A balancing act: Principles, criteria and indicator framework to operationalize social-ecological resilience of forests.

Against a background of intensifying climate-induced disturbances, the need to enhance the resilience of forests and forest management is gaining urgency. In forest management, multiple trade-offs exist between different demands as well as across and within temporal and spatial scales. However, methods to assess resilience that consider these trade-offs are presently lacking. Here we propose a hierarchical framework of principles, criteria, and indicators to assess the resilience of a social-ecological system by focusing on the mechanisms behind resilience. This hierarchical framework balances trade-offs between mechanisms, different parts of the social-ecological system, ecosystem services, and spatial as well as temporal scales. The framework was developed to be used in a participatory manner in forest management planning. It accounts for the major parts of the forest-related social-ecological system and considers the multiple trade-offs involved. We demonstrate the utility of the framework by applying it to a landscape dominated by Norway spruce (Picea abies (L.) Karst.) in Central Europe, managed for three different management goals. The framework highlights how forest resilience varies with the pursued management goals and related management strategies. The framework is flexible and can be applied to various forest management contexts as part of a participatory process with stakeholders. It thus is an important step towards operationalizing social-ecological resilience in forest management systems.

A spatially-explicit database of tree-related microhabitats in Europe and beyond.

Background: Tree to tree interactions are important structuring mechanisms for forest community dynamics. Forest management takes advantage of competition effects on tree growth by removing or retaining trees to achieve management goals. Both competition and silviculture have, thus, a strong effect on density and distribution of tree related microhabitats which are key features for forest taxa at the stand scale. In particular, spatially-explicit data to understand patterns and mechanisms of tree-related microhabitats formation in forest stands are rare. To train and eventually improve decision-making capacities related to the integration of biodiversity aspects into forest management plot of one hectare, so called marteloscopes were established in the frame of the 'European Integrate Network'. In each plot, a set of data is collected at the individual tree level and stored in a database, the 'I+ repository'. The 'I+ repository' is a centralised online database which serves for maintaining the data of all marteloscope plots. A subset of this repository was made publicly available via the Global Biodiversity Information Facility, based on a data-sharing policy. Data included are tree location in plot, tree species, forest mensuration data (diameter at breast height [cm], tree height [m]), tree status (living or standing dead) and tree-related microhabitats. Further, a visual assessment of timber quality classes is performed in order to provide an estimate of the economic value (market price) for each tree. This information is not part of the GBIF dataset. New information: Currently 42,078 individual tree observations from 111 plots are made available via the Global Biodiversity Information Facility (GBIF). As the network of plots continues to expand, so does the database of tree-related microhabitats. Therefore, the database will undergo a regular update. The current version has a temporal coverage from March 2014 to December 2020. The innovation of this unique dataset is that it is based on a commonly agreed catalogue of tree microhabitats as a field reference list when assessing assessment protocol. The reference list is available in 17 languages and, thus, helps to guarantee compatibility of tree-related microhabitat assessments across countries and plots.

Shifting public engagement: How media coverage of climate change conferences affects climate change audience segments.

While it is often assumed that media attention for events, such as international climate change conferences, can influence public opinion, research studying changes in public opinion concerning climate change is scarce. Research on climate change audience segments and the theory of motivated reasoning suggest that media effects depend on the level of audience engagement with climate change. We analyze how exposure to media coverage of the COP21 affected public opinion in the Netherlands. Based on a two-wave online panel survey (N = 876), we identified five audience segments that varied in their degree of climate change beliefs, involvement, policy preferences, and behavioral intentions. Different media effects across segments were found indicating (dis)confirmation bias, specifically, for medium levels of positive and negative engagement. The findings indicate that important events may cause limited changes in public opinion and emphasize the importance of studying segment-specific and content-specific media effects.

Treatment and outcome of the patients with rhabdomyosarcoma of the biliary tree: Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS).

BACKGROUND: Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The management of affected patients contains unique challenges because of the rarity of this tumor entity and its critical location at the porta hepatis, which can make achievement of a radical resection very difficult. METHODS: In a retrospective chart analysis we analysed children suffering from biliary RMS who were registered in three different CWS trials (CWS-96, CWS-2002P, and SoTiSaR registry). RESULTS: Seventeen patients (12 female, 5 male) with a median age of 4.3 years were assessed. The median follow-up was 42.2 months (10.7-202.5). The 5-year overall (OS) and event free survival (EFS) rates were 58% (45-71) and 47% (34-50), respectively. Patients > 10 years of age and those with alveolar histology had the worst prognosis (OS 0%). Patients with botryoid histology had an excellent survival (OS 100%) compared to those with non-botryoid histology (OS 38%, 22-54, p = 0.047). Microscopic complete tumor resection was achieved in almost all patients who received initial tumor biopsy followed by chemotherapy and delayed surgery. CONCLUSION: Positive predictive factors for survival of children with biliary RMS are age ≤ 10 years and botryoid tumor histology. Primary surgery with intention of tumor resection should be avoided.

Treatment and outcome of patients with thoracic tumors of the Ewing sarcoma family: A report from the Cooperative Weichteilsarkom Studiengruppe CWS-81, -86, -91, -96, and -2002P trials.

BACKGROUND: Ewing tumors are the most frequent malignant tumors of the chest wall in children and young adults. Surgical management of these tumors can be challenging. Optimal local control remains controversial. The aim of this study was to analyze treatment, outcome, and surgical procedures in patients with thoracic tumors of the Ewing sarcoma family (TES) treated within four Cooperative Soft-Tissue Sarcoma (CWS) trials and one registry. PATIENTS AND METHODS: Sixty-two patients from 0 to 21 years treated between 1981 and 2014 were selected for this analysis. A retrospective chart analysis was carried out. Institutional review board approval was obtained for all trials. RESULTS: The median age of the patients was 7 years. The 5-year overall (OS) and event-free survival (EFS) rates were 58.7% (52.7-64.7) and 52.8% (46.8-58.8). Patients with intrathoracic tumor localization (n = 24) had a worse outcome (EFS: 37.5%; 27.5-37.5) compared with those with chest wall tumors (n = 38; EFS: 62.3%; 54.3-70.3, P = 0.008). Patients ≤10 years (n = 38) had a better survival compared with those > 10 years (EFS: 65.7%; 57.7-73.7 vs 31.3%; 21.3-41.3, P = 0.01). Tumor size ≤5 cm (n = 15) was associated with significantly better survival compared with a size > 5 cm (n = 47, EFS: 93.3%; 87.3-99.3 vs 40%; 33-47, P = 0.002). Primary resections were carried out in 36 patients, of which 75% were incomplete resulting in inferior EFS (P = 0.006). Complete secondary resections were performed in 22 of 40. CONCLUSIONS: Positive predictive factors for outcome are age ≤10 years, size ≤5 cm, and localization at the chest wall. Diverse IRS groups require individual treatment.

Treatment and outcome of patients with thoracic tumors of the Ewing sarcoma family: A report from the Cooperative Weichteilsarkom Studiengruppe CWS-81, -86, -91, -96, and -2002P trials.

BACKGROUND: Ewing tumors are the most frequent malignant tumors of the chest wall in children and young adults. Surgical management of these tumors can be challenging. Optimal local control remains controversial. The aim of this study was to analyze treatment, outcome, and surgical procedures in patients with thoracic tumors of the Ewing sarcoma family (TES) treated within four Cooperative Soft-Tissue Sarcoma (CWS) trials and one registry. PATIENTS AND METHODS: Sixty-two patients from 0 to 21 years treated between 1981 and 2014 were selected for this analysis. A retrospective chart analysis was carried out. Institutional review board approval was obtained for all trials. RESULTS: The median age of the patients was 7 years. The 5-year overall (OS) and event-free survival (EFS) rates were 58.7% (52.7-64.7) and 52.8% (46.8-58.8). Patients with intrathoracic tumor localization (n = 24) had a worse outcome (EFS: 37.5%; 27.5-37.5) compared with those with chest wall tumors (n = 38; EFS: 62.3%; 54.3-70.3, P = 0.008). Patients ≤10 years (n = 38) had a better survival compared with those > 10 years (EFS: 65.7%; 57.7-73.7 vs 31.3%; 21.3-41.3, P = 0.01). Tumor size ≤5 cm (n = 15) was associated with significantly better survival compared with a size > 5 cm (n = 47, EFS: 93.3%; 87.3-99.3 vs 40%; 33-47, P = 0.002). Primary resections were carried out in 36 patients, of which 75% were incomplete resulting in inferior EFS (P = 0.006). Complete secondary resections were performed in 22 of 40. CONCLUSIONS: Positive predictive factors for outcome are age ≤10 years, size ≤5 cm, and localization at the chest wall. Diverse IRS groups require individual treatment.

Impact of the Interdisciplinary Tumor Board of the Cooperative Ewing Sarcoma Study Group on local therapy and overall survival of Ewing sarcoma patients after induction therapy.

BACKGROUND: The Interdisciplinary Tumor Board (ITB) of the Cooperative Ewing Sarcoma Study (CESS) Group was investigated to assess its impact on the overall survival (OAS) of Ewing sarcoma (EwS) patients. The ITB functions as a reference center for the international institutions participating in the clinical trials of the CESS group, but is also available internationally to patients who have not been treated within an appropriate clinical trial. The value of tumor boards in terms of benefit for the patients and the health care system in general is not well documented and is also the subject of controversial discussions. A review of the representative literature is included. METHODS: Data were analyzed from 481 patients who had been registered into the European Ewing Tumor Working Initiative of National Groups (EURO E.W.I.N.G.-99) clinical trial via the CESS data center between 2006 and 2009; this included 331 patients with localized disease and another 150 individuals with metastases at diagnosis. Median follow-up time was 3.2 years. RESULTS: Improved OAS was observed for patients with metastases who had received recommendations from the ITB compared with those who had not received recommendations. In patients with localized disease, a recommendation from the ITB had no influence on OAS. CONCLUSION: As a reference center for a rare disease, recommendations from our ITB impacted local therapy and led to higher OAS in patients with metastatic disease. To our knowledge, this is the first analysis that examines the value of a reference tumor board on a rare disease.

Treatment and outcome of patients with localized intrathoracic and chest wall rhabdomyosarcoma: a report of the Cooperative Weichteilsarkom Studiengruppe (CWS).

PURPOSE: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In 7% of the cases it is localized at the chest wall or intrathoracically. The aim of this study was to analyze the multimodal treatment concepts and outcomes of children suffering from intrathoracic and chest wall RMS treated within three different Cooperative Soft Tissue Sarcoma (CWS) trials and one registry (Soft Tissue Sarcoma Registry, SoTiSaR). METHODS: Data of 51 patients with thoracic RMS enrolled in three different CWS trials (CWS-86, -91, -2002P) and one registry (SoTiSaR) were analyzed retrospectively. Surgery and its influence on outcome were assessed. Median follow-up was 37.5 months (0.9-152.5). RESULTS: Median age of the patients was 8.8 years (range 0-19 years). The 5-year overall survival rate (OS) was 57% (95%-CI 49-65) and the 5-year event-free survival rate (EFS) was 45% (38-52). Thirty-five patients had tumors located at the chest wall (EFS: 51%, 43-59), and 16 patients had intrathoracic tumors (EFS: 26%, 13-39). Seventeen patients with tumors ≤ 5 cm had a better outcome (EFS: 64%, 52-76) compared to patients with tumors larger than 5 cm (EFS: 36%, 27-45). Radiotherapy (RT) significantly improved the survival of patients with alveolar RMS compared to patients with embryonal histology (EFS: 66%, 52-80 vs. 32%, 21-43 p = 0.02). Complete tumor excision during delayed surgery was the main prognostic factor for survival (p = 0.045). CONCLUSION: Thoracic RMS is a rare tumor entity. Completeness of tumor resection significantly improved survival of the patients.

Outcome, Treatment, and Treatment Failures in Patients Suffering Localized Embryonal Paratesticular Rhabdomyosarcoma: Results From the "Cooperative Weichteilsarkom Studiengruppe" Trials CWS-86, -91, -96, and -2002P.

OBJECTIVE: To evaluate outcome in respect to local treatment strategies in 4 prospective CWS trials in patients with paratesticular rhabdomyosarcoma (PTRMS). SUMMARY BACKGROUND DATA: PTRMS patients have a high number of surgical treatment failures. Retroperitoneal lymph node (LN) involvement is common in patients more than 10 years, and the optimal treatment is unknown. METHODS: A total of 173 patients with diagnosis of PTRMS were enrolled. Of these, 26 were excluded and 147 patients were finally analyzed. All patients were treated according to the Cooperative Soft Tissue Sarcoma (CWS) trial protocols. RESULTS: The 5-year overall survival was 95.5%, and the 5-year event-free survival (EFS) was 89.8%. Positive predictive factors for EFS were age younger than 10 years and tumor size less than 5 cm. Surgical treatment failures were observed in 34 of 135 patients undergoing primary resection. Primary inguinal/iliacal LN sampling was carried out in 15 of 147 patients with no impact on the EFS (87.5%; P = 0.666). Secondary retroperitoneal LN dissection was done in 32 of 147 patients, of which only 8 patients had viable tumor and a worse outcome (EFS: 50%; P = 0.01). Loco-regional, combined, and metastatic relapses were observed in 13 of 147 patients. CONCLUSIONS: The outcome of PTRMS patients is excellent and is hardly improvable. Positive predictors for outcome are age younger than 10 years and tumor size less than 5 cm. Primary LN sampling seems to have no impact on the EFS and should not be recommended. Inadequate surgery can be avoided by treatment in specialized centers. Secondary retroperitoneal LN dissection revealed a high number of unnecessary procedures, but patients with positive LN had a poor prognosis and require additional local therapy.

Improvements in the Treatment of Patients Suffering from Bladder-Prostate Rhabdomyosarcoma: A Report from the CWS-2002P Trial.

PURPOSE: Modern treatment concepts for bladder/prostate rhabdomyosarcoma (BPRMS) are designed to improve survival, to reduce therapy intensity, and to increase bladder preservation rates. Nevertheless, treatment is not optimal. The purpose of this study was to analyze BPRMS patients treated within the CWS-2002P trial regarding outcome, treatment modalities, complications, and to compare the data with the precursor trial CWS-96. METHODS: Fifty children with localized embryonal BPRMS were analyzed. Eight patients were excluded. Patients received neoadjuvant chemotherapy. At week 9, reassessment using MRI scan was performed. Depending on tumor size, age, and response, local therapy consisting of radiotherapy and/or surgery was initiated. After local therapy, systemic therapy was continued. RESULTS: Patients' median age was 35.6 months. Median follow-up was 59 months. The 5-year OS was 84.5 % and the 5-year ES 79.9 %. Ten patients underwent combined radiochemotherapy and tumor resection (5-year ES: 87.5 %). Six patients were treated solely with radiochemotherapy (5-year ES: 60 %). Twenty-six patients received preoperative chemotherapy followed by tumor resection (ES: 80.8). One patient was treated with chemotherapy only and survived. The bladder preservation rate was 80.9 %. CONCLUSIONS: The outcome within the CWS-2002P trial regarding OS and ES seemed to be better than in the precursor trial CWS-96 due to a reduction of protocol violations, but there was no statistical significant difference possibly due to low numbers. Radiotherapy was used less frequently, and the bladder preservation rate was slightly higher. Novel concepts will be required in the future to improve bladder preservation rates.

Challenges in the local treatment of large abdominal embryonal rhabdomyosarcoma.

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.

Treatment and outcome of patients suffering from perineal/perianal rhabdomyosarcoma: results from the CWS trials--retrospective clinical study.

OBJECTIVE: To analyze the clinical course, treatment, complications, outcome, and quality of life (QOL) in patients with perineal/perianal rhabdomyosarcoma (PRMS) treated within the CWS-86, -91, -96, and -2002P trials. BACKGROUND: Although multiple international study trials exist for the treatment of rhabdomyosarcoma, only very limited information is given on treatment, outcome, and QOL in PRMS. METHODS: A total of 35 patients suffering from PRMS were treated with neoadjuvant chemotherapy. Local therapy with radiation and/or surgery was performed, followed by adjuvant chemotherapy. Functional long-term follow-up was evaluated by a gastrointestinal/QOL survey. RESULTS: Thirty-two patients were evaluated (exclusion n = 3). Eight patients had embryonal histology, and 24 patients had alveolar histology. The median age was 108 months (median follow-up: 5.8 years). The 5-year overall survival was 47% (95% confidence interval: 29-64). Sixteen IRS (Intergroup Rhabdomyosarcoma Study) III and IV patients had locoregional lymph node involvement at diagnosis. Seven patients were treated with chemotherapy/surgery alone [5-year event-free survival (EFS): 85.7%]. Eleven patients received only radiochemotherapy (5-year EFS: 27.3%). Combined radiochemotherapy/surgery was used in 12 patients (5-year EFS: 63.6%). Two patients were treated only with chemotherapy and they died. Patients with embryonal histology had a significantly better 5-year EFS (87.5%) than patients with alveolar histology (39.1%; P = 0.013). Some patients reported symptoms of fecal incontinence. The median Wexner fecal incontinence score was 9 (possible range: 0-20), and the median QOL score was 90.5 (applicable range: 0-144). CONCLUSIONS: The outcome of these patients remains unsatisfactory. Prognostic factors for a favorable outcome are tumor size of smaller than 5 cm, negative locoregional lymph nodes, age less than 10 years, low IRS group, and embryonal histology. Fecal incontinence seems to be a problem.

Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma.

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.

Malignant ectomesenchymoma in children and adolescents: report from the Cooperative Weichteilsarkom Studiengruppe (CWS).

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.

Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: a report from the Cooperative Soft Tissue Sarcoma trial CWS-96.

BACKGROUND: To analyze the clinical course, treatment modalities, complications and outcome of patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma (BPRMS) treated on the CWS-96 trial. PROCEDURE: There were 85 patients with BPRMS enrolled and 63 patients with embryonal non-metastatic BPRMS were analyzed. Fifty-six patients received neoadjuvant chemotherapy and response was assessed radiographically after 9 weeks. Local therapy with radiation and or surgery was performed based on age, tumor size, and response. Patients were treated with adjuvant chemotherapy following local control. RESULTS: Patient's age ranged from 0 to 16 years with a median follow up of 5.3 years. Eighty nine percent of the patients had IRS group III disease. The 5-year overall survival (OS) for the whole group was 76.3 ± 5.6% and the 5-year event-free survival (EFS) 69.8 ± 6.2%. Seventeen patients underwent preoperative radiochemotherapy followed by tumor resection (5-year-OS: 87.8 ± 8.1%). Eight patients were treated with solely radiochemotherapy (87.5 ± 11.7%). Twenty-five patients received chemotherapy and tumor resection (OS: 83.6 ± 7.5%). Thirteen patients underwent incomplete tumor resection and were treated with radiochemotherapy postoperatively (OS: 39.9 ± 14.8%, P < 0.05 vs. other groups). CONCLUSIONS: Local therapy is an important factor for prognosis of localized embryonal BPRMS. Inadequate primary or secondary surgery compromises the outcome and should be avoided. Radiotherapy alone, complete surgical tumor resection or combined preoperative radiotherapy with surgical resection lead to similar good local control rates and prognosis.

Clinical outcomes of adjuvant external-beam radiotherapy for differentiated thyroid cancer - results after 874 patient-years of follow-up in the MSDS-trial.

AIM: Evaluate the clinical benefit of external beam radiotherapy (RTx) for locally invasive thyroid carcinoma with follicular cell differentiation (DTC). PATIENTS, METHODS: The Multicentre Study on Differentiated Thyroid Cancer (MSDS) was planned as a prospective multicenter trial on the benefit of adjuvant RTx in locally invasive DTC (pT4; UICC 1997) with or without lymph node metastases and no known distant metastases. All patients were treated with thyroidectomy, 131I-therapy, and TSH-suppression and were randomized to receive additional RTx or not. In 4/2003 the trial became a prospective cohort study after only 45 of then 311 patients had consented to randomization. 351 of 422 patients met the trial's inclusion criteria. Age was 48 +/- 12 years (mean +/- SD). 25% were men. Tumours were papillary in 90% and follicular in 10%. Of 47 patients randomized or allocated to RTx, 26 actually received RTx. RESULTS: Mean follow-up was 930 days. In an actual treatment analysis, 96% (25/26) of the RTx-patients reached complete remission (CR) vs. 86% in the non-RTx patients. Recurrences occurred in 0 vs. 3 % of patients: 6 reoperated for regional lymph node metastases, 1 tracheal invasion treated with tracheoplasty, 1 local invasion necessitating laryngectomy, 2 distant metastases (1 lung, 1 lung + bone). Serious chronic RTx toxicity occurred in 1/26 patients. CONCLUSION: The MSDS trial showed low mortality and recurrence rates and a weak benefit of RTx in terms of local control that did however not reach statistical significance. Routine RTx in locally invasive DTC can no longer be recommended.

Does the time-point of relapse influence outcome in pediatric rhabdomyosarcomas?

BACKGROUND: Childhood rhabdomyosarcoma (RMS), a soft tissue malignant tumor of skeletal muscle origin, accounts for approximately 3.5% of the cases of cancer among children 0-14 years and 2% of the cases among adolescents and young adults 15-19 years of age. PROCEDURE: We evaluated survival (SUR) after first relapse depending on the time to relapse (TTR) in RMSs of childhood and adolescence. Early, intermediate, and late relapsing patients were evaluated for prognostic risk factors. RESULTS: Two hundred thirty-four patients with RMS enrolled in the German sarcoma trial CWS-81, CWS-86, CWS-91, and CWS-96 met selection criteria. Of the 234 patients, 35%, 32%, and 33% relapsed within 6 (early), 6-12 (intermediate), and more than 12 (late) months respectively after the end of primary therapy. Four-year SUR was 12%, 21%, and 41% for early, intermediate, and late relapse respectively (P < 0.001). Four-year SUR after local relapse was 18% (early), 38% (intermediate), and 49% (late). Embryonal RMS showed four year SUR of 16%, 30%, and 46% (P < 0.001) whereas alveolar histology showed four year SUR of 8%, 6%, and 23% (P < 0.01) for early, intermediate, and late relapse respectively. CONCLUSION: TTR has significant influence on prognosis in relapsed RMS. It influences SUR independent of other features such as type of relapse, histology, tumor site, primary treatment time or irradiation in primary treatment.

Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients.

PURPOSE: The European Intergroup Cooperative Ewing's Sarcoma Study investigated whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk (SR) patients and whether the addition of etoposide improves survival in high-risk (HR) patients. PATIENTS AND METHODS: SR patients (localized tumors, volume <100 mL) were randomly assigned to receive four courses of vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy followed by 10 courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA; cyclophosphamide replacing ifosfamide). HR patients (volume >or=100 mL or metastases) were randomly assigned to receive 14 courses of either VAIA or VAIA plus etoposide (EVAIA). Outcome measures were event-free survival (EFS; defined as the time to first recurrence, progression, second malignancy, or death) and overall survival (OS). RESULTS: A total of 647 patients were randomly assigned: 79 SR patients were assigned to VAIA, 76 SR patients were assigned to VACA, 240 HR were assigned to VAIA, and 252 HR patients were assigned to EVAIA. The median follow-up was 8.5 years. In the SR group, the hazard ratios (VACA v VAIA) for EFS and OS were 0.91 (95% CI, 0.55 to 1.53) and 1.08 (95% CI, 0.58 to 2.03), respectively. There was a higher incidence of hematologic toxicities in the VACA arm. In the HR group, the EFS and OS hazard ratios (EVAIA v VAIA) indicated a 17% reduction in the risk of an event (95% CI, -35% to 5%; P = .12) and 15% reduction in dying (95% CI, -34% to 10%), respectively. The effect seemed greater among patients without metastases (hazard ratio = 0.79; P = .16) than among those with metastases (hazard ratio = 0.96; P = .84). CONCLUSION: Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity. In HR patients, the addition of etoposide seemed to be beneficial.

Bone tumors in adolescents and young adults.

OPINION STATEMENT: Bone tumors, particularly osteosarcomas and members of the Ewing Sarcoma Family of Tumors (ESFT), are typical malignancies of adolescents and young adults. Current diagnostic and therapeutic guidelines for patients of all ages were developed in this specific age group. The aim of bone sarcoma therapy should be to cure the patient from both the primary tumor and all (micro-)metastatic deposits while maintaining as much (extremity) function and causing as few treatment-specific late effects as possible. Bone sarcoma therapy requires close multidisciplinary cooperation. Usually, it consists of induction chemotherapy, followed by local therapy of the primary tumor (and, if present, primary metastases) and further, adjuvant chemotherapy. Local treatment for osteosarcoma should be surgery whenever feasible. Surgery is also gaining importance in ESFT, which was long considered a domain of radiotherapy. Modern reconstructive techniques continue to expand the indications for limb salvage, particularly for patients who have not yet reached skeletal maturity. Treatment within the framework of prospective, multi-institutional trials should be considered standard of care not only for children, but also for affected adolescents and (young) adults. Such trials are essential in guaranteeing that all patients have access to appropriate care and that progress from biological studies can be translated into prognostic improvements without undue delay. The rarity of bone sarcomas increasingly requires trials to be multinational.

Whole lung irradiation in patients with exclusively pulmonary metastases of Ewing tumors. Toxicity analysis and treatment results of the EICESS-92 trial.

BACKGROUND: In the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92, whole lung irradiation (WLI) was performed in patients with primary lung metastases. This retrospective analysis evaluates the pulmonary function and the outcome of patients with exclusively pulmonary metastases. PATIENTS AND METHODS: Between 1990 and 1999, 99 patients were registered into the EICESS-92-study trial with exclusively pulmonary metastases of Ewing tumors. The multimodal treatment regimen included polychemotherapy and local therapy to the primary tumor. WLI was performed with a dose between 12-21 Gy. 70 patients were treated with WLI, 13 of them received a further boost to their primary tumor in the thorax up to a cumulative dose of 54 Gy. RESULTS: Pulmonary function tests were available for 37 patients treated with WLI (+/- boost). None, mild, moderate or severe pulmonary complications were seen in 43%, 29%, 21% and 7% of patients treated with WLI without further boost (median follow-up 25.2 months). Patients with an additional radiation boost or surgery to the thorax showed slightly higher rates of complications. Overall survival (OAS) showed a trend towards better results for patients with WLI (5-year-OAS: 0.61 for WLI vs. 0.49 for no WLI, p = 0.36). CONCLUSION: These data indicate a benefit and acceptable toxicity for WLI in the presented collective of patients. As long as there is no randomized prospective analysis, the present data confirm the indication for WLI in Ewing tumor patients with primary exclusively lung metastases.