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.

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.

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.

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.

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.

Complete response with pembrolizumab in recurrent squamous cell carcinoma of the oral tongue: A case report.

Immunotherapies such as immune checkpoint inhibitors have shown promising results in solid tumors associated with BRCA2, but there are no consistent predictors for who will respond to immunotherapy. More research is needed on the impact of this mutation in head and neck squamous cell carcinomas, particularly for recurrent/metastatic tumors. We report a case of stage IV oral squamous cell carcinoma associated with BRCA2 mutation that achieved complete remission with pembrolizumab treatment for relapsed disease.

Impact of gender and mutational differences in hormone receptor expressing non-small cell lung cancer.

Background: The incidence of lung cancer in the US has been decreasing but a bigger decline has been observed in men despite similar declines in tobacco use between men and women. Multiple theories have been proposed, including exposure to exogenous estrogens. Our study seeks to understand the relationship between hormone receptors (HR), gender, and the genomic landscape of non-small lung cancer (NSCLC). Methods: 3,256 NSCLC tumor samples submitted for molecular profiling between 2013-2018 were retrospectively identified and assessed for HR expression. Hormone receptor (HR+) was defined as ≥ 1% nuclear staining of estrogen receptor-alpha (ER-a) or progesterone receptor (PR) by immunohistochemistry. DNA sequencing by NGS included cases sequenced by the Illumina MiSeq hot spot 47 gene panel (n=2753) and Illumina NextSeq 592 gene panel (n=503). An adjusted p-value (q-value) <0.05 was determined significant. Results: HR+ was identified in 18.3% of NSCLC. HR+ occurred more commonly in women compared to men (19.6% vs 11.4%, p <0.0001, q <0.0001). EGFR mutations occurred more commonly in HR+ NSCLC than HR- NSCLC (20.2% vs. 14.6%, p = 0.002, q=0.007). Overall, men with EGFR mutations were affected by HR status with a higher prevalence in HR+ NSCLC while such differences were not seen in women. However, in women ages ≤45, there was a trend towards greater prevalence HR+ NSCLC (25.25% vs. 11.32%, q= 0.0942) and 10/25 (40.0%) of HR+ cases in young women were found to be EGFR mutated. KRAS mutations and ALK+ IHC expression occurred more in HR+ NSCLC whereas TP53 mutations occurred more in HR- NSCLC. Conclusions: Women were more likely to have HR+ NSCLC than men and EGFR and KRAS mutations occurred more commonly in HR+ NSCLC. Additional studies with more strict inclusion criteria for HR+ are warranted to see if there is benefit to targeting HR in these subgroups.

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.

Real world prognostic utility of platelet lymphocyte ratio and nutritional status in first-line immunotherapy response in stage IV non-small cell lung cancer.

BACKGROUND: Elevated platelet lymphocyte ratio (PLR) and low body mass index (BMI) are associated with inferior survival in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We evaluated real-world prognostic utility of PLR, BMI, and albumin level in stage IV NSCLC patients receiving first line (1L) IO. METHODS: We identified 75 stage IV patients who received 1L IO therapy at USC Norris Comprehensive Cancer Center and Los Angeles General Medical Center from 2015 to 2022. The primary outcome was overall survival (OS) from time of IO with attention to pre-treatment BMI < 22, albumin < 3.5 g/dL, and PLR > 180. RESULTS: Median age was 66.5 years with 49 (65.3%) males. 25 (33.3%) had BMI < 22. 45/75 (60%) had PLR > 180. Patients with BMI < 22 had inferior OS (13.1 months (m) vs. 37.4 m in BMI > 28, p-value = 0.042) along with patients with albumin<3.5 g/dL (OS: 2.8 m vs. 14.6 m, p-value = 0.0027), and patients with PLR>180 (OS: 8.7 m vs. 23.0 m, p = 0.028). Composite BMI < 22, PLR > 180 had the worst OS, p-value = 0.0331. Multivariate analysis controlling for age, smoking, gender, PD-L1 tumor proportion score (TPS), and histology (adenocarcinoma, squamous, adenosquamous, and large cell) showed that BMI (HR: 0.8726, 95% CI: 0.7892-0.954) and PLR > 180 (HR: 2.48, 95% CI: 1.076-6.055) were significant in OS mortality risk. CONCLUSION: Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients receiving IO therapy of their prognosis and supportive care. MICROABSTRACT: We evaluated real-world prognostic utility of platelet lymphocyte ratio (PLR), body mass index (BMI), and albumin level in 75 Stage IV NSCLC patients receiving first line IO. Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients of their prognosis and to emphasize supportive care needs.

The Development and Role of Capmatinib in the Treatment of MET-Dysregulated Non-Small Cell Lung Cancer-A Narrative Review.

Non-small cell lung cancer (NSCLC) is a leading cause of death, but over the past decade, there has been tremendous progress in the field with new targeted therapies. The mesenchymal-epithelial transition factor (MET) proto-oncogene has been implicated in multiple solid tumors, including NSCLC, and dysregulation in NSCLC from MET can present most notably as MET exon 14 skipping mutation and amplification. From this, MET tyrosine kinase inhibitors (TKIs) have been developed to treat this dysregulation despite challenges with efficacy and reliable biomarkers. Capmatinib is a Type Ib MET TKI first discovered in 2011 and was FDA approved in August 2022 for advanced NSCLC with MET exon 14 skipping mutation. In this narrative review, we discuss preclinical and early-phase studies that led to the GEOMETRY mono-1 study, which showed beneficial efficacy in MET exon 14 skipping mutations, leading to FDA approval of capmatinib along with Foundation One CDx assay as its companion diagnostic assay. Current and future directions of capmatinib are focused on improving the efficacy, overcoming the resistance of capmatinib, and finding approaches for new indications of capmatinib such as acquired MET amplification from epidermal growth factor receptor (EGFR) TKI resistance. Clinical trials now involve combination therapy with capmatinib, including amivantamab, trametinib, and immunotherapy. Furthermore, new drug agents, particularly antibody-drug conjugates, are being developed to help treat patients with acquired resistance from capmatinib and other TKIs.

A Multicenter Retrospective Chart Review of Clinical Outcomes Among Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer.

BACKGROUND: On May 28, 2021, the United States Food and Drug Administration (FDA) granted accelerated approval to sotorasib for second-line or later treatment of patients with locally advanced or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC). This was the first FDA-approved targeted therapy for this patient population. Due to a paucity of real world data describing clinical outcomes in patients with locally advanced or metastatic KRAS G12C mutated NSCLC in the second-line or later, we sought to compile a large, academic medical center-based historical dataset to clarify clinical outcomes in this patient population. MATERIALS AND METHODS: The clinical outcomes of 396 patients with stage IV (n = 268, 68%) or recurrent, metastatic (n = 128, 32%) KRAS G12C mutant NSCLC were evaluated in this multicenter retrospective chart review conducted through the Academic Thoracic Oncology Medical Investigator's Consortium (ATOMIC). Patients treated at 13 sites in the United States and Canada and diagnosed between 2006 and 2020 (30% 2006-2015, 70% 2016-2020) were included. Primary outcomes included real-world PFS (rwPFS) and overall survival (OS) from time of stage IV or metastatic diagnosis, with particular interest in patients treated with second-line docetaxel-containing regimens, as well as clinical outcomes in the known presence or absence of STK11 or KEAP1 comutations. RESULTS: Among all patients with stage IV or recurrent, metastatic KRAS G12C mutant NSCLC (n = 201 with KRAS G12C confirmed prior to first line systemic therapy), the median first-line rwPFS was 9.3 months (95% CI, 7.3-11.8 months) and median OS was 16.8 months (95% CI, 12.7-22.3 months). In this historical dataset, first line systemic therapy among these 201 patients included platinum doublet alone (44%), PD-(L)1 inhibitor monotherapy (30%), platinum doublet chemotherapy plus PD-(L)1 inhibitor (18%), and other regimens (8%). Among patients with documented second-line systemic therapy (n = 123), the second-line median rwPFS was 8.3 months (95% CI, 6.1-11.9 months), with median rwPFS 4.6 months (95% CI, 1.4-NA) among 10 docetaxel-treated patients (9 received docetaxel and 1 received docetaxel plus ramucirumab). Within the total study population, 49 patients (12%) had a co-occurring STK11 mutation and 3 (1%) had a co-occurring KEAP1 mutation. Among the 49 patients with a co-occurring KRAS G12C and STK11 mutation, median rwPFS on first-line systemic therapy (n = 23) was 6.0 months (95% CI, 4.7-NA), and median OS was 14.0 months (95% CI, 10.8-35.3 months). CONCLUSION: In this large, multicenter retrospective chart review of patients with KRAS G12C mutant NSCLC we observed a relatively short median rwPFS of 4.6 months among 10 patients with KRAS G12C mutant NSCLC treated with docetaxel with or without ramucirumab in the second-line setting, which aligns with the recently reported CodeBreak 200 dataset.

Evaluating Real World Mutational Differences Between Hispanics and Asians in NSCLC at a Large Academic Institution in Los Angeles.

INTRODUCTION: Hispanics living in the United States have higher rates of Epidermal Growth Factor Receptor (EGFR) mutations compared with Non-Hispanic Whites. While this higher incidence is like Asian patients living in the United States, the outcomes for Hispanic patients differ. We looked to compare the variances in mutational profiles between Hispanics and Asians in Los Angeles. PATIENTS AND METHODS: Three hundred ninety three non-small cell lung cancer (NSCLC) patients treated at Los Angeles County + University of Southern California (LAC + USC) Medical Center and Norris Comprehensive Cancer Center who received comprehensive genomic profiling (CGP) were evaluated from July 2017 to August 2020. CGP was done using tissue biopsies (n = 211) from Caris Life Sciences and liquid biopsies (n = 231) from Guardant Health. Multivariate logistic regression evaluated the role of race between Hispanics and Asians. RESULTS: In the Hispanic cohort (n = 90), 50.0% were male, median age of diagnosis was 62, 54.5% were non-smokers, and 85.5% had adenocarcinoma. In Asians (n = 142), 47.5% were male, median age of diagnosis was 65, 59.6% were non-smokers, and 83.8% had adenocarcinoma. Hispanic patients had greater prevalence of Kirsten rat sarcoma virus (KRAS) mutations (odds ratio [OR] 4.42, 95% confidence interval [95% CI]: 1.63-12.83) and lesser prevalence of EGFR mutations (OR 0.31, 95% CI: 0.16-0.59). There were a greater proportion of Hispanic smokers with KRAS mutations (14/41; 34.1%) than Asian smokers (4/58; 6.9%). CONCLUSION: We saw a greater percentage of Hispanics with KRAS mutations despite similar smoking percentages along with a greater percentage of Asians with EGFR mutations. This study shows that ethnic and racial backgrounds of the patient can influence the effects of potentially carcinogenic exposures leading to variances of mutation frequency of NSCLC among different ethnicities.

Acute aortic occlusion associated with COVID-19: A rare complication of a not so rare disease.

Recent literature has reported a high prevalence of thrombotic events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for causing coronavirus disease 2019 (COVID-19) infection. Although venous thromboembolism complications have been well studied, arterial thrombosis is less well described. Our aim is to describe acute aortoiliac occlusion (AAO), itself a rare condition, as a complication of COVID-19 infection and review existing literature regarding its presentation and available treatment modalities. Over a 2-week span in late 2021, 2 patients with recent COVID-19 infection presented to our tertiary care hospital with AAO. Each case was treated with a multimodal therapeutic approach, including vascular interventional radiology guided thrombolysis, vascular surgical approach, and systemic anticoagulation. Although two separate primary approaches were taken, each resulted in high morbidity and death in both cases. Acute aortic occlusion is a rare disease associated with high morbidity and mortality. COVID-19 has further been associated with arterial thromboembolic complications, including AAO, as presented here. More research is needed to identify patients at highest risk of developing arterial thromboembolic disease after COVID-19 infection as well as to determine ideal therapeutic options in order to improve the exceedingly high morbidity and mortality associated with this complication.

Correction: Liao et al. Twelve-Week Lower Trapezius-Centred Muscular Training Regimen in University Archers. Healthcare 2022, 10, 171.

The authors would like to make the following corrections to the published paper [...].

Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study.

PURPOSE: Determine whether specific CTNNB1 or APC mutations in patients with desmoid tumor were associated with differences in clinical responses to systemic treatments. EXPERIMENTAL DESIGN: We established a multi-institutional dataset of previously treated patients with desmoid tumor across four U.S. sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, desmoid tumor location, and treatment regimen. RESULTS: A total of 259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First- and second-line cPFS, rPFS, and TTNT were not significantly affected by mutation subtype; however, APC-mutant desmoid tumors demonstrated nonstatistically significant inferior outcomes. Extremity/trunk desmoid tumor location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared with surgery or "other" therapies, including estrogen-receptor blockade and imatinib. OS was significantly worse with APC or CTNNB1 negative/other mutations. CONCLUSIONS: Mutation subtype did not affect responses to specific systemic therapies. APC mutations and nonextremity desmoid tumor locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk desmoid tumors should be prospectively evaluated. See related commentary by Greene and Van Tine, p. 3911.

Twelve-Week Lower Trapezius-Centred Muscular Training Regimen in University Archers.

Archery is a fine-motor-skill sport, in which success results from multiple factors including a fine neuromuscular tuning. The present study hypothesised that lower trapezius specific training can improve archers' performance with concomitant changes in muscle activity and shoulder kinematics. We conducted a prospective study in a university archery team. Athletes were classified into exercise and control groups. A supervised lower trapezius muscle training program was performed for 12 weeks in the exercise group. The exercise program focused on a lower trapezius-centred muscular training. Performance in a simulated game was recorded as the primary outcome, and shoulder muscle strength, kinematics, and surface electromyography were measured and analysed. In the exercise group, the average score of the simulation game increased from 628 to 639 after the training regimens (maximum score was 720), while there were no such increases in the control group. The lower trapezius muscle strength increased from 8 to 9 kgf after training regimens and shoulder horizontal abductor also increased from 81 to 93 body weight% for the exercise group. The upper/lower trapezius ratio decreased from 2.2 to 1.1 after training. The lower trapezius exercise training regimen could effectively improve the performance of an archer with a simultaneous increase in shoulder horizontal abductor and lower trapezius muscle strength.

Thyroid cancer incidence disparities among ethnic Asian American populations, 1990-2014.

PURPOSE: Asians and/or Pacific Islanders (APIs) are at high risk of thyroid cancer, hence we examined thyroid cancer's incidence among disaggregated API subgroups in the United States (U.S.) to identify potential ethnic-specific disparities. METHODS: Data from 1990 to 2014 in the Surveillance, Epidemiology, and End Results Program (SEER) were used to compare age-adjusted incidence rates (AAIRs) of thyroid cancer for seven API ethnic subgroups to non-Hispanic whites (NHWs) using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Sex, age, tumor histotype, and year of diagnosis were considered. Trends were evaluated using average annual percent change (AAPC) statistics. RESULTS: The highest AAIRs (per 100,000 person-years) were among Filipinos (female AAIR=20.49, male AAIR=7.06) and the lowest among Japanese (female AAIR=8.36, male AAIR=3.20). However, Filipinos showed significantly lower incidence of medullary tumors when compared to NHWs (female IRR=0.60, 95% CI 0.40-0.87, male IRR=0.26, 95% CI 0.26-0.51). The largest increasing trends were among Asian Indians and/or Pakistanis for females (AAPC=5.19, 95% CI 3.81 to 6.58) and Koreans for males (AAPC=4.57, 95% CI 3.14 to 6.03). CONCLUSIONS: There are clear differences in thyroid cancer incidence and trends when U.S. API ethnic subgroups are examined separately. Disaggregating APIs in research can provide critical information for understanding thyroid cancer risk.

Characterization of mortality and high-risk characteristics of thyroid cancer in Filipinos using the California Cancer Registry.

Introduction: Filipinos are the third largest Asian American subgroup and have the highest incidence of thyroid cancer among all races. To better understand this racial/ethnic disparity in thyroid cancer affecting Filipinos we analyzed the California Cancer Registry (CCR) data in Filipino thyroid cancer cases from 1988 to 2018. Methods: 97,948 thyroid cancer cases in California from 1988 to 2018 (until 2015 for Asian subgroups) were evaluated. We examined the case distribution by sex, age at diagnosis, race/ethnicity including Asian ethnic subgroups, histology, TNM stage, tumor size, lymph node involvement, lymphovascular invasion, and multifocality. We also looked at treatment data including surgery and radiation including radioactive iodine therapy. We calculated age-adjusted mortality rates (AAMR) for each major racial group and each Asian ethnic subgroup. Binary logistic regression was used to determine the likelihood of high-risk characteristics and treatment when comparing Filipinos to other racial/ethnic groups. Kaplan-Meier Estimate was performed to evaluate thyroid cancer survival across all race/ethnicities. Multivariate Cox proportion hazards regression was performed to evaluate mortality risk from all causes of death by race. Results: There were 5,243 (5.35%) Filipino thyroid cancer cases in California from 1988 to 2018. Filipinos had the highest AAMR (1.22 deaths per 100,000) in 2015. Filipinos had a higher likelihood of Stage IV thyroid cancer compared with Non-Hispanic Whites, Non-Hispanic Blacks, Hispanics and nearly all Asian subgroups. Filipinos had a worse 5-year and 10-year overall survival (OS) than the combination of all other Asian/Pacific Islanders. Filipinos compared to Non-Hispanic Whites had significant mortality risk in overall and papillary thyroid cancer cases (Overall HR: 1.10, 95% CI 1.07-1.13, p < 0.0001, Papillary HR: 1.11, 95% CI 1.07-1.14, p < 0.0001) when adjusted for race/ethnicity, age, gender, socioeconomic status, and stage. When stratified by Charlson comorbidity score, Filipinos compared to Non-Hispanic Whites still had significant mortality risk (Charlson 0 HR: 1.07, 95% CI 1.02-1.11, p = 0.0017, Charlson 1+ HR: 1.07 95% CI 1.002-1.14, p = 0.0434). Conclusions: Filipino thyroid cancer patients have higher incidences of high-risk pathological features and greater AAMR and mortality risk. These findings warrant further investigation into better understanding the connection between the greater incidence of high-risk characteristics and increased mortality in Filipinos.

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.

Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas.

Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.