Management of desmoid tumours: A nationwide survey of labelled reference centre networks in France.

PURPOSE: The optimal management of rare tumours (i.e. from accurate diagnosis to management in reference centres) is a public health challenge. In 2009, the French National Cancer Institute (INCa) identified and financially supported the two expert networks for pathological and clinical diagnosis and management of soft tissue tumours. METHODS: The activities of both networks were prospectively collected using a nationwide database (rreps.org). Data describing the diagnosis management of 863 successive cases of desmoids tumours (DT) were prospectively collected from 2010 to 2013 and analysed. RESULTS: The number of confirmed DT constantly improved from January 2010 to December 2013 (from 173 to 273 cases per year); the expected incidence ranged from 132 to 330 cases/year. The rate of cases diagnosed with core-needle biopsies and CTNNB1 mutational status analysis increased from 30.6 to 40.7% and from 87.8 to 94.1%, respectively. The mean delay for pathological diagnosis confirmation constantly decreased from 107 to 47 d. Among the 846 adult patients, 414 (48.9%) patients were treated by reference centres. The rate of patients managed by reference centres constantly increased with time from 36.9 to 49.5% since 2010. The median management time of the referral centres constantly decreased from 440 to 67 d. CONCLUSION: The two expert networks worked synergistically and improved diagnosis modalities of rare desmoid tumours at a national level. The impact of management by expert networks on the outcome will be prospectively analysed in the future.

Algorithm for the surgical management of mesenchymal tumors of the perineum in adults.

BACKGROUND: Perineal soft tissue tumors are rare, so that little is known about their management and the outcome of treatment. OBJECTIVE: The aim of this study is to describe the presentation, management, and outcome of the surgical treatment of soft tissue tumors and to provide a final decision algorithm. DESIGN: This is a retrospective study. SETTINGS: The study was conducted in a single tertiary care hospital with a dedicated unit on sarcoma. PATIENTS: Fifty-one consecutive patients from 1998 to 2013 were included. MAIN OUTCOME MEASURES: The primary outcomes measured are patient demographics, treatment decisions, and outcome of surgical treatment. RESULTS: Forty-nine patients presented with a primary soft tissue tumor, and 2 underwent simple excisions for isolated metastases. The median tumor size was 75 mm (50-110). Symptoms were nonspecific, and MRI had insufficient specificity for malignancy so that a preoperative biopsy was systematically performed according to European Society for Medical Oncology and National Comprehensive Cancer Network soft tissue tumor guidelines. Six benign soft tissue tumors (3 lipomas, 3 leiomyomas), 16 intermediate soft tissue tumors (12 aggressive angiomyxoma, 4 desmoid tumors), and 27 sarcomas were identified. Treatments and surgery were tailored from the beginning according to histology. All but 1 benign soft tissue tumor were treated by 'shelling out.' Aggressive angiomyxoma were treated with en bloc resection sparing uninvolved organs. Nonsurgical treatments were our first choice for desmoid tumors. Wide en bloc surgery was planned for all sarcomas (n = 27) after the induction treatment for 16 patients (chemotherapy, n = 12; radiotherapy, n = 4). In the sarcoma group, the 5-year estimated metastasis-free, local recurrence-free, and overall survival rates were 68.1% (95% CI, 50.7-91.5), 84.7% (95% CI, 66.7-100), and 85.7% (95% CI, 71.8-100). In the benign and intermediate tumor groups, there were no deaths, local recurrences, or progression. LIMITATIONS: This study was limited by the small number of patients, given the rarity of this disease in the perineum. CONCLUSION: We provide useful indications for the best strategy necessary to treat these rare tumors located in a complex site.

[Histopathological diagnostic concordance in bone and soft tissue sarcomas between two comprehensive cancer centers from eastern and western Europe: a collaborative experience]. / La concordance du diagnostic histopathologique des sarcomes osseux et des tissus mous entre deux centres anticancéreux de l'Europe de l'Est et de l'Ouest : une expérience de collaboration.

INTRODUCTION: This study aims to assess the degree of concordance of histological diagnosis of bone and soft tissue sarcomas between a Comprehensive Cancer Center (CCC) of Eastern Europe - not specialized in this area of pathology - and an important CCC of Western Europe, which is one of the coordinators of a clinical reference network in sarcoma pathology. The goal is to have an overview of the sarcomatous pathology in a region of Eastern Europe and to discover diagnostic discrepancies between the two centers, while determining their cause. MATERIALS AND METHODS: The initial diagnosis was compared with the revised diagnosis on 110 specimens from 88 patients with bone or soft tissue sarcomas from East-European CCC, in a one-year period of time. RESULTS: Complete diagnostic agreement was observed in 55 cases (62.5%), a partial agreement in 23 cases (26.1%) and a major disagreement in 10 cases (11.4%). Major discrepancies of the histological type was observed in only 3 cases (3.4%): one case of discordance benign/malignant and 2 cases of discordance mesenchymal/non mesenchymal. Minor histological discrepancies - not affecting the management of the patient - were observed in 18 cases (20.4%). A major discordance in grading - potentially changing the management of the patient - was noted in 7 cases (7.9%), and a minor discrepancy in 5 cases (5.7%). DISCUSSIONS: Some histological types were clearly overdiagnosed, like "adult fibrosarcomas" and "malignant peripheral nerve sheet tumors" (MPNST), mostly converted after the audit into "undifferentiated spindle cell sarcomas" or other types of sarcomas. Some "unclassified" sarcomas and "undifferentiated pleomorphic sarcomas" could be re-classified with the aid of an extensive panel of antibodies. Overall, immunohistochemistry was responsible, but not in exclusivity, for half of the minor discrepancies, and for 2 out of 3 cases of major histological discrepancies. Otherwise, the main cause of discrepancies was the difficulties in the interpretation of the morphology. Molecular biology was decisive in one case. Most grading discrepancies resulted from the appreciation of the mitotic index. CONCLUSIONS: The profile of the sarcomatous pathology in the northwest region of Romania does not appear to differ significantly from other parts of Europe or the world, but a prospective epidemiological study would be necessary to confirm this assessment. The expansion of immunohistochemical antibody panel, the over-specialization of pathologists and, in the future, the establishment of a national network of referral centers in sarcoma pathology, are required for a high level of histological diagnosis in Eastern Europe. A periodic external audit, continuing this trans-European collaboration between the two centers, would be beneficial for monitoring progress.

Persistent and anti-persistent pattern in stride-to-stride variability of treadmill walking: influence of rhythmic auditory cueing.

It has been observed that long time series of Stride Time (ST), Stride Length (SL) and Stride Speed (SS=SL/ST) exhibited statistical persistence (long-range auto-correlation) in overground walking. Rhythmic auditory cueing induced anti-persistent (or anti-correlated) patterns in ST series, while SL and SS remained persistent. On the other hand, it has been shown that SS became anti-persistent in treadmill walking, while ST and SL remained persistent. The aim of this study was to analyze the effect of the combination of treadmill walking (imposed speed) and auditory cueing (imposed cadence) on gait dynamics. Twenty middle-aged subjects performed 6×5 min walking trials at various imposed speeds on an instrumented treadmill. Freely chosen walking cadences were measured during the first three trials, and then imposed accordingly in the last three trials by using a metronome. Detrended fluctuation analysis (DFA) was performed on the times series of ST, SL, and SS. Treadmill induced anti-persistent dynamics in the time series of SS, but preserved the persistence of ST and SL. On the contrary, all the three parameters were anti-persistent under dual-constraints condition. Anti-persistent dynamics may be related to a tighter control: deviations are followed by a rapid over-correction, which produces oscillations around target values. Under single constraint condition, while SS is tightly regulated in order to follow the treadmill speed, redundancy between ST and SL would likely allow persistent pattern to occur. Conversely, under dual constraint conditions, the absence of redundancy among SL, ST and SS would explain the generalized anti-persistent pattern.

Hyperthermic isolated limb perfusion in locally advanced soft tissue sarcoma and progressive desmoid-type fibromatosis with TNF 1 mg and melphalan (T1-M HILP) is safe and efficient.

BACKGROUND: In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha. METHODS: We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg). The remnant tumor was resected 2 months later. RESULTS: Among 52 recurrences, 18 were in a previously irradiated field. Stages according to the American Joint Committee on Cancer classification were II (19 patients), III (78 patients), and IV (3 patients). The site/size were: 30 patients/57 mm and 70 patients/86 mm for the upper and lower limbs, respectively. Tumor grades (FNCLCC) were 1 (23 patients), 2 (34 patients), and 3 (43 patients). Fifty-one patients had received systemic chemotherapy before HILP. Responses on magnetic resonance imaging were 30% complete, 49% partial, 9% no change, and 12% progression. No mortality or systemic toxicity occurred. Local toxicity (Wieberdink) attained grade 2 (16 patients), 3 (5 patients), and 4 (1 patient). Limbs were able to be saved in 87% patients. Three-year overall survival and the local recurrence rate were 89% and 18%, respectively. Age, sex, tumor size, recurrence, uni- or multifocality, grade, preoperative chemotherapy, and a previously irradiated field were not predictive of response or local toxicity. CONCLUSIONS: We confirm that 1 mg of TNF-alpha is as effective as the standard dose and results in no systemic toxicity.