New Standard Of Care Research Articles

Economic evaluation of NALIRIFOX vs. nab-paclitaxel and gemcitabine regimens for first-line treatment of metastatic pancreatic ductal adenocarcinoma from U.S. perspective

BackgroundThe cost-effectiveness of NALIRIFOX as a potential new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) has yet to be established. Our objective was to evaluate the cost-effectiveness of NALIRIFOX vs. nab-paclitaxel and gemcitabine in this indication from the perspective of U.S. public payers.MethodsA partitioned survival model was constructed from the perspective of U.S. public payers, drawing on baseline patient characteristics and vital clinical data from the NAPOLI-3 trial. Costs and utilities were sourced from publicly accessible databases and literature. A lifetime horizon was applied, with an annual discount rate of 3%. We calculated and compared cumulative costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). To evaluate the model’s robustness, sensitivity analyses, scenario analyses, and subgroup analyses were carried out. Additionally, a price simulation for the costly liposomal irinotecan was conducted to inform the pricing strategy at the given willingness to pay (WTP) threshold.ResultsIn the base-case analysis, NALIRIFOX provided an additional 0.29 QALYs with an ICER of $206,340.69 /QALY compared to nab-paclitaxel and gemcitabine, indicating it is not cost-effective at a $150,000/QALY threshold. Sensitivity analysis showed the model was most sensitive to the costs of liposomal irinotecan, capecitabine, and post-progression care. Probabilistic sensitivity analysis indicated a 17.66% probability of NALIRIFOX being cost-effective at $150,000/QALY, rising to 47.48% at $200,000/QALY. Pricing simulations suggested NALIRIFOX could become cost-effective at $150,000/QALY if the price of irinotecan liposome drops to $53.24/mg (a 14.8% reduction).ConclusionsNALIRIFOX may not be cost-effective at its current price as a first-line treatment for patients with mPDAC in the long term. The cost of liposomal irinotecan has the greatest impact. It may become cost-effective only if its cost is reduced by 14.8%, with a WTP threshold of $150,000 /QALY.

Strategic Advances in Combination Therapy for Metastatic Castration-Sensitive Prostate Cancer: Current Insights and Future Perspectives.

The contemporary treatment for metastatic castration-sensitive prostate cancer (mCSPC) has evolved significantly, building on successes in managing metastatic castration-resistant prostate cancer (mCRPC). Although androgen deprivation therapy (ADT) alone has long been the cornerstone of mCSPC treatment, combination therapies have emerged as the new standard of care based on recent advances, offering improved survival outcomes. Landmark phase 3 trials demonstrated that adding chemotherapy (docetaxel) and androgen receptor pathway inhibitors to ADT significantly enhances overall survival, particularly for patients with high-volume, high-risk, or de novo metastatic disease. Despite these advancements, a concerning gap between evidence-based guidelines and real-world practice remains, with many patients not receiving recommended combination therapies. The challenge in optimizing therapy sequences, considering both disease control and treatment burdens, and identifying clinical and biological subgroups that could benefit from personalized treatment strategies persists. The advent of triplet therapy has shown promise in extending survival, but the uro-oncology community must narrow the gap between evidence and practice to deliver the most effective care. Current research is focused on refining treatment approaches and utilizing biomarkers to guide therapy selection, aiming to offer more personalized and adaptive strategies for mCSPC management. Thus, aligning clinical practices with the evolving evidence is urgently needed to improve outcomes for patients facing this incurable disease.

Posttransplant cyclophosphamide versus anti-thymocyte globulin versus combination for graft-versus-host disease prevention in haploidentical transplantation for adult acute myeloid leukemia: A report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

The optimal choice for graft-versus-host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo-SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo-SCT in complete remission between 2007 and 2021 at 260 EBMT-participating centers who received either PTCy (n=2999), ATG (n=358), or combination prophylaxis (n=292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow-up was 31.8 months. On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female-to-male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p=.003), worse leukemia-free survival (HR, 1.4; p=.002), overall survival (HR,1.49; p=.0009), and GVHD-free and relapse-free survival (HR,1.29; p=.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2-4 (HR, 0.51; p=.0003) and grade 3-4 (HR, 0.5; p=.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo-SCT for AML.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. Merck Sharp & Dohme, a subsidiary of Merck & Co.

Hypofractionated Dose Escalation Radiotherapy for High-Risk Prostate Cancer: the survival analysis of the Prostate Cancer Study-5 (PCS-5), a GROUQ-led phase III trial

Background and objectiveProstate Cancer Study 5 (PCS5) compared conventional fractionated radiotherapy (CFRT) with hypofractionated radiotherapy (HFRT) in high-risk prostate cancer (PCa) patients, hypothesizing similar toxicity and survival outcomes. This report presents the efficacy analysis. MethodsPCS5 is a Canadian multicenter, open-label, phase 3 randomized control trial. Men with histologically proven, clinically localized PCa with one or more high-risk features (T3/T4, Gleason score ≥8, and prostate-specific antigen >20) were eligible. Patients were randomized 1:1 to CFRT (76 Gy/38 fractions [Fx] to the prostate and 46 Gy/23 Fx to the pelvic lymph nodes [PLNs]) or HFRT (68 Gy/25 Fx to the prostate and 45 Gy/25 Fx to the PLNs) and 28 mo of androgen suppression. The primary endpoint was toxicity; secondary endpoints included survival outcomes. Key findings and limitationsOf 329 patients, 164 were randomized to HFRT and 165 to CFRT, with 159 in the HFRT arm and 160 in the CFRT arm included in survival analyses. At the 5-yr median follow-up, there were no significant differences in overall survival (OS; 90.3% vs 89.7%; risk ratio [RR]: 1.01; 95% confidence interval [CI]: 0.93–1.09), PCa-specific survival (PCSS; 97.4% vs 97.5%; RR: 1.00; 95% CI: 0.93–1.07), biochemical recurrence–free survival (BCRFS; 85.2% vs 85.2%; RR: 1.00; 95% CI: 0.91–1.10), or distant metastasis–free survival (DMFS; 87.1% vs 87.1%; RR: 1.00; 95% CI: 0.92–1.09). Hazard ratios were 0.92 (95% CI: 0.56–1.53) for OS, 1.31 (95% CI: 0.46–3.78) for PCSS, 0.85 (95% CI: 0.56–1.30) for BCRFS, and 0.90 (95% CI: 0.56–1.43) for DMFS. Sample size was a limiting factor. Conclusions and clinical implicationsThere were no differences in survival outcomes between HFRT (68 Gy/25 Fx) and CFRT (76 Gy/38 Fx). HFRT, including PLN radiotherapy and long-term androgen deprivation therapy, should be considered a new standard of care for high-risk PCa patients undergoing external beam radiotherapy.

Liver transplantation in metastatic colorectal cancer: a new standard of care?

Liver transplantation in metastatic colorectal cancer: a new standard of care?

425. PARACONDUIT HIATAL HERNIA FOLLOWING ESOPHAGECTOMY IN A PORTUGUESE TERTIARY CENTER

Abstract Background Esophageal Cancer is the seventh most common cancer worldwide with poor overall survival. As minimally invasive esophagectomy is becoming the new standard of care, an increased incidence of para-conduit hiatal hernias has been reported. Possible risk factors, other than those related to the operative approach have been suggested, such as location of the tumor. Histological type may also account for the increased incidence of hiatal hernias due to shift from esophageal squamous cell carcinomas to adenocarcinomas of the gastro-esophageal junction in Western world. We reviewed our center’s experience to determine whether the adoption of minimally invasive esophagectomy was associated with an increased incidence of para-conduit hernia. Methods A single-center, prospective database was used to retrospectively analyze consecutive patient who underwent esophagectomy between January 2007 and December 2023. Results Between January 2007 and December 2023, 497 patients were submitted to esophagectomy (Ivor-Lewis, McKeown or transhiatal) due to cancer (242 squamous cell carcinomas and 255 adenocarcinomas); 163 proximal esophageal cancers and 323 distal esophageal cancers. An hiatal hernia was diagnosed in 11 (2.21%) of 497 included patients submitted to esophagectomy; 5 (3.25%) after 154 totally minimally invasive esophagectomies, 3 (11.11%) after 27 hybrid esophagectomies and 3 (0.95%) after 316 open esophagectomies. The median days to diagnosis of hiatal hernia was 199 (6-3881) days. Surgical treatment consisted of cruroplasty in 1 patient, crurorrhaphy in 6 patients, reduction of herniated contents in 4 patients. The tumor was located proximally in 1 patient whereas the remaining 10 were at distal esophagus or at gastro-esophageal junction. Regarding pathologic evaluation, 2 were squamous cell carcinomas (0.82%) and 9 adenocarcinomas (3.53%). Conclusion In our experience, the adoption of minimally invasive esophagectomy has been associated with an increase of symptomatic para-conduit hernia, in line with the reports of recent meta-analyses. The prevalence of paraconduit hiatal hernia was also increased in adenocarcinomas, revealing the shift in the histological type in Western world. The true rate of herniation may be much higher, as our patients are not routinely submitted imaging diagnostic tests as part of their follow-up.

A call to action by the American Academy of Pediatrics Trainees and early career neonatologists' national advocacy campaign "Carousel care": best practice guidelines for NICU family mental health standard of care.

This article introduces the need for creating programs to address pervasive perinatal mood and anxiety disorders (PMAD) for neonatal-intensive care unit (NICU) families. When left unrecognized and untreated, PMADs impact the outcomes of NICU families and children. There is currently no standard of care for addressing NICU PMADs. This article highlights the work of the American Academy of Pediatrics Trainees and Early Career Neonatologist's National advocacy campaign, Carousel Care. This article introduces how Carousel Care helps provide a framework for providers and at individual, institutional, and national levels to implement new standards of care incorporating NICU mental health programs.

Probing the killing potency of tumor-infiltrating lymphocytes on microarrayed colorectal cancer tumoroids

Immunotherapy has emerged as a new standard of care for certain cancer patients with specific cellular and molecular makeups. However, there is still an unmet need for ex vivo models able to readily assess the effectiveness of immunotherapeutic treatments in a high-throughput and patient-specific manner. To address this issue, we have developed a microarrayed system of patient-derived tumoroids with recreated immune microenvironments that are optimized for the high-content evaluation of tumor-infiltrating lymphocyte functionality. Here we show that this system offers unprecedented opportunities to evaluate tumor immunogenicity, characterize the response to immunomodulators, and explore novel approaches for personalized immuno-oncology.

Zinc for GNAO1 encephalopathy: Preclinical profiling and a clinical case

De novo pathogenic variants in GNAO1-the gene encoding the major neuronal G protein Gαo-cause pediatric encephalopathies and other neurological deficiencies largely refractory to available therapies. Zn2+ emerged to restore guanosine triphosphate hydrolysis and cellular interactions of pathogenic Gαo; dietary zinc salt supplementation improves lifespan and motoric function in a Drosophila disease model. Using biochemical, animal, and first-in-human studies, we provide support for the patient stratification and application of zinc acetate in GNAO1-associated disorders. We show that 16 different pathogenic missense variants cluster in three distinct groups in their responsiveness to Zn2+, and we provide the safety study in a mouse disease model. We further describe treatment of a 3-year-old patient with the common pathogenic GNAO1 variant c607G>A, p.Gly203Arg with oral 50mg zinc (in the form of zinc acetate) daily, as applied in Wilson's disease. During 11months of treatment, the patient shows cessation of daily dyskinetic crises, improved Burke-Fahn Marsden Dystonia Rating Scale movement score, reduction in epileptic seizures, and an excellent safety profile. Our findings warrant a large-scale clinical trial and might set the new standard of care for GNAO1-related disorders. This work was funded by the Russian Science Foundation (grant #21-15-00138) and GNAO1 España.

Efficacy, safety, and patient-reported outcome of immune checkpoint inhibitor in gynecologic cancers: A systematic review and meta-analysis of randomized controlled trials.

Over the past decades, immune checkpoint inhibitors (ICIs) have shown dramatic efficacy in improving survival rates in multiple malignancies. Recently, gynecological cancer patients also showed to respond favorably to ICI treatment. This study aimed to evaluate the efficacy, safety, and patient-reported outcomes of ICI therapy in gynecological cancers. We conducted a systematic review and meta-analysis by retrieving literature from multiple electronic databases, such as MEDLINE, ScienceDirect, EBSCO, ProQuest, and Google Scholar. The protocol used in this study has been registered in PROSPERO (CRD42022369529). We included a total of 12 trials involving 8 therapies and 8,034 patients. ICI group demonstrated a longer OS (HR: 0.807; 95% CI: 0.719, 0.907; p = 0.000) and greater PFS improvement (HR: 0.809; 95% CI: 0.673, 0.973; p = 0.024) compared to the control group. There was no significant difference in the incidence of treatment-related adverse events [RR: 0.968; 95%CI: 0.936, 1.001; p = 0.061], but a higher incidence of immune-related adverse events (IRAEs) was observed in the ICI group (RR: 3.093; 95%CI: 1.933, 4.798; p = 0.000). Although the mean changes of QOL score from baseline was not significantly different between both groups (SMD: 0.048; 95% CI: -0.106, 0.202; p = 0.542), the time to definitive QOL deterioration was longer in the ICI group (HR: 0.508; 95% CI: 0.461, 0.560; p = 0.000). Despite having a higher incidence of IRAE, ICI was shown to improve survival rates and QOL of patients. Thus, it should be considered as a new standard of care for gynecologic cancers, especially in advanced stages.

Stereotactic radiotherapy for managing ovarian cancer oligoprogression under poly (ADP-ribose) polymerase inhibitors (PARPi)

ObjectivePoly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety...

Alectinib in Early-Stage Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: Current Evidence and Future Challenges.

Targeted therapies changed the treatment of advanced oncogene-addicted non-small cell lung cancer and could also improve outcomes in resectable disease. The ALINA trial evaluated the clinical benefit of adjuvant alectinib compared with standard chemotherapy and met the primary endpoint with a significant increase in disease-free survival at 2 years among anaplastic lymphoma kinase positive patients with stage IB-IIIA disease; two phase II trials (ALNEO and NAUTIKA1) are currently evaluating perioperative treatment with alectinib, and the results of the case reports published to date are encouraging. In resectable anaplastic lymphoma kinase-positive lung cancer, adjuvant alectinib represents the new standard of care and could soon be used in perioperative treatment.

Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial

The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial. COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting). Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis. Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups. Celgene and Acceleron Pharma.

Evolution of atrial septal defect closure: Is MICS a new standard of care?

Evolution of atrial septal defect closure: Is MICS a new standard of care?

Racial and ethnic disparities in access to total neoadjuvant therapy for rectal cancer

BackgroundTotal neoadjuvant therapy has revolutionized the treatment of locally advanced rectal cancer and quickly become the new standard of care. Whether patients from all racial and ethnic groups have had equal access to these potential benefits, however, remains unknown. MethodsWe identified all adults diagnosed with locally advanced rectal cancer in California who underwent neoadjuvant chemotherapy and radiation from 2010 to 2020 using the California Cancer Registry. We used logistic regression to estimate the predicted probability of receiving total neoadjuvant therapy as opposed to traditional chemoradiotherapy for each racial and ethnic group and used a time–race interaction to evaluate trends in access to total neoadjuvant therapy over time. We also compared survival by racial and ethnic group and total neoadjuvant therapy status using Kaplan-Meier plots and Cox proportional hazards models. ResultsIn total, 6,856 patients met inclusion criteria. Overall, 36.6% of patients received total neoadjuvant therapy in 2010 compared with 66.3% in 2020. Latino patients were significantly less likely than non-Latino White patients to undergo total neoadjuvant therapy ; however, there was no difference in the rate of growth in total neoadjuvant therapy over time between racial and ethnic groups. Non-Latino Black patients appeared to have lower risk-adjusted survival compared with non-Latino White patients, although not among patients who underwent total neoadjuvant therapy . ConclusionAccess to total neoadjuvant therapy has increased significantly over time in California with no apparent difference in the rate of growth between racial and ethnic groups. We found no evidence of racial or ethnic disparities in survival among patients treated with total neoadjuvant therapy, suggesting that increasing access to high-quality cancer care may also improve health equity.

Effect of Radical Prostatectomy on Survival for Men with High-risk Nonmetastatic Prostate Cancer Features Selected According to STAMPEDE Criteria: An EMPaCT Study

Background and objectiveA meta-analysis of two randomized STAMPEDE platform trials revealed that 3 yr of abiraterone acetate in addition to androgen deprivation therapy and radiation therapy significantly improved metastasis-free and overall survival (OS) in high-risk nonmetastatic prostate cancer (PCa) and should be considered a new standard of care. The aim of our study was to assess long-term cancer-specific survival (CSS) and OS for surgically treated patients with newly diagnosed nonmetastatic node-negative PCa meeting the STAMPEDE criteria for high risk. MethodsThis was a retrospective, multicenter cohort study of patients with European Association of Urology (EAU) high-risk PCa who underwent radical prostatectomy and extended pelvic lymph node dissection. CSS was assessed using cumulative incidence curves and the Kaplan-Meier method was used to evaluate OS. We used a Fine and Gray model to evaluate the prognostic value of STAMPEDE high-risk factors (SHRFs) for CSS, and a Cox proportional-hazards model to assess the association of SHRFs with OS. Key findings and limitationsA total of 2994 patients with EAU high-risk PCa were divided into groups with 0, 1, 2, or 3 SHRFs. The 10-yr survival estimates for patients with 0–1 versus 2–3 SHRFs were 95% versus 82% for CSS and 81% versus 64% for OS (both p < 0.0001). In comparison to patients with 0 SHRFs, hazard ratios were 1.2 (p = 0.5), 3.9 (p < 0.0001), and 5.5 (p < 0.0001) for CSS, and 1.1 (p = 0.4), 2.2 (p < 0.0001), and 2.5 (p = 0.0004) for OS for patients with 1, 2, and 3 SHRFs, respectively. Conclusions and clinical implicationsOur results confirm that the STAMPEDE high-risk criteria identify a subgroup of patients with highly aggressive PCa features and adverse long-term oncological outcomes. This population is likely to benefit most from aggressive multimodal treatment. Nevertheless, we have shown for the first time that surgery remains a viable treatment option for patients with STAMPEDE high-risk PCa. Patient summaryProstate cancer that meets the high-risk definitions from the STAMPEDE trial is an aggressive type of cancer. Our results for long-term cancer control outcomes indicate that surgery is a viable option for the subgroup of patients with this type of prostate cancer.

Immunomodulatory effects of antiangiogenic tyrosine kinase inhibitors in renal cell carcinoma models: Impact on following anti-PD-1 treatments

The approval of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic renal cell carcinoma (RCC), introducing several ICI-based combinations as the new standard of care for affected patients. Nonetheless, monotherapy with antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib or sunitinib, still represents a first-line treatment option for selected patients belonging to the favorable risk group according to the International mRCC Database Consortium (IMDC) model. After TKI monotherapy, the main second-line option is represented by ICI monotherapy with the anti-Programmed Death Receptor 1(PD-1) nivolumab.To date, the expected clinical outcomes are similar with pazopanib or sunitinib and there is no clear indication for selecting one TKI over the other. Moreover, their impact on subsequent ICI treatment outcomes is not well defined, yet.Based on these premises, we investigated the immunomodulatory activity of these drugs in vitro and in vivo.Both TKIs induced Programmed Cell Death Ligand-1 (PD-L1) expression and soluble PD-L1 release in RCC cells, and hampered T cell activation, reducing cytokine production and the proportion of activated T cells. Nevertheless, in a syngeneic co-culture system with peripheral blood mononuclear cells (PBMCs) and tumor cells, incubation with anti-PD-1 antibody following TKIs treatment significantly restored T cell function, potentiating the cytotoxic effects against tumor cells. Pazopanib and sunitinib followed by anti-PD-1 antibody produced a comparable inhibition of tumor growth in a RCC syngeneic mouse model. Our findings suggest that pazopanib and sunitinib, showing similar immunomodulatory effects, may have a comparable impact on the subsequent effectiveness of PD-1/PD-L1 blockade.

Rectal cavernous hemangioma: is endoscopic submucosal dissection the new standard of care?

Rectal cavernous hemangioma: is endoscopic submucosal dissection the new standard of care?

Short course irradiation in rectal cancer: Dosimetry study comparing 3D conformal radiotherapy versus intensity-modulated radiotherapy versus volumetric modulated arc therapy

The standard radiotherapy planning technique for locally advanced rectal cancer (LARC) was 3D Conformal Radiotherapy (3DCRT). Modern radiation delivery techniques, including Intensity-Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) techniques, have been developed in recent years in terms of dose delivery to the target while minimizing the dose to the organ at risk (OAR). The objective of this study was to identify the most suitable treatment plan technique from the available options of 3DCRT, IMRT and VMAT for LARC using short course radiotherapy (SCRT). Therefore, twenty-five adult patients with LARC in the last five-year period (2017–2021) were involved in this study. For each patient, three radiotherapy treatment plans were generated for dosimetric comparison of short course irradiation (25 Gy/5 fractions, which is the new standard of care) using Varian Eclipse software to generate 3DCRT in comparison with IMRT and VMAT plans. The conformity index (CI), the homogeneity index (HI), and the organs at risk (OAR), including bladder, small bowel, and femoral heads, were compared between the three plans. The results revealed that VMAT and IMRT plans had a higher level of conformity for the planning target volume (PTV) with 0.996 and 0.994, respectively, compared to the 3DCRT planning of 0.947 (both p < 0.005). The PTV dose distribution was less homogeneous with 3DCRT than with VMAT or IMRT plans. VMAT offered superior homogeneity to IMRT and 3DCRT plans with 1.055, 1.066, and 1.089, respectively (p < 0.005). The findings showed that VMAT is superior to IMRT and 3DCRT in almost all parameters, including dose distribution conformity and homogeneity of the target volume, as well as providing better OAR sparing in LARC patients.