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At least 109 records · Page 6Linked to original sources

Development and results of biochemotherapy in metastatic melanoma: the University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: Systemic therapy for metastatic melanoma includes chemotherapy, either with dacarbazine alone or a multiagent combination regimen, and biologic therapy with recombinant interferon-alpha and/or recombinant interleukin-2. However, neither of these treatment options has produced long-term control of disease except on rare occasions. We have therefore developed a combined biochemotherapy program in an effort to improve long-term control of metastatic melanoma. PATIENTS AND METHODS: Between October 1990 and October 1993, we treated 115 patients with a triple-drug chemotherapy regimen--CVD (cisplatin, vinblastine, dacarbazine)--in combination with biotherapy using recombinant interleukin-2 and recombinant interferon-alpha. This program of biochemotherapy has evolved from an initial protocol of sequential use of CVD followed by biotherapy, called sequential biochemotherapy, to a more recent protocol of concurrent administration of all five drugs, called concurrent biochemotherapy. Sixty-two patients have been treated with the sequential regimen and 53 patients with the concurrent regimen. RESULTS: Among the 114 evaluable patients, we have observed 24 complete responses (21%) and 45 partial responses (39%) for an overall response rate of 60%. From the group of 24 complete responders, 12 patients (10% of the total) have achieved long-term remissions and have remained disease free for periods of time ranging from 4+ to 6+ years. CONCLUSION: Although the overall results of sequential versus concurrent biochemotherapy are similar, the toxicity appears to be less severe in patients treated with the concurrent regimen. The overall median survival of patients treated with biochemotherapy appears to be longer compared with our previous experience with CVD chemotherapy used alone (12 vs 9 months). Based on the encouraging results obtained with biochemotherapy, phase III studies have been initiated to compare prospectively biochemotherapy with chemotherapy (CVD regimen) alone.

Adolescent↗

Biochemotherapy for melanoma.

Systemic therapy for advanced melanoma includes chemotherapy, either with dacarbazine (DTIC) alone or a multiagent combination chemotherapy, and biologic therapy with recombinant interferon-alpha and/or interleukin-2. However, none of these treatment options has produced long-term control of the disease except on rare occasions. Combined chemo-immunotherapy (biochemotherapy) has shown high objective response rates (approximately 50%) and a significant though small proportion of long-term complete responders in metastatic melanoma. It has, however, been associated with greater toxicity. Overall results of sequential versus concurrent biochemotherapy are similar, but the toxicity appears to be less severe in patients treated with the concurrent regimen. At this time, biochemotherapy is under evaluation in a well-designed prospective, randomized trial to identify whether there is benefit to this strategy, compared with chemotherapy alone.

Animals↗

[Result of registration and follow-up system of gestational trophoblastic disease in Shizuoka Prefecture (from 1977 to 1988)--recent trend and choriocarcinoma following term gestation].

The remission rate of choriocarcinoma has greatly improved since the introduction of effective multiagent chemotherapy combined with aggressive surgical therapy and radiotherapy. In addition to these, the registration and follow-up of gestational trophoblastic disease (GTD) also has been playing an important role in the early detection and treatment of choriocarcinoma following hydatidiform mole. The system for the registration and follow-up of GTD was started in 1977 in Shizuoka Prefecture. In the present series, the results obtained with this registration and follow-up system from 1977 to 1988 in Shizuoka Prefecture were reviewed and analysed. 1) One thousand, nine hundred and twenty-five cases of hydatidiform mole, 68 cases of invasive mole, 70 cases of persistent trophoblastic disease and 48 cases of choriocarcinoma were registered in 12 years. The overall registration rate was 97.4%. 2) The number of cases of hydatidiform mole registered has decreased from about 180 cases to about 140 cases per year, probably due to the decreasing birth rate. 3) The number of cases of choriocarcinoma registered has recently been decreasing significantly and the number of cases of registered invasive mole and persistent trophoblastic disease has decreased slightly. 4) Antecedent pregnancy with choriocarcinoma including clinical choriocarcinoma has been changing from "post-molar" to "post-term" in the past 12 years. The prognosis of the patient with choriocarcinoma following hydatidiform mole has improved by the early detection and treatment since the introduction of the registration and follow-up system. More attention should be paid to choriocarcinoma following term gestation not yet included in the registration and follow-up system to facilitate early detection and treatment.

Adult↗

Predictability of large future changes in a competitive evolving population.

The dynamical evolution of many economic, sociological, biological, and physical systems tends to be dominated by a relatively small number of unexpected, large changes ("extreme events"). We study the large, internal changes produced in a generic multiagent population competing for a limited resource, and find that the level of predictability increases prior to a large change. These large changes hence arise as a predictable consequence of information encoded in the system's global state.

Biological Evolution↗

Acute nonlymphocytic leukemia developing during the course of Ewing's sarcoma.

Two children with Ewing's sarcoma developed acute nonlymphocytic leukemia (ANLL) during the course of their illness. One patient developed ANLL after apparently successful treatment of his primary malignancy with radiation therapy and multiagent chemotherapy. In the second patient, acute leukemia developed before the administration of radiotherapy or systemic chemotherapy. The development of secondary ANLL after Ewing's sarcoma has been reported only twice previously, most likely representing a therapy-induced complication. The occurrence of ANLL in Patient 2 prior to therapy suggests that these two disorders may have a more than treatment-related association. Close follow-up of long-term survivors of Ewing's sarcoma with surveillance for secondary acute leukemia is advised.

Acute Disease↗

Continual planning and scheduling for managing patient tests in hospital laboratories.

Hospital laboratories perform examination tests upon patients, in order to assist medical diagnosis or therapy progress. Planning and scheduling patient requests for examination tests is a complicated problem because it concerns both minimization of patient stay in hospital and maximization of laboratory resources utilization. In the present paper, we propose an integrated patient-wise planning and scheduling system which supports the dynamic and continual nature of the problem. The proposed combination of multiagent and blackboard architecture allows the dynamic creation of agents that share a set of knowledge sources and a knowledge base to service patient test requests.

Artificial Intelligence↗

Bone density in survivors of childhood cancer.

Advances in combination chemotherapy, radiation therapy, surgery, and bone marrow transplantation have resulted in markedly improved survival rates for many children with cancer. Advancements in therapy, however, have led to new concerns, namely long-term consequences of effective treatments. Young adult and adult survivors of childhood cancer are at risk for a number of disorders related to therapy. Specifically, the young adult who has survived cancer, attendant treatments, and their complications is at risk for factors that can lead to suboptimal acquisition of peak bone mass. These factors include chronic illness, nutritional deficiencies, limited physical activity, and treatment with glucocorticoids, multiagent chemotherapy, and radiation. The long-term adverse effects of these therapies on endocrine systems, especially sex steroid and growth hormone deficiencies, are additional risk factors for some patients. After a brief review of the processes associated with acquisition of peak bone mass in the young adult, this article examines the impact of cancer and cancer therapy on bone mineral density in survivors of childhood cancer.

Adolescent↗

Malignant bone tumors in children: osteosarcoma.

Osteosarcoma is a rare malignant tumor of bone that produces osteoid. Most tumors arise in the metaphyses of long bones. At least 80 per cent of patients have subclinical metastases at diagnosis. Successful management of osteosarcoma requires surgical control of the primary tumor and chemotherapeutic control of systemic metastases. Wide resection of primary tumor is often compatible with limb-sparing surgery. Multiagent chemotherapy has significantly enhanced disease-free survival. Osteosarcoma metastasizes to lung and other bones. Aggressive surgical resection can sometimes control pulmonary metastases; bony metastases are almost always followed by death.

Adolescent↗

Alveolar rhabdomyosarcoma of the larynx: case report and literature review.

We report the 11th well-documented case of laryngeal rhabdomyosarcoma and only the second of laryngeal alveolar rhabdomyosarcoma. The optimum treatment of head and neck rhabdomyosarcoma has not yet been defined, but it appears that the ideal should consist of an aggressive multimodality approach. This includes surgical extirpation if it can be done without major morbidity, postoperative radiotherapy with a margin around known and suspected disease, and multiagent chemotherapy. Unlike most sarcomas, rhabdomyosarcoma (especially alveolar rhabdomyosarcoma) spreads by way of the lymphatic system as well as the blood stream. Inclusion of the draining lymphatics in the radiation field must be given strong consideration.

Combined Modality Therapy↗

Transboundary aquifers: a global program to assess, evaluate, and develop policy.

Transboundary aquifers are as important a component of global water resource systems as are transboundary rivers; yet, their recognition in international water policy and legislation is very limited. Existing international conventions and agreements barely address aquifers and their resources. To rectify this deficiency, the International Association of Hydrogeologists and UNESCO's International Hydrological Programme have established the Internationally Shared (transboundary) Aquifer Resource Management (ISARM) Programme. This multiagency cooperative program has launched a number of global and regional initiatives. These are designed to delineate and analyze transboundary aquifer systems and to encourage riparian states to work cooperatively toward mutually beneficial and sustainable aquifer development. The agencies participating in ISARM include international and regional organizations (e.g., Organization of American States, United Nations Environment Programme, United Nations Economic Commission for Europe, Food and Agriculture Organization, and South African Development Community). Using outputs of case studies, the ISARM Programme is building scientific, legal, environmental, socioeconomic, and institutional guidelines and recommendations to aid sharing nations in the management of their transboundary aquifers. Since its start in 2000, the program has completed inventories of transboundary aquifers in the Americas and Africa, and several ISARM case studies have commenced.

Conservation of Natural Resources↗

Intensive systemic chemotherapy in localized Ewing's sarcoma in childhood. A historical trial.

To assess the value in Ewing's sarcoma of a new multiagent therapy (vincristine, cyclophosphamide, Adriamycin, (doxorubicin) procarbazine), 30 children with a localized tumor (eight distal, nine proximal, 13 central lesions) treated at the Institut Gustave-Roussy between 1973 and 1976 (E3), were pair-matched by site of primary with 30 control patients treated without intensive chemotherapy between 1967 and 1972 (E1) at the same institution, both groups having the same local radiotherapy. Actuarial survival and disease-free survival rates at six years were significantly higher in E3 at P less than 0.01, respectively, 58% and 49% versus 25% in E1. The prognostic value of the primary site was ascertained only in children under chemotherapy. In this group there were six early relapses with death within 14 months and nine late relapses at 21 to 38 months. Among these nine patients, six died, one is living with disease, and two are currently alive in second remission. Fifteen patients are continuously free of disease 50 to 90 months after first treatment (median, 69 months): functional sequelae are minimal in six, moderate in seven, and severe in two children with limb amputation. It is concluded that in future treatments chemotherapy must be intensified and begun prior to local treatment which has to be reevaluated for radiation modalities and for radical surgery indication.

Adolescent↗

[Ewing's tumor].

Ewing's tumor (ET) is a malignant bone tumor occurring in children and young adults. ET affects mainly bones of the central axis, and almost always involves soft tissue infiltration. The discovery of a unique genetic alteration, which is a reciprocal translocation most frequently resulting in the fusion of the EWS gene situated on chromosome 22 with the FLI-1 gene on chromosome 11, currently places ET among neuroectodermal tumors. Moreover, this translocation is a tumor-specific genetic marker at the basis of defining ET today and is used as a diagnostic and potentially prognostic tool complementary to imaging and histopathological work-up. Since the 1970 s, important progress has been made in the clinical management of ET patients. Multiagent chemotherapy in association with local treatment (surgery and/or radiation) has clearly improved outcome. The introduction of systemic treatment was justified by the frequent sub-clinical diffusion of apparently localized ET. Intensified therapeutic strategies have for the first time cured some metastatic ET patients, but at the cost of major side effects. Treatment is currently adapted as a result of a better definition of prognostic factors as well as a better assessment of its adverse effects. Improvement in global patient care and increased management of specific acute complications associated with ET (often interwoven with iatrogeneous effects) represent an important step towards improving the quality of life for ET patients as well as preventing long term complications. In the light of present studies, the majority of surviving adults today describe their health and quality of life as good. ET is a fascinating example of the progress made not only in the diagnostic and therapeutic approach to cancer but also in the comprehension of the mechanisms behind carcinogenesis, and consequently reflects the revolution of medicine over the last century.

Adolescent↗

Rectal lymphoma in homosexual men.

Lymphoma of the rectum is a rare tumor and in most studies is not separated from other lymphomas of the large intestine. We have recently examined four homosexual men with lymphoma presenting in the rectum. Symptoms included rectal bleeding in three, pain on defecation in two, and mucoid rectal discharge in two. Systemic "B" symptoms (ie, fever, night sweats, and/or weight loss), as well as a rectal mass, were present in all four. All were high-grade tumors, with B-cell immunoblastic sarcoma in two and small noncleaved Burkitt-like lymphoma in two. Intracytoplasmic immunoperoxidase staining revealed monoclonal kappa light chains in three tumors, whereas the fourth was nonstaining. Immunologic abnormalities were similar to those reported in patients with acquired immunodeficiency syndrome. Antibodies to human T-cell lymphotropic virus type III were found in the three cases tested, and retrovirus was cultured from lymphomatous tissue in one. Despite multiagent chemotherapy, two patients died within six months of diagnosis and a third has recently suffered relapse within the central nervous system.

Acquired Immunodeficiency Syndrome↗

The Société Française d'Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia.

This study was undertaken to show that a high survival rate can be obtained in B-cell (Burkitt and large B-cell) lymphoma and L3 leukemia with multiagent chemotherapy adapted to the tumor burden (stage, resection status, percentage of blasts in bone marrow, and central nervous system [CNS] involvement) and early response to chemotherapy, to investigate actual prognostic factors, and to see if large B-cell lymphoma can be treated with the same regimen as Burkitt lymphoma. Patients were classified into 3 risk groups. Group A (resected stage I and abdominal stage II) received 2 courses of vincristine, cyclophosphamide, doxorubicin, and prednisone. Group B (patients not eligible for groups A or C) received 5 courses of chemotherapy with, in addition, high-dose methotrexate, 3 g/m(2) over 3 hours; infusional cytarabine; and intrathecal (IT) methotrexate. Group C (patients with CNS involvement and acute lymphoblastic leukemia with at least 70% of blasts in bone marrow) received 8 courses with, in addition, high-dose methotrexate, 8 g/m(2); high-dose cytarabine; etoposide; and triple IT. Except in group A, treatment started with a prephase (COP, low-dose vincristine and cyclophosphamide). It was intensified for patients who did not respond to COP in group B and any patient with residual viable cells after the consolidation phase. A total of 561 patients were enrolled in the SFOP LMB89 protocol (July 1989-June 1996). Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and event-free survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI, 77%-90%) for group A, B, and C, respectively. In group B, multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value, no response after COP, and age of at least 15 years were associated with a lower EFS. CNS involvement was the only prognostic factor in group C. (Blood. 2001;97:3370-3379)

Adolescent↗

Epidemiology, clinical characteristics, and management of AIDS-related lymphoma.

Although primary central nervous system (CNS) lymphoma was considered part of the spectrum of AIDS from the outset, systemic non-Hodgkin's lymphoma is considered a rather late manifestation of HIV infection. Any group at risk for AIDS may develop HIV-related lymphoma, and the characteristics of disease in all groups appear identical. The majority of these lymphomas are of the high-grade, B-cell types, including B-immunoblastic lymphoma and small noncleaved, Burkitt or non-Burkitt. Advanced, extranodal disease is seen at diagnosis in the majority of patients, who often present with widespread disease involving multiple organs. Central nervous system disease may be seen in the absence of systemic lymphoma ("primary CNS lymphoma") and carries a particularly poor prognosis. Leptomeningeal involvement is the most common central nervous system manifestation of systemic HIV-related lymphoma, and its presence does not imply a worse prognosis. Although very intensive regimens of multiagent chemotherapy have been employed in patients with HIV-related lymphoma, several studies indicate that these patients may not be able to tolerate such dose intensity. Newer regimens, employing lower dose-intensive regimens with early CNS prophylaxis, may be effective in inducing remissions in approximately half of treated individuals, who may attain long-term, lymphoma-free survival.

Acquired Immunodeficiency Syndrome↗

Systemic Hodgkin's lymphoma in a patient with Sézary syndrome.

We report a case of a 71-year-old male with Sézary syndrome diagnosed in 1996 who subsequently developed systemic Hodgkin's lymphoma. His only past treatment was bath psoralen plus ultraviolet A. He has since been treated with multiagent chemotherapy (ChlVPP/PABLOE) which induced a remission in his Hodgkin's disease. Eighteen months later he remains in remission from Hodgkin's disease but the Sézary syndrome remains active. He has also developed a squamous cell carcinoma on the upper lip. Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by a malignant proliferation of CD4-positive cells in the skin and peripheral circulation. The CD4 count may be markedly elevated but this results from expansion of a neoplastic T-cell clone and there is a relative lymphopenia of normal T cells leading to a degree of immunoparesis. Immunosuppression is known to be associated with an increased rate of malignancies and this may account for the occurrence of Hodgkin's disease and squamous cell carcinoma in this patient with Sézary syndrome.

Aged↗

A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.

AIM: Our experience of pre-operative intraarterial (i.a.) vs intravenous (i.v.) infusion of cisplatinum (CDP) in a multiagent neo-adjuvant chemotherapy for osteosarcoma of the extremity is reported. METHODS: Two successive randomized studies were performed. In the first, pre-operatively, CDP i.a. vs CDP i.v. was applied in combination with high-dose methotrexate (HDMTX) and adriamycin (ADM) within a three-drug regimen. In the second, a combination of HDMTX, ADM and IFO, within a four-drug regimen was tested. RESULTS: The rate of responses to chemotherapy (tumour necrosis > or = 90%) was significantly higher (P<0.04) for the 142 patients treated with the four-drug regimen than in the 79 patients treated with a three-drug regimen (76%vs 62%). According to the route of CDP infusion, in the three-drug regimen the rate of responses was significantly higher (P=0.004) in patients treated with i.a. CDP (77%) than in patients treated i.v. (46%); with the four-drug regimen the rate of response was not significantly different in patients treated i.a. (81%) and in patients treated i.v. (71%). No significant differences in the rates of limb salvages, local recurrence and event-free survival (EFS) were seen between the i.a. and the i.v. groups. CONCLUSION: In the treatment of osteosarcoma of the extremity, the i.a. infusion of CDP does not offer any significant advantage when this drug is used within an aggressive, multiagent, pre-operative four-drug regimen.

Adolescent↗

Combined modality treatment for osteosarcoma occurring as a second malignant disease. Cooperative German-Austrian-Swiss Osteosarcoma Study Group.

PURPOSE: The prognosis of osteosarcoma occurring as a second malignant disease (OS-SMD) is thought to be poor. We attempted to evaluate whether this holds true when OS-SMD is treated with combined modality therapy as developed for primary osteosarcoma and if factors that influence survival might be identified. PATIENTS AND METHODS: All patients with OS-SMD registered at the Cooperative German-Austrian-Swiss Osteosarcoma Study Group (COSS) study center between 1980 and June 1996 were evaluated for patient- and treatment-related factors, local and systemic outcome, and survival. Therapy was to be given according to contemporary COSS protocols for primary extremity osteosarcoma, including surgery and multiagent chemotherapy. RESULTS: Thirty patients with OS-SMD were registered (median latency period, 9 years 2 months). The first malignancies had been retinoblastoma (10 patients), sarcoma (10 patients), lymphoma (five patients), carcinoma (four patients), and medulloblastoma (one patient). Treatment for these malignancies had included radiotherapy in 24 patients, surgery in 20, and chemotherapy in 14. Twelve osteosarcomas were located axially and 18 were located in an extremity; 17 were radiation-related. Twenty-seven patients presented with localized disease; three presented with primary metastases (two skip, one lung). All 30 patients received chemotherapy, 29 with multiple drugs. Twenty-eight patients underwent operation. At 7 years, actuarial overall survival, survival free from osteosarcoma progression, and survival free from progression of any cancer were 50%, 34%, and 30%, respectively. In 24 patients with local tumor control, the corresponding values were 63%, 46%, and 38%. All seven local failures occurred in patients with axial osteosarcomas who did not undergo operation with wide surgical margins. CONCLUSION: Provided that local tumor control is achieved, OS-SMD treated with combined modality therapy may have a prognosis that approaches that of otherwise comparable primary osteosarcoma.

Adolescent↗