in human leukemias. Blood 15: 466, 1960. CrossrefMedlineGoogle Scholar21. PERILLIEFINCH PEC: The local exudative cellular response in leukemia. J. Clin. Invest. 39: 1353, 1960. CrossrefMedlineGoogle Scholar22. PERILLIEFINCH PESC: Quantitative studies of the local exudative cellular reaction in acute leukemia. J. Clin. Invest. 43: 425, 1964. CrossrefMedlineGoogle Scholar23. PAGEGOOD ARRA: A clinical and experimental study of the function of neutrophils in the inflammatory response. Amer. J. Path. 34: 645, 1958. MedlineGoogle Scholar24. RAABHOEPRICHWINTROBECARTWRIGHT SOPDMMGE: The clinical significance of fever in acute leukemia. Blood 16: 1609, 1960. CrossrefMedlineGoogle Scholar25. MILLER CP: The effect of irradiation on natural resistance to infection. Ann. N. Y. Acad. Sci. 66: 280, 1956. CrossrefGoogle Scholar26. DERBYROGERS BMDE: Studies on bacteremia. V. The effect of simultaneous leukopenia and reticuloendothelial blockade on the early blood stream clearance of staphylococci and Escherichia coli. J. Exp. Med. 113: 1053, 1961. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, MarylandFrom the Medicine Branch, Leukemia Service, and the Mathematical and Statistics and Applied Mathematical Section, National Cancer Institute, National Institutes of Health, Bethesda, Md.Requests for reprints should be addressed to Gerald P. Bodey, M.D., Building 10, Room 2B45, National Institutes of Health, Bethesda, Md. 20014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAssociation Between Lymphopenia at 1 Month Posttransplant and Infectious Outcomes or Death in Heart Transplant RecipientsPredicting fever in neutropenia with safety‐relevant events in children undergoing chemotherapy for cancer: The prospective multicenter SPOG 2015 FN Definition StudyEmergency management of fever and neutropenia in children with cancer: A reviewDe novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case reportCytomegalovirus reactivation in esophageal cancer patients receiving chemoradiotherapy: A retrospective analysisAssessing febrile neutropenia outcomes in patients receiving primary versus secondary prophylactic G-CSF treatment therapy with intermediate neutropenic risk chemotherapy regimensModelling and Simulation of the Effect of Targeted Decolonisation on Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections in Haematological PatientsThe impact of granulocyte colony stimulating factor on patients receiving chimeric antigen receptor T ‐cell therapyRetrospective comparison of reinfusion procedures and subsequent leukopenia in autologous stem cell transplantationCharacteristics, risk factors, and outcomes of neutropenia after liver or kidney transplantation in childrenHistory of whole pelvis plus para-aortic radiation is a risk factor associated with febrile neutropenia during chemotherapy for recurrent cervical cancerManagement of the Older Patient with Myelodysplastic SyndromeAssociation between the dietary regimen and infection-related complications in neutropenic high-risk patients with cancerGranulocyte transfusions in haematopoietic cell transplants and leukaemia: the phoenix or beating a dead horse?D‐index as a marker of bloodstream infections in patients with allogeneic hematopoietic stem cell transplantationFactors associated with neutropenia post heart transplantationAssociation of an emergency department febrile neutropenia intervention protocol with time to initial antibiotic treatmentPseudoneutropenia as a factor-limiting access to chemotherapy for cancer patients: the effect of a simple mealManagement of bacterial and fungal infections in cirrhosis: The MDRO challengeChest CT Has Higher Yield for Infection than CT Sinus in Febrile Neutropenic PatientsTherapeutic granulocyte infusion for patients with severe neutropaenia and neutrophilic dysfunction: New Zealand experienceTissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor SignalingFungal Infections of the Gastrointestinal TractAn Analysis of the Infections and Determination of Empiric Antibiotic Therapy in Cats and Dogs with Cancer-Associated InfectionsTrilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive‐stage small cell lung cancer: A multicentre, randomised, double‐blind, placebo‐controlled Phase II trialIncidence and predictive risk factors of neutropenic sepsis in post-chemotherapy febrile patients in emergency department: A single-center retrospective longitudinal studyInfectious Morbidity in Pediatric Patients Receiving Neoadjuvant Chemotherapy for SarcomaA place for neutrophils in the beneficial pathogen-agnostic effects of the BCG vaccineUnderstanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial ResistanceImmune‐related adverse events of a PD‐L1 inhibitor plus chemotherapy versus a PD‐L1 inhibitor alone in first‐line treatment for advanced non–small cell lung cancer: A meta‐analysis of randomized control trialsCarbapenem-Resistant Enterobacteriaceae—Implications for Treating Acute Leukemias, a Subgroup of Hematological MalignanciesNetwork mapping of primary CD34+ cells by Ampliseq based whole transcriptome targeted resequencing identifies unexplored differentiation regulatory relationshipsAlternative pneumocystis prophylaxis in solid organ transplant recipients at two large transplant centersFebrile Neutropenia: Decreasing Time to Antibiotic Administration in a Community Hospital Emergency DepartmentBenign ethnic neutropenia in a South African population, and its association with HIV acquisition and adverse event reporting in an HIV vaccine clinical trialCitrulline as a biomarker of bacteraemia during induction treatment for childhood acute lymphoblastic leukaemiaManagement of Infections in Neutropenic PatientsAntibacterial and Antiparasitic ProphylaxisFebrile NeutropeniaMyelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II StudyForewordManagement principles for patients with neutropeniaStress-buffering effect of social support on immunity and infectious risk during chemotherapy for breast cancerThe clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settingsThe Impact of Modifying Empirical Antibiotic Therapy Based on Intestinal Colonization Status on Clinical Outcomes of Febrile Neutropenic PatientsComparison of the etiologic, microbiologic, clinical and outcome characteristics of febrile vs. non-febrile neutropenia in hospitalized immunocompetent childrenComplete, yet partial: the benefits of complete response with partial haematological recovery as an endpoint in acute myeloid leukaemia clinical trialsAssessment of infection in newly diagnosed multiple myeloma patients: risk factors and main characteristicsSmoking is associated with pneumonia development in lung cancer patientsEfficacy and safety of oral magnesium supplementation in reducing febrile neutropenia episodes in children with solid tumors treated with cisplatin-based chemotherapy: randomized clinical trialInfection at diagnosis—a unique challenge in acute myeloid leukemia treatment in developing worldUtility of procalcitonin as a predictor of bloodstream infections and supportive modality requirements in critically ill cancer patientsAssessing Needs and Experiences of Preparing for Medical Emergencies Among Children With Cancer and Their CaregiversPossibilities of supportive therapy in patients with blood system tumors and malignant neoplasmsHigh Burden of Serious Bacterial Infections in African Children Treated for CancerEfficacy and safety of granulocyte transfusion in children: A single‐center experienceEvaluation of a 0.75 × 10 9 /L absolute neutrophil count cut‐off for antimicrobial prophylaxis in canine cancer chemotherapy patientsInfectious disease considerations in immunocompromised patientsRectal colonization with multidrug-resistant gram-negative bacteria in patients with hematological malignancies: a prospective studyThe Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile NeutropeniaAn in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopeniasPersonalized cancer supportive care in COVID-19 eraAssociation Between Depth of Neutropenia and Clinical Outcomes in Febrile Pediatric Cancer and/or Patients Undergoing Hematopoietic Stem-cell TransplantationPrediction of Survival Benefit of Filgrastim in Adult and Pediatric Patients With Acute Radiation SyndromeEvaluation of the HemoCue WBC DIFF in leukopenic patient samplesAge‐related prevalence and clinical significance of neutropenia ‐ isolated or combined with other cytopenias: Real world data from 373 820 primary care individualsInterventions aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN), a systematic reviewPreoperative Nutritional Status Contributes to the Development of Neutropenia Event in Patients With Gastric Cancer Receiving CAPEOX Adjuvant ChemotherapyThe cost of a “benign” condition: Healthcare utilization and infectious outcomes in young children with primary autoimmune neutropeniaComparison of two different anti-infectious approaches after high-dose chemotherapy and autologous stem cell transplantation for hematologic malignancies in a 12-year period in British Hospital, UruguayIn canine bacterial pneumonia circulating granulocyte counts determine outcome from donor cellsD-Index–Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority TrialProphylaxis of febrile neutropenia with colony-stimulating factors: the first 25 yearsNeutropenia management in patients receiving myelosuppressive polychemotherapy for early breast cancer in Belgium: BRONS study resultsTranscriptional regulation of neutrophil differentiation and function during inflammationAssociation of time to antibiotics and clinical outcomes in patients with fever and neutropenia during chemotherapy for cancer: a systematic reviewUp-to-Date Infection Control Practices for Febrile Neutropenic PatientsRecent advances and future directions in the management of the immunocompromised hostThe Role of Neutrophils in the Immune System: An OverviewEfficient Bayesian Expert Models for Fever in Neutropenia and Fever in Neutropenia with BacteremiaAntimicrobial Prophylaxis in High-Risk Oncology PatientsInfection in the Patient With Cancer Detection and Control of Biofilm Formation by <em>Staphylococcus aureus</em> from Febrile Neutropenic Patient Protocol for a systematic review of time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN) and interventions aiming to reduce TTAEffect of adjunctive corticosteroid on 28-day mortality in neutropenic patients with septic shockImpact of neutropenia on central venous catheter–related bloodstream infections in patients with hematological malignancies at the time of central venous catheter insertion: A matched-pair analysisPeritoneal GATA6+ macrophages function as a portal for Staphylococcus aureus disseminationPhysical Exercise during Radiation and ChemotherapyImpact of preleukemic mutations and their persistence on hematologic recovery after induction chemotherapy for AMLThe clinical management of invasive mold infection in children with cancer or undergoing hematopoietic stem cell transplantationInpatient Health Care Utilization in Children With Hemophilia Before and After the Joint Outcome Study PublicationUse of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health EmergencyUse of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health EmergencyNonneutropenic fever in children with cancer: A scoping review of management and outcomeHost and Graft Factors Impacting Infection Risk in Hematopoietic Cell TransplantationWork-up for Fever During Neutropenia for Both the Stem Cell Transplant Recipient and the Hematologic Malignancy PatientInappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug ResistanceOutpatient treatment for people with cancer who develop a low-risk febrile neutropaenic eventRisk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropeniaCan immune biomarkers predict infections in solid organ transplant recipients? A review of current evidenceManagement of Patients With Fever and Neutropenia Through the Arc of Time A Narrative ReviewPhilip A. Pizzo, MDSTUDY ON HAEMATOLOGICAL PROFILE AMONG HIV POSITIVE PATIENTSThe immune response to fungal challengeNeutrophil Heterogeneity as Therapeutic Opportunity in Immune-Mediated DiseaseSpecific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8+ T Cell ResponsesEpisodes of fever in neutropenia in pediatric patients with cancer in Bern, Switzerland, 1993–2012Prospective Evaluation of Multinational Association of Supportive Care in Cancer Risk Index Score for Gynecologic Oncology Patients With Febrile NeutropeniaAIDS-Related Kaposi Sarcoma, Version 2.2019Infections in Allogeneic Stem Cell TransplantationRespiratory Tract Infections: Sinusitis, Bronchitis, and PneumoniaOral Considerations for the Head and Neck Cancer PatientAntimicrobial Prophylaxis in High-Risk Oncology PatientsAntimicrobial Prophylaxis in High-Risk Oncology PatientsNeutropenic SepsisHematopoietic Growth Factors in the Management of Anemia and Febrile NeutropeniaCreation and evaluation of a cancer chemotherapy order review guide for use at a community hospitalOptimal Management of Neutropenic Fever in Patients With CancerFebrile Neutropenia: An Ounce of Prevention or a Pound of CureEffectiveness of filgrastim and polyethylene glycol-filgrastim in the treatment of postchemotherapy neutropenia in children: Phase I clinical trialPediatric patients at risk for fever in chemotherapy-induced neutropenia in Bern, Switzerland, 1993-2012One-year mortality and Periprosthetic infection rates after Total knee Arthroplasty in Cancer patients: a population-based cohort studyClinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapyCost-effectiveness analysis of lipegfilgrastim as primary prophylaxis in women with breast cancer in Australia: a modelled economic evaluationThe Lung Microvasculature Is a Functional Immune NicheLeukopenia and lack of ribavirin predict poor outcomes in patients with haematological malignancies and respiratory syncytial virus infectionInfectious complications in patients with acute leukemia according to the duration of neutropeniaAntimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline UpdateExtended vs Bolus Infusion of Broad-Spectrum β-Lactams for Febrile Neutropenia: An Unblinded, Randomized TrialAssociations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemiaA cohort study on protocol-based nurse-led out-patient management of post-chemotherapy low-risk febrile neutropeniaPulmonary Infections in Immunocompromised HostsAntibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendationsPrescribing Empiric Antibiotics for Febrile Neutropenia: Compliance with Institutional Febrile Neutropenia GuidelinesCharacteristics and Clinical Outcomes of Critically Ill Cancer Patients Admitted to Korean Intensive Care UnitsTissue macrophages as mediators of a healthy relationship with gut commensal microbiotaDrug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant PhysiciansThe Infectious and Noninfectious Etiology, Clinical Picture and Outcome of Neutropenia in Immunocompetent Hospitalized ChildrenFully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to G AlertPredictors of chemoradiation related febrile neutropenia prophylaxis in older adults – Experience from a resource and Extracellular in Pediatric Acute Leukemia the of in pediatric heart transplant of febrile neutropenia in childhood acute leukemia and of procalcitonin in neutropenic Control of Infections: from Studies and cells as a for infectious current and future of Infection and in a Antimicrobial Prophylaxis in the Transplant Patient in the of transfusions in the management of neutropenic A pediatric from to an on the use of granulocyte transfusions and colony-stimulating factors for prophylaxis and treatment of infectious complications in patients with hematologic malignant randomized of the of the neutropenic versus safety on infection in pediatric Care for Patients with A in and and and cost analysis of cancer patients treated with a cohort study based on the of chemotherapy-induced neutropenia and febrile neutropenia (FN) on cancer treatment An and clinical and major to hematopoietic stem cell transplant utilization and by children with cancer on factors for and infections in inflammatory disease patients with a normal for for Infections and in Cancer and Stem Cell Transplant and Acute for Analysis of to for the Prophylaxis of Neutropenia in Patients with a for in leukemia to and safety of versus of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced a systematic of similarity a proposed biosimilar pegfilgrastim and reference neutropenia is a for neutrophil during lung cancer Survival during Chronic Infection by Therapeutic to in Immune of Neutrophils vs. Staphylococcus of Filgrastim for Febrile Neutropenia Is Among Patients With and for Patients with Hematologic A factors and impact of on transfusions in the management of invasive fungal lung is a defense for During for Acute and Blood chemotherapy in A prospective of neutropenic fever in Hospital, a cancer PROFILE A of in the Cancer in with of Chemotherapy in Leukemia Multinational Association of Supportive Care of Cancer Index Score for Febrile Neutropenia Patients at Risk of at Care Hospital, transplant myeloid Emergency Care of Patients With Cancer: the of is a to the Risk of Infectious Hematopoietic Stem Cell of of and of antimicrobial resistance in bloodstream infections of cancer during of human of severe infections in neutropenic cancer aureus the current of and for genetic severe chemotherapy-induced neutropenia in breast cancer After Acute Leukemia A the Oncology of in a large cohort absolute neutrophil count of as a in African of lung macrophages infectious of bone transfusions in critically ill children with effects and rates from a single-center between and duration of chemotherapy-induced neutropenia and risk of infection patients with factors for time to in cancer patients with bloodstream aureus and neutropenia pediatric cancer patients in and of Infections in the Immunocompromised of from of pegfilgrastim versus filgrastim for the management of neutropenia during chemotherapy for malignant clinical evaluation of and safety of versus in patients of with febrile neutropenia in a care of chemotherapy and of use of antimicrobial in and prior to the safety of a human granulocyte colony-stimulating and white blood cell count as of bacterial and clinical significance of neutropenia in complete blood cell a longitudinal Infections in Children with of Children With Cancer or Admitted the Emergency Emergency Among Children with of Infections in the Immunocompromised agents for the of treatment neutropenia in adult cancer of absolute neutrophil counts in patients treated with pegfilgrastim on the of chemotherapy versus the after Randomized Phase Study of Administration of a for Prophylaxis of Neutropenia in Patients With Lung Cancer for Pediatric early versus early versus in children with
In this paper, we introduce a novel pipeline for predicting chemotherapy response in pediatric brain tumors that are not amenable to complete surgical resection, using pre-treatment magnetic resonance imaging combined with clinical information. Our method integrates a state-of-the-art pediatric brain tumor segmentation framework with radiomic feature extraction and clinical data through an ensemble of a Swin UNETR encoder and XGBoost classifier. The segmentation model delineates four tumor subregions enhancing tumor, non-enhancing tumor, cystic component and edema which are used to extract imaging biomarkers and generate predictive features. The Swin UNETR network classifies the response to treatment directly from these segmented MRI scans, while XGBoost predicts response using radiomics and clinical variables including legal sex, ethnicity, race, age at event (in days), molecular subtype, tumor locations, initial surgery status, metastatic status, metastasis location, chemotherapy type, protocol name and chemotherapy agents. The ensemble output provides a non-invasive estimate of chemotherapy response in this historically challenging population characterized by lower progression-f
Chemotherapy for cancer treatment is costly and accompanied by severe side effects, highlighting the critical need for early prediction of treatment outcomes to improve patient management and informed decision-making. Predictive models for chemotherapy outcomes using real-world data face challenges, including the absence of explicit phenotypes and treatment outcome labels such as cancer progression and toxicity. This study addresses these challenges by employing Large Language Models (LLMs) and ontology-based techniques for phenotypes and outcome label extraction from patient notes. We focused on one of the most frequently occurring cancers, breast cancer, due to its high prevalence and significant variability in patient response to treatment, making it a critical area for improving predictive modeling. The dataset included features such as vitals, demographics, staging, biomarkers, and performance scales. Drug regimens and their combinations were extracted from the chemotherapy plans in the EMR data and shortlisted based on NCCN guidelines, verified with NIH standards, and analyzed through survival modeling. The proposed approach significantly reduced phenotypes sparsity and impro
Chemotherapy dose optimization can be formulated as a dynamic treatment regime, requiring sequential decisions under uncertainty that must balance tumor suppression against toxicity. However, most reinforcement learning approaches assume full observability of the patient state, a condition rarely met in clinical practice. We investigate whether memory-augmented policies can improve chemotherapy control under partial observability. To this end, we employ a recurrent TD3-based approach with separate LSTM actor-critic networks and evaluate it on the AhnChemoEnv benchmark from DTR-Bench, considering both off-policy and on-policy recurrent architectures against feed-forward TD3 and Soft Actor-Critic. Pharmacokinetic and pharmacodynamic variability are held fixed to isolate hidden-state uncertainty and observation noise and to avoid confounding effects from inter-patient variability. Across ten random seeds, recurrence yields modest benefit under full observability but substantially stronger and more stable performance under partial observability, with more consistent tumor suppression and improved normal-cell preservation. These findings indicate that memory-based policies are particula
In general, the rates of infection and removal (whether through recovery or death) are nonlinear functions of the number of infected and susceptible individuals. One of the simplest models for the spread of infectious diseases is the SIR model, which categorizes individuals as susceptible, infectious, recovered or deceased. In this model, the infection rate, governing the transition from susceptible to infected individuals, is given by a linear function of both susceptible and infected populations. Similarly, the removal rate, representing the transition from infected to removed individuals, is a linear function of the number of infected individuals. While nonlinear infection and removal rates have been extensively studied in deterministic epidemiological models, analytic results for stochastic dynamics with general nonlinear rates remain limited. This work presents an analytic expression for the number of infected individuals considering nonlinear infection and removal rates. In particular, we examine how the number of infected individuals varies as cases emerge and obtain the expression accounting for the number of infected individuals at each moment. This work paves the way for
We study the stochastic SIR epidemic model with infection-age dependent infectivity for which a measure-valued process is used to describe the ages of infection for each individual. We establish a functional law of large numbers (FLLN) and a functional central limit theorem (FCLT) for the properly scaled measure-valued processes together with the other epidemic processes to describe the evolution dynamics. In the FLLN, assuming that the hazard rate function of the infection periods is bounded and the ages at time 0 of the infections of the initially infected individuals are bounded, we obtain a PDE limit for the LLN-scaled measure-valued process, for which we characterize its solution explicitly. The PDE is linear with a boundary condition given by the unique solution to a set of Volterra-type nonlinear integral equations. In the FCLT, we obtain an SPDE for the CLT-scaled measure-valued process, driven by two independent white noises coming from the infection and recovery processes. The SPDE is also linear and coupled with the solution to a system of stochastic Volterra-type linear integral equations driven by three independent Gaussian noises, one from the random infection functio
Airborne infection risk analysis is usually performed for enclosed spaces where susceptible individuals are exposed to infectious airborne respiratory droplets by inhalation. It is usually based on exponential, dose-response models of which a widely used variant is the Wells-Riley (WR) model. We revisit this infection-risk estimate and extend it to the population level. We use an epidemiological model where the mode of pathogen transmission, either airborne or contact, is explicitly considered. We illustrate the link between epidemiological models and the WR model. We argue that airborne infection quanta are, up to an overall density, airborne infectious respiratory droplets modified by a parameter that depends on biological properties of the pathogen, physical properties of the droplet, and behavioural parameters of the individual. We calculate the time-dependent risk to be infected during the epidemic for two scenarios. We show how the epidemic infection risk depends on the viral latent period and the event time, the time infection occurs. The infection risk follows the dynamics of the infected population. As the latency period decreases, infection risk increases. The longer a su
Identifying the infection sources in a network, including the index cases that introduce a contagious disease into a population network, the servers that inject a computer virus into a computer network, or the individuals who started a rumor in a social network, plays a critical role in limiting the damage caused by the infection through timely quarantine of the sources. We consider the problem of estimating the infection sources and the infection regions (subsets of nodes infected by each source) in a network, based only on knowledge of which nodes are infected and their connections, and when the number of sources is unknown a priori. We derive estimators for the infection sources and their infection regions based on approximations of the infection sequences count. We prove that if there are at most two infection sources in a geometric tree, our estimator identifies the true source or sources with probability going to one as the number of infected nodes increases. When there are more than two infection sources, and when the maximum possible number of infection sources is known, we propose an algorithm with quadratic complexity to estimate the actual number and identities of the in
Doctors are well aware that sometimes cancer treatments not only fail, but even work backwards, i.e. they make the treated tumor grow. In this work we present a mathematical perspective on this paradox in the case of chemotherapy, by studying a minimally parameterized mathematical model for the system composed of the tumor and the surrounding vasculature. To this end, we will use a system of two well-established nonlinear ordinary differential equations, which incorporates the cytotoxic (via the Norton-Simon hypothesis) and antiangiogenic effects of chemotherapy. Finally, we provide two theoretical ways to avoid these anomalies.
The move towards personalized treatment and digital twins for cancer therapy requires a complete understanding of the mathematical models upon which these optimized simulation-based strategies are formulated. This study investigates the influence of mathematical model selection on the optimization of chemotherapy and radiotherapy protocols. By examining three chemotherapy models (log-kill, Norton-Simon, and Emax), and three radiotherapy models (linear-quadratic, proliferation saturation index, and continuous death-rate), we identify similarities and significant differences in the optimized protocols. We demonstrate how the assumptions built into the model formulations heavily influence optimal treatment dosing and sequencing, potentially leading to contradictory results. Further, we demonstrate how different model forms influence predictions in the adaptive therapy setting. As treatment decisions increasingly rely on simulation-based strategies, unexamined model assumptions can introduce bias, leading to model-dependent recommendations that may not be generalizable. This study highlights the importance of basing model selection on a full analysis of bias, sensitivity, practical par
Studying the spatiotemporal distribution of SARS-CoV-2 infections among healthcare workers (HCWs) can aid in protecting them from exposure. Existing studies related to HCW infections have emphasized infection rates and protective measures. However, the spatiotemporal patterns and related external environmental factors of HCW infections remain unclear. To fill this gap, an open-source dataset of HCW diagnoses was provided, and the spatiotemporal distributions of SARS-CoV-2 infections among HCWs in Wuhan, China were explored. A geographical detector technique was then used to investigate the impacts of hospital level, type, distance from the infection source, and other external indicators of HCW infections. The results showed that the number of daily HCW infections over time in Wuhan followed a log-normal distribution, with and its mean observed on January 23, 2020 and a standard deviation of 10.8 days. The implementation of high-impact measures, such as the lockdown of the city, may have increased the probability of HCW infections in the short term, especially for HCWs in the outer ring of Wuhan. The infection of HCWs Wuhan exhibited clear spatial heterogeneity. The number of HCW in
The ChemoTimelines shared task benchmarks methods for constructing timelines of systemic anticancer treatment from electronic health records of cancer patients. This paper describes our methods, results, and findings for subtask 2 -- generating patient chemotherapy timelines from raw clinical notes. We evaluated strategies involving chain-of-thought thinking, supervised fine-tuning, direct preference optimization, and dictionary-based lookup to improve timeline extraction. All of our approaches followed a two-step workflow, wherein an LLM first extracted chemotherapy events from individual clinical notes, and then an algorithm normalized and aggregated events into patient-level timelines. Each specific method differed in how the associated LLM was utilized and trained. Multiple approaches yielded competitive performances on the test set leaderboard, with fine-tuned Qwen3-14B achieving the best official score of 0.678. Our results and analyses could provide useful insights for future attempts on this task as well as the design of similar tasks.
This study presents a mathematical model that captures the interactions among tumor cells, healthy cells, and immune cells in a tumor-bearing host, with a specific focus on breast cancer. Incorporating the concept of delay, the model consists of four differential equations to analyze these cellular dynamics. The findings demonstrate the superior efficacy of metronomic chemotherapy compared to the maximum tolerated dose (MTD) method and underscore the necessity of adjunct therapies. Oscillatory tumor cell dynamics revealed by the model highlight the challenges of achieving complete tumor elimination through chemotherapy alone. Sensitivity analysis confirms the robustness of the model, particularly under metronomic treatment protocols, aligning with experimental observations regarding metronomic-to-MTD dosage ratios. Furthermore, the results emphasize the importance of synergistic effects from combination therapies. This biologically consistent framework provides valuable insights into tumor-immune interactions and offers a foundation for optimizing therapeutic strategies in cancer treatment.
We study the dynamics and interactions between combined chemotherapy and chimeric antigen receptor (CAR-T) cells therapy and malignant gliomas (MG). MG is one of the most common primary brain tumor, with high resistance to therapy and unfavorable prognosis. Here, we develop a mathematical model that describes the application of chemo- and CAR-T cell therapies and the dynamics of sensitive and resistant populations of tumor cells. This model is a five-dimensional dynamical system with impulsive inputs corresponding to clinical administration of chemo- and immunotherapy. We provide a proof of non-negativeness of solutions of the proposed model for non-negative initial data. We demonstrate that if we apply both therapies only once, the trajectories will be attracted to an invariant surface that corresponds to the tumor carrying capacity. On the other hand, if we apply both treatments constantly, we find regions of the parameter where the tumor is eradicated. Moreover, we study applications of different combinations of the above treatments in order to find an optimal combination at the population level. To this aim, we generate a population of $10^{4}$ virtual patients with the model p
The problem of chemotherapy treatment optimization can be defined in order to minimize the size of the tumor without endangering the patient's health; therefore, chemotherapy requires to achieve a number of objectives, simultaneously. For this reason, the optimization problem turns to a multi-objective problem. In this paper, a multi-objective meta-heuristic method is provided for cancer chemotherapy with the aim of balancing between two objectives: the amount of toxicity and the number of cancerous cells. The proposed method uses mathematical models in order to measure the drug concentration, tumor growth and the amount of toxicity. This method utilizes a Multi-Objective Particle Swarm Optimization (MOPSO) algorithm to optimize cancer chemotherapy plan using cell-cycle specific drugs. The proposed method can be a good model for personalized medicine as it returns a set of solutions as output that have balanced between different objectives and provided the possibility to choose the most appropriate therapeutic plan based on some information about the status of the patient. Experimental results confirm that the proposed method is able to explore the search space efficiently in order
We study a stochastic epidemic model with multiple patches (locations), where individuals in each patch are categorized into three compartments, Susceptible, Infected and Recovered/Removed, and may migrate from one patch to another in any of the compartments. Each individual is associated with a random infectivity function which dictates the force of infectivity while the interactive infection process depends on the age of infection (elapsed time since infection). We prove a functional law of large number for the epidemic evolution dynamics including the aggregate infectivity process, the numbers of susceptible and recovered individuals as well as the number of infected individuals at each time that have been infected for a certain amount of time. From the limits, we derive a PDE model for the density of the number of infected individuals with respect to the infection age, which is a systems of linear PDE equations with a boundary condition that is determined by a set of integral equations.
We present a mathematical model of the evolutionary dynamics of a metastatic tumour under chemotherapy, comprising non-local partial differential equations for the phenotype-structured cell populations in the primary tumour and its metastasis. These equations are coupled with a physiologically-based pharmacokinetic model of drug delivery, implementing a realistic delivery schedule. The model is carefully calibrated from the literature, focusing on BRAF-mutated melanoma treated with Dabrafenib as a case study. By means of long-time asymptotic analysis, global sensitivity analysis and numerical simulations, we explore the impact of cell migration from the primary to the metastatic site, physiological aspects of the tumour sites and drug dose on the development of drug resistance and treatment efficacy. Our findings provide a possible explanation for empirical evidence indicating that chemotherapy may foster metastatic spread and that metastatic sites may be less impacted by chemotherapy.
The number of new cancer cases is expected to increase by about 50% in the next 20 years, and the need for chemotherapy treatments will increase accordingly. Chemotherapy treatments are usually performed in outpatient cancer centers where patients affected by different types of tumors are treated. The treatment delivery must be carefully planned to optimize the use of limited resources, such as drugs, medical and nursing staff, consultation and exam rooms, and chairs and beds for the drug infusion. Planning and scheduling chemotherapy treatments involve different problems at different decision levels. In this work, we focus on the patient chemotherapy multi-appointment planning and scheduling problem at an operational level, namely the problem of determining the day and starting time of the oncologist visit and drug infusion for a set of patients to be scheduled along a short-term planning horizon. We use a per-pathology paradigm, where the days of the week in which patients can be treated, depending on their pathology, are known. We consider different metrics and formulate the problem as a multi-objective optimization problem tackled by sequentially solving three problems in a lex