Biomedical subjects
Publications and source records attributed to S Ahrens.
Newer statistical methods for modeling and prediction of long-term follow-up in schizophrenia are presented. These include the extended Cox model, the Generalized Estimating Equations (GEE) method and the Artificial Neural Networks (ANN) approach.
BACKGROUND: The incidence of Ewing's tumors (ETs) is lower in Asians or African-Americans than in Caucasians. PATIENTS AND METHODS: Japanese ETs were available for analysis of chromosomal aberrations by comparative genomic hybridization (n = 16) and for expression of chimeric EWS transcripts by reverse-transcriptase polymerase chain reaction (n = 11). These results in Japanese patients were compared with those of 62 ETs in European Caucasian patients registered in the European Intergroup Cooperative Ewing's Sarcoma Study. RESULTS: Japanese patients with ET had lower overall survival (P = 0.0446) and relapse-free survival (P = 0.0371) compared with European Caucasian patients. Ten of 11 Japanese ETs and 31 of 62 European Caucasian ETs had type I (EWS exon 7 to FLI1 exon 6) fusion transcripts. In Japanese ETs, the median numbers of chromosomal aberrations were 2.0 and 6.0 in 11 primary tumors and five relapsed tumors, respectively. In European Caucasian ETs, the median number of changes were 2.5 and 5.0 in 52 primary and 10 relapsed tumors, respectively. Frequent gains were 8q (38%), 8p (31%) and 12q (25%) in Japanese ETs and 8q (52%), 8p (48%) and 12q (19%) in European Caucasian ETs. Frequent losses were 19q (44%), 19p (38%) and 17p (25%) in Japanese ETs and 16q (21%), 19q (18%) and 17p (15%) in European Caucasian ETs. The incidence of losses of 19p (P = 0.0215) and 19q (P = 0.0277) were significantly higher in Japanese ETs than in European Caucasian ETs. An amplification (1p33-p34) was observed in only one Japanese ET. CONCLUSIONS: Japanese patients with ET in this study had a worse prognosis than European Caucasian patients. In molecular genetic analyses, Japanese ETs had a higher frequency of loss of chromosome 19 than European Caucasian ETs. Different genetic aberrations may explain the different incidences and prognoses of ET between Caucasian and Japanese patients.
CONTEXT: Rizatriptan is a selective 5-HT1B/1D receptor agonist for the acute treatment of migraine. It is available in a unique wafer formulation that dissolves rapidly in the mouth and can be taken without liquids, thereby offering patients a very convenient way to take treatment. OBJECTIVE: To investigate the long-term efficacy of rizatriptan 10-mg and 5-mg wafers in migraineurs. SETTING: 19 headache clinics in 5 countries. PATIENTS: 458 patients diagnosed with migraine according to International Headache Society criteria. DESIGN: 6-month, open-label, extension, which followed a double-blind, placebo-controlled study. INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatments for moderate or severe migraines: rizatriptan 10-mg wafer, rizatriptan 5-mg wafer, or "standard care" (usual migraine treatment -- eg, nonsteroidal anti-inflammatory drugs [NSAIDs], analgesics, other triptans). Patients randomized to rizatriptan were blinded to the dose. MAIN OUTCOME MEASURES: Headache severity (none, mild, moderate, severe) and adverse events were recorded on a diary card. RESULTS: 181 patients treated 3393 attacks with rizatriptan 10-mg wafer, 191 treated 3254 attacks with rizatriptan 5-mg wafer, and 86 treated 1582 attacks with standard care. The median number of treated attacks per patient was 16 for rizatriptan 10-mg wafer, 13 for rizatriptan 5-mg wafer, and 14 for standard care. The median patient on rizatriptan 10-mg wafer reported pain relief at 2 hours (reduction of headache from moderate or severe at baseline to mild or none) in 82% of attacks, vs 73% of attacks for standard care (odds ratio [95% confidence interval] = 1.63 [1.14, 2.34], P <.01) and 72% of attacks for rizatriptan 5-mg wafer (OR [95% CI] = 1.60 [1.23, 2.08], P <.001). The median patient on rizatriptan 10-mg wafer was pain free at 2 hours in 46% of attacks, vs 30% of attacks for standard care (OR [95% CI] = 1.50 [1.06, 2.12], P <.05) and 25% of attacks for rizatriptan 5-mg wafer (OR [95% CI] = 1.93 [1.50, 2.49], P <.001). All treatments were generally well tolerated. Compared with standard care, rizatriptan 5-mg wafer was associated with fewer specific adverse events of asthenia/fatigue, back pain, nausea, pharyngeal discomfort, upper respiratory infection, and vomiting (P values <.05), and, compared with rizatriptan 10-mg wafer, fewer overall drug-related adverse events (P <.05). CONCLUSIONS: Rizatriptan 10-mg wafer was more effective than standard care and rizatriptan 5-mg wafer for treating intermittent moderate or severe migraine attacks occurring over periods of up to 6 months. Rizatriptan wafers were well tolerated.
PURPOSE: Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.
Ewing tumors are characterized by reciprocal translocations involving the EWS gene on 22q12 fused to ETS transcription-factor family members. Little is known about further aberrations contributing to tumor development and progression. Sixty-two frozen tumors with known EWS rearrangements (52 primary tumors, 10 relapses) of ET patients registered in the EICESS protocol were analyzed by comparative genomic hybridization (CGH). The median number of changes in 52 primary and 10 relapsed cases was 2.5 and 5.0 per tumor (P = 0.153). Frequent abnormalities included gains of chromosomes 8, 12, 20, and 1q and losses of 16q and 19q. Neither number nor type of aberration was associated with histology, tumor size, disease stage, tumor localization, or histologic tumor response to chemotherapy. Among the 52 primary tumors, 26 with Type I fusion (EWS exon 7 to FLI1 exon 6) and 26 with other fusion types had a median of 2.0 and 3.0 aberrations per tumor, respectively (P = 0.031). Combinations of gains of chromosomes 8 and 12, gains of chromosome 20, and either gains of 8q or 18q and losses of 16q and 17p frequently occurred. The cumulative overall survival (OAS) was different between 35 patients with <5 aberrations and 13 patients with > or =5 aberrations (P = 0.009). Univariate analysis showed that patients with gains of 1q, 2q, 12, and 20 or losses of 16q and 17p had significantly lower OAS than those without aberrations. By multivariate analysis, loss of 16q (relative risk [RR] = 5.3; P = 0.0006) was an independent prognostic factor.
BACKGROUND: Intratumoral hypoxia is associated with poor prognosis in various solid tumors. Severe and long-lasting hypoxia results in necrosis. The presence of necrosis therefore might also be correlated with unfavorable outcome. This has been demonstrated for head and neck cancers, gliomas and adult soft tissue sarcomas. We have investigated whether or not the patterns of contrast enhancement and the presence of visible necrosis on pretreatment MR images has prognostic impact in Ewing tumors. PATIENTS AND METHODS: From December 1993 though March 1997, 79 patients with Ewing tumors were prospectively analyzed for the presence and amount of necrosis in their tumors. The median age was 12 years (range 4-30 years). The median follow-up at the time of this analyses was 3 years. All patients were treated according to the multicentric EICESS-92 protocol with multi-agent chemotherapy (VACA or VAIA or EVAIA) and local therapy (radiotherapy with 50-60 Gy or surgery or surgery with pre- or postoperative irradiation with 45-50 Gy). For the measurement of necrosis, gadolinium contrast-enhanced T1-weighted MR images were used. Necrosis was defined as non-perfused areas in the tumor and the necrotic volume was expressed as percentage of total volume. RESULTS: Out of 79 tumors, 10 (13%) showed no necrosis, 30 (38%) had 1-25% necrosis, 21 (27%) had 26-50% necrosis and the remaining 18 (23%) more than 50% necrosis. There was a correlation between tumor size and necrosis (p = 0.001): the median tumor volume increased with amount of necrosis (47 cm3 in non-necrotic tumors, 59 cm3 vs 280 cm3 vs 284 cm3 for tumors with 1-25% vs 26-50% vs > 50% necrosis). Tumor site (central location vs proximal extremities vs distal extremities) had no impact on necrosis (p = 0.71). 23 out of 79 patients had metastases (M1) at the time of diagnosis. The frequency of metastatic spread increased with the amount of necrosis: 1/10 (10%) patients with non-necrotic tumors had metastases vs 7/30 (23%) vs 6/21 (28%) vs 9/18 (50%) for tumors with 1-25% vs 26-50% vs > 50% necrosis. "Unfavorable" metastatic spread (bone or multiple metastases) was only noted in patients with high amount of necrosis (> 25% necrosis) whereas even large tumors did not show unfavorable metastases if they contained no or only small amounts of necrosis. All patients with non-necrotic tumors survived event-free during the observation period. Patients with necrotic tumors had a 3-year event-free survival of 55% (p = 0.06 vs tumors without necrosis). CONCLUSIONS: The presence of non-perfused (presumably necrotic) areas on pretreatment contrast-enhanced MR-images is associated with an increased risk of metastases, especially an unfavorable pattern of metastatic spread at diagnosis. This observation may be explained by a more aggressive biological behavior of hypoxic tumor cells. The small group of patients with non-necrotic tumors (13%) had an excellent prognosis suggesting that the absence of necrosis might be helpful in identifying a very favorable prognostic subgroup in Ewing tumors.
BACKGROUND: Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients. PATIENTS AND METHODS: Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine. doxorubicin, ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide as a randomized question. Second cancer incidences were estimated by competing risk analyses; standardized incidence ratios (SIR) in comparison to registry data were compiled. RESULTS: After a median observation time of 56 months (32 months for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two, ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased 20-30 fold in comparison to the general population. The cumulative second cancer risk five years after diagnosis of the Ewing tumor was 0.0093 for the total group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after five years. CONCLUSIONS: The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.
BACKGROUND: An update of results from the High Risk Protocol of the Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centers of Düsseldorf and Vienna. In order to evaluate a possible therapeutic benefit after allogeneic SCT in patients with advanced Ewing tumors (AET), we compared outcome after autologous and allogeneic stem-cell transplantation (SCT). PATIENTS AND METHODS: We analyzed 36 patients treated with the myeloablative Hyper-ME protocol (hyperfractionated total body irradiation, melphalan, etoposide +/- carboplatin) between November 1986 and December 1994. Minimal follow-up for all patients was five years. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seventeen of thirty-six patients had multifocal primary Ewing's tumor, eighteen of thirty-six had early, multiple or multifocal relapse, one of thirty-six patients had unifocal late relapse. Twenty-six of thirty-six were treated with autologous and ten of thirty-six with allogeneic hematopoietic stem cells. We analyzed the following risk factors, that could possibly influence the event-free survival (EFS): number of involved bones, degree of remission at time of SCT, type of graft, indication for SCT, bone marrow infiltration, bone with concomitant lung disease, age at time of diagnosis, pelvic involvement, involved compartment radiation, histopathological diagnosis. RESULTS: EFS for the 36 patients was 0.24 (0.21) +/- 0.07. Eighteen of thirty-six patients suffered relapse or died of disease, nine of thirty-six died of treatment related toxicity (DOC). Nine of thirty-six patients are alive in CR. Age > or = 17 years at initial diagnosis (P < 0.005) significantly deteriorated outcome. According to the type of graft, EFS was 0.25 +/- 0.08 after autologous and 0.20 +/- 0.13 after allogeneic SCT. Incidence of DOC was more than twice as high after allogeneic (40%) compared to autologous (19%) SCT, even though the difference did not reach significance (P = 0.08, Fisher's exact test). CONCLUSIONS: Because of the rather short observation period. secondary malignant neoplasms (SMN) may complicate the future clinical course of some of our patients who are currently viewed as event-free survivors. EFS in AET is not improved by allogeneic SCT due to a higher complication rate. The patient group was to small to analyze for a possible graft-versus-tumor effect.
PURPOSE: To further elaborate on prognostic factors for Ewing's sarcoma of bone and to document improvements in relapse-free survival (RFS) and trends in local therapy over the study period (1977 to 1993). PATIENTS AND METHODS: A retrospective analysis was performed on a combined Gesellschaft Für Pädiatrische Onkologie und Hämatologie/Cooperative Ewing Sarcoma Study and United Kingdom Children's Cancer Study Group/Medical Research Council data set of 975 patients registered with the respective trial offices before the current collaborative European Intergroup Cooperative Ewing's Sarcoma Study trial. Both groups independently undertook studies with similar chemotherapy during the period. RESULTS: The key adverse prognostic factor is metastases at diagnosis (5-year RFS, 22% of patients with metastases at diagnosis v 55% of patients without metastases at diagnosis; P: <.0001). For the group with metastases, there was a trend for better survival for those with lung involvement compared with those with bone metastases or a combination of lung and bone metastases (P: <.0001). In the group of patients with no metastases at diagnosis, multivariate analysis demonstrated that site (axial v other), age-group (< 15 v > or = 15 years), and period of diagnosis had significant influence on RFS (all P: <.005). RFS was superior in the period after 1985 compared with the period before 1985 for nonmetastatic patients (45% v 60%, respectively; P: <.0001) and for metastatic patients (16% v 30%, respectively; P: =.016). Patients who relapsed within 2 years of diagnosis had a less favorable prognosis than patients who relapsed later (5-year survival after relapse, 4% v 23%, respectively; P: <. 0001). There were other changes over the period; in particular, radiotherapy or amputation were more common in the period before 1986, whereas endoprosthetic surgery was widely used in the later period. CONCLUSION: Survival and RFS improved over the period. Prognostic factors are metastases at diagnosis, primary site, and age.
BACKGROUND: This article reports on 241 patients each with pelvic Ewing sarcoma registered for studies in Germany, Austria, and the Netherlands from January 1, 1981, until January 31, 1994. One hundred sixty-four patients had localized disease and 87 had metastases at diagnosis (PMP). Eighty-four patients with localized disease were entered on protocol (PP) and 80 were followed (FP). METHODS: Statistics included an analysis of event free survival by the Kaplan-Meier method and a Cox regression analysis of factors influencing prognosis. RESULTS: In the Kaplan-Meier analysis, on February 1, 1995, the event free survival (EFS) rate was 32% at 12 years for all patients, 54% for PP, 25% for FP, and 13% for PMP. Cox regression analysis showed that response to chemotherapy, initial metastases, and less intense therapy were significant prognostic factors. Among patients who had surgery for local control, the histologic response to chemotherapy was analyzed in the surgical specimen and had a significant influence on survival: EFS 69% for PP with good response compared with 47% (P = 0.11) for patients with poor response, and for FP 56% versus 13% (P = 0.002). All PP with small tumors had relapse free survival, compared with 69% of patients with medium-sized tumors and 36% of patients with tumors larger than 200 mL (P = 0.006). The initial tumor volume was a significant predictor of survival. CONCLUSIONS: Combined modality treatment has resulted in definitive improvement of prognosis for patients with localized pelvic Ewing sarcoma. However, the results for patients with metastases at diagnosis are still discouraging, and their treatment requires new approaches. Tumor load, responsiveness to chemotherapy, and adequate surgical margins are the major factors influencing the prognosis of patients with localized Ewing sarcoma of the pelvis.
BACKGROUND: The Cooperative Ewing Sarcoma Study (CESS 86), conducted by the German Society of Pediatric Oncology and Hematology (GPOH), was planned on the basis of the results of the preceding CESS 81 study. The prognostic significance of tumor volume in localized Ewing sarcoma of bone was well documented in the CESS 81 trial. As a consequence, the treatment intensity was adapted to volume in the follow-up CESS 86 trial: the four-drug combination used in CESS 81 was amended for patients with large tumor volume (> or = 100 ml), where ifosfamide was substituted for cyclophosphamide. PROCEDURE: From January 1986 to June 1991, 177 protocol patients with localized Ewing sarcoma of bone were registered in CESS 86. The prognostic implication of tumor volume and several covariates was evaluated using Kaplan-Meier life table analysis and Cox's proportional hazard model. RESULTS: The estimated 5- and 8-year event-free survival (EFS) rates were both 59%. Age, gender, tumor site, and a tumor volume of 100 ml did not distinguish groups of patients with different prognosis. However, the prognosis of patients with tumors >200 ml (8-year EFS rate: 42%) was significantly inferior compared to patients with tumors both of 100 to 200 ml (70%) and of <100 ml (63%). In contrast to CESS 81, the histological response to chemotherapy was no longer a significant prognostic factor (EFS: 64% for good and 50% for poor responders, respectively). CONCLUSIONS: Despite risk-adapted treatment intensity, tumor volume retained its prognostic significance; the cut point, however, was shifted toward larger volumes.
BACKGROUND: Tumor volumes of more than 100 ml and the presence of primary metastases have been identified as determinants of poor prognosis in patients with Ewing tumors. We sought to assess the prevalence of critical tumor size and primary metastases in a large national sample of patients at the time of first diagnosis and to identify factors that are associated with their occurrence. PATIENTS: The present report is based on data of 945 German patients who were enrolled into the (EI)CESS therapy studies between 1980 and 1997. It is assumed that registration of German patients with Ewing tumors under the age of 15 years was almost complete since around 1985. Diagnoses of primary tumors were ascertained exclusively by biopsies. Analyses were restricted to patients with Ewing tumors of bone due to the few occurrences in soft tissues. METHODS: Tumor volume data as assessed by radiography, computed tomography or nuclear magnetic imaging were available for 821 patients. The diagnosis of primary metastases was based on thoracic computed tomography or on whole body bone scans in 936 patients. Suspicious lesions had to be confirmed by bone marrow biopsies. We explored how year of first diagnosis, age at first diagnosis, sex, histological subtype and site of the primary tumor related to tumor size and presence of metastases by univariate and multivariate statistical techniques. RESULTS: Sixty-eight percent of the patients (n = 559) had a volume above 100 ml with smaller tumors being more common in childhood than in late adolescence and early adulthood. Extensive volumes were observed in almost 90% of the tumors located in femur and pelvis while they were less common in other sites (P < 0.001). On average, 26% of all patients presented with clinically apparent primary metastases. The detection rate of metastases was markedly higher in patients diagnosed after 1991 (P < 0.001). Primary metastases were also significantly more common for tumors originating in the pelvis and for peripheral neuroectodermal tumors (PNET; P < 0.01). Tumors greater than 100 ml were positively associated with metastatic disease (P < 0.001). Multivariate analyses, which included simultaneously all univariate predictors in a logistic regression model, indicated that most of the observed associations were essentially unconfounded. The adjusted odds ratios (OR) for the presence of tumor volumes > or = 100 ml were OR = 1.5 per age rise of 10 years, and OR = 5.8 for pelvis and OR = 7.1 for femur as primary tumor site (all P < 0.001). The presence of metastases was significantly associated with the year of diagnosis (OR = 1.9, after 1991 vs. before 1986), pelvis as site of the primary tumor (OR = 1.8), a PNET (OR = 1.5), and tumor size > or = 100 ml (OR = 1.6). CONCLUSIONS: In conclusion, we find that the prevalence of established factors for an unfavorable prognosis is disturbingly high among patients diagnosed with Ewing tumors. Recent progress in imaging techniques seems to account for much of the rise in the detection rate of metastases after 1991. We identify age and, in particular pelvic and femoral site as the major determinants of local tumor extension. Occurrence of primary metastases is independently related to tumor size, pelvic site, and PNET.
PURPOSE: Treatment results and the pattern of relapse were evaluated in the multimodal treatment of Ewing's sarcomas of the chest wall. METHODS AND MATERIALS: In a retrospective analysis, 114 patients with non-metastatic Ewing's sarcoma of the chest wall were evaluated. They were treated in the CESS 81, CESS 86, or EICESS 92 studies between January 1981 and December 1993. The treatment consisted of polychemotherapy (VACA, VAIA, or EVAIA) and local therapy, either surgery alone (14 patients), radiotherapy alone (28 patients) or a combination of both (71 patients). The median follow-up was 46.6 months (range 5-170). A relapse analysis for all patients with local or combined relapses was performed. RESULTS: Overall survival was 60% after 5 years, event-free survival was 50%. Thirty-seven patients had a systemic relapse (32.4%), 11 patients had a local relapse alone (9.6%), and 3 patients had a combined local and systemic relapse (2.6%). The risk to relapse locally after 5 years was 0% after surgery alone, 19% after radiation alone, and 19% after postoperative irradiation. None of the 8 patients with preoperative irradiation have failed locally so far. With the introduction of central radiotherapy planning in CESS 86, local control of irradiated patients improved. Ten of 14 patients with local failure could be evaluated in the relapse analysis: 3 patients had an in-field relapse, 4 patients had a marginal relapse, 2 patients had a relapse outside the radiation fields, and 1 patient failed with pleural dissemination. Six treatment deviations were observed. CONCLUSION: Local control was best after surgery alone in a positively selected group of patients. Local control after radiation or combined radiation and surgery was good. With diligent performance of radiotherapy, it will be possible to further improve the results in the radiotherapy group.
PURPOSE: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. MATERIALS AND METHODS: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n = 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. RESULTS: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clinical remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1 % (3/328) of all deaths in the CESS-studies. CONCLUSIONS: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5 % after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.
BACKGROUND: In the multicenter European Intergroup Cooperative Ewing's Sarcoma Studies, localized Ewing tumors of bone were treated by combination chemotherapy with surgery and/or radiotherapy. Patients with primary metastases (pm-pts) were treated in high risk protocols. PATIENTS AND METHODS: One hundred seventy-seven pm-pts were registered from January 1990 to December 1995, 171 were evaluable for survival analyses. Thirty-six pm-pts received myeloablative megatherapy with stem cell rescue following conventional treatment. Bilateral whole lung irradiation (WLI) was administered in 57 pm-pts with pulmonary involvement. Event-free survival (EFS) rates were estimated by Kaplan-Meier analysis. Prognostic factors were identified by log-rank statistics, Cox procedures and logistic regression. RESULTS: Eighty-nine deaths were recorded by 1 February 1997, EFS four years after diagnosis for all 171 pm-pts was 0.27. EFS for isolated lung metastases was 0.34, for bone/bone marrow (BM) metastases, 0.28, and for combined lung plus bone/BM metastases, 0.14 (P < 0.005). WLI improved outcome in case of isolated pulmonary involvement (0.40 vs. 0.19, P < 0.05). In pm-pts with combined pulmonary/skeletal metastases, intensification by megatherapy and/or WLI improved EFS from 0.00 to 0.27 (P = 0.0001). CONCLUSIONS: EFS four years after diagnosis in patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing disease.
Clinical pathways are processes of care that use a multidisciplinary team effort to move patients toward a designed outcome. This article details the challenges of a Quality Enhancement and Clinical Resource Management Team in designing and implementing a successful congestive heart failure pathway at a teaching hospital. Academic institutions have the resources as part of their research mission, to enhance the development of clinical pathways and assess their outcomes.
PURPOSE: To analyze event-free survival (EFS) and prognostic factors in patients who present with Ewing's tumors (ET) of bone and synchronous pulmonary and/or pleural metastases (ppm). PATIENTS AND METHODS: Of 1,270 patients (pts) registered at the continental office of the German/European Intergroup Cooperative Ewing's Sarcoma Studies (CESS81, CESS86, EICESS92), 114 were diagnosed ET with ppm. Patients underwent neoadjuvant therapy and local treatment of the primary tumor. Whole-lung irradiation 15 to 18 Gy was applied to 75 ppm-pts. EFS and 95% confidence intervals (CIs) were estimated according to the Kaplan-Meier method, and prognostic factors were analyzed by log-rank tests and Cox and logistic regression procedures. RESULTS: On November 1, 1997, at a median time under study of 5.9 years, the 5-year EFS was 0.36 (95% CI, 0.26 to 0.46) and the 10-year EFS was 0.30 (95% CI, 0.19 to 0.41). Thirty-seven of 59 (63%) first relapses involved lung and/or pleura, and the lungs were the only site of relapse in 26 of 59 (44%) ppm-pts. Risk factors identified in univariate and multivariate tests were poor response of the primary tumor toward chemotherapy, metastatic lesions in both lungs, and treatment without additional lung irradiation. CONCLUSION: Chemotherapy response of the primary tumor is a prognostic factor in patients with ET with ppm. Strategies of treatment intensification warrant further evaluation.
STUDY DESIGN: Based on prospective assessment, patients with lumbar disc surgery were examined to determine reliable predictors for clinical outcome. OBJECTIVES: The prognostic value of a screening checklist developed in a previous study was evaluated in a 2-year follow-up. SUMMARY OF BACKGROUND DATA: Outcome studies of lumbar disc surgery document a success rate between 49-90%. It has been shown that a number of medical history data and sociodemographic and psychodiagnostic findings are of prognostic value for the outcome of lumbar spine surgery. METHODS: In addition to clinical and neuroradiologic examinations, 164 patients took part in a standardized interview. Eighty-two percent participated in a follow-up performed 2 years after the operation. Preoperative findings, outcome, and prediction of three diagnostic subgroups were compared. Eighty-three (51%) patients had disc herniation only, 29 (18%) had disc herniation and other relevant back diagnoses, and 51 (31%) had no disc herniation but had other relevant back diagnoses. RESULTS: In patients with disc herniation only, good results were observed in 53%, moderate in 19%, and bad in 28%. The accuracy of prediction of the postoperative result was 75% for the patients with good outcome and 86% for those with bad outcome. In the group of patients with diagnoses other than disc herniation, the success rate of the operation was 38% good, 28% moderate, and 41% bad, but the predictor score was not as useful as for the other groups. CONCLUSION: Patients with a high risk of a bad operation outcome after lumbar discectomy could be identified preoperatively. It is suggested that those patients take part in a pain management approach instead of or in addition to surgical intervention.