Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

BACKGROUND: To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. METHODS: TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. RESULTS: 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%). CONCLUSIONS: Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherap

Role of hydrodynamic factors in controlling the formation and location of unconformity-related uranium deposits: insights from reactive-flow modeling

The role of hydrodynamic factors in controlling the formation and location of unconformity-related uranium (URU) deposits in sedimentary basins during tectonically quiet periods is investigated. A number of reactive-flow modeling experiments at the deposit scale were carried out by assigning different dip angles and directions to a fault and various permeabilities to hydrostratigraphic units). The results show that the fault dip angle and direction, and permeability of the hydrostratigraphic units govern the convection pattern, temperature distribution, and uranium mineralization. Avertical fault results in uranium mineralization at the bottom of the fault within the basement, while a dipping fault leads to precipitation of uraninite below the unconformity either away from or along the plane of the fault, depending on the fault permeability. A more permeable fault causes uraninite precipitates along the fault plane,whereas a less permeable one gives rise to the precipitation of uraninite away from it. No economic ore mineralization can form when either very low or very high permeabilities are assigned to the sandstone or basement suggesting that these units seem to have an optimal window of permeability for the formation of uranium deposits. Physicochemical parameters also exert an additional control in both the location and grade of URU deposits. These results indicate that the difference in size and grade of different URU deposits may result from variation in fluid flow pattern and physicochemical conditions, caused by the change in structural features and hydraulic properties of the stratigraphic units involved

Phase I trial of oxaliplatin with fluorouracil, folinic acid and concurrent radiotherapy for oesophageal cancer

This dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended doses (RDs) of 5-fluorouracil (5FU), folinic acid and oxaliplatin (FOLFOX) with concomitant radiotherapy in inoperable/metastatic oesophageal squamous cell carcinoma or adenocarcinoma. Patients received three courses of LV5FU2 regimen (folinic acid 200 mg m−2, bolus 5FU 300–400 mg/m2, continuous infusion 5FU 400–600 mg m−2 on days 1 and 2) and escalating doses of oxaliplatin 50 to 100 mg m−2 on day 1 (FOLFOX). This regimen was repeated every 2 weeks, concomitant to a 50-gray radiotherapy per 5 weeks. Three more cycles were delivered after completion of radiation therapy. Three to six patients were allocated to each of the five dose levels until MTD was reached. Thirty-three patients were enroled and 21 had metastatic disease. Maximum tolerated dose was oxaliplatin 100 mg m−2, and continuous infusion 5FU was 600 mg m−2 day− (level 5). The most common toxicities were neutropenia, dysphagia and oesophagitis. The RDs were those of FOLFOX-4 regimen (oxaliplatin 85 mg m−2 and full doses of LV5FU2). The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably well tolerated and effective in inoperable/metastatic oesophageal carcinoma and warrants additional investigation

Comprehensive in vitro and in vivo studies of novel melt-derived Nb-substituted 45S5 bioglass reveal its enhanced bioactive properties for bone healing

The present work presents and discusses the results of a comprehensive study on the bioactive properties of Nb-substituted silicate glass derived from 45S5 bioglass. In vitro and in vivo experiments were performed. We undertook three different types of in vitro analyses: (i) investigation of the kinetics of chemical reactivity and the bioactivity of Nb-substituted glass in simulated body fluid (SBF) by 31P MASNMR spectroscopy, (ii) determination of ionic leaching profiles in buffered solution by inductively coupled plasma optical emission spectrometry (ICP-OES), and (iii) assessment of the compatibility and osteogenic differentiation of human embryonic stem cells (hESCs) treated with dissolution products of different compositions of Nb-substituted glass. The results revealed that Nb-substituted glass is not toxic to hESCs. Moreover, adding up to 1.3 mol% of Nb2O5 to 45S5 bioglass significantly enhanced its osteogenic capacity. For the in vivo experiments, trial glass rods were implanted into circular defects in rat tibia in order to evaluate their biocompatibility and bioactivity. Results showed all Nb-containing glass was biocompatible and that the addition of 1.3 mol% of Nb2O5, replacing phosphorous, increases the osteostimulation of bioglass. Therefore, these results support the assertion that Nb-substituted glass is suitable for biomedical applications

Lixiviation of argillaceous rocks : impact of oxidation degree states on organic compound mobilization.

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Efficacité et sécurité de la technique de radiothérapie mammaire avec complément d’irradiation concomitant : analyse de 121 cas traités à l’institut de cancérologie de Lorraine

International audiencePURPOSE:To evaluate the safety and efficacy of whole breast irradiation with a concomitant boost.PATIENTS AND MATERIALS:This is a retrospective study of 121 patients with node negative T1-T2 breast tumors inferior to 3 cm in diameter, previously treated by conservative surgery without chemotherapy. A dose of 50 Gy was delivered to the whole breast in 2 Gy daily fractions with 5 weekly treatments. A concomitant boost to the lumpectomy site delivered a total of 10 Gy in 1 Gy fractions twice a week. This would result in an equivalent tumour bed dose (assuming an α/β of 4) of approximately 65 Gy in 2 Gy fractions.RESULTS:Over 7 years, 121 patients were treated. The median age was 67 years (range, 46-86 years). Stage distribution was: 115 T1, 6 T2; 116 tumors had positive hormonal receptors, 6 grade SBR3. With a median follow-up of 6 years (range, 1.4-11.4 years), 5-year overall survival was 98.2% (95% confidence interval [CI] 0.95-1), disease-free survival was 100% and local recurrence-free survival 100%. The maximum acute skin toxicity by the end of treatment was grade 2. Cosmetic outcomes were good on the long term. One spontaneous rib fracture was observed 1 year after radiotherapy among 76 patients.CONCLUSIONS:The study shows that whole breast radiation therapy with a concomitant boost is safe and effective for selected patients with low risk of relapse, and gives excellent long term results. This protocol represents a good alternative to longer standard whole breast radiation therapy with sequential boost to the lumpectomy bed.Objectif de l’étudeÉvaluation de l’efficacité et de la sécurité de l’irradiation mammaire avec boost concomitant.Patientes et méthodeIl s’agit d’une étude rétrospective incluant 121 patientes atteintes d’un cancer du sein infiltrant de stade T1-T2 de moins de 3 cm, N0, précédemment traité par chirurgie conservatrice, sans chimiothérapie. L’ensemble du sein a reçu 50 Gy en 25 fractions de 2 Gy sur cinq semaines. Un boost concomitant de 10 Gy en dix fractions de 1 Gy a été délivré dans le lit opératoire à raison de deux séances par semaine. La dose équivalente par fraction de 2 Gy pour un rapport α/β de 4 était de 65 Gy.RésultatsAu cours d’une période de 7 ans, 121 patientes ont été traitées. L’âge médian était de 67 ans (46–86). Il s’agissait de 115 tumeurs de stade T1, 6 T2, 116 exprimaient des récepteurs hormonaux et six étaient de grade de Scarff, Bloom et Richardson (SBR) 3. Avec un suivi médian de six ans (1,4–11,4), la probabilité de survie globale à 5 ans était de 98,2 %, celle de survie sans récidive locale et celle de survie spécifique de 100 %. Durant le traitement, il n’a pas été observé de toxicité cutanée de grade supérieur à 2. Les résultats cosmétiques à long terme étaient bons. Il n’a été observé qu’une seule fracture de côte spontanée sur 76 patientes.ConclusionCette étude montre que l’irradiation du sein avec boost concomitant est une technique efficace et sûre pour notre population de patientes très sélectionnée atteinte de cancer du sein de pronostic favorable et à faible risque de rechute. Ce protocole est une bonne alternative au traitement standard avec boost séquentiel

Metal content and P-T evolution of CO2-bearing ore-forming fluids of the Haftcheshmeh Cu-Mo porphyry deposit, NW Iran

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: End of the commercialisation of 192Ir wires in France: Proposals of the groupe de Curiethérapie de la SFRO

International audienceIn 2014, the production of iridium 192 wires in France ended. Thus brachytherapy departments had to move to high-dose rate and pulsed-dose rate afterloading techniques. Most of them had already made this migration for some indications, based on the habits and investments. The brachytherapy group organised meetings and opened discussions to share the clinical knowledge and answer to the questions raised by this migration. This made it possible to resolve and describe quite all the clinical and technical cases of brachytherapy. The development of high technology included the use of 3D dosimetry and optimisation of dose distribution and fractionation. The teaching policy of new technologies contributes to the improvement of treatment quality. Last but not least, a better reimbursement of brachytherapy is necessary and currently negotiated.L’arrêt de la commercialisation des fils d’iridium 192 est intervenu au début de l’année 2014 en France. Cela a obligé les services de curiethérapie à reporter toutes leurs indications en utilisant des techniques avec projecteurs de source de débit pulsé ou de haut débit de dose. La plupart avaient déjà effectué cette migration pour une partie de leurs indications, selon les habitudes et les moyens. Les discussions et réunions organisées autour du groupe de curiethérapie ont permis un échange fructueux et la complémentarité des pratiques permet de répondre à la demande. La conversion est donc possible et effectuée pour quasiment toutes les indications habituelles de curiethérapie de bas débit de dose. Ce changement de pratiques oblige à la généralisation de la curiethérapie de haute technicité, fondée sur la dosimétrie tridimensionnelle et l’optimisation de la distribution de dose et la prescription du débit de dose ou du fractionnement. La poursuite de l’enseignement de ces techniques contribue également au maintien et à l’amélioration de la qualité. Une meilleure valorisation de cette curiethérapie est nécessaire et actuellement en cours de discussion