Response to chemotherapy is not related to chromosome instability in synovial sarcoma.

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

GROIN: a fast optical adjustment of a Kirkpatrick-Baez set-up.

A very simple and compact optical device aimed at the fast adjustment, alignment and bending of the mirrors of a Kirpatrick-Baez system used in the X-ray domain is described.

Unr, a cytoplasmic RNA-binding protein with cold-shock domains, is involved in control of apoptosis in ES and HuH7 cells.

Unr (upstream of N-ras) is a cytoplasmic RNA-binding protein involved in the regulation of messenger RNA stability and internal initiation of translation. We have used Unr-deficient murine embryonic stem (ES) cells to analyse Unr role in cell proliferation and response to stress. Disruption of both unr gene copies had no effect on ES cell proliferation. However, after ionizing radiation (IR), clonogenic survival of unr(-/-) ES cells was approximately 3-fold enhanced as compared to unr(+/+) cells. We further determined that IR-induced apoptosis was decreased in unr(-/-) ES cells, and that reintroduction of the unr gene in unr(-/-) cells restored normal IR-induced apoptosis. Three pro-apoptotic genes, p53, caspase-3 and Gadd45gamma, were downregulated in unr(-/-) ES cells, indicating that Unr, as other cytoplasmic RNA-binding proteins, regulates a complex genetic program, promoting cell death after IR. In contrast, in the human hepatoma cell line HuH7, Unr knockdown using unr-specific small interfering RNAs induced apoptosis, both in untreated and gamma-irradiated cells. Thus, our results establish that Unr acts as a positive or negative regulator of cell death, depending on the cell type. Manipulating the level of Unr may constitute a specific approach to sensitize cancer cells to anticancer treatments.

[Radiotherapy for soft tissue sarcomas of extremities. Preliminary comparative dosimetric study of 3D conformal radiotherapy versus helical tomotherapy]. / Radiothérapie postopératoire des sarcomes des tissus mous des extrémités. Etude dosimétrique préliminaire comparative de la radiothérapie conformationnelle avec la tomothérapie hélicoïdale.

PURPOSE: To evaluate dosimetry of helicoidal tomotherapy versus three-dimensional conformal radiotherapy (3D-CRT) with and without IMRT for the treatment of soft tissue sarcoma (STS) of the thigh. METHODS AND PATIENTS: A retrospective study was performed for three patients who received 3D-CRT as adjuvant radiation therapy for STS of the thigh. These three patients had a tumor in posterior, adductor or anterior compartment of the thigh. In each case, three treatments plans were optimised in tomotherapy, without bloc, with directional bloc and complete bloc of controlateral limb, to adequately treat the planning target volume and spare organ at risk. For each patient, we compare the three modalities of tomotherapy or "classical" IMRT from a clinac with the 3D-CRT actually performed for the treatment. RESULTS: Tomotherapy provides improved PTV coverage and dose homogeneity. This benefit was comparable in the three tomotherapy plans. The average D95% for tomotherapy and 3D-CRT were 97.6% and 94.8% respectively and the standard deviation is, at least, divided by two with conformal and is always better than performed with a clinac. The volume of the surrounding soft tissues receiving at least full prescription and hot spots, as evaluated by D2%, were significantly reduced in tomotherapy. Nevertheless, the results concerning the skin, the femur and the gonads were dependent on the tumor site in the thigh and not always improved with tomotherapy dosimetric studies. CONCLUSIONS: For this preliminary study, tomotherapy can provide better coverage and dose uniformity in PTV and minimize the volume of surrounding muscular tissues receiving high doses. However, in this study, there is no benefit for others OAR (skin, femur and gonads) except in particular constraint (for instance for a precise sparing of cutaneous or bony area). Other dosimetric studies, followed by prospective evaluations with long-term follow-up are needed to determine whether tomotherapy can improve outcome for patients with STS of the thigh.

[Lung dose constraints for normo-fractionated radiotherapy and for stereotactic body radiation therapy]. / Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : les poumons.

Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15-20Gy. For a thoracic SBRT, V20Gy<10% and MLD<6Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.

[Conservative and functional management for soft tissue sarcomas of the extremities: role of radiotherapy]. / Approche conservatrice et fonctionnelle dans les sarcomes des tissus mous des membres : place de la radiothérapie.

Recent publications have permitted to quantify the benefit of radiotherapy in the conservative treatment of soft tissue sarcoma of the limbs. The aim of this review is to focus on aspects of radiotherapy witch influence local control and functional outcome for early and late normal tissue damage. The evaluation of late effects is performed according to Soma-Lent (Subjective-Objective-Management-Analytic-Late Effects of Normal Tissues) classification. About complications, neurological complications are probably under estimated and are related to total dose of radiation therapy.

Study by EXAFS of the local structure around Si on silicene deposited on Ag(1 1 0) and Ag(1 1 1) surfaces.

The local structure around the silicon atoms of silicene deposited onto Ag(1 1 0) and Ag(1 1 1) has been determined by extended x-ray absorption fine structure spectroscopy at the silicon K-edge. This study shows that silicon atoms are not in a flat honeycomb network locally buckled, but that this structure mimics the double Si(1 1 1)-plane of crystalline silicon with almost the same first and second interatomic distances (2.35 and 3.83 Å) on a regularly buckled geometry. Moreover the results evidence silver atoms at a well-defined distance from the silicon ones, a signature for an interaction between the silicene sheet and silver atoms released from the substrate.

[Practice evolution of hypofractionation in breast radiation therapy and medical impact]. / Évolution des pratiques médicales d'hypofractionnement en radiothérapie pour cancer du sein et impact économique.

PURPOSE: Whole breast irradiation after conservative surgery is the standard treatment for invasive breast cancer. Randomized studies indicate that hypofractionation can be equivalent for selected patients. This study focuses on fractionation practice evolution in a single centre, and analyses the economic impact of practice modification. MATERIAL AND METHODS: All prescriptions for invasive breast cancer between January 2010 and June 2014 were analyzed. Female patients 60 years or older, pN0 were considered for the economic study. Patients included in clinical trials or patient with high-grade tumours were excluded from the hypofractionation practice study, because physician could not choose fractionation. We used data from the Medical public health system to calculate cost per fraction and transportation cost. RESULTS: Two thousand thirty one patients were treated; 399 were eligible for the economic study (20%) and 282 for the practice study (14%). Treatment with 25 fractions decreased from 90% to 16% in the first half of 2014. Meanwhile, treatment with 15 or 16 fractions increased from 6% in 2010 to 68% in the first half of 2014. Hypofractionated treatment proportion was 100% with 42.5Gy in 16 fractions in 2010 and 100% 40Gy in 15 fractions in 2014, according to long-term follow-up publication of START trials. Treatment with five fractions remained stable around 7% (4 to 16%), reserved for patients over 80 years (P<0.0001). Based on data from 3451 fractions in 2013, transport cost was calculated at 62 € per fraction, in addition to a 170.77 € reimbursement per fraction, giving a cost per fraction of 232.77 €. CONCLUSION: Practice change led to an increase of hypofractionation in recent years. Hypofractionation may be currently prescribed and may concern 20% of patients. This practice evolution is beneficial for patients and the public health system.

[Adjuvant radiation therapy for soft tissue sarcoma of the extremities: analysis of local control according to volume and dose]. / Radiothérapie adjuvante des sarcomes des tissus mous des membres: analyse du contrôle local en fonction des volumes irradiés et de la dose.

PURPOSE: To evaluate retrospectively the anatomical definition of target volumes in the treatment of soft tissue sarcomas of the limbs and to study the radiation dose in the local control and toxicity. METHODS AND PATIENTS: Seventy-seven patients were consecutively treated for primary soft tissue sarcoma of the extremity with limb sparing surgery and external beam radiotherapy (EBRT) in the same institution. The median follow up was 56 months (17-89 months). RESULTS: Fifty-two patients (67%) had clear microscopic surgical margin (R0 resection), 23 (30%) had histologically positive microscopic margin (R1 resection), 2 had a macroscopic residual disease (R2 resection). An anatomical definition of target volumes has been realised. The mean dose was 50 Gy in 25 or 28 fractions; 23 patients received a boost restricted to the tumor bed: 13 with EBRT, 10 with brachytherapy (BRT). Thirty-four patients had an adjuvant chemotherapy. The overall 5 year local relapse rate was 10%. Seven local relapses were described, five of the high-grade tumours, and five in patients with positive margin. In univariate analysis, quality of surgery shows a significant effect for local control. By using LENT-SOMA scale for late toxicity, a significant difference was found for neurological complications for patients receiving a boost. CONCLUSIONS: The results of the series validate the concept of anatomical definition of the initial target volume. A boost should be realised for positive margin tumors and may be for high-grade tumors. Neurological toxicity must be considered for the evaluation of the prescribed dose.

[Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)]. / Proposition de sélection et délimitation des volumes cibles microscopiques péritumoraux dans les cancers de la cavité buccale et de l'oropharynx (aires ganglionnaires exclues).

This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.

Radiobiological features of acute myeloblastic leukemia: comparison of self-renewal versus terminally differentiated populations.

PURPOSE: To evaluate the radiosensitivity of self-renewing progenitor cells in acute myeloblastic leukemia (AML), we have compared the radiosensitivity of the cells grown either in methylcellulose alone for 7 days, or first in suspension culture for 7 days before being plated in methylcellulose. Methylcellulose selects for terminal-dividing cells and suspension cultures have been developed because they allow self-renewal to occur: The exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. METHODS AND MATERIALS: Cells were harvested from previously untreated leukemic human bone marrows. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical, and immunophenotypic analysis, and by the use of growth factors that did not stimulate the growth of T-lymphocytes. The cell-cycle distribution of the blasts was analyzed by flow cytometry and was comparable for all samples. The irradiation was performed with gamma-photons at a dose-rate of 0.05 Gy/min, similar to the clinical conditions used in our institution for total body irradiation (TBI). RESULTS: The culture methods selected aggressive leukemias. There were large variations of the individual radiosensitivity whatever culture method was used. The progenitor cells capable of self-renewal were more radiosensitive than terminal dividing cells. In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. In these two cases, the best fit for the data was the linear quadratic model (survival = e-alpha D-beta D2) with alpha/beta values of 1.49 Gy and 3.12 Gy, respectively. CONCLUSION: The very low values of alpha/beta suggest a reduced antileukemic effect in case of fractionated TBI, and may lead to more reliable screening methods to determine the most appropriate technique for radiation ablation of bone marrow prior to bone marrow transplantation (BMT).

Ethmoidal cancers: a retrospective study of 22 cases.

From April 1978 to June 1990, 22 patients with ethmoidal cancer were treated at Fondation Bergonié by a combination of surgery and radiation therapy. The mean age was 59.6 years (range 34-79 years) and the sex ratio is 2.7 (16 males/6 females). Histologic types were: adenocarcinoma, 13 cases; squamous carcinoma, 4 cases; undifferentiated carcinoma, 3 cases and esthesioneuroblastoma, 2 cases. Exposure to wood dust was encountered in 11 patients, especially in cases of adenocarcinoma: 10/13 (77%). Staging according to the classification of the University of Florida was: Stage I, 10 patients; Stage II, 5 patients and Stage III, 7 patients. Resection was considered as complete in 16 cases and only one orbital exenteration was performed. The postoperative radiation therapy delivered a mean given dose of 55.7 Gy (range 50-70 Gy) expressed to the hot spot using a technique adapted to tumor location and extension. Complete remission was achieved in 20 cases. Median follow-up is 28 months. The 5-year overall and disease-free survival are 44% and 38%, respectively. Analysis of recurrences according to staging gives: 5/10 Stage I, 2/5 Stage II and 5/7 Stage III. Recurrence is pejorative since death occurs in all cases within an average of 6 months following salvage treatment, except for three patients still alive within less than 6 months and in second remission. Prognosis of ethmoidal cancer depends on staging and local control.

Results of postoperative radiation therapy in medullary carcinoma of the thyroid: a retrospective study by the French Federation of Cancer Institutes--the Radiotherapy Cooperative Group.

Between 1971 and 1989, 59 patients received external radiation therapy with a curative intent. There were 25 females and 34 males, ranging in age from 19 to 87. No patients had distant metastasis at the onset of treatment. The majority of patients had a total thyroidectomy (55/59), generally combined with neck dissection. Residual tumour was left in 11 cases, and 44 patients had positive cervical nodes. Using megavoltage radiotherapy, the whole neck and the upper mediastinum area were most often irradiated through a large anterior Y-shaped field without laryngeal shielding. The mean dose to the tumoral bed was 54 Gy. Dysphagia was observed in 32 patients (11, 17 and 5 scores were grade 1, 2 and 3, respectively). Dyspnea occurred in five cases and in two of these cases, it was considered to be severe. Local recurrences were noted in 18 (30%) patients, most of them occurring within the fields of irradiation. Parameters such as age, sex, total dose, irradiated volumes or cervical node enlargement did not modify the local control rate. The same conclusions can be drawn for distant failures. Thirty five patients are still alive and among them, 24 have no evidence of disease. The average length of survival is 70.5 months and is shortened by the occurrence of distant failures except in patients with bone metastases.

Memory-free conic anchoring of liquid crystals on a solid substrate

We show that the anchoring memory of liquid crystals on solid substrates can be completely removed by grafting highly mobile polymer chains. Using grafted polystyrene, we obtain uniform, stable, and reproducible memory-free and conically degenerated anchoring of the nematic 5CB. The symmetry of the conic anchoring enables two different zenithal anchoring breakings, towards homeotropic and planar states. Under external torques we observe both of them, with weak thresholds.

What does inductance plethysmography really measure?

Inasmuch as it has been claimed that inductance plethysmography can measure cross-sectional area changes, we tested this assumption. We present experimental and computed relationships between self-inductance (L) of coils and areas (A) included inside for a coil with a well-defined side wavy pattern (triangular or sinusoidal) and for a real belt (Respitrace) placed on elliptical or rectangular configurations. The results are applied to the physiological field using measurements obtained from a computed tomography experiment. We demonstrate that the L-A relationships vary not only with shape or ellipticity of the cross section but also with the wavy pattern shape. This last parameter is critical because it is difficult to actually control. When the coil wavy pattern remains steady, there are some physiological situations where inductance plethysmography can more accurately estimate area changes: when the configuration shape is constant, the correspondence between delta L and delta A is almost linear with a shape-dependent sensitivity; when the configuration is nearly circular (ellipticity in the range 0.8-1), the relative error in delta A estimation is less than 5%.

Respiratory cross-sectional area-flux measurements of the human chest wall.

A new device that utilizes the voltages induced in separate coils encircling the rib cage and abdomen by a magnetic field is described for measurement of cross-sectional areas of the human chest wall (rib cage and abdomen) and their variation during breathing. A uniform magnetic field (1.4 X 10(-7) Tesla at 100 kHz) is produced by generating an alternating current at 100 kHz in two square coils, 1.98 m on each side, parallel to the planes of the areas to be measured and placed symmetrically cephalad and caudad to these planes at a mean distance of 0.53 m. We demonstrated that the accuracy of the device on well-defined surfaces (squares, circles, rectangles, ellipses) was within 1% in all cases. Observed errors are due primarily to small inhomogeneities of the magnetic field and variation of the orientation of the coil relative to the field. Using a second magnetic field (80 kHz) perpendicular to the first, we measured the errors due to nonparallel orientation during quiet breathing and inspiratory capacity maneuvers. In 10 normal subjects, orientation effects were less than 2% for the rib cage and less than 0.7% for the abdomen. In five of these subjects, orientation effects at functional residual capacity in lateral and seated postures were generally less than or equal to 5%, but estimated tidal volume during spontaneous breathing was comparable to measurements in the supine posture. In five curarized patients, we assessed the linearity of volume-motion relationships of the rib cage and abdomen, comparing cross-sectional area and circumference measurements. Departures from linearity using cross-sectional areas were only one-third of those using circumferences. In seven normal subjects we compared cross-sectional area measurements with respiratory inductive plethysmography (RIP) and found comparable estimates of lung volume change over a wide range of relative rib cage contributions to tidal volume (-5 to 105%), with slightly higher standard deviations for the RIP (SD = 10% for RIP; SD = 4% for cross-sectional area).

Surface X-ray absorption spectroscopy: principles and some examples of applications.

The application of X-ray spectroscopy to surface problems has started almost at the same time as that in materials science. While the theoretical bases are obviously the same, SEXAFS has some experimental peculiarities which are reviewed here. Some examples of this technique will then be given.

[Pure ovarian dysgerminoma. Evaluation of experiences and definition of a therapeutic strategy]. / Le dysgerminome ovarien pur. bilan d'une expérience et définition d'une stratégie thérapeutique.

The authors present a series of 10 pure dysgerminoma of the ovary treated between 1976 and 1984; mean age = 19.5 years, range 15-46 years. All patients had initial surgery: 8 annexectomies for 5 stages Ia and 3 stages IIIc nodal disease, 1 hysterectomy with bilateral adnexectomy for a 46 year old stade Ib patient and 1 case of salvage surgery for a progressive disease after a single adnexectomy. Two patients had no adjuvant therapy after initial adnexectomy (stage Ia tumors less than 10 cm in diameter). Four patients received a prophylactic subdiaphragmatic radiation therapy (3 stages Ia tumors larger than 10 cm, 1 stage Ib disease). Three patients received an irradiation for a subdiaphragmatic bulky disease and a prophylactic supradiaphragmatic irradiation (stage IIIc nodal disease). Two patients received chemotherapy, one for recurrence, the other for progressive disease. The authors discuss the therapeutic indications of pure dysgerminoma of the ovary, especially the conservative management of young patients wishing to preserve an hormonal and obstetric future and the value of radiologic and serologic follow-up. Recent data in the literature underline the efficacy of new combinations of cytotoxic agents and their role as an adjuvant of surgery in early as well as in advanced stages.

[In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions)]. / Effets in vitro du piracetam sur la radiosensibilité des cellules hypoxiques (adaptation du test au MTT aux conditions d'hypoxie).

This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass versus reference polystyrene plates were comparable and confirm the validity of using special glass plates. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. However, this does not preclude a potential in vivo effect of piracetam on the radiosensitivity owing to its action on microcirculation and its rheologic properties. The adaptation of the MTT assay to hypoxic irradiation conditions yields the easy screening of radiosensitizing drugs: shorter incubation, semi-automatic method and simultaneous analysis with different serial concentrations thanks to the special 48-well glass plates.

[Conservative treatment of extremity soft tissue sarcomas. Functional evaluation using LENT-SOMA scales and Enneking scoring]. / Traitement conservateur des sarcomes des tissus mous des membres. Evaluation du résultat fonctionnel selon l'échelle LENT-SOMA et le score de Enneking.

OBJECTIVE: The aim of this prospective study is the feasibility of late effects assessment by LENT-SOMA scales after conservative treatment of soft tissue sarcomas of the extremities and a comparison with the functional evaluation by the Enneking score. PATIENTS AND METHODS: During the systematic follow-up consultations, a series of 32 consecutive patients was evaluated in terms of late effects by LENT-SOMA scales and functional results by the Enneking score. The median time after treatment was 65 months. The treatment consisted of conservative surgery (all cases) followed by radiation therapy (29 cases), often combined with adjuvant therapy (12 concomitant radio-chemotherapy association cases out of 14). The assessment of the toxicity was retrospective for acute effects and prospective for the following late tissue damage: skin/subcutaneous tissues, muscles/soft tissues and peripheral nerves. RESULTS: According to the Enneking score, the global score for the overall series was high (24/30) despite four the scores zero for the psychological acceptance. According to LENT-SOMA scales, a low rate of severe sequellae (grade 3-4) was observed. The occurrence of high-grade sequellae and their functional consequences were not correlated with quality of exerese, dose of radiotherapy or use of concomitant chemotherapy. A complementarity was observed between certain factors of the Enneking score and some criteria of the LENT-SOMA scales, especially of muscles/soft tissues. CONCLUSION: The good quality of functional results was confirmed by the two mean scoring systems for late normal tissue damage. The routine use of LENT-SOMA seems to be more time consuming than the Enneking score (mean time of scoring: 13 versus five minutes). The LENT-SOMA scales are aimed at a detailed description of late toxicity and sequellae while the Enneking score provides a more global evaluation, including the psychological acceptance of treatment. The late effects assessment by the LENT-SOMA scales should be carried on in prospectives studies, especially in case of concomitant radio-chemotherapy.