One-bloc percutaneous large biopsy of soft-tissue tumours: feasibility study and possible indications.

AIM: To report the early results of the Intact lesion excision system (LES) regarding feasibility, tolerance and efficiency in obtaining soft-tissue tumour samples under ultrasound guidance. MATERIALS AND METHODS: The feasibility and tolerance of Intact LES procedures under ultrasound guidance were studied prospectively in 15 patients. The procedure was performed on an outpatient basis under local anaesthesia by a single interventional radiologist with 6 years of experience and lasted around 30 min. RESULTS: The feasibility of the Intact LES for soft-tissue masses was good except when lesions were hard and calcified. Tolerance was good, with median pain experienced during the procedure evaluated at 4.5/10 (SD 2.2) and median post-procedural pain at day 1 evaluated at 1.8/10 (SD 2.5). No major complications were observed; however, for vascularised lesions, one case of acute wound bleeding and two post-procedural haematomas led to delayed pain. CONCLUSION: Percutaneous biopsy of suspected soft-tissue sarcoma using the LES device under ultrasound guidance is well tolerated and feasible. After a first non-contributing core biopsy, and especially, in the case of lipomatous lesions, it is a valuable option to consider, as is surgical incision biopsy.

Description of late onset neutropenia in indolent lymphoma patients treated with bendamustine plus rituximab.

Bendamustine (B) associated with rituximab (R) is widely described in literature for the management of patients with chronic lymphoid leukaemia (CLL) and indolent non-Hodgkin lymphoma. Safety data regarding late hematotoxicity such as late onset neutropenia (LON) are scarce. The aim of our study was to assess the incidence and to identify risk factors for LON in patients with indolent non-Hodgkin lymphoma and CLL treated with B and R (B-R). One hundred forty five patients were treated with B-R as first or second line. Patients with neutropenia prior induction treatment, treated beyond second line and relapsing within 3 months after the end of induction treatment, were excluded. Patients receiving at least 1 cycle of B-R and having LON during follow-up period were included and considered as eligible for toxicity assessment. A complete blood count was performed 4 weeks after the last cycle of induction treatment and thereafter every 3 months for 1 year. Thirty six patients were identified in our cohort (incidence of 25%), mostly affected by CLL (n = 11) and follicular lymphoma (FL) (n = 15). During follow-up, 84 events of LON were recorded, 61% and 39% were of grades 1/2 and 3/4, respectively. No episode of febrile neutropenia was documented. Amongst 13 of the 15 patients with FL undergoing R maintenance, 8 had treatment discontinuation because of LON. Median time for LON (grade > 2) and time to recovery (grade < 3) were of 11.2 and 17.3 weeks, respectively. One year after B-R induction, LON persisted in 4 patients. The risk of LON was increased both in patients with FL or CLL and performance status >1. The LON in B-R treated patients is clinically relevant. Close clinical and biological follow-up and treatment prophylaxis (eg, valaciclovir and cotrimoxazole) especially for FL patients undergoing maintenance with R monotherapy seems relevant.

Improved survival using specialized multidisciplinary board in sarcoma patients.

BACKGROUND: Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. RESULTS: Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P < 0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis. CONCLUSION: The compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB.

Meningeal SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1)-deficient tumours: an emerging group of meningeal tumours.

AIMS: Bi-allelic inactivation of SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1; also known as INI1) and loss of immunohistochemical expression of SMARCB1 define the group of SMARCB1-deficient tumours. Initially highlighted in malignant rhabdoid tumours, this inactivation has subsequently been observed in several intra and extracranial tumours. To date, primary meningeal SMARCB1-deficient tumours have not been described. We report two cases of meningeal SMARCB1-deficient tumours occurring in adults. METHODS: We performed immunohistochemical analyses, comparative genomic hybridization, fluorescence in situ hybridization and targeted next-generation sequencing. RESULTS: The first meningeal tumour was a solitary mass, composed of rhabdoid, adenoid, chordoid and sarcomatoid areas. The second case presented as multiple, bilateral, supra and infratentorial nodules, was composed of fusiform and ovoid cells embedded in a myxoid stroma. Tumour cells were positive for epithelial membrane antigen (EMA), vimentin and CD34 and negative for SMARCB1 and meningothelial, melanocytic, muscular, glial markers. In the first case, one allele of SMARCB1 was completely deleted, whereas in the second case, loss of expression of SMARCB1 was observed as a consequence of a homozygous deletion of SMARCB1. CONCLUSIONS: The phenotype and genotype of these two cases did not fit diagnostically with entities already known to be SMARCB1-deficient tumours. As both tumours shared common features, they are regarded as belonging to an emerging group of primary meningeal SMARCB1-deficient tumours, not described to date. To facilitate the identification and characterization of these tumours, we recommend SMARCB1 immunohistochemistry for primary meningeal tumours which are difficult to classify, especially if immunopositive for EMA and CD34.

Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study.

BACKGROUND: The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma. METHODS: A multicentre, single-arm phase II trial was conducted. The primary objective was to determine the non-progression rate (RECIST) at 24 weeks for patients receiving sorafenib at a dose of 800 mg per day. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and HRQoL. RESULTS: Thirty-two patients were included. Ten patients showed non-progression at 24 weeks (31.2%) without objective tumour responses. The estimated 24-week PFS was 31.2% (95% CI: 14.8%-47.6%) and the estimated 24-week OS was 62.5% (95% CI: 45.4%-79.6%). Ten patients (34.3%) had at least one grade 3 or 4 adverse reaction and 12 patients (41.4%) required dose modifications due to toxicity. At 24 weeks, no patient had an improvement in global HRQoL and 87.5% experienced a permanent increase in physical fatigue. CONCLUSIONS: Sorafenib demonstrated non-progression at 24 weeks in 31.2% of patients. However, 41.4% of patients required dose modifications due to toxicity and no improvement in HRQoL was demonstrated.

[Role of radiotherapy in the management of non-Hodgkin lymphomas]. / Place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens.

The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.

Effect on survival of local ablative treatment of metastases from sarcomas: a study of the French sarcoma group.

AIMS: Recent data suggest that patients with pulmonary metastases from sarcomas might benefit from ablation of their metastases. Some data are available regarding osteosarcomas/angiosarcomas and lung metastases. The purpose of this study was to assess the efficacy of local ablative treatment on the survival of patients with oligometastases (one to five lesions, any metastatic site, any grade/histology) from sarcomas. MATERIALS AND METHODS: A multicentric retrospective study of the French Sarcoma Group was conducted in sarcoma patients with oligometastases who were treated between 2000 and 2012. Survival was analysed using multivariate sensitivity analyses with propensity scores to limit bias. RESULTS: Of the 281 patients evaluated, 164 patients received local treatment for oligometastases between 2000 and 2012. The groups' characteristics were similar in terms of tumour size and remission of the primary tumours. The median follow-up was 25.7 months; 129 (45.9%) patients had died at this point. The median overall survivals were 45.3 (95% confidence interval = 34-73) months for the local treatment group and 12.6 for the other group (95% confidence interval = 9.33-22.9). Survival was better among patients who received local treatment (hazard ratio = 0.47; 95% confidence interval = 0.29-0.78; P < 0.001). Subgroup analyses revealed similar findings in the patients with single oligometastases (hazard ratio = 0.48; 95% confidence interval = 0.28-0.82; P = 0.007); a significant benefit was observed for grade 3, and a trend was observed for grade 2. CONCLUSION: Local ablative treatment seemed to improve the overall survival of the patients who presented with oligometastatic sarcomas, including soft tissue and bone sarcomas. The survival benefit remained after repeated local treatments for several oligometastatic events. Surgery yielded the most relevant results, but alternative approaches (i.e. radiofrequency ablation and radiotherapy) seemed to be promising. The relevance of these results is strengthened by our analysis, which avoided biases by restricting the population to patients with oligometastatic disease and used propensity scores.

[Radiation therapy of cardiac sarcomas]. / Irradiation des sarcomes cardiaques de l'adulte.

PURPOSE: Primary cardiac sarcomas represent less than 10 yearly cases in France. Their median survival is approximately 18 months. The treatment consists of surgery when possible. The role of chemotherapy and radiation therapy is controversial, especially with respect to limiting cardiac radiation dose that is theoretically incompatible with the requirement of a tumoricidal dose for sarcoma. A recent series of 124 cases of the French Sarcoma Group suggested a benefit of radiation therapy on progression-free survival. PATIENTS AND METHODS: The dosimetric data of 12 patients were analyzed. RESULTS: There was variety in radiotherapy modalities and definition of target volumes, doses and techniques are evolving more conformal plans. Irradiation appeared feasible with conventional fractionation with respect to toxicities (although probably underestimated due to short follow-up and dismal prognosis) and previously demonstrated benefit of radiotherapy for primitive cardiac sarcomas. CONCLUSION: A scheme of 45Gy in 1.8Gy per fraction to a preoperative volume with an additional dose of 14Gy in 7 fractions on areas at risk or residual disease and margins 1cm, may be proposed based on the preliminary data of this study. Intensity modulated radiotherapy with daily cone-beam CT-scanner should be evaluated.

[Follicular dendritic cell sarcoma in head and neck region]. / Sarcome à cellules folliculaires dendritiques de la région ORL.

Follicular dendritic cell sarcomas are a recently described entity, with biphenotypic characteristics of lymphomas and sarcomas. The treatment is hardly consensual in the literature. We report two head and neck cases, of favorable outcome after surgery and radiotherapy. Histopathology and differential diagnoses are discussed as well as the therapeutic strategies used.

Prostatic and renal aspergillosis due to Aspergillus fumigatus in a patient receiving alemtuzumab for chronic lymphocytic leukaemia.

OBJECTIVE: Treatment of chronic lymphocytic leukaemia (CLL) is rapidly evolving, with emerging new drugs. Alemtuzumab is a monoclonal antibody recognizing CD52 antigen approved in the treatment of relapsing-refractory CLL. A frequent side effect is the immunosuppression and patients treated with alemtuzumab risk to develop fungal infections such as aspergillosis. PATIENT AND METHODS: This case report is about a patient who developed an uncommon localization of aspergillosis: prostatic and renal, after a treatment by alemtuzumab monotherapy. During the week 8 of alemtuzumab, the patient presented fever, urinary frequency and urologic symptoms. Persistance of fever with common antibiotherapy led to realize a tomography that showed prostatic and renal abscess (70mm and 29mm). It was decided to realize a prostatic biopsy. RESULTS: Histological findings showed suppurative abscess with ischemic necrosis and fungal proliferation, with branched fungal hyphae. Direct examination was negative. Culture on Sabouraud's agar revealed a mould identified as Aspergillus fumigatus. The organism was susceptible to voriconazole (MIC: voriconazole 0,25ug/mL). CONCLUSION: Because of the main side effect of alemtuzumab is immunosuppression, we have to research fungal infections such as Aspergillosis, particularly in patients with fever resistant to common antibiotherapy.

Management of anticancer treatment in patients under chronic dialysis: results of the multicentric CANDY (CANcer and DialYsis) study.

BACKGROUND: One million people worldwide benefit from chronic dialysis, with an increased rate in Western countries of 5% yearly. Owing to increased incidence of cancer in dialyzed patients, the management of these patients is challenging for oncologists/nephrologists. PATIENTS AND METHODS: The CANcer and DialYsis (CANDY) retrospective multicenter study included patients under chronic dialysis who subsequently had a cancer (T0). Patients were followed up for 2 years after T0. Prescriptions of anticancer drugs were studied with regard to their renal dosage adjustment/dialysability. RESULTS: A total of 178 patients from 12 institutions were included. The mean time between initiation of dialysis and T0 was 30.8 months. Fifty patients had received anticancer drug treatment. Among them, 72% and 82% received at least one drug needing dosage and one drug to be administered after dialysis sessions, respectively. Chemotherapy was omitted or prematurely stopped in many cases where systemic treatment was indicated or was often not adequately prescribed. CONCLUSIONS: Survival in dialysis patients with incident cancer was poor. It is crucial to consider anticancer drug treatment in these patients as for non-dialysis patients and to use current available specific drug management recommendations in order to (i) adjust the dose and (ii) avoid premature elimination of the drug during dialysis sessions.

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.

High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial.

BACKGROUND: Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. RESULTS: From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. CONCLUSION: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.

Chemotherapy in patients with desmoid tumors: a study from the French Sarcoma Group (FSG).

BACKGROUND: Data regarding the role of chemotherapy (CT) in patients with recurrent and/or unresectable desmoid tumors (DTs) are scarce. PATIENTS AND METHODS: Records of patients with DT who were treated with CT in centers from the French Sarcoma Group were reviewed. RESULTS: Sixty-two patients entered the study. The two most common locations were extremities (35.5%) and internal trunk (32.5%). Twelve patients (19.5%) were diagnosed with Gardner syndrome. Thirty-seven patients (54.7%) received previously one or more lines of systemic therapies (nonsteroidal anti-inflammatory drugs: 43.5%, antiestrogens: 43.5% and imatinib: 30.5%). Combination CT was delivered in 44 cases (71%) and single agent in 18 patients (29%), respectively. Thirteen patients (21%) received an anthracycline-containing regimen. The most frequent nonanthracycline regimen was the methotrexate-vinblastine combination (n=27). Complete response, partial response, stable disease and progressive disease were observed in 1 (1.6%), 12 (19.4%), 37 (59.6%) and 12 (19.4%) patients, respectively. The response rate was higher with anthracycline-containing regimens: 54% versus 12%, P=0.0011. Median progression-free survival (PFS) was 40.8 months. The sole factor associated with improved PFS was the nonlimb location: 12.1 months (95% confidence interval 5.6-18.7) versus not reached, P=0.03. CONCLUSIONS: CT has significant activity in DT. Anthracycline-containing regimens appear to be associated with a higher response rate.

[Six cases of pulmonary MALT lymphoma: a heterogeneous therapeutic management]. / Six cas de lymphomes pulmonaires de type MALT : une prise en charge thérapeutique hétérogène.

Pulmonary mucosa-associated lymphoid tissue lymphomas (PMALT) account for around 1% of lymphomas. Clinical and radiological presentations, and the treatment of six PMALT were collected from 1993 to 2008. All patients received chemotherapy before disease progression. Two patients had a lobectomy and one received thoracic radiotherapy. In 2008, all the patients were alive and three were in remission. A "watch and wait" strategy is widely accepted for stable, asymptomatic patients and patients with low tumour mass. Surgery may be proposed for symptomatic patients who have localised PMALT. When a chemotherapy treatment is to be suggested, chlorambucil-based chemotherapy is preferred. There may be room for rituximab alone or in combination, but this remains to be precisely defined. Several larger studies are currently ongoing to assess the role of monoclonal antibodies and chemotherapy in MALT lymphomas. Subgroup analysis should help us to define the optimal treatment for PMALT.

The role of radiotherapy in the treatment of pterygium: a review of the literature including more than 6000 treated lesions.

Pterygium is a benign conjunctival neoformation usually treated by surgical excision, but recurrences may affect 30% to 89% of cases, so that adjunctive therapies like conjunctival autografting, antimitotic drugs and beta-irradiation (ß-irradiation) are often used to improve the rate of local control. Our essay has reviewed relevant studies addressing the role of postoperative irradiation in the treatment of pterygium in the last 30 years through an Internet-based search and hand search in libraries. Sixteen studies on ß-irradiation and one on soft X-ray irradiation were accessible. They covered more than 6000 lesions treated by surgical excision and postoperative ß-irradiation using strontium-90 ((90)Sr) applicators at doses varying from 10 to 60 Gy/1-6 fractions/1-6 weeks starting within 3 days postoperatively. The rates of local recurrence were in general lower than 15% and major complications such as scleral thinning, ulceration, infections, or radiation-induced cataract were rarely encountered. Early postoperative ß-irradiation at a dose of 30 Gy/three fractions/2-3 weeks starting within 24h from surgical excision is an effective and safe procedure with local control rates comparable to chemotherapeutic agents and conjunctival autografting and superior to simple excision alone.

Aromatase inhibition in male breast cancer patients: biological and clinical implications.

BACKGROUND: The role of aromatase inhibitors (AIs) and their impact on estradiol (E(2)) levels remain unknown in male breast cancer (MBC) patients. PATIENTS AND METHODS: MBC patients with metastatic disease and those treated with AIs were selected from the breast cancer database of the Centre Antoine-Lacassagne (Nice, France). Sex hormone levels were retrospectively assessed on serum samples from our institutional serum bank. RESULTS: Fifteen patients entered the study. Two patients (13%) had complete response, four patients (27%) had partial response, two patients (13%) had stable disease and seven patients (47%) had progressive disease. The median progression-free survival and overall survival were 4.4 months [95% confidence interval (CI) 0.1-8.6] and 33 months (95% CI 18.4-47.6), respectively. All assessable patients (n = 6) had E(2) levels less than the lower limit of the assay during AI treatment. Among them, three had partial response, one had stable disease and two had progressive disease. A large increase in follicle-stimulating hormone, luteinizing hormone and E(2) levels was observed in one responding patient at progression. CONCLUSIONS: AIs are active in MBC patients. This activity is correlated with a significant reduction in E(2) levels. Secondary resistance is in part related to a deleterious feedback loop resulting in a significant increase in substrate for aromatization.