| 1. |
- Dantonello, Tobias M, et al.
(författare)
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Malignant ectomesenchymoma in children and adolescents : Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited.METHODS: Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed.RESULTS:The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7).CONCLUSIONS: Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma.
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| 2. |
- Scheer, Monika, et al.
(författare)
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Synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups : a report of the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2020
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : SPRINGER. - 0171-5216 .- 1432-1335. ; 146:4, s. 953-960
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older age is associated with worse outcome in synovial sarcoma (SS) patients. Differences in disease presentation among distinct age groups, however, are currently unknown.Methods: SS patients < 21 years registered in consecutive CWS trials over the period of 1981-2018 were evaluated. Characteristics were analyzed according to age groups using the Fisher's exact test.Results: The study population included 432 SS patients. Disease characteristics differed according to age groups of children (0-12 years, n = 176), adolescents (13-16 years, n = 178), and young adults (17-21 years, n = 78). The proportion of invasive tumors (T2) was significantly higher in older patients: children 33%, adolescents 39% and young adults 54%, p = 0.009805. Similarly, the proportion of tumors > 10 cm was higher (13%, 21%, 31%; p = 0.005657) whereas conversely, the proportion of small tumors < 3 cm was lower in older patients (29%, 24%, 6%; p = 0.000104). The presence of metastases at first diagnosis was also highest in older patients (6%, 10%, 21%, p = 0.000963). Notably, the proportion of thigh tumors was higher in older patients (p = 0.04173), whereas the proportion of head-neck tumors was lower in older patients (p = 0.08896).Conclusions The rates of large, invasive tumors and the presence of metastases are significantly associated with older patient age. Localization to the thigh is more frequent in older patients.Discussion The causes for these variations require further exploration.
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| 3. |
- Sparber-Sauer, Monika, et al.
(författare)
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Infantile myofibromatosis : Excellent prognosis but also rare fatal progressive disease. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry
- 2022
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 69:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infantile myofibromatosis (IM) is a rare benign soft tissue tumor and often a self-limiting disease but rarely includes life-threatening complications. Little is known about optimal treatment of primary localized (LD) and multifocal disease (MFD).Methods: Treatment and outcome of 95 children with IM registered within five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1981-2016) were evaluated.Results: LD was diagnosed in 71 patients at a median age of 0.4 years (range 0.0-17.7). MFD was present in 24 patients. The mainstay of treatment was watch-and-wait strategy (w&w) after initial biopsy or resection. Low-dose chemotherapy (CHT) was administered to 16/71 (23%) patients with LD and eight of 24 (33%) patients with MFD, imatinib was added in two. A delayed resection was possible in eight of 71 (11%) and five of 24 (21%) patients with LD and MFD, respectively. Overall, patients were alive in complete remission (n = 77) and partial remission (n = 10) at a median follow-up time of 3.4 years after diagnosis (range 0.01-19.4); no data available (n = 5). Three patients died of progressive disease (PD) despite CHT. Gender, tumor size, and location correlated with a favorable event-free survival (EFS) in patients with LD. The 5-year EFS and overall survival of patients with LD were 73% (±12, confidence interval [CI] 95%) and 95% (±6, CI 95%), respectively; for MFD 51% (±22, CI 95%) and 95% (±10, CI 95%).Cconclusion: Prognosis is excellent in patients with LD and MFD. Targeted treatment needs to be evaluated for rare fatal PD.
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| 4. |
- Whelan, Jeremy, et al.
(författare)
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High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk ewing sarcoma : Results of Euro-E.W.I.N.G.99 and Ewing-2008
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:31, s. 3110-3119
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Tidskriftsartikel (refereegranskat)abstract
- Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis >200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year eventfree survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel comparedwith VAI: HR, 0.64 (95%CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0%(95% CI, 60.2%to 76.6%) versus 56.7%(95%CI, 47.6%to 65.4%) and 60.7%(95%CI, 51.1%to 69.6%) versus 47.1%(95%CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5%(95%CI, 54.4% to 73.5%) versus 55.6%(95%CI, 45.8%to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.
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| 5. |
- Ameline, Baptiste, et al.
(författare)
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NTRK fusions in osteosarcoma are rare and non-functional events
- 2020
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Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 6:2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- Neurotrophic tyrosine receptor kinase (NTRK) fusions are promising molecular targets that have been described in a broad range of malignant tumours. Fusions commonly lead to the expression of chimeric proteins with constitutive tyrosine kinase activation that drives tumorigenesis. Despite a low prevalence among most solid tumours (<1%), the first encouraging results with pan-NTRK tyrosine kinase inhibitors (TKIs) such as larotrectinib or entrectinib stimulated the search for eligible patients. Here, we report the first three cases of osteosarcoma harbouring NTRK fusions, among 113 patients sequenced. It is also the first report on NTRK fusions within a tumour type characterised by highly rearranged genomes and abundant passenger mutations. Whereas the presence of NTRK gene fusions in many tumours is considered to be one of the main driver events for tumour progression, the three chimeric transcripts described here appear non-functional and likely represent randomly occurring passenger alterations. Particularly in tumours with complex karyotypes, it may therefore be advisable to specifically investigate the fusion transcripts for functional impact before considering targeted treatment approaches using pan-NTRK TKIs.
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| 6. |
- Bielack, Stefan S, et al.
(författare)
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Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:20, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.
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| 7. |
- Budde, Axel, et al.
(författare)
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Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma
- 2022
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 170, s. 209-235
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The available questionnaires for quality-of-life (QoL) assessments are age-group specific, limiting comparability and impeding longitudinal analyses. The comparability of measurements, however, is a necessary condition for gaining scientific evidence. To overcome this problem, we assessed the viability of harmonising data from paediatric and adult patient-reported outcome (PRO) measures. Method: To this end, we linked physical functioning scores from the Paediatric Quality of Life Inventory (PedsQL) and the Paediatric Quality of Life Questionnaire (PEDQOL) to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) for adults. Samples from the EURAMOS-1 QoL sub-study of 75 (PedsQL) and 112 (PEDQOL) adolescent osteosarcoma patients were concurrently administered both paediatric and adult questionnaires on 98 (PedsQL) and 156 (PEDQOL) occasions. We identified corresponding scores using the single-group equipercentile linking method. Results: Linked physical functioning scores showed sufficient concordance to the EORTC QLQ-C30: Lin's ρ = 0.74 (PedsQL) and Lin's ρ = 0.64 (PEDQOL). Conclusion: Score linking provides clinicians and researchers with a common metric for assessing QoL with PRO measures across the entire lifespan of patients.
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| 8. |
- Calaminus, Gabriele, et al.
(författare)
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Quality of life of patients with osteosarcoma in the european american osteosarcoma study-1 (EURAMOS-1) : Development and implementation of a questionnaire substudy
- 2019
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Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The quality of life (QoL) of patients with osteosarcoma (OS) may be adversely affected by the disease or its treatment. Therefore, it is important to understand the QoL of patients undergoing treatment for OS to improve the QoL. We report on the first prospective international QoL study that was embedded within a large randomized clinical trial from 4 national study groups. Objective: This paper aimed to describe the QoL study development, methodology, accrual details, and characteristics of the QoL cohort. Methods: A total of 2260 patients registered in the EURopean AMerican Osteosarcoma Study-1 (EURAMOS-1), of whom 97.92% (2213/2260) were eligible for the optional QoL assessment and could participate in terms of questionnaire availability. Overall, 61.86% (1369/2213) of patients and/or proxies completed the QoL evaluation at the first assessment time point (E1) after the start of preoperative treatment. The QoL measures used (self- and/or proxy reports) depending on the patient’s age and national study group. Participants and nonparticipants in the ancillary QoL study were compared regarding relevant demographic and disease-related characteristics at registration in the trial. Results: The participation rate at time point E1 did not differ with regard to age, gender, the occurrence of pathological fracture, or the presence of any metastases at diagnosis. No differences were found regarding the primary tumor site. Only the national study group affiliation had an influence on participation. Participation decreased linearly with trial progress up to 20% at the final time point of QoL assessment. Conclusions: This study demonstrates the feasibility of international cooperation for the purpose of assessing and understanding the QoL of pediatric and adolescent/young adult patients with cancer. Future outcomes of this QoL substudy will help to adapt interventions to improve QoL.
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| 9. |
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| 10. |
- Collins, Marnie, et al.
(författare)
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Benefits and Adverse Events in Younger Versus Older Patients Receiving Neoadjuvant Chemotherapy for Osteosarcoma: Findings From a Meta-Analysis.
- 2013
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 31:18, s. 130-2303
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEThe LIVESTRONG Young Adult Alliance has conducted a meta-analysis of individual patient data from prospective neoadjuvant chemotherapy osteosarcoma studies and registries to examine the relationships of sex, age, and toxicity on survival. PATIENTS AND METHODSSuitable data sets were identified by a survey of published data reported in PubMed. The final pooled data set comprised 4,838 patients from five international cooperative groups.ResultsAfter accounting for important variables known at study entry such as tumor location and histology, females experienced higher overall survival rates than males (P = .005) and children fared better than adolescents and adults (P = .002). Multivariate landmark analysis following surgery indicated that a higher rate of chemotherapy-induced tumor necrosis was associated with longer survival (P < .001), as was female sex (P = .004) and the incidence of grade 3 or 4 mucositis (P = .03). Age group was not statistically significant in this landmark analysis (P = .12). Females reported higher rates of grade 3 or 4 thrombocytopenia relative to males (P < .001). Children reported the highest rates of grade 3 or 4 neutropenia (P < .001) and thrombocytopenia (P < .001). The achievement of good tumor necrosis was higher for females than for males (P = .002) and for children than for adults (P < .001). CONCLUSIONThese results suggest fundamental differences in the way chemotherapy is handled by females compared with males and by children compared with older populations. These differences may influence survival in a disease in which chemotherapy is critical to overall outcomes.
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