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Sylvette Hoffstetter

Bio: Sylvette Hoffstetter is an academic researcher. The author has contributed to research in topics: Brachytherapy & Epidermoid carcinoma. The author has an hindex of 28, co-authored 54 publications receiving 2072 citations.


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TL;DR: In this paper, a prospective study of 174 patients treated for medulloblastoma was conducted to correlate targeting deviation in external beam radiation therapy with site of relapse, and the authors found that minor deviations in therapy technique are slightly associated with an increased risk of relapse in the same range as the group with only one major deviation.
Abstract: Purpose: To correlate targeting deviation in external beam radiation therapy with site of relapse in a prospective study of 174 patients treated for medulloblastoma. Methods and Materials: Between February 1992 and February 1998 the radiotherapy treatment records were reviewed by a panel of radiation oncologists for 174 children treated with radiation therapy for medulloblastoma. The review was done without knowledge of patient outcome. Patterns of relapse were correlated with the results of the quality control review. Results: Among the 174 patients five relapsed before the start of radiotherapy. One hundred sixty-nine patients were evaluable for correlation between targeting deviation and site of relapse. Number of major deviations in radiation therapy treatment is strongly correlated with the risk of tumor relapse (67% [95% CI: 28–91] of 3-year relapse rate in patient group with 2 major deviations and 78% [95% CI: 35–96] with 3 major deviations). This is particularly correlated with relapse in the frontal region of the brain: 5 relapses occurred in the frontal region in patients with major deviation in this area. An erroneous choice of electron beam energy is also linked with craniospinal fluid (CSF) relapse (3-year relapse rate of 68% [95% CI: 42–86]). Minor deviations in therapy technique are slightly associated with an increased risk of relapse in the same range as the group with only one major deviation. Conclusion: The quality of medulloblastoma radiation therapy technique is strongly correlated with outcome. Pretreatment central quality assurance review or standardized computer-designed blocks would improve survival to an extent equivalent to that attributed to adjuvant chemotherapy.

134 citations

Journal ArticleDOI
TL;DR: Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF, similar to those observed in children.
Abstract: Purpose: To assess prognostic factors for adults with medulloblastoma in a multicenter, retrospective study Methods and Materials: Data were collected by file review or mail inquiry for 253 adults treated between 1975 to 2004 Radiologists or surgeons assessed disease characteristics, such as volume and extension Patients were classified as having either high- or standard-risk disease Prognostic factors were analyzed Results: Median patient age was 29 years Median follow-up was 7 years Radiotherapy was delivered in 246 patients and radiochemotherapy in 142 Seventy-four patients relapsed Respective 5- and 10-year overall survival rates were 72% and 55% Univariate analysis showed that survival significantly correlated with metastasis, postsurgical performance status, brainstem involvement, involvement of the floor of the fourth ventricle (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF) By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were negative prognostic factors In the standard-risk subgroup there was no overall survival difference between patients treated with axial doses of ≥34 Gy and patients treated with craniospinal doses Conclusion: We report the largest series of medulloblastoma in adults Prognostic factors were similar to those observed in children Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF The role of chemotherapy for this group is still unclear A randomized study should be performed to confirm these results, but because frequency is very low, such a study would be difficult

124 citations

Journal ArticleDOI
TL;DR: The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC.
Abstract: We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermiol cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC). Methods and Materials: From 1976 until 1994, 118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1–3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192 Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal resection (APR). The mean follow-up was 6 years. Results: At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for T1, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (≥4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3, 16 patients; and Grade 4, 1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for T1, 82% for T2, 58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control. Conclusion: The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case of obtain better tumor control, with as few sequele as possible, to yield a better rate of SC.

118 citations

Journal ArticleDOI
TL;DR: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children, and intellectual function seemed to be preserved, which is promising.
Abstract: Purpose: Between December 1998 and October 2001, patients Results: A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to >60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years. Conclusion: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

91 citations


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TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

1,545 citations

Journal ArticleDOI
TL;DR: Differences in cognitive development have been described most thoroughly among children treated for posterior-fossa tumours, specifically medulloblastomas and ependymomas, which account for about 30% of all newly diagnosed cases of brain tumours in children.
Abstract: As survival among children treated for cancer continues to improve, more attention is being focussed on the late effects of cancer treatment. In children treated for brain tumours, chronic neurocognitive effects are especially challenging. Deficits in cognitive development have been described most thoroughly among children treated for posterior-fossa tumours, specifically medulloblastomas and ependymomas, which account for about 30% of all newly diagnosed cases of brain tumours in children. Most children who have survived brain tumours have required surgical resection and focal or craniospinal radiotherapy (irradiation of the entire subarachnoid volume of the brain and spine), with or without systemic chemotherapy. Historically, intelligence quotient (IQ) scores have provided a benchmark against which to measure changes in cognitive development after treatment. Observed declines in IQ are most likely a result of failure to learn at a rate that is appropriate for the age of the child, rather than from a loss of previously acquired knowledge. The rate of IQ decline is associated with a several risk factors, including younger age at time of treatment, longer time since treatment, female sex, as well as clinical variables such as hydrocephalus, use of radiotherapy and radiotherapy dose, and the volume of the brain that received treatment. Loss of cerebral white matter and failure to develop white matter at a rate appropriate to the developmental stage of the child could partly account for changes in IQ score. Technical advances in radiotherapy hold promise for lowering the frequency of neurocognitive sequelae. Further efforts to limit neurocognitive sequelae have included design of clinical trials to test the effectiveness of cognitive, behavioural, and pharmacological interventions.

783 citations

Journal ArticleDOI
TL;DR: This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.

624 citations

Journal ArticleDOI
Marcel Kool1, David T.W. Jones1, Natalie Jäger1, Paul A. Northcott1, Trevor J. Pugh2, Volker Hovestadt1, Rosario M. Piro1, L. Adriana Esparza3, Shirley L. Markant3, Marc Remke, Till Milde4, Franck Bourdeaut5, Marina Ryzhova, Dominik Sturm1, Elke Pfaff1, Sebastian Stark1, Sonja Hutter1, Huriye Seker-Cin1, Pascal Johann1, Sebastian Bender1, Christin Schmidt1, Tobias Rausch6, David Shih, Jüri Reimand7, Laura Sieber1, Andrea Wittmann1, Linda Linke1, Hendrik Witt4, Hendrik Witt1, Ursula D. Weber1, Marc Zapatka1, Rainer König8, Rainer König1, Rameen Beroukhim2, Rameen Beroukhim9, Rameen Beroukhim10, Guillaume Bergthold2, Guillaume Bergthold10, Guillaume Bergthold11, Peter van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Sabine Schmidt1, Stephan Wolf1, Chris Lawerenz1, Cynthia C. Bartholomae1, Christof von Kalle1, Andreas Unterberg1, Christel Herold-Mende1, Silvia Hofer12, Andreas E. Kulozik4, Andreas von Deimling13, Andreas von Deimling1, Wolfram Scheurlen14, Jörg Felsberg15, Guido Reifenberger15, Martin Hasselblatt, John R. Crawford16, John R. Crawford14, Gerald A. Grant17, Nada Jabado18, Arie Perry19, Cynthia Cowdrey19, Sydney Croul, Gelareh Zadeh, Jan O. Korbel6, François Doz5, François Doz20, Olivier Delattre5, Gary D. Bader7, Martin G. McCabe21, V. Peter Collins22, Mark W. Kieran10, Yoon Jae Cho23, Scott L. Pomeroy14, Olaf Witt1, Benedikt Brors1, Michael D. Taylor, Ulrich Schüller24, Andrey Korshunov13, Andrey Korshunov1, Roland Eils1, Robert J. Wechsler-Reya3, Peter Lichter1, Stefan M. Pfister4, Stefan M. Pfister1 
TL;DR: Functional assays in different SHH-MB xenograft models demonstrated that SHh-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.

610 citations