Publications by authors named "Philippe Thiesse"

39 Publications

Isolated uveal melanoma metastases to the heart: take a look at chest X-ray!

Eur Heart J Cardiovasc Imaging 2017 12;18(12):1423

Cardiology Department, Institut Mutualiste Montsouris, 42 Bd Jourdan, 75014, Paris, France.

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http://dx.doi.org/10.1093/ehjci/jex196DOI Listing
December 2017

Loco-regional extensions of central nervous system germ cell tumors: a retrospective radiological analysis of 100 patients.

Neuroradiology 2018 Jan 23;60(1):27-34. Epub 2017 Sep 23.

Imaging Department, Institut Curie, 26 rue d'Ulm, 75005, Paris, France.

Purpose: The current staging system of central nervous system (CNS) germ cell tumors (GCT) includes a binary classification in "localized" or "metastatic" disease based on the absence or presence of leptomeningeal dissemination. Loco-regional tumor dissemination has been barely described whereas its accurate definition might be useful in terms of prognosis and treatment, especially for radiation therapy planning. Our purpose was therefore to describe MR patterns and prevalence of loco-regional extensions of these tumors.

Methods: One hundred consecutive patients (median age 16.3 years, range 7-41 years, sex ratio 7:1) with a histologically or biologically proven CNS GCT were retrospectively included. Brain and spinal MRI at diagnosis were reviewed by two neuroradiologists focusing on MR patterns of primaries and loco-regional extensions. When available, follow-up MR exams were analyzed.

Results: Pure germinoma represented 84/100 cases. Primaries were unifocal pineal (n = 49/100), bifocal pineal and supra-sellar (n = 27/100), isolated supra-sellar (n = 21/100), isolated basal ganglia (n = 2/100) or trifocal pineal, supra-sellar, and basal ganglia (n = 1/100). Metastatic disease occurred in 6/100 patients (depicted by MRI in two and CSF cytology in four). Loco-regional extensions were observed in all patients and classified as follows: third ventricle (n = 88/100), thalamus (n = 47/100), midbrain (n = 42/100), distant sub-ependymal areas (n = 19/100), optic pathways (n = 19/100), lateral ventricles (n = 7/100), cavernous sinus (n = 6/100), corpus callosum (n = 4/100), and fourth ventricle (n = 3/100).

Conclusion: CNS GCT present with specific loco-regional extensions at diagnosis. Improving their recognition will be helpful to further understand their prognostic value and potentially to optimize the treatment.
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http://dx.doi.org/10.1007/s00234-017-1928-6DOI Listing
January 2018

Visual complaints in intracranial germinomas.

Pediatr Blood Cancer 2017 Oct 24;64(10). Epub 2017 Apr 24.

Department of Radiotherapy, Institut d'Hématologie et d'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France.

Objective: Patients with brain tumors often report having visual complaints. This may be due to increased intracranial pressure, compression/invasion of the optic pathway or diplopia. We assessed the incidence and the etiology of visual symptoms in patients with intracranial germinoma tumors (ICGTs).

Methods And Materials: We performed a blinded retrospective review of the clinical charts and the initial magnetic resonance imaging (MRI) of 28 patients with ICGT. Thirteen tumors were pineal, five suprasellar, seven bifocal, and further three involved either the optic nerve, the corpus callosum, or the brainstem.

Results: Twelve patients reported visual disturbances, seven of whom mainly experienced a decrease in vision. Two of those were initially managed as "retrobulbar neuritis" when endocrinologic symptoms prompted assessment by MRI. Involvement of the optic pathway was underestimated, and both relapsed. Field deficits were definitive sequelae, whereas visual acuity was sometimes regressive in the absence of optic atrophy.

Conclusions: Compression or invasion of the optic pathway by germinomas is not a rare occurrence, and this possibility should not be overlooked when thickening or contrast enhancement is detected. Radiotherapy fields should be extended accordingly.
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http://dx.doi.org/10.1002/pbc.26543DOI Listing
October 2017

Survival impact of centralization and clinical guidelines for soft tissue sarcoma (A prospective and exhaustive population-based cohort).

PLoS One 2017 3;12(2):e0158406. Epub 2017 Feb 3.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France.

Purpose: The outcome of sarcoma has been suggested in retrospective and non-exhaustive studies to be better through management by a multidisciplinary team of experts and adherence to clinical practice guidelines (CPGs). The aim of this prospective and exhaustive population based study was to confirm the impact of adherence to CPGs on survival in patients with localized sarcoma.

Experimental Design: Between 2005 and 2007, all evaluable adult patients with a newly diagnosis of localized sarcoma located in Rhone Alpes region (n = 634), including 472 cases of soft-tissue sarcoma (STS), were enrolled. The prognostic impact of adherence to CPGs on progression-free survival (PFS) and overall survival (OS) was assessed by multivariate Cox model in this cohort.

Results: The median age was 61 years (range 16-92). The most common subtypes were liposarcoma (n = 133, 28%), unclassified sarcoma (n = 98, 20.7%) and leiomyosarcoma (n = 69, 14.6%). In the initial management phase, from diagnosis to adjuvant treatment, the adherence to CPGs for patients with localized STS was 36% overall, corresponding to 56%, 85%, 96% and 84% for initial surgery, radiation therapy, chemotherapy and follow-up, respectively. Adherence to CPGs for surgery was the strongest independent prognostic factor of PFS, along with age, gender, grade, and tumor size. For OS, multivariate analysis adherence to CPGs for surgery was a strong independent prognostic factor, with an important interaction with a management in the regional expert centers.

Conclusions: This study demonstrates impact of CPGs and treatment within an expert center on survival for STS patients in a whole population-based cohort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158406PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291382PMC
August 2017

Utility of post-therapy brain surveillance imaging in the detection of primary central nervous system lymphoma relapse.

Eur J Cancer 2017 02 22;72:12-19. Epub 2016 Dec 22.

Centre Léon Bérard, Department of Hematology, Université Claude Bernard Lyon 1, Lyon, France; Department of Hematology, Centre Hospitalier Lyon Sud, Université Claude Bernard Lyon 1, Pierre-Bénite, France. Electronic address:

Background: The optimal follow-up strategy for primary central nervous system lymphoma (PCNSL) patients after first-line therapy is unclear. The goal of this study is to determine the utility of planned brain surveillance imaging in the detection of relapse in a retrospective cohort of PCNSL patients.

Methods: Patients were consecutive PCNSL cases treated in Leon Berard Cancer Centre, Lyon, France, from 1985 to 2011. Histology was diffuse large B-cell lymphoma in 94%. Patients were treated by methotrexate (92%) and cytarabine (63%) based-chemotherapy followed by radiotherapy for 108 patients (51%). Clinical records were reviewed for details at relapse and relationship to planned imaging. The imaging follow-up strategy was performed according to each treating physicians.

Results: Among 209 PCNSL patients, 127 complete response patients entered in post-treatment observation and 63 (50%) subsequently relapsed. Among the 125 evaluable patients, the majority of relapses (N = 49, 80%) was asymptomatic and identified before the planned brain imaging. Surveillance imaging detected relapses before symptoms in 12 patients who entered in post-therapy observation (10%). The median number of brain imaging during the follow-up was 7 (0-13). A total of 819 MRI/CT-scan were performed leading to the detection of 12 asymptomatic relapses. The one year OS rates were 41% and 58% for symptomatic and non-symptomatic relapses, respectively (P = 0.21).

Conclusion: The majority of PCNSL relapses occurred outside planned follow-up with no difference in patient outcome between symptomatic and asymptomatic relapses. The role of brain imaging for the detection of relapses in the follow-up of PCNSL patients remains to be clarified.
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http://dx.doi.org/10.1016/j.ejca.2016.10.036DOI Listing
February 2017

Percutaneous guided biopsy for diagnosing suspected primary malignant bone tumors in pediatric patients: a safe, accurate, and cost-saving procedure.

Pediatr Radiol 2017 Feb 10;47(2):235-244. Epub 2016 Dec 10.

Institut d'Hématologie et d'Oncologie Pédiatriques (IHOPe), 1, place du Pr. Joseph Renault, 69008, Lyon, France.

Background: Percutaneous biopsy is the reference diagnostic procedure for adult musculoskeletal tumors. Its place in pediatrics is controversial and open biopsy remains recommended.

Objective: To assess diagnostic performance and feasibility of percutaneous biopsy performed on children and young adults for suspected malignant bone tumors.

Materials And Methods: We conducted a 5-year retrospective study including patients ≤21 years who underwent a bone biopsy for a suspected malignant bone tumor. We assessed diagnostic yield (percentage of analyzable biopsies), accuracy (percentage of accurate diagnoses among all analyzable biopsies) and efficacy (percentage of accurate diagnoses among all biopsies), costs, anesthetic requirements and sample availability for biomedical research. Patients diagnosed with an open biopsy were used to compare diagnostic performances, anesthetic requirements and costs.

Results: We included 90 percutaneous and 27 open biopsies in 117 patients. For percutaneous biopsy, diagnostic yield was 95.5% (95% confidence interval [CI] 88.8-98.7%), accuracy was 96.2% (95% CI 86.8-99.5%) and efficacy was 89.3% (95% CI 78.1-96.0%). There was no statistical difference with open biopsy (Fisher exact test, P > 0.05). Mean costs were reduced with percutaneous biopsy: €1,937 (standard deviation [SD] €2,408) versus €6,362 (SD €5,033; Mann-Whitney, P < 0.0001). Thirty-two of the 48 (67%) patients included in clinical trials and diagnosed with percutaneous biopsy had suitable samples for ancillary analyses.

Conclusion: Percutaneous biopsy is a valid alternative to open biopsy for diagnosing pediatric and young adult primary malignant bone tumors.
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http://dx.doi.org/10.1007/s00247-016-3735-3DOI Listing
February 2017

Spinal bone marrow necrosis after retroperitoneal lymph node dissection.

Spine J 2016 Aug 27;16(8):e509-10. Epub 2016 Jan 27.

Department of Radiology, Centre Léon Bérard, 28 rue Laennec, Lyon 69008, France.

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http://dx.doi.org/10.1016/j.spinee.2016.01.184DOI Listing
August 2016

Diagnostic Accuracy of PET/CT-Guided Percutaneous Biopsies for Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1 Patients.

PLoS One 2015 7;10(10):e0138386. Epub 2015 Oct 7.

Centre Léon Bérard, Lyon, France.

Background: Malignant peripheral nerve sheath tumors (MPNST) are one of the most frequent causes of death in patients with neurofibromatosis type 1 (NF1). Early detection is crucial because complete surgical resection is the only curative treatment. It has been previously reported that an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) image with a T/L (Tumor/Liver) SUV max ratio > 1.5 provides a high negative predictive value; however, it is not specific enough to make a NF1-related MPNST diagnosis. A formal proof of malignant transformation from a histological analysis is necessary before surgical excision because the procedure can cause mutilation. The objective of the present work was to investigate the effectiveness of and complications associated with PET/CT-guided percutaneous biopsies for an NF1-related MPNST diagnosis.

Methods: PET/CT-guided percutaneous biopsy procedures performed on 26 NF1 patients with a clinical suspicion of MPNST and a suspect lesion from a PET/CT scan (T/L SUV max ratio > 1.5) were retrospectively evaluated. The localization of the suspected malignant site was determined using PET/CT. A stereotactic (ultrasonic and CT control) core biopsy technique was used with a local anesthesia.

Results: The first PET/CT-guided percutaneous biopsies enabled a pathological diagnosis for all of the patients (no "inconclusive " results were obtained), and no secondary procedures were needed. Among the 26 patients, the histopathological results from the biopsy were malignant in 17 cases and benign (BPNST with atypical cells) in nine cases. No complications from the diagnostic procedure were observed. A surgical resection was performed in 18 patients (seven benign and 11 malignant biopsies), removing the fine needle biopsy scar. In addition, six locally advanced/metastatic MPNST were treated with chemo/radiotherapy, and two BPNST had no progression after a follow-up of 14 and 39 months, respectively. The PET/CT-guided percutaneous biopsy gave 25 accurate diagnoses and one false negative (BPNST with atypical cells on the biopsy and MPNST on the operated tumor), resulting in a diagnostic accuracy rate of 96%. This false negative case may be explained by the high heterogeneity of the tumor: benign areas were contiguous with the malignant ones and associated with inflammation.

Conclusions: PET/CT-guided percutaneous biopsies are an effective and relatively non-traumatic procedure for diagnosis of NF1-related MPNST. It is the most reliable approach for early detection of MPNST.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138386PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596851PMC
June 2016

[To answer rare cancer issues. Geographical analysis of EMS sarcoma cohort in the Rhône-Alpes region].

Bull Cancer 2014 Feb;101(2):127-36

Centre Léon-Bérard Lyon, EA « Santé Individu Société », 28, rue Laënnec, 69008 Lyon, France.

Rare cancer issues have not been much explored yet because of their low incidence. That is why epidemiological studies have difficulties in identifying indisputable etiological risk factors. An expert opinion, mainly concentrated in some establishments, is required for these cancers' management. However, on account of the potential remoteness of these therapeutic resources, the patients' way of care remains also unstudied. By means of a geographical analysis of a regional exhaustive cohort of sarcoma, diagnosed in 2006 and 2007 and followed during five years at least, we can make progress on these different issues. Gastro-Intestinal and Stromal Tumors (GIST) occur more frequently in privileged territories while liposarcomas arise in more deprived areas. The association between liposarcomas and areas deprivation is significant (P=0.05). Moreover, pre-operative biopsy and some clinical patient characteristics, age, grade or tumor localization, are associated with an increase in the distance covered by patients for the first-line treatment (p ≤ 0,001). In the scope of an interdisciplinary collaboration, the geographical approach develops some hypothesis for rare cancers research, which must be tested by other larger scale studies.
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http://dx.doi.org/10.1684/bdc.2014.1891DOI Listing
February 2014

Territorial inequalities in management and conformity to clinical guidelines for sarcoma patients: an exhaustive population-based cohort analysis in the Rhône-Alpes region.

Int J Clin Oncol 2014 Aug 10;19(4):744-52. Epub 2013 Aug 10.

Centre Léon Bérard, 28 Rue Laennec, 69008, Lyon, France,

Background: Sarcomas are rare cancers with great variability in clinical and histopathological presentation. The main objective of clinical practice guidelines (CPGs) is to standardize diagnosis and treatment.

Methods: From March 2005 to February 2007, all patients diagnosed with localized sarcoma in the Rhône-Alpes region were included in a cohort-based study, to evaluate the compliance of sarcoma management with French guidelines in routine practice and to identify predictive factors for compliance with CGPs.

Results: 634 (71 %) patients with localized sarcoma satisfying the inclusion criteria were included out of 891 newly diagnosed sarcomas. Taking into account initial diagnosis until follow-up, overall conformity to CPGs was only 40 % [95 % confidence interval (CI) = 36-44], ranging from 54 % for gastrointestinal stromal tumor to 36 % for soft tissue sarcoma and 42 % for bone sarcoma. In multivariate analysis, primary tumor type [relative risk (RR) = 4.42, 95 % CI = 2.79-6.99, p < 0.001], dedicated multidisciplinary staff before surgery (RR = 4.19, 95 % CI = 2.39-7.35, p < 0.001) and management in specialized hospitals (RR = 3.71, 95 % CI = 2.43-5.66, p < 0.001) were identified as unique independent risk factors for conformity to CPGs for overall treatment sequence.

Conclusions: With only 40 % of total conformity to CPGs, the conclusions support the improvement of initial sarcoma management and its performance in specialized centres or within specialized dedicated networks.
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http://dx.doi.org/10.1007/s10147-013-0601-2DOI Listing
August 2014

Pazopanib for the treatment of soft-tissue sarcoma.

Clin Pharmacol 2012 26;4:65-70. Epub 2012 Oct 26.

Department of Medical Oncology, Leon Berard Center, Lyon, France.

Pazopanib is a multikinase inhibitor which potently inhibits the activity of major receptor tyrosine kinases, including vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, platelet-derived growth factor receptor-a, platelet-derived growth factor receptor-a, and c-Kit. Approved by the Food and Drug Administration in 2009 in the United States for the treatment of metastatic renal cell carcinoma, pazopanib has been tested in advanced or metastatic soft-tissue sarcoma. Unlike other tyrosine kinase inhibitors, a statistically significant efficacy in phase II but also in randomized phase III studies has been shown. In comparison with sunitinib or sorafenib, pazopanib has a similar toxicity profile and is generally well tolerated. This review details the development of this new therapeutic class in the treatment of metastatic soft-tissue sarcomas.
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http://dx.doi.org/10.2147/CPAA.S33195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508654PMC
December 2012

Percutaneous cytologic diagnosis of solid pseudopapillary tumors of pancreas in children.

J Pediatr Hematol Oncol 2013 Mar;35(2):90-2

Centre Leon Berard, Lyon, France.

Solid pseudopapillary tumors of the pancreas, formerly known as Frantz tumors, are rare exocrine tumors that electively affect young women in their second and third decades of life, and are rarely observed in children. Histologic confirmation is nevertheless desirable before proceeding with treatment of pancreatic lesions, as appropriate treatment can range from conservative to ablative surgery. Here, we report 3 cases of solid pseudopapillary tumors of the pancreas and we postulate that percutaneous cytologic sample analysis (instead of biopsy) may be sufficient to reach an accurate diagnosis and eliminate differential diagnosis.
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http://dx.doi.org/10.1097/MPH.0b013e318276b270DOI Listing
March 2013

Parosteal osteosarcoma mimicking osteochondroma: A radio-histologic approach on two cases.

Clin Sarcoma Res 2011 Jul 25;1(1). Epub 2011 Jul 25.

Background: Parosteal osteosarcoma is a well-differentiated variant of osteosarcoma that affects the surface of the bone. The imaging pattern is very typical. We report two cases mimicking an osteochondroma, radiologically and histologically and propose an explanation.

Methods: The review of 86 parosteal osteosarcomas of bone revealed this atypical pattern only once. A consultation case was received in the same time, and added to ours. Patients were 28 years old and 56 years old females. Imaging studies included two radiographs, two CTscans, one MRI examination and one bone scan and the results were compared to histology.

Results: On imaging, both lesions presented as ossified lobulated masses attached with a broad base to the underlying cortex. No radiolucent cleft separated the masses and the host bone and cortex continuity between the mass and the femur was seen, with medullary communication. The marrow of the mass had a different density and intensity compared to normal marrow. So, there were features of an osteochondroma (cortex and medullary continuity) and of a parosteal osteosarcoma (ossified marrow). Pathological assessment on the final specimen confirmed the presence of low-grade parosteal osteosarcomas, after an erroneous diagnosis of osteochondroma on the initial biopsy.

Conclusions: Parosteal osteosarcoma can be rarely confused with osteochondroma. A radiologic-pathologic correlation is essential. Cortex continuity is the most misleading imaging feature that may occur in parosteal osteosarcomas. A knowledge of this misleading pattern will help diagnose the lesion from the beginning.
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http://dx.doi.org/10.1186/2045-3329-1-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372285PMC
July 2011

Multidisciplinarity and medical decision, impact for patients with cancer: sociological assessment of two tumour committees' organization.

Bull Cancer 2012 Apr;99(4):E34-42

Centre Leon-Bérard, Lyon, France.

Purpose: Medical practices in oncology are expected to be multidisciplinary, yet few articles studied how this may be concretely applied. In the present study, we evaluated the organization of two multidisciplinary committees, one for breast cancer and one for sarcoma, in a French Comprehensive Cancer Centre.

Methods: Both tumours were specifically chosen so as to emphasise substantial differences in relation with incidence, histological subtypes, management strategy, and scientific evidence. Between 2003 and 2004, 404 decision processes were observed, 210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number of physicians who took part in the discussions and their medical specialties were systematically noted as well as the number of contradictory discussions, medical specialties represented in these contradictory discussions and the topics of contradiction. The last measured data was whether the final committee's decision was in conformity with the referent preferences or not. All these measures were related to the referent's medical speciality and working place, to the stage of the disease and to the disease management stage.

Results: Committees' specificities concerned their organization, referent's medical specialties, the number of participants in discussions and their medical specialties. Discussions in the sarcoma committee tended to be more multidisciplinary, involving more specialties. Initial strategy proposal for one patient was modified during the discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%) respectively for sarcoma and breast cancer. However, there was no significant difference in the rate of contradictory discussions between breast cancer and sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of contradictory discussions were similar for localized cancers, local relapse and metastasis disease (37%, 41% and 34% respectively; P = 0.86).

Conclusions: The present study reports more than 30% of changes concerning strategy for patient with cancer due to multidisciplinary discussions. This indicates that, providing tumour committees are adapted to the pathologies' characteristics, they can promote a collective and multidisciplinary approach to oncology.
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http://dx.doi.org/10.1684/bdc.2012.1559DOI Listing
April 2012

Clinicians' adherence versus non adherence to practice guidelines in the management of patients with sarcoma: a cost-effectiveness assessment in two European regions.

BMC Health Serv Res 2012 Mar 28;12:82. Epub 2012 Mar 28.

University of Lyon, F-69007 Lyon, France.

Background: Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not.

Methods: Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhône-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros (€) at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method.

Results: A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%.

Conclusions: Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma.
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http://dx.doi.org/10.1186/1472-6963-12-82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382421PMC
March 2012

Streptococcus pneumoniae retroperitoneal and pelvic abscess.

Lancet Infect Dis 2011 Sep;11(9):720

Department of Oncology and Hematology, Hôpital Pierre Oudot, Bourgoin-Jallieu, France. fl

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http://dx.doi.org/10.1016/S1473-3099(10)70254-1DOI Listing
September 2011

Additional Benefit of F-18 FDG PET/CT in the staging and follow-up of pediatric rhabdomyosarcoma.

Clin Nucl Med 2011 Aug;36(8):672-7

Service de Médecine Nucléaire, Centre Léon-Bérard, Université de Lyon, Lyon, France.

Purpose: The therapeutic management of rhabdomyosarcoma (RMS) is strongly dependent on initial staging. This study aimed to evaluate F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) as an adjunct to conventional imaging (CI) in the staging and follow-up of pediatric RMS.

Materials And Methods: A total of 13 consecutive children and adolescents (12 males, 1 female; mean age, 9.6 years) with histologically proven RMS (10 alveolar, 3 embryonal), in whom FDG PET/CT was performed at staging and follow-up, were retrospectively included. In total, 35 FDG PET/CT were compared with CI (MRI, CT, and bone scintigraphy) performed with a less than a 15-day interval. Histologic data, follow-up (mean, 27 months), and the final judgment of a multidisciplinary tumor board were considered as the standard of reference for result interpretation.

Results: At staging, FDG PET/CT revealed 1 RMS of the prostate missed by CI, and found 19 true-positive lymph node territories in 4 patients and 11 bone metastases in 3 patients, versus 12 and 3, respectively, with CI. Conversely, FDG PET/CT was less sensitive for detecting infracentimetric lung nodules in 1 patient. On the whole analysis, FDG PET/CT modified lymph node staging in 4 of 13 patients, bone involvement in 2 patients, and led to treatment alteration in 2 children.

Conclusions: FDG PET/CT can be useful in staging and restaging pediatric RMS, especially for assessing lymph nodes and bone involvement, and for detecting unknown primary sites of RMS, with potential therapeutic strategy alteration.
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http://dx.doi.org/10.1097/RLU.0b013e318217ae2eDOI Listing
August 2011

Use of F-18 FDG PET/CT in non-Hodgkin lymphoma with central nervous system involvement.

Clin Nucl Med 2011 Jun;36(6):e45-9

Département de Médecine Nucléaire, Centre Léon-Bérard, Université de Lyon, Lyon, France.

Central nervous system (CNS) is a rare site of involvement by non-Hodgkin lymphoma (NHL). Therapeutic approach for primary and secondary CNS NHL is different and remains challenging. Therefore imaging data are essential at staging to discriminate these 2 clinical entities and during follow-up to assess therapy response. The adjunct role of positron emission tomography using F-18 fluorodeoxyglucose to morphologic imaging is still undefined. We report 2 didactic cases of primary and secondary CNS NHL assessed by F-18 fluorodeoxyglucose positron emission tomography. Metabolic imaging seems to be complementary to conventional imaging techniques for the extent-of-disease evaluation and therapy monitoring of CNS lesions.
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http://dx.doi.org/10.1097/RLU.0b013e31821739e3DOI Listing
June 2011

Correlation between pre- or postoperative MRI findings and cerebellar sequelae in patients with medulloblastomas.

Pediatr Blood Cancer 2010 Dec;55(7):1310-6

Pediatric Neurosurgical Department, Neurological and Neurosurgical Pierre Wertheimer Hospital, Lyon, France.

Introduction: Immediate and delayed cerebellar dysfunction may be expected after surgical resection of a medulloblastoma. We investigated whether pre-operative and delayed post-operative MRI may correlate with such sequelae.

Material And Methods: The data of 31 patients in continuous complete remission after removal of medulloblastoma, irradiation and chemotherapy, were retrospectively reviewed. Magnetic Resonance Imaging (MRI) was analyzed for the following items: preoperative MRI (ratio of the surface of the tumor/posterior fossa, presence of ventricular dilatation or tonsilar hernia, involvement of the dentate nucleus) and delayed post-operative MRI (amount of cerebellar parenchyma removed, degree of cerebellar atrophy, presence of T1 hypointense regions in remaining cerebellar area and removal of region containing dentate nucleus). These data were correlated with immediate and long-term cerebellar syndrome and daily life repercussions.

Results: On preoperative MRI, the ratio of the surface of the tumor/posterior fossa and the presence of tonsilar hernia were significantly correlated with long-term sequelae on speech (respectively P = 0.027 and P = 0.05). Initial supratentorial ventricular dilatation was correlated with ability to sustain adequately daily tasks (P = 0.002). On delayed MRI, cerebellar atrophy was inversely correlated with ability to sustain daily tasks (P = 0.002). Hypointense T1 territory in remaining cerebellar parenchyma significantly correlated with immediate post-operative cerebellar syndrome (P = 0.01) and showed a tendency for post-operative mutism (P = 0.087) but was not correlated with any long-term sequelae.

Conclusion: Increased cranial pressure on initial MRI and cerebellar atrophy detected on subsequent MRI studies correlated with immediate and long-term cerebellar sequelae.
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http://dx.doi.org/10.1002/pbc.22802DOI Listing
December 2010

Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience.

Neuro Oncol 2010 Dec 17;12(12):1318-25. Epub 2010 Aug 17.

Department of Radiotherapy, Institut Curie, Paris, France.

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.
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http://dx.doi.org/10.1093/neuonc/noq093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018943PMC
December 2010

Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution.

Anticancer Drugs 2010 Jan;21(1):113-9

Department of Medicine, Unité INSERM, Centre Léon Bérard, Lyon, France.

Trabectedin was recently approved for patients failing doxorubicin, the standard treatment for advanced/metastatic sarcoma. This retrospective study aimed to compare trabectedin efficacy between compassionate use in unselected patients and clinical trials. From May 1999 to January 2006, 92 patients were treated at the Centre Léon Bérard, either in phase II studies or on a named patient compassionate basis. All cases were retrospectively analyzed to assess trabectedin efficacy in terms of response, progression-free, and overall survival.The objective response rate was 10% (N=9): 4% (N=2) for patients treated in compassionate use program and 16% (N=7) for those in clinical trials (P=0.18); 26 (28%) patients had stable disease for at least 6 months, 11 (23%) in the compassionate group and 15 (33%) in clinical trials. Median progression-free and overall survivals were, respectively, 2.2 [95% confidence interval (CI): 1.9-3.6] and 8.9 (95% CI: 6.4-14.2) months for all patients, 2.3 (95% CI: 1.9-4.3) and 10.4 (95% CI: 6.9-24.2) months for patients in clinical trials and 1.8 (95% CI: 1.4-3.4) and 6.4 (95% CI: 3.3-14.2) months for patients under compassionate treatment. In this retrospective analysis, the reported grade 3-4 toxicities were increased transaminase (34 patients, 37%) and neutropenia (38 patients; 42%). Higher efficacy was observed in phase II studies than with compassionate treatment, but no significant difference remained after adjustment in multivariate analysis for performance status, a well-established prognosis factor. The safety and tolerability of trabectedin shown in clinical trials is confirmed for patients in real-life situation treated in compassionate use programs, but its benefit is higher for patients with performance status 0-1.
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http://dx.doi.org/10.1097/CAD.0b013e328333057bDOI Listing
January 2010

Is surgical biopsy mandatory in case of atypical ductal hyperplasia on 11-gauge core needle biopsy? A retrospective study of 300 patients.

Am J Surg 2008 Sep 30;196(3):339-45. Epub 2008 Jun 30.

Department of Pathology, Leon Berard Centre, 28 rue Laennec, 69373 Lyon Cedex 08, France.

Background: Atypical ductal hyperplasia (ADH) is diagnosed in 4% to 10% of directional vacuum-assisted stereotactic biopsies (DVABs) performed for microcalcifications. Since the underestimation rate varies from 7% to 36%, surgical excision is still recommended, although some authors have tried to identify a subset of patients who can be spared surgery.

Methods And Results: In this study, we analyzed a retrospective series of 300 patients with ADH on 11-gauge DVAB. The only 4 events that occurred (3%) in 135 of 184 patients (61%) who were followed may not be due to underestimation. Comparing the diagnoses on DVAB and surgical excisions for 116 patients (39%), we identified 3 subsets of patients: no underestimation (size <6 mm and complete removal), low rate of 4% (< or =2 foci ADH in microcalcifications either <6 mm with incomplete removal or > or =6 mm and <21 mm), and high rate of 36% to 38% (>2 foci ADH in microcalcifications either <6 mm with incomplete removal or > or =6 mm and <21 mm, lesion size > or =21 mm).

Conclusions: Our results suggest that strict follow-up can be a safe option for the first 2 groups of patients, but that surgical excision is mandatory for patients from the third group.
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http://dx.doi.org/10.1016/j.amjsurg.2007.07.038DOI Listing
September 2008

Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial.

Neuro Oncol 2008 Aug 24;10(4):599-607. Epub 2008 Jun 24.

Pediatric Department, Centre Léon Bérard, Lyon, France.

Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of frontline chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosoureacisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10-23 months, vs. 9 months, 95% CI, 8-10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents.
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http://dx.doi.org/10.1215/15228517-2008-029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666234PMC
August 2008

Revisiting the role of doxorubicin in the treatment of rhabdomyosarcoma: an up-front window study in newly diagnosed children with high-risk metastatic disease.

Eur J Cancer 2008 Feb 22;44(3):427-31. Epub 2008 Jan 22.

Centre Léon Bérard, Paediatric Oncology Unit, 28 Rue Laennec, 69373 Lyon Cedex 08, France.

Purpose: Many cooperative groups have reported on the chemo-sensitivity of rhabdomyosarcoma (RMS). Doxorubicin has been tested but remains a controversial treatment option. We report here the results of the up-front evaluation of the efficacy of doxorubicin in children and adolescents with high-risk metastatic RMS.

Patients And Methods: Patients younger than 18 years of age (>6 months) with newly diagnosed, histologically confirmed high-risk metastatic RMS were required to have measurable disease, to have undergone no prior chemotherapy or radiation therapy and to have normal liver, renal and cardiac function before treatment. Doxorubicin was administered intravenously over 48h to a total dose of 60mg/m2. Two courses were given separated by a 21day interval. Response to therapy was assessed by diagnostic imaging after the second course. The study was designed as a two-stage procedure according to the multistep plan described by Fleming.

Results: Twenty patients were eligible for analysis. Median age at diagnosis was 9.8 years (range from 2 to 16). Thirteen of the 20 patients treated in the first step responded to treatment, corresponding to an overall response to doxorubicin of 65% [95% confidence interval (CI), 44-85%]. The rates of CR and PR were 5% [95% CI, 0-14%] and 60% [95% CI, 39-81%], respectively. Four (20%) patients had progressive disease, corresponding to a progression rate of 20% [95% CI, 2-38%].

Conclusion: This window study provides the definitive demonstration of the efficacy of doxorubicin in untreated RMS. Given the inconclusive results obtained from previous studies using differing schedules chemotherapy incorporating doxorubicin, the next step should be a randomised study testing dose intensity in high-risk localised RMS. This issue is being addressed in a current European study (EpSSG RMS 2005).
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http://dx.doi.org/10.1016/j.ejca.2007.12.007DOI Listing
February 2008

Primary desmoplastic small round cell tumor of the kidney: a case report in a 14-year-old girl with molecular confirmation.

Pediatr Dev Pathol 2007 Jul-Aug;10(4):320-4

Service d'Anatomie Pathologique, Hôpital Edouard Herriot, Lyon, France.

We report a case of desmoplastic small round cell tumor (DSRCT) arising in the kidney of a 14-year-old female. The subject presented with gross hematuria. Medical imaging uncovered a left renal mass without regional or metastatic extension. The tumor showed morphological, immunohistochemical, and molecular features of DSRCT. Immunostaining revealed polyphenotypic differentiation. Molecular analysis detected the fusion transcript resulting from the t(11;22)(p13;q12) reciprocal translocation, which characterized this neoplasm. Desmoplastic small round cell tumor is a rare, aggressive neoplasm that mainly affects young males and that usually presents with widespread abdominal serosal involvement. This unusual localization should lead one to consider this tumor in the differential diagnosis of small blue round cell tumors of the kidney.
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http://dx.doi.org/10.2350/06-10-0177.1DOI Listing
September 2007

[Measurement of tumour response to cancer treatment: morphologic imaging role].

Bull Cancer 2007 Feb;94(2):171-7

Département d'imagerie, Institut Curie, 26, rue d'Ulm, 75005 Paris.

New forms of cancer chemotherapy are tested in therapeutic trials (phase I, phase II or phase III) while chemotherapeutic agents whose efficacy has already been demonstrated are used, in routine clinical practice, in the context of protocols. The overall survival rate is the best objective parameter of efficacy of the treatments tested, but this parameter is obtained too late, as the effect on the tumour must be determined as soon as possible in order to institute another treatment if necessary. Tumour response, or objective response, is based on changes in the number and size of measurable primary or secondary tumour "targets". These parameters are obtained more rapidly than survival data, but their reliability is highly dependent on the quality of comparative clinical and especially radiological measurements of tumour targets. Medical imaging plays an essential role in these assessments. The absence of standardized techniques, poor selection of targets and inaccurate measurements can bias the results, particularly those of therapeutic trials. In view of the economic, scientific and patient-related stakes involved, a very rigorous approach is essential, directly implicating the responsibility of radiologists performing assessment examinations. The World Health Organization (WHO) guidelines defining the method of measurement of solid tumours and response criteria are no longer adapted to technical progress in imaging. Recently these guidelines have been updated and a new set of criteria has been proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Group, taking into account progress in imaging. They remain based on measurement of the size of the target lesion. The use of this single criterion of size to evaluate response to treatment needs to be discussed in the light of new technologies able to provide information on tumour composition, metabolism or neovascularization, modifications of which reflect response to treatment before a reduction in tumour volume can be detected.
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February 2007

Osteosarcoma metastatic to the kidney and iatrogenic hemorrhage.

Pediatr Blood Cancer 2008 Mar;50(3):690-2

Department of Pediatrics, Centre Léon Bérard, Lyon Cedex, France.

A 16-year old female presented painful masses in the lumbar region 5 years after the initial diagnosis of a localized osteosarcoma of the tibia. Abdominal X-ray revealed calcified masses. A bone scan confirmed an increased uptake in the renal areas. An ultrasound-guided fine needle biopsy confirmed the diagnosis of metastases. The procedure was complicated by subcapsular hemorrhage and gross hematuria. Renal metastases from osteosarcoma are usually asymptomatic and invisible on abdominal X-rays. The diagnosis is generally established by radionuclide bone scan or abdominal CT-scan. Our observation suggests that histological documentation of these unusual clinical presentations should be carefully weighed against the risk of the procedure.
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http://dx.doi.org/10.1002/pbc.21117DOI Listing
March 2008

Active breathing control for Hodgkin's disease in childhood and adolescence: feasibility, advantages, and limits.

Int J Radiat Oncol Biol Phys 2007 Apr 8;67(5):1470-5. Epub 2007 Jan 8.

Department of Radiotherapy, Centre Léon Bérard, Lyon, France.

Purpose: The challenge in early Hodgkin's disease (HD) in children is to maintain good survival rates while sparing organs at risk. This study assesses the feasibility of active breathing control (ABC) in children, and compares normal tissue irradiation with and without ABC.

Methods And Materials: Between May 2003 and June 2004, seven children with HD with mediastinal involvement, median age 15, were treated by chemotherapy and involved-field radiation therapy. A free-breathing computed tomography simulation scan and one additional scan during deep inspiration using ABC were performed. A comparison between planning treatment with clinical target volume including supraclavicular regions, mediastinum, and hila was performed, both in free breathing and using ABC.

Results: For a prescription of 36 Gy, pulmonary dose-volume histograms revealed a mean reduction in lung volume irradiated at more than 20 Gy (V20) and 30 Gy (V30) of 25% and 26%, respectively, using ABC (p = 0.016). The mean volume of heart irradiated at 30 Gy or more decreased from 15% to 12% (nonsignificant). The mean dose delivered to breasts in girls was small in both situations (less than 2 Gy) and stable with or without ABC. Considering axillary irradiation, the mean dose delivered to breasts remained low (<9 Gy), without significant difference using ABC or not. The mean radiation dose delivered to thyroid was stable using ABC or not.

Conclusions: Using ABC is feasible in childhood. The use of ABC decreases normal lung tissue irradiation. Concerning heart irradiation, a minimal gain is also shown. No significant change has been demonstrated concerning breast and thyroid irradiation.
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http://dx.doi.org/10.1016/j.ijrobp.2006.11.008DOI Listing
April 2007

ET-743: a novel agent with activity in soft-tissue sarcomas.

Curr Opin Oncol 2006 Jul;18(4):347-53

Hôpital Edouard Herriot, Service d'oncologie médicale, France.

Purpose Of Review: ET-743 (ecteinascidin-743, trabectedin, Yondelis) is a natural marine product that has shown clinical activity in sarcoma. This paper reviews the current knowledge on this compound.

Recent Findings: ET-743 interferes with several transcription factors, traps protein from the nucleotide-excision repair system, thus resulting in DNA damage, modulates gene expression, and blocks cells in the G2-M phase. In the clinical setting, after failure of standard treatment, ET-743 at 1.5 mg/m2 in 24 h continuous infusion every 21 days yielded an overall response rate close to 8% and stabilization rates of 30-40%, some lasting beyond 3 years. Leiomyosarcomas, liposarcomas, and synovial sarcomas may be the more sensitive histotypes. The major toxicities of ET-743 are hepatic--through biliary duct destruction--and hematologic. They are not cumulative and a significant number of patients may receive 12 courses or more. In a randomized Phase II study testing weekly ET-743 with treatment every 3 weeks, an improved progression-free survival rate was observed in the 3-weekly arm; the results of the follow-up Phase III trial should be available at the American Society of Clinical Oncology meeting of 2006. Phase I combination studies are in currently progress.

Summary: ET-743 is a novel active drug for sarcoma which yields prolonged disease-free survival in subsets of patients.
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http://dx.doi.org/10.1097/01.cco.0000228740.70379.3fDOI Listing
July 2006

[News of the year 2005 in sarcomas].

Bull Cancer 2006 Jan;93(1):83-9

Hôpital Edouard-Herriot, Service d'oncologie médicale, Pavillon E, 5 place d'Arsonval, 69003 Lyon.

This year, the innovations were numerous in sarcomas. Important progress were accomplished in the search for predictive factors which make it possible to propose to the patient a personalized treatment with the therapeutic ones reduced in the event of good prognosis or on the contrary aggressive steps in the event of bad prognosis. These prognostic factors can be genetic or clinical. Progress were also accomplished in the clinical field with the research of the most adapted therapeutic strategies and of advanced in various drugs of chemotherapy in particular the ET-743. Lastly, research is active and of many ways are tested into preclinic with a detailed attention on the way of the angiogenesis.
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January 2006