Oligodendroglioma, IDH-mutant and 1p/19q-codeleted-prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted is known for their relative chemosensitivity and indolent clinical course among diffuse gliomas of adult type. Based on the data from phase 3 clinical trials, the standard of post-surgical care for those tumors is considered to be initial chemoradiotherapy regardless of histopathological grade, particularly with PCV. However, partly due to its renewed definition in late years, prognostic factors in patients with those tumors are not well established. Moreover, the survival rate declines over 15 years, with only a 37% OS rate at 20 years for grade 3 tumors, even with the current standard of care. Given that most of this disease occurs in young or middle-aged adults, further improvements in treatment and management are necessary. Here, we discuss prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy in those tumors.

An initiative to implement a triage and referral system to make exercise and rehabilitation referrals standard of care in oncology.

BACKGROUND: Clinical guidelines suggest that patients should be referred to exercise while undergoing cancer treatment. Oncology clinicians report being supportive of exercise referrals but not having the time to make referrals. Toward the goal of making exercise referrals standard of care, we implemented and evaluated a novel clinical workflow. METHODS: For this QI project, a rehabilitation navigator was inserted in chemotherapy infusion clinics. Patients were offered a validated electronic triage survey. Exercise or rehabilitation recommendations were communicated to patients during a brief counseling visit by the rehabilitation navigator. The implementation approach was guided by the EPIS framework. Acceptability and feasibility were assessed. RESULTS: Initial meetings with nursing and cancer center leadership ensured buy-in (exploration). The education of medical assistants contributed to the adoption of the triage process (preparation). Audit and feedback ensured leadership was aware of medical assistants' performance (implementation). 100% of medical assistants participated in implementing the triage tool. A total of 587 patients visited the infusion clinics during the 6-month period when this QI project was conducted. Of these, 501 (85.3%) were offered the triage survey and 391 (78%) completed the survey (acceptability). A total of 176 (45%) of triaged patients accepted a referral to exercise or rehabilitation interventions (feasibility). CONCLUSIONS: Implementation of a validated triage tool by medical assistants and brief counseling by a rehabilitation navigator resulted in 45% of infusion patients accepting a referral to exercise or rehabilitation. The triage process showed promise for making exercise referrals standard of care for patients undergoing cancer treatment.

Adolescent HIV Screening and Opt-Out Testing as a Standard of Care.

Despite the significant steps made in the diagnosis and treatment of HIV, there is still a notable amount of people living with HIV without being diagnosed, with a fair portion of these infections occurring in adolescents and young adults. For some individuals, by the time they are diagnosed they are living with advanced-staged disease, missing the opportunity for receiving antiretroviral treatment that would have markedly reduced their morbidity, mortality, and risk of transmission to others. Opt-out testing, or notifying the patient the test will be performed unless explicitly declined or deferred, increases the rates of testing while reducing the stigma of the disease. It is a universal recommendation for those between ages 13 and 55 years to have an HIV screening test. It should be standard of care for HIV tests in the adolescent population to be structured as an opt-out screening in both the ambulatory and acute care settings. [Pediatr Ann. 2024;53(4):e111-e113.].

Toward more accurate preclinical glioblastoma modeling: Reverse translation of clinical standard of care in a glioblastoma mouse model.

Glioblastoma (GBM) is the deadliest of all brain cancers. GBM patients receive an intensive treatment schedule consisting of surgery, radiotherapy and chemotherapy, which only modestly extends patient survival. Therefore, preclinical studies are testing novel experimental treatments. In such preclinical studies, these treatments are administered as monotherapy in the majority of cases; conversely, in patients the new treatments are always combined with the standard of care. Most likely, this difference contributes to the failure of clinical trials despite the successes of the preclinical studies. In this methodological study, we show in detail how to implement the full clinical standard of care in preclinical GBM research. Systematically testing new treatments, including cellular immunotherapies, in combination with the clinical standard of care can result in a better translation of preclinical results to the clinic and ultimately increase patient survival.

Investigational Approaches for Treatment of Melanoma Patients Progressing After Standard of Care.

ABSTRACT: The advent of effective immunotherapy, specifically cytotoxic T-lymphocyte associated protein 4 and programmed cell death 1 inhibitors, as well as targeted therapy including BRAF/MEK inhibitors, has dramatically changed the prognosis for metastatic melanoma patients. Up to 50% of patients may experience long-term survival currently. Despite these advances in melanoma treatment, many patients still progress and die of their disease. As such, there are many studies aimed at providing new treatment options for this population. Therapies currently under investigation include, but are not limited to, novel immunotherapies, targeted therapies, tumor-infiltrating lymphocytes and other cellular therapies, oncolytic viral therapy and other injectables, and fecal microbiota transplant. In this review, we discuss the emerging treatment options for metastatic melanoma patients who have progressed on standard of care treatments.

Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study.

Glioblastoma (GB), a highly aggressive primary brain tumor, presents a poor prognosis despite the current standard therapy, including radiotherapy and temozolomide (TMZ) chemotherapy. Tumor microtubes involving connexin 43 (Cx43) contribute to glioma progression and therapy resistance, suggesting Cx43 inhibition as a potential treatment strategy. This research aims to explore the adjuvant potential of tonabersat, a Cx43 gap junction modulator and blood-brain barrier-penetrating compound, in combination with the standard of care for GB. In addition, different administration schedules and timings to optimize tonabersat's therapeutic window are investigated. The F98 Fischer rat model will be utilized to investigate tonabersat's impact in a clinically relevant setting, by incorporating fractionated radiotherapy (three fractions of 9 Gy) and TMZ chemotherapy (29 mg/kg). This study will evaluate tonabersat's impact on tumor growth, survival, and treatment response through advanced imaging (CE T1-w MRI) and histological analysis. Results show extended survival in rats receiving tonabersat with standard care, highlighting its adjuvant potential. Daily tonabersat administration, both preceding and following radiotherapy, emerges as a promising approach for maximizing survival outcomes. The study suggests tonabersat's potential to reduce tumor invasiveness, providing a new avenue for GB treatment. In conclusion, this preclinical investigation highlights tonabersat's potential as an effective adjuvant treatment for GB, and its established safety profile from clinical trials in migraine treatment presents a promising foundation for further exploration.

Stereotactic body radiation therapy for spinal metastases: A new standard of care.

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.

Vulvar Carcinoma: Standard of Care and Perspectives.

PURPOSE: Treatment of vulvar carcinoma (VC) is challenging. The objectives of this review were to describe for clinicians the epidemiologic and clinical aspects of VC, the standard of care in terms of primary local treatment and systemic therapies, and the recent innovations and perspectives emerging from translational research in immuno-oncology. DESIGN: We conducted a comprehensive review outlying the clinical aspects and biologic background of vulvar cancer, highlighting modern treatment strategies on the basis of a personalized approach. RESULTS: Epidemiologic data showed a recent rise in incidence of VC, attributed to human papillomavirus. Surgery is the mainstay of primary treatment, but multimodal approaches are frequently required in the presence of adverse prognosis histopathologic factors. Chemoradiation is indicated when organ-sparing surgery is not feasible. However, inability to achieve high locoregional control rates in advanced cases and the morbidity associated with local treatments are still key issues. Recent clinical data showed the benefit of individualized strategies combining organ-sparing surgical strategies, less invasive lymph node staging procedures, and refinement in radiotherapy modalities. Among the most important research area, there is a sound rationale for testing modern systemic approaches such as immune checkpoint inhibitors in selected patients with recurrent and/or metastatic tumors. Although no specific data exist for VC, the role of supportive care and post-treatment rehabilitation strategies is also crucial. CONCLUSION: There are still insufficient studies dedicated to patients with VC. Public health programs for prevention, screening, and early diagnosis are required, and clinical research should be strengthened to provide high-quality clinical evidence and improve patients' oncologic and functional outcomes.

Immunotherapy Combined With Standard Therapies in Head and Neck Squamous Cell Carcinoma - A Meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is a deadly disease with a poor prognosis due to late diagnosis and limited treatment options. Immunotherapy (IT) is emerging as a promising approach, especially after the failure of standard of care therapies (STs). The objective of this systematic review and meta-analysis was to evaluate whether the addition of IT to STs improves outcomes for patients with HNSCC, including overall survival (OS), progression-free survival (PFS), and quality of life (QoL). This review employed the Population Intervention Comparison and Outcome (PICO) framework to identify relevant search terms in electronic databases, and also included supplementary hand searches. Six primary research articles were selected using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) flow chart, and were critically appraised. Data extraction from these studies was conducted, and a meta-analysis was performed to aid in the generation of forest plots. The addition of IT to standard anticancer therapies was found to enhance patient outcomes, such as OS, PFS, and QoL. The toxicity profile of IT was acceptable, with minimal treatment-related deaths. The most frequently observed adverse events (AE) were related to the skin, followed by hematological toxicities. Based on our analysis, the addition of IT to STs is a suitable treatment option and is supported by current research. However, further studies are needed to investigate factors that influence treatment effectiveness and to develop optimal therapies. To achieve this, we recommend a comprehensive treatment approach that involves the multidisciplinary team (MDT) and patient assessment tools.

Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn's disease (ASTIClite): an open-label, multicentre, randomised controlled trial.

BACKGROUND: A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population. METHODS: This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 µg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440. FINDINGS: Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure. INTERPRETATION: Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease. FUNDING: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

A Prospective Multicenter Standard of Care Study of Outpatient Laparoscopic Sleeve Gastrectomy.

A global shift is occurring as hospital procedures move to ambulatory surgical settings. Surgeons have performed outpatient sleeve gastrectomy (SG) in bariatric surgery since 2010. However, prospective trials are needed to ensure its safety before widespread adoption. PURPOSE: The study aimed to present a comprehensive report on the prospective data collection of 30-day outcomes of outpatient primary laparoscopic SG (LSG). This trial seeks to assess whether outpatient LSG is non-inferior to hospital-based surgery in selected patients who meet the outpatient surgery criteria set by the American Society for Metabolic and Bariatric Surgery. MATERIALS AND METHODS: This study is funded by the Society of American Gastrointestinal and Endoscopic Surgeons and has been approved by the Advarra Institutional Review Board (Pro00055990). Cognizant of the necessity for a prospective approach, data collection commenced after patients underwent primary LSG procedures, spanning from August 2021 to September 2022, at six medical centers across the USA. Data centralization was facilitated through ArborMetrix. Each center has its own enhanced recovery protocols, and no attempt was made to standardize the protocols. RESULTS: The analysis included 365 patients with a mean preoperative BMI of 43.7 ± 5.7 kg/m2. Rates for 30-day complications, reoperations, readmissions, emergency department visits, and urgent care visits were low: 1.6%, .5%, .2%, .2%, and 0%, respectively. Two patients (0.5%) experienced grade IIIb complications. There were no mortalities or leaks reported. CONCLUSION: The prospective cohort study suggests that same-day discharge following LSG seems safe in highly selected patients at experienced US centers.

Gemcitabine with cisplatin and nivolumab: Redefining standard of care for first-line metastatic urothelial carcinoma?

Nivolumab with gemcitabine/cisplatin in the CheckMate 901 trial improved overall and progression-free survival in front-line locally advanced/metastatic urothelial cancer. The EV-302 trial establishes enfortumab-vedotin plus pembrolizumab as the preferred standard in this setting. Personalized decisions are crucial given patient eligibility and economics. Ongoing trials and predictive biomarkers will further refine treatment strategies.

Active case-finding of tuberculosis compared with symptom-driven standard of care: a modelling analysis.

BACKGROUND: In settings with large case detection gaps, active case-finding (ACF) may play a critical role in the uberculosis (TB) response. However, ACF is resource intensive, and its effectiveness depends on whether people detected with TB through ACF might otherwise spontaneously resolve or be diagnosed through routine care. We analysed the potential effectiveness of ACF for TB relative to the counterfactual scenario of routine care alone. METHODS: We constructed a Markov simulation model of TB natural history, diagnosis, symptoms, ACF and treatment, using a hypothetical reference setting using data from South East Asian countries. We calibrated the model to empirical data using Bayesian methods, and simulated potential 5-year outcomes with an 'aspirational' ACF intervention (reflecting maximum possible effectiveness) compared with the standard-of-care outcomes. RESULTS: Under the standard of care, 51% (95% credible interval, CrI: 31%, 75%) of people with prevalent TB at baseline were estimated to be diagnosed and linked to care over 5 years. With aspirational ACF, this increased to 88% (95% CrI: 84%, 94%). Most of this difference represented people who were diagnosed and treated through ACF but experienced spontaneous resolution under standard-of-care. Aspirational ACF was projected to reduce the average duration of TB disease by 12 months (95% CrI: 6%, 18%) and TB-associated disability-adjusted life-years by 71% (95% CrI: 67%, 76%). CONCLUSION: These data illustrate the importance of considering outcomes in a counterfactual standard of care scenario, as well as trade-offs between overdiagnosis and averted morbidity through earlier diagnosis-not just for TB, but for any disease in which population-based screening is recommended.

Novel hormonal therapy versus standard of care-A registry-based comparative effectiveness evaluation for mCRPC-patients.

BACKGROUND: This paper presents results from one of the few comparative effectiveness evaluations of novel antiandrogen medications (NHT) against standard of care (SoC) for patients suffering from metastatic castrate-resistant prostate cancer (mCRPC). METHODS: The design and the analysis are published in a protocol before accessing outcome data. Two groups of patients are balanced on hundreds of important covariates measured before the prostate cancer diagnosis and up to the date of the prescription. While the design yields balance on the observed covariates, one cannot discard the possibility that unobserved confounders are not balanced. The unconfoundedness assumption is assessed by estimating placebo regressions on two health measures, not included in the design but added together with the outcome data after protocol publication. RESULTS: We find a substantial (64 percent) increase in mortality for patients prescribed with NHT rather than SoC. However, based on the results from one of the two placebo regressions, we cannot rule out that the difference in mortality may be due to confounding. Using a bounding strategy of the effect, we can, however, rule out that NHT reduces mortality compared to SoC. Under an empirical valid assumption that most mCRPC patients who die suffer from bone metastases, we have a strong indication of increased skeleton-related events in patients if prescribed NHT against SoC. CONCLUSIONS: Generally, the SoC for this group of patients is docetaxel. Given the substantially higher costs of many of the NHT, the finding of no positive effects from NHT on both mortality and SRE is important. More comparative studies, including studies analysing quality of life outcomes, are thus needed.

Treatment Outcomes with Standard of Care in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis.

INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used. METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen. RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% with ≥ 2 and ≥ 3 prior LOTs, respectively). Median duration of follow-up was 7.7 months. Most patients (57.1%) were male; mean standard deviation (SD) age was 63 (14.7) years. Overall and complete response rates (95% confidence interval (CI) were 52% (48-56) and 23% (19-27). Median duration of response and duration of complete response were 3.5 and 18.4 months. Median progression-free and overall survival (95% CI) was 3.0 (2.8-3.3) and 12.9 (10.1-16.9) months, respectively. Patients with a higher number of prior LOTs, primary refractoriness, refractoriness to last LOT, refractoriness to last anti-CD20-containing regimen, and prior CAR T exposure had worse outcomes (i.e., challenging-to-treat R/R DLBCL) compared with those without these characteristics. CONCLUSIONS: Outcomes in patients with R/R DLBCL treated with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents remain poor, especially for those with challenging-to-treat R/R DLBCL. These findings underscore the unmet need for new, safe, and effective therapies, especially for challenging-to-treat R/R DLBCL populations.

New standards of care for treatment of diffuse large B-cell lymphoma.

Treatment of newly diagnosed diffuse large B-cell lymphoma with rituximab and CHOP (R-CHOP) has been largely unchanged for the last two decades. The Guideline by Fox et al. provides new evidence-based therapeutic strategies informed by positive results of randomised clinical trials. Commentary on: Fox et al. The management of newly diagnosed large B-cell lymphoma: A British Society for Haematology Guideline. Br J Haematol 2024; 204:1178-1192.