Papers by Frederic Dhermain
Neuro-oncology, Jan 18, 2014
Glioma follow-up is based on MRI parameters, which are correlated with survival. Although establi... more Glioma follow-up is based on MRI parameters, which are correlated with survival. Although established criteria are used to evaluate tumor response, radiological markers may be confounded by differences in instrumentation including the magnetic field strength. We assessed whether MRIs obtained at 3 Tesla (T) and 1.5T provided similar information. We retrospectively compared imaging features of 30 consecutive patients with WHO grades II and III gliomas who underwent MRI at 1.5T and 3T within a month of each other, without any clinical changes during the same period. We compared lesion volumes on fluid attenuation inversion recovery (FLAIR), ratio of cerebral blood volume (rCBV) on perfusion-weighted imaging, contrast-to-noise ratio (CNR) on FLAIR, and on post-gadolinium 3D T1-weighted sequences between 1.5T and 3T using intraclass correlation coefficient (ICC). Concordance between observers within and between modalities was evaluated using weighted-kappa coefficient (wκ). The mean ± S...
A Treatment Planning Comparison of Combined Photon–Proton Beams Versus Proton Beams–Only for the Treatment of Skull Base Tumors
To compare treatment planning between combined photon-proton planning (CP) and proton planning (P... more To compare treatment planning between combined photon-proton planning (CP) and proton planning (PP) for skull base tumors, so as to assess the potential limitations of CP for these tumors. Plans for 10 patients were computed for both CP and PP. Prescribed dose was 67 cobalt Gray equivalent (CGE) for PP; 45 Gy (photons) and 22 CGE (protons) for CP. Dose-volume histograms (DVHs) were calculated for gross target volume (GTV), clinical target volume (CTV), normal tissues (NT), and organs at risk (OARs) for each plan. Results were analyzed using DVH parameters, inhomogeneity coefficient (IC), and conformity index (CI). Mean doses delivered to the GTVs and CTVs with CP (65.0 and 61.7 CGE) and PP (65.3 and 62.2 Gy CGE) were not significantly different (p > 0.1 and p = 0.72). However, the dose inhomogeneity was drastically increased with CP, with a mean significant incremental IC value of 10.5% and CP of 6.8%, for both the GTV (p = 0.01) and CTV (p = 0.04), respectively. The CI(80%) values for the GTV and CTV were significantly higher with PP compared with CP. Compared with CP, the use of protons only led to a significant reduction of NT and OAR irradiation, in the intermediate-to-low dose (< or =80% isodose line) range. These results suggest that the use of CP results in levels of target dose conformation similar to those with PP. Use of PP significantly reduced the tumor dose inhomogeneity and the delivered intermediate-to-low dose to NT and OARs, leading us to conclude that this treatment is mainly appropriate for tumors in children.
Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuro-ectodermic tumors
Pediatric Blood & Cancer, 2014
To assess the feasibility and effectiveness of high-dose chemotherapy (HDC) with stem cell suppor... more To assess the feasibility and effectiveness of high-dose chemotherapy (HDC) with stem cell support followed by conventional craniospinal radiotherapy (RT) as treatment for children older than 5 years of age with newly diagnosed high-risk medulloblastoma (MB) or supratentorial PNET (sPNET). Between May 2001 and April 2010, 24 children older than 5 years of age (MB = 21; sPNET = 3), fulfilling inclusion criteria at diagnosis, were treated at Gustave Roussy. After conventional chemotherapy, they received two courses of high-dose thiotepa (600 mg/m(2)) followed by craniospinal RT. The median follow-up was 4.4 years (range, 0.8-11.3 years). For children with metastatic MB, the 5-year event-free survival (EFS) and overall survival (OS) were 72% and 83%, respectively. The toxicity was manageable. No toxic death occurred. At the most recent evaluation, among the 24 children who had at least one Full Scale Intellectual Quotient (FSIQ) examination at a median follow-up of 3.79 years after diagnosis, the mean estimated FSIQ was 82 (range, 56-114). In children with metastatic MB, tandem HDCT with ASCT followed by conventional craniospinal RT proved its feasibility without jeopardizing survival.
Journal of Neuro-Oncology, 2012
The purpose of this study is to evaluate the efficacy and toxicity of radiation therapy (RT) with... more The purpose of this study is to evaluate the efficacy and toxicity of radiation therapy (RT) with concurrent temozolomide (TMZ) chemotherapy followed by adjuvant TMZ in children with diffuse intrinsic pontine glioma (DIPG). Newly diagnosed patients younger than 18 years with histologically proven DIPG were treated with focal radiotherapy to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m 2 /day). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m 2 /day, days 1-5) was given every 28 days up to six cycles. Responses/progressions were assessed by clinical and 2-monthly MRI follow-up studies. Between September 2005 and September 2009, 21 patients with newly diagnosed histologically confirmed DIPG were eligible for this study. Median age at diagnosis was 6.4 years (range 4-16 years). At last update in August 2010, 17 children have died, 1 child was alive with progressive disease and 3 with stable disease. Metastatic relapse was documented in the cerebral site in two patients and in spinal cord in two cases. The median time to progression was 7.5 months (range 28 days-14.5 months) and the median survival was 11.7 months (range 26 days-17.5 months). The 1-year PFS and the 1-year OS were 33 and 50%, respectively. Five patients presented radiological findings compatible with pseudoprogression during the treatment. Haematological toxicity (Grade III/IV thrombocytopenia and leucopenia) was the most commonly found and led to dose reductions of TMZ in 58% of the patients. TMZ with radiation therapy has not yielded any significant improvement in outcome of children with DIPG and is associated with higher toxicity compared with radiotherapy alone. Novel treatment modalities are needed to improve the outcome of these patients.
Journal of Neuro-Oncology, 2011
We report herein our institutional experience in the treatment of diffuse intrinsic pontine gliom... more We report herein our institutional experience in the treatment of diffuse intrinsic pontine glioma (DIPG) with a hypofractionated external-beam radiotherapy schedule. Between April 1996 and January 2004, 22 patients (age 2.9-12.5 years) with newly diagnosed DIPG were treated by hypofractionated radiation therapy delivering a total dose of 45 Gy in daily fractions of 3 Gy, given over 3 weeks. No other treatment was applied concomitantly. Fourteen of the 22 patients received the prescribed dose of 45 Gy in 15 fractions of 3 Gy, and 2 patients received a total dose of 60 and 45 Gy with a combination of two different beams (photons and neutrons). In five cases the daily fraction was modified to 2 Gy due to intolerance, and one patient died due to serious intracranial hypertension after two fractions of 3 Gy and one of 2 Gy. Among 22 children, 14 patients showed clinical improvement, usually starting in the second week of treatment. No grade 3 or 4 acute toxicity from radiotherapy was observed. No treatment interruption was needed. In six patients, steroids could be discontinued within 1 month after the end of radiotherapy. Median time to progression and median overall survival were 5.7 months and 7.6 months, respectively. External radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting. It could represent a short-duration alternative to more protracted regimens.
Risks of Radiation Therapy in Patients With Neurofibromatosis
International Journal of Radiation Oncology*Biology*Physics, 2009
A Treatment Planning Comparison of Combined Photon–Proton Beams Versus Proton Beams–Only for the Treatment of Skull Base Tumors
International Journal of Radiation Oncology*Biology*Physics, 2007
To compare treatment planning between combined photon-proton planning (CP) and proton planning (P... more To compare treatment planning between combined photon-proton planning (CP) and proton planning (PP) for skull base tumors, so as to assess the potential limitations of CP for these tumors. Plans for 10 patients were computed for both CP and PP. Prescribed dose was 67 cobalt Gray equivalent (CGE) for PP; 45 Gy (photons) and 22 CGE (protons) for CP. Dose-volume histograms (DVHs) were calculated for gross target volume (GTV), clinical target volume (CTV), normal tissues (NT), and organs at risk (OARs) for each plan. Results were analyzed using DVH parameters, inhomogeneity coefficient (IC), and conformity index (CI). Mean doses delivered to the GTVs and CTVs with CP (65.0 and 61.7 CGE) and PP (65.3 and 62.2 Gy CGE) were not significantly different (p > 0.1 and p = 0.72). However, the dose inhomogeneity was drastically increased with CP, with a mean significant incremental IC value of 10.5% and CP of 6.8%, for both the GTV (p = 0.01) and CTV (p = 0.04), respectively. The CI(80%) values for the GTV and CTV were significantly higher with PP compared with CP. Compared with CP, the use of protons only led to a significant reduction of NT and OAR irradiation, in the intermediate-to-low dose (< or =80% isodose line) range. These results suggest that the use of CP results in levels of target dose conformation similar to those with PP. Use of PP significantly reduced the tumor dose inhomogeneity and the delivered intermediate-to-low dose to NT and OARs, leading us to conclude that this treatment is mainly appropriate for tumors in children.
Accelerated fractionation in esophageal cancers: A multivariate analysis on 88 patients
International Journal of Radiation Oncology*Biology*Physics, 1997
Accelerated fractionation was used to shorten overall treatment time to increase locoregional con... more Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.
Dramatic response to radiotherapy combined with vemurafenib. Is vemurafenib a radiosensitizer?
European journal of dermatology : EJD
Uploads
Papers by Frederic Dhermain