| 1. |
- Dantonello, Tobias M, et al.
(författare)
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Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma
- 2014
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 21:11, s. 3579-3586
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear.METHODS:We analyzed patients with LARME treated in four consecutive CWS trials. All diagnoses were confirmed by reference reviews. Treatment included multiagent chemotherapy and local treatment of the primary tumor with surgery and/or radiotherapy. The impact of primary debulking surgery (PDS) also was studied.RESULTS:One hundred patients <21 years with a median age of 4 years had LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was performed in 19 of 100 children. The outcomes of patients with PDS were similar to those of the other patients. In 36 children, the tumor was resected after induction chemotherapy; 60 RME were irradiated. The toxic effects of radiochemotherapy were not significantly increased compared with the nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and OS were 52 ± 10 and 65 ± 9 %, respectively. Significant risk factors in multivariate analysis were age >10 years; no achievement of complete remission; and inadequate secondary local treatment, defined as incomplete secondary resection or no radiation.CONCLUSIONS:Children with LARME have a fair prognosis, despite an often huge tumor size and unfavorable primary site, if the tumors can either be resected or irradiated following induction chemotherapy. PDS was only performed in a small subgroup. Radiation performed concomitantly with chemotherapy did not increase the acute toxicity significantly.
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| 2. |
- Dantonello, Tobias M., et al.
(författare)
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Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma
- 2008
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 26:3, s. 406-413
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor- directed surveillance program for patients with localized rhabdomyosarcoma (RMS). Patients and Methods One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 ( median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed. Results Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis ( range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size. Conclusion Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor- directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor- directed guidance for detection of recurrent disease in localized RMS.
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| 3. |
- Dantonello, Tobias M., et al.
(författare)
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Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:8, s. 1267-1273
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Tidskriftsartikel (refereegranskat)abstract
- Background Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. Methods Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. Results Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 +/- 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection+radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 +/- 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. Conclusion Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment.
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| 4. |
- Klingebiel, Thomas, et al.
(författare)
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Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial.
- 2008
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Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 50:4, s. 739-45
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We prospectively studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcoma (STS). PATIENTS AND METHODS: Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m(2)) and melphalan (120 mg/m(2)) plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus etoposide (10 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy. RESULTS: From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P = 0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or "RMS-like" tumors (77.1% of all patients) demonstrated an independent benefit of OMT on outcome. CONCLUSION: Oral maintenance therapy seems to be a promising option for patients with RMS-like stage IV tumors.
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| 5. |
- Koscielniak, Ewa, et al.
(författare)
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Extraskeletal Ewing sarcoma in children, adolescents, and young adults. An analysis of three prospective studies of the Cooperative Weichteilsarkomstudiengruppe (CWS)
- 2021
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 68:10
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Tidskriftsartikel (refereegranskat)abstract
- Background We have analyzed the outcome of patients with localized extraskeletal Ewing sarcoma (EES) treated in three consecutive Cooperative Weichteilsarkomstudiengruppe (CWS) soft tissue sarcoma (STS) studies: CWS-91, CWS-96, and CWS-2002P. Methods Patients were treated in CWS-91 with four- (vincristine, dactinomycin, doxorubicin, and ifosfamide [VAIA] or cyclophosphamide [VACA II]) or five-drug (+etoposide [EVAIA]) cycles, in CWS-96 they were randomly assigned to receive VAIA or CEVAIE (+carboplatin and etoposide), and in CWS-2002P with VAIA III plus optional maintenance therapy (MT) with cyclophosphamide and vinblastine. Local therapy consisted of resection and/or radiotherapy (RT). Results Two hundred forty-three patients fulfilled the eligibility criteria. The 5-year event-free survival (EFS) and overall survival (OS) were 63% (95% confidence interval [CI] 57-69) and 73% (95% CI 67-79), respectively. The 5-year EFS by study was 64% (95% CI 54-74) in CWS-91, 57% (95% CI 48-66) in CWS-96, and 79% (95% CI 67-91) in CWS-2002P (n.s.). The 5-year OS was 72% (95% CI 62-82) in CWS-91, 70% (95% CI 61-79) in CWS-96, and 86% (95% CI 76-96) in CWS-2002P (n.s.). In CWS-96, 5-year EFS and OS in the VAIA arm versus the CEVAIE were 65% (95% CI 52-81) versus 55% (95% CI 39-76) log-rank p = .13, and 85% (95% CI 75-96) versus 61% (95% CI 45-82), log-rank p = .09. Conclusion Our analysis provides interesting information on the treatment and specificities of EES, which can be useful for a better understanding of this rare entity and should be considered in the development of future clinical trials for Ewing sarcoma defined as FET-ETS fusion positive tumors.
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| 6. |
- Koscielniak, Ewa, et al.
(författare)
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Which Patients With Rhabdomyosarcoma Need Radiotherapy? : Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry
- 2023
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Ingår i: Journal of Clinical Oncology. - : Lippincott Williams & Wilkins. - 0732-183X .- 1527-7755. ; 41:31, s. 4916-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSETo analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS).METHODSOne thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5).RESULTSThe 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% (P = .03), respectively. Ninety-five percent of patients in IRS I (90% embryonal RMS [eRMS]) were nonirradiated (EFS, 87%). Irradiated patients with IRS II had improved LCS (91% v 80%; P = .01) and EFS (not significant). In IRS III, EFS and LCS were significantly better for RT patients: 71% versus 56% (P = 3.1e-06) and 76% versus 61% (P = 4.1e-07). Patients with tumors in the head and neck region (orbita, parameningeal, and nonparameningeal) and in other sites had significantly better EFS and LCS and in parameningeal also overall survival (OS). The efficacy of low RT doses of 32 Gy (hyperfractionated, accelerated RT [HART]) and 36 and 41.4 Gy (conventional fractionated RT [CFRT]) in the favorable groups and higher doses of 44.8 Gy (HART) and 50.4 and 55.4 Gy (CFRT) in the unfavorable groups was comparable. Proton RT was used predominantly in head/neck-parameningeal (HN-PM) tumors, with similar EFS and LCS to photon RT.CONCLUSIONRT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.
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| 7. |
- Meister, Michael T., et al.
(författare)
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Malignant peripheral nerve sheath tumors in children, adolescents, and young adults : Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry
- 2020
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Ingår i: Journal of Surgical Oncology. - : WILEY. - 0022-4790 .- 1096-9098. ; 122:7, s. 1337-1347
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that present as large, invasive tumors. Our aim was to assess outcomes, identify prognostic factors, and analyze treatment strategies in a prospectively collected pediatric cohort. Methods Patients less than 21 years with MPNST treated in the consecutive prospective European Cooperative Weichteilsarkom Studiengruppe (CWS)-trials (1981-2009) and the CWS-SoTiSaR registry (2009-2015) were analyzed. Results A total of 159 patients were analyzed. Neurofibromatosis type I (NF1) was reported in thirty-eight patients (24%). Most were adolescents (67%) with large (>10 cm, 65%) tumors located at extremities (42%). Nodal involvement was documented in 15 (9%) and distant metastases in 15 (9%) upon diagnosis. Overall, event-free survival (EFS) was 40.5% at 5 and 36.3% at 10 years, and overall survival (OS) was 54.6% at 5 and 47.1% at 10 years. Age, NF1 status, tumor site, tumor size, Intergroup Rhabdomyosarcoma Study (IRS) group, metastatic disease, and achieving first complete remission (CR1) were identified as prognostic factors for EFS and/or OS in the univariate analysis. Conclusions Prognostic factors were identified and research questions for future clinical trials were addressed.
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| 8. |
- Scheer, Monika, et al.
(författare)
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Desmoplastic small round cell tumors : Multimodality treatment and new risk factors
- 2019
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Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 8:2, s. 527-542
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate optimal therapy and potential risk factors.Methods: Data of DSRCT patients <40 years treated in prospective CWS trials 1997‐2015 were analyzed.Results: Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high‐dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three‐year event‐free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra‐abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.Conclusion: Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
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| 9. |
- Scheer, Monika, et al.
(författare)
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Pre-operative radiotherapy is associated with superior local relapse-free survival in advanced synovial sarcoma
- 2023
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Nature. - 0171-5216 .- 1432-1335. ; 149:5, s. 1717-1731
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Optimization of local therapies in synovial sarcoma (SS) considered unresectable at diagnosis is needed. We evaluated the effects of neoadjuvant versus adjuvant radiation versus surgery only on long-term outcomes. Methods Patients with macroscopic SS tumors before chemotherapy (IRS-group-III) in the trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P and SoTiSaR-registry were analyzed. Local therapies were scheduled after 3 neoadjuvant chemotherapy cycles. Results Median age of 145 patients was 14.5 years. 106 survivors had median follow-up of 7.0 years. Tumor site was 96 extremities, 19 head-neck, 16 shoulder/hip, 14 trunk. Tumors were < 3 cm in 16, 3-5 cm in 28, 5-10 cm in 55, > 10 cm in 34 patients. In a secondary resection during chemotherapy, R0-status was accomplished in 82, R1 in 30, R2 in 21 (12 missing). Radiotherapy was administered to 115 (R0 61, R1 29, R2 20, missing 5), thereof 57 before and 52 after tumor resection. 23 were treated with surgery only. For all patients, 5 year event-free (EFS) and overall survival (OS) was 68.9% +/- 7.6 (95%CI) and 79.1% +/- 6.9. To establish independent significance, tumor site, size, surgical results and sequencing of local therapies were analyzed in a Cox regression analysis. Variables associated with EFS and OS are site, size and sequencing of local therapies. Variables associated with local recurrence are site, surgical results and sequencing of local therapies. The only variable associated with suffering metastatic recurrence is tumor size. Conclusion Differences in sequencing of local therapy procedures are independently associated with outcomes. Best local control is achieved when tumors are irradiated pre-operatively and undergo R0 or R1 resection thereafter.
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| 10. |
- Schober, Sebastian Johannes, et al.
(författare)
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No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatients with stage IV alveolar rhabdomyosarcoma (RMA) have a 5-year-survival rate not exceeding 30%. Here, we assess the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients in comparison to standard-of-care regimens. We also compare the use of HLA-mismatched vs. HLA-matched grafts after reduced vs. myeloablative conditioning regimens, respectively. Patients and MethodsIn this retrospective analysis, we compare event-free survival (EFS), overall survival (OS), and toxicity of HLA-mismatched vs. -matched transplanted patients in uni- and multivariate analyses (total: n = 50, HLA-matched: n = 15, HLA-mismatched: n = 35). Here, the factors age at diagnosis, age at allo-HSCT, sex, Oberlin score, disease status at allo-HSCT, and HLA graft type are assessed. For 29 primarily transplanted patients, three matched non-transplanted patients per one transplanted patient were identified from the CWS registry. Outcomes were respectively compared for OS and EFS. Matching criteria included sex, age at diagnosis, favorable/unfavorable primary tumor site, and metastatic sites. ResultsMedian EFS and OS did not differ significantly between HLA-mismatched and -matched patients. In the mismatched group, incidence of acute GvHD was 0.87 (grade III-IV: 0.14) vs. 0.80 in HLA-matched patients (grade III-IV: 0.20). Transplant-related mortality (TRM) of all patients was 0.20 and did not differ significantly between HLA-mismatched and -matched groups. A proportion of 0.58 relapsed or progressed and died of disease (HLA-mismatched: 0.66, HLA-matched: 0.53) whereas 0.18 were alive in complete remission (CR) at data collection. Multivariate and competing risk analyses confirmed CR and very good partial response (VGPR) status prior to allo-HSCT as the only decisive predictor for OS (p < 0.001). Matched-pair survival analyses of primarily transplanted patients vs. matched non-transplanted patients also identified disease status prior to allo-HSCT (CR, VGPR) as the only significant predictor for EFS. Here, OS was not affected, however. ConclusionIn this retrospective analysis, only a subgroup of patients with good response at allo-HSCT survived. There was no survival benefit of allo-transplanted patients compared to matched controls, suggesting the absence of a clinically relevant graft-versus-RMA effect in the current setting. The results of this analysis do not support further implementation of allo-HSCT in RMA stage IV patients.
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