Cancer Medicine最新文献

Introduction

CIC-rearranged sarcomas (CRS) are rare tumors predominantly affecting young adults. Despite distinct biology, CRS are often treated like Ewing sarcomas with multi-agent chemotherapy, surgery, and radiotherapy, although the benefits of each remain unclear. We report the impact of treatment on response and survival.

Methods

This retrospective multicenter study included patients diagnosed with CRS between 2002 and 2023. Demographic, treatment, and outcome data were collected. Event-free (EFS) and overall survival (OS) were estimated using Kaplan–Meier analysis; risk factors were assessed via log-rank tests and Cox regression. Treatment response was assessed using RECIST.

Results

Among 27 patients (median age 21.5 years; range 8–83), 14 (52%) had localized and 12 (44%) metastatic disease (1 unknown). In the localized group, 6 (43%) received chemotherapy (Response: 2 complete, CR; 1 partial, PR; 1 mixed, MR; 1 stable, SD; 1 progressive disease, PD); 5 (36%) died—3 (21%) had received chemotherapy. Among metastatic patients, 10 (83%) received chemotherapy (1 CR, 5 PR, 2 MR, 1 PD); 9 died (one without chemotherapy). Local control was achieved in 12/14 (86%) localized and 7/12 (56%) metastatic patients. Only surgical resection was associated with improved OS (HR 0.13; p < 0.01) and EFS (HR 0.26; p < 0.01), particularly with R0 resection (EFS HR 0.23; p = 0.02). At median follow-up of 18 months, 2-year EFS was 56% vs. 8% (p = 0.02) and OS was 67% vs. 23% (p = 0.02) for localized vs. metastatic disease.

Conclusion

Complete resection is critical in CRS. Chemotherapy benefit remains uncertain, underscoring the need for improved local control and novel, biology-driven therapies.

Background

Relationships between socioeconomic factors and metastatic cancer at diagnosis have not been well studied. Using CDC's Social Vulnerability Index (SVI) we studied the association of metastatic cancer at initial diagnosis with 16 social factors and their interaction with insurance status.

Methods

California and Texas cancer registries, merged with the SVI database, were used to identify adult patients diagnosed with breast, colorectal, liver, lung, ovarian, pancreatic, or prostate cancer from 2015 to 2019. To determine the association of SVI with metastatic cancer at initial diagnosis, multivariable binary logistic regression analyses were performed.

Results

Of the 654,016 patients included, 149,476 (21.5%) were diagnosed with metastatic cancer at diagnosis. Overall, the adjusted odds of metastasis at diagnosis increased by 5% for every 10 unit increase in SVI. Stratified by cancer type, the odds (95% confidence interval) of metastatic cancer at diagnosis were: breast 1.04 (1.03–1.05), colorectal 1.01 (1.01–1.02), liver 1.03 (1.02–1.05), lung 1.01 (1.01–1.02), pancreatic 1.02 (1.01–1.03), prostate 1.06 (1.05–1.07). Interaction analysis of insurance with SVI revealed that the marginal effect of the association between SVI and the risk of metastasis at initial diagnosis increased most substantially as SVI increased for patients who had insurance. It was relatively constant for uninsured and Medicaid patients, who had the overall highest average risk.

Conclusions

Increased neighborhood social vulnerability is associated with an increased risk of metastatic cancer at initial diagnosis. While uninsured patients or those on Medicaid had a higher risk, patients with other insurance types experienced the largest increases in risk associated with increasing SVI.

Background

This study investigated recent trends and demographic patterns in tongue cancer surgeries in Japan using nationwide insurance claims data.

Methods

Annual surgery counts and rates (per 100,000 person-years) were analyzed using medical (2014–2022) and dental (2016–2022) claims. Trends were evaluated using linear and Poisson regression to estimate annual risk ratios (RRs).

Results

An average of 4470.7 surgeries per year was observed (rate: 3.4). The male-to-female ratio was 1.6:1 overall but nearly 1:1 under 40s and over 2.0:1 in the 60s–70s. Surgery rates peaked at ages 75–79 in males (12.0) and 75–84 in females (5.9). Age-adjusted surgery counts rose significantly from 2014 to 2022. Rates increased significantly among all females (RR = 1.020) and overall (RR = 1.010). Significant increases were seen in females aged 40–44 and 60–64 (RR = 1.083 and 1.055).

Conclusions

Distinct age- and sex-related trends were identified, particularly rising rates among middle-aged and older females.

Background

Cancer-associated fibroblasts (CAFs) significantly influence tumor behavior in head and neck squamous cell carcinoma (HNSCC) and other malignancies. We identified the extracellular sulfatase SULF1 as a key stromal factor highly expressed in CAFs and associated with poor prognosis.

Methods and Results

Using CRISPR/Cas9-edited SULF1-knockout primary HNSCC CAFs, we demonstrate that loss of SULF1 reduces fibroblast proliferation and markedly impairs cancer cell migration and invasion in vitro. Two-photon microscopy in 3D spheroid cocultures revealed that SULF1-deficient CAFs fail to support invasiveness of Cal33 cells, resulting in spheroids with fewer invasive projections and altered morphology. Proteomic analysis confirmed the absence of SULF1 in the knockout cell cultures and revealed that SULF2, expressed in tumor cells, does not compensate for its loss.

Conclusion

These findings highlight the importance of CAF-derived SULF1 in regulating tumor invasion and suggest that SULF1 is a promising therapeutic target in HNSCC.

Background

Plasma fibrinogen (FNG) is a prognostic marker in esophageal squamous cell carcinoma (ESCC). However, its predictive value for immune checkpoint inhibitor (ICI) efficacy and the underlying mechanisms remain unclear. This study aimed to evaluate the clinical significance of plasma FNG levels in ICI-treated ESCC patients and investigate its association with tumor-associated neutrophils (TANs) and genomic alterations.

Methods

A retrospective, multicenter analysis of 167 ESCC patients treated with ICIs was performed. TANs were quantified via immunohistochemistry using CD11b and CD66b staining, and PD-L1 expression was assessed using the tumor proportion score (TPS). Whole-exome and RNA sequencing were conducted to analyze genomic and transcriptomic profiles.

Results

Elevated plasma FNG levels correlated with lower ICI response rates and decreased survival. In first-line treatment, chemo-ICI therapy demonstrated superior efficacy compared to dual-ICI therapy in high-FNG patients, while the reverse trend was observed in low-FNG patients. High-FNG tumors showed increased TAN infiltration, independent of PD-L1 expression. RNA sequencing revealed enrichment of neutrophil activation and extravasation pathways in high-FNG tumors.

Conclusions

Elevated plasma FNG levels predict poor prognosis and reduced ICI efficacy in ESCC. They may be potential biomarkers for first-line ICI-based therapy and correlate with TAN infiltration. Further validation and mechanistic investigations are warranted.

Background and Aim

Combining systemic chemotherapy with transarterial chemoembolization (TACE) has demonstrated improved outcomes, with promising results for the efficacy of lenvatinib pretreatment combined with TACE in single-arm studies involving patients with hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy of a scheduled upfront lenvatinib combined with a TACE regimen in patients with HCC, representing both the first study to comparatively analyze this approach and to focus specifically on patients unsuitable for TACE.

Methods

We conducted a multicenter retrospective study between 2018 and 2024, enrolling 41 patients with unresectable Barcelona Clinic Liver Cancer intermediate-stage HCC who were considered unsuitable for TACE owing to factors such as exceeding the up-to-7 criteria, having infiltrative HCC, or multiple asynchronous recurrent HCC. Of these patients, 25 received upfront lenvatinib administration prior to TACE (LEN-TACE group), followed by continuous lenvatinib and on-demand TACE, and 16 received lenvatinib monotherapy.

Results

Radiological evaluation revealed significantly higher complete response (CR) and objective response rates (ORR) in the LEN-TACE group than in the lenvatinib group. The median overall survival (OS) was not reached in the LEN-TACE group, whereas it was 16.2 months in the lenvatinib monotherapy group, indicating a significantly superior OS in the LEN-TACE group (hazard ratio [HR]: 2.99; 95% CI: 1.01–8.95; p = 0.0496). Superiority in both PFS and OS was also observed in the propensity score-matched (PSM) cohort for the LEN-TACE group.

Conclusion

Scheduled upfront lenvatinib combined with TACE is superior to lenvatinib monotherapy for intermediate-stage HCC, particularly in patients unsuitable for TACE.

Background

This study aimed to analyze the clinical and echocardiographic characteristics, pathological profiles, and outcomes of right heart masses, and to explore the role of echocardiography in the evaluation of these masses.

Methods

We retrospectively analyzed 171 patients with echocardiographically diagnosed and pathologically confirmed right heart masses from two centers (2010–2023). Data on clinical presentation, echocardiographic features, pathology, and follow-up were collected. Survival analysis using Kaplan–Meier curves and multivariable Cox regression was performed to identify prognostic factors.

Results

Among 171 patients, 114 had primary cardiac tumors (82 benign, 30 malignant, and 2 of uncertain biological behavior), 41 had metastatic tumors, and 16 had thrombi or other lesions. Myxomas (63.4%) and angiosarcomas (63.3%) were the most common benign and malignant tumors, respectively. Patients with benign tumors had significantly better survival than those with malignant tumors, metastases, or thrombi (all p < 0.01). In the primary tumor subgroup (n = 112), better survival was associated with pedunculated morphology, well-defined margins, high mobility, and absence of metastasis (all p < 0.01). Multivariable analysis identified malignant tumor type (HR = 10.072, p < 0.001; reference: benign tumor), absence of a pedicle (HR = 2.610, p = 0.044; reference: presence of a pedicle), and presence of metastasis (HR = 3.210, p = 0.025; reference: no metastasis) as independent prognostic factors. The median follow-up was 26 months, with a recurrence rate of 4.7% and overall mortality of 35.7%.

Conclusion

Tumor type, pedicle presence, and metastasis are key prognostic factors for primary right heart tumors. Echocardiography is essential for diagnosis and differential diagnosis of right heart masses.

Background

Inactivating BRCA1/2 mutations confer sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPi) in prostate cancer (PCA). However, secondary BRCA1/2 reversion mutations (BRCArev) can restore BRCA function and mediate acquired PARPi resistance. While BRCArev typically arise under PARPi selective pressure, their occurrence in PARPi-naïve settings remains incompletely understood. We sought to characterize the frequency, clinical context, and therapeutic correlates of BRCArev detection in men with advanced PCA, including those without prior PARPi exposure.

Methods

We restrospectively analyzed clinical liquid biopsy results from men with PCA using FoundationOneLiquid CDx between January and December 2023. BRCArev were defined as sequence alterations predicted to restore open reading frame of BRCA1 or BRCA2 harboring pathogenic inactivating variants. Clinical and treatment histories, including chemotherapy and PARPi exposure, were abstracted from medical records.

Results

Over a one-year period, we identified 10 PCA patients with inactivating BRCA1/2 alterations, BRCArev and available treatment history. BRCArev were detected in three of 10 (30%) patients who had not received prior PARPi therapy. All three PARP-naïve patients had previously received chemotherapy (platinum or docetaxel) and radiation, and each exhibited multiple BRCArev events. The remaining 7 patients (70%) had prior olaparib exposure. Among these, the duration of PARPi response was longer in chemo-naïve patients compared with previously treated with chemotherapy (median: 22 vs. 7.5 months, respectively).

Conclusions

BRCArev can emerge in PCA in the absence of prior PARPi therapy, particularly following exposure to cytotoxic chemotherapy and radiation. These findings support that DNA-damaging therapies may promote BRCArev formation, potentially predisposing to primary PARPi resistance. Early integration of PARPi therapy before chemotherapy may enhance clinical benefit and circumvent emergence of primary resistance.

Introduction

Renal cell carcinoma (RCC) is the most common renal malignancy—bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

Methods

A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

Results

There were 139,859 patients diagnosed with RCC, of which 9021 had RCC with bone metastases (BM). Among these, 999 patients received only bisphosphonates (BPs), 973 received only RANK ligand inhibitors (RANKLi), and 119 patients initially received BPs before switching to RANKLi.

Presence of BM results in a ~2.5-fold increase in 5-year mortality rate (p < 0.0001) and a statistically significant increase in all SREs compared to those without BM. Patients receiving bisphosphonates had significantly higher rates of opioid use (p < 0.001) and comparable rates of chronic pain diagnoses to the overall BM group (p = 0.9217). In contrast, patients receiving RANKLi had a statistically significant reduction in opioid use (p < 0.001) and hypocalcemia (p < 0.001) compared to those on BPs, and an improved 5-year survival rate (p < 0.0001) and median survival (p < 0.0001) relative to the overall BM cohort.

Conclusion

Patients receiving RANKLi have significantly improved survival, reduced opioid use and lower rates of SREs. Patients with RCC and BMs experienced significantly worse outcomes compared to those without BM. Surprisingly, among RCC patients with BMs, those treated with BPs only experienced even poorer outcomes.

Objective

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays context-dependent roles in cancer. It functions as either a tumor suppressor or an oncogene depending on tumor type and cellular context. This review aimed to comprehensively summarize the roles of KLF4 in the tumor microenvironment (TME) and evaluate its potential as a therapeutic target.

Methods

We conducted a comprehensive literature review to elucidate the expression patterns, regulatory mechanisms, and functional roles of KLF4 across different TME components, including cancer cells, immune cells, cancer-associated fibroblasts, pericytes, and extracellular matrix.

Results

KLF4 exhibits dual roles in cancer cells, acting as a tumor suppressor in gastric, lung, and pancreatic cancers while promoting oncogenesis in breast, colorectal, and prostate cancers. In the TME, KLF4 regulates macrophage polarization (M1/M2), T-cell exhaustion, NK cell activity, and MDSC recruitment. Additionally, KLF4 modulates CAF activation and ECM remodeling. KLF4 expression is regulated by miRNAs, lncRNAs, and epigenetic modifications. Emerging therapeutic strategies targeting KLF4, such as APTO-253, show promise in preclinical and early clinical trials.

Conclusions

KLF4 serves as a hub gate orchestrating cell crosstalk within the TME. Understanding its context-dependent functions may facilitate the development of KLF4-targeted therapies for precision oncology.