Cancer Medicine最新文献

Background

Darolutamide plus androgen-deprivation therapy (ADT) improved metastasis-free survival (MFS) by 2 years and reduced the risk of death by 31% in nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS. Prior local therapy may influence the efficacy of subsequent systemic therapy. This post hoc analysis of ARAMIS evaluated the effect of prior local therapy on the efficacy and health-related quality of life (HRQoL) of darolutamide.

Methods

Patients with nmCRPC were randomized to darolutamide (n = 955) or placebo (n = 554) while continuing ADT. MFS, overall survival (OS), time to prostate-specific antigen (PSA) progression, and HRQoL deterioration-free survival (DetFS) were estimated for patients with and without local therapy and by treatment using Kaplan–Meier methods.

Results

Darolutamide increased MFS versus placebo in patients with (HR, 0.36; 95% CI, 0.26–0.48) and without (HR, 0.46; 95% CI, 0.36–0.59) local therapy. Median OS was 48.6 months for placebo without local therapy and not reached in either the darolutamide group or placebo group with local therapy. Darolutamide 3-year OS rates were 86.9% (95% CI, 83.0–90.8) and 79.0% (95% CI, 66.2–78.1) in patients with and without local therapy, respectively. Darolutamide showed evidence of improved OS versus placebo in patients with prior local therapy (HR, 0.80; 95% CI, 0.50–1.30) and a greater effect in those without local therapy (HR, 0.67; 95% CI, 0.50–0.90). Darolutamide delayed time to PSA progression and HRQoL deterioration regardless of local therapy.

Conclusions

Darolutamide versus placebo improved MFS, OS, time to PSA progression, and HRQoL DetFS independent of prior local therapy, consistent with the overall ARAMIS population.

Trial Registration: ClinicalTrials.gov registration: NCT02200614

Background

Paracentesis temporarily relieves malignant ascites but causes hypoalbuminemia. Cell-free and concentrated ascites reinfusion therapy (CART) reinfuses autologous proteins to prevent hypoalbuminemia and has been increasingly used in Japan. However, CART has not been widely adopted outside of Japan, and its benefit remains unclear. We evaluated the clinical outcomes and healthcare costs of CART compared with paracentesis in metastatic cancer.

Methods

This retrospective cohort study included hospitalized patients with metastatic solid cancer receiving CART or paracentesis across Japan (April 2016–March 2023). Baseline characteristics were balanced using overlap propensity-score weighting. Primary outcomes were in-hospital mortality, functional disability, and 30-day unplanned readmission. Secondary outcomes were length of stay (LOS), albumin administration or re-drainage rates, and costs. Mortality risk was assessed using a modified Poisson regression. The composite primary outcomes were assessed using a win-ratio approach.

Results

Among 1159 patients (CART: 457, paracentesis: 702) from 51 hospitals, the CART group had lower mortality than the paracentesis group (28.6% vs. 36.7%; risk ratio: 0.78, 95% confidence intervals [95% CI]: 0.64–0.94). The win-ratio analysis also favored the CART group over the paracentesis group (win ratio: 1.34, 95% CI: 1.09–1.64). Additionally, CART was associated with lower mortality and better composite outcomes than paracentesis, particularly among males, patients with serum albumin ≤ 2.5 g/dL, and those with non-gastrointestinal cancer. Despite higher procedural costs, CART was associated with shorter median LOS (14.1 vs. 19.0 days), lower albumin administration (11.6% vs. 17.3%) and re-drainage (32.7% vs. 52.7%) rates, and lower total median costs (4490.9 [interquartile range: 2042.3–7054.5] vs. 5084.1 [interquartile range: 3054.7–8659.7] USD) than paracentesis.

Conclusions

CART was associated with improved clinical outcomes and healthcare costs over paracentesis among hospitalized patients with metastatic cancer, particularly in males, patients with serum albumin ≤ 2.5 g/dL, and those with non-gastrointestinal cancer. These findings may support clinical decision-making and resource allocation.

Background

The impact of social determinants of health (SDoH) on survival outcomes is unclear in the universal Canadian health care system. We investigated the impact of distance to treatment center and income quintile on survival outcomes in pediatric extracranial solid tumors in Canada.

Methods

Children < 15 years old diagnosed with 7 common solid extracranial tumors from 2001 to 2020 were included using the Cancer in Young People in Canada (CYP-C) data tool. We used logistic regression to examine the association of income quintile and distance on cancer outcomes. We used Cox proportional hazard models to examine associations with time-to-event outcomes (OS) and Fine–Gray competing risk regression (recurrence) adjusting for metastasis, age, region, and tumor location.

Results

The cohort included 3969 patients. Median age was 3.6 years (IQR: 1.3–8.9); 48.7% were female. Tumor diagnosis: 34% neuroblastoma, 21% Wilms tumor, 13% rhabdomyosarcoma, 11% osteosarcoma, 8% Ewing sarcoma, 7% hepatoblastoma, and 6% germ cell tumors. On multivariable analysis, income quintile and distance did not significantly or consistently impact survival across all tumors. In rhabdomyosarcoma, the second lowest income quintile had inferior survival compared to the highest income quintile (p = 0.0264, HR 1.91, 95% CI 1.08, 3.37). In neuroblastoma, the lowest income quintile had inferior survival compared to the highest (p = 0.0052, HR 1.82, 95% CI 1.20, 2.77). Patients diagnosed with hepatoblastoma living > 500 km from a pediatric treatment facility had inferior OS compared to those within 50 km (p = 0.0065, HR 3.29, 95% CI 1.40, 7.79).

Conclusion

Overall, distance and income did not show a consistent significant impact on survival outcomes for children with extracranial solid tumors.

Background

Colorectal cancer (CRC) with synchronous peritoneal metastasis (SPM) presents poor prognosis and complex treatment challenges. This study aimed to identify independent prognostic factors and develop nomogram-based prediction models for overall survival (OS) and progression-free survival (PFS) in CRC patients with SPM (CRC-SPM) undergoing cytoreductive surgery (CRS).

Methods

We retrospectively analyzed 218 CRC-SPM treated with CRS between October 2010 and April 2022. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for OS and PFS. Nomogram models were constructed based on these factors, and their predictive accuracy was assessed using calibration curves, ROC curves, and Decision Curve Analysis (DCA).

Results

For OS, independent factors included age > 65 years (HR = 2.464, p = 0.005), N2 stage (HR = 2.720, p = 0.005), > 13 lymph nodes resected (HR = 0.496, p = 0.018), and postoperative chemotherapy (HR = 0.300, p = 0.020). For PFS, independent factors were age > 65 years (HR = 1.578, p = 0.040), concurrent liver metastasis (HR = 1.664, p = 0.016), > 14 PCI score (HR = 1.630, p = 0.031), and presence of ascites (HR = 1.706, p = 0.011). Nomogram models for predicting OS and PFS had AUC values of 0.717, 0.759, and 0.773 for OS, and 0.659, 0.689, and 0.790 for PFS at 1, 2, and 3 years, respectively.

Conclusion

This study identified key prognostic factors and developed reliable nomogram models for predicting OS and PFS in CRC-SPM. The findings highlight the importance of postoperative chemotherapy and intraoperative lymph node dissection and suggest focusing on high-risk factors such as age and N2 stage in clinical practice. The nomogram models provide a valuable tool for personalized prognosis assessment and treatment planning.

Background

Mitochondrial permeability transition (MPT)-driven necrosis, a recently identified form of programmed cell death, significantly influences tumor progression, therapy response, and prognosis. However, research on mitochondrial permeability transition-driven necrosis-related long non-coding ribonucleic acids (MPTDNRlncRNAs) in hepatocellular carcinoma (HCC) remains limited.

Methods

In the current study, we aimed to construct an MPTDNRlncRNA signature to predict survival and classify patients with HCC. RNA sequencing and clinical data were sourced from the Cancer Genome Atlas database, while MPT-driven necrosis-linked genes were obtained from the Gene Set Enrichment Analysis database. We identified MPTDNRlncRNAs in HCC tumor tissues and deployed the least absolute shrinkage and selection operator-Cox analysis to construct a predictive lncRNA signature. Immune cell infiltration variations were analyzed between high- and low-risk subgroups. The MPTDNRlncRNA signature performance was estimated using statistical methodologies, and bioinformatics methods were utilized to investigate functional and pathway differences across risk groups.

Results

A seven-lncRNA signature specific to HCC was developed, and its predictive accuracy was systematically evaluated using survival analysis, time-dependent receiver operating characteristic curves, and Cox regression analyses. Correlation analysis demonstrated a strong association between the lncRNA signature and immune cell infiltration, several immune checkpoint targets, and its significant prognostic value for patients with HCC. Additionally, LINC02313 was recognized as a hub lncRNA in vitro, demonstrating its role in promoting cell proliferation and tumor metastasis. Finally, we validated the function of LINC02313 using a liver cancer organoid model.

Conclusion

The effective construction of an MPT-driven necrosis-related prognostic model highlights its potential to independently predict the prognosis of patients with HCC. These findings not only deepen our understanding of MPT-driven necrosis but also offer novel theoretical foundations for developing more effective treatment strategies. The gene LINC02313 has been identified as a promoter of HCC's ability to proliferate and invade, underscoring its potential as a therapeutic target for HCC.

Background

Adiposity-Based Chronic Disease (ABCD), a novel model housing obesity, insulin resistance, and adipokine-related inflammation, increases the risk of aggressive prostate cancer (PCa), posttreatment PCa recurrence, and PCa mortality. This paper provides a new network analysis of relevant metabolic drivers to provide insight into the ABCD–PCa relationship.

Methods

A literature search was performed using the terms “prostate cancer” AND “obesity” AND “inflammation”, with 629 references found, from which 17 reviews were chosen. Biomarkers identified from these reviews were characterized by cellular origin, signaling pathway, and oncogenic effect. The Webgestalt gene analysis toolkit was then used to generate modular-based network analyses and gene ontology (GO) categories of these biomarkers for interpretation.

Results

14 prominent biomarkers were identified influencing PCa risk through cellular proliferation, resisting cell death, metabolic reprogramming, tumor-promoting inflammation, avoiding immune destruction, angiogenesis, and activating invasion. Network analyses of biomarker interactions highlighted prominent roles of monocyte chemoattractant protein-1, interleukin-1β, and C-X-C motif chemokine ligand 1. Top GO categories for the wider ABCD-PCa network found key roles of ABCD-gut microbiome dysbiosis and exposure of periprostatic white adipose tissue to the prostate microbiome (involving bacterial and lipopolysaccharide-induced inflammation).

Conclusion

Top hypotheses to guide molecular targeted therapies and lifestyle biomarker panels for PCa in ABCD relate to MCP-1, IL-1β, and CXCL1 signaling, as well as gut microbiome dysbiosis and the exposure of the periprostatic adipose tissue to the prostate microbiome. Further research and possible clinical trials allowing histological examination of pre- and post-lifestyle intervention PCa tissue may provide further insights.

Introduction

The tumor control rate after stereotactic radiosurgery (SRS) for neurofibromatosis type 2-associated vestibular schwannomas (NF2-VSs) compared to sporadic vestibular schwannomas (S-VSs) remains unclear. This nationwide, multicenter, retrospective study (KGKRS-21-001) aimed to clarify this issue.

Methods

A total of 4718 patients treated with SRS for vestibular schwannomas were analyzed from 13 nationwide institutions in Korea. NF2-VS cases were propensity score-matched with S-VS cases at a ratio of 1:1, based on age, tumor volume, and marginal dose, resulting in 122 cases in each group.

Results

No significant differences in age, tumor volume, or marginal dose were observed between the matched cohorts. The overall tumor control rates at 1, 3, and 10 years after SRS were 93.3%, 87.7%, and 80.7%, respectively, with no significant difference between NF2-VS and S-VS groups (p = 0.63). Subgroup analysis showed that age ≤ 19 years was a significant negative prognostic factor for tumor control in NF2-VS patients (p < 0.001), whereas no such correlation was found in the S-VS cohort (p = 0.78).

Conclusions

SRS provides comparable tumor control for NF2-VSs and S-VSs. However, among NF2-VS patients, younger age (≤ 19 years) was associated with poorer tumor control, suggesting that age may be a critical factor in treatment decisions.

Background

Colorectal cancer (CRC) is a prevalent cancer worldwide, but encouraging healthier lifestyle choices among survivors may improve their prognosis. We aimed to evaluate health habits adopted after diagnosis and their impact on prognosis.

Methods

For this population-based retrospective cohort study, we used data from the Cancer Public Library Database (CPLD), which consists of four major population-based public sources in Korea with cancer patients diagnosed between 2012 and 2019. Information on anthropometric measures, physical activity, alcohol consumption, and smoking status before and after cancer diagnosis was used. Hazard ratios (HRs) for all-cause deaths with 95% confidence intervals (CIs) were estimated via the Cox proportional hazards model.

Results

Among the 7553 CRC patients, postdiagnosis physical activity was significantly related to decreased risk of death among those who were diagnosed with stage I or III CRC (p for trend < 0.05). The analysis of 4588 patients revealed that increased physical activity (stage I: adjusted HR [aHR] = 0.60, 95% CI = 0.29–1.22; stage II: aHR = 0.86, 95% CI = 0.49–1.52; stage III: aHR = 0.60, 95% CI = 0.36–0.99) or smoking cessation (stage I: aHR = 0.81, 95% CI = 0.28–2.35; stage II: aHR = 0.36, 95% CI = 0.16–0.81; stage III: aHR = 0.89, 95% CI = 0.42–1.87), were associated with poor prognosis compared to those who consistently remained physically inactive or continued to smoke.

Conclusion

The present study provides compelling evidence on the benefits of increased physical activity and smoking cessation after CRC diagnosis for improved survival.

Purpose

Accurate classification of prostate cancer (PC) disease states defined by the presence or absence of metastasis and castration resistance (CRPC) is critical but challenging in population-based research. As chart review is not feasible on a large scale, accurate automated methods are needed.

Methods

We conducted a retrospective study using data from the Veterans Affairs Health Care System to evaluate algorithms for identifying CRPC and metastatic PC, with manual chart review as the gold standard. Our analysis included 8336 patients for CRPC classification and 721 for metastatic disease classification. For CRPC classification, we assessed one novel algorithm using criteria including rising prostate-specific antigen levels or progression to metastatic disease while receiving androgen deprivation therapy or initiating CRPC-specific treatments. For metastatic disease detection, we assessed four algorithms based on: ICD codes alone, natural language processing (NLP) alone, a novel algorithm combining ICD codes and treatment patterns, and an enhanced version of the novel algorithm integrating NLP, evaluating the sensitivity and specificity of each. Positive and negative predictive values were reported across a range of assumed disease prevalence.

Results

Out of 8336 patients with PC, 1190 (14.3%) were identified as having CRPC through chart review, with the CRPC algorithm achieving 85.1% sensitivity and 96.1% specificity. Among 721 patients evaluated for metastatic disease, 179 (24.8%) were identified as having metastatic disease through chart review. The algorithm combining ICD codes, treatment patterns, and NLP demonstrated the highest sensitivity (94.4%) and high specificity (93.0%), while other methods had lower sensitivity with varied specificity.

Conclusions

Our findings suggest that our CRPC algorithm and the combined ICD codes, treatment patterns, and NLP algorithm for metastasis are effective automated approaches for identifying advanced states of PC. In particular, integrating NLP boosted sensitivity for metastatic classification with minimal specificity trade-off, highlighting the value of a multifaceted approach to large-scale PC research.

Introduction

Although covalent Bruton's tyrosine kinase inhibitors (cBTKis) have transformed treatment of chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL), cBTKi-related cardiotoxicity is a known side effect. This real-world study evaluated incident cardiovascular adverse events (CVAE), healthcare resource utilization (HCRU), and costs among patients with CLL/SLL receiving cBTKis.

Methods

Adult patients with CLL/SLL who initiated ibrutinib or acalabrutinib treatment (index date) between 2020 and 2023 were identified using US claims data and followed up to 36 months post-index. Incident CVAEs (not present pre-index) were assessed during cBTKi treatment and patients were stratified by CVAE status. HCRU and costs were evaluated per 1000 patient-months (PPPM).

Results

Overall, 2069 patients were identified (mean age of 73.7 ± 9.1 years, 40.4% female) with a mean treatment-specific observation period of 11.4 ± 9.5 months. At least one incident CVAE was observed in 442 (21.4%) patients. The incidence rate was 21.6 PPPM for hypertension, 8.9 PPPM for atrial fibrillation, 8.6 PPPM for ventricular arrhythmias, and 8.3 PPPM for atrial flutter. Patients with incident CVAEs had significantly more total medical service days PPPM (4334 vs. 3138, p < 0.001), primarily driven by increased inpatient (690 vs. 230), outpatient (2798 vs. 2425), other visit (662 vs. 375), and ER days (184 vs. 109) than those without CVAEs. Total healthcare costs (PPPM) were substantially higher for patients with incident CVAEs ($20,250,560 vs. $17,413,460, p < 0.001) mainly due to higher inpatient ($3,417,948 vs. $915,839, p < 0.001), outpatient ($2,415,060 vs. $1,769,628, p < 0.01), and ER costs ($186,820 vs. $87,585, p < 0.001).

Conclusions

The observed class-effect of high CVAEs with cBTKis underscores the unmet need for safer, more selective agents for CLL/SLL treatment. The HCRU and economic burden remain high for CLL/SLL, especially among patients experiencing CVAEs during cBTKi treatment. These findings emphasize the importance of optimizing clinical management to reduce CVAE risk and downstream impacts on HCRU and costs.