Search

Item does not contain fulltext Background: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. Patients and methods: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. Results: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. Conclusion: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

The natural history of localized high-grade sarcomas of the digestive tract (SDT) excluding GIST has been rarely considered owing to their low incidence and heterogeneity. We describe the histoclinical characteristics of SDT and correlate them with patients' outcomes.We retrospectively collected medical files from a European database covering connective tissue tumors listed in Europe for about twenty years. Only untreated localized primary high-grade SDT were included. A central histological review was performed for each case. Patients' characteristics were compared and correlated with clinical outcomes.A total of 45 patients were identified. Leiomyosarcomas (LMS) and undifferentiated sarcomas (UDS) were predominant, the former having better overall survival (OS) and progressionfree survival (PFS) while the latter having a worse outcome than the other histological types. Complete remission was obtained in 34 patients (75%) and was associated with male sex, age over 40 years and monofocal tumor. Complete surgery and LMS histology were associated with a better prognosis without any significant difference in baseline characteristics or in treatment modalities.Complete surgery and histological type seem to be prognostic indicators of SDT. These results suggest the importance of treating these patients in a reference center.

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

Background Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown. Methods To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society. Results Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2–27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive. Conclusion The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.

Synovial sarcoma is an aggressive sarcoma subtype characterized by a recurrent translocation t(X;18). We report here that the genomic complexity assessed by comparative genomic hybridization is strongly associated with outcome independently of response to neoadjuvant chemotherapy.Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy.The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen.Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity.The absence of significant association between response to chemotherapy and genomic complexity suggests that the prognostic value of chromosome instability in SS is independent of response to chemotherapy; mechanisms leading to metastatic relapse of SS are intrinsic to the biology of the tumor and current cytotoxic drugs are only poorly efficient to prevent it.

Background The predictive value of grade for benefit from adjuvant chemotherapy (AC) in soft tissue sarcoma (STS) patients has never been explored. Patients and methods From 1980 to 1999, 1513 adult patients with non-metastatic STS were included prospectively in the French Sarcoma Group database. Grade was assessed according to the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system after central review. Results AC was delivered to 13 grade 1 patients (3%), 145 grade 2 patients (35%) and 262 grade 3 patients (62%). Young age, non-well-differentiated liposarcoma histology, deep location, bone and/or neurovascular invasion and grade 2 or 3 were significantly associated with a higher likelihood to receive AC. Median follow-up was 9 years. On multivariate analysis, AC was significantly associated with improved metastasis-free survival (MFS) [5-year MFS: 58% versus 49%, hazard ratio (HR) 0.7 (95% confidence interval (CI) 0.6–0.9), P = 0.01] and overall survival (OS) [5-year OS: 58% versus 45%, HR 0.6 (95% CI 0.5–0.8), P = 0.0002] in grade 3 patients. This was not observed in grade 2 patients [5-year MFS: 76% versus 73%, HR 0.8 (95% CI 0.5–1.2), P = 0.27; 5-year OS: 75% versus 65%, HR 0.8 (95% CI 0.6–1.1), P = 0.15]. Conclusions This large cohort-based analysis with long-term follow-up indicates that patients with FNCLCC grade 3 disease may benefit from AC.

Gastrointestinal stromal tumours (GISTs) are the most frequent mesenchymal tumours of the digestive tract and occur typically in the stomach for two-third or in the small intestine for 25% in most series (Emile et al, 2004). Gain of function mutations of either KIT or platelet-derived growth factor receptor alpha polypeptide (PDGFRA) receptor tyrosine kinases play a critical role in GIST pathogenesis, and are found in 85% of GISTs (Rubin et al, 2007). Many types of gain of function mutations of KIT and PDGFRA have been described in GISTs, but 60% occurred within the exon 11 of KIT (Corless et al, 2004; Emile et al, 2004), which comprises 33 codons (codons 550–582). The two tyrosines Tyr568 and Tyr570, first residues to be phosphorylated during activation, are consensus sites for binding of Src family kinases and could be implicated in activation of different signalling pathways (Roskoski, 2005). More than 90 mutations of exon 11 have been published, and consist in insertions, substitutions and deletions; however, delWK557–558, in the proximal part of exon 11, is the most frequent, accounting for 8–25% of KIT exon 11 mutations. Others deletions, in the distal part of the exon, include in particular deletions of Tyr568 and/or Tyr570, and may thus have more specific effects on KIT signalling pathways and degradation. Such deletions account for 3–8% of exon 11 mutations in published series (Ernst et al, 1998; Taniguchi et al, 1999; Debiec-Rychter et al, 2004, 2006; Wardelmann et al, 2004; Martin et al, 2005; Penzel et al, 2005; Andersson et al, 2006; Emile et al, 2006; DeMatteo et al, 2008). After surgical resection, the type of KIT mutations may be a prognostic factor of relapse. KIT exon 11 deletions and deletions affecting codons 557–558 of KIT exon 11 were described to be independent adverse prognostic factors in patients with GIST (Wardelmann et al, 2003; Martin et al, 2005; DeMatteo et al, 2008). Conversely, in another study, GISTs in which the last part of exon 11 (codons 562–579) was deleted were most frequently associated with malignancy than GISTs with deletion of the first part of exon 11 (codons 550–561; Emile et al, 2004, 2006). So, the prognostic value of some types of KIT exon 11 mutations for risk of relapse is still debated. The mutational status of KIT or PDGFRA is predictive of clinical response to imatinib (Glivec, Gleevec, Novartis, Basel, Switzerland) and best results are obtained in patients with GISTs harbouring KIT exon 11 mutations (Heinrich et al, 2003; Debiec-Rychter et al, 2006). Nevertheless, the role of the type of KIT exon 11 mutations for the response and survival under imatinib remains to be determined. Thus, to better understand the prognostic significance of the type of KIT exon 11 deletions, we have compared the clinical characteristics and outcome of patients with GIST and deletion of both Tyr568 and Tyr570 with the most frequent deletion of KIT exon 11, delWK557–558.

Objective To evaluate the impact of surgery as first-line treatment on event-free survival (EFS) of primary aggressive fibromatosis. Patients and methods Treatments were categorized into: surgery with or without radiotherapy and nonsurgical strategies with systemic treatment alone or wait and see policy. Eighty-nine patients had initial resection of their primary tumour followed by postoperative radiotherapy in 13 cases. Twenty-three did not undergo surgery but received systemic treatment or watch and wait policy. Results Median follow-up was 76 months. Overall 3 years EFS was 49%. In the univariate analysis, patients with microscopically complete surgery had a similar outcome to patients in the no-surgery group (3 years EFS of 65% and 68%, respectively). Gender, age, tumour size, treatment period and strategy (surgery versus no-surgery) were not statistically significant. Quality of resection according to margins and the tumour site were the only prognostic factors. There was a significant correlation between tumour site and quality of surgery (p = 0.0002). Conclusions A subset of patients with extra-abdominal fibromatosis could be managed with a nonaggressive policy, as growth arrest concerned 2/3 of nonoperated patients. When surgery is finally necessary, it should be performed with the aim of achieving negative margins.

The role for surgery in patients with “unresectable” gastrointestinal stromal tumors (GIST) treated with imatinib is still not defined. The objective of this retrospective study was to evaluate the feasibility and benefit of this secondary surgery. Progression-free survival (PFS) in a group of patients who underwent secondary surgery was compared to that of patients treated exclusively with imatinib. Of 180 patients with unresectable GIST treated with Imatinib, 22 (12%) underwent secondary surgery, following which one patient achieved a complete radiological response, 19 achieved a partial response (PR), in one patient the disease was stable, and in one patient there was reactivation of local occlusive disease after an initial PR. No patient with overall progression was to undergo surgery. At the beginning of imatinib therapy, five patients with metastases underwent emergency surgery [hemorrhage (n = 3) due to rupture of large necrotic masses], which ultimately resulted in three of the five patients dying postoperatively. A macroscopically complete resection was achieved in all primary tumors (5/5) and in ten of the 17 metastases. Pathological analysis revealed two complete response (CR) and 17 PR, and no treatment effect was evidenced in three patients. Two-year overall survival after surgery was 62%. The median PFS calculated from the initiation of imatinib therapy was 18.7 months for all operated patients and 23.4 months after planned surgery. Primary tumors that become amenable to surgery with prior imatinib therapy, evolving necrosis and localized progression (to avoid life-threatening complications) could benefit from this secondary surgery. For the majority of other residual lesions, the potential benefit of secondary surgery should be evaluated in randomized studies in the future since PFS is similar to that reported among non-operated patients.

Purpose In order to decrease loco-regional relapse after complete resection of peritoneal sarcomatosis (PS), the role of intraperitoneal chemotherapy (IPEC) was prospectively evaluated. Methods Patients (pts) with completely resected PS were randomized between adjunction of IPEC or not. IPEC consisted of doxorubicin, 0.1mg/kg and cisplatin, 15mg/m 2 per day for 5 consecutive days. Primary endpoint was survival, measured as time from randomization to death. The scheduled number of patients needed was 40 in order to detect a minimal increase of 40% overall survival with the adjunction of IPEC with a power of 80%. Results Thirty-eight consecutive pts have been randomized, 19 in each group. Ratio of retroperitoneal (RPS) and visceral (VS) sarcomatosis were 9/10 and 6/13 in IPEC− and IPEC+ group, respectively. Histoprognostic grade, Sugarbaker's score and mean number of resected organs were similar in both groups. There were no toxic deaths and morbidity was similar in both groups (four pts in each group). The median follow-up is 60 months. The median local relapse-free, metastatic relapse-free survival and overall survival were identical in both groups (12.5, 18 and 29 months, respectively), with no difference between RPS and VS sarcomatosis. Conclusion Administration of IPEC after a macroscopically complete surgery did not allow to increase greatly the outcome of pts. Complete surgery remains the cornerstone of the treatment of patients with sarcomatosis with best results for low grade sarcomatosis.

Purpose: To describe the pathologic characteristics and prognostic factors of primary breast sarcomas (PBSs). Patients and Methods: We reviewed the clinical records and pathologic slides of 83 women with PBS treated in our institution between 1954 and 1991, with a median follow-up of 7.8 years. The majority of patients had undergone surgical treatment. Results: The main histologic type was malignant fibrohistiocytoma (n = 57). For the whole population, the 10-year overall survival (OS) and disease-free survival (DFS) rates were 62% and 50%, respectively. For Fédération Nationale des Centres de Lutte Contre le Cancer grade 1, 2, and 3 tumors, the 10-year OS and DFS rates were 82% and 61%, 62% and 51%, and 36% and 25%, respectively (P = .00007 and .004, respectively). For tumors measuring less than 5 cm, 5 to 10 cm, and more than 10 cm, the 10-year OS and DFS rates were 76% and 66%, 68% and 55%, and 28% and 15%, respectively (P = .002 and .009, respectively). In the multivariate analysis, the tumor size and histologic grade were correlated with the 10-year DFS rate (P = .04 and .01, respectively), but only the histologic grade was correlated with OS (P = .01). Angiosarcoma was the only histologic type significantly associated with a poorer outcome in the multivariate analysis. Conclusion: PBSs have the same clinical history and prognostic factors as sarcomas arising at other sites. Therefore, it is legitimate to use a similar treatment strategy for PBS as for other sarcomas.

Aim To report initial results of observation as well as surgery in patients with desmoid tumors (DTs) of the breast, a rare tumor for which data are scarce. Patients and methods The initial approaches were categorized as either front-line loco-regional treatment [(surgery or radiotherapy group, SRG) n = 20] or initial observation [(no surgery/no radiotherapy group, NSRG) n = 11]. Results A total of 27 women and 4 men were assessed between 1992 and 2013 and included in this study. Patient characteristics were adequately balanced in the 2 groups. Fifteen patients (48.4%) had a past history of breast surgery in the previous 24 months. The median initial DT size on MRI was 50 mm. The median follow-up was 36 months. In the SRG, 8/20 patients (40%) experienced recurrence. The median time to recurrence was 29 months. During the study period, 6 patients in the SRG (30%) received a mastectomy at the time of diagnosis (n = 3) or at relapse (n = 3), 7 patients (35%) received a thoracic wall resection and 8 patients (40%) received radiotherapy at the time of diagnosis (n = 2) or at recurrence (n = 5). In the NSRG, the median tumor size change was −4 mm (range −13 to +20). Three patients changed treatment strategies during the observation period; one received surgery, and 2 were administered anti-hormonal treatment. Conclusions Loco-regional treatments of breast DTs resulted in undesired disfigurement. Front-line observation yielded encouraging results and could enable the identification of patients who require loco-regional treatment. This strategy needs further evaluation.

Retroperitoneal sarcomas (RPS) are heterogeneous. No previous study has investigated the impact of specialized surgery, evaluated locoregional relapse (LRR), abdominal sarcomatosis and distant metastatic relapse as separate events, or considered histological subtypes separately. This study addresses these specific points in a homogeneous cohort of patients with completely resected primary RPS.We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 and eventually referred to one of 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist.Five hundred eighty-six patients were included. Median follow-up was 6.5 years [95% confidence interval (CI) 5.9-7.1]. Five hundred thirty-seven patients had localized disease and 389 patients (76%) had macroscopically complete resection of the tumor. In this latter group, the 5-year LRR-free survival rate was 46% [41-52] and the 5-year overall survival (OS) rate was 66% [61-71]. In multivariate analysis, gender, adjacent organ involvement, specialization of the surgeon, piecemeal resection and perioperative radiotherapy were independently associated with LRR. Specialization of the surgeon and piecemeal resection were independently associated with abdominal sarcomatosis whereas histology and adjacent organ involvement were independently associated with distant metastasis. Age, gender, grade, adjacent organ involvement and piecemeal resection were significantly associated with OS. Prognostic factors for LRR and OS were analyzed in well-differentiated and dedifferentiated liposarcomas and leiomyosarcomas. Grade 3 was an independent prognostic factor for OS of dedifferentiated liposarcomas.This study underlines the crucial role of pretherapeutic assessment and meticulous histological examination of RPS as well as the need to consider histological subtypes separately. Surgery in a specialized center and avoidance of piecemeal resection stand out as the two most important prognostic factors for RPS and highlight the importance of treating these patients in specialized centers.

More than 100 drugs have been registered as inducing subacute cutaneous lupus erythematosus (SCLE). Recently, some types of chemotherapy have also been incriminated. If SCLE develops in a setting of neoplasia, two possibilities should be considered: it is either a paraneoplastic syndrome or it is caused by the chemotherapy, thus calling for important decisions on the benefit/risk of stopping potentially effective medication. We report a case of SCLE induced by Xeloda (capecitabine).A 50-year-old female patient consulted with an annular erythematosquamous and pruriginous eruption, predominantly on areas of the body exposed to sunlight, occurring 4 months after the initiation of capecitabine for advanced colon cancer. She had presented systemic lupus erythematosus (SLE) for many years, which was not treated, was not progressive and had no cutaneous manifestations. The appearance of the cutaneous lesions, positivity for anti-SSA antibodies and the histological aspect led to diagnosis of SCLE. The lesions were resistant to treatment with hydroxychloroquine and systemic corticosteroids, but disappeared after discontinuation of capecitabine, suggesting chemotherapy-induced SCLE.Some types of chemotherapy such as capecitabine may reveal or induce SCLE lesions, whether or not there is a previous history of SLE. Cases of chemotherapy-induced cutaneous lupus reported to the French pharmacovigilance agency are rare, but this side effect must be recognised due to the constantly rising use of this type of anticancer agent.

Background Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately. Patients and methods We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. Results Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0–8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9–7.3] and median overall survival (OS), 15.8 months [13–18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit. Conclusion These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.

PURPOSE To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.

To assess the acute toxicity of intensity modulated radiotherapy as post-operative adjuvant treatment for retroperitoneal sarcoma.Patients who received adjuvant intensity modulated radiotherapy from January 2009 to September 2010 were retrospectively reviewed.Fourteen patients entered the study (seven primary tumours and seven relapses). All tumours were liposarcoma and had macroscopically complete resection, epiploplasty was systematically realized. Median tumour size was 21 cm (range: 15-45), median planning target volume was 580 cm(3) (range: 329-1172) and median prescribed dose was 50.4 Gy (range: 45-54). Median follow-up was 11.5 months (range: 2-21.4). Acute toxicity was mild: acute digestive toxicity grade 1-2 occurred in 12/14 patients (86%). However, there was no weight loss of more than 5% during radiotherapy and no treatment interruption was required. Two months after completion of radiotherapy, digestive toxicity grade 1 remained present in 1/14 patients (7%). One case of grade 3 toxicity occurred during follow-up (transient abdominal pain). Three relapses occurred: two were outside treaded volume and one was both in and outside treated volume.Intensity modulated radiotherapy in the postoperative setting of retroperitoneal sarcoma provides low acute toxicity. Longer follow-up is needed to assess late toxicity, especially for bowel, kidney and radio-induced malignancies.

Background: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for β-catenin mutations in a European multicentre series of fibromatosis tumours to relate β-catenin mutational status to disease outcome. Methods: Direct sequencing of exon 3 β-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). Results: Mutations of β-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with β-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in β-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). Conclusion: A high frequency (87%) of β-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type β-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

In the seventies, limb-sparing surgery and radiation therapy appeared capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremities. No survival benefit could be demonstrated in the patients selected for amputation. Microscopically positive surgical margins are related to a greater risk of local recurrence, whereas overall survival is compromised by high grade and large tumor size. Presurgery multidisciplinary discussion, management in reference center and management within cancer network independently predict conformity to the clinical practice guidelines. Reoperation should be a planned part of definitive management whenever the initial surgical procedure was done without a histologic diagnosis or was not planned to be a wide excision. Soft tissue flap reconstruction facilitates therapy for patients with locally advanced tumors so that patients with larger tumors can undergo resection, limiting complications and limb sacrifice. Vascular reconstruction is a feasible option in case of involvement of major vessels. Isolated limb perfusion (ILP) with TNF and chemotherapy is an efficient limb-sparing neoadjuvant therapy for locally advanced limb soft tissue sarcomas. Efficacy and safety of low-dose TNFalpha could greatly facilitate ILP procedures in the near future.

The presence of inorganic foreign bodies in granulomatous cutaneous lesions is not infrequent. In this paper, we describe the first case of cerium-induced cutaneous granulomatous dermatitis.A 57-year-old woman seriously burned four years ago presented with papulonodular lesions affecting only the burned areas treated with topical cerium nitrate-silver sulfadiazine cream (Flammacérium). Biopsies revealed sarcoidal granuloma associated with exogenous particles. Electron probe X-ray microanalysis demonstrated a high cerium content. Screening for systemic sarcoidosis was negative. The patient was treated with hydroxychloroquine. After four months of follow-up, clinical and histological evidence of decreased infiltrate was noted.Cerium nitrate-silver sulfadiazine cream (Flammacérium) is widely used for the topical treatment of burns. The main effect of cerium is to create superficial calcification, which decreases wound colonization and prevents the formation of granulation tissue (no hypertrophic scar formation) in burns. Prior to our case, no cutaneous side-effects of cerium had been encountered. Inoculation of foreign matter may or may not induce granuloma formation or sarcoidosis in different subjects, according to their immunologic status. The favorable outcome in this case could in fact be due to a change in the pattern of cytokinin production (TH1=TH2) rather than the effects of hydroxychloroquine therapy.

Retroperitoneal sarcomas comprise approximately 15% of all soft tissue sarcomas and 50% of all retroperitoneal tumours. Helical CT of the abdomen and pelvis, with selective use of MRI will establish the extent of the tumour, its retroperitoneal location, the degree of necrosis, and the evidence of metastasis. A CT guided core needle biopsy is the optimal pre operative tissue sampling. A complete surgical resection is the mainstay of the treatment with a rim of normal tissue that often requires removal of adjacent organs. The 5-year probability of local control is approximately 50%. The role of adjuvant therapy is evolving and at present should not be used outside the investigational setting.

BACKGROUND: The optimal dose of TNF-alpha delivered by isolated limb perfusion (ILP) in patients with locally advanced soft tissue sarcoma is still unknown. PATIENTS AND METHODS: Randomised phase II trial comparing hyperthermic ILP (38-40 degrees ) with melphalan and one of the four assigned doses of TNF-alpha: 0.5 mg, 1 mg, 2 mg, and 3/4 mg upper/lower limb. The main end point was objective tumour response on MRI. Secondary end points were histological response, rate of amputation and toxicity. Resection of the remnant tumour was performed 2-3 months after ILP. The sample size was calculated assuming a linear increase of 10% in the objective response rates between each dose level group. RESULTS: One hundred patients (25 per arm) were included. Thirteen per cent of patients had a systemic leakage with a cardiac toxicity in six patients correlated with high doses of TNF-alpha. Objective tumour responses were: 68%, 56%, 72% and 64% in the 0.5 mg, 1 mg, 2 mg and 3 or 4 mg arms, respectively (NS). Sixteen per cent of patients were not operated, 71% had a conservative surgery and 13% were amputated with no difference between the groups. With a median follow-up of 24 months, the 2 year overall and disease-free survival rates (95% CI) were 82% (73% to 89%) and 49% (39% to 59%), respectively. CONCLUSION: At the range of TNF-alpha doses tested, there was no dose effect detected for the objective tumour response, but systemic toxicity was significantly correlated with higher TNF-alpha doses. Efficacy and safety of low-dose TNF-alpha could greatly facilitate ILP procedures in the near future.

Background:: The aim of this study was to prospectively evaluate the use of Doppler ultrasonography with perfusion software and contrast agent injection (DUPC) during isolated limb perfusion (ILP) with high-dose chemotherapy and TNF-α(biochemotherapy) in patients with locally advanced extremity soft tissue sarcoma (STS). Patients and methods:: Fifty-two patients were prospectively included in this monocentric imaging trial. Three were excluded because the study was incomplete in two patients and one tumour did not exhibit any contrast uptake. DUPC was performed before ILP and on days 1, 7, 15, 30 and 60 after ILP. A total of 292 DUPC were performed on 55 target lesions in 49 evaluable patients. The percentage of contrast uptake was evaluated at each tumour site by two radiologists. The criterion tested was a decrease of more than 50% in intra-tumour contrast uptake compared to the pre-ILP examination. Results were compared with both MRI and histological analysis after resection of residual disease. Results:: According to MRI and the histological analysis, 25 (51%) patients were good responders (no difference between the four treatment arms) with tumour necrosis exceeding 90% and 24 (49%) were poor responders. As of day +1, the accuracy of DUPC in predicting tumour response was 82% (18/25 good responders and 22/24 poor responders) increasing to 91% at day +7, 95% at day +15 and 96% at day +30. At day +15, DUPC was predictive of a good response in 100% of the cases. Conclusion:: DUPC is a simple technique, allowing early prediction of tumour response after ILP. A new treatment planning scheme can be proposed based on the results of this study.

Adjuvant radiotherapy (RT) is routinely recommended for most soft-tissue sarcomas (STS) of the extremities. However, its impact on local control is not clearly established after wide complete excision. We performed a retrospective analysis of patients who underwent wide resection in our institution (first or second resection in cases of incomplete surgery) and either did or did not receive adjuvant RT. All histological specimens of patients operated upon between 1975 and 1996 were carefully analysed and only patients with free tumour margins (ftm) were retained for the analysis. The histopathological classification was as follows: minimal resection (mR) (ftm10 mm) and optimal resection (oR) (ftm/=10 mm). There were 133 patients with a median age of 44 years (range 16-88 years). The median tumour size was 6 cm (range 1-20 cm) with 28, 44 and 28% of stage I, II and III lesions, respectively. 93 patients (70%) were reoperated upon and residual tumour was found in 55% of the patients (51/93). 69 patients (17 oR and 52 mR) received adjuvant RT and 64 patients did not (54 oR and 10 mR). Other patient characteristics (age, tumour size, stage, deep-seated lesion, histoprognostic grade, adjuvant chemotherapy) were similar in both the RT and no-RT groups. Median follow-up was 10 years (3-25 years). The 5- and 10-year local relapse-free survival rates were 78 and 71%, respectively. 33 patients relapsed locally: 11 in the RT group and 22 patients in the control group (P=0.01). In the univariate analysis, adjuvant RT was correlated with relapse-free survival, while tumour grade and tumour margin status were correlated with overall survival. The multivariate analysis demonstrated a favourable impact of RT and negative influence of malignant fibrous histiocytoma (MFH) on local relapse-free survival; the tumour grade was correlated with overall survival. RT had a positive influence on local control exclusively in patients with mR resection (P=0.005) and in patients with residual tumour cells after re-excision (P=0.001). RT had no influence on 5- and 10-year overall survival. The 5- and 10-year overall survival for the entire population were 77 and 67%, respectively. Optimal resection seems to be the best predictive parameter for a favourable outcome in localised STS. Adjuvant RT is indicated after mR resection and for residual tumour after definitive surgery, but its role after oR resection (primary resection or no residual tumour after re-excision) should be evaluated in a prospective randomised trial.

Hydropic degeneration of a uterine leiomyoma is common. Giant forms are uncommon. Positive diagnosis may be challenging because the differential diagnosis includes other rare uterine tumors such as leiomyosarcoma. Uterine localization, the leiomyoma volume, margins with adjacent structures are best evaluated at MRI. Final diagnosis requires gross and microscopic examination. We describe such a diagnostic challenge in a 46-year-old woman with a giant hydropic leiomyoma.

We report a case of perforated infectious crystalline keratopathy in a 88-year-old woman. Corneal surgery like keratoplasty and topical corticosteroids are the main causative factors present in the rare reported cases. Clinically, the anterior layers of cornea exhibit slowly progressive stellate infiltrates. "Viridans streptococci" are the most common micro-organisms involved but their culture for identification is difficult. As compared to cultures, histologic examination is more sensitive for diagnosis, by showing clusters of bacteria in the corneal stroma with no inflammatory response.

Calcium phosphate-adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants.A double-blind, placebo-controlled study was performed in order to confirm the safety and assess the efficacy of a standardized five-grass-pollen extract adsorbed onto calcium phosphate for specific immunotherapy (IT).Twenty-nine patients with seasonal rhinoconjunctivitis were randomized to receive either the active preparation (16 patients) or placebo (13 patients), in a 1-year study. During the increasing dose phase, an extract ranging from 0.1 IR per ml to 50 IR per ml was administered at a rate of one subcutaneous injection per week until a maintenance dose was reached. The patients were assessed by symptom diary and rescue medications during seasonal exposure and specific nasal and skin reactivity before and after IT. Immunological parameters (specific IgE and IgG4 antibodies) were assessed before, during and after IT.The overall symptoms score (mean AUC) was not significantly different between the IT group and the placebo group during grass-pollen exposure (49.6 vs. 56, respectively). The total medication score (mean AUC) was significantly lower in the IT group than in the placebo group (11 vs. 41, P0.01, Mann-Whitney U-test). The cumulative symptom/medication score was significantly lower in the IT group than in the placebo group (64.5 vs. 102.3, P0.05, U-test). A significant increase in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL before IT vs. 63.4 IR/mL after IT, P0.01, Wilcoxon), whereas no significant changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL after IT). IT induced a significant reduction in grass pollen cutaneous reactivity in the actively treated group (P0.001). A significant increase in serum-specific IgG4 antibody response was observed in the IT group (3.1% before IT vs. 10.1% after IT, P0.001). Nine patients in the IT group developed moderate immediate systemic reactions vs. two patients in the placebo group.Specific immunotherapy with calcium phosphate-adsorbed standardized grass pollen extract was safe and effective for the treatment of patients with seasonal allergic rhinoconjunctivitis.

The aim of this retrospective study was to assess the advantages of free-lap reconstruction in locally advanced soft tissue sarcomas.From October 1997 to October 2000, among 256 procedures for sarcomas, 25 were associated with free-lap reconstruction. There were 16 women and nine men (mean age: 45 years). The tumor was located on inferior limbs (n = 15), superior limbs (n = 3) and trunk (n = 7), had a mean size of 12, 10 and 12 cm respectively, and was multifocal (n = 6), or recurrent (n = 10). Ten patients received a neoadjuvant chemotherapy. Tumoral excision was associated with a complementary procedure in 10 patients. Reconstruction was performed with free-laps of the latissimus dorsi (n = 21) and transverse rectus abdominis myocutaneous (TRAM) (n = 4). Early postoperative radiotherapy was associated in 15 patients.Median duration of the procedure was 6.5 hours. There were no postoperative deaths. Two free-laps necrotized and another free-lap was constructed. Tumoral excision was Ro (n = 20), R1 (n = 4) and R2 (n = 1). With a median follow-up of 20 months, there were no local recurrences in patients Ro. Ten patients developed pulmonary metastases and five of them died.With free-lap reconstruction, tumoral excision was larger, amputation of the limb was avoided in 14 patients, and early postoperative radiotherapy was possible in 15 patients. Multidisciplinary management and collaboration of the oncologist and plastic surgeon are associated with a better prognosis of locally advanced soft tissue sarcomas.

Hibernomas are benign tumors derived from brown fat of hibernating animals and of human infants. The pathogenesis and malignant potential of hibernomas remain unclear. They occur generally in adults with a peak incidence in the third decade and with a predominance in women. However, the lesions may have an heterogeneous presentation that may mimic liposarcomas on MRI. Our report presents a case of hibernoma of the thigh whose the diagnosis initially suggested that it was a mixed liposarcoma with myxoid and well differentiated components.

Synovial sarcoma (SS) is a relatively rare sarcoma, which may be confused with several other mesenchymal and nonmesenchymal lesions. It bears the t(X;18) (SYT;SSX) translocation, which seems to be specific for this tumor type and can be detected in paraffin-embedded tissue, using reverse transcriptase-polymerase chain reaction (RT-PCR). However, the specificity and sensitivity of this detection method have rarely been examined in a large series. Using RT-PCR, we examined 250 mesenchymal and nonmesenchymal, benign and malignant, paraffin-embedded lesions for the SS t(X;18) (SYT-SSX) translocation. PCR products were obtained from 221 tumors (88.5%). There were 135 non-SS tumors, 22 biphasic, and 64 monophasic spindle/round cell SS, of which 10 were cytogenetically confirmed as t(X;18)-positive. SYT-SSX gene fusion transcripts were detected in the SS tumor category only (100% specificity), including 100% of the biphasic SS and 86% of monophasic spindle/round cell SS. Nine tumors originally diagnosed as SS were t(X;18) (SYT-SSX)-negative. Following reassessment, only 3 of these tumors showed clinicopathologic, immunohistochemical, and/or ultrastructural features consistent with that diagnosis, thus raising the overall detection sensitivity to 96%. With regard to the potential adverse effect of the fixatives used, PCR products were obtained in 100%, 91.5%, 90.5%, and 0% of tumors fixed with AFA, buffered formalin, Holland Bouin, and conventional Bouin's fluid, respectively. This study shows that the detection of the SS t(X;18) (SYT-SSX) in paraffin-embedded tissue is feasible with a 100% specificity and an overall 96% sensitivity, provided non-Bouin's fluid fixation is used.

We report three cases of bronchial mucoepidermoid carcinoma (BMEC) of low-grade malignancy with a relafase-free follow up. BMEC are rare tumors. The microscopic findings distinguish low-grade tumors which occur in children and young adults and high-grade tumors concerning older patients; this grading is based on the study of the epidermoid component. If possible, conservative therapy is appropriate in low-grade tumors. The prognosis of high-grade tumors is poor.

Forty-four malignant fibrous histiocytomas (MFHs) were studied by comparative genomic hybridization. Among the observed imbalances, losses of the 13q14-q21 region were observed in almost all tumors (78%), suggesting that a gene localized in this region could act as a tumor suppressor gene and that its inactivation could be relevant for MFH oncogenesis and/or progression. We determined by CA repeat analyses a consensus region of deletion focusing on the RB1 region. The RB1 gene was then analyzed by protein truncation test, direct sequencing, fluorescence in situ hybridization, Southern blotting, and immunohistochemistry. RB1 mutations and/or homozygous deletions were found in 7 of the 34 tumors analyzed (20%). Among the 35 tumors with comparative genomic hybridization imbalances analyzed by immunohistochemistry, 30 (86%) did not exhibit significant nuclear labeling. The high correlation between chromosome 13 losses and absence of RB1 protein expression and the mutations detected strongly suggest that RB1 gene inactivation is a pivotal event in MFH oncogenesis. Moreover, the observation of a high incidence of MFH in patients previously treated for hereditary retinoblastoma fits well this hypothesis.

The human COMA cell line has been established from a storiform pleomorphic malignant fibrous histiocytoma (MFH). As expected for this tumor type, a very complex karyotype was observed after R-banding analysis. An extensive analysis by 24-color painting, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) was performed. Twelve complex marker chromosomes recurrently observed were clearly identified; among them, three were systematically present in all analyzed metaphases. Amplifications detected by CGH were refined by FISH with probes specific for various candidate loci. A significant aneuploidy and numerous micronuclei were observed, which could be related to the anomalies of centriole numbers detected in a proportion of cells. Such an analysis, performed on a series of MFH cell lines, would allow the delineation of the genomic alterations specific for the oncogenesis or progression of this complex tumor type or both.

Thirty six cases of clear cell sarcoma of soft tissue are reported. The median age was 44 years (5 to 80 years). The principal sites were the foot (11 cases), the hand and wrist (7 cases) and the knee (6 cases). The architecture was fascicular with lobular arrangement of cells delimited by delicate fibrous septa intimately bound to tendons or aponeuroses. Tumoral cells were round or fusiform with abundant clear cytoplasm sometimes epithelioid with round nuclei and prominent nucleoli. The mitotic rate was evaluated to 9/10 HPF. S100 protein was expressed in 33/36 cases and HMB45 marked 29/31 cases, without expression of cytokeratin. Three-year and 5-year survival rate were respectively 72% and 62%. Prognosis factors for global survival were efficiency of initial treatment with distal location and necrosis and FNCLCC grade. The distinction of clear cell sarcoma from metastatic melanoma is important because of the difference of prognosis.

A 36-year-old man presented with a pleural tumor. The first pathologic analysis diagnosed biphasic pleural malignant mesothelioma. However, the atypical clinical course, the early development of lung metastases and a new reading of histologic documents led to the diagnosis of primary pleural synovial sarcoma. The literature review is limited, as only nine other cases have been reported to date. Chest pain is the only constant clinical feature. Misleading interpretation of histologic material is frequent (6 of 10 cases). Only a complete immuno-histochemical study confronted with the clinical course can lead to the correct diagnosis. Because the efficacy of chemotherapy and/or radiotherapy is poor, surgery remains the basis of treatment, whenever possible. Evolution is mainly intra-thoracic, with multiple local recurrences and lung metastases. Prognostic is poor, a survival rate is similar to that of primary pulmonary sarcomas.

The cases of 16 adult patients with spermatic cord sarcoma were retrospectively reviewed. Patient ages had a bimodal distribution (median 57.5 years). Presentation was scrotal mass, inguinal mass or both, with an average diameter of 6.7 cm. Radical orchiectomy was performed in 9 patients, and simple tumorectomy in 7. Lymph node dissection was performed in 6 patients, including retroperitoneal dissection in 4 patients. Various types of soft tissue sarcomas were found. Embryonal rhabdomyosarcomas were evident only in young patients. Lymph node metastases were found in 2 out of 6 cases. Testicular atrophy was observed in 3 young patients, germline destruction by the tumor in 2, and partial spermatogenesis in 2 patients. The median time to first relapse in 13 patients was 5.5 months. Surgery was the primary treatment and the best salvage modality. The role of chemotherapy and radiation therapy as true adjuvant or post-salvage-surgery adjunctive treatments remains unclear.

Regional chromosome localizations of DNA copy number imbalances were studied by comparative genomic hybridization in 30 malignant fibrous histiocytomas: 13 primary tumors (2 myxoid, 9 storiform pleomorphic, and 2 with more undifferentiated phenotype) and 17 local recurrences (2 myxoid, 11 storiform pleomorphic, and 4 with more undifferentiated phenotype). Abnormal comparative genomic hybridization (CGH) profiles were observed in 25 tumors (83%). The most frequent gains (ratio1.2) corresponded, by order of frequency, to entire Xp, and bands 1q21, 19q13.1, 19p13, 5p13-p14, 1p31, 17p, 18p, 20q, 1p35, 17q23, and 22q12. High levels of gains (ratio1.5) were recurrently detected for Xp (10 cases), and in bands 1q21-q22 (8 cases), 3q27 (4 cases), 5p13-p14 (3 cases), 13q32-q34 (3 cases), 15q22-q26 (3 cases), and 17p11-p12 (3 cases). Losses of 13q12-q14 or 13q21 were observed in a large proportion of tumors (17 cases), suggesting that a gene localized in this region could act as a tumor suppressor gene. Losses of 11q23, 2q32, 11p13, 10p, 1q4, 9p2, 16q12, 4q3, 10q25, 3p23, 2p24, and 12p were also recurrently observed. Taken together, these results provide an overview of chromosome imbalances present in MFH, which could be of use for diagnostic purposes. They point to various chromosome regions which may harbor genes important for malignant fibrous histiocytomas (MFH) oncogenesis and progression.

Liver involvement by soft tissue sarcoma is an unfavorable prognostic factor for survival. Complete resection of liver metastases can bring improvement in selected patients, but chemotherapy remains the only palliative treatment option for most. Anecdotal long-term survival of patients with unresectable liver metastases treated with systemic chemotherapy has been reported, such as the patient presented here.

Report of one case of hamartomatous adiposity of the thyroid gland. Only eight cases have been reported. The lesion is composed of thyroid tissue and mature adipose elements. Previously reported cases are reviewed and the pathogenesis is discussed.

The discovery of a tumour mass of the appendix, in an acute or chronic context, raises the problem of its benign or malignant, inflammatory or infectious nature. We report five cases of patients operated by the same surgical team between June 1991 and September 1996, who presented macroscopically and histologically with unusual appendicular pseudotumours: appendicular diverticulosis (n = 1), Crohn's disease localized to the appendix (n = 2), yersiniosis (n = 1), actinomycosis (n = 1). The preoperative diagnosis was acute appendicitis (n = 2) or tumour (n = 3). The postoperative course was uneventful in every case, and specific medical treatment was prescribed in two cases (yersiniosis and actinomycosis). These differential diagnoses must be considered in all appendicular diseases, but they are extremely difficult to confirm preoperatively.

Retroperitoneal space is an exceptional location of extrauterine pregnancy (four cases have been previously reported). The authors report a case of retroperitoneal ectopic pregnancy. Pathogenesis is discussed.

We describe the clinical and pathological features of a case of desmoid tumour of the breast. The lesion was approximately 3.0 cm in greatest dimension. Histologically, it had infiltrating borders and extended to the pectoral muscle. The differential diagnosis is discussed.