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.

Agents and intermediaries

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Characterization of modern and fossil mineral dust transported to high altitude in the Western Alps: Saharan sources and transport patterns

Mineral dust aerosols recently collected at the high-altitude Jungfraujoch research station (46 degrees 33'51 `' N, 7 degrees 59'06 `' E; 3580 m a.s.l.) were compared to mineral dust deposited at the Colle Gnifetti glacier (45 degrees 52'50 `' N, 7 degrees 52'33 `' E; 4455 m a.s.l.) over the last millennium. Radiogenic isotope signatures and backward trajectories analyses indicate that major dust sources are situated in the north-central to north-western part of the Saharan desert. Less radiogenic Sr isotopic compositions of PM10 aerosols and of mineral particles deposited during periods of low dust transfer likely result from the enhancement of the background chemically-weathered Saharan source. Saharan dust mobilization and transport were relatively reduced during the second part of the Little Ice Age (ca. 1690-1870) except within the greatest Saharan dust event deposited around 1770. After ca. 1870, sustained dust deposition suggests that increased mineral dust transport over the Alps during the last century could be due to stronger spring/summer North Atlantic southwesterlies and drier winters in North Africa. On the other hand, increasing carbonaceous particle emissions from fossil fuel combustion combined to a higher lead enrichment factor point to concomitant anthropogenic sources of particulate pollutants reaching high-altitude European glaciers during the last century.

Tectonomagmatic evolution of Western Amazonia: Geochemical characterization and zircon U-Pb geochronologic constraints from the Peruvian Eastern Cordilleran granitoids

The results of a coupled, in situ laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) U-Pb study on zircon and geochemical characterization of the Eastern Cordilleran intrusives of Peru reveal 1.15 Ga of intermittent magmatism along central Western Amazonia, the Earth's oldest active open continental margin. The eastern Peruvian batholiths are volumetrically dominated by plutonism related to the assembly and breakup of Pangea during the Paleozoic-Mesozoic transition. A Carboniferous-Permian (340-285 Ma) continental arc is identified along the regional orogenic strike from the Ecuadorian border (6 degrees S) to the inferred inboard extension of the Arequipa-Antofalla terrane in southern Peru (14 degrees S). Widespread crustal extension and thinning, which affected western Gondwana throughout the Permian and Triassic resulted in the intrusion of the late- to post-tectonic La Merced-San Ramon-type anatectites dated between 275 and 220 Ma, while the emplacement of the southern Cordillera de Carabaya peraluminous granitoids in the Late Triassic to Early Jurassic (220-190 Ma) represents, temporally and regionally, a separate tectonomagmatic event likely related to resuturing of the Arequipa-Antofalla block. Volcano-plutonic complexes and stocks associated with the onset of the present Andean cycle define a compositionally bimodal alkaline suite and cluster between 180 and 170 Ma. A volumetrically minor intrusive pulse of Oligocene age (ca. 30 Ma) is detected near the southwestern Cordilleran border with the Altiplano. Both post-Gondwanide (30-170 Ma), and Precambrian plutonism (691-1123 Ma) are restricted to isolated occurrences spatially comprising less than 15% of the Eastern Cordillera intrusives. Only one remnant of a Late Ordovician intrusive belt is recognized in the Cuzco batholith (446.5 +/- 9.7 Ma) indicating that the Famatinian arc system previously identified in Peru along the north-central Eastern Cordillera and the coastal Arequipa-Antofalla terrane also existed inboard of this parautochthonous crustal fragment. Hitherto unknown occurrences of late Mesoproterozoic and middle Neoproterozoic granitoids from the south-central cordilleran segment define magmatic events at 691 +/- 13 Ma, 751 +/- 8 Ma, 985 +/- 14 Ma, and 1071-1123 +/- 23 Ma that are broadly coeval with the Braziliano and Grenville-Sunsas orogenies, respectively. Our data suggest the existence of a continuous orogenic belt in excess of 3500 km along Western Amazonia during the formation of Rodinia, its ``early'' fragmentation prior to 690 Ma, and support a model of reaccretion of the Paracas-Arequipa-Antofalla terrane to western Gondwana in the Early Ordovician with subsequent detachment of the Paracas segment in form of the Mexican Oaxaquia microcontinent in Middle Ordovician. A tectonomagmatic model involving slab detachment, followed by underplating of cratonic margin by asthenospheric mantle is proposed for the genesis of the volumetrically dominant Late Paleozoic to early Mesozoic Peruvian Cordilleran batholiths.