Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study.

BACKGROUND The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.

Neuropathie optique rétrobulbaire post-actinique [Post-actinic retrobulbar optic neuropathy]

BACKGROUND: Radiation optic neuropathy (RON) is a rare, unpredictable, late complication of radiotherapy secondary to obliterative endarteritis. Tumor recurrence has to be ruled out by a clinical and neuroradiological examination. METHODS: Five patients with RON were investigated by magnetic resonance imaging (MRI) during 1992. RESULTS: Radiation-induced lesions of the intracranial visual pathways were easily visible on MRI. Without Gadolinium, a sectorial swelling was detectable, which markedly enhanced with Gadolinium. Intracranial optic nerve was affected in 5/5 cases, optic chiasm in 3/5 cases, and optic tract in 2/5 cases. CONCLUSIONS: MRI is the examination of choice when RON is suspected: it will easily delineate the extent of the lesion, and compression/infiltration by a recurrent tumor will be formally ruled out. A segmental swelling of visual pathway with marked Gadolinium enhancement on MRI is highly suggestive of radionecrosis.

Catalogue des livres portraits, gravures & instruments d'optique. Composant la Bibliothèque et le Cabinet De feu M. Grangeret de Lagrange conservateur-adjoint à la bibliothèque de l'Arsenal, membre du conseil de la Société asiatique, ancien correcteur pour les livres orientaux à l'Imprimerie impériale, etc. : La vente aura lieu ... Les Mardi 19, Mercredi 20, Jeudi 21 et Vendredi 22 Juillet 1859 / [expert] M. Auguste Aubry, Libraire

[Vente. Livres. 1859-07-19 - 1859-07-22]

Faiblesse et douleurs musculaires generalisees chez une patiente de 88 ans: avez-vous pense aux medicaments [88 years old woman with acute muscular weakness and diffuse muscular pain: have you thought about the drugs?].

An 88 years old woman was admitted for muscular pain and weakness. She was under a treatment of simvastatin and was recently prescribed clarithromycin for a lung infection. The diagnosis of statin induced rhabdomyolysis by drug interaction was made. The evolution is good with eviction of the statin and aggressive hydratation. This case shows how important it is to know the risks factors and drug interactions predisposing to statin-induced myopathy.

Intérêt de la tomographie par émission de positons couplée à la scanographie (TEP/TDM) dans les cancers urologiques [Value of positron emission tomography and computer tomography (PET/CT) for urologic malignancies].

Positron emission tomography is a functional imaging technique that allows the detection of the regional metabolic rate, and is often coupled with other morphological imaging technique such as computed tomography. The rationale for its use is based on the clearly demonstrated fact that functional changes in tumor processes happen before morphological changes. Its introduction to the clinical practice added a new dimension in conventional imaging techniques. This review presents the current and proposed indications of the use of positron emission/computed tomography for prostate, bladder and testes, and the potential role of this exam in radiotherapy planning.

Salvage Regimen With Autologous Stem Cell Transplantation With Or Without Rituximab Maintenance For Relapsed Diffuse Large B-Cell Lymphoma (Dlbcl): Coral Final Report

Times Cited: 0 References: 0 Citation MapAbstract : Background: Chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard treatment for relapsed DLBCL. No study has compared salvage therapies and evaluated maintenance post ASCT.Methods: DLBCL CD 20+ in first relapse or pts refractory after first therapy were randomized between R ICE (rituximab, ifosfamide, etoposide, carboplatinum) or R DHAP (rituximab dexamethasone cytarabine cisplatinum). Responding patients received BEAM and ASCT then randomized between observation or maintenance with rituximab every 2 m for 1 yr (Gisselbrecht J Clin Oncol; 2010).Results: Analysis was made on 477 pts (R ICE: 243 pts; R DHAP: 234 pts): 255 relapses >12m, 213 refractory/early relapses; 306 pts had prior rituximab; secondary(s) IPI 0-1: 281 pts; s IPI 2-3:181pts. There was no difference in response rate between R ICE 63.6% and R DHAP 64.3%. There was no difference between R ICE and R DHAP at 4 yrs for EFS (26% vs 37% p=0.2) and OS (43% vs 51%, p=0.3). Factors affecting 4 yrs EFS, PFS and OS were: prior treatment with rituximab; early relapse< 12 m; s IPI 2-3. ASCT was performed in 255 pts and 242 randomized for maintenance: 122 pts rituximab (R), 120 pts observation (O). Distribution between R/O arms were respectively: median age 54 /53 yrs, Male 76/83; female 46/37; secondary IPI 0-1: 84/81; sIPI 2-3: 36/36. 89/76 relapses >12m., 33/41 refractory/early relapses. Median follow up was 44 m with 111 events. 4 yrs EFS was 52.8 % (CI 46-59) with 63% (CI 56-69) OS. There was no difference in EFS, PFS and OS between R and O arms. In multivariate analysis, sIPI2-3 significantly affected EFS, PFS, OS (p=0.0004). Women (83pts) had a better 4 yrs EFS 63% than male (159pts) 37% (p=0.01). The difference was only in the R arm (p=0.004). Gender was an independent prognostic factor in the R arm. Toxicity was mild with 12% SAE versus 4% for R /O respectively.Conclusions: There was no difference between R ICE and R DHAP and between post ASCT maintenance with R or O. Women did significantly better after ASCT with rituximab. Early relapses to upfront rituximab-based chemotherapy have a poor prognosis.

Acvbp Versus Acvbp Plus Rituximab For Young Patients With Localized Low-Risk Diffuse Large B-Cell Lymphoma: A Study By The Groupe D'etude Des Lymphomes De L'adulte

Introduction: In a prior study, we demonstrated that ACVBP + consolidation was superior to 3 cycles of CHOP + radiotherapy in young patients (pts) with localized aggressive lymphoma (Reyes F et al. N Engl J Med 2005;352:1197). This randomized trial compared in these pts ACVBP vs. ACVBP + a short course of rituximab (R-ACVBP).Methods: untreated pts between 18 and 65y with stage I/II DLBCL and no adverse prognostic factors according to the aa-IPI were eligible. ACVBP consisted of 3 induction cycles given every 2 weeks: doxorubicin (75 mg/m2) day 1, cyclophosphamide (1.2g/m2) day 1, vindesine (2 mg/m2) day 1 and 5, bleomycin (10 mg) day 1 and 5, prednisone (60 mg/m2) day 1 to 5 followed by consolidation with metothrexate, ifosfamide, VP-16 and cytarabine. R-ACVBP consisted of the same regimen combined with 4 doses of rituximab (375 mg/m2) on day 1, 15, 29 and 43. Primary objective was EFS.Results: From 01/04 to 03/08, 223 pts were randomized, 113 in ACVBP and 110 in R-ACVBP arm. Characteristics were: median age 49y (18-65), stage I 63%, extranodal involvement 45%, bulky disease 4%. CR was 94% in ACVBP and 97% in ACVBP arm (ns). With a median follow-up of 43 months, the 3-y EFS was 82% (95% CI, 73% to 88%) in ACVBP and 93% (95% CI, 87% to 97%) in R-ACVBP group (P=0.0487). The 3-y PFS was 83% (95% CI, 74% to 89%) and 95% (95% CI, 89% to 98%) respectively (P=0.0205). OS did not significantly differ with a 3-y estimates of 97% (95% CI, 90% to 99%) for ACVBP and 98% (95% CI, 92% to 100%) for R-ACVBP (P=0.686). In multivariate analysis, a longer PFS was associated with R-ACVBP arm (P=0.0302) and lower b2-m level (P=0.0164). The same proportion of pts (27%) experienced at least 1 SAE in both groups. There were 4 deaths in each arm, with 1 treatment-related death in R-ACVBP (pneumocystis jiroveci pneumonia).Conclusion: the addition of only 4 doses of rituximab to ACVBP significantly improves EFS and PFS in younger pts with low-risk localized DLBCL.

Optimisation des doses en tomographie computérisée pédiatrique [Patient dose optimization in pediatric computerized tomography]

The development of CT applications might become a public health problem if no effort is made on the justification and the optimisation of the examinations. This paper presents some hints to assure that the risk-benefit compromise remains in favour of the patient, especially when one deals with the examinations of young patients. In this context a particular attention has to be made on the justification of the examination. When performing the acquisition one needs to optimise the extension of the volume investigated together with the number of acquisition sequences used. Finally, the use of automatic exposure systems, now available on all the units, and the use of the Diagnostic Reference Levels (DRL) should allow help radiologists to control the exposure of their patients.

Bilateral Uveal Pigmented Alterations With Remarkable Evolution: Long Term Follow-Up in a Case of Possible Bilateral Diffuse Uveal Melanocytic Proliferation

Purpose: to describe a case of probable bilateral diffuse uveal melanocytic proliferation (BDUMP) with scleral involvement, free from systemic malignancies and cataract. Methods: fifty months of follow up with recurrent complete ophthalmological examinations, including fundus photography, fluorescein/indocyanine green angiography (FA) and optical coherence tomography (OCT). Investigations also included an electroretinography (ERG) and histological examination of scleral biopsy. Extraocular malignancies were repeatedly searched. Results: the patient was a 61 year-old Italian man with chronic hepatitis type C. At first visit his best corrected visual acuity (BCVA) was 20/32 in OS and 20/25 in OD. Funduscopy showed multiple patch-shaped pigmented alterations involving macular region and mid retinal periphery. FA showed corresponding areas of late-phase hyperfluorescent pinpoints (figure 1a, OS) and intemediate-phase hypocyanescence (figure 1b, OS), with subtle serous neurosensory retinal detachment confirmed by OCT. Photopic and scotopic ERG tested normal. Systemic prednisone was administered for one month without any improvement. After ten months round pigmentary lesions appeared also in superior scleral surface of both eyes. Biopsy allowed to disclose slightly pigmented spindle cells. BCVA worsened for further 10 months, with enlargement of FA alteration areas but lenses still clear. After 30 months spontaneous coalescence and atrophy of retinal lesions started, paralleled by progressive visual recovery. At the end of our follow up BCVA was 20/25 in OU while scleral pigmentary lesions remained unchanged. Conclusions: we report the case of a patient with main features of BDUMP and some unusual findings. Although not all classical diagnostic criteria were fulfilled, the presence of scleral pigmented lesions and spontaneous visual recovery may enlarge clinical spectrum of the disease.

A noninvasive method for measuring the velocity of diffuse hydrothermal flow by tracking moving refractive index anomalies

Diffuse flow velocimetry (DFV) is introduced as a new, noninvasive, optical technique for measuring the velocity of diffuse hydrothermal flow. The technique uses images of a motionless, random medium (e.g.,rocks) obtained through the lens of a moving refraction index anomaly (e.g., a hot upwelling). The method works in two stages. First, the changes in apparent background deformation are calculated using particle image velocimetry (PIV). The deformation vectors are determined by a cross correlation of pixel intensities across consecutive images. Second, the 2-D velocity field is calculated by cross correlating the deformation vectors between consecutive PIV calculations. The accuracy of the method is tested with laboratory and numerical experiments of a laminar, axisymmetric plume in fluids with both constant and temperaturedependent viscosity. Results show that average RMS errors are ∼5%–7% and are most accurate in regions of pervasive apparent background deformation which is commonly encountered in regions of diffuse hydrothermal flow. The method is applied to a 25 s video sequence of diffuse flow from a small fracture captured during the Bathyluck’09 cruise to the Lucky Strike hydrothermal field (September 2009). The velocities of the ∼10°C–15°C effluent reach ∼5.5 cm/s, in strong agreement with previous measurements of diffuse flow. DFV is found to be most accurate for approximately 2‐D flows where background objects have a small spatial scale, such as sand or gravel