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Deutsch E.,University Paris - Sud | Deutsch E.,French Institute of Health and Medical Research | Haie-Meder C.,University Paris - Sud | Bayar M.A.,Biostatistics and Epidemiology Unit | And 15 more authors.
Oncotarget | Year: 2016

Purpose: This phase I trial aimed to assess the safety and determine the recommended Phase II dose (RP2D) of Cidofovir combined with chemoradiotherapy in patients with stage IB2-IVA cervical cancer. Results: A total of 15 patients were treated with Cidofovir. Dose-limiting toxicities occurred in 2/6 patients at the 6.5 mg/kg dose level (G3 proteinuria, and G3 acute pyelonephritis with G3 febrile neutropenia). No toxicity occurred at the 5 mg/kg dose level, but only 3 patients received this dose due to trial interruption because of low accrual. The most frequent G3-4 adverse effects observed during the trial were: abdominal pain (n=3), infection (n=2), leuckoneutropenia (n=2), and others (n=6). No toxic death or major renal side effect occurred. The best response was that 8/9 evaluable patients achieved a complete response (89%). In the intention to treat population, the 2-year overall and progression-free survival rates were 93% and 76%, respectively. Biological monitoring of HPV-related markers (decreased p16 expression, and increased p53 and pRb levels) was possible on sequential tumor biopsy samples. The genomic alterations identified were PIK3CA (n=5; one also had a KRAS mutation), and HRAS (n=1) mutations. Patients and Methods: Incremental doses (1, 2.5, 5 and 6.5 mg/kg) of IV Cidofovir were administered weekly for two weeks, and then every 2 weeks from the start of chemoradiotherapy to the initiation of utero-vaginal brachytherapy. Biological expression of HPV was analyzed during treatment and tumor response was assessed according to RECIST v1.0 criteria. Conclusion: Cidofovir at a dose of 5mg/kg combined with chemoradiotherapy appeared tolerable and yielded tumor regressions. Due to early trial interruption, the RP2D was not confirmed. Source


Mery B.,Lucien Neuwirth Cancer Institute | Trone J.-C.,Institute Of Cancerologie Of La Loire Lucien Neuwirth | Moriceau G.,Lucien Neuwirth Cancer Institute | Falk A.T.,Center Antoine Lacassagne | And 4 more authors.
Chemotherapy | Year: 2015

We report the case of an 80-year-old patient who presented with a progressive prostate metastatic cancer with poor performance status. The patient had already benefitted from docetaxel and abiraterone. A new line of chemotherapy by cabazitaxel was started with good response, and there was a dramatic improvement in general status and pain symptoms. Age and performance status alone should not be limiting decision factors for elderly cancer patients. © 2015 S. Karger AG, Basel. Source


Guy J.-B.,Institute Of Cancerologie Of La Loire Lucien Neuwirth | Falk A.T.,Center Antoine Lacassagne | Chargari C.,Radiation Oncology | Bertoletti L.,Jean Monnet University | And 2 more authors.
Journal of Contemporary Brachytherapy | Year: 2015

Pulsed-dose-rate (PDR) brachytherapy is a recent brachytherapy modality combining the radiobiological advantages of low-dose-rate (LDR) brachytherapy with increased possibilities of dose optimization and radiation safety. However, treatment duration remains protracted, as the prescribed dose is typically delivered through pulses that do not exceed 0.5 Gy/h for critical organs. It is frequently used for the treatment of gynaecological malignancies. Although, the relationship between thrombosis and cancer is well known, specific data on thromboembolic events during brachytherapy are scarce. We report two cases of major thromboembolic events during brachytherapy treatment for gynaecological malignancies. We discuss the possible causal relationship between brachytherapy procedures and the occurrence of thromboembolic events, drawing a preventive practical attitude. Source


Guy J.-B.,Institute Of Cancerologie Of La Loire Lucien Neuwirth | Falk A.T.,Center Antoine Lacassagne | Auberdiac P.,Clinique Claude Bernard | Cartier L.,Institute Of Cancerologie Of La Loire Lucien Neuwirth | And 6 more authors.
Medical Dosimetry | Year: 2016

Introduction: For patients with cervical cancer, intensity-modulated radiation therapy (IMRT) improves target coverage and allows dose escalation while reducing the radiation dose to organs at risk (OARs). In this study, we compared dosimetric parameters among 3-dimensional conformal radiotherapy (3D-CRT), "step-and-shoot" IMRT, and volumetric intensity-modulated arc radiotherapy (VMAT) in a series of patients with cervical cancer receiving definitive radiotherapy. Computed tomography (CT) scans of 10 patients with histologically proven cervical cancer treated with definitive radiation therapy (RT) from December 2008 to March 2010 at our department were selected for this study. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated following the guidelines of the Gyn IMRT consortium that included cervix, uterus, parametrial tissues, and the pelvic nodes including presacral. The median age was 57 years (range: 30 to 85 years). All 10 patients had squamous cell carcinoma with Federation of Gynecology and Obstetrics (FIGO) stage IB-IIIB. All patients were treated by VMAT. OAR doses were significantly reduced for plans with intensity-modulated technique compared with 3D-CRT except for the dose to the vagina. Between the 2 intensity-modulated techniques, significant difference was observed for the mean dose to the small intestine, to the benefit of VMAT (< 0.001). There was no improvement in terms of OARs sparing for VMAT although there was a tendency for a slightly decreased average dose to the rectum: - 0.65 Gy but not significant (= 0.07). The intensity modulation techniques have many advantages in terms of quality indexes, and particularly OAR sparing, compared with 3D-CRT. Following the ongoing technologic developments in modern radiotherapy, it is essential to evaluate the intensity-modulated techniques on prospective studies of a larger scale. © 2016 American Association of Medical Dosimetrists. Source


Wozny A.-S.,University Claude Bernard Lyon 1 | Wozny A.-S.,Center Hospitalier Lyon Sud | Alphonse G.,University Claude Bernard Lyon 1 | Alphonse G.,Center Hospitalier Lyon Sud | And 13 more authors.
Frontiers in Oncology | Year: 2016

Nowadays, head and neck squamous cell carcinoma (HNSCC) treatment failure is mostly explained by locoregional progression or intrinsic radioresistance. Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional RT or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72 MeV/n carbon ions at a dose rate of 0.5, 2, or 10 Gy/min. For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure. This variation of radiosensitivity was associated with the number of initial and residual DNA double-strand breaks (DSBs). By contrast, the dose rate change did not affect neither cell survival nor the residual DNA DSBs after carbon ion irradiation. As a result, the relative biological efficiency at 10% survival increased when the dose rate decreased. In conclusion, in the RT treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes toward altered fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation. © 2016 Wozny, Alphonse, Battiston-Montagne, Simonet, Poncet, Testa, Guy, Rancoule, Magné, Beuve and Rodriguez-Lafrasse. Source

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