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1.
Cancer Radiother ; 27(5): 370-375, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37156711

ABSTRACT

PURPOSE: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. MATERIAL AND METHODS: Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). RESULTS: Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. CONCLUSION: FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.


Subject(s)
Epidural Neoplasms , Lymphoma, Follicular , Adult , Female , Humans , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin , Epidural Neoplasms/drug therapy , Incidence , Lymphoma, Follicular/radiotherapy , Neoplasm Recurrence, Local/drug therapy , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome
2.
Breast Cancer Res Treat ; 191(3): 577-587, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34984582

ABSTRACT

PURPOSE: Older cancer patients are underrepresented in clinical trials. We aimed to evaluate the enrollment of older women aged 70 years old (yo) or over with metastatic breast cancer (MBC) in clinical trials. METHODS: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real-life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment in older ones. RESULTS: 5552 women were aged ≥ 70 (median 74yo; IQR 72-77). 14,611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI 0.08-0.27] for the PS 2-4 class), HER2 + disease (OR 1.78 [95%CI 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI 3.13-8.18]), and period (OR 1.65 [95%CI 1.22-2.26] for 2012-2016, compared to 2008-2011). CONCLUSION: In this large database, few older MBC patients were enrolled in a trial compared with younger ones.


Subject(s)
Breast Neoplasms , Neoplasms, Second Primary , Aged , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Cohort Studies , Databases, Factual , Female , Humans , Receptor, ErbB-2 , Retrospective Studies
3.
Cancer Radiother ; 25(6-7): 679-683, 2021 Oct.
Article in French | MEDLINE | ID: mdl-34452822

ABSTRACT

Due to the continuously increasing number of newly diagnosed breast cancer and limited health resources hypofractionated radiotherapy is a major topic. Recent results from randomized clinical trials assessing extreme hypofractionated radiotherapy for whole or partial breast radiotherapy are practice changing. Here we report toxicity and oncological outcomes from major recent trials of extreme hypofractionated breast irradiation and present an ongoing prospective implementation program. For whole breast irradiation, with a 10 years follow up, the UK-FAST trial demonstrated no significant difference in toxicity between a once weekly 5 fractions (5,7Gy/fr) regimen and a conventional 50Gy/25fr regimen. With a 5 years follow up, the FAST-Forward trial showed non inferiority on local control for a 5 fractions over 1 week (5,2Gy/fr) regimen versus standard 40Gy/15fr over 3 weeks with safe toxicity profile. For accelerated partial breast irradiation, in low-risk breast cancers patients, several phase III randomized trials confirmed that extreme hypofractionation is a valid option. With our "One Week Breast Radiotherapy" program, we propose the implementation of a one-week full workflow preparing and delivering 5 fractions over 1 week (26Gy) in selected patients with prospective follow-up. Several extreme hypofractionated breast radiotherapy regimens are validated and can be routinely discussed with patients in a share decision-making process following patient selection criteria and dosimetric constraints.


Subject(s)
Breast Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Clinical Trials, Phase III as Topic , Equivalence Trials as Topic , Female , Follow-Up Studies , Humans , Multicenter Studies as Topic , Patient Selection , Program Evaluation , Randomized Controlled Trials as Topic , Time Factors , Treatment Outcome
4.
Cancer Radiother ; 25(3): 237-241, 2021 May.
Article in French | MEDLINE | ID: mdl-33419606

ABSTRACT

PURPOSE: Stereotactic body radiotherapy (SBRT) of prostate cancer is associated with rectal toxicities, which can be reduced by using a hydrogel spacer. The object of this retrospective study was to show the feasibility of spacer placement under local anesthesia and utility of hydrogel spacer to reduce the dose to the rectal wall. MATERIAL AND METHODS: We collected data from all patients with localised prostate cancer treated with SBRT (40Gy in 5 fractions) between 2018 and 2020. A hydrogel spacer (SpaceOAR®) was placed depending on the availability of the product. We collected dosimetric data for target volumes and organs at risk. We calculated mean values, which were compared using non-parametric tests. RESULTS: Among 35 patients, mean age was 75 years. Seventeen had a spacer placed, with a mean space created of 10mm. No complication was reported during the intervention. High doses to the rectal wall were significantly lower in spacer group (V38: 0.39 cm3 vs. 0.72 cm3; P=0.02). PTV were better covered in spacer group (P=0.07). Doses to the bladder wall were similar in both groups. CONCLUSION: Spacer procedure under local anesthesia was well tolerated. Hydrogel spacer allowed to reduce doses to the rectum while improving PTV coverage.


Subject(s)
Hydrogels/administration & dosage , Prostatic Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Radiosurgery/methods , Rectum/radiation effects , Aged , Aged, 80 and over , Anesthesia, Local , Feasibility Studies , Humans , Male , Middle Aged , Organs at Risk/radiation effects , Prostatic Neoplasms/pathology , Radiosurgery/adverse effects , Radiotherapy Dosage , Retrospective Studies , Statistics, Nonparametric , Urinary Bladder/radiation effects
5.
Pharmacogenomics J ; 17(4): 351-359, 2017 07.
Article in English | MEDLINE | ID: mdl-26975228

ABSTRACT

Screening for drug compounds that exhibit therapeutic properties in the treatment of various diseases remains a challenge even after considerable advancements in biomedical research. Here, we introduce an integrated platform that exploits gene expression compendia generated from drug-treated cell lines and primary tumor tissue to identify therapeutic candidates that can be used in the treatment of acute myeloid leukemia (AML). Our framework combines these data with patient survival information to identify potential candidates that presumably have a significant impact on AML patient survival. We use a drug regulatory score (DRS) to measure the similarity between drug-induced cell line and patient tumor gene expression profiles, and show that these computed scores are highly correlated with in vitro metrics of pharmacological activity. Furthermore, we conducted several in vivo validation experiments of our potential candidate drugs in AML mouse models to demonstrate the accuracy of our in silico predictions.


Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Transcriptome/genetics , Animals , Cell Line, Tumor , Drug Discovery/methods , HL-60 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude
6.
CPT Pharmacometrics Syst Pharmacol ; 4(7): 415-25, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26312165

ABSTRACT

Cancer drug discovery is an involved process spanning efforts from several fields of study and typically requires years of research and development. However, the advent of high-throughput genomic technologies has allowed for the use of in silico, genomics-based methods to screen drug libraries and accelerate drug discovery. Here we present a novel approach to computationally identify drug candidates for the treatment of breast cancer. In particular, we developed a Drug Regulatory Score similarity metric to evaluate gene expression profile similarity, in the context of drug treatment, and incorporated time-to-event patient survival information to develop an integrated analysis pipeline: Integrated Drug Expression Analysis (IDEA). We were able to predict drug candidates that have been known and those that have not been known in the literature to exhibit anticancer effects. Overall, our method enables quick preclinical screening of drug candidates for breast cancer and other diseases by using the most important indicator of drug efficacy: survival.

7.
Ann Oncol ; 26(8): 1748-53, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25969368

ABSTRACT

BACKGROUND: Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. PATIENTS AND METHODS: We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. RESULTS: In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. CONCLUSION: Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.


Subject(s)
Carcinoma, Giant Cell/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinosarcoma/genetics , Lung Neoplasms/genetics , AMP-Activated Protein Kinase Kinases , Adult , Aged , Carcinoma/genetics , Cohort Studies , ErbB Receptors/genetics , Female , GTP Phosphohydrolases/genetics , High-Throughput Nucleotide Sequencing , Humans , Male , Membrane Proteins/genetics , Middle Aged , Mutation , Nuclear Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Receptor, Notch1/genetics , Retrospective Studies , Transcription Factors/genetics , Tumor Suppressor Protein p53/genetics
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