The US population-based cancer registry Surveillance, Epidemiology, and End Results (SEER) database provides an opportunity to evaluate the incidence and survival rates of Ewing sarcoma (ES) for the ...past 3 decades. This analysis reflects trends for the diagnosis of localized versus metastatic disease and changes in ES survival in a setting of wide-ranging cancer care institutions across the United States, which is expected to be different from clinical trials published to date.
Data from the SEER public-access database were reviewed for the diagnosis of ES of the bone among patients of 1 to 19 years of age between 1973 and 2004. Age-adjusted incidence was analyzed for the entire group and for localized and metastatic disease separately over the past 3 decades. Actuarial survival rates were examined for 3 intervals: 1973 to 1982, 1983 to 1992, and 1993 to 2004.
The overall incidence of ES seemed to remain unchanged with an average of 2.93 cases/1,000,000 reported annually between 1973 and 2004. The proportion of patients with distant metastasis among all ES cases remained in the 26% to 28% range, whereas the percent of localized cases slightly increased from 57% in 1973 to 1982 to 67% in 1993 to 2004 and the proportion of unstaged cases decreased from 17% to 5%. The 5-year survival of localized disease increased from 44% in the first study decade to 68% in the period after 1993, whereas 5-year survival of metastatic disease increased from 16% to 39%. The corresponding 10-year survival increased from 39% to 63% for localized disease and from 16% to 32% for metastatic ES.
The incidence of ES has not increased appreciably over the last 30 years. A marked decrease in the proportion of unstaged cases may be reflective of diagnostic improvement or changes in reporting. There is a clear improvement in survival for both localized and metastatic disease. Poorer outcome of metastatic patients still warrants intensification of therapy, which is currently being tested in several ongoing trials.
Obinutuzumab is an anti-CD20 antibody engineered to elicit killing mechanisms distinct from rituximab. In a trial of chemotherapy plus obinutuzumab or rituximab that used the antibody as maintenance ...therapy for 2 years, obinutuzumab prolonged progression-free survival.
Purpose The GALLIUM study ( ClinicalTrials.gov identifier: NCT01332968) showed that obinutuzumab (GA101; G) significantly prolonged progression-free survival (PFS) in previously untreated patients ...with follicular lymphoma relative to rituximab (R) when combined with cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P; CHOP); CVP; or bendamustine. This report focuses on the impact of chemotherapy backbone on efficacy and safety. Patients and Methods A total of 1,202 patients with previously untreated follicular lymphoma (grades 1 to 3a), advanced disease (stage III or IV, or stage II with tumor diameter ≥ 7 cm), Eastern Cooperative Oncology Group performance status 0 to 2, and requiring treatment were randomly assigned 1:1 to G 1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375 mg/m
on day 1 of each cycle, for six to eight cycles, depending on chemotherapy (allocated nonrandomly by center). Responding patients received G or R for 2 years or until disease progression. Results Baseline Follicular Lymphoma International Prognostic Index risk, bulky disease, and comorbidities differed by chemotherapy. After 41.1 months median follow-up, PFS (primary end point) was superior for G plus chemotherapy (overall hazard ratio HR, 0.68; 95% CI, 0.54 to 0.87; P = .0016), with consistent results across chemotherapy backbones (bendamustine: HR, 0.63; 95% CI, 0.46 to 0.88; CHOP: HR, 0.72; 95% CI, 0.48 to 1.10; CVP: HR, 0.79; 95% CI, 0.42 to 1.47). Grade 3 to 5 adverse events, notably cytopenias, were most frequent with CHOP. Grade 3 to 5 infections and second neoplasms were most frequent with bendamustine, which was associated with marked and prolonged reductions in T-cell counts. Fatal events were more frequent in patients treated with bendamustine, possibly reflecting differences in patient risk profiles. Conclusion Improved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation.
The final stage of planet formation is dominated by collisions between planetary embryos. The dynamics of this stage determine the orbital configuration and the mass and composition of planets in the ...system. In the solar system, late giant impacts have been proposed for Mercury, Earth, Mars, and Pluto. In the case of Mercury, this giant impact may have significantly altered the bulk composition of the planet. Here we present the results of smoothed particle hydrodynamics simulations of high-velocity (up to ~5v esc) collisions between 1 and 10 M {circled plus} planets of initially terrestrial composition to investigate the end stages of formation of extrasolar super-Earths. As found in previous simulations of collisions between smaller bodies, when collision energies exceed simple merging, giant impacts are divided into two regimes: (1) disruption and (2) hit-and-run (a grazing inelastic collision and projectile escape). Disruption occurs when the impact parameter is near zero, when the projectile mass is small compared to the target, or at extremely high velocities. In the disruption regime, we derive the criteria for catastrophic disruption (when half the total colliding mass is lost), the transition energy between accretion and erosion, and a scaling law for the change in bulk composition (iron-to-silicate ratio) resulting from collisional stripping of a mantle.
In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance ...treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the maintenance phase was 33 months. Now, we report the long-term outcome of maintenance treatment, with a median follow-up of 6 years.
Overall, 465 patients were randomly assigned to induction with either six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab plus CHOP (R-CHOP). Those in complete remission or partial remission after induction (n = 334) were randomly assigned to maintenance treatment with rituximab (375 mg/m(2) intravenously once every 3 months) or observation.
Rituximab maintenance significantly improved progression-free survival (PFS) compared with observation (median, 3.7 years v 1.3 years; P < .001; hazard ratio HR, 0.55), both after CHOP induction (P < .001; HR, 0.37) and R-CHOP (P = .003; HR, 0.69). The 5-year overall survival (OS) was 74% in the rituximab maintenance arm, and it was 64% in the observation arm (P = .07). After progression, a rituximab-containing salvage therapy was given to 59% of patients treated with CHOP followed by observation, compared with 26% after R-CHOP followed by rituximab maintenance. Rituximab maintenance was associated with a significant increase in grades 3 to 4 infections: 9.7% v 2.4% (P = .01).
With long-term follow-up, we confirm the superior PFS with rituximab maintenance in relapsed/resistant FL. The improvement of OS did not reach statistical significance, possibly because of the unbalanced use of rituximab in post-protocol salvage treatment.
To report early outcomes with image-guided proton therapy for prostate cancer.
We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray ...equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years.
One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE.
Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.
Observational studies and stand-alone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have ...poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of patients with FL in the pre- and postrituximab eras to identify clinical factors that predict POD24. Logistic regression models evaluated the association between clinical factors and POD24. Cox regression evaluated the association between POD24 as a time-dependent factor and subsequent overall survival (OS). A landmark analysis evaluated the association of POD24 with OS for the subset of patients who were alive at 24 months after trial registration. Patients without progression at 24 months at baseline had favorable performance status (PS), limited-stage (I/II) disease, low-risk FL International Prognostic Index (FLIPI) score, normal baseline hemoglobin, and normal baseline β2 microglobulin (B2M) level. In a multivariable logistic regression model, male sex (odds ratio OR, 1.30), PS ≥2 (OR, 1.63), B2M (≥3 mg/L; OR, 1.43), and high-risk FLIPI score (3-5; OR, 3.14) were associated with increased risk of progression before 24 months. In the time-dependent Cox model and the 24-month landmark analysis, POD24 was associated with poor subsequent OS (hazard ratio, 4.85 and 3.06, respectively). This is the largest pooled analysis of clinical trials data validating POD24 as a robust indicator of poor FL survival and identified clinical predictors of early death and progression that can aid in building comprehensive prognostic models incorporating clinical and molecular predictors of POD24.
•Risk factors for POD24 included male sex, poor performance status, high-risk FLIPI score, and elevated β2-microglobulin.•We validated POD24 as a significant prognostic marker among >5000 patients on 13 international clinical trials.
Display omitted
Water-rich super-Earth exoplanets are expected to be common. We explore the effect of late giant impacts on the final bulk abundance of water in such planets. We present the results from smoothed ...particle hydrodynamics simulations of impacts between differentiated water(ice)-rock planets with masses between 0.5 and 5 M{sub +} and projectile to target mass ratios from 1:1 to 1:4. We find that giant impacts between bodies of similar composition never decrease the bulk density of the target planet. If the commonly assumed maximum water fraction of 75 wt% for bodies forming beyond the snow line is correct, giant impacts between similar composition bodies cannot serve as a mechanism for increasing the water fraction. Target planets either accrete materials in the same proportion, leaving the water fraction unchanged, or lose material from the water mantle, decreasing the water fraction. The criteria for catastrophic disruption of water-rock planets are similar to those found in previous work on super-Earths of terrestrial composition. Changes in bulk composition for giant impacts onto differentiated bodies of any composition (water rock or rock iron) are described by the same equations. These general laws can be incorporated into future N-body calculations of planet formation to track changes in composition from giant impacts.
PDF
