SEARCH · PubMed Health

Results for “multiagent systems”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1998

Recognition and treatment of osteosarcoma in the military health care system.

Forty-two patients with high-grade intramedullary osteosarcoma treated at Walter Reed Army Medical Center between 1985 and 1995 were reviewed to determine what effects military "managed health care" had on diagnosis, treatment, and outcome. Five-year survival was 61% overall (SE +/- 9.9%), despite local disease control obtained in 95% of patients. There was a statistically significant difference between active duty members and dependents in time to diagnosis (p = 0.008), yet there was no significant difference in survival between the two groups. Five-year survival in our patient population was slightly lower than 5-year survival reported in some large civilian medical centers despite good local disease control and intensive multiagent chemotherapy. Delays in diagnosis and military status had no apparent effect on survival, although limb salvage was not possible in nearly 40% of patients because of tumor size, disease extent, and involvement of neurovascular structures.

Adult↗

PubMed2004

Analysis of treatment for small cell cancer of the bladder and report of three cases.

OBJECTIVES: To present our experience with 3 patients with small cell cancer (SCC) of the bladder who were treated with different modalities and review the literature for patients undergoing primary chemoradiotherapy. SCC of the bladder is a rare tumor, with patients commonly presenting with metastatic disease. Surgery, radiotherapy, and chemotherapy, either alone or as part of combined therapy, have been used. Because of the rarity of this disease, no prospective studies evaluating the most effective treatment have been done. METHODS: The medical records of 3 patients diagnosed with SCC of the bladder at our institution were reviewed. Additionally, we reviewed published reports to identify all cases of SCC of the bladder treated with primary chemoradiotherapy. RESULTS: Three patients with SCC of the bladder were identified at our institution. A total of 23 patients with SCC of the bladder who were treated with primary chemoradiotherapy were identified: 22 in published reports and 1 at our institution. Patients presented with muscle-invasive disease (17%), extravesical disease only (26%), and metastatic disease (52%). Multiagent chemotherapy was administered to most patients. The reported median radiation dose was 6000 cGy. A total of 16 patients (70%) were alive at a median follow-up of 34 months. The median survival of patients had not yet been reached in this study at the last follow-up. We did not find any reports of SCC recurrence in the bladder, and the bladder was preserved in most patients (87%). CONCLUSIONS: SCC of the bladder should be viewed as a systemic disease, because most patients present with metastatic disease. Primary chemoradiotherapy appears to be an effective treatment modality. Prospective studies are needed to evaluate the optimal treatment further.

Aged↗

PubMed2003

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.

Adolescent↗

PubMed1992

Immunohistochemical identification of P-glycoprotein in previously untreated, diffuse large cell and immunoblastic lymphomas.

Expression of P-glycoprotein has been linked to multidrug resistance in cancer cell lines and human tumors. We investigated the frequency and clinical significance of P-glycoprotein immunoreactivity in 57 previously untreated diffuse large cell and immunoblastic lymphomas. Banked frozen tissue, which had been obtained prior to chemotherapy, was tested for reactivity with 2 monoclonal antibodies (MRK16 and C219) that recognize different domains of P-glycoprotein, using an immunoperoxidase technique. Thirteen of 57 lymphomas (23%) showed strong staining of greater than 50% of neoplastic cells; 15 of 57 (26%) showed labeling of a minority (11-50%) of neoplastic lymphocytes; 14 of 57 (25%) yielded equivocal results (reactivity in less than 10% of cells); and 15 of 57 (26%) were negative for P-glycoprotein. The 2 monoclonal antibodies were comparable in reactivity. Expression of MDR-1 mRNA was determined in 6 cases with sufficient available tissue, and did not correlate well with the percentages of cells reactive for P-glycoprotein by immunohistochemistry. Thirty-nine of our 57 patients completed multiagent chemotherapy. Contrary to our expectations, we found that P-glycoprotein immunoreactivity did not decrease the likelihood of response to induction chemotherapy. Median survival also was not adversely affected.

ABO Blood-Group System↗

PubMed2003

Principles of treatment for mast cell tumors.

Mast cell tumors (MCT) are the most common malignant cutaneous tumors that occur in dogs. They are most commonly found on the trunk, accounting for approximately 50% to 60% of all sites. MCTs associated with the limbs account for approximately 25% of all sites. Cutaneous MCTs have a wide variety of clinical appearances. Histologic grade is the most consistent prognostic factor available for dogs. MCTs located at 'nail bed' (subungual), inguinal/preputial area, and any mucocutaneous area like perineum or oral cavity carry a guarded prognosis and tend to metastasize. MCTs usually exfoliate well and are cytologically distinct. The extent of staging procedures following fine-needle aspirate cytologic diagnosis is based on the presence or absence of negative prognostic indicators. Surgery is the treatment of choice for solitary MCTs with no evidence of metastasis. Reponses rates to chemotherapy, (partial response) as high as 78% have been reported, and preliminary evidence suggests that multiagent (prednisone and vinblastine) protocols may confer a higher response rate than single-agent therapy. MCTs are the second most common cutaneous tumor in the cat. There are two distinct forms of cutaneous MCTs in the cat. The more common form is the mastocytic form, and the less common is the histiocytic form. Unlike in the dog, the head and neck are the most common sites for MCTs in the cat followed by the trunk and limbs. Cats with disseminated forms of MCT often present with systemic signs of illness, which include depression, anorexia, weight loss, and vomiting. The diagnosis and staging of MCTs in cats is similar to that in the dog. As with dogs with cutaneous MCTs, surgery is the treatment of choice. Little is known about the effectiveness of adjunctive chemotherapy options for cutaneous MCTs. Adjunctive chemotherapy does not appear to increase survival times.

Animals↗

PubMed1981

Immunoblastic sarcoma of T-cell versus B-cell origin: I. Clinical features.

Within the Lukes-Collins classification system of malignant lymphoma, a tumor of large transformed lymphocytes, termed immunoblastic sarcoma (IBS), is described. This morphological type would have been included within the "histiocytic" category of Rappaport. Immunoblastic sarcoma may be of B-lymphocytic or T-lymphocytic origin. Since differences or similarities of these two variants have not yet been described, we reviewed the case histories of 35 such patients, all of whom had immunologic marker studies performed. Nineteen patients had T-cell IBS (T-IBS), whereas 16 had B-cell IBS (B-IBS). Median age for both groups was approximately 50 yr. A history of prior immune disorder was found in 31% of B-IBS and 16% of T-IBS cases. Prior lymphoproliferative malignancy was noted in 21% of T-IBS and 13% of B-IBS patients. All T-IBS patients first presented because of lymphadenopathy, whereas 56% of B-IBS cases initially presented because of extranodal disease. Systemic "B" symptoms were common in both. Similarly, most patients had widespread disease (stage III or IV) at diagnosis. Clinically suspected hepatic (p = 0.05) and retroperitoneal node (p = 0.01) involvement were more often found in T-IBS. Forty-one percent of T-IBS patients demonstrated polyclonal hypergammaglobulinemia, a finding seen in no B-IBS patient (p = 0.02). Although not statistically significant because of small numbers of patients, data on therapy and survival suggest that IBS of B-cell type may be successfully treated with aggressive, multiagent chemotherapy, while alternative approaches appear warranted in T-cell disease.

Adult↗

PubMed2002

Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms.

We describe five patients with treated low-grade B-cell neoplasms who subsequently developed Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma in one patient. All patients had received treatment with fludarabine for the low-grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs arose 2-12 months after completion of fludarabine therapy and morphologically resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency. Molecular genetic studies showed that these lesions were clonally distinct from the low-grade B-cell neoplasm in three of four cases assessed. Two patients did not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both patients but recurred in one. One patient underwent surgical excision and remains without evidence of the EBV-BLPD. One patient received aggressive multiagent chemotherapy with a complete response initially, but the EBV-BLPD recurred after 12 months. One patient received antiviral therapy and responded completely but died 2 months later of an opportunistic infection. We conclude that patients with low-grade B-cell neoplasms treated with fludarabine, possibly in combination with other immune suppressive agents, may subsequently develop EBV-BLPDs that morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of these lesions may regress without systemic therapy.

Antineoplastic Agents↗

PubMed1996

Treatment of femoral Ewing's sarcoma.

BACKGROUND: The treatment of Ewing's sarcoma consists of chemotherapy for systemic and local disease. However, the role of radiation therapy, and/or surgical resection for definitive local treatment has yet to be determined. METHODS: A retrospective review of 32 patients (24 males and 8 females) treated for femoral Ewing's sarcoma between 1970 and 1985 was performed. Patients were divided into 3 treatment groups: chemotherapy and radiotherapy (CR) (10); chemotherapy and surgery (CS) (9); and chemotherapy, surgery, and radiotherapy (CSR) (13). Patients in the CR group received a mean of 5320 centigray (cGy) of radiation and patients in the CSR group received a mean of 3590 cGy. Multiagent cyclophosphamide/doxorubicin based chemotherapy was used in all cases. Surgery consisted of wide resection or amputation. RESULTS: Patients in the CR group had a higher risk of local recurrence than patients in the CS and CSR groups (P=0.02, log rank). The combination of local recurrences and treatment complications necessitated surgery for 7 of 10 CR patients, whereas 1 of 9 and 4 of 13 in the CS and CSR groups required additional surgery. The median survival for the entire group was 39 months. Minimum follow-up for surviving patients was 45 months. Five-year survival consisted of 1 of 10 patients in the CR group, 2 of 9 in the CS group, and 7 of 13 in the CSR group. There were no statistically significant differences among the three survival curves. Tumor location within the femur was a significant prognostic variable. Distal femoral location had a survival advantage compared with proximal and mid-femur locations (P = 0.049, log rank). CONCLUSIONS: Femoral Ewing's sarcoma remains a disease with a poor prognosis. Radiation alone for local treatment results in a high rate of local recurrence and complications. Our current local treatment strategy for femoral Ewing's sarcoma includes surgery in all and adjuvant radiotherapy in many of the patients.

Adolescent↗

PubMed1990

Ranitidine compared to cimetidine in multiagent pharmacological treatment of porcine Pseudomonas ARDS.

The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists.

Animals↗

PubMed1993

Richter's syndrome: a report on 39 patients.

PURPOSE: The incidence, clinical features, laboratory findings, and treatment results of 39 patients with Richter's syndrome (RS) are reported. PATIENTS AND METHODS: Thirty-nine of 1,374 patients with chronic lymphocytic leukemia (CLL) developed RS. RESULTS: Features associated with RS included systemic symptoms (59%), progressive lymphadenopathy (64%), extranodal involvement (41%), elevation of lactate dehydrogenase (LDH; 82%), and a monoclonal gammopathy (44%). Analysis of the CLL karyotype showed no specific chromosomal abnormality that conferred increased risk; however, multiple abnormalities were common. Patients at all Rai stages and in complete response (CR) were at risk, including three CR patients with no residual disease at the level of detection by dual-parameter flow cytometry or restriction analysis for immunoglobulin (Ig) gene rearrangements. The incidence was not higher in patients who had received prior fludarabine or chlorodeoxyadenosine. The median survival duration was only 5 months, despite multiagent therapy. Patients who responded had prolonged survival durations (P < .001). Three of eight patients who survived more than 1 year had a de novo presentation of both CLL and large-cell lymphoma (LCL). Comparison of surface light-chain analysis from both low- and high-grade components demonstrated isotypic light-chain expression in 12 of 15 patients. Ig heavy- and light-chain gene rearrangement analysis showed identical rearrangement patterns in five of five patients. CONCLUSION: The clinical, laboratory, and survival characteristics of our RS patients were similar to those reported in earlier studies. Ig gene rearrangement and light-chain isotype analysis support a common origin for CLL and LCL. Despite progress in the treatment of CLL, the development of LCL remains a serious complication and continued surveillance in all CLL patients is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Primary osteosarcoma in adults older than 40 years.

The aim of the current study was to determine the prognostic factors of primary osteosarcoma in adults. This is a review of 47 patients older than 40 years (27 men and 20 women) who were treated between 1977 and 1998 at the authors' institution. Tumors involved the lower limbs in 26 patients and the axial skeleton in 18 patients (38.3%). Eight patients (17%) had synchronous pulmonary metastasis and seven had a pathologic fracture before the definitive surgery. At review, 33 patients had died and 13 were alive. Twenty-one patients (44.7%) did not receive any form of systemic treatment. Tumors were treated surgically in 42 patients (89%). Local recurrence was documented in seven patients (17%). Metastasis after diagnosis appeared in 29 patients (61.7%). The 5-year disease-free survival and overall survival rates were 32.54% and 41.64%, respectively. Adult patients (> 19 years) with primary osteosarcoma had a poor clinical outcome. Metastatic disease at presentation or later, a pathologic fracture, large tumor volumes, and inadequate margins at the time of surgery were associated with significantly lower survival. The high number of adults presenting with advanced stage lesions and more tumors in the axial location might explain the high rate of recurrences. Aggressive multiagent regimens are needed to improve survival.

Adult↗

PubMed1990

Lymphoblastic lymphoma in adult patients: clinicopathological features and response to intensive multiagent chemotherapy analogous to that used in acute lymphoblastic leukemia.

This paper analyzes the clinicopathological features of 31 consecutive adult patients with lymphoblastic lymphoma (LBL) and reports on our experience in treating them with two successive multidrug programs analogous to those used in acute lymphoblastic leukemia (ALL) in adults. Protocol 1 (18 patients) consisted of an intensive four-drug induction therapy (daunorubicin, cyclophosphamide, vincristine, prednisone), CNS prophylaxis (cranial irradiation and intrathecal methotrexate), and continuous maintenance with methotrexate and mercaptopurine for three years, with periodical reinductions with vincristine and prednisone. Protocol 2 (13 patients) included a similar induction regimen (doxorubicin instead of daunorubicin, dexamethasone instead of prednisone), followed by post-remission intensification with alternating courses of non-cross-resistant agents (amsacrine and high dose cytarabine; vincristine, cyclophosphamide and doxorubicin; etoposide and conventional dose cytarabine) given in a cyclical eight-month program. CNS prophylaxis consisted of intrathecal methotrexate and systemic high-dose cytarabine. The patient characteristics of the two therapy groups were comparable. The complete remission (CR) rate for both groups was 77%, with a median overall and relapse-free survival of 18 and 29 months, respectively. The three-year overall survival of complete remitters was 59%. No correlation was found between CR rate and age, mediastinal, or bone marrow involvement. Stage I disease had a significantly higher CR rate (100%) than did stages II-IV (64%). Leukemic evolution occurred in 32% of cases, within a median time of 11 months from diagnosis; meningeal disease developed in six cases (19%); in four of them leukemia was concomitant. No significant differences were found between the two successive treatments for CR rate, survival, CNS relapses or toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2006

Just for Us: an academic medical center-community partnership to maintain the health of a frail low-income senior population.

PURPOSE: To promote health and maintain independence, Just for Us provides financially sustainable, in-home, integrated care to medically fragile, low-income seniors and disabled adults living in subsidized housing. DESIGN AND METHODS: The program provides primary care, care management, and mental health services delivered in patient's homes by a multidisciplinary, multiagency team. RESULTS: After 2 years of operation, Just for Us is serving nearly 300 individuals in 10 buildings. The program is demonstrating improvement in individual indices of health. Medicaid expenditures for enrollees are shifting from ambulances and hospital services to pharmacy, personal care, and outpatient visits. The program is not breaking even, but it is moving toward that goal. The program's success is based on a partnership involving an academic medical center, a community health center, county social and mental health agencies, and a city housing authority to coordinate and leverage services. IMPLICATIONS: Just for Us is becoming a financially sustainable way of creating a "system within a nonsystem" for low-income elderly persons in clustered housing.

Academic Medical Centers↗

PubMed2005

Cooperative multiagent congestion control for high-speed networks.

An adaptive multiagent reinforcement learning method for solving congestion control problems on dynamic high-speed networks is presented. Traditional reactive congestion control selects a source rate in terms of the queue length restricted to a predefined threshold. However, the determination of congestion threshold and sending rate is difficult and inaccurate due to the propagation delay and the dynamic nature of the networks. A simple and robust cooperative multiagent congestion controller (CMCC), which consists of two subsystems: a long-term policy evaluator, expectation-return predictor and a short-term rate selector composed of action-value evaluator and stochastic action selector elements has been proposed to solve the problem. After receiving cooperative reinforcement signals generated by a cooperative fuzzy reward evaluator using game theory, CMCC takes the best action to regulate source flow with the features of high throughput and low packet loss rate. By means of learning procedures, CMCC can learn to take correct actions adaptively under time-varying environments. Simulation results showed that the proposed approach can promote the system utilization and decrease packet losses simultaneously.

Algorithms↗

PubMed1982

A pilot study of high-dose 1-beta-D-arabinofuranosylcytosine for acute leukemia and refractory lymphoma: clinical response and pharmacology.

1-beta-D-Arabinofuranosylcytosine (ara-C), 2 or 3 g/sq m, was administered as a 1-hr i.v. infusion every 12 hr for 10 or 12 doses to patients with acute leukemia and refractory lymphoma. Four of seven patients with relapsed or refractory acute myelocytic leukemia and two of four patients with previously untreated acute myelocytic leukemia achieved complete remission. Of five treatment failures, two patients had leukemia which was clearly resistant to high-dose ara-C, and three patients died of infections or hemorrhagic complications during periods of pancytopenia. Three patients with acute myelocytic leukemia in remission received high-dose ara-C as consolidation therapy following previous courses of intensive, multiagent consolidation chemotherapy. Two of these three patients had prolonged thrombocytopenia following high-dose ara-C. Five patients with refractory acute lymphocytic leukemia were treated. Three patients achieved partial remission, and two patients had drug-resistant disease. Complete or partial disappearance of measurable disease parameters was seen in three of three patients with refractory lymphoma. Response was seen in five of five patients with meningeal leukemia, including complete response in one patient with extensive meningeal infiltration. Toxicity of this regimen was generally moderate and limited to pancytopenia and mild nausea. Patients who had received prior multiagent consolidation chemotherapy appeared to be at greater risk for hematopoietic toxicity. Patients who had received prior cranial irradiation or intrathecal chemotherapy appeared to be at greater risk for neurological toxicity. Plasma levels of ara-C immediately after completion of the infusion were 17.96 +/- 8.02 (S.D.) and 35.0 +/- 2.8 micrograms/ml for doses of 2 and 3 g/sq m, respectively. From 160 to 720 min following completion of the infusion, the plasma levels of drug were comparable to steady-state levels achieved with a continuous infusion of ara-C at 100 mg/sq m over 24 hr. A high degree of penetration into the central nervous system was demonstrated. High-dose ara-C has substantial activity against leukemic and lymphomatous cell populations, including cell populations resistant to conventional doses of the drug, and is an effective treatment modality for patients with these diseases. The high degree of penetration into the central nervous system suggests that this drug regimen may be useful as consolidation therapy for patients at high risk for central nervous system disease.

Adolescent↗

PubMed1999

Antiproliferative activity of conditioned medium from lymphocytes of neuroblastoma (NB) patient and inhibition with NB serum.

Neuroblastoma (NB) is a pediatric malignancy and results in high mortality rate. Cellular immunity has been shown to play an important role in killing tumors 'in vitro'. Human lymphocytes were activated in vitro with phytohaemagglutinin (PHA) and the effect of supernatants collected at 24, 48, 72 and 96 h were tested on proliferation of human NB cell line-SK-N-MC and glioma cell line U87-MG. The SK-N-MC cells were observed to be more susceptible to the supernatants compared to U87-MG with higher inhibition of proliferation as evaluated by [3H]thymidine incorporation (P < 0.05 for 24 and 72 h and P < 0.0005 for 48 and 96 h). Conditioned medium from lymphocytes of NB patient collected at 48 and 96 h after activation inhibited proliferation (P < 0.005) of SK-N-MC cells. The presence of serum from NB patient decreased the antiproliferative activity of supernatants from normal lymphocytes and NB patient's autologous lymphocytes (P < 0.01). This preliminary data demonstrates the capability of the activation of lymphocytes from NB patient undergoing aggressive multiagent chemotherapy and controlling proliferation of tumor cells on one hand and the role of serum from NB patient in abrogating to a certain extent the effect of activated immune cells thereby protecting tumor cells, on the other hand. Both these aspects need to considered with equal importance to study mechanisms in designing strategies for immune therapies.

Blood Proteins↗

PubMed1995

Gestational trophoblastic disease metastatic to the central nervous system.

OBJECTIVE: To evaluate characteristics of patients with central nervous system (CNS) lesions of gestational trophoblastic disease (GTD) and determine prognostic and therapeutic implications applicable to management. METHODS: We retrospectively reviewed the records of 454 patients treated at the Southeastern Regional Trophoblastic Disease Center between 1966 and 1992 with at least 2 years of follow-up, and identified 42 (9.3%) with CNS metastases. Sixteen patients presented for primary therapy and 27 patients had received significant therapy prior to presentation. Three heavily treated moribund patients died before their first cycle of chemotherapy and were excluded from analysis. Brain metastases were documented by physical exam and radionuclide imaging (before 1976), computed tomography scan (after 1976), or magnetic resonance imaging (after 1986). Patients received multiagent chemotherapy with methotrexate, actinomycin D, and chlorambucil (MAC)- or etoposide-based regimens. All patients received radiation therapy. No intrathecal chemotherapy was given. Craniotomy was employed in seven cases. Remission was defined as three weekly hCG levels below assay sensitivity (< 5 mIU/ml). RESULTS: Overall survival was 44%. Twelve of 16 patients (75%) who presented with CNS metastases with no prior therapy (Group A), 5 of 13 (38%) patients who had prior treatment (Group B), and none of 10 patients who developed CNS metastases during therapy (Group C) survived (P < 0.05). Two of four patients who failed in the CNS after treatment for CNS lesions were salvaged. Demographic characteristics of Groups A and B were similar. No significant differences with respect to WHO score, interval from pregnancy to onset of disease, or age among these groups were found. Group B patients had a four-fold higher incidence of liver metastases. Survival of Group A patients was not related to conventional clinical prognostic factors. Inverse (nonsignificant) correlations were found for Group B patients between survival and WHO score, hCG level, size and number of metastatic lesions, but not type of prior therapy. Survival was higher in those with prior molar pregnancies (56%) as contrasted with aborted (50%) or term (27%) gestations. Selective use of craniotomy helped alleviate intracranial pressure and resect refractory foci. CONCLUSIONS: Chemotherapy combined with radiation therapy in GTD patients with CNS metastases yields survival rates comparable to those reported for intrathecal methotrexate regimens. Tumor burden as indicated by hCG level and size/number of metastases in previously treated patients may correlate with survival. Patients who develop CNS metastases during active therapy have a very poor outcome.

Adolescent↗

PubMed2002

Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997.

BACKGROUND: We reviewed 611 patients with parameningeal sarcoma entered on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978-1997), to delineate treatment results and evaluate prognostic factors. PROCEDURE: Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or surgery followed by multiagent chemotherapy and radiation therapy (XRT). Beginning in 1977, patients with cranial nerve palsy, cranial base bony erosion, and/or intracranial extension at diagnosis were considered as having meningeal involvement. They received triple intrathecal medications, whole brain XRT, and then spinal XRT. These treatments were successively eliminated from 1980 to 1991. RESULTS: The 611 patients' overall survival rate at 5 years was 73% (95% confidence interval, 70-77%). Favorable prognostic factors were: age 1-9 years at diagnosis; primary tumor in the nasopharynx/nasal cavity, middle ear/mastoid, or parapharyngeal areas; no meningeal involvement; and non-invasive tumors (T1). Thirty-five of 526 patients (6.7%) with information about presence/absence of meningeal involvement at diagnosis developed central nervous system (CNS) extension at 5-164 weeks (median, 46 weeks) after starting therapy. The estimated 5-year cumulative incidence rate of CNS extension during the study period was 5-7% (P = 0.88). CONCLUSIONS: Biopsy, XRT to the target volume, and systemic chemotherapy are successful treatments for the large majority of patients with localized parameningeal sarcoma. Carefully defining and irradiating the initial volume should reduce the risk of CNS failure. Aggressive initial surgical management of these patients is unnecessary.

Adolescent↗