Assessing hypoxic respiratory failure in mechanically ventilated neonates: A comparative study of oxygen saturation index and oxygenation index.

OBJECTIVE: To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs. METHODS: A prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI. RESULTS: A total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p<0.001) was observed. The OSI cut-off value for predicting an OI of >15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05). CONCLUSION: The findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates.

Design and Realization of Polymeric Waveguide/Microring Structures for Telecommunication Domain.

Polymer-based micro-optical components are very important for applications in optical communication. In this study, we theoretically investigated the coupling of polymeric waveguide and microring structures and experimentally demonstrated an efficient fabrication method to realize these structures on demand. First, the structures were designed and simulated using the FDTD method. The optical mode and loss in the coupling structures were calculated, thereby giving the optimal distance for optical mode coupling between two rib waveguide structures or for optical mode coupling in a microring resonance structure. Simulations results then guided us in the fabrication of the desired ring resonance microstructures using a robust and flexible direct laser writing technique. The entire optical system was thus designed and manufactured on a flat base plate so that it could be easily integrated in optical circuits.

Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.

In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named 'hLMS'. The integration of multi-omics data and functional analysis suggests that hLMS originate from vascular smooth muscle cells and show that hLMS transcriptional program reflects both modulations of smooth muscle contraction activity controlled by MYOCD/SRF regulatory network and activation of the cell cycle activity controlled by E2F/RB1 pathway. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway amplification, essential for hLMS survival, concomitant with PTEN absence and RB1 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness.

Main Clinical and Laboratory Features of Children with Bacterial Meningitis: Experience from a Tertiary Paediatric Centre in Central Vietnam.

Objective: Our study aimed to summarize symptoms and laboratory findings of bacterial meningitis at a Vietnam tertiary care hospital. Methods: We performed a retrospective study and enrolled 33 children diagnosed with bacterial meningitis admitted at the Pediatric Center, Hue Central Hospital, between January 2019 and July 2021. Results: Only 24.2% (8 out of 33) cases can determine etiology of bacterial meningitis. Streptococcus pneumonia was the most common pathogen. The mortality in this study was 12.1%. The most commn symptoms were fever (93.9%) and vomiting (60.6%). Loss of consciousness and poor appetite were predominant among patients who died (75%); seizures and local paralysis accounted for a half. For cerebrospinal fluid (CSF), the cloudy or turbid color was the most common in bacterial meningitis (54.5%), CSF leucocytes in a half of patients were greater than 500 cells/mm3 (48.5%). CSF white blood cells count was higher among children who died. Conclusion: Streptococcus pneumonia was the most common pathogen. Fever, vomiting, loss of consciousness, local paralysis, and increased leucocytes, neutrophils of CSF were more common in severe cases.

Loeffler's syndrome mimicking lung tumor and pneumonia in a child: A case report.

Loeffler's syndrome is a rare and benign eosinophilic pneumonia which is commonly transient and self-limiting. Herein we report a 12-year-old boy who presented with dry cough, hemoptysis, chest pain, no fever and diminished breath sounds on the right lung. Chest imaging showed a consolidation lesion with bronchograms in the right upper and middle lobes, accompanied by a right free-flowing pleural effusion. Laboratory studies showed elevated C-reactive protein levels, and an eosinophil count of 13.7%. A lung biopsy was performed to diagnose the Loeffler's syndrome. The patient's condition was improving significantly with antibiotic therapy and is now followed up closely.

Is Serum Lactate a Good Predictor of Mortality in Children Aged 2 Months to 5 Years With Pneumonia in Central Vietnam.

Pneumonia is a major cause of morbidity and mortality in children globally. Lactate, a product of anaerobic cellular metabolism, has been used as an indicator of poor tissue oxygenation and cellular hypoxia. Our objective was to determine whether serum lactate concentration at hospital admission predicted mortality in children aged 2 months to 5 years with pneumonia. Two hundred and eighty-one pediatric patients admitted to the Department of Pediatrics of a provincial hospital with WHO-defined pneumonia and severe pneumonia were included; of whom, 8 died during hospital stay. The median serum lactate concentration was 4.8 mmol/l (IQR 2.6-6.9) among children who died and 3.6 mmol/l (IQR 2.8-4.3) among children who survived (P > .05); 4.1 mmol/l (IQR 2.7-4.7) among children with severe pneumonia and 3.5 mmol/l (IQR 2.8-4.3) among children with pneumonia (P > .05). Serum lactate concentration had a low value in predicting pneumonia-related mortality (AUC 0.68, 95% CI 0.62-0.73); and the concentration cut-off of >4.06 mmol/l had the best sensitivity and specificity (75% and 68.9%, respectively) with a 2.4-fold risk of death (LR+ 2.4; 95% CI 1.6-3.7). Although hyperlactatemia was associated with severity and mortality in children 2 months to 5 years of age with pneumonia, its benefit was unclear.

Medium levels of transcription and replication related chromosomal instability are associated with poor clinical outcome.

Genomic instability (GI) influences treatment efficacy and resistance, and an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP "hotspotness" magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (transcription-associated chromosomal instability index) and iRACIN (replication-associated chromosomal instability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in Leiomyosarcoma (LMS) and that they may be combined to form a new classifier called MAGIC (mixed transcription- and replication-associated genomic instability classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.

Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting.

BACKGROUND: Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. PATIENTS AND METHODS: Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. RESULTS: Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation. CONCLUSION: Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.

Primary cutaneous and subcutaneous Ewing sarcoma.

BACKGROUND: Primary cutaneous/subcutaneous Ewing sarcoma (scEWS) is extremely rare. We describe clinical features, treatment, and outcome of this Ewing localization. PROCEDURE: Retrospective study (1996-2012) on 56 patients. RESULTS: Most primary scEWS occurred in late adolescent/young adult females (F/M = 1.9; median age 21.5 years), with primary tumor in the extremity/trunk (48.5%/39%). Only 35/56 samples had Real-Time-Polymerase-Chain-Reaction/Fluorescent-In-Situ-Hybridization analysis, 32/35 had EWS-translocation. Most of them exhibited known favorable prognostic factors: localized disease (54/56), initial tumor volume < 200 ml (51/53). Thirty and 25 patients received chemotherapy according to Euro-Ewing99 or a shorter/less intense chemotherapy regimen associated with milder toxicity. One patient had not received chemotherapy. Surgery was performed at diagnosis in 37 patients (18/37 marginal/intra-lesional resections) followed by secondary surgery in 8/37 (three remained marginal). Nineteen other patients had an initial biopsy followed by chemotherapy, 15/19 underwent late surgery (4/15 marginal/intra-lesional resections). Overall, 27/56 patients received radiotherapy. Median follow-up was six years (1-15). Two patients with metastatic disease progressed at metastatic sites. Four patients with localized disease experienced progression/relapse (local n = 3, metastatic n = 1). Survival was excellent: 5y-OS and 5y-EFS were 93.8% (95%CI = 83-98%) and 88.5% (95%CI-= 77-95), respectively. CONCLUSIONS: Unplanned primary surgery should be avoided to try to minimize potential long term sequels due to secondary surgery or radiotherapy. Biopsy with molecular analysis and staging should be performed at diagnosis to inform treatment recommendations. Patients with metastases should be treated aggressively as for other metastatic EWS. Further studies are necessary to clarify whether a less intensive chemotherapy regimen could be safely used in localized disease to minimize acute/late toxicities.

Percutaneous cryoablation of symptomatic localized venous malformations: preliminary short-term results.

Short-term outcomes after percutaneous image-guided cryoablation of symptomatic venous malformations in four consecutive patients (mean age, 42.5 y) are reported. Two patients had local recurrences after previous treatment. Mean preoperative pain was estimated on a visual analog scale at 5 (range, 3-7). Cryoablation was performed in a single session under general anesthesia. Postoperative pain and superficial edema disappeared within 2 weeks. No pain was subsequently reported, and magnetic resonance imaging demonstrated a significant volume decrease at 3 months (75%; P = .01) and at 6 months (95%; P = .01). Percutaneous cryoablation shows promising local control in patients with symptomatic venous malformations.

Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: an analysis of 181 patients of the French ATU compassionate use program.

BACKGROUND: The long term outcome of advanced sarcoma patients treated with trabectedin outside of clinical trials and the utility of maintenance treatment has not been reported. METHODS: Between 2003 and 2008, patients with advanced sarcoma failing doxorubicin could be treated within a compassionate use program (ATU, Temporary Use Authorization) of trabectedin in France using the standard 3-weekly regimen. Data from 181 patients (55%) were collected from 11 centres and analyzed. RESULTS: Trabectedin was given in first, second, third or fourth line in metastatic phase in 6%, 37%, 33% and 23% of patients respectively. With a median follow-up of 6 years, median PFS and OS were 3.6 months and 16.1 months respectively. The median number of cycles was 3 (range 1-19). Best response were partial response (PR, n = 18, 10%), stable disease (SD, n = 69, 39%) and progressive disease (PD, n = 83, 46%), non evaluable (NE, n = 9, 5%). Thirty patients (17%) had to be hospitalized for treatment- related side effects. Independent prognostic factors in multivariate analysis (Cox model) were myxoid LPS and line of trabectedin for PFS, and myxoid LPS and retroperitoneal sarcomas for OS. Patients in PR or SD after 6 cycles continuing treatment had a better PFS (median 5.3 vs 10.5 months, p = 0.001) and OS (median 13.9 vs 33.4 months, p = 0.009) as compared to patients who stopped after 6 cycles. CONCLUSIONS: In this compassionate use program, trabectedin yielded similar or better PFS and OS than in clinical trials. Maintenance treatment beyond 6 cycles was associated with an improved survival.

Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series.

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts were highly responsive to anti-VEGF agents such as bevacizumab. We report here the clinical activity of sunitinib in eight patients with DSCRT. Our data suggest that sunitinib may be associated with clinical benefit even in heavily pretreated patients.

High-dose pre-operative helical tomotherapy (54 Gy) for retroperitoneal liposarcoma.

PURPOSE: To evaluate the feasibility of pre-operative radiotherapy (54 Gy) with Helical Tomotherapy (HT) followed by surgery. METHODS AND MATERIALS: Ten patients with non-metastatic resectable retroperitoneal liposarcomas were treated by pre-operative tomotherapy (54 Gy) and surgery. Clinical and biological toxicities were evaluated on the CTCAEV3.0 scale. For nine patients, delivered tomotherapy plans were compared with retrospectively-planned dynamic intensity-modulated radiotherapy (IMRT) dosimetric studies. RESULTS: No immediate or late Grade>2 toxicities were observed after radiotherapy. Post-operatively, one patient died and three patients experienced Grade 3 toxicity (two digestive and one metabolic). These toxicities disappeared and only two patients presented persistent Grade 1 paresthesia. R0 resection was obtained for four patients, R1 for four, and R2 resection for two. With a median follow-up of 26 months, no local or metastatic relapse was observed. Dosimetric comparisons between HT and retrospectively-planned IMRT demonstrate adequate target volume coverage for both techniques. Gastrointestinal sparing is higher with HT with a D200cc reduced by 5 Gy. Integral dose (ID) was increased in HT. CONCLUSIONS: High dose pre-operative radiotherapy (54 Gy) for retroperitoneal liposarcoma is feasible and mostly well tolerated. Cumulative toxicity and tolerance depend mainly on patient's general status. Image-guided radiation therapy (IGRT) is essential, irrespective of the IMRT technique used. Furthermore, HT offers the possibility of sparing selected areas in such complex volumes.

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.

BACKGROUND: We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection. METHODS: Patients with well-differentiated or dedifferentiated liposarcoma were enrolled at four centres in France. Patients received up to three 28-day neoadjuvant treatment cycles of RG7112 1440 mg/m(2) per day for 10 days. If a patient progressed at any point after the first cycle, the lesion was resected or, if unresectable, an end-of-study biopsy was done. The primary endpoint was to assess markers of RG7112-dependent MDM2 inhibition and P53 pathway activation (P53, P21, MDM2, Ki-67, macrophage inhibitory cytokine-1 [MIC-1], and apoptosis). All analyses were per protocol. This trial is registered with EudraCT, number 2009-015522-10. RESULTS: Between June 3, and Dec 14, 2010, 20 patients were enrolled and completed pretreatment and day 8 biopsies. 18 of 20 patients had TP53 wild-type tumours and two carried missense TP53 mutations. 14 of 17 assessed patients had MDM2 gene amplification. Compared with baseline, P53 and P21 concentrations, assessed by immunohistochemistry, had increased by a median of 4·86 times (IQR 4·38-7·97; p=0·0001) and 3·48 times (2·05-4·09; p=0·0001), respectively, at day 8 (give or take 2 days). At the same timepoint, relative MDM2 mRNA expression had increased by a median of 3·03 times (1·23-4·93; p=0·003) that at baseline. The median change from baseline for Ki-67-positive tumour cells was -5·05% (IQR -12·55 to 0·05; p=0·01). Drug exposure correlated with blood concentrations of MIC-1 (p<0·0001) and haematological toxicity. One patient had a confirmed partial response and 14 had stable disease. All patients experienced at least one adverse event, mostly nausea (14 patients), vomiting (11 patients), asthenia (nine patients), diarrhoea (nine patients), and thrombocytopenia (eight patients). There were 12 serious adverse events in eight patients, the most common of which were neutropenia (six patients) and thrombocytopenia (three patients). DISCUSSION: MDM2 inhibition activates the P53 pathway and decreases cell proliferation in MDM2-amplified liposarcoma. This study suggests that it is feasible to undertake neoadjuvant biopsy-driven biomarker studies in liposarcoma. FUNDING: F Hoffmann-La Roche.

Risk adapted chemotherapy for localised Ewing's sarcoma of bone: the French EW93 study.

AIM OF THE STUDY: To determine whether a risk factor adapted chemotherapy would improve the outcome of non-metastatic bone Ewing's sarcoma. METHODS: Standard risk tumours (SR, good histological response to chemotherapy or small unresected tumours) received the previous EW88 chemotherapy. Ifosfamide/etoposide (IE) were introduced after 3 courses of cyclophosphamide/doxorubicine when tumour regression was <50% or during consolidation therapy for the intermediate risk tumours (IR, intermediate histological response 5-30% residual cells or large unresected tumours >100ml). High risk tumours (HR, histological poor response >30% residual cells or clinical poor response <50% for unresectable tumours), received IE prior high dose busulfan/melphalan with stem cell rescue. RESULTS: From 1993 to 1999, 214 patients were enrolled. 5 y-EFS and OS were 60% (95% confidence interval (CI), 53-66) and 69% (95% CI, 63-75), respectively. 116 (54%), 46 (21%), 48 (22%) patients were considered as SR, IR and HR of relapse, respectively. No advantage to IE was observed in the IR group. As compared to previous study, tumour with poor histological response to induction chemotherapy seemed to benefit from the consolidation strategy including busulfan/melphalan: EFS were 45% (95% CI, 30-60) and 20% (95% CI, 7-43) for EW93 and EW88, respectively. Despite a risk-adapted strategy, histological response to chemotherapy remains the main prognostic factor in resected tumours, while initial tumour volume is the main prognostic factor for unresected tumours. CONCLUSION: These results showing a potential benefit of a consolidation strategy including busulfan/melphalan as compared to conventional chemotherapy needed confirmation by a randomised trial and were one of the bases of the ongoing EuroEwing99.

Bone marrow metastases in a patient with primary mediastinal non-seminomatous germ cell tumor - an unusual pattern of relapse.

BACKGROUND: Bone marrow is a very unusual site of metastasis for germ cell tumors. CASE REPORT: We report the case of a 21-year-old male patient who was treated with chemotherapy and secondary surgery for a primary mediastinal non-seminomatous germ cell tumor (NSGCT). The patient achieved complete remission. However, 4 months after completion of therapy, he complained of rapidly worsening bone pain. No evidence for disease relapse was found in the computed tomography scan of thorax and abdomen, magnetic resonance imaging of the spine, or bone scan. A blood test revealed pancytopenia and elevated serum tumor markers. A bone marrow aspirate showed infiltration by tumor cells positive for AE1/AE3 and AFP confirming the diagnosis of isolated bone marrow metastatic relapse. Salvage chemotherapy was started and resulted in a rapid decrease of serum tumor markers. However, pancytopenia did not improve and the patient died of severe sepsis 3 weeks later. CONCLUSION: We report here the first case of isolated bone marrow metastatic relapse of an NSGCT. 2 other cases of bone marrow metastasis in patients with NSGCT have been reported. In these 2 cases, as in our patient, the primary site was not testicular but mediastinal suggesting a non-fortuitous association.

Comparison of doxorubicin and weekly paclitaxel efficacy in metastatic angiosarcomas.

BACKGROUND: Data regarding the role of anthracyclines and taxanes as first-line treatments of metastatic angiosarcoma are limited. METHODS: Records of 117 metastatic angiosarcoma patients who were treated with either doxorubicin or weekly paclitaxel were reviewed. RESULTS: Seventy-five patients (64%) were treated with weekly paclitaxel and 42 (36%) with single-agent doxorubicin. Patients in the weekly paclitaxel group were older and more frequently had angiosarcomas arising from the skin. In the doxorubicin group, 34 patients were evaluable for response: 2 (6%) had complete response, 8 (23.5%) had partial response, 10 (29.5%) had stable disease, and 14 (41%) had progressive disease. In the weekly paclitaxel group, 68 patients were evaluable for response: 9 (13%) had complete response, 27 (40%) had partial response, 20 (29.5%) had stable disease, and 12 (17.5%) had progressive disease. Objective responses to weekly paclitaxel were more frequent in cutaneous angiosarcomas, whereas tumor location did not impact response to doxorubicin. Median progression-free survival (PFS) was 4.9 months (95% confidence interval [95% CI], 3.9-6.0 months). Median overall survival (OS) was 8.5 months (95% CI, 6.4-10.7 months). On multivariate analysis, ECOG performance status (PS) was the sole independent factor associated with PFS and OS. CONCLUSIONS: First-line single-agent doxorubicin and weekly paclitaxel seem to have similar efficacy in metastatic angiosarcomas. Cutaneous angiosarcomas respond favorably to weekly paclitaxel. Best supportive care should be considered in patients with poor PS.

Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib.

BACKGROUND: Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited. METHODS: Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed. RESULTS: The three most frequent drugs used in the 3rd-line setting were: nilotinib n = 67 (29.5%), sorafenib n = 55 (24.5%), and imatinib n = 40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd-line treatment were 3.6 months [95% confidence interval (95% CI), 3.1-4.1] and 9.2 months (95% CI, 7.5-10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC. CONCLUSION: In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib.

Prognostic factors influencing progression-free survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation.

PURPOSE: Desmoid tumors are mesenchymal fibroblastic/myofibroblastic proliferations with locoregional aggressiveness and high ability to recur after initial treatment. We present the results of the largest series of sporadic desmoid tumors ever published to determine the prognostic factors of these rare tumors. PATIENTS AND METHODS: Four hundred twenty-six patients with a desmoid tumor at diagnosis were included, and the following parameters were studied: age, sex, delay between first symptoms and diagnosis, tumor size, tumor site, previous history of surgery or trauma in the area of the primary tumor, surgical margins, and context of abdominal wall desmoids in women of child-bearing age during or shortly after pregnancy. We performed univariate and multivariate analysis for progression-free survival (PFS). RESULTS: In univariate analysis, age, tumor size, tumor site, and surgical margins (R2 v R0/R1) had a significant impact on PFS. PFS curves were not significantly different for microscopic assessment of surgical resection quality (R0 v R1). In multivariate analysis, age, tumor size, and tumor site had independent values. Three prognostic groups for PFS were defined on the basis of the number of independent unfavorable prognostic factors (0 or 1, 2, and 3). CONCLUSION: This study clearly demonstrates that there are different prognostic subgroups of desmoid tumors that could benefit from different therapeutic strategies, including a wait-and-see policy.

Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial.

BACKGROUND: The role of surgery in the management of patients with advanced gastrointestinal stromal tumors (GIST) in the era of imatinib mesylate (IM) remains debated. We analyzed the outcome of patients with non metastatic locally advanced primary GIST treated with IM within the prospective BFR14 phase III trial. METHODS: The database of the BFR14 trial was searched for patients with no metastasis at time of inclusion. Patients treated for recurrent disease were excluded. Twenty-five of 434 patients met these criteria. RESULTS: Fifteen of 25 patients (60%) had a partial response to IM. Nine of the 25 patients (36%) underwent surgical resection of their primary tumor after a median of 7.3 months of IM treatment (range 3.4-12.0). Per protocol patients received continuous IM treatment in the post resection period, in an adjuvant setting. With a median follow-up of 53.5 months, there was a significant improvement in progression-free survival (PFS) and overall survival (OS) for patients who underwent surgical resection versus those who did not (median not reached vs 23.6 months, p = 0.0318 for PFS and median not reached vs 42.2 months, p = 0.0217 for OS). In the group of patients who underwent resection followed by IM, the 3-year PFS and OS rates were 67% and 89% respectively CONCLUSIONS: Following neoadjuvant IM for non metastatic locally advanced GIST 9 of 25 patients (36%) were selected for resection of the primary tumor. OS and PFS figures were close to those of localised intermediate or high risk GIST (70% at 5 years) in the subgroup of operated patients, while the outcome of the non-operated subgroup was similar to that of metastatic GIST.