Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma

An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m²), doxorubicin (50 mg/m²), prednisone (100 mg days 3–7) and vincristine (1·4 mg/m²) (O‐CHOP), as frontline treatment for follicular lymphoma (FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg (n = 29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) scores in the 500‐ and 1000‐mg dose groups, respectively. Overall response rate was 90% for the 500‐mg group and 100% for the 1000‐mg group. 62% of patients achieved complete response (CR)/unconfirmed CR (CRu). 76% of patients with FLIPI score 3–5 attained CR/CRu. Longer follow‐up time is needed for analysis of survival end points. The most common Common Terminology Criteria grade 3–4 investigator‐reported adverse events were leucopenia (29%) and neutropenia (22%). No deaths have been reported. O‐CHOP was safe and efficacious in patients with previously untreated FL, including high‐risk FLIPI groups. This trial was registered at www.clinicaltrials.gov (NCT00494780).     

Surgical strategy in grade II astrocytoma: a population-based analysis of survival and morbidity with a strategy of early resection as compared to watchful waiting

Background

We recently demonstrated a survival benefit of early resection in unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG entity warrants investigation in a homogenous subgroup. Astrocytoma represents the largest subgroup of LGG, and is characterized by diffuse growth and inferior prognosis. We aimed to study the effects of early resection compared to biopsy and watchful waiting in this subgroup.

Methods

Patient data was retrospectively reviewed in two neurosurgical departments with regional referral practice. In one hospital, initial diagnostic biopsies and watchful waiting was favored, while early resections guided with three-dimensional (3D) ultrasound were advocated in the other hospital. This created a natural experiment with patient management heavy influenced by residential address. In the hospitals’ histopathology databases, all adult patients diagnosed with supratentorial LGG from 1998 through 2009 were screened (n?=?169) and underwent blinded histopathological review. Histopathological review concluded with 117 patients with grade II astrocytomas that were included in the present study. The primary end-point was overall survival assessed by a regional comparison.

Results

Early resections were performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p?<?0.001). The two patient populations were otherwise similar. Median survival was 9.7 years (95 % CI 7.5–11.9) if treated in the hospital favoring early resections compared to 5.6 years (95 % CI 3.5–7.6) if treated at the hospital favoring biopsy and watchful waiting (p?=?0.047). No difference in surgical-related neurological morbidity was seen (p?=?0.843).

Conclusions

Early 3D ultrasound guided resections improve survival, apparently without increased morbidity, compared to biopsy and watchful waiting in patients with diffuse World Health Organization (WHO) grade II astrocytomas.     

Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment: A LIFE Study

BackgroundPharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP).MethodsData from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI).ResultsAtenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03).ConclusionsContrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)American Journal of Hypertension, (2012); doi:10.1038/ajh.2012.81.     

MicroRNA expression profiling of carcinoma in situ cells of the testis

Testicular germ cell tumours, seminoma (SE) and non-seminoma (NS), of young adult men develop from a precursor cell, carcinoma in situ (CIS), which resembles foetal gonocytes and retains embryonic pluripotency. We used microarrays to analyse microRNA (miRNA) expression in 12 human testis samples with CIS cells and compared it with miRNA expression profiles of normal adult testis, testis with Sertoli-cell-only that lacks germ cells, testis tumours (SE and embryonal carcinoma (EC), an undifferentiated component of NS) and foetal male and female gonads. Principal components analysis revealed distinct miRNA expression profiles characteristic for each of the different tissue types. We identified several miRNAs that were unique to testis with CIS cells, foetal gonads and testis tumours. These included miRNAs from the hsa-miR-371-373 and -302-367 clusters that have previously been reported in germ cell tumours and three miRNAs (hsa-miR-96, -141 and -200c) that were also expressed in human epididymis. We found several miRNAs that were upregulated in testis tumours: hsa-miR-9, -105 and -182-183-96 clusters were highly expressed in SE, while the hsa-miR-515-526 cluster was high in EC. We conclude that the miRNA expression profile changes during testis development and that the miRNA profile of adult testis with CIS cells shares characteristic similarities with the expression in foetal gonocytes.