Search

Hollow sphere polymeric pigments prepared from styrene-acrylate copolymer referred to as organic opacifiers (OP) are the primary substitutes of TiO.sub.2 in water-based architectural paints. This study describes the method for the quantification of OP in water-based paints using dynamic mechanical thermal analysis (DMTA). The significance of DMTA in visualizing the glass transitions over differential scanning calorimetry (DSC) is showcased. The glass transition temperature (T.sub.g) of OP was found to be ~109°C by DSC method and ~125°C by DMTA method. The peak intensity of tan [delta] at T.sub.g of OP in paints (tan [delta].sub.2) is not affected by the curing time and linearly increases as a function of OP concentration in water-based paints, irrespective of the difference in volume solids. DMTA can efficiently quantify OP in paint film if it is [greater than or equal to]3.3% (w/w). Increasing concentration of a coalescing solvent in water-based paints has a detrimental effect on the peak intensity of tan [delta].sub.2. Two commercially available grades of OP having difference in the core-shell morphology have been studied. Internal morphology of the OP studied by scanning electron microscopy has a significant effect on the peak intensity of tan [delta].sub.2 thereby affecting its opacity performance in paints. Owing to the limited effect of curing time, volume solids and coalescing solvent on the peak intensity of tan [delta].sub.2 of paints, this method can be used for the quantification of OP in paints, as it has been validated with seven commercially available paints with known OP contents., Author(s): Ritesh A. Bhavsar [sup.1] , Venugopal B. Raghavendra [sup.1] Author Affiliations: (1) grid.464770.6, 0000 0004 1776 8649, Asian Paints Limited, R&T center, Plot No. C-3B/1, TTC Industrial Area, MIDC [...]

Psoriasis is a chronic inflammatory skin disease that affects both localized and systemic regions of the body. This condition is characterized by the hyperproliferation of keratinocytes, resulting in skin thickening, scaling, and erythema. The severity of psoriasis depends on the extent of skin involvement, the location of the infection, and the symptoms that the person exhibits. While no cure exists, conventional therapies such as topical and systemic drugs are generally used to manage the exacerbation of symptoms. However, chronic use and overdose can lead to other severe adverse effects. Therefore, scientists and researchers are exploring potential nutraceuticals that can be considered as an alternative source of management for psoriasis. Current research aims to use different combinations of natural compounds like cannabidiol, myo-inositol, eicosapentaenoic acid, and krill oil to study the effect of these compounds in the prevention and treatment of psoriasis in the imiquimod (IMQ)-induced psoriatic mice model. The Psoriasis Area Severity Index (PASI) scoring system is used to analyze skin thickness, scales, and erythema. The results indicate that the krill oil combined with the cannabidiol and myo-inositol shows better results than other nutraceutical combinations. In the future, the natural products of krill oil can be combined with cannabidiol and myo-inositol to create an improved alternative to existing steroidal and nonsteroidal anti-inflammatory drugs for psoriasis treatment., (© 2023 John Wiley & Sons Ltd.)

Introduction: Real-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC)., Patients and Methods: In this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI-CPI or tyrosine kinase inhibitor (TKI)-CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS)., Results: Data from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI-CPI therapy (n = 171) and 5.0 months for TKI-CPI therapy (n = 58). After 1L CPI-CPI or TKI-CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies., Conclusion: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI-CPI or TKI-CPI therapy is used., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies., Methods: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response)., Results: A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P = 0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P = 0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively., Conclusions: Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Objective: Adjuvant pembrolizumab significantly improved overall survival (OS) in renal cell carcinoma (RCC), but real-world data on sequential treatment are scarce. We sought to evaluate the clinical outcomes of first-line (1L) systemic therapy following adjuvant immune oncology (IO)-based regimens., Methods: A retrospective study including patients with recurrent RCC following adjuvant IO across 29 international institutions was conducted. The primary endpoint was progression-free survival (PFS) on 1L systemic therapy estimated using the Kaplan-Meier method. Preplanned subanalyses of clinical outcomes by type of 1L systemic therapy, recurrence timing, and International Metastatic RCC Database Consortium (IMDC) risk groups were performed. Treatment-related adverse events leading to treatment discontinuation, dose reduction, or corticosteroid use were assessed., Key Findings and Limitations: A total of 94 patients were included. Most received adjuvant pembrolizumab (n = 37, 39%), atezolizumab (n = 28, 30%), or nivolumab + ipilimumab (n = 15, 16%). The cohort included 49 (52%) patients who had recurrence within 3 mo of the last adjuvant IO dose, whereas 45 (48%) recurred beyond 3 mo. Bone metastases were significantly higher in tumors recurring at <3 mo (10/49, 20%) than those recurring at >3 mo (1/45, 2.2%; p = 0.008). Most patients received 1L vascular endothelial growth factor-targeted therapy (VEGF-TT; n = 37, 39%), IO + VEGF-TT (n = 26, 28%), or IO + IO (n = 12, 13%). The remaining underwent local therapy. The median follow-up for the 1L systemic therapy cohort was 15 mo. The 18-mo PFS and OS rates were 45% (95% confidence interval [CI]: 34-60) and 85% (95% CI: 75-95), respectively. Treatment-related adverse events occurred in 32 (42%) patients and included skin toxicity (n = 7, 9.2%), fatigue (n = 6, 7.9%), and diarrhea/colitis (n = 4, 5.3%). Limitations included selecting patients from large academic centers and the short follow-up period., Conclusions and Clinical Implications: A subset of patients with recurrent RCC following adjuvant IO respond to systemic therapies, including VEGF-TT and IO-based regimens. Notably, patients with favorable-risk disease may derive more benefit from VEGF-TT than from IO therapies in this setting. Future approaches utilizing radiographic tools and biomarker-based liquid biopsies are warranted to detect occult metastatic disease and identify candidate patients for adjuvant IO therapy., Patient Summary: Adjuvant pembrolizumab significantly improved overall survival in renal cell carcinoma (RCC). There are limited data on clinical outcomes after the recurrence of RCC tumors following adjuvant immunotherapy. In this study, we find that patients respond to subsequent systemic therapies across different treatment options., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: We conducted a systematic literature review (SLR) to identify clinical evidence on treatments in advanced renal cell carcinoma (aRCC) after the failure of prior therapy with cytokines, tyrosine kinase inhibitors, or immune checkpoint inhibitors. Herein, we summarise the evidence for axitinib in aRCC after the failure of prior therapy with cytokines or sunitinib., Methods: This SLR was registered with PROSPERO (CRD42023492931) and followed the 2020 PRISMA statement and the Cochrane guidelines. Comprehensive searches were conducted in MEDLINE and Embase as well as for conference proceedings. Study eligibility was defined according to population, intervention, comparator, outcome, and study design., Results: Of 1252 titles/abstracts screened, 266 peer-reviewed publications were reviewed, of which 182 were included. In addition, 28 conference abstracts were eligible. Data on axitinib were reported in 55 publications, of which 16 provided efficacy and/or safety outcomes on axitinib after therapy with sunitinib or cytokines. In these patients, median progression-free and overall survival ranged between 5.5 and 8.7 months and 11.0 and 69.5 months, respectively., Conclusions: Axitinib is commonly used in clinical practice and has a well-characterised safety and efficacy profile in the treatment of patients with aRCC after the failure of prior therapy with sunitinib or cytokines.

Background: Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma., Methods: 1) African Green monkeys (AGM) received doxorubicin (30-60 mg/m 2 /biweekly IV, cumulative dose: 240 mg/m 2 ). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT., Results: In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses., Conclusions: In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.

Introduction: Diabetes mellitus is one of the most common metabolic disorder and leading cause of death and disability in the world. Magnesium deficiency can lead to development of diabetic complications such as nephropathy, retinopathy, thrombosis and hypertension. This is a cross sectional study designed to determine whether there is any association between serum magnesium concentration [Mg2 +] and the rate of renal function deterioration in patients with diabetes mellitus type 2 (DM2). Materials & Methods: A cross sectional study was done in randomly chosen 50 Type 2 diabetic patients without renal dysfunction,50 diabetic with renal dysfunction of age between 40 and 60 years, 50 non diabetic controls with age and sex matched attending our institute during November-February2018 were included. All patients and controls underwent thorough clinical examination and estimation of serum Magnesium, FBS, PPBS, hemoglobin A(1C), urinary albumin creatine ratio(UACR), as well as history of hypertension and pharmacy profiles were retrieved. Results: The mean serum magnesium levels among Type 2 DM with renal dysfunction , Type 2 DM without renal dysfunction and healthy controls were 0.795±0.199mg/dl, 1.319±0.103mg/dl, 2.33±0.28mg/dl respectively. Conclusion: There was a significant reduction in serum Magnesium [Mg] levels in diabetics compared to the controls. Lower “Mg” is associated with a faster renal function deterioration rate in Type 2 DM patients

Background: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain., Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point., Results: A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P = 0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy., Conclusions: Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.)., (Copyright © 2024 Massachusetts Medical Society.)

Remote Vision-Based digital Patient Monitoring (VBPM) of pulse (PR) and respiratory rate (RR) was set up in six single rooms in an acute medical and an orthopaedic ward. We compared 102 PR and 154 RR VBPM measurements (from 27 patients) with paired routine nurse measurements. VBPM measurements of RR were validated by reviewing video footage. Nurse measurements of RR were often 16-18 breaths/minute, and did not match VBPM RR (overestimating at low RR and underestimating at high RR). Nurse measurements of pulse were on average 3.9 beats per minute greater than matched VBPM measurements. VBPM was unobtrusive and well accepted., Competing Interests: Competing interests: Oxehealth Ltd provided funds for AL and LS to be employed as researchers on this study. VG was previously employed by Oxehealth during this study, and BV and OG are current employees of Oxehealth. MG is a paid consultant to Oxehealth., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Risk of massive intraoperative hemorrhage and the difficulty to control it makes the laparoscopic treatment of giant hepatic hemangiomas (GH) a challenge for minimally invasive hepatobiliary surgeons. Symptomatic GHs of more than 20 cm (extremely giant hepatic hemangiomas) are typically treated with an open resection. There is a paucity of literature on laparoscopic resection of extremely giant hepatic hemangiomas. We describe (with video), here, the technical nuances of pure laparoscopic resection of an extremely giant hepatic hemangioma using modified port positions and the anterior approach.

Background: Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors (VEGFIs) has improved cancer outcomes and is increasingly used. These drug classes are associated with cardiovascular toxicities when used alone, but heterogeneity in trial design and reporting may limit knowledge of toxicities in patients receiving these in combination., Objectives: The aim of this study was to assess consistency and clarity in definitions and reporting of cardiovascular eligibility criteria, baseline characteristics, and cardiovascular adverse events in ICI and VEGFI combination trials., Methods: A scoping review was conducted of phase 2 to 4 randomized controlled trials of ICI and VEGFI combination therapy for solid tumors. Trial cardiovascular eligibility criteria and baseline cardiovascular characteristic reporting in trial publications was assessed, and cardiovascular adverse event definitions and reporting criteria were also examined., Results: Seventeen trials (N = 10,313; published 2018-2022) were included. There were multiple cardiovascular exclusion criteria in 15 trials. No primary trial publication reported baseline cardiovascular characteristics. Thirteen trials excluded patients with prior heart failure, myocardial infarction, hypertension, or stroke. There was heterogeneity in defining cardiovascular conditions. "Grade 1 to 4" cardiovascular adverse events were reported when incidence was ≥5% to 25% in 15 trials. Incident hypertension was recorded in all trials, but other cardiovascular events were not consistently reported. No trial specifically noted the absence of cardiovascular events., Conclusions: In ICI and VEGFI combination trials, there is heterogeneity in cardiovascular exclusion criteria, reporting of baseline characteristics, and reporting of cardiovascular adverse events. This limits an optimal understanding of the incidence and severity of events relating to these combinations. Better standardization of these elements should be pursued. (Exclusions and Representation of Patients With Kidney Disease and Cardiovascular Disease in Drug Trials of the Novel Systemic Anti-Cancer Therapies VEGF-Signalling Pathway Inhibitors Alone or in Combination With Immune Checkpoint Inhibitors; CRD42022337942)., Competing Interests: Drs Petrie and Lang are supported by a British Heart Foundation Centre of Research Excellence Aware (RE/18/6/34217). Dr Rankin has received support through an unrestricted grant from Roche Diagnostics. Dr Lang has received research grants from Roche Diagnostics, AstraZeneca, and Boehringer Ingelheim; and has received consulting and speaker fees from Roche Diagnostics, MyoKardia, Pharmacosmos, Akero Therapeutics, CV6 Therapeutics, Jazz Pharma, and Novartis, all outside the submitted work. Dr Lees has received personal lectureship honoraria from AstraZeneca, Pfizer, and Bristol Myers Squibb, outside the submitted work. Dr Mark has received grants and personal fees from Boehringer Ingelheim; and has received honoraria from AstraZeneca, GlaxoSmithKline, Pharmacosmos, and Astellas, outside the submitted work. Dr Venugopal is a consultant or adviser for Bristol Myers Squibb, EUSA Pharma, and Merck Sharp & Dohme; has received travel and accommodation expenses from Bristol Myers Squibb, EUSA Pharma, and Ipsen; has received research funding to the institution from Bristol Myers Squibb, Exelixis, Ipsen, Merck Sharp & Dohme, and Pfizer; has received honoraria from Bristol Myers Squibb, Ipsen, and Pfizer; and is a Speakers Bureau member and has provided expert testimony for Bristol Myers Squibb, Eisai, EUSA Pharma, Merck Serono, Merck Sharp & Dohme, and Pfizer. Dr Jones has received grants from Astellas, Clovis, Exelixis, Bayer, and Roche; has received honoraria from Astellas, Janssen, Bayer, Pfizer, Merck Serono, Merck Sharpe & Dohme, Novartis, Roche, Ipsen, and Bristol Myers Squib. Dr Petrie has received grants from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, Horizon, and Phramacosmos, all outside the submitted work; has received honoraria from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, and Vifor. Dr Elyan has reported that he has no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: In patients with renal cell carcinoma (RCC) enrolled in the phase III KEYNOTE-564 trial (NCT03142334), disease-free survival (DFS) following nephrectomy was prolonged with use of adjuvant pembrolizumab therapy versus placebo. Patient-reported outcomes (PROs) provide an important measure of health-related quality of life (HRQoL) and can complement efficacy and safety results., Patients and Methods: In KEYNOTE-564, 994 patients were randomly assigned to receive pembrolizumab 200 mg (n = 496) or placebo (n = 498) intravenously every 3 weeks for ≤17 cycles. Patients who received ≥1 dose of treatment and completed ≥1 HRQoL assessment were included in this analysis. HRQoL end points were assessed using the EORTC QLQ-C30, FKSI-DRS, and EQ VAS. Prespecified and exploratory PRO end points were mean change from baseline in EORTC QLQ-C30 GHS/QoL score, EORTC QLQ-C30 physical function subscale score, and FKSI-DRS score., Results: No clinically meaningful difference in least squares mean scores for pembrolizumab versus placebo were observed at week 52 for EORTC QLQ-C30 GHS/QoL (-2.5; 95% CI -5.2 to 0.1), EORTC QLQ-C30 physical functioning (-0.87; 95% CI -2.7 to 1.0), and FKSI-DRS (-0.7; 95% CI -1.2 to -0.1). Most PRO scores remained stable or improved for the EORTC QLQ-C30 GHS/QoL (pembrolizumab, 54.3%; placebo, 67.5%), EORTC QLQ-C30 physical functioning (pembrolizumab, 64.7%; placebo, 68.8%), and FKSI-DRS (pembrolizumab, 58.2%; placebo, 66.3%)., Conclusions: Adjuvant treatment with pembrolizumab did not result in deterioration of HRQoL. These findings together with the safety and efficacy findings support adjuvant pembrolizumab treatment following nephrectomy., Trial Registration: Clinicaltrials.gov Identifier: NCT03142334., (© The Author(s) 2023. Published by Oxford University Press.)

Real-world cabozantinib use has increased since its approval to treat patients with advanced renal cell carcinoma (RCC) in 2016. We reviewed cabozantinib use in real-world clinical practice and compared outcomes with pivotal cabozantinib randomized control trials (RCTs). This PRISMA-standard systematic literature review evaluated real-world effectiveness and tolerability of cabozantinib in patients with RCC (PROSPERO registration: CRD42021245854). Systematic MEDLINE, Embase, and Cochrane database searches were conducted on November 2, 2022. Eligible publications included ≥ 20 patients with RCC receiving cabozantinib. After double-screening for eligibility, standardized data were abstracted, qualitatively summarized, and assessed for risk of bias using the Newcastle-Ottawa Scale. Of 353 screened publications, 41 were included, representing approximately 11,000 real-world patients. Most publications reported cabozantinib monotherapy cohort studies (40/41) of retrospective (39/41) and multicenter (32/41) design; most included patients from North America and/or Europe (30/41). Baseline characteristics were demographically similar between real-world and pivotal RCT populations, but real-world populations showed greater variation in prevalence of prior nephrectomy, multiple-site/brain metastasis, and nonclear-cell RCC histology. Cabozantinib activity was reported across real-world treatment lines and tumor types. Overall survival, progression-free survival, and objective response rate values from pivotal RCTs were within the ranges reported for equivalent outcomes across real-world studies. Common real-world grade ≥ 3 adverse events were consistent with those in pivotal RCTs (fatigue, palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension), but less frequent. No new tolerability concerns were identified. Real-world RCC survival outcomes for cabozantinib monotherapy were broadly consistent with pivotal RCTs, despite greater heterogeneity in real-world populations., Competing Interests: Disclosure MG-G: Consultancy or advisory role: Amgen, Astellas Medivation, AstraZeneca, Bayer/Onyx, Bristol Myers Squibb, Eisai, Ipsen, Janssen-Cilag, MSD Oncology, Pfizer, Roche, and Sanofi; Research funding (to institution): AstraZeneca, Ipsen, Janssen-Cilag, Merck, MSD Oncology, Pfizer, and Roche; Travel, accommodations, and expenses: Astellas Pharma, AstraZeneca, Ipsen, Janssen-Cilag, Pfizer, and Roche. LB: Consultancy or advisory role: AstraZeneca, Ipsen, MSD, Novartis, Pfizer, and Roche. MTC: Consultancy or advisory role: Astellas, AstraZeneca, AXDev, Eisai, EMD Serono, Exelixis, Genentech, Pfizer, and SeaGen; Research funding: ApricityHealth, Aravive, AstraZeneca, Exelixis, Janssen, and Pfizer/EMD Serono; Nonbranded educational programs: Bristol Myers Squibb, Merck, Pfizer/EMD Serono, and Roche. AM: Consultancy or advisory role: Bristol Myers Squibb, Clovis Oncology, Eisai, GSK, Ipsen, Pfizer, and Tesaro. BV: Consultancy or advisory role: Bristol Myers Squibb, EUSA Pharma, and Merck Sharp & Dohme; travel/accommodation/expenses: Bristol Myers Squibb, EUSA Pharma, and Ipsen; Research funding (institution): Bristol Myers Squibb, Exelixis, Ipsen, Merck Sharp & Dohme, and Pfizer; Honoraria (self): Bristol Myers Squibb, Ipsen, and Pfizer; Speaker bureau/expert testimony: Bristol Myers Squibb, Eisai, EUSA Pharma, Merck Serono, Merck Sharp & Dohme, and Pfizer. JZ: Research funding: Ipsen. PD: Employment: Ipsen; Stock and other ownership interests: Biogen and Ipsen. GP: Consulting or advisory role: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Janssen, Ipsen, Lilly, Merck, MSD, Novartis, Pfizer, and Roche. LA: Consulting or advisory role: Astellas Pharma, Bristol Myers Squibb, Ipsen, Janssen, Merck, MSD, Pfizer, and Roche; Travel, accommodation, expenses: Bristol Myers Squibb, Ipsen, and MSD., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile., Methods: Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy., Results: Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively., Conclusion: Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.

BACKGROUND: EMBARK, a controlled trial reported elsewhere, showed enzalutamide plus leuprolide (combination) and enzalutamide monotherapy prolonged metastasis-free survival versus placebo plus leuprolide (alone) in patients with high-risk biochemically recurrent prostate cancer. Health-related quality of life was also analyzed but not reported. METHODS: In EMBARK, patients with biochemical recurrence (prostate-specific antigen doubling time of ≤9 months) were randomly assigned (1:1:1) to combination (n=355), leuprolide-alone (n=358), or enzalutamide monotherapy (n=355). In this article we provide the patient-reported outcomes (PROs) from EMBARK at baseline and every 12 weeks until metastasis or death. The key end point was time to first and confirmed clinically meaningful deterioration (TTFD/TTCD) in pain and health-related quality of life using four PRO measures and predefined thresholds. RESULTS: At baseline, all groups had high health-related quality of life. For worst pain, the median TTFD was 19.35 months with leuprolide alone, 13.93 months with combination (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.30) and 16.59 months with monotherapy (hazard ratio, 1.09; 95% CI, 0.90 to 1.31). The median TTCD was 66.27 months with leuprolide alone, 80.00 months with combination (hazard ratio, 0.82; 95% CI, 0.65 to 1.04), and 60.91 months with monotherapy (hazard ratio, 1.02; 95% CI, 0.82 to 1.28). For Functional Assessment of Cancer Therapy–Prostate total score, the median TTFD was 11.10 months with leuprolide alone, 8.31 months with combination (hazard ratio, 1.14; 95% CI, 0.95 to 1.36), and 8.38 months with monotherapy (hazard ratio, 1.17; 95% CI, 0.98 to 1.39). The median TTCD was 36.53 months with leuprolide alone, 38.77 months with combination (hazard ratio, 1.04; 95% CI, 0.85 to 1.28), and 30.55 months with monotherapy (hazard ratio, 1.16; 95% CI, 0.95 to 1.41). CONCLUSIONS: The PROs from EMBARK show that both enzalutamide combination and monotherapy versus leuprolide alone, with oncologic benefits noted above, preserved high health-related quality of life in patients with high-risk biochemical recurrence of prostate cancer. (Funded by Pfizer and Astellas Pharma; ClinicalTrials.gov number, NCT02319837.)

Background: Cancer mortality has doubled in India, a lower and middle-income country, from 1990 to 2016, depicting the ever-increasing burden of non-communicable disease. Karnataka, situated in the south of India, is one of the states with a rich medical college and hospital milieu. We present the status of cancer care across the state from the data collected by the investigators through public registries and personal communication to the concerned units to know the distribution of various services across the districts and give probable directives to improve on the present situation with emphasis on radiation therapy. This study may be taken as a bird's eye view of the situation across the country and form a basis based on which future planning of services and areas to emphasize on, may be considered., Purpose: The establishment of a radiation therapy center holds the key to the establishment of comprehensive cancer care centers. The existing situation of such centers and the need and scope for inclusion and expansion of cancer units is presented in this article.