ABSTRACT
OBJECTIVE: We implemented the two-step OPTIMA program to anticipate chemotherapy prescription which aims to assess the discrepancy rate between anticipated and real prescription and its impact on waiting time and quality of care. METHODS: This prospective study included cancer patients receiving any intravenous chemotherapy. The OPTIMA program consists in a nurse phone call and a blood sample two days before the planned treatment. Collected information and biological results were used by a physician to issue a non-effective (step 1) or effective (step 2) anticipated prescription the day before the consultation. The real prescription was given as usual by another physician on the day of the consultation. Waiting time was collected, and patients' satisfaction with care was assessed with the OUT-PATSAT35 questionnaire. RESULTS: Respectively, 540 and 979 consultations (283 and 294 patients) were analysed in both steps. The discrepancy rate was 8.7% (step 1). In routine practice, the OPTIMA program (step 2) reduced patients' waiting time (median time 55 vs. 95 min, p < 0.001). A high general care satisfaction score was observed in both steps (80.7% and 80.2%). CONCLUSIONS: This anticipation program demonstrated the accuracy of chemotherapy prescription, whatever the regimen and cancer site, and its impact on waiting time optimisation.
Subject(s)
Antineoplastic Agents/therapeutic use , Delivery of Health Care/methods , Neoplasms/drug therapy , Quality of Health Care , Adult , Aged , Ambulatory Care , Delivery of Health Care/organization & administration , Female , Humans , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Time FactorsABSTRACT
BACKGROUND: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A known side effect is the increase of haemoglobin level (HbL) during treatment with a suspected correlation with better outcome. Our objective was to examine whether HbL increase during the first three months of axitinib treatment is associated with better prognosis. METHODS: Retrospective multicentre analysis including patients with mRCC treated with axitinib for at least three months from 2012 to 2014. Progression-free survival (PFS) was analysed by a Cox model according to gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score, high blood pressure (hBP), and maximum increase in HbL within the first three months of treatment. RESULTS: Ninety-eight patients were analysed (71% men; median age at treatment initiation: 62 years; IMDC: 24%, 50%, and 26% in the favourable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months. During the first three months, the median increase of HbL was +2.3 g/dL (-1.1; 7.2). Fifty-six (57%) patients developed hBP. In multivariate analysis, after adjustment for performance status (P < 0.0001) and gender (P = 0.0041), the combination of HbL increase ≥2.3 g/dL and any grade hBP was significantly associated with longer PFS (HR = 0.40, 95%CI [0.24; 0.68]). CONCLUSIONS: Early HbL increase during axitinib treatment combined with hBP is an independent predictive factor of PFS. These results require validation in a prospective setting.
Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Renal Cell/blood , Hemoglobins/metabolism , Imidazoles/therapeutic use , Indazoles/therapeutic use , Kidney Neoplasms/blood , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Axitinib , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Disease-Free Survival , Female , Humans , Imidazoles/adverse effects , Indazoles/adverse effects , Kaplan-Meier Estimate , Kidney Neoplasms/drug therapy , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Polycythemia/blood , Polycythemia/chemically induced , Proportional Hazards Models , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.
Subject(s)
Carcinoma, Squamous Cell , Cetuximab , Drug-Related Side Effects and Adverse Reactions , Head and Neck Neoplasms , Radiodermatitis , Adult , Aged , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Cetuximab/administration & dosage , Cetuximab/adverse effects , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Female , France , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Patient Selection , Product Surveillance, Postmarketing , Radiodermatitis/diagnosis , Radiodermatitis/etiology , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival AnalysisABSTRACT
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) still remain frequent. The procedure for announcing the diagnosis (PAD) was an emblematic measure of the first French Plan Cancer aiming at providing patients with time to listen, information after cancer diagnosis, and discussion on treatments and their side effects. We aimed at assessing the risk factors of CINV, focusing on patients' satisfaction with the PAD. METHODS: This prospective multicentre study assessed the frequency and intensity of CINV among chemonaïve patients during the first cycle of treatment. CINV was defined by ≥1 emetic episode or reported nausea intensity ≥3 on a 0-10 scale. Multivariate analysis was used to identify factors related to global CINV onset including satisfaction with the PAD (satisfaction score ≥the median on a 0-10 scale). RESULTS: Data from 291 patients (women, 85.2%; mean age, 57 years) were analyzed. Most patients (69.4%) received highly emetogenic chemotherapy regimens and 77.7% received antiemetic drugs consistent with international guidelines. Acute, delayed and overall CINV were experienced by 40.4, 34.8 and 52.4% of patients, respectively. Sixty-seven per cent of patients were satisfied with the PAD. No relation was noted between PAD satisfaction and CINV onset. The nausea and vomiting dimension of the QLQ-C30 questionnaire before chemotherapy (OR 3.62), motion sickness history (OR 2.73), highly emetogenic CT (OR 2.73), anxiety (OR 1.99) and younger age (OR 1.96) were independent predictive factors. CONCLUSIONS: Although patients were mostly satisfied with the PAD, half of them experienced CINV. A state of anxiety could be identified during the PAD to be managed.
Subject(s)
Antiemetics/therapeutic use , Nausea/prevention & control , Neoplasms/complications , Vomiting/prevention & control , Antineoplastic Agents/adverse effects , Female , France , Humans , Male , Middle Aged , Nausea/chemically induced , Neoplasms/drug therapy , Prospective Studies , Vomiting/chemically inducedABSTRACT
Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT-737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl-1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1. Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who were chemo-naïve and had undergone surgery were prospectively exposed ex vivo to ABT-737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved-caspase 3 immunostaining. We also studied the association between baseline Bcl-2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT-737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT-737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66-100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT-737).
Subject(s)
Biphenyl Compounds/metabolism , Cystadenocarcinoma, Serous/therapy , Nitrophenols/metabolism , Ovarian Neoplasms/therapy , Sulfonamides/metabolism , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Bcl-2-Like Protein 11 , Biomarkers, Tumor/metabolism , Carboplatin/pharmacology , Combined Modality Therapy , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/pathology , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Membrane Proteins/metabolism , Middle Aged , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Piperazines/metabolism , Prognosis , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
PURPOSE: Point spread function (PSF) reconstruction improves spatial resolution throughout the entire field of view of a PET system and can detect smaller metastatic deposits than conventional algorithms such as OSEM. We assessed the impact of PSF reconstruction on quantitative values and diagnostic accuracy for axillary staging of breast cancer patients, compared with an OSEM reconstruction, with emphasis on the size of nodal metastases. METHODS: This was a prospective study in a single referral centre in which 50 patients underwent an (18)F-FDG PET examination before axillary lymph node dissection. PET data were reconstructed with an OSEM algorithm and PSF reconstruction, analysed blindly and validated by a pathologist who measured the largest nodal metastasis per axilla. This size was used to evaluate PET diagnostic performance. RESULTS: On pathology, 34 patients (68%) had nodal involvement. Overall, the median size of the largest nodal metastasis per axilla was 7 mm (range 0.5 - 40 mm). PSF reconstruction detected more involved nodes than OSEM reconstruction (p = 0.003). The mean PSF to OSEM SUVmax ratio was 1.66 (95 % CI 1.01 - 2.32). The sensitivities of PSF and OSEM reconstructions were, respectively, 96% and 92% in patients with a largest nodal metastasis of >7 mm, 60% and 40% in patients with a largest nodal metastasis of ≤7 mm, and 92% and 69% in patients with a primary tumour ≤30 mm. Biggerstaff graphical comparison showed that globally PSF reconstruction was superior to OSEM reconstruction. The median sizes of the largest nodal metastasis in patients with nodal involvement not detected by either PSF or OSEM reconstruction, detected by PSF but not by OSEM reconstruction and detected by both reconstructions were 3, 6 and 16 mm (p = 0.0064) respectively. In patients with nodal involvement detected by PSF reconstruction but not by OSEM reconstruction, the smallest detectable metastasis was 1.8 mm. CONCLUSION: As a result of better activity recovery, PET with PSF reconstruction performed better than PET with OSEM reconstruction in detecting nodal metastases ≤7 mm. However, its sensitivity is still insufficient for it to replace surgical approaches for axillary staging. PET with PSF reconstruction could be used to perform sentinel node biopsy more safely in patients with a primary tumour ≤30 mm and with unremarkable PET results in the axilla.
Subject(s)
Breast Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Image Processing, Computer-Assisted/methods , Positron-Emission Tomography , Radiopharmaceuticals , Algorithms , Axilla , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/secondary , Female , Humans , Limit of Detection , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Multimodal Imaging , Tomography, X-Ray ComputedABSTRACT
AIMS: After an old myocardial infarction (MI), patients are at risk for reentrant ventricular tachycardia (VT) due to scar tissue that can be accurately identified by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Although the ability of LGE-CMR to predict sustained VT in implantable cardioverter-defibrillator (ICD) recipients has been well established, its use to predict monomorphic VT (sustained or not) cycle length (CL) and so, optimize ICD programming has never been investigated. METHODS AND RESULTS: We included retrospectively 49 consecutive patients with an old MI who had undergone LGE-CMR before ICD implantation over a 4-year period (2006-09). Patients with amiodarone used were excluded. Scar extent was assessed by measuring scar mass, percent scar, and transmural scar extent. The endpoint was the occurrence of monomorphic VT, requiring an ICD therapy or not. The endpoint occurred in 26 patients. The median follow-up duration was 31 months. Scar extent parameters were significantly correlated with the study endpoint. With univariate regression analysis, the scar mass had the highest correlation with the VT CL (R = 0.671, P = 0.0002). Receiver-operating characteristic curve showed that scar mass can predict VT CL (area under the curve = 0.977, P < 0.0001). For a cut-off value of scar mass at 17.6 g, there is 100% specificity and 94.4% sensitivity. CONCLUSION: In this observational and retrospective study, scar mass studied by LGE-CMR was specific and sensitive to predict VT CL and so could be a promising option to improve ICD post-implantation programming and decrease appropriate and inappropriate shocks. These conclusions must now be confirmed in a large and prospective study.
Subject(s)
Cicatrix/etiology , Defibrillators, Implantable , Electric Countershock/instrumentation , Magnetic Resonance Imaging , Myocardial Infarction/complications , Myocardium/pathology , Tachycardia, Ventricular/therapy , Aged , Area Under Curve , Cicatrix/pathology , Contrast Media , Female , Humans , Male , Meglumine , Middle Aged , Myocardial Infarction/pathology , Organometallic Compounds , Patient Selection , Predictive Value of Tests , ROC Curve , Retrospective Studies , Risk Assessment , Risk Factors , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Treatment OutcomeABSTRACT
OBJECTIVES: The aim of this study was to appreciate the safety and effectiveness of transradial percutaneous coronary intervention (PCI) with rotational atherectomy for highly calcified left main coronary artery (LMCA) disease in octogenarians. BACKGROUND: Conventional surgery is still considered the preferred management for LMCA disease; but, when the lesion is severely calcified, and the patient is unsuitable for surgery, the interventional cardiologist faces a complex PCI traditionally approached by femoral access. METHODS: Between June 2004 and December 2010, octogenarians with calcified LMCA disease who were primary denied for surgical revascularization were enrolled. Procedural success and major adverse cerebral and cardiovascular events (MACCE) including death, nonfatal myocardial infarction, target lesion revascularization (TLR), or stroke during long-term follow-up were evaluated. RESULTS: Forty-two consecutive patients ≥80 years had undergone stenting for calcified LMCA disease (13 with rotational atherectomy, the "Rota" group, and 29 without rotational atherectomy, the "without Rota" group). Procedural success was good (92.3% vs. 96.6%, respectively, p = NS). Mean follow-up time was 25.7 ± 21.4 and 28 ± 32.3 months, respectively. There was a TLR in 25% and 11.1%, respectively; p = NS. No difference was detected in terms of overall in-hospital or long-term mortality or MACCE. CONCLUSION: Rotational atherectomy followed by stent implantation by transradial approach, when applied to heavily calcified lesions, appeared to be a safe and effective strategy for the treatment of LMCA disease in octogenarians who were refused for surgery.
Subject(s)
Atherectomy, Coronary/methods , Coronary Artery Disease/surgery , Percutaneous Coronary Intervention/methods , Postoperative Complications/etiology , Radial Artery/surgery , Stents/adverse effects , Vascular Calcification/surgery , Aged , Aged, 80 and over , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/mortality , Coronary Artery Disease/mortality , Female , Follow-Up Studies , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Postoperative Complications/epidemiology , Retrospective Studies , Survival Rate , Tertiary Care Centers , Treatment OutcomeABSTRACT
BACKGROUND: Coronary artery disease (CAD) patients are at risk for life-threatening ventricular arrhythmias (VA) related to scar tissue. Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) can accurately identify myocardial scar extent. It has been shown that scar extent, particularly scar transmurality, percent scar and scar mass, are associated with the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapy. However, quantification of transmurality extent has never been studied. The purpose of our study was to evaluate whether different methods quantifying scar transmurality, percent scar and scar mass (assessed with LGE-CMR) can predict appropriate ICD therapy in CAD patients with a long term follow-up period. METHODS AND RESULTS: We enrolled retrospectively 66 patients with chronic CAD referred for primary or secondary preventive ICD implantation and LGE-CMR before ICD implantation. Using LGE-CMR, scar extent was assessed by measuring scar mass, percent scar and transmural scar extent using four different methods. The median follow-up duration was 41.5 months (interquartile range 22-52). The endpoint was the occurrence of appropriate device therapy and occurred in 14 patients. Pre-ICD revascularization and transmural scar extent were significantly associated with the study endpoint but the latter was especially highly dependent on the method used. Patients with appropriate device therapy had also larger scar mass (29.6 ± 14.5 g vs 17.1 ± 8.8 g, p = 0.004), and larger percent scar (15.1 ± 8.2% vs 9.9 ± 5.6%, p = 0.03) than patients without appropriate device therapy. In multivariate analysis, scar extent variables remained significantly associated with the study end-point. CONCLUSIONS: In this study of CAD patients implanted for primary or secondary preventive ICD, pre-ICD revascularization and scar extent studied by LGE-CMR were significantly associated with appropriate device therapy and can identify a subgroup of CAD patients with an increased risk of life-threatening VA. Depending of the method used, transmural scar extent may vary significantly and needs further studies to obtain a validated and consensual study method.
Subject(s)
Arrhythmias, Cardiac/prevention & control , Contrast Media , Coronary Artery Disease/therapy , Defibrillators, Implantable , Electric Countershock/instrumentation , Magnetic Resonance Imaging, Cine , Meglumine , Myocardium/pathology , Organometallic Compounds , Primary Prevention , Secondary Prevention , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Coronary Artery Disease/complications , Coronary Artery Disease/diagnosis , Coronary Artery Disease/physiopathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Proportional Hazards Models , Retrospective Studies , Risk Factors , Stroke Volume , Time Factors , Treatment Outcome , Ventricular Function, LeftABSTRACT
PURPOSE: Our aim was to compare the impact of two types of sunglasses on visual field and glare: one ("thick sunglasses") with a thick plastic frame and wide temples and one ("thin sunglasses") with a thin metal frame and thin temples. METHODS: Using the Goldmann perimeter, visual field surface areas (cm²) were calculated as projections on a 30-cm virtual cupola. A V4 test object was used, from seen to unseen, in 15 healthy volunteers in the primary position of gaze ("base visual field"), then allowing eye motion ("eye motion visual field") without glasses, then with "thin sunglasses," followed by "thick sunglasses." Visual field surface area differences greater than the 14% reproducibility error of the method and having a p < 0.05 were considered significant. A glare test was done using a surgical lighting system pointed at the eye(s) at different incidence angles. RESULTS: No significant "base visual field" or "eye motion visual field" surface area variations were noted when comparing tests done without glasses and with the "thin sunglasses." In contrast, a 22% "eye motion visual field" surface area decrease (p < 0.001) was noted when comparing tests done without glasses and with "thick sunglasses." This decrease was most severe in the temporal quadrant (-33%; p < 0.001). All subjects reported less lateral glare with the "thick sunglasses" than with the "thin sunglasses" (p < 0.001). CONCLUSIONS: The better protection from lateral glare offered by "thick sunglasses" is offset by the much poorer ability to use lateral space exploration; this results in a loss of most, if not all, of the additional visual field gained through eye motion.
Subject(s)
Eye Protective Devices , Glare , Visual Fields/physiology , Adult , Female , Healthy Volunteers , Humans , Male , Reproducibility of Results , Visual Field TestsABSTRACT
BACKGROUND: O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation status was proposed as a prognostic biomarker for patients with glioblastoma. However, the prognostic impact of MGMT in patients with newly diagnosed glioblastoma who receive carmustine-releasing wafers (Gliadel) along with temozolomide (TMZ) is still unknown. METHODS: MGMT promoter methylation status and protein expression were analyzed in formalin-fixed, paraffin-embedded tumor specimens obtained from 111 French patients with newly diagnosed glioblastoma. Patients received the Gliadel wafers followed by radiotherapy plus concomitant and adjuvant TMZ chemotherapy while they were enrolled in a French multicenter prospective study. RESULTS: For the whole cohort, the median overall survival (OS) was 17.5 months, and the progression-free survival was 10.3 months. Patients with tumors that harbored MGMT methylation had a significantly longer OS compared with patients who had wild-type MGMT (21.7 months vs 15.1 months; P = .025). Similarly, patients who had low MGMT protein expression (≤15%) had a significantly improved OS compared with patients who had high MGMT expression (27.0 months vs 15.1 months; P = .021). The extent of resection was the strongest clinical predictor of outcome. In multivariate Cox models that were adjusted for sex, performance status, and extent of surgery, both MGMT methylation and protein expression were identified as independent prognosticators, and the finding was validated internally using a bootstrap resampling technique. Discrepancies were identified between protein expression and MGMT methylation status, thus suggesting that the 2 assays probably assess different biologic features. CONCLUSIONS: MGMT promoter methylation status and low MGMT expression both were identified as positive prognosticators in patients with newly diagnosed glioblastoma who underwent surgical resection and received Gliadel wafer implants followed by adjuvant radiotherapy and concomitant oral TMZ chemotherapy (the Stupp protocol).
Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/therapy , DNA Methylation , Glioblastoma/genetics , Glioblastoma/therapy , O(6)-Methylguanine-DNA Methyltransferase/genetics , Promoter Regions, Genetic , Adult , Aged , Antineoplastic Agents, Alkylating/therapeutic use , Biomarkers, Tumor , Carmustine/therapeutic use , Chemoradiotherapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Disease-Free Survival , Female , Humans , Male , Middle Aged , O(6)-Methylguanine-DNA Methyltransferase/biosynthesis , Prognosis , TemozolomideABSTRACT
Germline allele specific expression (ASE), resulting in a lowered expression of one of the BRCA1 alleles, has been described as a possible predisposition marker in Hereditary Breast or Ovarian Cancer (HBOC), usable for molecular diagnosis in HBOC. The main objective of this prospective case-control study was to compare the proportion of ASE between controls without familial history of breast or ovarian cancer, and HBOC cases without BRCA1 or BRCA2 deleterious mutation. BRCA1 ASE evaluated on three SNPs among controls and HBOC patients without deleterious mutation were assessed by pyrosequencing. The allelic ratios and the proportion of ASE were compared between controls and cases using a Student's t test and a Fisher exact test, respectively. The linearity and reproducibility of the ASE dosage was demonstrated with R2 > 0.99 and a coefficient of variation below 10 %, and ASE was detected in two positive controls harbouring BRCA1 truncated mutations. In the heterozygote population, composed of 99/264 controls (37.5 %) and 96/227 patients (42.3 %), we detected a 5 % ASE without truncated mutations, in each population. We failed to detect any significant difference of ASE between controls and patients. So far, BRCA1 Allelic specific expression is not usable in routine diagnosis as a possible predisposition marker in HBOC patients except for the detection of truncated mutations.
Subject(s)
Allelic Imbalance/genetics , BRCA1 Protein/genetics , Genes, BRCA1 , Genetic Predisposition to Disease/genetics , Germ-Line Mutation/genetics , Hereditary Breast and Ovarian Cancer Syndrome/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Case-Control Studies , Female , Heterozygote , Humans , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies , Young AdultABSTRACT
We describe how to estimate progression-free survival while dealing with interval-censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM-ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution. Clin Cancer Res; 22(23); 5629-35. ©2016 AACR.
Subject(s)
Software/statistics & numerical data , Statistics as Topic/methods , Algorithms , Clinical Trials as Topic/statistics & numerical data , Disease-Free Survival , Humans , Likelihood Functions , Models, Statistical , Survival AnalysisABSTRACT
BACKGROUND: The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18F-choline (CH) PET/CT after external beam radiation therapy (EBRT). METHODS: In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. RESULTS: Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. CONCLUSIONS: We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive factor of PET/CT positivity in univariate analysis, this was most noticeable for high PSAs. For low PSAs, trigger PSA remains most relevant. Larger series with intermediate PSA values need to be studied to fully apprehend nadir impact.
ABSTRACT
BACKGROUND: Tail vein injection under short anesthesia is the most commonly used route for administering radiopharmaceuticals. However, the small caliber of the vein in rodents may lead to tracer extravasation and thereby compromise quantitative accuracy of PET. We aimed to evaluate a method for correction of interstitial radiotracer leakage in the context of pre-clinical therapeutic response assessment. METHODS: In two separate studies involving 16 nude rats, a model of human ovarian cancer was xenografted and each was treated with a Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor or used as a control. Tracer injections were performed via the tail vein by a single operator. Two observers qualitatively evaluated the resulting images and if appropriate drew a volume of interest (VOI) over the injection site to record extravasated activities. Uncorrected and corrected tumors' mean standardized uptake value (SUV)mean was computed (corrected injected activity = calibrated activity - decay corrected residual syringe activity - decay corrected tail extravasated activity). Molecular analyses were taken as a gold standard. The frequency and magnitude of extravasation were analyzed, as well as the inter-observer agreement and the impact of the correction method on tumor uptake quantification. RESULTS: Extravasation never exceeded 20 % of the injected dose but occurred in more than 50 % of injections. It was independent of groups of animals and protocol time points with p values of 1.00 and 0.61, respectively, in the first experiment and 0.47 and 0.13, respectively, in the second experiment. There was a good inter-observer agreement for qualitative analysis (kappa = 0.72) and a moderate agreement when using quantitative analysis (ρ c = 0.94). In both experiments, there was significant difference between uncorrected and corrected SUVmean. Despite this significant difference, mean percent differences between uncorrected and corrected SUVmean in the first and the second experiments were -3.61 and -1.78, respectively. Concerning therapy assessment, in both experiments, significant differences in median %SUVmean between control and treated groups were observed over all time points with either uncorrected and corrected data (p < 0.05). CONCLUSIONS: Although extravasation is common and can be reproducibly corrected, this is probably not required for validation of response to drugs that induce large SUV changes. However, further studies are required to evaluate the impact of extravasation in situations where less marked metabolic responses are observed or important extravasations occur.
ABSTRACT
Humans' and apes' convergent (front-facing) orbits allow a large overlap of monocular visual fields but are considered to limit the lateral visual field extent. However, humans can greatly expand their lateral visual fields using eye motion. This study aimed to assess whether the human orbital morphology was unique compared with that of apes in avoiding lateral visual field obstruction. The orbits of 100 human skulls and 120 ape skulls (30 gibbons; 30 orangutans; 30 gorillas; 30 chimpanzees and bonobos) were analyzed. The orbital width/height ratio was calculated. Two orbital angles representing orbital convergence and rearward position of the orbital margin respectively were recorded using a protractor and laser levels. Humans have the largest orbital width/height ratio (1.19; p < 0.001). Humans and gibbons have orbits which are significantly less convergent than those of chimpanzees/bonobos, gorillas and orangutans (p < 0.001). These elements suggest a morphology favoring lateral vision in humans. More specifically, the human orbit has a uniquely rearward temporal orbital margin (107.1°; p < 0.001), suitable for avoiding visual obstruction and promoting lateral visual field expansion through eye motion. Such an orbital morphology may have evolved mainly as an adaptation to open-country habitat and bipedal locomotion.
Subject(s)
Skull/anatomy & histology , Animals , Female , Hominidae , Humans , Male , Visual Fields/physiologyABSTRACT
PURPOSE: We compared conventional filtered back-projection (FBP), two-dimensional-ordered subsets expectation maximization (OSEM) and maximum a posteriori (MAP) NEMA NU 4-optimized reconstructions for therapy assessment. PROCEDURES: Varying reconstruction settings were used to determine the parameters for optimal image quality with two NEMA NU 4 phantom acquisitions. Subsequently, data from two experiments in which nude rats bearing subcutaneous tumors had received a dual PI3K/mTOR inhibitor were reconstructed with the NEMA NU 4-optimized parameters. Mann-Whitney tests were used to compare mean standardized uptake value (SUV(mean)) variations among groups. RESULTS: All NEMA NU 4-optimized reconstructions showed the same 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) kinetic patterns and detected a significant difference in SUV(mean) relative to day 0 between controls and treated groups for all time points with comparable p values. CONCLUSION: In the framework of therapy assessment in rats bearing subcutaneous tumors, all algorithms available on the Inveon system performed equally.
Subject(s)
Image Processing, Computer-Assisted , Positron-Emission Tomography , Tomography, X-Ray Computed , Algorithms , Animals , Enzyme Inhibitors/chemistry , Female , Multimodal Imaging , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/drug therapy , Phantoms, Imaging , Phosphoinositide-3 Kinase Inhibitors , Radiopharmaceuticals/chemistry , Rats , Rats, Nude , Scattering, RadiationABSTRACT
OBJECTIVES: In advanced non-small cell lung cancer (NSCLC), maintenance therapy has emerged as a novel therapeutic reference for patients with non-progressive disease after platinum-based induction chemotherapy. However, the use of double maintenance (DM) with pemetrexed and bevacizumab is still being evaluated in terms of its clinical benefits and safety profile. The objective of this retrospective study was to describe the reasons for DM discontinuation in a real-world setting. MATERIALS AND METHODS: Patients with advanced non-squamous NSCLC were eligible if they had received at least 4 cycles of induction chemotherapy, followed by at least 1 cycle of DM. They were identified by using the oncology pharmacy database of 17 French centers. RESULTS: Eighty-one patients who began a DM after induction chemotherapy were identified from September 2009 to April 2013. Among the 78 patients who had stopped DM at the time of the analysis, the main reasons for discontinuation were disease progression (42%), adverse events (33%), and personal preference (8%). The most frequent toxicity responsible for DM discontinuation was renal insufficiency (54%). CONCLUSION: For patients with advanced NSCLC eligible for DM therapy, a particular attention should be paid to potential renal failure. Kidney function should be monitored carefully before and during DM to detect and manage early this adverse event.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Renal Insufficiency/etiology , Adult , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Induction Chemotherapy , Kidney Function Tests , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Maintenance Chemotherapy , Male , Middle Aged , Neoplasm Staging , Prevalence , Renal Insufficiency/diagnosis , Renal Insufficiency/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Three-dimensional echocardiography (3DE) is a reliable and reproducible tool for assessing left ventricular (LV) function but remains sensitive to patient echogenicity. Contrast-enhanced 3DE (C3DE) has the potential to improve quantification in challenging patients. The aim of this study was to evaluate the impact of temporal resolution, spatial resolution, and image dynamic range on LV function assessed using C3DE compared with cardiac magnetic resonance imaging (MRI) in patients with poor echogenicity. METHODS: Forty-one patients with poor echogenicity who underwent two-dimensional echocardiography (2DE), 3DE, C3DE, and MRI were retrospectively investigated. RESULTS: Before contrast injection, 24 patients had three or more nonvisible segments. Three cases of 2DE and 12 cases of 3DE were not suitable for quantification. LV end-diastolic volumes were systematically underestimated by 2DE (142 ± 58 mL), 3DE (146 ± 69 mL), and C3DE (172 ± 61 mL) compared with MRI (216 ± 85 mL) (P < .001). Similar results were found for LV end-systolic volumes (81 ± 65 mL for 2DE, 82 ± 69 mL for 3DE, and 102 ± 80 mL for C3DE vs 129 ± 94 mL for MRI; P < .001). C3DE provided the best agreement with MRI (Lin concordance correlation coefficients of 0.67, 0.93, and 0.99, respectively, for end-diastolic volume, end-systolic volume, and ejection fraction) as well as the best measurement reproducibility. Finally, ultrasound settings had no significant effect on LV volumes and ejection fraction measurements. CONCLUSIONS: In these patients with poor ultrasound image quality, C3DE, regardless of instrument settings, outperformed 2DE and 3DE to assess LV volumes and ejection fraction and can thus be proposed as an acceptable alternative when MRI cannot be performed in this subgroup.
Subject(s)
Echocardiography, Three-Dimensional/methods , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging, Cine/methods , Phospholipids , Stroke Volume , Sulfur Hexafluoride , Ventricular Dysfunction, Left/diagnosis , Algorithms , Contrast Media , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
AIMS: Obesity may have implications in the myocardial structural change, which may contribute to mechanical consequences. Using 2D speckle echocardiography, we looked for myocardial changes and investigated their relation to obesity, inflammation, insulin resistance and physical capacity in children with isolated obesity. METHODS AND RESULTS: Standard echocardiography and 2D strain were prospectively performed in obese children and compared them with age- and sex-matched controls. Z-score body mass index (BMI Z-score), ultra-sensitive C reactive protein, indices of insulin resistance (HOMA-IR) and metabolic stress test were assessed in obese children. Thirty-two consecutive obese patients [age: 12.8 (8-17) years; 15 males; BMI Z-score: 5.8 [2.05-8.6)] were compared with 32 controls. Longitudinal strain and circumferential strain were significantly lower in the obese group (respectively -18.0 ± 2.4% vs. -20.6 ± 2.5%; P = 0.0001 and -18.2 ± 3.5% vs. -20.1 ± 2.3%; P = 0.013), while radial strain did not differ. Longitudinal strain was correlated with HOMA-IR (Pearson's rho = -0.39) and with the exercise capacity (Pearson's rho = 0.62). In the multivariate analysis, after adjusting for age, the mean arterial pressure and left ventricular (LV) mass, the BMI Z-score remained independently related to the longitudinal and circumferential strain. CONCLUSION: Childhood obesity may be associated with an early alteration of the longitudinal and circumferential LV strain. These findings have potentially significant clinical implications for the outcomes and follow-up of obese children meriting further studies.