Publications by authors named "Olivier Collard"

45 Publications

Effectiveness of a nurse-led telephone follow-up in the therapeutic management of patients receiving oral antineoplastic agents: a randomized, multicenter controlled trial (ETICCO study).

Support Care Cancer 2021 Jan 7. Epub 2021 Jan 7.

Medical Oncology Department, Lucien Neuwirth Cancer Institute, 108 bis Avenue Albert Raimond, 42270, Saint Priest en Jarez, France.

Purpose: The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life.

Methods: A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018.

Results: Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC à 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point.

Conclusions: In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD.

Trial Registration: Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.
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http://dx.doi.org/10.1007/s00520-020-05955-3DOI Listing
January 2021

Vaccination and Immune Checkpoint Inhibitors: Does Vaccination Increase the Risk of Immune-related Adverse Events? A Systematic Review of Literature.

Am J Clin Oncol 2021 Mar;44(3):109-113

Medical Oncology Department.

Introduction: Immune checkpoint inhibitors (ICIs) have become part of cancer treatments. Their main side effects are immune-related adverse events (irAEs). So far, there has been no recommendation regarding routine vaccinations during ICIs treatment. Clinicians are aware of the risk of irAEs increases in this specific situation. The aim of this review of literature is to summarize the main studies about vaccination and ICIs interactions.

Methods: A systematic assessment of literature articles was performed by searching in PubMed (MEDLINE), and major oncology meeting following PRISMA guidelines.

Results: This review highlights the lack of literature. Indeed, most of the studies published were about influenza vaccination. Vaccination for patients under ICIs causes a humoral response and seems to be associated with an increase rate of seroconversion. Interestingly vaccination may provoke irAEs in ICIs-treated patients. So far, inactivated vaccines have not been contraindicated during ICI treatment.

Conclusion: Larger prospective studies are needed in order to define a consensus on the use of vaccines under immunotherapy.
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http://dx.doi.org/10.1097/COC.0000000000000788DOI Listing
March 2021

Dose-intensive regimen treatment for small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT).

Gynecol Oncol 2020 Oct 25;159(1):129-135. Epub 2020 Jul 25.

Gynecology Unit, Institut Gustave-Roussy, 114 rue Édouard-Vaillant, 94800 Villejuif, France. Electronic address:

Purpose: Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort.

Methods: Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes.

Results: Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p < .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC.

Conclusion: Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.
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http://dx.doi.org/10.1016/j.ygyno.2020.07.019DOI Listing
October 2020

Methotrexate-Etoposide-Ifosfamide Compared with Doxorubicin-Cisplatin-Ifosfamide Chemotherapy in Osteosarcoma Treatment, Patients Aged 18-25 Years.

J Adolesc Young Adult Oncol 2020 04 8;9(2):172-182. Epub 2019 Nov 8.

Department of Medical Oncology, Institut Curie, Paris, France.

The French standard chemotherapy for osteosarcoma combines high-dose methotrexate (HDM) and etoposide-ifosfamide (EI) in children and adolescents, and API-AI (doxorubicin-cisplatin-ifosfamide) in adults. We herein present the results of M-EI and API-AI in 18- to 25-year-old patients. Patients, 18-25 years old, received either M-EI or API-AI regimens. M-EI comprised seven M and two EI doses preoperatively then M-EI in standard-risk patients (good histological response without metastasis) and five M-AP (methotrexate-doxorubicin-cisplatin) in high-risk patients (poor histological response, metastasis, and/or unresectable primary), postoperatively. API-AI comprised three API and two AI doses preoperatively, then two AI and two PI in standard-risk patients and five EI in high-risk patients, postoperatively. We analyzed 95 patients 18-25 years of age: 55 received M-EI and 40 API-AI. The groups had similar baseline characteristics. Eighty-nine patients (94%) had surgery. Twenty-nine of 55 M-EI patients (60%) and 16/40 API-AI patients (41%) had good histological responses to preoperative chemotherapy. At 5 years, event-free survival was 50% (95% confidence interval [CI]: 39-60) and overall survival was 65% (95% CI: 54-74). Acute toxicity was similar, without treatment-related deaths. Survival outcomes with M-EI and API-AI were not significantly different. Tolerance was acceptable with both regimens. HDM is thus feasible for young adults. However, our study limitations preclude any definitive conclusions.
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http://dx.doi.org/10.1089/jayao.2019.0085DOI Listing
April 2020

Actionable molecular alterations in advanced gynaecologic malignancies: updated results from the ProfiLER programme.

Eur J Cancer 2019 09 24;118:156-165. Epub 2019 Jul 24.

Medical Practices Evaluation Team - HESPER EA7425, Centre Léon Bérard, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Department of Medical Oncology, Centre Léon Bérard, Lyon, France. Electronic address:

Objectives: The objectives of this study were to identify actionable genomic alterations in the gynaecological subpopulation of the ProfiLER programme and to report clinical efficacy of recommended targeted treatment (RTT).

Methods: The ProfiLER programme (NCT01774409) is a multicentric prospective trial aiming to implement molecular profiling in patients with advanced refractory cancers. In this programme, tumour DNA is analysed by targeted next-generation sequencing (69 genes) and by whole genome array comparative genomic hybridisation. Clinical cases and genomic profiles are presented in a dedicated molecular tumour board to guide treatment strategies. We report here an analysis of patients with gynaecological cancers included in this trial.

Results: From February 2013 to February 2017, 309 patients with gynaecologic cancer were included; 279 (90%) had sufficient quality, and 131 patients (42.4%) had at least one actionable genomic alteration in cancer cells. Four alterations were shared by at least 3% of the patients: 27 (9.7%) PIK3CA mutations, 15 (5.4%) KRAS mutations, 11 (3.9%) ERBB2 amplifications and 9 (3.2%) CDKN2A deletions. Forty-one treatments were initiated among 39 patients (12.6% of the screened population): 8 (20%) had a partial response, and other 10 (24%) had a stable disease. The median progression-free survival was 2.7 months. The median overall survival was 15.6 months for patients who received a RTT.

Conclusion: Molecular profiling identified actionable alterations in 42.4% of patients with advanced refractory gynaecologic cancer, but only 12.6% were treated with a RTT. Among them, 46% derived clinical benefit (5.8% of the screened population).
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http://dx.doi.org/10.1016/j.ejca.2019.06.017DOI Listing
September 2019

Results of API-AI based regimen in osteosarcoma adult patients included in the French OS2006/Sarcome-09 study.

Int J Cancer 2020 01 19;146(2):413-423. Epub 2019 Jul 19.

Department of Medical Oncology, Centre Léon Bérard, University Claude Bernard Lyon I, Lyon, France.

In the OS2006 study, patients younger than 18 years were treated with a methotrexate-based regimen (MTX), patients older than 25 years with a doxorubicin-cisplatin-ifosfamide-based regimen (API-AI), whereas patients aged 18-25 years received either API-AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API-AI. Preoperative chemotherapy combined three doxorubicin-ifosfamide-cisplatin (API) and two doxorubicin-ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin-ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide-ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18-67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety-six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28-48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow-up of 4.8 years, the 5-year event-free survival and overall survival rates were 46% (95% CI 36-56) and 57% (95% CI 47-67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API-AI proved feasible with no excess of toxicity, and favourable activity despite poor-prognosis factors.
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http://dx.doi.org/10.1002/ijc.32526DOI Listing
January 2020

Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study.

Lancet Oncol 2019 01 23;20(1):120-133. Epub 2018 Nov 23.

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

Background: Regorafenib has proven activity in patients with pretreated gastrointestinal stromal tumours and colorectal and hepatocellular carcinoma. We designed REGOBONE to assess the efficacy and safety of regorafenib for patients with progressive metastatic osteosarcoma and other bone sarcomas. This trial comprised four parallel independent cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. In this Article, we report the results of the osteosarcoma cohort.

Methods: In this non-comparative, double-blind, placebo-controlled, phase 2 trial, patients aged 10 years or older with histologically confirmed osteosarcoma whose disease had progressed after treatment with one to two previous lines of chemotherapy for metastatic disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly assigned (2:1) to receive either oral regorafenib (160 mg/day, for 21 of 28 days) or matching placebo. Patients in both groups also received best supportive care. Randomisation was done using a web-based system and was stratified (permuted block) by age at inclusion (<18 vs ≥18 years old). Investigators and patients were masked to treatment allocation. Patients in the placebo group, after centrally confirmed progressive disease, could cross over to receive regorafenib. The primary endpoint was the proportion of patients without disease progression at 8 weeks. Analyses were done by modified intention to treat (ie, patients without any major entry criteria violation who initiated masked study drug treatment were included). All participants who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02389244, and the results presented here are the final analysis of the osteosarcoma cohort (others cohorts are ongoing).

Findings: Between Oct 10, 2014, and April 4, 2017, 43 adult patients were enrolled from 13 French comprehensive cancer centres. All patients received at least one dose of assigned treatment and were evaluable for safety; five patients were excluded for major protocol violations (two in the placebo group and three in the regorafenib group), leaving 38 patients who were evaluable for efficacy (12 in the placebo group and 26 in the regorafenib group). 17 of 26 patients (65%; one-sided 95% CI 47%) in the regorafenib group were non-progressive at 8 weeks compared with no patients in the placebo group. Ten patients in the placebo group crossed over to receive open-label regorafenib after centrally confirmed disease progression. 13 treatment-related serious adverse events occurred in seven (24%) of 29 patients in the regorafenib group versus none of 14 patients in the placebo group. The most common grade 3 or worse treatment-related adverse events during the double-blind period of treatment included hypertension (in seven [24%] of 29 patients in the regorafenib group vs none in the placebo group), hand-foot skin reaction (three [10%] vs none), fatigue (three [10%] vs one [3%]), hypophosphataemia (three [10%] vs none), and chest pain (three [10%] vs none). No treatment-related deaths occurred.

Interpretation: Regorafenib demonstrated clinically meaningful antitumour activity in adult patients with recurrent, progressive, metastatic osteosarcoma after failure of conventional chemotherapy, with a positive effect on delaying disease progression. Regorafenib should be further evaluated in the setting of advanced disease as well as potentially earlier in the disease course for patients at high risk of relapse. Regorafenib might have an important therapeutic role as an agent complementary to standard cytotoxic chemotherapy in the therapeutic armamentarium against osteosarcoma.

Funding: Bayer HealthCare.
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http://dx.doi.org/10.1016/S1470-2045(18)30742-3DOI Listing
January 2019

Impact of Chemotherapy-induced Menopause in Women of Childbearing Age With Non-metastatic Breast Cancer - Preliminary Results From the MENOCOR Study.

Clin Breast Cancer 2019 02 23;19(1):e74-e84. Epub 2018 Oct 23.

Université Clermont Auvergne, Centre Jean Perrin, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Clermont-Ferrand, France.

Background: Young patients with breast cancer treated with chemotherapy can experience ovarian failure, which can lead to chemotherapy-induced menopause (CIM) impacting the quality of life (QoL). A prospective study was set out to evaluate the impact of CIM on QoL in women of childbearing age with non-metastatic breast cancer, and this article reports results of the interim analysis conducted to evaluate feasibility and to see preliminary results.

Patients And Methods: A total of 58 women (age, 18-46 years) with newly diagnosed breast cancer and treated with chemotherapy were eligible. QoL was assessed by self-administered questionnaires (Quality of Life Questionnaire-Core 30 [QLQ-C30], Quality of Life Questionnaire-Breast 23 [QLQ-BR23], and Kupperman index) and hormonal variations (anti-Müllerian hormone [AMH], follicle-stimulating hormone, and estradiol) were explored. We compared patients with ≥ 12 months amenorrhea (CIM) (n = 41) to patients with < 12 months of amenorrhea (non-CIM) (n = 17).

Results: A good inclusion rate (approximately 4/month) and sufficient data enabled us to perform this analysis. QLQ-C30 failed to show any difference between CIM and non-CIM patients (P = .5). In contrast, at 6 months post-chemotherapy, CIM patients tended to have lower QoL as shown by QLQ-BR23 (P = .16) and more severe climacteric symptoms (P = .01). Regarding hormonal variations, AMH pre-treatment level was higher in non-CIM patients (P = .0032). We also noted that CIM patients were older (P = .00013), had shorter menstruation cycle (P = .082), and experienced faster amenorrhea (P = .088).

Conclusions: The study is technically feasible, and our preliminary results underline that age in association with pre-treatment AMH level could be helpful to predict ovarian function. QLQ-BR23 seemed to be stronger, more precise, and appropriate to evaluate QoL changes in patients with breast cancer than the QLQ-C30.
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http://dx.doi.org/10.1016/j.clbc.2018.10.003DOI Listing
February 2019

Cancer patients treated with intravenous chemotherapy for the first time. What are their needs? What do they lack? A qualitative-quantitative mixed approach.

Patient Prefer Adherence 2018 19;12:1853-1861. Epub 2018 Sep 19.

Hygee Center, Lucien Neuwirth Cancer Institut, INSERM - CIC-EC, CIC 1408, Saint Priest en Jarez, France,

Introduction: The announcement of cancer coupled with initiation of its treatment impacts patients' psychological and physical states as well as their lifestyles. The objective of this study was to identify and confirm the needs of patients starting off on anticancer chemotherapy treatment.

Methods: This study was based on a qualitative-quantitative mixed method. In 2009, a qualitative study was conducted at the Lucien Neuwirth Cancer Institut for cancer patients undergoing intravenous chemotherapy for the first time. Exploratory and semi-directed interviews were carried out by a sociologist. In 2014, a questionnaire was hetero-administered to 100 patients starting off on chemotherapy.

Results: Forty patients were interviewed in 2009. Ninety-seven patients answered the questionnaire in 2014. Food was a theme that was identified by a majority of patients in 2009 (13/40) and confirmed in 2014: 63% needed help in identifying favorable food and 67% in identifying those that had to be avoided. The other needs identified were those linked to better understanding of the treatment, of how it may affect the couple, its side effects, hygiene and beauty, and knowledge about other treatments. These needs were confirmed in 2014. New needs were elicited in 2014: activities and leisure (33%), psychological needs (32.6%), and family relations (29.9%).

Conclusion: This study enabled us to identify, confirm, and enrich our knowledge of the needs of cancer patients starting off on intravenous chemotherapy. These results led to the modification of an existing patient education program for these patients, in order to fulfill their needs in an updated and tailored manner.
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http://dx.doi.org/10.2147/PPA.S169810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159784PMC
September 2018

EPIGIST: An observational real-life study on patients with metastatic gastrointestinal stromal tumors receiving imatinib.

PLoS One 2018 18;13(9):e0204117. Epub 2018 Sep 18.

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

Background: Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. EPIdemiology GIST, is an observational multicenter longitudinal follow-up cohort study reporting the prescribing patterns of imatinib in patients with GIST and the impact of the treatment in a real-world (standard clinical) setting.

Methods: Eligible patients had a confirmed diagnosis of unresectable or metastatic KIT-positive GIST and started treatment with imatinib for the first time between May 24, 2002, and June 30, 2010. During routine visits, annual collection of clinical characteristics was requested, i.e., age, GIST stage at diagnosis, history, imatinib treatment duration and dosage, adherence, and concomitant medications. Survival outcomes were estimated using the Kaplan-Meier method. Other data were analyzed using descriptive statistics.

Results: Of 151 patients enrolled, imatinib was initiated for 126 patients before enrollment and for 25 patients on the day of enrollment or soon after. The patient characteristics were similar to those in published prospective trials. The estimated 1-, 2-, 3-, and 4-year overall survival rates were 90.4% (95% confidence interval [CI; 84.8%-94.0%]), 84.7% (95% CI [78.1%-89.4%]), 73.0% (95% CI [65.0%-79.4%]), and 60.7% (95% CI [51.4%-68.8%]), respectively. The most common adverse events (AEs) were diarrhea (39%), asthenia (39%), eyelid or periorbital edema (32%), abdominal pain (23%), and anemia (21%). Eight of 126 serious AEs were possibly related to the treatment as assessed by investigators.

Conclusions: Study results showed that patients in real-life populations are generally treated in accordance with national and international clinical recommendations and have outcomes comparable to those of patients in clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204117PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143255PMC
March 2019

Treatment patterns and survival in an exhaustive French cohort of pazopanib-eligible patients with metastatic soft tissue sarcoma (STS).

BMC Cancer 2017 Feb 7;17(1):111. Epub 2017 Feb 7.

Centre Léon-Bérard, University Claude Bernard Lyon I, 28 rue Laennec, 69008, Lyon, France.

Background: The French EMS study prospectively collected exhaustive data from STS patients diagnosed in the Rhone-Alpes region from 2005 to 07.

Methods: The database included diagnosis/histology, surgery, radiotherapy, systemic treatments and treatment response. Treatment patterns and outcomes of patients with metastatic disease, excluding adipocytic sarcoma and GIST were analyzed.

Results: Of 888 total patients, 145 were included based on having metastatic disease and appropriate subtypes. All patients received treatment with systemic therapy being most common (74%, n = 107), followed by radiotherapy (30%, n = 44) and surgery (23%, n = 33). Doxorubicin, alone or in combination, was the most common first line systemic therapy (65%, n = 46). Drugs without license in sarcoma were used in 38-83% of treatments depending on treatment line. 24% of frontline patients demonstrated an objective response, decreasing to 11% objective responses in second line but no responses were documented beyond second line, with median PFS declining with each additional line. Median PFS also declined in patients receiving surgery compared to those receiving no surgery (8-15 m vs 5 m). Median OS from metastatic diagnosis for patients receiving systemic therapy was double that of patients without systemic treatment (24 m vs 12 m, p = 0.007).

Conclusions: Outcomes in this population were poor and declined with successive treatment. However, results suggest that further anticancer therapies in recurrent sarcoma might be beneficial.
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http://dx.doi.org/10.1186/s12885-017-3057-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297166PMC
February 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

The eight year evolution of an osseous PEComa.

Pathol Int 2017 03 9;67(3):181-182. Epub 2017 Jan 9.

Department of Pathology, North Hospital, University Hospital of St-Etienne, France.

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http://dx.doi.org/10.1111/pin.12500DOI Listing
March 2017

Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet Oncol 2016 Dec 14;17(12):1732-1742. Epub 2016 Oct 14.

Methodology and Clinical Research Platform of SIRIC OncoLille, Lille, France. Electronic address:

Background: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline.

Methods: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment. These patients were randomly assigned (1:1) into one of the following four cohorts: liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas. Participants were treated with oral regorafenib (160 mg per day 3 weeks on and 1 week off) or matched placebo. Patients receiving placebo were offered optional crossover in case of centrally confirmed disease progression. The random allocation schedule was computer-generated with permuted blocks of four patients, with two stratification factors: country (France or Austria) and previous exposure to pazopanib (yes or no). Eligibility criteria included patients with histologically proven advanced and inoperable soft tissue sarcomas with intolerance or failure to doxorubicin or other anthracycline-based chemotherapy and at least one unidimensionally or bidimensionally measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The primary endpoint was RECIST-based progression-free survival after central radiological review in the intention-to-treat population. Patients, physicians, and radiologists of the panel were masked to treatment allocation. This study is still open for recruitment for an additional stratum (patients previously treated with pazopanib) and registered with ClinicalTrials.gov, NCT01900743.

Findings: From Aug 5, 2013, to Nov 26, 2014, 182 patients were randomly assigned to one of four cohorts and included in the final analysis. At the cutoff date (Jan 7, 2016), the number of required events was reached for the four cohorts. In the liposarcoma cohort, progression-free survival was 1·1 months (95% CI 0·9-2·3) with regorafenib versus 1·7 months (0·9-1·8) with placebo (HR 0·89 [95% CI 0·48-1·64] p=0·70). In the leiomyosarcoma cohort, progression-free survival was 3·7 months (95% CI 2·5-5·0) with regorafenib versus 1·8 (1·0-2·8) months with placebo (HR 0·46 [95% CI 0·46-0·80] p=0·0045). In the synovial sarcoma cohort, progression-free survival was 5·6 months (95% CI 1·4-11·6) with regorafenib versus 1·0 (0·8-1·4) with placebo (HR 0·10 [95% CI 0·03-0·35] p<0·0001). In the other sarcoma cohort, progression-free survival was 2·9 months (95% CI 1·0-7·8) with regorafenib versus 1·0 (0·9-1·9) with placebo (HR 0·46 [95% CI 0·25-0·81] p=0·0061). Before crossover, the most common clinically significant grade 3 or higher adverse events were arterial hypertension (17 [19%] events in the 89 patients in the regorafenib group vs two [2%] events in the 92 patients in the placebo group), hand and foot skin reaction (14 [15%] vs no events) and asthenia (12 [13%] vs six [6%]). One treatment-related death occurred in the regorafenib group due to liver failure.

Interpretation: Regorafenib has an important clinical antitumour effect in non-adipocytic soft tissue sarcomas, improving progression-free survival. Regorafenib should be further evaluated in this setting, and its therapeutic role has to be defined in the context of the growing therapeutic armamentarium, already including one approved multikinase inhibitor, pazopanib.

Funding: Bayer HealthCare.
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http://dx.doi.org/10.1016/S1470-2045(16)30507-1DOI Listing
December 2016

Les métastases des cancers.

Rev Prat 2016 Sep;66(7):e298

Département d'oncologie médicale, institut de cancérologie Lucien-Neuwirth, 42270 Saint-Priest-en-Jarez, France.

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September 2016

Signes d'appel et investigations paracliniques ; caractérisation du stade ; pronostic.

Rev Prat 2016 Sep;66(7):e291-e297

Département d'oncologie médicale, institut de cancérologie Lucien-Neuwirth, 42270 Saint-Priest-en-Jarez, France.

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September 2016

Radiotherapy for gynecologic cancer in nonagenarian patients: a framework for new paradigms.

Chin J Cancer 2016 May 9;35:43. Epub 2016 May 9.

Department of Radiotherapy, Lucien Neuwirth Cancer Institute, 42271, Saint Priest En Jarez, France.

No consensus exists regarding the role of radiotherapy in the management of gynecologic cancer in nonagenarian patients. We retrospectively reviewed the outcomes of 19 consecutive nonagenarian patients with gynecologic cancer (6 endometrial cancers, 6 cervical cancers, 4 vulvar cancers, and 3 vaginal cancers) who were treated with radiotherapy. Radiotherapy was performed mainly in a palliative setting (n = 12; 63.2%), with a median dose of 45 Gy (range, 6-76 Gy). Infrequent major acute or late toxicities were reported. Among 19 patients, 9 (47.4%) experienced tumor progression, 5 (26.3%) experienced complete response, 2 (10.5%) experienced stable disease and/or partial response. At last follow-up, 12 patients (63.2%) had died; most deaths (n = 9) occurred because of the cancer. These results suggest that radiotherapy is feasible in the treatment of nonagenarian patients with gynecologic cancer.
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http://dx.doi.org/10.1186/s40880-016-0104-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862062PMC
May 2016

Improving Adherence to Adjuvant Endocrine Therapy in Breast Cancer Through a Therapeutic Educational Approach: A Feasibility Study
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Oncol Nurs Forum 2016 05;43(3):E94-E103

Lucien Neuwirth Cancer Institute.

Purpose/objectives: To develop and test the feasibility of a tailored therapeutic educational program, with the aim of improving adherence to oral endocrine adjuvant chemotherapy in women with breast cancer. 
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Design: A qualitative study to identify educational needs and a feasibility study assessing the efficacy of the program.
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Setting: A comprehensive cancer center, the Lucien Neuwirth Cancer Institute in Saint-Priest-en-Jarez, France.
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Sample: Two consecutive samples (N = 11, N = 6) of women taking adjuvant oral endocrine chemotherapy for breast cancer. 
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Methods: A mixed qualitative and quantitative method was used. The participants' representations of disease and treatment were explored through one-on-one interviews and then translated into educational needs, which were used to develop a tailored therapeutic education program. The pilot study evaluated the reach and efficacy using before-and-after comparisons. 
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Main Research Variables: Educational objectives, knowledge, trust in the treatment, and anxiety.
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Findings: Five educational objectives (acquiring knowledge, improving communication skills, managing anxiety, managing side effects, and improving adherence) were identified through 11 interviews. A three-session program was developed. Eight of the 23 patients invited to participate in a pilot study accepted, and six completed the intervention. Knowledge improved from 38.9 of 100 preintervention to 69.4 of 100 postintervention (p = 0.045). Trust in treatment showed a trend to improvement from 5.5 of 10 to 8 of 10 (p = 0.14), but anxiety did not change significantly; anxiety went from 6 to 7 (p = 0.88).
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Conclusions: Results from the feasibility study showed promising efficacy for the educational objectives and provided information about how the program could be improved. 
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Implications For Nursing: Tailored educational programs conducted by trained nurses may help patients to adhere to and live with the effects of endocrine therapy.
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http://dx.doi.org/10.1188/16.ONF.E94-E103DOI Listing
May 2016

[Validation of a questionnaire assessing patients' adherence and skill level of management for oral capecitabine treatment].

Bull Cancer 2016 Mar 23;103(3):241-51. Epub 2016 Feb 23.

Centre Hygée, institut de cancérologie Lucien-Neuwirth, 108 bis, avenue A.-Raimond, 42270 Saint-Priest-en-Jarez, France; CIC-EC, Inserm 1408, 42000 Saint-Étienne, France. Electronic address:

Introduction: There is a plea for the development of tools allowing the screening of fragile patients under oral chemotherapy. Such tools would identify patients with difficulties for being adherent or for having low side effects management skills. The aim of this study is to validate psychometric characteristics of a questionnaire assessing patients' adherence and skill level of management for oral capecitabine treatment.

Methods: Questionnaire's psychometric validation study. Prospective monocentric cohort. Cases-simulated questionnaire was constructed, according to recommendations, from the results of a socio-anthropological study. Validation phases included: a pre-testing and a field-testing including acceptability, scale reliability and internal consistency were conducted involving experts and patients sample.

Results: Pre-testing excluded 1 item. Acceptability phase included 15 patients, who did not change any of the questions. Reliability and internal consistency were tested with 67 patients. Cancer site did not statistically influence questionnaire answers. No correlation was identify with the analyse performed for the internal consistency testing.

Conclusion: This questionnaire has shown to be a valid tool for the assessment of the adherence and side effect management skill for patients with capecitabine treatment. It can easily be uses as a screening tool for prescribers. It can also be used as an evaluation tool for a therapeutic education programme in this field.
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http://dx.doi.org/10.1016/j.bulcan.2016.01.010DOI Listing
March 2016

Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting.

Eur J Cancer 2016 Apr 4;57:31-8. Epub 2016 Feb 4.

Univ. de Bordeaux, Bordeaux, F-33000, France; INSERM, U1219, Bordeaux, F-33000, France; CHU de Bordeaux, Bordeaux, F-33000, France. Electronic address:

Background: Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST.

Patients And Methods: Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively.

Results: Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation.

Conclusion: Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.
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http://dx.doi.org/10.1016/j.ejca.2015.12.029DOI Listing
April 2016

Translating Clinical Evidence-Based Medicine into the Real World: Single-Center Experience with Cabazitaxel in Metastatic Prostate Cancer Patients.

Chemotherapy 2016 12;61(3):127-33. Epub 2016 Jan 12.

Background: We studied the efficacy and safety of cabazitaxel in unselected real-life patients.

Patients And Methods: We retrospectively investigated all patients with metastatic prostate cancer (mPC) treated with cabazitaxel 25 mg/m2 i.v. every 3 weeks combined with oral prednisolone (10 mg once daily) after first-line docetaxel chemotherapy. Study issues were to report patient characteristics and cabazitaxel data in terms of tolerance and efficacy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. All data were compared with TROPIC results.

Results: From 2011 to 2014, 41 patients received cabazitaxel; 15 patients (37%) had a performance status (PS) ≥2 versus 7% (p < 0.0001) in TROPIC, and 38 patients (93%) presented a Gleason score ≥7 at baseline (vs. 60%; p < 0.0001). All patients had metastatic disease at baseline. Previous therapies were radiotherapy in 17 patients (41 vs. 61%; p = 0.01) and surgery in 24 patients (59 vs. 52%; p = 0.4). The median number of cabazitaxel cycles was 5 (1-10) versus 6 (3-10) in TROPIC. Five patients completed 10 cycles of cabazitaxel (12%) versus 28% in TROPIC (p = 0.03). Toxicities were anemia (12 patients, 29%), diarrhea (9 patients, 22%), nausea (7 patients, 17%), pain (6 patients, 15%), sepsis (4 patients, 10%), neutropenia (3 patients, 7%) and urinary tract infection (1 patient, 2%). The tumor response rate was 19.5 versus 14.4% in TROPIC (nonsignificant). PFS was 4.5 months (95% CI 3.3-6.4) in our analysis and 2.8 months (95% CI 2.4-3.0) in TROPIC. OS was 12.1 months (95% CI 9.2 to not reached) and 15.1 months (95% CI 14.1-16.3), respectively.

Conclusion: In our unselected mPC patients with poorer baseline clinical conditions and aggressive disease, cabazitaxel seems efficient and not more toxic than in the TROPIC study.
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http://dx.doi.org/10.1159/000441379DOI Listing
November 2016

What makes real world outcomes in soft tissue sarcomas? A mono-institutional trabectedin experience.

Bull Cancer 2015 Oct 16;102(10):814-22. Epub 2015 Sep 16.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 42270 Saint-Priest-en-Jarez, France. Electronic address:

Introduction: Trabectedin proved its efficacy in relapsed advanced soft tissue sarcomas (STS) in 3 multicenter phase II studies with selected patients. The aim of the present study is to investigate trabectedin efficacy and tolerance in a cohort of "real-life" unselected patients with sarcoma.

Methods: A single-center analysis was carried out on all consecutive patients with histologically proven unresectable advanced or metastatic STS, who received at least one cycle of trabectedin. Data on efficacy and tolerance were retrospectively reported.

Results: From 2004 to 2014, data of 59 patients were reviewed. Median age was 62 years (from 23 to 87). A total of 317 cycles of trabectedin were administered. Twenty-five patients (42%) suffered grade 3-4 hematological toxicity, mainly with neutropenia (22 patients, 37%). Disease control rate was 24%, mainly with stable disease, and 45 patients (76%) experienced disease progression. Median overall survival was 6.6 months (95%CI [4.9-12.6]).

Conclusion: Trabectedin might be an option for patients without any other validated alternative, but phase III study evaluating trabectedin+best supportive care (BSC) versus BSC is necessary.
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http://dx.doi.org/10.1016/j.bulcan.2015.07.010DOI Listing
October 2015

Paclitaxel Given Once Per Week With or Without Bevacizumab in Patients With Advanced Angiosarcoma: A Randomized Phase II Trial.

J Clin Oncol 2015 Sep 27;33(25):2797-802. Epub 2015 Jul 27.

Isabelle L. Ray-Coquard, Philippe A. Cassier, and Jean-Yves Blay, Centre Léon Bérard and Claude Bernard University, Lyon; Julien Domont, Olivier Mir, and Axel Le Cesne, Gustave Roussy, Villejuif; Emmanuelle Tresch-Bruneel and Stéphanie Clisant, Centre Oscar Lambret; Nicolas Penel, Centre Oscar Lambret and Lille-Nord-de-France Medical School, Lille; Emmanuelle Bompas, Centre René Gauducheau, Nantes; Sophie Piperno-Neumann, Institut Curie, Paris; Antoine Italiano, Institut Bergonié, Bordeaux; Christine Chevreau, Institut Claudius Regaud, Toulouse; Didier Cupissol, Institut de Cancérologie de Montpellier, Val d'Aurelle, Montpellier; François Bertucci, Institut Paoli Calmette, Marseille; Jacques-Olivier Bay, Centre Jean Perrin, Clermont-Ferrand; Olivier Collard, Institut de Cancérologie de la Loire Lucien Neuwirth, Saint Priest en Jarez; Esma Saada-Bouzid, Centre Antoine Lacassagne, Nice; Nicolas Isambert, Centre Georges-François Leclerc, Dijon; and Corinne Delcambre, Centre François Baclesse, Caen, France.

Purpose: The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS).

Methods: Patients were treated with paclitaxel alone (90 mg/m(2) per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug.

Results: A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion).

Conclusion: The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS.
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http://dx.doi.org/10.1200/JCO.2015.60.8505DOI Listing
September 2015

Real-World Vinflunine Outcomes in Bladder Cancer in a Single-Institution Study: Moving Beyond Clinical Trials.

Clin Genitourin Cancer 2015 Dec 6;13(6):588-92. Epub 2015 Jun 6.

Radiation Oncology Department, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France. Electronic address:

Purpose: Intravenous vinflunine 320 mg/m(2) every 3 weeks plus best supportive care resulted in better overall survival in comparison with best supportive care alone for eligible patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). The objective of the present study was to describe our real-life experience of vinflunine for treatment of patients with TCCU.

Patients And Methods: We retrospectively investigated all patients with TCCU who received at least 1 cycle of vinflunine.

Results: Nineteen patients were treated between May 2010 and March 2014 in a compassionate-use program. Performance status was poor in our real-life cohort, with 6 patients (32%) with an Eastern Cooperative Oncology Group performance status of 2. Median duration of vinflunine treatment was 2.4 months (range, 0-4.3 months), and median number of cycles was 3 (range, 1-6). Total response rate was 32%, with partial responses only. Disease control rate was 53%, with a median duration of 7.7 months (range, 6.0-9.4 months). Median progression-free survival was 87 days, or 2.9 months (range, 0.7-11.7 months). After vinflunine treatment, 42% of patients received from 1 to 3 additional lines of chemotherapy. The most frequent grade 4 toxicities were constipation (26%), with 3 intestinal obstructions (16%) and 1 mechanical ileus (5%); and asthenia and fatigue (21%).

Conclusion: Vinflunine, as a TCCU second-line chemotherapy, brings benefits, particularly in cases where there is no alternative treatment.
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http://dx.doi.org/10.1016/j.clgc.2015.05.008DOI Listing
December 2015

The Combination of 80 Years of Age and Metastatic Castration-Resistant Prostate Cancer Remain an Uphill Battle: A Case Report with Cabazitaxel as a Double-Edged Sword.

Chemotherapy 2014 20;60(5-6):300-1. Epub 2015 May 20.

Medical Oncology, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France.

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.
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http://dx.doi.org/10.1159/000377620DOI Listing
April 2016

Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial.

Lancet Oncol 2015 Apr 18;16(4):457-64. Epub 2015 Mar 18.

Department of Medical Oncology, La Timone University Hospital, Marseille, France.

Background: Metastatic leiomyosarcomas of uterine or soft-tissue origin have poor prognosis and moderate chemosensitivity. Trabectedin has shown activity in pretreated leiomyosarcoma. We did a single-group, multicentre, phase 2 trial (LMS-02) to assess the effect of first-line doxorubicin and trabectedin combination on disease control and survival.

Methods: Adults (18 years to physiological age ≤70 years) with measurable metastatic or unresectable uterine leiomyosarcoma or soft-tissue leiomyosarcoma who had not received any previous chemotherapy were enrolled at 19 centres in France. Treatment consisted of 60 mg/m(2) intravenous doxorubicin followed by 1·1 mg/m(2) trabectedin in a 3 h intravenous infusion on day 1, both by the central venous route, and 6 mg subcutaneous pegfilgrastim on day 2, repeated every 3 weeks for up to six cycles. Surgery for residual disease was permitted. The primary endpoint was the proportion of patients achieving disease control, defined as complete or partial response or stable disease. Stratification was done by anatomical site and analyses were per protocol. This study is registered with ClinicalTrials.gov, number NCT02131480.

Findings: Between July 28, 2010, and May 10, 2013, 109 patients were enrolled and treated, of whom 108 were assessable for response: 47 in the uterine leiomyosarcoma group and 61 in the soft-tissue leiomyosarcoma group. 32 (68%) patients in the uterine leiomyosarcoma group and 45 (74%) in the soft-tissue leiomyosarcoma group received all six cycles of treatment. Of 47 patients with uterine leiomyosarcoma, 28 (59·6%, 95% CI 44·3-73·6) achieved a partial response and 13 (27·7%, 15·6-42·6) stable disease; 41 (87·2%, 74·3-95·2) patients achieved disease control. Of 61 patients with soft-tissue leiomyosarcoma, two (3·3%, 95% CI 0·4-11·7) achieved a complete response, 22 (36·1%, 25·0-50·8) had a partial response, and 32 (52·5%, 40·8-67·3) had stable disease; 56 (91·8%, 81·9-97·3) of patients achieved disease control. The most common grade 3-4 treatment-associated adverse events were neutropenia (84 [78%] of 108 patients), increased alanine aminotransferase concentration (42 [39%]), thrombocytopenia (40 [37%]), anaemia (29 [27%]), febrile neutropenia (26 [24%]), and fatigue (21 [19%]).

Interpretation: Despite expected but manageable toxic effects, these results support the activity of doxorubicin plus trabectedin as first-line treatment for uterine leiomyosarcoma and soft-tissue leiomyosarcoma. This combination should be developed further in a phase 3 trial against the present standard of care.

Funding: Pharmamar and Amgen.
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http://dx.doi.org/10.1016/S1470-2045(15)70070-7DOI Listing
April 2015

The off-label use of targeted therapies in sarcomas: the OUTC'S program.

BMC Cancer 2014 Nov 24;14:870. Epub 2014 Nov 24.

Centre Léon Bérard, 28 rue Laennec 69 373, LYON CEDEX 08, France.

Background: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs.

Methods: Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice.

Results: From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n=48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n=39, receiving sorafenib in 79%), and angiosarcoma (n=18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95% CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively.

Conclusion: Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials.
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http://dx.doi.org/10.1186/1471-2407-14-870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289372PMC
November 2014

Transferability of health cost evaluation across locations in oncology: cluster and principal component analysis as an explorative tool.

BMC Health Serv Res 2014 Nov 18;14:537. Epub 2014 Nov 18.

Background: The transferability of economic evaluation in health care is of increasing interest in today's globalized environment. Here, we propose a methodology for assessing the variability of data elements in cost evaluations in oncology. This method was tested in the context of the European Network of Excellence "Connective Tissues Cancers Network".

Methods: Using a database that was previously aimed at exploring sarcoma management practices in Rhône-Alpes (France) and Veneto (Italy), we developed a model to assess the transferability of health cost evaluation across different locations. A nested data structure with 60 final factors of variability (e.g., unit cost of chest radiograph) within 16 variability areas (e.g., unit cost of imaging) within 12 objects (e.g., diagnoses) was produced in Italy and France, separately. Distances between objects were measured by Euclidean distance, Mahalanobis distance, and city-block metric. A hierarchical structure using cluster analysis (CA) was constructed. The objects were also represented by their projections and area of variability through correlation studies using principal component analysis (PCA). Finally, a hierarchical clustering based on principal components was performed.

Results: CA suggested four clusters of objects: chemotherapy in France; follow-up with relapse in Italy; diagnosis, surgery, radiotherapy, chemotherapy, and follow-up without relapse in Italy; and diagnosis, surgery, and follow-up with or without relapse in France. The variability between clusters was high, suggesting a lower transferability of results. Also, PCA showed a high variability (i.e. lower transferability) for diagnosis between both countries with regard to the quantities and unit costs of biopsies.

Conclusion: CA and PCA were found to be useful for assessing the variability of cost evaluations across countries. In future studies, regression methods could be applied after these methods to elucidate the determinants of the differences found in these analyses.
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http://dx.doi.org/10.1186/s12913-014-0537-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241216PMC
November 2014

[Carcinosarcomas in female genital tracts: general review].

Bull Cancer 2014 Jul-Aug;101(7-8):760-4

Institut de cancérologie de la Loire Lucien Neuwirth, Département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France.

Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time.
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http://dx.doi.org/10.1684/bdc.2014.1937DOI Listing
September 2014

[Re-entrainment to physical activity in the global management of breast cancer: pilot study in a mono-institutional experience].

Bull Cancer 2014 Jul-Aug;101(7-8):698-702

Institut de cancérologie Lucien-Neuwirth, Département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez cedex, France.

The objective of the present study is to report the pilot experience at the "Loire cardiorespiratory readaptation center" of re-entrainment of physical activity for patients suffering from breast cancer. Between January 2012 and February 2013, 63 patients took the program at the readaptation center. The program is composed of three sessions a week during seven weeks. During the care, a medical team intervenes. It is composed of a cardiologist, a physiotherapist, a sophrologist, a psychologist and a dietician who take part in turns and/or together. During the first session of the program, the warm-up power chosen on the exercise bike was on average of 14.72 watts (min = 5; max = 30), and it went up to 44.84 watts (min = 15; max = 85) on average during the last session. The maximal power used by the patient was on average of 39.08 watts (min = 10; max = 70) during the first session. On the last day of training, the average maximal power between the patients was of 76.03 watts (min = 30; max = 110). The tests used into practice tend to confirm a physical progression between the beginning and the end of the re-training program. This study particularly shows that it is possible today to propose this type of program to the patients in daily practice.
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http://dx.doi.org/10.1684/bdc.2014.2009DOI Listing
September 2014