Cancer Medicine最新文献

Objective

This study aimed to analyze disease cost levels among colorectal cancer (CRC) patients, examining differences in disease costs between those with type 2 diabetes mellitus (T2DM) and those without T2DM while considering various demographic characteristics.

Methods

The study included respondents from colorectal cancer patients diagnosed and managed within the population-based cancer registry system of the Shanghai Municipal Center for Disease Control and Prevention from 2020 to 2022. Diabetic colorectal cancer cases were matched with nondiabetic colorectal cancer controls using propensity scores, maintaining a 1:1 ratio between cases and controls; bias for the majority of the matched variables is below 10%. Direct, indirect, and intangible costs were estimated for study subjects.

Results

After propensity score matching, the analysis encompassed 376 cases of T2DM-related CRC and 376 non-T2DM CRC cases. The T2DM group exhibited higher direct medical costs (¥57,059.65 vs. ¥48,933.93, p < 0.05), direct nonmedical costs (¥9292.45 vs. ¥7969.35), indirect costs (¥300.13 vs. ¥241.11), intangible costs (¥3601.70 vs. ¥2631.96), and total disease costs (¥70,253.93 vs. ¥59,776.36, p < 0.05) compared to the non-T2DM group. In Stage II CRC, direct medical costs were ¥74,008.39 for the T2DM group versus ¥57,368.84 for the non-T2DM group. Among surgical patients, direct medical costs were ¥57,658.81 for the T2DM group versus ¥1337.00 for the non-T2DM group, and ¥49,061.52 for the non-T2DM surgical group versus ¥1089.00 for the non-T2DM nonsurgical group.

Conclusion

Colorectal cancer imposes a substantial economic burden. Patients with CRC and concurrent T2DM experience a higher economic burden compared to nondiabetic patients. Notably, individuals with both T2DM and Stage II cancer face a significantly higher economic burden, whereas surgical patients exhibit a significantly greater disease burden than nonsurgical patients. Efforts should concentrate on primary prevention and secondary prevention to alleviate the economic burden associated with colorectal cancer.

Background

There may be heterogeneity in lung cancer-related outcomes for individuals who are Asian, Native Hawaiian, and Pacific Islanders (ANHPI).

Objectives

The aims of this study were to investigate possible disparities in cardiovascular disease (CVD) risk between ANHPI and Non-Hispanic White (NHW) lung cancer survivors and evaluate potential CVD risk factors.

Methods

A total of 3920 ANHPI and 11,760 NHW lung cancer patients aged 66 years and older were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry from 1999 to 2017. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident CVD, comparing ANHPI lung cancer patients and their race/ethnicity subgroups to NHW lung cancer patients.

Results

Compared to NHW lung cancer patients, ANHPI lung cancer patients had a lower risk of developing heart failure (HR, 0.64, 95% CI, 0.53–0.76) and ischemic heart disease (HR, 0.76, 95% CI, 0.60–0.95). Additionally, compared to Chinese lung cancer patients, Pacific Islander, South Asian, and Southeast Asian lung cancer patients had a higher risk of heart failure.

Conclusion

While ANHPI lung cancer patients had lower risks of heart failure and ischemic heart disease than NHW lung cancer patients, heterogeneity in risk was observed among ANHPI subgroups. Further research is needed to investigate the reasons for the higher risk of several CVDs among Pacific Islander, South Asian, and Southeast Asian lung cancer patients.

Background

Myxoid liposarcomas (MLS) can exhibit a disseminated metastatic pattern, necessitating extensive diagnostics during follow-up. With no tumor markers available, early diagnosis of recurrences and tumor monitoring is difficult. The detection of circulating tumor DNA (ctDNA; liquid biopsy) in MLS with the characteristic translocations t(12;16) and t(12;22) can provide an additional diagnostic. However, due to the often very low tumor fraction, distinguishing actual tumor variants from sequencing artifacts remains a key challenge.

Methods

Using MLS as a model for translocation-driven tumors, this study evaluates a refined analytical approach for detecting both single nucleotide variants (SNVs) and structural variants (SVs) with the highest possible sensitivity and specificity. Different analysis pipelines using Unique Molecular Identifiers (UMIs) were compared in dilution series of tumor DNA from MLS patients (n = 11) and a cell line. The results were validated on plasma samples (n = 36) from two MLS patients and one patient with Synovial Sarcoma (SS).

Results

In dilution series, the use of UMIs significantly reduced false positive events in SNV analysis while maintaining high sensitivity without significant differences. In SV analysis, the effect of UMIs was not consistently detectable, as some dilution series exhibited no false positive events even without UMI correction. Additional filter criteria further improved specificity without significantly compromising assay sensitivity. Validation on patient plasma samples confirmed these findings, demonstrating the advantages of the differentiated analytical approach.

Conclusion

By integrating a refined analytical approach for SNVs and SVs, we achieved reliable ctDNA detection that corresponded with the clinical course of the patients’ disease. This method enables non-invasive tumor detection in translocation-driven tumors with low mutational burden and can easily be adapted into routine clinical diagnostics.

Background

The therapeutic management of metastatic hormone-sensitive prostate cancer (mHSPC) is still based on clinical and pathological parameters due to the lack of biomarkers that may drive tailored treatment.

Methods

In this non-randomized, single-center, retrospective trial, we searched for a genetic signature using the NanoString nCounter PanCancer Pathways Panel on formalin-fixed paraffin embedded prostate cancer samples belonging to 48 patients with de novo or relapsed mHSPC. Patients were divided into a high-clinical-risk group (n = 36) and a low-clinical-risk group (n&amp;#x02009;=&amp;#x02009;12) according to the mean time to metastatic relapse.

Results

The analysis of Nanostring nCounter Panel data revealed differential expression of 42 genes between high-clinical-risk and low-clinical-risk groups. All the genes except for NR4A1 and FOS were upregulated in the high-clinical-risk group. A general overexpression of apoptosis, PI3K and MAPK pathway-related genes, including AKT2, was observed in the high-clinical-risk group.

Conclusion

The differential genetic signature identified between the two study groups revealed novel biomarkers in mHSPC, additionally suggesting new therapeutic targets within the hormone sensitive phase, such as AKT2. Further prospective larger cohort studies are needed to assess the prognostic value of our findings and their exact role in prostate cancer progression.

Background

Bladder intracavitary hyperthermic perfusion chemotherapy (HIPEC) is a promising treatment for non-muscular invasive bladder cancer (NMIBC). However, the molecular mechanisms underlying the response to HIPEC remain poorly understood. This study aimed to elucidate the transcriptomic profiles associated with the response to HIPEC in NMIBC patients.

Methods

RNA sequencing was performed on bladder tumor samples from NMIBC patients who underwent HIPEC treatment. Differentially expressed genes (DEGs) between responders and non-responders to HIPEC were identified. Gene ontology and pathway analysis were conducted to explore the biological functions and pathways enriched in the DEGs. Additionally, the expression of specific immune-related genes was evaluated for their association with HIPEC response. The diagnostic efficiency of selected genes in predicting relapse before and after HIPEC treatment was assessed in a validation cohort.

Results

We assessed the expression status of differentially expressed genes (DEGs) between responders and non-responders to HIPEC. Gene ontology and pathway analysis revealed that DEGs were enriched in immune-related pathways, including cytokine-cytokine receptor interaction, chemokine signaling pathway, and antigen processing and presentation. Furthermore, the expression of several immune-related genes, including ZMAP4, UPP2, and GALR1, was significantly associated with the response to HIPEC. Therefore, the immune system's reaction plays a crucial role in the response to HIPEC in patients with NMIBC. At last, a considerable diagnostic efficiency that tissue TMEFF2, KRT222, and GTSF1 in predicting relapse in NMIBC patients after HIPEC treatment, and ZMAP4, UPP2, and GALR1 in predicting relapse in NMIBC patients before HIPEC treatment in the validation cohort.

Conclusion

Transcriptomic profiling revealed that immune-related pathways and genes play a crucial role in the response to HIPEC in NMIBC patients. These findings suggest that transcriptomic profiling could provide a valuable tool for predicting treatment outcomes and identifying therapeutic targets for NMIBC.

Background

There remains significant variability in the surgical management of thick melanoma patients with clinically node-negative disease. We evaluated factors influencing overall survival (OS) in these patients, focusing on the surgical management of the primary tumor and nodal basin.

Methods

Using the National Cancer Database, we identified 7647 patients diagnosed between 2012 and 2017 with thick melanoma (> 4 mm, T4) and clinically node-negative disease. 4332 patients had complete data and met all inclusion criteria. These patients were stratified into three groups based on nodal assessment: sentinel lymph node biopsy (SLNB), elective lymphadenectomy (ELND), or no nodal evaluation (NNE). OS was compared using Kaplan–Meier analyses and multivariable Cox proportional hazard regression.

Results

In the cohort, 2851 (65.8%) had a SLNB, 799 (18.4%) had an ELND, and 682 (15.7%) had NNE. OS significantly decreased for each millimeter of increasing Breslow thickness. Ulceration, lymphovascular invasion, and tumor-positive SLN (+SLN) were associated with worse OS (all p < 0.001). The size of surgical margins was not significantly associated with OS. Five-year OS of patients with SLNB was 67.1% ± 1.2% compared to 57.9% ± 2.3% with ELND and 46.8% ± 2.5% with NNE (p < 0.001). Among +SLN patients, a complete lymph node dissection (CLND) was performed in 400 (62.3%) but was not associated with improved OS (p = 0.67) when compared to the nodal observation group.

Conclusion

Our results suggest that increasing Breslow thickness and nodal assessment provide important prognostic information regarding OS for thick melanoma patients, which emphasizes the importance of SLNB for staging and confirm the lack of benefit of CLND after +SLN in thick melanoma. The size of surgical margins did not affect OS.

Objective

Because of its high prognostic value, neuropsychological assessment plays a crucial role in the neuro-oncology setting. Subjective and objective cognitive performance correlate only to a limited extent, and subjective cognitive performance is strongly dependent on emotional state. We postulate that the relation of subjective and objective cognitive performance depends on tumor laterality.

Methods

In this prospective study, N = 63 patients with brain tumors underwent a neuropsychological test battery, including assessment of subjective cognitive function (attention, memory, executive), and symptoms of depression and anxiety before surgery. Patients with psychiatric comorbidity or severe neurological conditions were excluded.

Results

There were no significant differences in subjective and objective cognitive function, symptoms of depression and anxiety between left (N = 37) and right (N = 26) hemisphere tumors. All measures of subjective cognitive function correlated highly significantly with symptoms of depression and anxiety in left hemisphere tumor patients (all r ≥ 0.470). In right hemisphere tumor patients, there was no relation between subjective cognitive function and emotional state. Significant laterality differences for correlations of subjective and objective cognitive function were not found and were not significant within the two groups.

Conclusions

Even when unbiased by symptoms of anxiety and depression, right hemisphere tumor patients show the same discrepancy in subjective and objective cognitive function as left hemisphere tumor patients. This discrepancy may be based on a different mechanism in right hemisphere tumor patients.

Background

Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody–drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune-checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real-world analysis comparing the effectiveness of EV to chemotherapy in this setting.

Methods

The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum-based chemotherapy. Patients were assessed for overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and duration of response (DoR).

Results

Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2–10.7) in the overall study population, 13.6 months (95%CI 10.0–31.0) in patients receiving EV and 6.8 months (95%CI 6.0–8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum-based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5–17.0] vs. 3.0 months [95%CI 2.6–3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort.

Conclusions

The results of our international analysis of real-world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum-based chemotherapy and anti-PD-1 pembrolizumab, regardless of commonly considered prognostic factors.

Trial Registration: ClinicalTrials.gov identifier: NCT05290038