Radioligand therapy (RLT) with
Lu-prostate-specific membrane antigen (PSMA) inhibitors (
LuLu-PSMA) is currently approved for patients with metastatic castration-resistant prostate cancer (mCRPC) ...after progression with at least 1 taxane and 1 androgen-receptor-pathway inhibitor. However, the impact of prior chemotherapy on
LuLu-PSMA-RLT outcomes is debatable, with various studies showing inconsistent results. This study was conducted to precisely evaluate the impact of prior taxane chemotherapy on response and survival outcomes in mCRPC patients after
LuLu-PSMA-RLT.
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches in PubMed, Scopus, and Embase were made using relevant key words, and articles up to December 2022 were included. The endpoints included prostate-specific antigen (PSA) response rate (RR), progression-free survival, and overall survival (OS). Individual patient data were pooled when feasible. Univariate odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates and 95% CIs were generated using metaanalysis.
Thirteen articles comprising 2,068 patients were included. In 6 articles (553 patients), taxane-naïve patients had significantly better odds of biochemical response after
LuLu-PSMA-RLT (pooled OR, 1.82; 95% CI, 1.21-2.71). Individual patient data metaanalysis for PSA RRs in 3 articles revealed a significantly higher PSA RR in the taxane-naïve versus taxane-treated patients (57.1% vs. 39.5%; difference, 17.6%; 95% CI, 5.6%-28.9%). Further, taxane-naïve status was also a predictor of significantly better progression-free survival (5 articles; 1,027 patients; pooled HR, 0.60; 95% CI, 0.51-0.69) and OS (8 articles; 1,594 patients; pooled HR, 0.54; 95% CI, 0.43-0.68) after
LuLu-PSMA-RLT. There was no evidence of publication bias.
mCRPC patients with no prior taxanes had significantly better outcomes after
LuLu-PSMA-RLT than did taxane-treated patients. Further trials evaluating
LuLu-PSMA-RLT in the taxane-naïve setting are now required.
•Design methodology of a cryogenic radial turbine is proposed.•Turbine design parameters are validated with available results.•For optimization and performance prediction, ANN and ANFIS models are ...developed.•Experimental analysis is performed for performance measurement.
As a major component of cryogenic turboexpander, the design and performance estimation of a radial inflow turbine determines the effectiveness of the system. To explore the performance, this paper focuses on to investigate the effect of mass flow rate and operating temperature on isentropic efficiency, temperature drop, enthalpy drop, pressure variation, and power output of a cryogenic turboexpander. Firstly, the mean-line design of a radial inflow turbine is conducted by considering different loss models. Sobol sensitivity analysis is performed to identify the major geometrical parameters which have a significant effect on the performance of the turbine. Based on the geometrical data sets, an ANN and ANFIS models are developed to predict the ranges in which maximum efficiency of the turbine is obtained with minimum losses. The designed turbine is validated with available data in the literature. Secondly, an experimental set-up with extended measuring points for data collection is developed to investigate the performance of a turboexpander at cryogenic temperature. A detailed experimental analysis is carried out to compare the temperature drop, isentropic efficiency, and power output of the turboexpander for mass flow rate in the range of 0.03–0.08 kg/s and the inlet temperature of 130, 140, and 150 K. It is noticed that the highest temperature drop is obtained for the inlet temperature of 150 K. Thirdly, based on the experimental data, an ANN and ANFIS model is developed to predict the optimal range in which the turboexpander have maximum isentropic efficiency and temperature drop. The results deduce some valuable experimental data and also accumulate the design methodology of radial inflow turbine for cryogenic applications.
Summary
Carbon capture by cryogenic treatment is one of the emerging methods in curbing carbon dioxide (CO2) emissions, because it not only offers energy‐saving, but also environmental benefits due ...to the absence of chemicals as used by other methods. However, the cryogenic system used for CO2 capture demands a high‐effectiveness heat exchanger. In this case, a plate‐fin heat exchanger (PFHE) is used. In this study, PFHE is analyzed for decreasing the temperature of CO2 and N2 mixture with cold N2 gas. The study consists of three parts that are (i) a comparative study of Aspen EDR with heat exchanger parameter evaluation correlations such as Joshi & Webb, Manglik & Bergles, and Maiti & Sarangi, and (ii) validation of Aspen EDR software with experimental results which is available from open literature. Hence, validation of heat exchanger design is indirectly done with experimental results. (iii) Besides this, the research is aimed at studying the influence of the gas mixture inlet temperature, the concentration of CO2, pressure drop, and the mass flow rate on PFHE's effectiveness. The study results are analyzed and presented in this research article.
Application of the plate‐fin heat exchanger to the cryogenic carbon capture is described.
The effect of CO2 concentration, mass flow rate and inlet temperature of feed gas on the performance of the plate‐fin heat exchanger is discussed.
To the Editor:
Choueiri et al. (Aug. 19 issue)
1
reported a significant improvement in disease-free survival with the addition of adjuvant pembrolizumab after nephrectomy in patients with renal-cell ...carcinoma (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio, 0.68; 95% confidence interval, 0.53 to 0.87; P=0.002). Although the results are encouraging, the arbitrary duration of 12 months of adjuvant treatment is a concern. In the pembrolizumab group, 61.1% of the patients completed 17 cycles of treatment over 1 year, and the most common reason for treatment discontinuation was an adverse event (which occurred in 21.3% of patients).
1
In patients . . .
To the Editor:
Stone et al. (Aug. 3 issue)
1
found that adding midostaurin to a standard chemotherapy regimen containing daunorubicin at a dose of 60 mg per square meter of body-surface area ...significantly prolonged overall and event-free survival among patients with acute myeloid leukemia (AML) and a
FLT3
mutation (point mutation in the tyrosine kinase domain TKD or internal tandem duplication ITD mutation) as compared with placebo plus standard chemotherapy. In a previous study, a nonsignificant trend for benefit beyond 12 months was shown in patients with a
FLT3
mutation of the ITD subtype who received daunorubicin at a dose . . .
Summary
The separation of carbon dioxide (CO2) from the flue gas is a challenging one in terms of the energy penalty. The development of a cryogenic or low‐temperature CO2 separation method helps to ...overcome the energy penalty associated with CO2 separation. In this study, a preliminary investigation is carried out in a theoretically modified Linde process which can be used for CO2 separation from a gas mixture containing CO2 and N2. A cryogenic cooling process is also studied for CO2 separation of the same quality of the gas mixture. The compression work and cooling loads in each case are analyzed using Aspen Plus software. The effect of CO2 volume in the mixture, compressor efficiency, and compressor discharge pressure on the energy consumption is studied for both the theoretically modified Linde and the cryogenic cooling processes, and the results are compared between them. The results indicated in the CO2 separation by the cooling process are better than the modified Linde process. The energy penalty shows for 20% CO2 composition of separation by the cooling process with the single‐stage compression is lower by around 123.9% and 128.8% in terms of compression work and compressor cooling load, respectively, than those of the modified Linde process working in a single‐stage compression. The separation by the cooling process refrigeration effect is 15.9% more than in the modified Linde process.
For CO2 separation, a comparison of modified Linde and cryogenic cooling is carried out by using Aspen Plus software and mathematical modelling.
The effect of CO2 concentration in the feed gas and recovery of liquid CO2 on energy penalty is discussed.
To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS).
Open ...label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2.
108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%.
Modified gemcitabine and oxaliplatin (mGemOx)—gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)—gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks.
Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval CI: 7·9–9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8–12·6) in mGemOx and 10·4 months (95% CI: 9·1–11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (−1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem.
This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority.
CTRI/2010/091/001406.
•No randomised controlled trials have compared CisGem and mGemOx in unresectable gallbladder cancer.•A phase III randomised equivalence study with 2 months of equivalence margin was conducted.•243 subjects were analysed in modified ITT analysis.•Median overall survival in mGemOx was 9 months and 8·3 months in CisGem.•Results confirmed that 8 cycles of CisGem were not equivalent to 6 cycles of mGemOx.
To the Editor:
The benefit of nivolumab maintenance therapy in the study by Bajorin et al. (June 3 issue)
1
appears to have been driven mainly by the 308 patients who received cisplatin as ...neoadjuvant therapy and reflects cross-sensitivity (hazard ratio, 0.52; 95% confidence interval CI 0.38 to 0.71) rather than by the 401 patients who did not (hazard ratio, 0.92; 95% CI, 0.69 to 1.21). This also explains the lack of benefit in the 309 patients with a creatinine clearance of less than 60 ml per minute (hazard ratio, 0.87; 95% CI, 0.64 to 1.18) and by those with primary . . .
The prognosis of patients with multiple myeloma (MM) has improved significantly in the past two decades. This is attributed to use of novel agents for induction, high-dose chemotherapy and autologous ...stem cell transplantation (ASCT), maintenance therapy, and improved supportive care. Currently, evidence-based management guidelines/recommendations developed by International societies/groups are being followed partially in low-resource settings. Lack of quality diagnostics (eg, cytogenetics/fluorescence in situ hybridization (FISH), serum free light chains), novel therapeutics, and trained manpower, and limited financial resources are key challanges. An optimal utilization of available resources with continued educational activities of treating physicians focused on improving knowledge in the management of such patients may be a way forward to improve the outcome of myeloma patients in these countries. Our current approach to the management of this disease is presented here through a discussion of clinical vignettes.
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