Publications by authors named "Loïc Chaigneau"

62 Publications

Tumors and pseudotumors of the soft tissues: Imaging semiology and strategy.

J Clin Imaging Sci 2021 3;11:13. Epub 2021 Mar 3.

Department Radiology, Musculoskeletal Imaging Unit, CHU Besancon, Besancon, France.

The aims of this educational review are to learn the semiological basis of soft-tissue lesions and, with the help of diagnostic algorithms, to apply the current recommendations for the management of soft-tissue tumors. Pseudotumors must first be identified and excluded. Among primary tumors, the search for macroscopic fat content on MRI is decisive; since it restricts the diagnostic range to adipocytic tumors. Key imaging features of non-adipocytic tumors are highlighted. When a deep soft-tissue mass is found, therapeutic abstention or simple monitoring is only appropriate when there is diagnostic certainty: This is only the case for typical pseudotumors, typical benign tumors, and fat tumors without atypical criteria. In all other cases, histological evidence is required. If there is any suspicion of soft-tissue sarcoma or any undetermined lesion, the patient should be referred to a sarcoma referral center before biopsy.
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http://dx.doi.org/10.25259/JCIS_135_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981940PMC
March 2021

Angiosarcoma: A population-based cancer registry descriptive study of 45 consecutive cases diagnosed between 1979 and 2016.

Rare Tumors 2020 14;12:2036361320979216. Epub 2020 Dec 14.

Sce de Dermatologie, Inserm 1098 RIGHT, Université de Franche Comté, Centre Hospitalier Universitaire, Besançon, France.

Angiosarcoma (AS) is a rare aggressive sarcoma with differentiation toward blood or lymphatic endothelium. There are few epidemiological data available on AS. To address this limitation, we investigated the epidemiological and clinical features of angiosarcoma diagnosed in a French administrative area (the Doubs department) from 1979 to 2016. A retrospective cohort study was conducted using the Doubs cancer registry database. A total of 45 patients with invasive AS were diagnosed between 1979 and 2016 in the Doubs department. Among the 45 AS, 51% were either cutaneous AS (27%), including head and neck and extremities, or breast AS (24%) as compared to visceral AS (42%). Eleven patients had metastasis at diagnosis (26%). Age-standardized incidence rate was 0.15 per 100,000 persons-years (95%CI, 0.10-0.20) for the entire study period (1979-2016) and 0.26 (95%CI, 0.15-0.42) for the last decade (2007-2016). Crude survival at 1, 3, 5 years after diagnosis was 44%, 21%, and 12%, respectively. Our population-based study provides updated data on the incidence and overall survival of AS in a French population-based cancer registry.
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http://dx.doi.org/10.1177/2036361320979216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739202PMC
December 2020

Analysis of the StoRM cohort reveals physical activity to be associated with survival in metastatic breast cancer.

Sci Rep 2020 07 1;10(1):10757. Epub 2020 Jul 1.

Oncology Department, Centre Léon Bérard, Lyon, France.

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.
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http://dx.doi.org/10.1038/s41598-020-67431-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329808PMC
July 2020

Development of a disease-specific graded prognostic assessment index for the management of sarcoma patients with brain metastases (Sarcoma-GPA).

BMC Cancer 2020 Feb 12;20(1):117. Epub 2020 Feb 12.

Gustave Roussy Cancer Campus, Villejuif, France.

Background: Brain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the specifics of different primary histologies and molecular profiles. Thus far, a prognostic index to direct treatment decisions is lacking for adult sarcoma patients with brain metastases.

Methods: We performed a multicentre analysis of a national group of expert sarcoma tertiary centres (French Sarcoma Group, GSF-GETO) with the participation of one Canadian and one Swiss centre. The study cohort included adult patients with a diagnosis of a bone or soft tissue sarcoma presenting parenchymal or meningeal brain metastases, managed between January 1992 and March 2012. We assessed the validity of the original GPA index in this patient population and developed a disease-specific Sarcoma-GPA index.

Results: The original GPA index is not prognostic for sarcoma brain metastasis patients. We have developed a dedicated Sarcoma-GPA index that identifies a sub-group of patients with particularly favourable prognosis based on histology, number of brain lesions and performance status.

Conclusions: The Sarcoma-GPA index provides a novel tool for sarcoma oncologists to guide clinical decision-making and outcomes research.
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http://dx.doi.org/10.1186/s12885-020-6548-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014599PMC
February 2020

A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib in non-adipocytic sarcoma patients previously treated with both chemotherapy and pazopanib.

Eur J Cancer 2020 02 6;126:45-55. Epub 2020 Jan 6.

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

Background: Metastatic soft tissue sarcomas (STSs) management remains an unmet medical need. We assessed the activity and safety of regorafenib in patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib.

Patients And Methods: This double-blind, placebo-controlled, multicenter comparative randomized phase II trial included patients with histologically proven advanced and inoperable STS. Patients receiving placebo were offered optional cross-over for centrally confirmed disease progression. Primary end-point was centrally reviewed Response Evaluation Criteria in Solid Tumours-based progression-free survival (PFS), analysed on the intent-to-treat data set. In total, 24 events were required for 90% power, hazard ratio (HR) = 0.33 (median PFS, 3.6 versus 1.2 months), and 1-sided α = 0.1 (ClinicalTrials.gov, NCT01900743).

Results: From December 2015 to October 2017, 37 patients were randomized; 18 to regorafenib and 19 to placebo. Thirteen patients assigned to placebo switched to regorafenib after progression. Median follow-up was 27.2 months (95% confidence interval [CI]: 24.4-not reached). We observed a significant PFS benefit of regorafenib compared with placebo (adjusted HR = 0.33; 95% CI: 0.15-0.74; p = 0.0007 median PFS = 2.1 versus 1.1 months, respectively), and a large and nearly significant overall survival (OS) benefit despite the cross-over (adjusted HR = 0.49; 95% CI: 0.23-1.06; p = 0.007; median OS = 17.8 versus 8.2 months). Before cross-over, the most common grade III or higher adverse events were lymphopenia (5 versus 1, respectively), diarrhoea (4 versus 0), dyspnoea (3 versus 1), skin toxicity (3 versus 0), arterial hypertension (2 versus 0), and increased transaminases (2 versus 0).

Conclusion: The present study demonstrated a meaningful clinical anti-tumour activity with regorafenib in heavily pre-treated patients with non-adipocytic STS.
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http://dx.doi.org/10.1016/j.ejca.2019.12.001DOI Listing
February 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

[Adjuvant hormonal therapy for early breast cancer: Assessment of patients' satisfaction].

Bull Cancer 2019 Dec 12;106(12):1104-1114. Epub 2019 Oct 12.

CHU de Besançon, pôle pharmaceutique, 3, boulevard Fleming, 25030 Besançon cedex, France; Université Bourgogne Franche-Comté, fédération Hospitalo-Universitaire INCREASE, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, EFS BFC, UMR1098, Inserm, 8, rue du Dr Jean-François-Xavier-Girod, 25000 Besançon, France. Electronic address:

Introduction: Since the cancer plan, evaluation of professional practices is essential to ensure the implementation of high-quality health care. Assess patient satisfaction is one of the pillars of high-quality health care. The main objective of the study was to assess the satisfaction of patients with early breast cancer taking a hormonal therapy, the secondary objective was to identify factors associated with their satisfaction.

Methods: The modified EORTC OUT-PATSAT-35 questionnaire was sent to a sample of patients in Franche-Comté in order to evaluate nine dimensions of satisfaction among which interpersonal skills, provided information, and overall satisfaction. For each dimension, a satisfaction score between 0 (no satisfaction) and 100 (highest satisfaction) was measured. Logistic regression analyses were used to study the factors associated with satisfaction.

Results: The mean overall satisfaction score for the 280 patients who answered was 73 [0-100]. Practicing an extra-professional activity was associated with higher satisfaction for several dimensions (odds ratio between 2.80 and 4.12, P<0.05) whereas it was decreased in the case of a modified appetite (odds ratio between 0.27 and 0.52, P<0.05). No link has been shown between satisfaction and adherence.

Discussion: The patients were satisfied and several factors impacting their satisfaction were identified, based on a questionnaire that must evolve to take into account the ambulatory aspect of their care. During the consultations, particular attention will be paid to these factors.
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http://dx.doi.org/10.1016/j.bulcan.2019.08.019DOI Listing
December 2019

[Oesophagus polyps: Giant fibrovascular polyp of the oesophagus disappears!]

Ann Pathol 2019 Jun 16;39(3):221-226. Epub 2019 Apr 16.

Service d'anatomie et cytologie pathologiques, CHRU de Besançon, 25030 Besançon, France. Electronic address:

The giant fibrovascular polyp of the esophagus is a rare, benign and typical entity described in 1957. This lesion is easily identifiable in its macroscopic and microscopic aspects. However, recent studies question the existence of the giant fibrovascular polyp of the esophagus. The demonstration of an amplification of the MDM2 gene poses the diagnosis of well-differentiated liposarcoma. We describe here a case of an esophagus polyp in a 67-year-old man. The diagnosis of giant fibrovascular polyp of the esophagus was initially retained. Secondly, the immunohistochemical and fluorescence in situ hybridization techniques showed amplification of the MDM2 gene and reclassified the lesion to a well-differentiated liposarcoma. The search for an undifferentiated contingent is essential to not ignore a dedifferentiated liposarcoma, which is a high-grade sarcoma with a poorer prognosis.
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http://dx.doi.org/10.1016/j.annpat.2019.02.011DOI Listing
June 2019

Sarcomas in patients over 90: Natural history and treatment-A nationwide study over 6 years.

Int J Cancer 2019 10 15;145(8):2135-2143. Epub 2019 Apr 15.

Centre Léon Bérard, University Claude Bernard Lyon I, Lyon, France.

Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow-up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs. 66.3%), are less frequently metastatic (5.3% vs. 14·7%) at diagnosis, have more often superficial tumors (39.8% vs. 14.7%), as well as limbs and head and neck sites (75.2% vs. 38.7%) (all p < 0.001). Optimal diagnostic procedures and surgery were less frequently performed in patients over 90 (p < 0.001). These patients were less frequently operated in NETSARC centers, as compared to those of younger age groups including aged 80-90. However, local relapse-free survival, metastatic relapse-free survival and relapse-free survival were not significantly different from those of younger patients, in the whole cohort, as well as in the subgroup of operated patients. As expected overall survival was worse in patients over 90 (p < 0.001). Patients over 90 who were not operated had worse overall survival than younger patients (9.9 vs. 27.3 months, p < 0.001). Patients with STS diagnosed after 90 have distinct clinicopathological features, but comparable relapse-free survival, unless clinical practice guidelines recommendations are not applied. Standard management should be proposed to these patients if oncogeriatric status allows.
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http://dx.doi.org/10.1002/ijc.32307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767526PMC
October 2019

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

Brain Metastases from Adult Sarcoma: Prognostic Factors and Impact of Treatment. A Retrospective Analysis from the French Sarcoma Group (GSF/GETO).

Oncologist 2018 08 22;23(8):948-955. Epub 2018 Jun 22.

Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France.

Background: Brain metastases (BM) from adult soft tissue or bone sarcomas are rare, and sparse data exist on their prognostic factors and management.

Subjects, Materials And Methods: A retrospective study was conducted in 15 centers of the French Sarcoma Group, plus one Canadian and one Swiss center, to report on clinical, histological, and treatment characteristics and to identify predictive factors of outcome.

Results: Between 1992 and 2012, 246 patients with a median age of 50 years (range: 16-86) were managed for BM. BM included 221 cerebral and cerebellar metastases and 40 cases of meningeal sarcomatosis. The most frequent histopathological subtype was leiomyosarcoma (18.7%). Histological grade was high in 118 (48%) cases. Surgery of BM was carried out for 38 (15.5%) patients. Radiotherapy and chemotherapy were administered in 168 (68.3%) and 91 (37.0%) patients, respectively. Irrespective of treatment modality, BM were controlled in 113 patients (45.9%), including 31 partial responses (12.6%) and 18 complete responses (7.3%). The median overall survival from diagnosis of brain metastasis was 2.7 months (range: 0-133). In the multivariate analysis, the following parameters influenced overall survival: chemotherapy (hazard ratio [HR] = 0.38; 95% confidence interval [CI]: 0.26-0.48), surgery (HR = 0.40; 95% CI: 0.22-0.72), stereotactic radiotherapy (HR = 0.41; 95% CI: 0.19-0.90), whole-brain radiotherapy (HR = 0.51; 95% CI: 0.35-0.76), and grade (HR = 0.65; 95% CI: 0.43-0.98).

Conclusion: BM of sarcomas are rare and associated with a dismal outcome. Multidisciplinary management with chemotherapy, radiation therapy, and surgery is associated with a better survival.

Implications For Practice: The incidence of brain and meningeal metastasis in bone and soft tissue sarcomas is estimated between 1% and 8%. Published data are derived from small retrospective case series, often in the pediatric population. A prognostic index is important to guide both clinical decision-making and outcomes research, but one such is lacking for adult sarcoma patients with brain metastases. The current study describes brain metastasis in a large cohort of sarcoma patients. This study, conducted within the French Sarcoma Group, describes the natural history of sarcoma brain metastasis and enables the proposal of strategic recommendations for subsequent clinical trials and for the management of such patients.
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http://dx.doi.org/10.1634/theoncologist.2017-0136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156185PMC
August 2018

Adjuvant hormonal therapy for early breast cancer: an epidemiologic study of medication adherence.

Breast Cancer Res Treat 2018 May 23;169(1):153-162. Epub 2018 Jan 23.

Department of Pharmacy, Besançon University Hospital, Boulevard Fleming, 25030, Besançon Cedex, France.

Purpose: The aim of this study was to determine the prevalence of adherence to adjuvant hormonal therapy (AHT) and to identify risk factors for medication non-adherence in clinical practice in patients with early-stage hormone receptor (HR)-positive breast cancer (BC) previously treated with chemotherapy.

Methods: We carried out a cross-sectional, observational, prospective, and multicenter survey based on a structured self-report postal questionnaire (35 items investigating six areas). A sample of 474 patients was drawn from 676 patients potentially eligible. The structured and validated Morisky Medication Adherence Scale-4 items was used for measuring medication adherence. An analysis of risk factors for non-adherence to AHT was performed using a two-step approach: univariate, then multivariate analysis.

Results: A total of 280 patients out of the 428 analyzed patients participated in the survey, yielding a response rate of 65.4% [60.9-69.9]. The prevalence of adherence to AHT was estimated at 68.6% [63.1-74.0], corresponding to a high level of adherence. Three risk factors for non-adherence to AHT were identified: > 2 medications to treat comorbidities (p-value = 0.003), age less than 65 years (p-value = 0.008), and patient management in a university hospital setting (p-value = 0.014).

Conclusions: Non-adherence is a common, complex, and multidimensional healthcare problem. This better understanding and knowledge of risk factors will allow healthcare providers (such as oncologists, general practitioners, pharmacists) to more easily identify patients at risk for non-adherence and help them provide appropriate information about AHT and its management, thus improving medication adherence in their patients.
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http://dx.doi.org/10.1007/s10549-018-4676-3DOI Listing
May 2018

A Retrospective Multicentric Study of Ewing Sarcoma Family of Tumors in Patients Older Than 50: Management and Outcome.

Sci Rep 2017 12 20;7(1):17917. Epub 2017 Dec 20.

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

Ewing's sarcoma family of tumors (EFTs) is a group of rare and aggressive tumors. Data on EFTs in patients (pts) ≥ 50 years are limited and these pts are often not eligible for clinical trials. Some, but not all, studies have reported inferior outcome for older pts with EFTs. We conducted an IRB-approved retrospective analysis among centers of the French Sarcoma Group on pts diagnosed with EFTs at age ≥50 between 2000 and 2012. Clinical features, treatment modality and outcomes were analyzed. Seventy-seven pts were identified, including 36 females (46.8%) and the median age at diagnosis was 56 years (range: 50-86). The primary tumor was located in soft tissue in 59 pts (76.6%). Fifty-six pts (72.7%) had localized disease, among them 49 (87.5%) received chemotherapy in addition to local therapy. Their estimated 3-yr OS and event-free survival (EFS) rates were respectively 73.3% and 62.2%. Recurrence occurred in 43 pts. The estimated 3-yr OS rate was 37% in pts with metastatic disease at presentation. EFTs in pts ≥50 years are more likely to originate from soft tissue and their outcomes appear to be worse than that of younger pts treated with modern protocols.
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http://dx.doi.org/10.1038/s41598-017-17733-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738347PMC
December 2017

TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer.

Oncoimmunology 2018;7(12):e1386826. Epub 2017 Oct 11.

Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France.

Natural Killer (NK) cells control metastatic dissemination of murine tumors and are an important prognostic factor in several human malignancies. However, tumor cells hijack many of the NK cell functional features compromising their tumoricidal activity. Here, we show a deleterious role of the TNFα/TNFR2/BIRC3/TRAF1 signaling cascade in NK cells from the tumor microenvironment (TME). TNFα induces BIRC3/cIAP2 transcripts and reduces NKp46/NCR1 transcription and surface expression on NK cells, promoting metastases dissemination in mice and poor prognosis in GIST patients. NKp30 engagement, by promoting the release of TNFα, also contributes to BIRC3 upregulation, and more so in patients expressing predominantly NKp30C isoforms. These findings reveal that in the absence of IL-12 or a Th1-geared TME, TNFα can be considered as a negative regulatory cytokine for innate effectors.
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http://dx.doi.org/10.1080/2162402X.2017.1386826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279330PMC
October 2017

Giant cell tumor of bone under Denosumab treatment.

Joint Bone Spine 2018 07 29;85(4):491. Epub 2017 Sep 29.

Department of Rheumatology, CHRU de Besançon, boulevard Fleming, 25030 Besançon, France.

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http://dx.doi.org/10.1016/j.jbspin.2017.09.012DOI Listing
July 2018

New advances in DPYD genotype and risk of severe toxicity under capecitabine.

PLoS One 2017 8;12(5):e0175998. Epub 2017 May 8.

Centre Antoine Lacassagne, Nice, France.

Background: Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequencing and to examine relationships between DPYD variants and toxicity in advanced breast cancer patients receiving capecitabine.

Methods: Two-hundred forty-three patients were analysed (88.5% capecitabine monotherapy). Grade 3 and grade 4 capecitabine-related digestive and/or neurologic and/or hemato-toxicities were observed in 10.3% and 2.1% of patients, respectively. DPYD exome, along with flanking intronic regions 3'UTR and 5'UTR, were sequenced on MiSeq Illumina. DPD phenotype was assessed by pre-treatment plasma uracil (U) and dihydrouracil (UH2) measurement.

Results: Among the 48 SNPs identified, 19 were located in coding regions, including 3 novel variations, each observed in a single patient (among which, F100L and A26T, both pathogenic in silico). Combined analysis of deleterious variants *2A, I560S (*13) and D949V showed significant association with grade 3-4 toxicity (sensitivity 16.7%, positive predictive value (PPV) 71.4%, relative risk (RR) 6.7, p<0.001) but not with grade 4 toxicity. Considering additional deleterious coding variants D342G, S492L, R592W and F100L increased the sensitivity to 26.7% for grade 3-4 toxicity (PPV 72.7%, RR 7.6, p<0.001), and was significantly associated with grade 4 toxicity (sensitivity 60%, PPV 27.3%, RR 31.4, p = 0.001), suggesting the clinical relevance of extended targeted DPYD genotyping. As compared to extended genotype, combining genotyping (7 variants) and phenotyping (U>16 ng/ml) did not substantially increase the sensitivity, while impairing PPV and RR.

Conclusions: Exploring an extended set of deleterious DPYD variants improves the performance of DPYD genotyping for predicting both grade 3-4 and grade 4 toxicities (digestive and/or neurologic and/or hematotoxicities) related to capecitabine, as compared to conventional genotyping restricted to consensual variants *2A, *13 and D949V.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421769PMC
September 2017

NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients.

Oncoimmunology 2017;6(1):e1137418. Epub 2016 Apr 25.

Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, U1015, IGR, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT), Villejuif, France; University of Paris Sud XI, Villejuif, France.

Despite effective targeted therapy acting on and tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST. Phenotypes based on disbalanced NKp30B/NKp30C ratio (ΔBC) and low expression levels of NKp30A were identified in one third of patients with dismal prognosis across molecular subtypes. This ΔBC blood phenotype was associated with a pro-inflammatory and immunosuppressive tumor microenvironment. In addition, detectable levels of the NKp30 ligand sB7-H6 predicted a worse prognosis in metastatic GIST. Soluble BAG6, an alternate ligand for NKp30 was associated with low NKp30 transcription and had additional predictive value in GIST patients with high NKp30 expression. Such GIST microenvironments could be rescued by therapy based on rIFN-α and anti-TRAIL mAb which reinstated innate immunity.
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http://dx.doi.org/10.1080/2162402X.2015.1137418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283614PMC
April 2016

Somatic mutational spectrum analysis in a prospective series of 104 gastrointestinal stromal tumors.

Oncol Rep 2017 Mar 17;37(3):1671-1681. Epub 2017 Jan 17.

CHRU Besançon, Besançon, France.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis. All patients with GISTs diagnosed at the University Hospital of Besançon between August 2005 and October 2014 were prospectively included in the present study. KIT, PDGFRA and KRAS-codons 12 and 13 as well as BRAF codon 600 mutations were analyzed by Sanger sequencing or SNaPshot. KIT and PDGFRA mutations were detected in 71.2 and 19.2% of the cases, respectively. A total of 43 different mutations were detected of which 13 had never been described. As expected, KIT exon 9 and PDGFRA exon 18 mutations were associated with small bowel and gastric localizations respectively. No mutation was found in KRAS and BRAF. Molecular studies are critical to improve the management of GISTs. Our study enhances the current knowledge by describing 13 new mutations in KIT. A common molecular pattern in all KIT exon 11 substitutions is also described for the first time in this study but its significance remains unknown since genetic and environmental risk factors favoring the development of GISTs such as DNA repair defects and exposure to carcinogens are not currently known.
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http://dx.doi.org/10.3892/or.2017.5384DOI Listing
March 2017

[Prevalence and management of pain in patients with metastatic cancer in Franche-Comté].

Bull Cancer 2016 Oct 29;103(10):849-860. Epub 2016 Sep 29.

CHRU de Besançon, pôle pharmacie, 3, boulevard Alexandre-Fleming, 25030 Besançon cedex, France; Université Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, interactions hôte-greffon-tumeur - ingénierie cellulaire et génique, Besançon, France. Electronic address:

Introduction: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain.

Methods: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included.

Results: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life.

Conclusion: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate.
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http://dx.doi.org/10.1016/j.bulcan.2016.08.007DOI Listing
October 2016

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

Angiosarcoma: A Case Report of Gingival Disease with Both Palatine Tonsils Localization.

Rare Tumors 2016 Sep 5;8(3):5907. Epub 2016 Oct 5.

Department of Oncology, University Hospital Center Jean Minjoz , Besançon, France.

Angiosarcomas are one of the rarest subtypes of sarcomas; those are malignant vascular tumors arising from vascular endothelial cells. Occurrence of intra-oral angiosarcoma is extremely rare (0.0077% of all cancers in Europe). We present here, to our knowledge, the first case of a 83-year-old man with gingival and both palatine tonsils localization of a grade-two angiosarcoma discovered after a two months history of a painful lesion followed by hematoma and spontaneous bleeding. Chemotherapy with paclitaxel and hemostatic radiotherapy were inefficient and he died seven months after the first symptoms. It is essential to use the vascular markers, such as CD34, CD31, ERG and FLI1, for a correct histological diagnosis, which remains difficult because it displays a wide range of morphological appearances and multiple patterns may be present in the same tumor. The main prognostic factors are chronic pre-existing lymphedema and tumor size greater than five centimeters. Malignancy grade and stage classification should be provided in all cases in which this is feasible because of predictive meaning. When possible, wide surgical resection with negative margins remains the cornerstone for the treatment of localized angiosarcomas, but despite the improvement of surgical techniques the prognosis is poor with more than half of patients died within the first year. Adjuvant radiotherapy is the standard treatment of high-grade (two and three), deep lesions, regardless of size, because it improved the local recurrence-free survival. For advanced disease, if possible, metastasectomy should be considered. The first-line chemotherapy with doxorubicin or paclitaxel should be discussed compared to best supportive care according to patient comorbidities and preference.
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http://dx.doi.org/10.4081/rt.2016.5907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064291PMC
September 2016

Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors.

Clin Drug Investig 2017 Jan;37(1):85-94

Department of Pharmacy, University Hospital, Boulevard Fleming, 25030, Besançon Cedex, France.

Introduction: The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown.

Objective: The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib/best supportive care [BSC]); S2 (imatinib/imatinib/BSC); S3 (imatinib/sunitinib/BSC); and S4 (imatinib/imatinib/sunitinib/BSC).

Methods: A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed.

Results: The least costly and effective strategy was S1, at a cost of €65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of €48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of €363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies.

Conclusion: Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs.
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http://dx.doi.org/10.1007/s40261-016-0463-2DOI Listing
January 2017

Prospective 1-year follow-up pilot study of CT-guided microwave ablation in the treatment of bone and soft-tissue malignant tumours.

Eur Radiol 2017 Apr 23;27(4):1477-1485. Epub 2016 Aug 23.

Department of Musculoskeletal Imaging, University Hospital of Besancon, 25000, Besancon, France.

Purpose: The aims of this work were to assess the feasibility, efficacy, short-term outcome and safety of microwave ablation (MWA) in the treatment of malignant musculoskeletal tumours.

Materials And Methods: Sixteen bone and soft-tissue malignant tumours were prospectively included and were treated by CT-guided MWA. The percentage and size of necrosis of the lesions were measured by contrast-enhanced MRI before the procedure and after 1, 3, 6 and 12 months. mRECIST criteria were used to assess tumour response. Procedural success was defined as ≥80 % necrosis. Patient pain (as assessed using a numeric visual scale (NVS)) and side effects were noted.

Results: Six osteolytic metastases, five osteoblastic metastases and five soft tissue sarcomas were treated. At 1 month, 40 % were treated completely, the percentage of necrosis was 85 ± 30.4 %, and the success rate was 80 %. At 3, 6 and 12 months the success rate was 80 %, 76.9 % and 63.6 %, respectively. At 12 months, four lesions (36.3 %) still had no recurrence. Mean NVS during the procedure was 3.5 ± 2.8. One patient had transitory sciatica without neurological deficit that was treated medically.

Conclusion: CT-guided MWA of bone and soft-tissue malignant tumours is efficient, well tolerated and has good short-term anti-cancer effects.

Key Points: • CT-guided MWA is efficient in treating musculoskeletal malignant tumours. • This prospective pilot study showed MWA induces high percentages of tumour necrosis. • MWA has good short-term anti-cancer effects. • MWA has healing potential when lesions can be completely necrosed. • CT-guided MWA under equimolar mixture of oxygen-nitrous oxide inhalation is well tolerated.
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http://dx.doi.org/10.1007/s00330-016-4528-7DOI Listing
April 2017

Impact of Chemotherapy Beyond the Third Line in Patients With Recurrent Epithelial Ovarian Cancer.

Int J Gynecol Cancer 2016 Feb;26(2):261-7

*EA4267-UFR-33, School of Medecine and Pharmacy; †Medical Oncology Unit, J. Minjoz University Teaching Hospital; ‡INSERM U 645, EA-2284 IFR-133; and §Department of Surgery and ∥Pharmacy Department, J. Minjoz University Hospital, Besançon, France.

Objectives: The goal of this study was to determine the benefit in terms of time disease control (TDC) achieved by the succession of chemotherapy beyond the third line in patients treated for recurrent epithelial ovarian cancer. Secondary objectives were to identify patients who benefited from treatments beyond 3 lines and to estimate overall survival and disease-free progression lengths.

Materials And Methods: The cohort of 122 patients was identified from a pharmacy database of patients treated with chemotherapy between 1992 and 2010. The evaluation of benefit obtained by each line was based on TDC duration, defined as the interval between the beginning of the treatment and the date of progressive disease or death.

Results: Median TDC durations was 4.15 (0-54.7), 4 (0-21.7), 3.34 (0-29.6), 4.97 (0-29.2), and 3.13 months (0-15) for the fourth to eighth lines, respectively. Time to disease control was longer than 6 months in 34% to 40% of patients treated by lines 4 to 8. The most important factor influencing TDC length beyond the third line was the TDC duration observed in the 2 previous lines of therapy. Median overall survival after the third line was 15.3 months (95% confidence interval, 12-20 months). Factors associated with longer overall survival after 3 lines were performance status lower than 2 (P = 0.0058), no hepatic metastasis (P = 0.0098), no pulmonary metastasis (P = 0.0003), and platinum sensitivity (P = 0.04) CONCLUSIONS: These results may justify the administration of chemotherapy beyond the third line, in particular when the 2 previous lines are effective and resulted in disease control longer than 6 months.
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http://dx.doi.org/10.1097/IGC.0000000000000592DOI Listing
February 2016

Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors.

J Neuropathol Exp Neurol 2016 Feb;75(2):111-20

Chordomas are slow-growing malignant neoplasms. Determination of histopathologic prognostic factors using a large cohort study has been limited by their low incidence. In this retrospective study, we investigated the clinical, histopathologic, and immunohistochemical prognostic factors in 287 chordomas from 111 patients assessed by central pathologic review. Expression patterns of a variety of markers, including vascular endothelial growth factor (VEGF), mTOR pathway, c-kit, HER2, epidermal growth factor receptor (EGFR) and STAT3, and KRAS, BRAF, EGFR, and PIK3CA mutations were analyzed. On univariate analysis, the results confirm surgery as the best treatment, as judged by patient progression-free survival (PFS) and overall survival (OS). Proton therapy, the presence of a dedifferentiated component, mitotic figures, and Ki67 and p53 labeling indices correlated with PFS . Necrosis and apoptosis correlated with OS. Based on these findings, we propose a histopathologic grading system that correlates with PFS and OS. On multivariate analysis, extent of resection, tumor grade, and proton therapy were independent prognostic factors of PFS; extent of resection, tumor location, and grade were independent prognostic factors of OS. Based on the expression of EGFR, pSTAT3, VEGF, and mTOR pathway proteins, (in 85.9%, 79.1%, 85.7%, and 46% of chordomas, respectively), and 2 new mutations in the PIK3CA gene, we also provide evidence for potential therapeutic targets.
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http://dx.doi.org/10.1093/jnen/nlv010DOI Listing
February 2016

Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes).

BMC Cancer 2015 Nov 5;15:854. Epub 2015 Nov 5.

Department of Pediatric Oncology, Léon Bérard Cancer Center, 28, rue Laennec, 69008, Lyon, France.

Background: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry.

Methods: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed.

Results: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively.

Conclusion: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.
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http://dx.doi.org/10.1186/s12885-015-1894-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635968PMC
November 2015

[Efficacy, safety and cost of eribulin in patients with metastatic breast cancer].

Bull Cancer 2015 Sep 26;102(9):737-48. Epub 2015 May 26.

CHU de Besançon, hôpital Jean-Minjoz, pôle cancérologie-oncologie médicale, boulevard Fleming, 25000 Besançon cedex, France; Inserm U1098, 25000 Besançon, France; Université de Franche-Comté, SFR SMP, 25000 Besançon, France; EFS Bourgogne Franche-Comté, UMR1098, 25000 Besançon, France.

Eribulin gained its approval in March 2011 for the treatment of patients with locally advanced or metastatic breast cancer (MBC) whose disease has progressed despite anthracycline and taxane-containing regimens. This study retrospectively assessed the efficacy, safety and cost of this treatment for all patients with MBC treated by eribulin in Franche-Comté. Ninety-four patients received eribulin between July 2006 and October 2013. The median age was 62 years (35-83). Median overall survival was 10.3 months [95% CI: 7.6 to 17.9]. Median progression-free-survival was 3.8 months [95% CI: 2.9 to 5.0]. Clinical benefit was obtained in 55% evaluable patients [95% CI: 43.1 to 66.9] by RECIST criteria. Most common grade 3-4 adverse events (AEs) were neutropenia (38%), asthenia (10%) and peripheral neuropathy (7%). Median cost of the treatment was 9767 € per patient (6344-17,517). This analysis found similar results to the EMBRACE study despite less selected population. A medico-economic evaluation cost-utility type would assess the effectiveness of this strategy compared to standard treatments.
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http://dx.doi.org/10.1016/j.bulcan.2015.03.021DOI Listing
September 2015

In the era of genomics, should tumor size be reconsidered as a criterion for neoadjuvant chemotherapy?

Oncologist 2015 Apr 20;20(4):344-50. Epub 2015 Mar 20.

Departments of Medical Oncology, Gynecology, Pathology, and Statistics, University Hospital Jean Minjoz, Besançon, France; University of Franche-Comté, UMR1098, SFR IBCT, Besançon, France; INSERM, UMR1098, Besançon, France; EFS Bourgogne Franche-Comté, UMR1098, Besançon, France; Genomic Health, Inc., Redwood City, California, USA.

Background: The Oncotype DX recurrence score (RS) assay has been validated for prediction of 10-year risk of distant recurrence and likelihood of benefit from chemotherapy in patients with estrogen receptor (ER)-positive, HER2-negative early breast cancer. Patients with high RS tumors have substantial benefit, and patients with low RS tumors have minimal if any benefit from chemotherapy. Tumor size is used as a key parameter when selecting patients for neoadjuvant chemotherapy. The aim of this study was to assess the distribution of RS in patients selected for neoadjuvant chemotherapy primarily according to tumor size.

Patients And Methods: Patients with ER-positive and HER2-negative tumors that were node-negative or had no more than 1 positive node from three trials were included in this study. Oncotype DX was performed at Genomic Health, Inc., blinded to the clinical data. Descriptive statistics were calculated for distribution of RS for all cases.

Results: Of 277 patients, 96 met eligibility criteria, and 81 had sufficient material for analysis. Median tumor size was 40 mm (interquartile range [IQR], 30-50 mm). Grade I, II, and III were observed in 13, 49, and 17 cases, respectively. There was a wide distribution of RS with a median of 21.4 (IQR, 16.05-26.75). In total, 23 (28.3%) had high, 28 (34.6%) intermediate, and 30 (37%) low RS results.

Conclusion: The RS may provide relevant information for neoadjuvant treatment decisions in select patients both in clinical practice and in studies. Inclusion of low RS disease patients in neoadjuvant trials will likely only dilute the ability to look at treatment effects.
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http://dx.doi.org/10.1634/theoncologist.2014-0198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391758PMC
April 2015

Trabectedin in patients with advanced soft tissue sarcoma: a retrospective national analysis of the French Sarcoma Group.

Eur J Cancer 2015 Apr 23;51(6):742-50. Epub 2015 Feb 23.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France. Electronic address:

Aim: The French Sarcoma Group performed this retrospective analysis of the 'RetrospectYon' database with data of patients with recurrent advanced soft tissue sarcoma (STS) treated with trabectedin 1.5 mg/m(2) as a 24-h infusion every three weeks.

Methods: Patients who achieved non-progressive disease after six initial cycles could receive long-term trabectedin treatment until disease progression.

Results: Overall, 885 patients from 25 French centres were included. Patients received a median of four trabectedin cycles (range: 1-28). The objective response rate was 17% (six complete/127 partial responses) and 50% (n = 403) of patients had stable disease for a disease control rate of 67%. After a median follow-up of 22.0 months, median progression-free survival (PFS) and overall survival (OS) were 4.4 and 12.2 months, respectively. After six cycles, 227/304 patients with non-progressive disease received trabectedin until disease progression and obtained a significantly superior median PFS (11.7 versus 7.6 months, P<0.003) and OS (24.9 versus 16.9 months, P < 0.001) compared with those who stopped trabectedin treatment. Deaths and unscheduled hospitalisation attributed to drug-related events occurred in 0.5% and 9.4% of patients, respectively.

Conclusion: The results of this real-life study demonstrate that treatment with trabectedin of patients with STS yielded comparable or improved efficacy outcomes versus those observed in clinical trials. A long-term treatment with trabectedin given until disease progression is associated with significantly improved PFS and OS.
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http://dx.doi.org/10.1016/j.ejca.2015.01.006DOI 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