Treatment of intracranial ependymomas of children: review of a 15-year experience

PURPOSE: There are still major controversies in the optimal management of children with intracranial ependymomas. To assess the impact of tumor site, histology, and treatment, the outcome of children treated at the Institut Gustave Roussy was reviewed retrospectively. METHODS AND MATERIALS: Between 1975 and 1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave Roussy for postoperative management of an intracranial ependymoma. Location of tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment consisted of complete resection in 38, incomplete resection in 38 and biopsy only in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33. Surviving patients have been followed from 12-197 months with a median of 54 months. RESULTS: The 5-year actuarial survival and event-free survival are 56% and 38%, respectively. Thirty-four patients relapsed from 3-72 months after diagnosis (median 25 months). In 20 patients, the only site of failure was the original tumor site. Three patients failed locally and at distance, while 10 others failed only at distance. Survival at 5 years was significantly better for patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free survival at 5 years was superior in patients with complete resection of the tumor (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs. 0%, p < 0.001). Sex and tumor site had no impact on survival or event-free survival. There was no difference in survival, event-free survival, or pattern of failure between patients treated with local field, whole brain or craniospinal irradiation, while severe longterm sequelae were noted predominantly in the latter two groups. CONCLUSION: Considering that failures were predominantly local and that there was no apparent benefit from prophylactic irradiation, we recommend local field irradiation with doses above 50.0 Gy for all children with intracranial ependymomas, without meningeal dissemination at diagnosis. Special considerations are necessary for children < 3 years of age.     

Safety and efficacy of ECT in patients with head injury: a case series

BACKGROUND: The role of postoperative radiotherapy and adjuvant chemotherapy in the treatment of synovial sarcoma remains to be determined. PROCEDURE: Twenty-five children were treated during a 23-year period with a multimodality approach. All of them had resection of the primary tumor (three amputations), followed by surgical retreatment in eight. Postoperative radiotherapy was delivered to 16 patients and adjuvant chemotherapy was given to 22. RESULTS: At the time of the report, 19 patients were alive and without evidence of disease. Six developed distant metastases (one associated with local recurrence); five of them died of their disease and one was alive in complete remission at 4 years from relapse. With a median follow-up of 9 years (range 2-23), the survival and the event-free survival at 5 years were 80% (SE 8.2) and 74% (SE 9.2), respectively. All relapsing patients had been classified as T2B. CONCLUSIONS: Multimodality treatment yielded satisfying survival results using limb-preserving surgery in most cases. Tumor size > 5 cm and invasiveness, which defined stage T2B, were the most important predictors of poor outcome. Evaluation of the role of adjuvant chemotherapy and radiotherapy awaits prospective studies, even if T2B patients, as well as children having nonradical surgery, seem worth managing by adjuvant treatments.     

Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure

OBJECTIVES: We sought to study the relationship between survival and right ventricular ejection fraction (RVEF) in a subgroup of patients with moderate congestive heart failure (CHF). BACKGROUND: It has been demonstrated that RVEF is an independent predictor of survival in patients with advanced CHF. METHODS: Cardiopulmonary exercise testing and radionuclide angiography (to determine right and left ventricular ejection fraction) were prospectively performed in 205 consecutive patients with moderate CHF (140 patients in New York Heart Association [NYHA] class II, 65 in class III). RESULTS: Left ventricular ejection fraction was 29.3%+/-10.1%, RVEF was 37.5%+/-14.6% and peak oxygen consumption (VO2) was 16.2+/-5.4 ml/min/kg (60.2%+/-19% of maximal predicted VO2). After a median follow-up period of 755 days, there were 44 cardiac-related deaths, 3 deaths from noncardiac causes and 15 transplantations of whom 2 were urgent; 1 patient was lost to follow-up. Multivariate analysis showed that three variables-NYHA classification, percent of maximal predicted VO2 and RVEF-were independent predictors of both survival and event-free cardiac survival. Left ventricular ejection fraction and peak VO2 normalized to body weight had no predictive value. The event-free survival rates from cardiovascular mortality and urgent transplantation at 1 year were 80%, 90% and 95% in patients with an RVEF <25%, with a RVEF > or =25% and <35% and with a RVEF > or =35%, respectively. At 2 years, survival rates were 59%, 77% and 93% in the same subgroups, respectively. CONCLUSIONS: In addition to the NYHA classification and to the percent of maximal predicted VO2, RVEF is an independent predictor of survival in patients with moderate CHF.     

Long-term (10-year) outcome in patients with unstable angina pectoris treated by coronary balloon angioplasty

OBJECTIVES: We sought to examine completed 10-year survival and event-free survival in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty. BACKGROUND: Patients with unstable angina are at increased risk for recurrent acute coronary events. METHODS: The study included 208 consecutive patients (133 with stable and 75 with unstable angina pectoris) undergoing angioplasty from 1984 to 1986. The balloon crossed the lesion in 185 patients (121 with stable and 64 with unstable angina pectoris). Angioplasty was performed in patients with unstable angina pectoris 12+/-15 days (median 8) after symptom onset. Patients with unstable angina pectoris were classified retrospectively into Braunwald class I (n=3), class II (n=20), class III (n=28), class B (n=52) and class C (n=12). Follow-up data were obtained from hospital charts, telephone interview and official death certificates where applicable. The study had >80% power to detect a clinically significant 20% difference in survival and a 20% difference in event-free survival between the stable and unstable patient groups. RESULTS: Despite similar baseline characteristics, early (40-day) mortality was slightly higher in patients with unstable angina (4.7% [3 of 64 patients] vs. 0.8% [1 of 121 patients], p=NS). Long-term outcome was not different, because survival curves were parallel thereafter (10-year survival was 83% for those with stable and 77% for those with unstable angina, p=NS). Survival free of myocardial infarction or coronary artery bypass graft surgery at 10 years was 53% in patients with stable and 47% in patients with unstable angina (p=NS), and survival free of infarction, bypass surgery or repeat angioplasty was 32% for both groups at 10 years. In patients with Braunwald class III unstable angina, 10-year survival was 80%, as compared with 85% in other patients with unstable angina, due to the early hazard (p=NS). Survival and event-free survival were similar in patients who had had a recent myocardial infarction (Braunwald class C) and in patients with acute electrocardiographic changes. Repeat hospital admissions were not more frequent in patients with unstable angina (3.1+/-3.5 vs. 3.0+/-2.6, p=NS). CONCLUSIONS: Ten-year survival and event-free survival were similar in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty, with no evidence of an increased rate of recurrent cardiovascular events in the unstable group.     

High-intensity physical training in adults with asthma. A comparison between training on land and in water

BACKGROUND: The objectives of this study were to compare vincristine/actinomycin D/cyclophosphamide/adriamycin (VACA) with VACA/plus imidazole carboxamide (DTIC) (VACAD) therapy in regards to complete/partial response and event free survival rates in children and adolescents with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) or previously chemotherapy-naive recurrent NRSTS or locally persistent gross residual tumor after surgery and radiation therapy. PROCEDURES: Between 1986 and March 1994, 75 patients entered this randomized study comparing VACA and VACAD, given at 3 week intervals. Sixty-one patients were considered eligible and received chemotherapy and radiation therapy to the primary tumor and areas of metastases. Thirty-six patients had regional unresected (Group III) disease, and 25 had metastatic disease (Group IV) at time of accession. Thirty-six patients received VACA (11 were not randomized), and 25 received VACAD. RESULTS: With a median follow-up of greater than 4 years, overall and event-free survival for all eligible patients are 30.6% and 18.4% respectively (S.E: 9.5% and 6.8%). There was insufficient evidence that DTIC offered any advantage to event free survival, but there was evidence for better outcome for patients in Group III disease in comparison to patients with Group IV disease, and for patients with a Grade 1 and 2 histology in comparison to Grade 3 lesions. CONCLUSIONS: Combination chemotherapy with VACA and VACAD were insufficient to prevent recurrent or progressive disease in children and adolescents with high stage NRSTS. The use of vincristine/ifosfamide/doxorubicin with cytokine support is under study.     

Treatment results of Hodgkin's disease in Indian children

This is a retrospective study of Hodgkin's disease in children less than 15 years of age who were registered at Tata Memorial Hospital in India from January 1985 through December 1990. Clinicopathologic characteristics and response were evaluated in 147 patients and survival was calculated in 187. There were 126 boys and 21 girls (6:1). All patients were treated with combination chemotherapy and involved field radiotherapy. The COPP schedule was given to 108 patients. COPP/ABVD to 33, and ABVD to 6. Ninety-three patients (63%) had stage I or II disease and 54 (37%) had stage III or IV disease. B symptoms were observed in 65 patients (56%) and bulky disease in 40 (27%). Histologically, the most common subtype was mixed cellularity, seen in 95 patients (65%). Complete response was observed in 136 (89%), partial response in 6 (4%), and there were 4 treatment-related deaths. Relapse has been observed in 11%. Seven-year actuarial survival was 73% and event-free survival was 64%. Median survival has not yet been reached, with a median follow-up of 36 months.     

Prognostic factors in the acute lymphoid and myeloid leukemias of infants

The age boundaries and prognostic factors that define the infant leukemias are still controversial. We therefore analyzed event-free survival according to age group in 96 children treated for acute lymphoblastic leukemia (ALL) and 51 treated for acute myeloid leukemia (AML) before the age of 2 years. The study population was registered in consecutive institutional trials of multiagent chemotherapy conducted between 1980 and 1994. Among infants with ALL, event-free survival was significantly poorer in the 0- to 6-month-old group than in patients treated between 6 and 12 months of age (P = 0.03), whose outcome was in turn inferior to that in the 12- to 18-month and 18- to 24-month age groups (P = 0.013). Leukemic cells from ALL patients younger than 12 months had a significantly higher frequency of 11q23/MLL abnormalities, as well as better growth in stromal cell culture, compared to lymphoblasts from the older groups (P < 0.01). The only independent predictor of adverse prognosis among infants diagnosed with ALL before age 12 months was the presence of an 11q23/MLL rearrangement (P = 0.03). These findings contrast sharply with results for the AML cohort, whose event-free survival did not vary significantly by age group (P = 0.58). Male sex (P = 0.01) and leukocyte count > or = 50 x 10(9/l) (P = 0.04), but not 11q23 abnormalities, were independently associated with a poorer outcome for children with AML younger than 12 months at diagnosis. Thus, in very young children with ALL (but not AML), the rearrangement status of the 11q23/MLL region supersedes age group as a determinant of treatment outcome.     

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.     

Successful management of low-stage neuroblastoma without adjuvant therapies: a comparison of two decades, 1972 through 1981 and 1982 through 1992, in a single institution

PURPOSE: A review was undertaken of 119 children seen at the Children's Hospital of Philadelphia between 1972 and 1992 to assess the impact of adjuvant therapies for patients with low-stage neuroblastoma (NBL). PATIENTS AND METHODS: Twenty-one of 119 International Neuroblastoma Staging System (INSS) stage 1, 2a, 2b, and 4s patients seen received initial adjuvant treatment postoperatively and 98 did not. The patients were further subdivided according to decade, age, presence of residual disease, and lymph node status. Outcomes were then compared. RESULTS: The event-free survival (EFS) rate for those who received adjuvant therapy was 52% versus 86% for those who did not. The 5-year survival rate was 68% and 94%, respectively. Age (< or > 12 months), extent of residual disease, and status of lymph nodes did not influence survival. Over the two decades, the reasons for selecting treatment changed as new and powerful additional prognostic factors were identified; 71% of patients received no adjuvant treatment in the first decade, compared with 90% in the second. EFS rates for untreated patients by decade were 79% and 89%, and 5-year survival rates were 85% and 98%, respectively. CONCLUSION: It is possible to define most low-stage NBL as favorable-even in patients with positive lymph nodes and gross residual disease-and to omit initial adjuvant treatments successfully.     

CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology

The purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level >/=800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.     

Cys2/His2 zinc-finger protein family of petunia: evolution and general mechanism of target-sequence recognition

In recent pediatric trials of acute myeloid leukemia (AML), children with Down syndrome (DS) have had significantly more megakaryoblastic leukemia and have experienced better outcome than other children. To further characterize AML in DS, Children's Cancer Group Studies 2861 and 2891 prospectively studied demography, biology, and response in AML and myelodysplastic syndrome (MDS) of children with and without DS. These studies evaluated timing of induction therapy and compared postremission chemotherapy with marrow transplantation in 1,206 children. One-hundred eighteen (9.8%) had DS, a fourfold increase in 20 years. DS patients were younger, had lower white blood cell and platelet counts, more antecedent MDS, acute megakaryoblastic leukemia or undifferentiated AML, and an under-representation of chromosomal translocations (P < .001 for each variable). Four-year event-free survival in DS was 69% versus 35% in others (P < .001). Intensively timed induction conferred significantly higher mortality in DS patients; bone marrow transplantation offered no advantage. Conventional induction followed by chemotherapy achieved an 88%, 4-year, disease-free survival in DS patients versus 42% in others (P < .001). Megakaryoblastic leukemia was unfavorable in others but prognostically neutral in DS. AML in DS is demographically and biologically distinct from AML in other children. It is singularly responsive to conventional chemotherapy and may warrant even less therapy. The increasing proportion of DS patients with AML most likely reflects changes in attitudes about entering DS patients on AML trials and possibly increasing ability to distinguish megakaryoblastic leukemia from lymphoid leukemia.     

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission. Spanish Working Party for BMT in Children

The purpose of this study was to evaluate the outcome of children with acute lymphoid leukemia (ALL) in second remission who have undergone high-dose chemotherapy and radiotherapy and autologous bone marrow transplantation (ABMT) with monoclonal antibody purged marrow, and to determine the main prognostic factors. From 1987 to 1992, 55 children with ALL in second remission underwent ABMT. The conditioning regimen consisted of total body irradiation (TBI) plus cyclophosphamide in 21 patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28 patients; the remaining six patients were treated with chemotherapy alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was purged using monoclonal antibodies and complement or magnetic microspheres in all cases. All patients engrafted. Three patients (5%) died early post transplant from infections. Twenty-six patients (47%) relapsed (median 150 days); 26 patients (47%) are alive and in complete remission (CR) at a median of 36 months. The Kaplan-Meier estimation showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In the univariate analysis, first CR length and conditioning with TBI plus two or more cytotoxic drugs were found to be the most significant predictors of EFS. ABMT with purged marrow is a treatment modality which offers a chance of cure in children with ALL after relapse, including children who relapse early.     

Loss of chromosome 1p may have a prognostic value in localised neuroblastoma: results of the French NBL 90 Study. Neuroblastoma Study Group of the Société Fran?aise d'Oncologie Pédiatrique (SFOP)

Between March 1990 and December 1994, 316 consecutive children with localised neuroblastoma were registered in the French NBL 90 study. In addition to the assessment of a new chemotherapy regimen in unresectable neuroblastoma, we evaluated the prognostic significance of MYCN amplification and loss of the short arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and associated with unfavourable clinical features such as age at diagnosis > 1 year and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of whom some had favourable prognostic factors such as age at diagnosis < 1 year (n = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall survival (OS) and event-free survival (EFS) were, respectively, 56% and 22% (median follow-up: 36 months) for children with LOH1p compared with 97% and 94% for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN amplification and LOH1p relapsed and ultimately died of the disease. Among the 4 with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1 metastatic), all alive in second remission after salvage therapy (12-19 months after the relapse). In multivariate analysis, LOH1p was the strongest prognostic indicator for subsequent relapse. LOH1p appears more discriminant than MYCN amplification for predicting the risk of recurrence in children with localised neuroblastoma. However, its analysis was possible in only 30% of our patients and its final impact on survival should be confirmed in larger, prospective studies in order to stratify subsequent treatment.     

Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report

PURPOSE: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.     

Stage IV neuroblastoma in patients over 1 year of age at diagnosis: consolidation of poor responders with combined busulfan, cyclophosphamide and melphalan followed by in vitro mafosfamide-purged autologous bone marrow transplantation

In an attempt to improve the poor prognosis of poor responders with stage IV neuroblastoma, a new combined high-dose chemotherapy conditioning regimen was tested. Event-free and overall survival, as well as the incidence of complications, were analysed. Twenty-five children aged 12-146 months at diagnosis entered this study. All were in complete remission (CR) at the time of high-dose chemotherapy. Two or three different protocols had been necessary for them to achieve a CR. High-dose chemotherapy consisted of a combination of busulfan (600 mg/m2), cyclophosphamide (4400 mg/m2) and melphalan (140 mg/m2). It was followed by autologous bone marrow transplantation (ABMT). The bone marrow graft was purged in vitro with mafosfamide. The probability of event-free survival (EFS) at 5 years post-ABMT was 34%, compared to < 8% in a historical series. Toxicity was severe but manageable and 2 complication-related deaths were observed. Veno-occlusive disease was the most frequent extrahaematopoietic complication encountered, but its outcome was always favourable. By using a very intensive conditioning regimen consisting of a combination of three alkylating agents, the EFS of poor responders with metastatic neuroblastoma was improved and similar to that of good responders. When compared with a previously published similar series of patients, the improvement in survival appears probably related to intensification of the conditioning regimen.     

Unresectable localized neuroblastoma: improved survival after primary chemotherapy including carboplatin-etoposide. Neuroblastoma Study Group of the Société Fran?aise d'Oncologie Pédiatrique (SFOP)

Neuroblastomas (NBs) were assessed according to INSS recommendations including MIBG scan and extensive bone marrow staging to eliminate metastatic spread. Patients with unresectable tumour received primary chemotherapy including two courses of carboplatin-etoposide (CE) and two of vincristine-cyclophosphamide-doxorubicin (CAdO). Post-operative treatment was to be given only in children over 1 year of age at diagnosis who had residual disease or lymph node (LN) involvement. Between 1990 and 1994, 130 consecutive children were registered. In comparison with resectable primaries, these tumours were more commonly abdominal, larger and associated with N-myc amplification (NMA). Complete, very good and partial response (CR, VGPR, PR) to CE were, respectively, 1%, 7% and 44%, overall response rate (RR) to two courses of CE and two courses of CAdO was 71%, and the tumour could be removed in all but four of the children. The toxicity was manageable. The 5-year overall survival (OS) and event-free survival (EFS) were, respectively, 88% and 78% with a median follow-up of 38 months. In multivariate analysis, only NMA and LN involvement adversely influenced the outcome, particularly NMA. Children with unresectable NBs and no NMA fared as well as children with resectable ones as OS were, respectively, 95% and 99% and EFS 89% and 91%. Our data show encouraging results in localized but unresectable NBs as 90% of children may be considered as definitely cured, especially those without NMA.     

Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17

PURPOSE: In 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings. PATIENTS AND METHODS: Women (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented. RESULTS: The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics. CONCLUSION: Through 8 years of follow-up, our findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.     

Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996

BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (P=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (P<.001) and was inversely related to presentation with progressive or rest angina (P<.001). Surgical candidates with ejection fractions > or = 40% had an in-hospital survival of 98% and a 9-month event-free survival of 86+/-5%, whereas patients with ejection fractions < 40% had 67% and 22+/-12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge. CONCLUSIONS: While results for selected patients appear promising, until early post-hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.