Osteosarcopenia (OSP), a degenerative syndrome characterized by concurrent osteoporosis and sarcopenia, exhibits persistently high global prevalence due to aging and disuse, yet lacks targeted therapies. p38 MAPK plays a key regulatory role in musculoskeletal degeneration. Increased expression of DUSP4, a key inhibitor of the Mitogen-Activated Protein Kinase (MAPK) pathway, inhibits the phosphorylation of p38 MAPK. Thus, targeted delivery of microRNAs that inhibit DUSP4 expression can activate the p38 MAPK pathway and promote osteogenic and myogenic differentiation. However, the therapeutic efficacy of nucleic acid drugs critically depends on delivery systems with targeted specificity, stability, and biocompatibility. Therefore, we engineered a hybrid nanovesicle (miR@DT/iMNV) by fusing bone-muscle dual-targeting peptide-modified liposomes (miR@DT-Lipo) and iPSC-derived MSC-EVs (iMSC-EVs). The miR@DT/iMNV enables the dual-tissue targeted delivery of miR-206-5p (which is downregulated in OSP and can target and inhibit DUSP4) and exhibits excellent biocompatibility. Results demonstrated that miR@DT/iMNV enhances osteogenic/myogenic capacities of stem cells, modulates macrophage phenotypes, restores mitochondrial function, and increases bone/muscle mass in a disused OSP murine model. This dual-targeted, multi-mechanistic strategy presents an innovative therapeutic approach for OSP.

Objectives: Our objectives were to evaluate symptom prevalence, severity, and temporal trends ≤ 18 months from gynecologic cancer (Gyn-Ca) diagnosis using the ESAS-r questionnaire and to identify predictors of elevated symptom burden. Methods: We performed a retrospective population-based study of newly diagnosed Gyn-Ca patients in Ontario, Canada, from January 2007 to March 2022 using linked provincial healthcare databases. Patients with ≥1 ESAS-r completed ≤18 months from diagnosis were included. Diagnosis groups were created using WHO ICD-O3 codes. ESAS-r data were linked to provincial healthcare databases using unique coded identifiers. Primary outcome was a severe score (≥7) on any symptom by month (30-day block) from diagnosis, and secondary outcome was a moderate-severe score (≥4). Multivariable logistic regression identified predictors of elevated scores, with p < 0.05 being significant. Results: A total of 35,559 of 59,175 diagnosed patients (59.5%) completed ≥1 ESAS-r, with 207,000 unique assessments. Moderate-severe (≥4) or severe (≥7) scores were most common for tiredness (62.6%, 33.5%) and poor wellbeing (60.2%, 28.5%). All scores improved over time, with anxiety ≥ 4 dropping from 48.1% at diagnosis to 24.2% at 18 months. Patients with uterine cancer had the lowest incidence of elevated scores. Older age, lower rates of material deprivation and increased time from diagnosis were protective against elevated scores. Higher stage and comorbidity were predictive of elevated scores across all symptoms. Patients with vulvar/vaginal and cervix cancers had the highest odds of elevated scores. Conclusions: Patients with newly diagnosed Gyn-Ca report significant symptom burden in the first 18 months after diagnosis. Stage, diagnosis, and level of comorbidity were predictive of elevated scores, whereas older age, material resources and time from diagnosis were protective.

Bullying is associated with a range of psychosocial problems, including depression, anxiety, social anxiety, low self-esteem, and loneliness. However, no studies have been conducted to systematically summarize the literature on the associations between bullying and psychosocial problems in China. This study conducted a meta-analysis of the existing research on these associations. The present study quantitatively analyzed 71 empirical studies, encompassing a total of 130,176 Chinese participants. Various research characteristics (including gender, age group, region, publication language, article type, bullying measurement, measures of psychosocial problems, and bullying type) were analyzed as moderators. The findings revealed a significant association between bullying perpetration and anxiety (r = 0.191), depression (r = 0.261), social anxiety (r = 0.230), loneliness (r = 0.226), and self-esteem (r = −0.262). There were significant associations between bullying victimization and anxiety (r = 0.353), depression (r = 0.327), social anxiety (r = 0.296), loneliness (r = 0.296), and self-esteem (r = −0.253). In addition, gender, region, publication language, article type, and bullying measurements significantly moderated the associations between bullying and most psychosocial problems. The current findings suggest that there is a significant association between both perpetration and victimization of bullying and psychosocial problems among Chinese children and adolescents.

The intercellular crosstalk and reciprocal activation between Kupffer cells (KCs) and hepatic stellate cells (HSCs) are critical drivers of liver fibrosis progression. Nonetheless, the co-regulation of KCs and HSCs is hindered by their distinct anatomical locations and the pathological barriers driven by liver sinusoidal capillarization and aberrant extracellular matrix (ECM) deposition. To address this challenge, we developed a sequential drug delivery nanoplatform (AP13-Cur@DPMLip) which comprises curcumin-loaded liposomes (Cur@Lip) and a desialylated platelet membrane (DPM) camouflage featuring matrix metalloprotease 9 (MMP-9)-responsive release of a platelet-derived growth factor receptor (PDGFR) antagonistic peptide (termed AP13). This biomimetic system exhibits liver-specific distribution and targets KCs via DPM-derived homing capability, followed by Cur-mediated modulation of pro-inflammatory KC phenotypes. Concurrently, AP13 is rapidly released in response to MMP-9 secreted by KCs, subsequently penetrating the sinusoidal capillarization-induced decrescent fenestrae and dense ECM, and inhibited the activation of HSCs. Additionally, rats with liver fibrosis exhibit inflammation remission, collagen reduction and negligible side effects after AP13-Cur@DPMLip treatment. Our findings propose a new strategy for the regulation of KCs and HSCs and highlight the potential of their synergistic deactivation in the treatment of liver fibrosis.

ImportanceHead and neck cancers (HNC) impose a significant economic burden on healthcare systems. Understanding the direct medical costs across different phases of care is crucial for resource allocation and cost-effectiveness evaluations, particularly in universal healthcare settings.ObjectiveTo quantify the direct medical costs of HNC over 60 months postdiagnosis and examine cost variations by cancer subsite, stage, and treatment modality.DesignPopulation-based, matched case-control study using administrative healthcare data.SettingOntario, Canada, a province with a publicly funded universal healthcare system.ParticipantsWe included 19,832 adults diagnosed with HNC between 2007 and 2020. Each case was matched with 5 noncancer controls based on age, sex, and comorbidity.ExposuresHNC diagnosis, categorized by cancer subsite, stage, and treatment modality.Main Outcome MeasuresMean per-person direct medical costs attributable to HNC over a 63-month period, analyzed by phase of care, cancer subsite, stage, and treatment modality.ResultsThe mean per-person cost attributable to HNC over 63 months was $53,812.9 ± $762.2. Costs peaked in the first 3 months postdiagnosis ($9709.7 ± $36.1 per month) and declined over time. Larynx/hypopharynx cancers incurred the highest costs across most phases. Advanced-stage cancers were associated with increased costs, with stage IV cancers nearly doubling the costs of stage I. Multimodal treatments, particularly surgery combined with chemoradiation, resulted in the highest costs across all phases (P < .01).ConclusionsHNC results in substantial healthcare costs, with significant variations by subsite, stage, and treatment modality. The highest costs occur in the early treatment phase and remain elevated for patients requiring multimodal therapies.RelevanceThese findings provide critical data for policymakers and health system authorities to optimize resource allocation and assess cost-effectiveness. Future research should explore indirect costs and the impact of early detection strategies to reduce the economic burden of HNC.Level of evidence3.

Endothelial cells (ECs), as integral components of the vascular intima, play a pivotal role in the regulation of vascular tone, maintenance of blood flow homeostasis, and control of inflammatory responses. In response to pathological insults such as oxidative stress, mitochondrial dysfunction, and persistent inflammatory stimulation, ECs undergo senescence-associated phenotypic transitions, characterized by cell cycle arrest, endothelial dysfunction, and the establishment of a chronic pro-inflammatory microenvironment. Senescent ECs exacerbate inflammatory signaling, impair vascular homeostasis, and reshape intercellular communication networks, thereby constituting a fundamental pathological mechanism underlying the development and progression of cardiometabolic diseases, including atherosclerosis (AS), diabetes mellitus (DM), and hypertension (HTN). This review comprehensively summarizes the major triggers, molecular regulatory pathways, and functional consequences of endothelial cell senescence, with a particular focus on the central role of inflammation in mediating senescence-driven cardiometabolic disease progression. Furthermore, potential therapeutic strategies targeting endothelial cell senescence are briefly discussed, providing theoretical insights for the prevention and management of cardiometabolic disorders.

During the COVID-19 pandemic, operating room restrictions led to triaging of breast cancer (BC) surgery. This study assessed the impact of the pandemic on wait times for BC surgery at a population level. Patients diagnosed with BC between January 2018 and December 2021 in Ontario, Canada, were categorized as pre-pandemic (January 1, 2018, to March 14, 2020), immediate (March 15, 2020, to June 13, 2020), and peri-pandemic (June 14, 2020, to December 31, 2021). Time-to-event analysis evaluated the time to first BC surgery, with subgroup analyses for patients receiving neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy (NET). Among 37,520 patients with newly diagnosed BC, the probability of undergoing surgery each month from their diagnosis date was significantly lower during the immediate and peri-pandemic period than during the pre-pandemic period (log-rank p < 0.01). However, the use of NAC and NET increased during the immediate pandemic compared with the pre-pandemic (NAC: 24.3

AIM:Osteoarthritis (OA) is a prevalent degenerative joint disease characterized primarily by chronic pain. Currently, there are no highly effective treatments for OA pain. This study aimed to assess the efficacy of M2 macrophage-derived small extracellular vesicles (M2-sEVs) in treating OA and alleviating its associated pain, and to investigate their mechanism of action in pain relief. METHODS:M2-sEVs were isolated via ultracentrifugation. A sodium iodoacetate-induced rat OA model was established to assess the effects of M2-sEVs. RNA sequencing was utilized to identify the molecular mechanisms underlying these analgesic effects, with subsequent validation experiments conducted via RT-qPCR, Western blot, and ELISA assays. Human end-stage OA synovial tissues cultured ex vivo were also utilized to confirm clinical relevance. RESULTS:M2-sEVs administration alleviated pain behaviors and joint pathology in OA rats, suppressing pain-related molecules in synovium and dorsal root ganglia. Mechanistically, M2-sEVs inhibited synovial macrophage-derived nerve growth factor (NGF) by modulating the Notch pathway. Importantly, this therapeutic mechanism was validated in ex vivo cultured human synovial tissues. CONCLUSION:M2-sEVs effectively reduce OA-related pain by suppressing macrophage-derived NGF expression via the Notch pathway, highlighting their promising potential as a nanomedicine-based therapeutic strategy for OA pain management.

Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro-inflammatory factors. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have shown anti-inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on senescent chondrocytes is required to facilitate the translation of MSC-sEVs in OA treatment. In this study, versatile engineered MSC-sEVs are developed to targetedly clear senescent chondrocytes and maintain cartilage metabolic homeostasis. Specifically, MSC-sEVs are loaded with siRNA mouse double minute 2 homologue (siMDM2) and modified with cartilage-targeting peptide WYRGRL-PEG2K-DSPE (WPD), named WPD-sEVssiMDM2. The results demonstrate versatile modification improves the cellular uptake of MSC-sEVs in chondrocytes, and thus improves the antiaging effects. Importantly, multifunctional modification enhances cartilage penetration ability and extends joint retention time of MSC-sEVs. In both post-traumatic OA mice and naturally aged mice, WPD-sEVssiMDM2 more effectively eliminates senescent chondrocytes and maintained matrix metabolic homeostasis. By using the P53 phosphorylation inhibitor, the essential role MDM2-P53 pathway in the antiaging function of WPD-sEVssiMDM2 on chondrocytes is verified. In ex vivo cultured human OA cartilage explants, it is confirmed that WPD-sEVssiMDM2 alleviates senescent phenotype. Altogether, the findings suggest that WPD-sEVssiMDM2 have promising translational potential for OA treatment.

MUC5AC is an important component of mucins, which is often disproportionately increased in response to cigarette smoke and allergens, thereby increasing health problems. As a traditional Chinese medicine, Inula japonica Thunb. is used mainly to treat cough and phlegm. 1-O-Acetylbritannilactone (ABL), one of the main ingredients in I. japonica, may be an anti-inflammatory and anti-MUC5AC drug candidate. ABL significantly decreased the production of NO and the mRNA expression of IL-1β, IL-6, TNF-α, and iNOS in LPS-stimulated RAW264.7 cells. Network pharmacology suggested that ABL might inhibit inflammation and MUC5AC expression, and EGFR, MAPK, SRC, and PKC-α might be key proteins involved. The results of molecular docking, molecular dynamics simulations, CETSA and MST suggested that ABL interacted with PKC-α, indicating that PKC-α was a target of ABL. ABL reduced the expression of the SRC/EGFR/MAPK signaling pathway in PMA-induced NCI-H292 cells and LPS-stimulated RAW264.7 cells. In animal experiments, ABL significantly ameliorated COPD in mice by improving pulmonary function, suppressing oxidative stress, and decreasing inflammatory cell infiltration and mucus production in lung tissue. The results of the phenol red test showed that ABL had a significant expectorant effect. In conclusion, ABL exhibited anti-inflammatory and anti-MUC5AC effects by targeting PKC-α and downregulating the SRC/EGFR/MAPK signaling pathway. This study revealed that ABL is a natural candidate molecule with anti-inflammatory and expectorant effects.

INTRODUCTION:Adolescents and young adults (AYA) with cancer are at risk of adverse mental health outcomes during and after treatment. Tools identifying AYA at the highest risk would guide screening and interventions. We determined whether self-reported symptoms following cancer diagnosis were associated with early and late severe mental health events (SMHEs). METHODS:Ontario AYA diagnosed with cancer aged 15-29 between 2010 and 2018 were identified and linked to healthcare databases, including one capturing self-reported Edmonton Symptom Assessment System (ESAS) scores at cancer-related visits. Scores for depression, anxiety, and poor well-being were categorized as not measured, mild, moderate, or severe. SMHEs were defined as mental health-related Emergency Department visits or hospitalizations. We determined the association of ESAS scores with subsequent early SMHEs (< 5 years). Among 5-year survivors, we determined the association between the maximum ESAS score within 1 year of cancer diagnosis and late SMHEs (occurring > 5 years from cancer diagnosis). RESULTS:Among 5435 AYA, symptom severity was associated with subsequent SMHE risk. AYA who reported severe versus mild anxiety were at > 3-fold higher risk of subsequent early SMHEs [adjusted hazard ratio (aHR) 3.6, 95th confidence interval (CI) 1.9-6.7; p < 0.001]. Among 3518 (64.7%) 5-year survivors, symptom severity predicted late SMHE. At 5 years postcancer diagnosis, those who reported severe versus mild depression within 1 year following cancer diagnosis were at 3-fold elevated risk (aHR 3.0, 95 CI 1.8-4.9; p < 0.0001). CONCLUSION:Systematic symptom screening early postcancer diagnosis identifies AYA at high risk of both early and late SMHEs who may benefit from targeted screening and interventions.

New immunosenescence targets for preventing senescence-associated pathological cardiac hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically aged human and mouse samples, the IL-17A level increased with physiological aging, heart failure (HF), and SA-PCH and was negatively correlated with thymic Bmi-1 expression. Bmi-1 f/f LckCre + mice and Bmi-1 f/f littermates were generated to determine whether Bmi-1 delayed T cell aging by maintaining thymic T cell development to prevent SA-PCH. As a result, Bmi-1 promoted thymic T cell development by upregulating Notch signaling and prevented DN1 T cells from differentiating into γδT17 cells by downregulating γδT17 cell differentiation signaling. Bmi-1 upregulated Notch signaling by inhibiting p53-mediated Ikzf1 transcription at the −1,863 to −1,849 Ikzf1 promoter region. Bmi-1–RING1B promoted RORγt ubiquitination and degradation by proteasome to inhibit the production of IL-17A in γδT17 cells. Bmi-1 also downregulated Rorc transcribed by c-Maf by trimethylating H3K27 at the −1,511 to −1,497 Rorc promoter region. Subsequently, the number of peripheral γδT17 cells infiltrating the heart tissues was reduced, while alleviating IL-17A-dependent cardiac aging, hypertrophy, dysfunction, senescence-associated secretory phenotype (SASP), and macrophage–myofibroblast transition, ultimately improving SA-PCH. The RORγt inhibitor SR1001 and IL-17A neutralizing antibody ixekizumab prevented thymic RORγt-IL-17A-dependent SA-PCH. Furthermore, RORγt bound to Bmi-1 through ARG237 and to RING1B through GLU235, which could be used as a therapeutic strategy for SA-PCH to construct binding peptides promoting Bmi-1–RING1B binding to RORγt and degrading RORγt for inhibiting γδT17 cell differentiation and IL-17A production. Thus, thymic Bmi-1 prevented IL-17A-dependent SA-PCH by decreasing γδT17 cell numbers.

Human mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have demonstrated significant immunomodulatory and pro-regenerative potentials. However, the lack of specific markers to define MSC-sEVs presents a major challenge for their clinical application. Here, the proteomic datasets of MSC-sEVs from three cell sources were synchronously analyzed, and several surface antigens commonly found on MSCs were selected as candidate markers due to their high abundances in MSC-sEVs. Next, MSC-sEVs from three cell sources (adipose tissue, umbilical cord, and induced pluripotent stem cells) were stained with fluorescein-conjugated antibodies and analyzed by NanoFCM at single-vesicle resolution. The positive rates of CD13, CD29, and CD90 all exceeded 60% across sEVs derived from three MSCs sources, whereas other candidates generally exhibited lower positive rates. The high positive rates of them were further verified in MSC-sEVs purified via other methods. Moreover, high-resolution microscopy, as an orthogonal method, visually validated their high presence in MSC-sEVs. Meanwhile, none of the non-MSC-sEVs showed concurrent positive rates for CD13, CD29, and CD90 exceeding 40%, suggesting that this marker panel (with a positive rate threshold of 50% for all three markers) could specifically distinguish MSC-sEVs from non-MSC-sEVs. Finally, the positive rates of this panel of markers were assessed in sEVs derived from MSCs at successive passages. The results revealed a progressive diminution of the positive rates of CD29 and CD90 in the sEVs secreted by MSCs with successive passages, accompanied by a reduction in the pro-proliferative activity of these sEVs. Taken together, we have identified a specific and quantifiable marker panel for MSC-sEVs characterization, which facilitates the development of standardized assays for defining MSC-sEVs and ultimately accelerates the clinical translation of MSC-sEVs.

BACKGROUND: Fragmented care (FC) occurs when patients receive treatment across several different hospitals. Regionalization of surgery for patients with high-grade endometrial cancer means that patients must travel longer distances to receive care; these patients often require adjuvant treatment after surgery. OBJECTIVE: To determine whether the fragmentation of surgery and adjuvant treatment impacts survival in patients with high-grade nonendometrioid endometrial cancer. METHODS: This population-based retrospective cohort study included patients diagnosed between 2003 and 2017 with high-grade nonendometrioid endometrial cancer who received adjuvant treatment postoperatively. Nonfragmented care was defined as receiving surgery and adjuvant treatment at the same institution. The primary outcome was overall survival. RESULTS: We identified 1795 patients, of whom 583 (32.5%) had FC. Patients with nonfragmented care were more likely to have had surgery by a gynecologic oncologist (92.4 vs 58.8%, P<.001), surgical staging (66.6 vs 44.8%, P<.001), and less travel for surgery (mean 30.8 km 93.7 km, P<.001). They were less likely to receive chemotherapy (26.3 30%, P<.001) and chemoradiation (38.4 vs 41.3%, P<.001). Median survival was 9 years. There was no significant difference in overall survival between patients who received FC and nonfragmented care; 92.4% 93.5% of the patients in the FC and nonfragmented care groups were treated a specialized gynecologic oncology center for at least part of their treatment (surgery, adjuvant treatment, or both). CONCLUSION: We have previously shown that regionalization surgery in high-grade endometrial cancer is associated with improved survival. Fragmentation of surgery and adjuvant treatment in this population does not have an adverse effect on survival. After receiving surgical treatment with a gynecologic oncologist, these patients receive adjuvant treatment closer to home to decrease financial travel burden.

Importance:Head and neck cancer (HNC) and its associated treatments are associated with substantial functional, psychological, and financial consequences. Patient-reported outcome measures (PROMs) play a crucial role in capturing the full impact of disease. Understanding how PROMs are associated with health care costs is critical for cancer care planning; however, the association of health care expenditure and PROMs is yet to be clarified. Objective:To assess the association between Edmonton Symptom Assessment System (ESAS) scores and direct health care costs incurred in 30 days for adult patients with HNC. Design, Setting, and Participants:This cohort study used linked administrative datasets from Ontario, Canada, of adult patients who received a diagnosis of HNC between January 1, 2007, and December 31, 2022. Included patients had at least 1 ESAS assessment completed from the date of diagnosis to the date of death or January 31, 2023. Coprimary exposures were the highest individual symptom score (h-ESAS, from 0 to 10) and the sum total of the individual scores of the 9 symptoms (t-ESAS, from 0-90). Multivariable negative binomial regression models using a generalized estimating equation approach under an exchangeable correlation structure were used to assess the association between each primary exposure and 30-day costs, accounting for patient age, sex, immigration status, socioeconomic status, cancer type, and recent cancer-directed treatment modality, updated to each ESAS assessment date. Data analysis was performed from September 2024 to February 2025. Main Outcomes and Measures:A 30-day cost-capturing window was defined around each ESAS assessment date to comprise a 7-day interval before this date and a 22-day interval after this date. Direct health care costs incurred during this 30-day window were estimated using a patient-level case-costing algorithm adjusted to 2023 Canadian dollars. Results:The total sample population was 16 544 adult patients with HNC (mean [SD] age at diagnosis, 63.7 [11.5] y; 12 526 [75.7%] male individuals ) and their 90 025 ESAS assessments completed since the date of diagnosis. Each 1-point increase in h-ESAS was associated with a 22% increase in 30-day costs (rate ratio [RR], 1.22; 95% CI, 1.21-1.22). Likewise, relative costs increased progressively with higher t-ESAS scores, peaking among patients with scores of 71 to 80 (RR, 4.82; 95% CI, 4.32-5.39). Conclusions and Relevance:This cohort study found that both h-ESAS and t-ESAS were significantly associated with 30-day costs. These findings highlight the potential role of PROMs in cost-mitigation strategies for HNC care.

Background New highly effective, but expensive, immunotherapies have revolutionized the treatment of relapsed pediatric acute lymphoblastic leukemia (ALL) but their long-term clinical and economic impact is unclear. We developed the ALL Policy microsimulation model to estimate long-term clinical and economic outcomes for patients with pediatric ALL aged 0-17 in Ontario, Canada. We also illustrate the model's clinical utility through a cost-effectiveness analysis of blinatumomab in relapsed B-cell ALL.Methods The ALL Policy model is informed using health administrative data and chart abstracted data from Ontario, Canada, and published literature. The model estimates lifetime risk of relapse, bone marrow transplant (BMT), conditional life expectancy, quality-adjusted life years (QALYs), and total health-care costs for individuals with pediatric ALL and can be stratified by relevant clinical characteristics (eg, B-cell or T-cell lineage). Additionally, we subset the model to patients with relapsed B-cell ALL to illustrate use of the model in estimating the cost-effectiveness of blinatumomab vs standard chemotherapy.Results Simulated pediatric ALL patients diagnosed from 2002 to 2012 had a projected conditional life expectancy of 64.90 years. The lifetime risk of BMT was estimated at 12.5%. Lifetime health-care costs were $244 433 Canadian Dollars (CAD) (95% confidence interval = $213 314 to $303 430). Treatment with blinatumomab compared to standard chemotherapy post-relapse was estimated to result in 1.08 additional QALYs and an additional cost of $59 410 CAD (incremental cost-effectiveness ratio of $54 885/QALY).Conclusion The ALL policy model can serve as a modeling foundation for timely economic evaluation. Introduction of blinatumomab in relapsed B-cell ALL may be a cost-effective strategy.

Importance:The care for a small subset of patients is responsible for a disproportionately large share of health care expenditures. Head and neck cancer is associated with significant health care costs due to complex treatment regimens and long-term sequelae. Given this high baseline cost, identifying patients with high care costs within a population with cancer might help inform interventions to optimize resource allocation. Objective:To characterize patients with head and neck cancer with the highest health care costs during the first year after diagnosis. Design, Setting, and Participants:A population-based, retrospective cohort study was conducted using administrative data from the Institute for Clinical and Evaluative Sciences in Ontario, Canada, and included adults diagnosed with head and neck cancer between January 2007 and October 2020 (identified from the provincial cancer registry) with a full 1.5-year follow-up from the date of diagnosis to the date of death or October 31, 2021. The total 1-year health care costs were estimated using a patient-level algorithm and were collected in 2020 Canadian dollar values. The main analyses were performed in April 2023 and a sensitivity analysis was performed in April 2025. Main Outcomes and Measures:High health care costs (>75th percentile) during the first year after a head and neck cancer diagnosis. Predictors of high health care costs were identified using a multivariable logistic regression model. Results:The cohort included 13 795 patients (mean age, 63.2 [SD, 11.7] years and 3452 [25.0%] were female), 3448 (25%) of whom had high health care costs. Cancer stage was the strongest predictor of high health care costs. Compared with patients with stage I cancer, those with stage II cancer had 2-fold greater odds for high health care costs (odds ratio [OR], 3.14 [95% CI, 2.56-3.84]), those with stage III cancer had 5-fold greater odds for high health care costs (OR, 6.08 [95% CI, 4.99-7.41]), and those with stage IV cancer had 8-fold greater odds for high health care costs (OR, 8.94 [95% CI, 7.43-10.80]). Receiving multiple treatment modalities also was associated with greater odds for high-cost care. Conclusions and Relevance:This cohort study found that more advanced disease stage and receiving multiple treatment modalities were the strongest predictors of high-cost care among patients diagnosed with head and neck cancer. Prioritizing research and implementation of screening programs, earlier cancer diagnoses, and effective treatment deescalation strategies might mitigate a significant portion of these high costs.