Evaluation of markers of immunity in different metastatic immune microenvironments suggests more suppression within breast to liver metastases in breast cancer.

PURPOSE: Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease. METHODS: 3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell fraction within the TME was calculated by QuantiSeq and MCP-counter. RESULTS: Compared to BrT, more LvM samples had a high TMB (≥ 10 mutations/Mb) and fewer LvM samples had PD-L1+ expression. Evaluation of the TME revealed that LvM sites harbored lower infiltration of adaptive immune cells, such as CD4+, CD8+, and regulatory T-cells compared with the BrT foci. We saw differences in innate immune cell infiltration in LvM compared to BrT, including neutrophils and NK cells. CONCLUSIONS: LvMs are less likely to express PD-L1+ tumor cells but more likely to harbor high TMB as compared to BrTs. Unlike AxMs, LvMs represent a more immunosuppressed TME and demonstrate lower gene expression associated with adaptive immunity compared to BrTs. These findings suggest biopsy site be considered when interpreting results that influence ICI use for treatment and further investigation of immune composition and biomarkers expression by metastatic site.

Attitudes and beliefs about how chefs can promote nutrition and sustainable food systems among students at a US culinary school.

OBJECTIVE: Chefs have the potential to influence diet quality and food systems sustainability through their work. We aimed to assess the attitudes and perceptions of culinary students about nutrition and sustainability as part of their roles, responsibilities and future work as chefs. DESIGN: We surveyed students attending the Culinary Institute of America (CIA) in the fall of 2019 (n 546). Descriptive statistics compared food priority rankings and Likert-scale distributions of nutrition and sustainability attitudes and beliefs. Adjusted generalised linear models were used to evaluate whether there were differences in attitudes and beliefs across demographic groups. SETTING: The CIA, a private, not-for-profit college and culinary school with US campuses in New York, California and Texas. PARTICIPANTS: Students >18 years old currently enrolled in any of the school's associate's or bachelor's degree programs. RESULTS: Students agreed that chefs should be knowledgeable about nutrition (96·0 %) and the environmental impact of their ingredients (90·8 %) but fewer considered healthfulness (57·8 %) and environmental impact (60·2 %) of their food to be primary considerations in their career as a chef. Taste was the primary factor influencing culinary students' food choices but food priorities differed by race/ethnicity. CONCLUSIONS: Culinary students believe nutrition and sustainability are important. Opportunities exist to empower them with knowledge and skills for promoting public health and sustainable food systems in their future work as chefs.

Warning Labels Reduce Sugar-Sweetened Beverage Intake among College Students.

BACKGROUND: Health-related warning labels may reduce the intake of sugar-sweetened beverages (SSBs), but the effectiveness of such labels in real-world settings is not well established. OBJECTIVES: We investigated the influence of warning labels on SSB intake among college students at a large public Midwestern university. METHODS: We conducted a quasi-experimental intervention study among 840 undergraduate students recruited from 3 dining halls on 1 university campus. One dining hall was selected as the intervention (I) site, whereas the other dining halls served as control (C) sites. In January 2019, warning labels were posted on SSB dispensers at the I site. All students reported their beverage intake using a modified beverage frequency questionnaire 2 mo before and 2 mo after the warning label implementation. Generalized linear models examined the influence of the warning labels on SSB consumption at the I site compared with the C sites, adjusting for students' sociodemographic characteristics. RESULTS: In the sample, 68% were aged 17-18 y old at baseline, and 51% identified as female. From baseline to follow-up, there was a 19% decrease in SSB intake at the I site, compared with a 5% decrease at the C sites (P = 0.049 comparing I with C). This difference was driven by significant decreases in the intakes of fruit-flavored drinks, sweetened teas, and flavored milk at the I site compared with the C sites. Although not an SSB, 100% fruit juce consumption decreased 21% at the I site, compared with a 1% increase at the C sites (P = 0.01 comparing I with C). No significant differences were observed in the intakes of soda, energy drinks, sweetened coffees, and nonsugary drinks at the I site compared with the C sites. CONCLUSIONS: Warning labels were effective in reducing SSB intake among college students, particularly for fruit-flavored drinks, sweetened teas, and flavored milk.This trial was registered at clinicaltrials.gov as NCT04435145.

Effect of high body mass index on knee muscle strength and function after anterior cruciate ligament reconstruction using hamstring tendon autografts.

BACKGROUND: Increased body mass index (BMI) has been associated with poorer function in patients who have undergone anterior cruciate ligament (ACL) reconstruction. However, the effect of high BMI on muscle strength in these patients remained unclear. The current study aimed to compare knee muscle strength and Knee injury and Osteoarthritis Outcome Score (KOOS) in ACL-reconstructed patients with a variety of different BMIs. METHODS: From November 2013 to March 2016, we prospectively enrolled 30 patients who underwent ACL reconstruction (18-60 years of age). Anthropometric parameters, body compositions, isokinetic muscle strength and KOOS were assessed preoperatively, and at post-operative 16th week and 28th week. The patients were stratified into two groups by BMI, i.e. normal BMI (18.5-24.9 kg/m2) and high BMI (≥25.0 kg/m2). RESULTS: Twelve patients in the normal BMI group completed the follow-up, while sixteen patients did so in the high BMI group. In comparison of muscle strength between baseline and 28th week follow-up, the normal BMI group had significant increases in overall knee muscle strength, while the high BMI group only had increases in extensors of uninjured knee and flexors of the injured knee. However, there were significant increases in all KOOS subscales for the high BMI group. The high BMI patients reported increased KOOS, which may reflect the contribution of ligament stability in the presence of inadequate muscle strength. CONCLUSIONS: The normal BMI patients had improvement in all knee muscle strength following ACL reconstruction, while high BMI patients only had increases in certain knee muscles. High BMI patients had a decreased quadriceps muscle symmetry index, as compared to their normal BMI counterparts. Increases in quadriceps muscle strength of the uninjured knee and ACL reconstruction were associated with improvements in KOOS in high BMI patients.

Novel Pathophysiological Mechanisms in Hypertension.

Hypertension is the most common disease affecting humans and imparts a significant cardiovascular and renal risk to patients. Extensive research over the past few decades has enhanced our understanding of the underlying mechanisms in hypertension. However, in most instances, the cause of hypertension in a given patient continues to remain elusive. Nevertheless, achieving aggressive blood pressure goals significantly reduces cardiovascular morbidity and mortality, as demonstrated in the recently concluded SPRINT trial. Since a large proportion of patients still fail to achieve blood pressure goals, knowledge of novel pathophysiologic mechanisms and mechanism based treatment strategies is crucial. The following chapter will review the novel pathophysiological mechanisms in hypertension, with a focus on role of immunity, inflammation and vascular endothelial homeostasis. The therapeutic implications of these mechanisms will be discussed where applicable.

Effects of teriparatide on cementless bipolar hemiarthroplasty in patients with osteoporotic femoral neck fractures.

BACKGROUND: For osteoporotic femoral neck fractures, suitable bone-implant stability is critical for pain relief, early return to daily activities and reduction of complications. Teriparatide (parathyroid hormone [PTH1-34]) can improve bone-implant stability in some basic studies. However it's use in osteoporotic femoral neck fractures treated by cementless hemiarthroplasties for the beneficial effects on bone-implant stability is sparse in the literature. The aim of this study was to determine if post-operative teriparatide administration can reduce femoral stem migration and improve early functional recovery and health-related quality of life (HRQoL). METHODS: Between 2010 and 2014, patients with osteoporotic femoral neck fracture who underwent cementless bipolar hemiarthroplasty were included into this retrospective cohort study. Group A included patients treated with cementless bipolar hemiarthroplasty only; Group B patients had additional teriparatide. Demographic data, complications, radiographic and functional outcomes as well as health-related quality of life (HRQoL) were compared. RESULTS: There were 52 hips in group A (no teriparatide) and 40 hips in group B (patient who received teriparatide). The subsidence of the femoral stem tended to be significantly decreased in the teriparatide group at 6 and 12 weeks post-operatively (p = 0.003 and p = 0.008, respectively). The Harris Hip Score (HHS) increased significantly from pre-operation to 6 weeks post-operatively and thereafter up to one year in both groups. However, there were no significant differences in terms of subsequent fracture, mortality, HHS, and HRQoL between two groups during the entire study period. CONCLUSIONS: Teriparatide significantly reduces the subsidence of the cementless femoral stem in elderly patients in the early post-operative period, but this benefit does not reflect better functional outcomes and HRQoL. Further prospective randomized large-scale cohort study is warranted for evidence-based recommendations.

Outcomes and second-look arthroscopic evaluation after combined arthroscopic treatment of tibial plateau and tibial eminence avulsion fractures: a 5-year minimal follow-up.

BACKGROUND: Tibial eminence avulsion fracture often co-occurs with tibial plateau fracture, which leads to difficult concomitant management. The value of simultaneous arthroscopy-assisted treatment continues to be debated despite its theoretical advantages. We describe a simple arthroscopic suture fixation technique and hypothesize that simultaneous treatment is beneficial. METHODS: Patients with a tibial eminence avulsion fracture and a concurrent tibial plateau fracture who underwent simultaneous arthroscopically assisted treatment between 2005 and 2008 were enrolled in this retrospective study. Second-look arthroscopic evaluation and Rasmussen scores of clinical and radiographic parameters were used to assess simultaneous treatment. RESULTS: Forty-one patients (41 knees) met the inclusion criteria. All 41 fractures were successfully united. All patients had side-to-side differences of less than 3 mm and negative findings in Lachman and pivot-shift tests at their final follow-up. The mean postoperative Rasmussen clinical score was 27.3 (range: 19-30), and the mean radiologic score was 16.5 (range: 12-18). Clinical and radiographic outcomes in 98 % of the patients were good or excellent. There were no complications directly associated with arthroscopy in any patient. CONCLUSIONS: Simultaneous arthroscopic suture fixation of associated tibial eminence avulsion fracture did not interfere with the plates and screws used to stabilize the tibial plateau fracture. It gave the knee joint adequate stability, minimal surgical morbidity, and satisfactory radiographic and clinical outcomes in a minimum follow-up of 5 years and in the arthroscopic second-look assessments.

The Influence of Alignment on Midterm Outcome after Total Knee Arthroplasty in Patients With Marked Coronal Femoral Bowing.

Whether the mechanical axis should be restored to neutral remains controversial when the patient has marked coronal femoral bowing. Eighty-four total knee arthroplasties were retrospectively reviewed. In the neutral-aligned group A the immediate postoperative mechanical axis of 179 ± 1° held stable (P = 0.841). The postoperative mechanical axis decreased from 176 ± 1° to 173 ± 1° (P = 0.024) in the outlier group. Progressive varus in the outlier group at follow-up was probably due implant instability and ligament imbalance as well as excessive polyethylene wear. At a mean follow-up of 75.8 months, no statistically significant difference was detected between the two groups. Long-term follow up will be needed to determine if the maintenance in radiographic results translates to better clinical outcomes.

Comparison of computer-navigated and conventional total knee arthroplasty in patients with Ranawat type-II valgus deformity: medium-term clinical and radiological results.

BACKGROUND: Arthritic knees with Ranawat type-II valgus deformity present with soft tissue contracture and osseous anomalies that make total knee arthroplasty (TKA) difficult. We hypothesized that computer-navigated-TKA (CN-TKA) may be superior to conventional techniques and provide better mid-term radiographic and clinical outcomes in such cases. METHODS: Between January 2002 and January 2009, patients with Ranawat type-II valgus deformity who underwent primary TKA were entered into this retrospective study. Conventional TKA and CN-TKA were compared for the accuracy of component placement, joint line level, and postoperative limb alignment. International Knee Society scores and patellar scores were used for clinical assessment. RESULTS: A total of 62 patients (70 knees) with a minimum of 5 years of follow-up were studied. Conventional TKA was performed in 36 knees and CN-TKA in 34 knees. A significantly higher rate of lateral retinaculum release was recorded in the conventional TKA group compared to the CN-TKA group. Proper restoration of joint line was achieved using CN-TKA. The range of motion of the knees was similar in both groups preoperative and postoperatively. There were no significant differences in reconstructed mechanical axes, accuracy of component positioning, and difference in perioperative hemoglobin level between the two groups. At a mean follow-up of 6.2 years, both groups had significant postoperative improvements in clinical performance, however the difference did not reach statistical significance between both techniques. CONCLUSIONS: Our findings demonstrate that CN-TKA can properly restored the joint line level for arthritic knees with Ranawat type II valgus deformity. However, no differences in clinical function, limb and component alignment, or survival of the prostheses were noted between the CN-TKA and conventional TKA groups at a mean follow-up of 6.2 years.

Differences in component and limb alignment between computer-assisted and conventional surgery total knee arthroplasty.

PURPOSE: Marked coronal femoral bowing may bear a risk for mal-alignment of femoral component and reconstructed mechanical axis (MA) by using conventional instrumentations. The aim of this study was to investigate the usefulness of computer-assisted surgery-total knee arthroplasty (CAS-TKA) under this circumstance. METHODS: We retrospectively analyzed patients with osteoarthritic knee and marked coronal femoral bowing who underwent TKA at our institution. The CAS-TKA and the conventional techniques were compared by radiographic parameters in coronal and sagittal planes, and rotational alignment of femoral component was assessed by computed tomography (CT) scans. The Hospital for Special Surgery (HSS) and International Knee Society (IKS) scores were obtained for all patients preoperatively and at the last follow-up. RESULTS: A total of 65 knees were enrolled in this study. Twenty-eight TKAs implanted using a CT-free navigation system, and the remaining 37 TKAs implanted using the conventional technique. CAS-TKAs were more consistent than conventional TKAs in aiding proper postoperative MA and ideal alignments of femoral component in the coronal and sagittal planes. However, CAS-TKA group was not obtained at significantly higher rates of femoral component in axial plane. At a mean follow-up of 43 months, there was no significant difference in HSS and IKS scores between the groups. CONCLUSIONS: Although CAS-TKA did not have superior functional outcomes in the short-term follow-up, proper coronal and sagittal alignment of femoral component and postoperative MA were obtained in patients with marked coronal femoral bowing. The long-term follow-up will be needed to clarify the eventual benefits. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Computed tomography evaluation in total knee arthroplasty: computer-assisted navigation versus conventional instrumentation in patients with advanced valgus arthritic knees.

Arthritic knees with advanced valgus deformity present with soft tissue and osseous anomalies that make total knee arthroplasty (TKA) difficult. We conducted a retrospective chart review of 41 patients (51 knees) to determine whether computer-assisted surgery-TKA (CAS-TKA) is superior to TKA using conventional guiding systems. A significantly higher rate of lateral retinaculum release as well as outlier of sagittal mechanical axes and position of the femoral component (femoral flexion and femoral rotational angle) was recorded in the conventional TKA group versus the CAS-TKA group. Both groups had significant postoperative improvement in clinical performance, but results did not differ significantly between groups. Despite its radiographic benefit, CAS-TKA showed no significant benefit over TKA in short-term clinical functional outcomes when performed by an experienced surgeon.

The effect of renal function on surgical outcomes of intracapsular hip fractures with osteosynthesis.

BACKGROUND: Chronic kidney disease (CKD) affects many physiologic systems, including bone quality, nutrition, and cardiovascular condition. Femoral neck fractures in patients on dialysis are associated with frequent complications and a high risk of mortality. However, the effect of CKD on clinical outcomes of patients with hip fractures treated with osteosynthesis remains unclear. METHODS: One hundred and thirty patients with 130 femoral neck fractures treated with internal fixation were divided into two groups and the data were then analyzed. Group 1 consisted of 98 patients (98 hip fractures) with normal renal function (estimated glomerular filtration rate, or eGFR, ≥60 ml/min/1.73 m(2)). Group 2 was composed of 32 patients (32 hip fractures) with CKD (eGFR <60 ml/min/1.73 m(2)) without dialysis. Clinical outcomes as well as early and late complications were recorded for each group. Survivorship analysis was performed, and the mortality and complication rates for the groups were then compared. RESULTS: In Group 1, 32 complications (32.6%) occurred in 98 hips, including 5 cases of nonunion and 16 cases of osteonecrosis. In Group 2, 24 complications (75%) developed in 32 hips; these included 8 cases of nonunion and 3 cases of osteonecrosis. The mean duration of follow-up was 32 months. The overall mortality rate was 11.5%. No difference was noted in early, late, or overall mortality rate between two groups. Patient with CKD had a higher nonunion rate (OR = 5.9, P = 0.023). Meanwhile, CKD and displaced fracture pattern were independent predictors for revision surgery (OR = 3.0, P = 0.032; OR = 6.9, P = 0.001, respectively). CONCLUSIONS: Osteosynthesis is a safe and effective treatment for femoral neck fractures; however, patients with femoral neck fracture and CKD have a higher risk of nonunion and subsequent surgical revision. LEVEL OF RELEVANCE: Prognostic studies, Level III.

Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions.

Background/Objectives: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal-epithelial transition (MET) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (EGFR) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. Methods: A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. Conclusions: MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.

Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified as potent oncogenic drivers in several malignancies, including non-small cell lung cancer (NSCLC). The discovery of ALK inhibition using a tyrosine kinase inhibitor (TKI) has dramatically improved the outcomes of patients with ALK-mutated NSCLC. However, the emergence of intrinsic and acquired resistance inevitably occurs with ALK TKI use. This review describes the molecular mechanisms of ALK TKI resistance and discusses management strategies to overcome therapeutic resistance.

Cost effectiveness of immunotherapy combination therapies for endometrial cancer.

Over the past five years (2019-2023), several new targeted therapies and immunotherapy has been approved in treating relapsed cervical, ovarian, and endometrial cancers. Concurrently, there has been growing recognition of financial toxicity associated with cancer care during this time period. As such, we reviewed FDA approvals from 2019 to 2013 and identified the following approvals in gynecologic oncology: pembrolizumab plus lenvatinib, pembrolizumab for recurrent endometrial cancer that is MSI-H/dMMR, tisotumab vedotin, dostarlimab as single-agent therapy, and dostarlimab plus chemotherapy. We focused on approvals for endometrial cancer, and conducted a cost-effectiveness analysis for combination options approved in treating recurrent or advanced endometrial cancer (i.e. pembrolizumab plus lenvatinib versus placebo; dostarlimab plus chemotherapy versus placebo), and found neither regimen was cost-effective at a willingness-to-pay of $100,000 per Equal Value of Life Years Gained (evLYG). While these costs may not necessarily be translated to an individual patient, these costs are absorbed by healthcare systems and insurance providers on a larger scale with downstream effects on individuals contributing to healthcare costs a whole.

A narrative review on perioperative systemic therapy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) that is operable still carries a high risk of recurrence, approaching 50% of all operable cases despite adding adjuvant chemotherapy. However, the utilization of immunotherapy and targeted therapy moving beyond the metastatic NSCLC setting and into early-stage perioperative management has generated tremendous enthusiasm and has been practice-changing. Adjuvant atezolizumab in NSCLC first demonstrated a clinical benefit with an immune checkpoint inhibitor. Then, with studies studying a significant benefit in major pathologic response in surgical patients treated preoperatively with immunotherapy compared to only chemotherapy, neoadjuvant nivolumab and chemotherapy were evaluated and showed significant event-free survival benefit leading to subsequent studies evaluating perioperative immunotherapy and chemotherapy. Meanwhile, with regards to targeted therapies, adjuvant osimertinib in EGFR-mutated NSCLC and adjuvant alectinib in ALK-rearranged NSCLC have both received regulatory approvals following demonstrated clinical benefit in clinical trials. With rapidly evolving changes in the field, new combinations such as multiple immunotherapy agents and antibody-drug conjugates in development, perioperative NSCLC management has quickly become complicated with different pathways to perioperative treatment. Furthermore, circulating tumor DNA and studies looking at better tools to prognosticate immunotherapy response will help with decision-making regarding which patients should receive immunotherapy and if so, either only pre-operatively or both pre- and post-operatively. In this review, we look at the evolution of systemic therapy in the perioperative setting from adjuvant chemotherapy to adjuvant immunotherapy to perioperative immunotherapy and look at perioperative targeted therapy while looking ahead to future considerations.

Assessing platelet-lymphocyte ratio in EGFR-mutated non-small cell lung cancer patients treated with tyrosine kinase inhibitors: An analysis across TKI generations.

Introduction : The prognostic utility of laboratory markers in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) is an ongoing area of research. The utility of the platelet-lymphocyte ratio (PLR) in patients treated with osimertinib is undetermined. Methods : 151 patients treated with EGFR TKIs in Los Angeles were grouped into one of two groups according to generation of TKI. Differences in progression free survival (PFS) by stratification by PLR was determined using Kaplan-Meier analysis. Differences in median change in laboratory markers by generation of TKI was analyzed using Mann-Whitney tests. Cox Hazard Regression was used to perform multivariate analysis. Results : Median PFS of those managed with 1st or 2nd generation TKIs was significantly lower in patients with a PLR ≥ 180 (10.5 months) compared to those with PLR < 180 (16.6 months, p = 0.0163). Median PFS was comparable in those treated with osimertinib regardless of PLR. Patients managed with osimertinib had a significant decrease in absolute lymphocyte count (ALC) at 6 weeks and in platelets at 6 weeks and 3 months compared to those managed with 1st or 2nd generation TKIs. Discussion : The prognostic value of PLR was more apparent in patients treated with 1st or 2nd generation TKIs compared to those treated with osimertinib. Third generation EGFR TKIs may be more efficacious in treating patients with laboratory findings previously shown to predict poor survival. The significant changes in peripheral cell counts suggest variability tumor microenvironment changes dependent on the generation of TKI received.

Characterization of Thyroid Cancer among Hispanics in California, USA, from 2010 to 2020.

BACKGROUND: Previous studies on Hispanic thyroid cancer cases show sex disparities and an increased prevalence of large tumor sizes and nodal involvement. Here, we characterized Hispanic thyroid cancer cases in California. METHODS: We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry by sex, race/ethnicity, histology, TNM stage, tumor size, lymph node involvement, and Charlson comorbidity score. The age-adjusted incidence rate (AAIR) and age-adjusted mortality rate (AAMR) for all causes of death were calculated. A Cox proportional hazards regression analysis was performed to evaluate the mortality risk from all causes of death by race. RESULTS: Overall, 56,838 thyroid cancer cases were identified, including 29.75% in Hispanics. Hispanics had the highest female-to-male incidence rate ratio (IRR 3.54) and the highest prevalence of T3/T4 tumor size (28.71%), the highest N1 nodal status (32.69%), and the highest AAMR (0.79 per 100,000 people). After adjusting for demographic and tumor covariates, compared to non-Hispanic White people, Hispanic ethnicity, with an HR of 1.22 (95% CI 1.18-1.25, p < 0.0001), remained a significant independent contributor to mortality risk. CONCLUSIONS: Hispanics had the greatest female-to-male IRR ratio, a greater prevalence of advanced disease features at diagnosis, along with the highest AAMR and increased mortality risk despite adjustments for demographic and tumor covariates. Further investigation into other risk factors is needed.

Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy.

The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.

A narrative review of antibody-drug conjugates in EGFR-mutated non-small cell lung cancer.

In the past 15 years, non-small cell lung cancer (NSCLC) treatment has changed with the discovery of mutations and the development of new targeted therapies and immune checkpoint inhibitors. Epidermal growth factor receptor (EGFR) was the first mutation in NSCLC to have a drug that was FDA-approved in 2013. Osimertinib, a third-generation tyrosine kinase inhibitor, is approved as first-line therapy for advanced NSCLC and in the adjuvant setting for Stage IB-IIIA resected NSCLC. However, resistance to osimertinib is inevitably an issue, and thus patterns of resistance to EGFR-mutated NSCLC have been studied, including MET amplification, EGFR C797X-acquired mutation, human epidermal growth factor 2 (HER2) amplification, and transformation to small cell and squamous cell lung cancer. Current management for EGFR-mutated NSCLC upon progression of EGFR TKI is limited at this time to chemotherapy and radiation therapy, sometimes in combination with the continuation of osimertinib. Antibody-drug conjugates (ADCs) are made up of a monoclonal antibody linked to a cytotoxic drug and are an increasingly popular class of drug being studied in NSCLC. Trastuzumab deruxtecan has received accelerated FDA approval in HER2-mutated NSCLC. ADCs offer a possible solution to finding a new treatment that could bypass the intracellular resistance mechanism. In this review article, we summarize the mechanism of ADCs and investigational ADCs for EGFR-mutated NSCLC, which include targets to MET amplification, HER3, Trop2, and EGFR, along with other ADC targets being investigated in NSCLC, and discuss future directions that may arise with ADCs in EGFR-mutated NSCLC.