Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years.

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.

Humeral metastasis as the only recurrence of a 5-year resected gastrointestinal stromal tumor: a case report.

INTRODUCTION: Gastrointestinal stromal tumors represent the most frequently encountered primary mesenchymal tumors. Whereas the liver and the peritoneum are known to be the preferential metastasis sites, no therapeutic standard has yet been established for the management of bone metastases because of their very low incidence. We report a unique example of a single humerus metastasis of a jejunal gastrointestinal stromal tumor. CASE PRESENTATION: We report the case of a 72-year-old European woman whose jejunal gastrointestinal stromal tumor was resected in 2013 and treated during the following 3 years with imatinib (400 mg daily). In 2018, she developed a single humeral bone lesion that was identified as a gastrointestinal stromal tumor metastasis. After 7 months of imatinib intake, reconstructive surgery was performed. Pathologists confirmed the satisfactory histological regression and assessed the complete tumor resection. The patient is still on imatinib maintenance therapy, with no recurrence reported so far. She fully recovered the upper limb function after following an appropriate rehabilitation program. DISCUSSION: Current literature and published case reports indicate that bones are one of the rarest locations of gastrointestinal stromal tumor metastasis (about 1%), with occurrence mainly in the spine. Patients initially diagnosed with gastrointestinal stromal tumor of the small intestine and stomach are more likely to suffer from bone metastasis, compared with other gastrointestinal stromal tumor locations. The median overall survival rate is higher for patients with isolated bone metastasis compared with those having liver metastasis. Metastasis occurs on average 4 years after the primary, but it may take up to 20 years, emphasizing the need for long-term clinical and radiological monitoring. Although specific guidelines for such cases have not yet been established, we suggest that a multimodal concerted approach involving surgery or radiotherapy associated with tyrosine kinase inhibitor intake should be considered. CONCLUSION: Bones are one of the rarest locations of gastrointestinal stromal tumor metastasis. A multidisciplinary collaboration was set up to allow conservative surgery of our patient after several months of imatinib treatment. A year and a half later, the patient is still in complete remission. This specific case supports the concept of an intermediate stage between local and oligometastatic disease that should be managed with a curative aim, as much as possible.

A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial.

BACKGROUND: The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m2 every 3 weeks or BSC, stratified into L-STS (liposarcoma/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from the BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. RESULTS: Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. CONCLUSION: Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.

Systemic high-dose intravenous methotrexate in patients with central nervous system metastatic breast cancer.

BACKGROUND: Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer. METHODS: Twenty-two patients with CNS metastases treated by MTX (3 g/m2) between April 2004 and October 2009 were enrolled. Clinical response rate, time to progression (TTP), overall survival (OS), and safety were assessed. RESULTS: In terms of brain metastases, 2 patients (9%) achieved a partial response, 10 patients (45%) had disease stabilization, and 10 patients (45%) had disease progression. In others metastatic sites, 7 patients (39%) achieved a disease stabilization, and 11 patients (61%) had disease progression. TTP and OS were 2.1 (95%CI 1.4-2.9) and 6.3 (95%CI 1.8-10) months, respectively. CONCLUSION: High-dose MTX demonstrated a moderate activity at 3 g/m2. Nonetheless, the favorable toxicity profile should suggest the possibility to increase the dosage and further study are planned.

Surgery in reference centers improves survival of sarcoma patients: a nationwide study.

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

[Evaluation of the management of soft tissue sarcomas in Franche-Comté since the establishment of a multidisciplinary meeting at University Hospital. About 47 cases]. / Évaluation de la prise en charge des sarcomes des tissus mous en Franche-Comté depuis l'instauration d'une réunion de concertation pluridisciplinaire au CHRU. À propos de 47 cas.

GOALS OF STUDY: A multidisciplinary meeting (RCP) dedicated to the treatment of sarcoma was established in Franche-Comte in 2010. The goals of the study are: (a) To evaluate the treatment of sarcomas by confrontation with the existing literature; (b) To evaluate the influence of the multidisciplinary meeting on the management of sarcomas by hospitals at the regional level. MATERIALS AND METHODS: This is a retrospective single center study from 2010 to 2015 on patients with sarcoma and peripheral soft tissue drawn from a Netsarc database (National Network of sarcomas) and communicating cancer record. A database Cleanweb especially dedicated is created. RESULTS: Forty-seven patients were included: ten sarcomas at the upper member 26 to the lower limbs, 11 on the trunk. Forty patients were operated on: ten out of the university hospital, 28 at the university hospital and two in a coordinating center. Ninety percent of patients treated at the university hospital were in accordance with the recommandations. None of the patients operated out of the university hospital benefited from medical care in accordance to the recommendations. There is an increase in the number of files sent by the hospitals out of the university hospital discussed in multidisciplinary meeting, before treatment. CONCLUSION: The creation of a dedicated multidisciplinary meeting sarcoma improves the medical management of these tumors and decreases inappropriate medical managements thanks to a better education of the regional physicians.

[Large surgical resection of a shoulder sarcoma's and secure one stage reconstruction with lattissimi dorsi and serratus anterior flap. Updating about a case]. / Exérèse large d'un sarcome de l'épaule et reconstruction en un temps par double lambeau de grand dorsal et de grand dentelé pédiculé. Discussion à propos d'un cas.

INTRODUCTION: The soft tissue sarcomas (STM) are tumors developed at the expense of connective tissue. They are rare and have severe prognosis. The principles of management are recalled through an extended case of shoulder sarcoma. CLINICAL CASE: A 48-year-old patient has a sarcoma of the right pectoralis major muscle confirmed by biopsy. After multidisciplinary meeting, a wide surgical excision exposing the subclavian vessels and brachial plexus is performed with double cover flap pedicled latissimus dorsi and serratus and thin skin graft. RESULT: Healing process is acquired at 3 months. Adjuvant chemotherapy is established (adriamycin, ifosfamide) along with radiotherapy (54Gy). CONCLUSION: Sarcomas treatment has to be realized after considering multidisciplinary meeting (RCP) in dedicated structures. Surgery is the main treatment, it should ideally be R0, that is to say, integral with healthy tissue margin around the tumor (or healthy anatomical barrier). Optimal surgery performs a resection "without seen tumor". The diagnosis has to be made with a biopsy before the surgical treatment. Healing is quickly obtained due to adjuvant treatments.

Efficacy of trabectedin in malignant solitary fibrous tumors: a retrospective analysis from the French Sarcoma Group.

BACKGROUND: Advanced malignant solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas with a poor prognosis. Several treatment options have been reported, but with uncertain rates of efficacy. Our aim is to describe the activity of trabectedin in a retrospective, multi-center French series of patients with SFTs. METHODS: Patients were mainly identified through the French RetrospectYon database and were treated between January 2008 and May 2013. Trabectedin was administered at an initial dose of 1.5 mg/m(2), q3 weeks. The best tumor response was assessed according to the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) and overall survival (OS). The growth-modulation index (GMI) was defined as the ratio between the time to progression with trabectedin (TTPn) and the TTP with the immediately prior line of treatment (TTPn-1). RESULTS: Eleven patients treated with trabectedin for advanced SFT were identified. Trabectedin had been used as second-line treatment in 8 patients (72.7 %) and as at least third-line therapy in a further 3 (27.3 %). The best RECIST response was a partial response (PR) in one patient (9.1 %) and stable disease (SD) in eight patients (72.7 %). Disease-control rate (DCR = PR + SD) was 81.8 %. After a median follow-up of 29.2 months, the median PFS was 11.6 months (95 % CI = 2.0; 15.2 months) and the median OS was 22.3 months (95 % CI = 9.1 months; not reached). The median GMI was 1.49 (range: 0.11-4.12). CONCLUSION: Trabectedin is a very promising treatment for advanced SFTs. Further investigations are needed.

Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial.

BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. RESULTS: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted.

Conservative surgery vs. duodeneopancreatectomy in primary duodenal gastrointestinal stromal tumors (GIST): a retrospective review of 114 patients from the French sarcoma group (FSG).

BACKGROUND: Duodenal GISTs represent 3-5% of all GISTs with limited understanding of patient outcomes. We conducted a retrospective analysis of primary localized duodenal GISTs. METHODS: Patients were identified via a survey from 16 FSG centers (n = 105), and a group of 9 patients enrolled in the BFR14 trial. Data were collected from the original database and patient files, in agreement with French legislation. RESULTS: 114 patients were included, with a median age of 57. Tumors originated mainly in D2 (33%), or D3 (24%), with a median size of 5 cm. 109 patients had resection of the primary tumor; with a Local Resection (LR, n = 82), a pancreaticoduodenectomy (PD, n = 23), and data were missing for 4 patients. Resections were R0 (n = 87, 79%), R1 (n = 8, 7%), R2 (n = 6). Tumor characteristics were: KIT+ (n = 104), CD34+ (n = 58). Miettinen risk was low (n = 43), and high (n = 52). Imatinib was administered preoperatively (n = 11) and post-operatively (n = 20). With a median follow-up of 36 months (2-250), 98 patients are alive, and 33 relapsed. The 5-year OS and EFS rates are 86.5% and 54.5%. EFS was similar for patients in the LR and the PD groups (P > 0.05). In multivariate analysis, ECOG PS, and CD34 expression are independent prognostic factors on OS. Miettinen risk and spindle cell type are independent predictive factors for relapse. CONCLUSIONS: Patients with resected duodenal GIST have a reasonably favorable prognosis. This study favors a preservation of pancreas when there are no anatomical constraints. LR exhibit similar survival and smaller morbidity then PD.

Advanced chondrosarcomas: role of chemotherapy and survival.

BACKGROUND: There are limited data about the role of chemotherapy in patients with advanced chondrosarcomas. METHODS: The medical charts of 180 patients with advanced chondrosarcomas having received chemotherapy in 15 participating institutions between 1988 and 2011 were reviewed. RESULTS: Median age was 52 years. Sixty-three percent of patients had conventional chondrosarcoma and 88% had metastatic disease. Combination chemotherapy was delivered in 98 cases (54.5%). One hundred and thirty-one patients (73%) received an anthracycline-containing regimen. Using RECIST, the objective response rate was significantly different according to histological subtype, being 31% for mesenchymal chondrosarcoma, 20.5% for dedifferentiated chondrosarcoma, 11.5% for conventional chondrosarcoma and 0% for clear-cell chondrosarcoma (P = 0.04). Median progression-free survival (PFS) was 4.7 months [95% confidence interval (CI) 3-6.5]. Performance status (PS) ≥2, number of metastatic sites ≥1 and single-agent regimen were independently associated with poor PFS. Median overall survival (OS) was 18 months (95% CI 14.5-21.6). PS, number of metastatic sites and palliative surgery were independently associated with OS. CONCLUSIONS: Conventional chemotherapy have very limited efficacy in patients with advanced chondrosarcoma, the highest benefit being observed in mesenchymal and dedifferentiated chondrosarcoma. These data should be used as a reference for response and outcome in the assessment of investigational drugs in advanced chondrosarcoma.

Sorafenib in patients with progressive malignant solitary fibrous tumors: a subgroup analysis from a phase II study of the French Sarcoma Group (GSF/GETO).

Malignant solitary fibrous tumors are rare soft-tissue sarcomas. They are considered as low-grade malignancies, but may display metastatic potential in 20% of the cases. In case of metastatic or locally advanced, unresectable disease, standard treatments, like anthracycline-based regimens, are poorly effective. Previous studies suggested that antiangiogenic drugs, such as sorafenib, could be efficient to treat vascular sarcomas and solitary fibrous tumors. Five patients with progressive SFT were included in this phase 2 study, and treated with sorafenib at a dose of 800 mg daily. Two patients out of the five achieved a 9 months disease control with sorafenib, while their disease had progressed within the month preceding their inclusion. Consequently, our data suggest a potential efficacy of sorafenib in SFT, Further investigation is needed to confirm these data.

Correlation between overall survival and growth modulation index in pre-treated sarcoma patients: a study from the French Sarcoma Group.

BACKGROUND: Growth modulation index (GMI), the ratio of two times to progression measured in patients receiving two successive treatments (GMI = TTP2/TTP1), has been proposed as a criterion of phase II clinical trials. Nevertheless, its use has been limited until now. PATIENTS AND METHODS: We carried out a retrospective multicentre study in soft tissue sarcoma patients receiving a second-line treatment after doxorubicin-based regimens to evaluate the link between overall survival and GMI. Second-line treatments were classified as 'active' according to the EORTC-STBSG criteria (3-month progression-free rate >40% or 6-month PFR >14%). Comparisons used chi-squared and log-rank tests. RESULTS: The population consisted in 106 men and 121 women, 110 patients (48%) received 'active drugs'. Median OS from the second-line start was 317 days. Sixty-nine patients experienced GMI >1.33 (30.4%). Treatments with 'active drug' were not associated with OS improvement: 490 versus 407 days (P = 0.524). Median OS was highly correlated with GMI: 324, 302 and 710 days with GMI <1, GMI = [1.00-1.33], and GMI >1.33, respectively (P < 0.0001). In logistic regression analysis, the sole predictive factor was the number of doxorubicin-based chemotherapy cycles. CONCLUSION: GMI seems to be an interesting end point that provides additional information compared with classical criteria. GMI >1.33 is associated with significant OS improvement.

Phase II study assessing lapatinib added to letrozole in patients with progressive disease under aromatase inhibitor in metastatic breast cancer-Study BES 06.

This trial evaluated the effect of adding lapatinib to letrozole after clinical resistance to aromatase inhibitor (IA) treatment in hormone receptor-positive metastatic breast cancer. Postmenopausal women received daily letrozole plus lapatinib (1,500 mg). The primary end point was objective rate response (ORR) at week 12. Secondary objectives included time to response, duration of response, clinical benefit (CB), progression-free survival (PFS), overall survival, and safety. Twenty-four human epidermal growth factor receptor 2 (HER2)-negative patients were included with secondary resistance to IA. ORR at 12 weeks was 4 % (95 % confidence interval (CI), 0.7-20). Stable and progression diseases were reported in 25 % (95 % CI, 12-45) and 71 % (95 % CI, 51-85) of cases, respectively. At 24 weeks, the ORR increased to 8 %. CB was 21 % (95 % CI, 9-40). At a median follow-up of 27 months, median PFS was 3.4 months (95 % CI, 2.8-5.4). Grade 3 or 4 adverse events were rarely reported. No clinical cardiac toxicity was observed. Lapatinib was discontinued in two patients due to severe diarrhea. This trial was prematurely closed due to low recruitment. These preliminary results suggest that the addition of lapatinib to letrozole has a favorable safety profile and could overcome tumoral resistance to letrozole among HER2-negative tumors.

Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.

Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial.

PURPOSE: To compare the overall survival rates of good-prognosis carcinomas of an unknown primary site (CUPS) patients treated with cisplatin alone (C) or in combination with gemcitabine (CG). PATIENTS AND METHODS: Good prognosis was defined according to the GEFCAPI (Groupe d'Etude Français des Carcinomes de site Primitif Inconnu) classification by PS (Performance Status) ≤ 1 and LDH (Lactate Deshydrogenase) within the normal range. Patients were randomly assigned to receive C or CG. Patients in the C arm received cisplatin 100 mg/m(2) repeated every 3 weeks. In the CG arm, chemotherapy consisted of gemcitabine 1250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) IV on day 1, repeated every 3 weeks. The original plan was to accrue 192 patients in order to detect a 20% difference in overall survival. RESULTS: Fifty-two patients were enrolled (arm A: 25; arm B: 27). The trial was stopped early due to insufficient accrual. The median overall survival (OS) rate was 11 months [95% confidence interval: 9-20] and 8 months [95%CI: 6-12], in the CG arm and in the C arm, respectively. The 1-year survival rate was 46% [95%CI: 28-64] in the combination arm and 35% [95%CI: 19-56] in the C arm (log rank test: p=0.73). The median progression-free survival (PFS) rate was 5 [95%CI: 3-11] and 3 [95%CI: 1-8] months in the CG and in the C arm, respectively. The 1-year PFS rate was 29% [95%CI: 15-48] in the combination arm and 15% [95%CI: 5-35] in the C arm (log rank test: p=0.27). No toxic deaths occurred. Grade 3-4 neutropenia (63% versus 12%) and grade 3-4 thrombocytopenia (37% versus 4%) were more frequent in the CG arm than in the C arm. CONCLUSION: A non-significantly better outcome was observed with CG as compared to C in patients with CUP and a non-unfavourable prognosis. The toxicity profile of the combined arm was represented by haematologic toxicity with thrombocytopenia and leuconeutropenia. International collaboration is required to conduct phase III trials in patients with CUP.

Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve the outcome.

BACKGROUND: Angiosarcomas are a rare but aggressive form of soft tissue sarcoma. At metastatic stage, the clinical benefit of therapeutic intervention remains debatable. PATIENTS AND METHODS: We have carried a retrospective analysis of 149 cases treated between 1996 and 2009 in the French Sarcoma Group. RESULTS: The median age was 60; the sex ratio was 0.80. Sixty-two percentage of cases presented with metastasis at the diagnosis. About 20% arose in irradiated fields. The median overall survival was 11 months. Treatment consisted in metastasectomy (5.4%), doxorubicin-based regimen (46.9%), weekly paclitaxel (Taxol) (31.5%), other chemotherapy regimens (10.7%) or exclusive palliative care (10.9%). Clinical prognostic factors identified by univariate analysis were presence of bone metastasis (P = 0.0107), presence of other metastasis (P = 0.0327) and performance status (P < 0.0001). The Cox model retained a performance status of two or more as the sole independent prognostic factor (HR [hazard ratio] = 2.49, P < 0.0001). After adjustment to the performance status and compared with exclusive palliative care, the following treatments significantly improve the outcome: doxorubicin-based regimen as first-line chemotherapy (HR = 0.38, P = 0.0165), weekly paclitaxel as first-line regimen (HR = 0.36, P = 0.0146) and metastasectomy (HR = 0.09, P = 0.0221). CONCLUSIONS: This retrospective analysis indicates that some therapeutic interventions may significantly improve the outcome of this aggressive disease. Doxorubicin-based regimens and weekly paclitaxel seem to provide the same range of efficacy.

Incidence and risk factors of anemia in patients with early breast cancer treated by adjuvant chemotherapy.

BACKGROUND: The study's objective was to assess the predictive factors of anemia induced by chemotherapy in early breast cancer patients. PATIENTS AND METHODS: Patients treated by adjuvant or neo-adjuvant anthracyclin-based regimens with or without taxanes between 1998 and 2006 in a French university hospital were studied. Chemotherapy included. Anemia was defined as a hemoglobin (Hb) concentration lower than 12 g/dL. Multivariate analysis by logistic regression was used to search for baseline risk factors linked to the occurrence of anemia. RESULTS: Among 378 patients, anemia was observed in 64% of cases. The occurrence of anemia was significantly related to 6 risk factors: exposure to taxanes (HR 11.5, 95% CI, 2.5-52.6), high dose of anthracyclin (epirubicin 100 mg/m²)(HR 4.3; 95% CI, 2.8-8), Hb at baseline < 13.5 g/d (HR 4.3; 95% CI, 2.6-7.1), mastectomy (HR 2.5; 95% CI, 1.4-3.3), age >60 (HR 2.5; 95% CI, 1.4-5) years old (HR 2.5; 95% CI, 1.4-5) and Body Mass Index (BMI) ≤ 25 kg/m² (HR 1.7; 95% CI, 1.0-2.8). CONCLUSION: Taking into account the following factors: type of chemotherapy, BMI, age, Hb at baseline should allow a better identification of patients at risk of anemia.