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PubMedDate not supplied

Long-term follow-up and prognostic factors in Ewing's sarcoma. A multivariate analysis of 116 patients from a single institution.

The records of 116 patients from a single center (1970-1993) with newly diagnosed Ewing's sarcoma or primitive neuroectodermal tumor were reviewed retrospectively. The aim of this study was to ascertain the impact of pretreatment variables on disease-free survival. Median age was 14 years (range 1-34). Twenty patients presented with metastatic disease. Treatment consisted of systemic multiagent chemotherapy plus local irradiation (39%), wide resection (22%), or both (35%). Median potential follow-up was 10.7 years (range 2-26). Three patients developed second malignancies (1 breast carcinoma, 2 acute myeloid leukemias). Median time to relapse was 24 months (range 3-143). The actuarial disease-free survival was 37.4% at 5 years, 33.3% at 10 years and 27.8% at 15 years. Neoadjuvant chemotherapy and a therapy-induced tumor necrosis > or = 90% were associated with a better outcome. Patients undergoing surgical resection had a superior disease-free survival than those treated without surgery (45 vs. 18% at 10 years, p = 0.0009). Multiple regression analysis showed that raised serum lactate dehydrogenase levels (p < 0.001), hypoalbuminemia (p = 0.001) and distant metastases at diagnosis (p = 0.03) were independent adverse prognostic factors. In conclusion, one third of patients with Ewing's sarcoma become long-term survivors with combined modality treatment. Late relapses and second neoplasms are of concern. Prognostic factors should be considered in the selection of therapy, and the value of serum albumin warrants confirmatory studies.

Actuarial Analysis↗
PubMed1996

Aggressive bone metastases in urachal carcinoma.

A 38-year-old female with urachal carcinoma showed extensive bone metastases 1 year after wide excision of the urachal tumor, including partial cystectomy. A combination of radiotherapy and systemic chemotherapy was offered. Local radiotherapy of 8 Gy as a single fraction or 10 Gy in two fractions was delivered to the painful regions of the skeletal system. Multiagent chemotherapy consisting of methotrexate, vinblastine, Adriamycin, and cisplatin was given for three cycles. The patient died 28 months after the initial presentation with progression of the disease to pelvis and skeletal sites. The problem of metastatic spread after initial resection should be considered in urachal carcinoma, and adjuvant chemoradiotherapy should improve the outcome in this rare neoplasm.

Adenocarcinoma↗
PubMed2003

Toward a formalization of emergence.

Emergence is a concept widely used in the sciences, the arts, and engineering. Some effort has been made to formalize it, but it is used in various contexts with different meanings, and a unified theory of emergence is still distant. The ultimate goal of a theory of emergence should include using emergence to model, design, or predict the behavior of multiagent systems. The author proposes a formal definition of a basic type of emergence using a language-theoretic and grammar systems approach. It is shown which types of phenomena can be modeled in this sense and what the consequences are for other more complex phenomena.

Artificial Intelligence↗
PubMed1995

Artificial symbiogenesis.

Symbiosis is the phenomenon in which organisms of different species live together in close association, resulting in a raised level of fitness for one or more of the organisms. Symbiogenesis is the name given to the process by which symbiotic partners combine and unify-forming endosymbioses and then potentially transferring genetic material-giving rise to new morphologies and physiologies evolutionarily more advanced than their constitutents. In this article we begin by using the NKC model of coevolution to examine endosymbiosis and its effect on the evolutionary performance of the partners involved. We are then able to suggest the conditions under which endosymbioses are more likely to occur and why; we find they emerge between organisms within a window of their respective "chaotic gas regimes" and hence that the association represents a more stable state for the partners. The conditions under which gene transfer is more likely to represent an advantage for such endosymbionts are then examined within the same model. We find that, providing a suitable pathway exists, such a process can lead to a more efficient genetic configuration for the symbionts within a window that overlaps that in which endosymbioses occur. Finally, the results are used as grounds for implementing symbiogenesis within artificial evolutionary multiagent systems.

Algorithms↗
PubMedDate not supplied

Non-Hodgkin's lymphoma of the larynx in children.

Non-Hodgkin's lymphomas (lymphosarcomas) of the larynx are rare occurrences in children. This paper reports a child 9 years 3 months of age with isolated non-Hodgkin's lymphoma of the larynx, and gives a 15-year follow-up report of a previously published case of a child 4 years 7 months of age. Both children presented with the chief complaint of progressive airway obstruction, and both cases were misdiagnosed, as chronic allergic epiglottitis in the first patient, and nonresponsive croup in the second patient. Once we established a histologic diagnosis and excluded disseminated disease, we instituted treatment with local irradiation and systemic multiagent chemotherapy. Complete remission was achieved, and the two patients have been free of disease since their treatments were started 2 years and 9 years ago, respectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87.

PURPOSE: Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria. PATIENTS AND METHODS: Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed. RESULTS: The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 +/- 0.03 and 0.37 +/- 0.03, respectively, with significant differences between the strategic groups (A, 0.18 +/- 0.05 and 0.20 +/- 0.05; B, 0.44 +/- 0.05 and 0.52 +/- 0.05; C, 0.35 +/- 0.09 and 0.42 +/- 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses. CONCLUSION: With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Phase I clinical trial of mafosfamide in infants and children aged 3 years or younger with newly diagnosed embryonal tumors: a pediatric brain tumor consortium study (PBTC-001).

PURPOSE: A phase I trial of intrathecal (IT) mafosfamide was performed to determine the optimal dose, dose-limiting toxicities, and incidence and severity of other toxicities when administered in association with concomitant multiagent systemic chemotherapy to children younger than 3 years with newly diagnosed embryonal tumors. PATIENTS AND METHODS: Twenty-five assessable patients received IT mafosfamide at one of six dose levels ranging from 5 mg to 17 mg. Patients were premedicated with dexamethasone (0.15 mg/kg) and morphine (0.1 mg/kg) before receiving IT mafosfamide. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. RESULTS: Irritability, presumably secondary to pain or headache during mafosfamide administration, was dose limiting in two of three patients at the 17-mg dose level. The maximum-tolerated dose of IT mafosfamide following premedication with dexamethasone and morphine was 14 mg. CONCLUSION: The maximum tolerated dose and recommended phase II dose of IT mafosfamide in patients younger than 3 years with newly diagnosed embryonal CNS tumors is 14 mg. A trial to assess the efficacy of regional therapy with IT mafosfamide administered with intensive systemic chemotherapy in children younger than 3 years with primary intracranial embryonal tumors is now in progress.

Affect↗
PubMed2001

[Clinical analysis of intracranial metastases in gestational trophoblastic tumour].

OBJECTIVE: To evaluate characteristics of patients with intracranial metastases of gestational trophoblastic tumour (GTT) and determine the prognostic factors and therapeutic modality. METHODS: We retrospectively reviewed the records of 814 GTT patients treated at Peking Union Medical College Hospital from 1984 to 1998. Of them, 382 were choriocarcinoma and 61 developed brain metastases (16.0%); 432 were invasive mole and 8 of them presented brain metastases (1.9%). Patients with brain metastases were divided into three categories: Group A, individuals with no prior chemotherapy (30 cases); Group B, patients who had received chemotherapy before transferred to our hospital (31 cases); Group C, individuals who developed brain metastases during therapy in our hospital (8 cases). Apart from 12 patients died before or during the first cycle of chemotherapy, the remaining 57 patients were treated with 5-FU combined chemotherapy or etopside, methotrexate, kengshengmycin, /vincristine, cyclophosphamide (EMA/CO) regimen, the number of courses varied from 3 to 17 cycles. The median number of chemotherapy for each patient was 8.2. Intrathecal methotrexate chemotherapy was utilized for all patients. Emergency surgical decompression was performed in 4 cases who had symptoms of highly increased intracranial pressure. RESULTS: Apart from 12 patients died before they received regular therapy in our hospital, remission rate of other 57 patients was 71.9%. The cumulative survival rate for these 57 patients at 5 years was 45.8%. Women with no prior chemotherapy (group A) had outcomes significantly better than those who had been treated before transfer to our hospital (group B) and there were no survivors among the patients who developed brain metastases during active chemotherapy (group C) [P < 0.05 (A Vs B); P < 0.01 (A or B Vs C)]. CONCLUSIONS: Multiagent systemic chemotherapy combined with intrathecal methotrexate chemotherapy still play the key role in the management of brain metastatic GTT patients; Surgical decompression should be performed if significant neurologic symptoms are present.

Adult↗
PubMed2005

[Evaluation of emergency craniotomy for the treatment of patients with intracranial metastases of choriocarcinoma].

OBJECTIVE: To study the diagnosis, management and prognosis of intracranial metastases of gestational trophoblastic tumour (GTT) patients who had emergency surgical decompression due to highly increased intracranial pressure. METHODS: Ninety-three patients with intracranial metastases of gestational trophoblastic tumour were hospitalized in our department of Peking Union Medical College Hospital from 1985 to 2004. Thirteen of them who underwent emergency craniotomy were retrospectively analyzed, and all of them presented with raised intracranial pressure and intracerebral haemorrhagic mass. RESULT: Of the thirteen patients who underwent surgery in combination with multiagent systemic chemotherapy, seven achieved complete remission (CR), five had partial remission (PR), and one died of disease progression. CONCLUSIONS: Emergency surgical treatment is the important method of choice for brain metastasis in patients displaying rapidly deteriorating signs. An undetermined intracranial haemorrhage in young female patients of reproductive age group should raise the suspicion of cerebral metastatic choriocarcinoma.

Adult↗
PubMed2005

Management of patients with muscle-invasive and metastatic bladder cancer.

Bladder cancer is the fifth most common cancer diagnosed in the United States. Prognosis for this disease is dependent on both tumor stage and grade. Radical cystectomy has been the standard treatment for muscle-invasive local disease; however, combined-modality approaches with the use of chemotherapy are gaining momentum with data suggesting survival improvement. Patients with metastatic disease have poor long-term survival rates despite systemic multiagent chemotherapy. A variety of agents, including newer cytotoxic drugs and biologically targeted agents, are under investigation to determine the most effective regimen. The special needs of specific patient populations, such as the elderly, those with a suboptimal performance status, and patients with medical comorbidities have gained more attention. Progress in the treatment of this disease is dependent on supporting ongoing and future clinical trials.

Aged↗
PubMed1991

The role of radiation therapy in the treatment of testicular germ cell tumors.

Infradiaphragmatic radiotherapy remains the treatment of choice for patients with stage I and II (small volume) testicular seminoma. With this approach, the disease-free survival rate exceeds 90% to 95%, and the ultimate disease-free survival rate (including salvage) is 95% to 100%. Initial therapy for patients with large-volume stage II, III, and IV disease should include multiagent systemic chemotherapy. Involved field radiotherapy is recommended for these patients following the chemotherapy, especially in patients with residual masses larger than a few centimeters. Although not used frequently in the United States, infradiaphragmatic radiotherapy is a viable treatment option for patients with clinical stage I testicular nonseminomas. Such therapy results in approximately an 85% to 90% relapse-free survival rate, with an ultimate survival rate (including salvage) approaching 100%. Initial therapy for patients with stage II or greater disease generally should include chemotherapy and/or surgery. Radiotherapy is often useful as post-chemotherapy consolidation, especially for unresectable masses. For extra-gonadal seminomas, radiotherapy is useful as definitive therapy for small-volume disease and as consolidative therapy (postchemotherapy) for more advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Large cell lymphoma complicating acute lymphoblastic leukemia.

Non-Hodgkin's lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). We present the pathologic, clinical, immunologic, and ultrastructural features of the third reported example of NHL following successfully treated ALL. This white girl developed ALL with predominantly L1 cells at 3.5 yr of age. The lymphoblasts were terminal deoxynucleotidyl transferase (TdT) positive and were non-B, non-T cells. She achieved a complete remission with standard induction therapy and has remained in continuous complete remission. Four and one-third years after the onset of ALL, she developed multifocal, pleomorphic large cell lymphoma of the small bowel, which resulted in episodes of intussusception and obstruction. These pleomorphic and frequently multinucleated lymphoma cells lacked TdT, common ALL antigen, and all tested markers of B cell, T cell, and histiocyte differentiation. Following three small bowel resections, systemic multiagent chemotherapy, and abdominal irradiation, she is currently free of disease.

Bone Marrow↗
PubMed2005

Description and preliminary evaluation of a Multiagent Intelligent Dosing System (MAIDS) to manage combination insulin-oral agent therapy in type 2 diabetes.

BACKGROUND: Computer decision support systems are potentially effective methods for adjusting insulin, but current models do not take into account simultaneous changes of more than one agent. We describe the development of the Multiagent Intelligent Dosing System (MAIDS, Dimensional Dosing Systems, Wexford, PA) for predicting glycemic outcome in response to concurrent dose adjustments in oral hypoglycemic agents and insulin. METHODS: Retrospective data from a patient cohort with type 2 diabetes who had simultaneous changes in insulin and metformin were analyzed. Glycemic markers (fasting glucose, random glucose, or hemoglobin A1c) expected at the visit subsequent to dose changes were calculated using two methods: the previously reported Intelligent Dosing System (IDStrade mark, Dimensional Dosing Systems), which accounts for changes in only one agent, and the MAIDS. Expected results from both systems were correlated with levels actually observed. RESULTS: We analyzed 32 patients with 40 paired visits. For fasting glucose (n = 8 paired visits), the correlation between expected and observed values was 0.07 when using the IDS but 0.78 when using the MAIDS. For random glucose (n = 16 paired visits) the correlation between expected and observed levels was 0.49 for the IDS but 0.79 for the MAIDS. With hemoglobin A1c as the marker (n = 16 paired visits), the correlation was 0.40 when using the IDS but 0.60 with the MAIDS. CONCLUSIONS: The MAIDS allows better prediction of glycemic outcome in circumstances where both insulin and an oral hypoglycemic drug are changed concurrently. Application of the MAIDS to other clinical scenarios, such as simultaneous adjustment of insulin and carbohydrate intake, requires further study.

Algorithms↗
PubMed2005

A design of multiagent-based framework for volume image construction and analysis.

This paper describes a design of a multiagent-based system that can be used to manage the acquisition and analysis of ultrasonograph images. The major concept is to design a management framework consisting of multiple intelligent agents to direct the ultrasonograph image acquisition and analysis operations carried out using a high-speed bit-parallel architecture efficiently as well as to allow for the construction of 3D images from 2D ones. Volume image operations need reactivity, autonomy, and intelligence of software. Therefore, agents can play an important role in enhancing the overall operation of medical image analysis. The system suggests a set of image analysis operations including smoothing, noise removal, and enhancing techniques. These operations will be implemented using parallel processing architectures while the management framework will consist of different agent types such as: simple reflex agents, agents that keep track of the world, goal-based agents, and utility-based agents. These agents interact with each other and exchange data among themselves in order to achieve a comprehensive speed in performing the volume image construction operations. Guided with the fact that the agent consists of program and architecture, the system deploys parallel processing architectures to implement the image analysis operations. The system is considered a step towards a complete multiagent-based framework for medical image acquisition and analysis.

Algorithms↗
PubMed2026

Artificial intelligence agents and agentic artificial intelligence applied to precision medicine.

Precision medicine seeks to individualise care by integrating multimodal biomedical data, yet most deployed clinical artificial intelligence (AI) remains assistive, providing predictions without managing workflows or adapting autonomously. Agentic AI, built on large language models (LLMs), has emerged as a paradigm characterised by autonomy, goal-directed reasoning, memory, planning and tool use. This review synthesises evidence on agentic AI and LLMs applied to precision medicine, encompassing drug discovery, genomics, oncology, rare disease diagnostics and clinical pharmacology. This review also examines architectural components, recent validation milestones and emerging challenges, including hallucination, sociodemographic bias and evolving regulatory frameworks across the FDA, the EU AI Act and the WHO.

agentic AI↗
PubMed1978

[Juvenile rhabdomyosarcoma. Diagnosis and new therapeutic possibilities].

Seventeen children with rhabdomyosarcoma stage I to III diagnosed since 1973 are presented. The coordinated management utilizing surgical excision, irradiation (5000 rad) and systemic adjuvant multiagent chemotherapy is described. The favorable sites were head and neck sites and genitourinary region. The mean survival is at present 19 months. 14 children are alive and well. 13 children had no tumor recidivation, 1 child had 8 months after beginning of the therapy lung metastases which after irradiation with 2000 rad disappeared. 3 children (stage III) died 9, 14 and 20 months after diagnosis during therapy by metastases. Acute and late effects on normal tissues from radiation and chemotherapy were noted in 12 cases. A review of the literature and therapeutic alternatives in the future are indicated.

Child↗
PubMed2001

Erythrodermic cutaneous T-cell lymphoma with disseminated pustulosis. Production of high levels of interleukin-8 by tumour cells.

Interleukin (IL) -8 is a neutrophil chemoattractant cytokine with proinflammatory and growth-promoting activities, which is involved in the pathogenesis of several inflammatory diseases. It is found in high amounts in lesional biopsies of pustular diseases such as psoriasis and palmoplantar pustulosis. We report a 50-year-old woman with a 10-year history of erythroderma with disseminated pustulosis. Skin biopsies showed an epidermotropic infiltrate composed of atypical CD4+ CD8+ lymphocytes with numerous admixed neutrophils. Peripheral blood flow cytometric analysis revealed a major clonal subset of CD3+ CD4+ CD8+ T-cell receptor Vbeta22+ atypical lymphocytes. Bone marrow biopsy, lymph node biopsy and computed thoracoabdominal tomography were normal. Serologies for human T-cell lymphotropic virus type I and human immunodeficiency virus were negative. Our patient's status deteriorated despite topical (nitrogen mustard, psoralen plus ultraviolet A) and systemic (interferon, methotrexate, multiagent chemotherapy) treatments, and she finally died. We showed that our patient's peripheral blood lymphocytes (PBL) spontaneously produced high amounts of IL-8. In contrast, PBL of patients with classical Sézary syndrome produced lower amounts of IL-8. The production of IL-8 by tumour T cells could explain this unusual clinical and histopathological presentation of cutaneous T-cell lymphoma as disseminated pustulosis.

Dermatitis, Exfoliative↗