BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy

On September 22, 2021, the Food and Drug Administration approved ruxolitinib for the treatment of chronic graft-versus-host disease (cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-365 (REACH-3; CINC424D2301; {"type":"clinical-trial","attrs":{"text":"NCT03112603","term_id":"NCT03112603"}}NCT03112603), a randomized, open-label, multicenter trial of ruxolitinib in comparison to best available therapy (BAT) for the treatment of corticosteroid-refractory cGVHD occurring after the allogeneic hematopoietic stem cell transplantation. A total of 329 patients were randomized 1:1 to receive either ruxolitinib 10 mg twice daily (n = 165) or BAT (n = 164). BAT was selected by the investigator prior to randomization. The overall response rate through Cycle 7 Day 1 was 70% (95% CI, 63-77) in the ruxolitinib arm, and 57% (95% CI, 49-65) in the BAT arm. The median duration of response, calculated from first response to progression, death, or initiation of new systemic therapies for cGVHD, was 4.2 months (95% CI, 3.2-6.7) for the ruxolitinib arm and 2.1 months (95% CI, 1.6-3.2) for the BAT arm; and the median time from first response to death or initiation of new systemic therapies for cGVHD was 25 months (95% CI, 16.8-not estimable) for the ruxolitinib arm and 5.6 months (95% CI, 4.1-7.8) for the BAT arm. Common adverse reactions included anemia, thrombocytopenia, and infections. Given the observed response rate with durability, the clinical benefit of ruxolitinib appears to outweigh the risks of treatment for cGVHD after the failure of one or two lines of systemic therapy.     

Predictors of respiratory failure after thoracic surgery: a retrospective cohort study with comparison between lobar and sub-lobar resection

ObjectiveOnly approximately 15% of patients with lung cancer are suitable for surgery and clinical postoperative outcomes vary. The aim of this study was to investigate variables associated with post-surgery respiratory failure in this patient cohort.MethodsPatients who underwent surgery for lung cancer were retrospectively studied for respiratory function. All patients had undergone lung resection by a mini-thoracotomy approach. The study population was divided into two subgroups for comparison: lobectomy group, who underwent lobar resection; and sub-lobar resection group.ResultsA total of 85 patients were included, with a prevalence of lung cancer stage IA and adenocarcinoma histotype. Lobectomy (versus sub-lobar resection), the presence of chronic obstructive pulmonary disease (COPD), and a COPD assessment test (CAT) score >10, were all associated with an increased risk of respiratory failure. The partial pressure of arterial oxygen decreased more in the lobectomy group than in the sub-lobar resection group following surgery, with a significant postoperative between-group difference in values. Postoperative CAT scores were also better in the sub-lobar resection group.ConclusionsPost-surgical variations in functional parameters were greater in the group treated by lobectomy. COPD, high CAT score and surgery type were associated with postoperative development of respiratory failure.     

Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: Lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues

Purpose

To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues.

Methods

A total of 36 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle.

Results

Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ = 0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ = 0.95–0.97; p < 0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ = 0.91; p < 0.0001), while moderate correlations were found for the other normal organ tissues (ρ = 0.36–0.61; p < 0.05).

Conclusions

PET/MRI showed equivalent performance in terms of qualitative lesion detection to PET/CT. Despite significant differences in tracer uptake quantification, due to either methodological and biological factors, PET/MRI and PET/CT measurements in lesions and normal organ tissues correlated well. This study demonstrates that integrated whole-body PET/MRI is feasible in a clinical setting with high quality and in a short examination time.     

Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis

Background

Complete pathologic response (CPR) after neoadjuvant chemoradiotherapy (combined modality treatment, CMT) for rectal cancer seems associated with improved survival compared to partial or no response (NPR). However, previous reports have been limited by small sample size and single-institution design.

Methods

A systematic literature review was conducted to detect studies comparing long-term results of patients with CPR and NPR after CMT for rectal cancer. Variables were pooled only if evaluated by 3 or more studies. Study end points included rates of CPR, local recurrence (LR), distant recurrence (DR), 5-year overall survival (OS), and disease-free survival (DFS).

Results

Twelve studies (1,913 patients) with rectal cancer treated with CMT were included. CPR was observed in 300 patients (15.6%). CPR and NPR patient groups were similar with respect to age, sex, tumor size, distance of tumor from the anus, and stage of disease before treatment. Median follow-up ranged from 23 to 46?months. CPR patients had lower rates of LR [0.7% vs. 2.6%; odds ratio (OR) 0.45, 95% confidence interval (CI) 0.22?C0.90, P?=?0.03], DR (5.3% vs. 24.1%; OR 0.15, 95% CI 0.07?C0.31, P?=?0.0001), and simultaneous LR?+?DR (0.7% vs. 4.8%; OR 0.32, 95% CI 0.13?C0.79, P?=?0.01). OS was 92.9% for CPR versus 73.4% for NPR (OR 3.6, 95% CI 1.84?C7.22, P?=?0.002), and DFS was 86.9% versus 63.9% (OR 3.53, 95% CI 1.62?C7.72, P?=?0.002).

Conclusions

CPR after CMT for rectal cancer is associated with improved local and distal control as well as better OS and DFS.     

Identification of novel biomarkers differentially expressed between African-American and Caucasian-American prostate cancer patients

Prostate cancer (PCa) incidence and mortality rate vary among racial and ethnic groups with the highest occurrence in African American (AA) men who have mortality rates twice that of Caucasians (CA). In this study, we focused on differential expression of proteins in AA prostate cancer compared to CA using Protein Pathway Array Analysis (PPAA), in order to identify protein biomarkers associated with PCa racial disparity. Fresh frozen prostate samples (n=90) obtained from radical prostatectomy specimens with PCa, including 25 AA tumor, 21 AA benign, 23 CA tumor, 21 CA benign samples were analyzed. A total of 286 proteins and phosphoproteins were assessed using PPAA. By PPAA analysis, 33 proteins were found to be significantly differentially expressed in tumor tissue (n=48, including both CA and AA) in comparison to benign tissue (n=42). We further compared protein expression levels between AA and CA tumor groups and found that 3 proteins were differentially expressed (P<0.05 and q<5%). Aurora was found to be significantly increased in AA tumors, while Cyclin D1 and HNF-3a proteins were downregulated in AA tumors. Predicted risk score was significantly different between AA and CA ethnic groups using logistic regression analysis. In conclusion, we identified Aurora, Cyclin D1 and HNF-3a proteins as being differentially expressed between AA and CA in PCa tissue. Our study suggests that these proteins might be involved in different pathways that lead to aggressive PCa behavior in AA patients, potentially serving as biomarkers for the PCa racial disparity.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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Value of procalcitonin as a marker of surgical site infection following spinal surgery

Aim

To compare the value of Procalcitonin (PCT) as a marker of surgical site infection to other inflammatory markers, including C-Reactive Protein (CRP), White Cell Count (WCC) and Erythrocyte Sedimentation Rate (ESR) in patients undergoing a number of spinal procedures. This study also aims to describe the biokinetic profile of the above-named markers in patients developing surgical site infection and those remaining infection-free post-operatively.