Cancer Research and Treatment最新文献

Purpose: The risk of suicide is approximately two times higher in patients with breast cancer compared to the general population. Suicide risk factors are widely investigated but research on the protective factors is lacking. We investigated whether each subscale of grit, consistency of interest, and perseverance of effort, could serve as a protective factor against suicidality.

Materials and methods: Participants were recruited at the Stress Clinic for Cancer Patients, a psycho-oncology clinic at Asan Medical Center from May 2019 to March 2021. A total of 140 female patients with breast cancer completed self-administered questionnaires including Grit scale, Distress thermometer, and Mini International Neuropsychiatric Interview (MINI) suicidality module. We used PROCESS macro for analyzing the mediation model to identify the protective factors for suicidality.

Results: Our findings showed that perseverance of effort showed statistically non-significant associations with psychological distress (p=0.403) and suicidality (p=0.945), however, consistency of interest decreased suicidality through psychological distress (β=-0.015; 95% confidence interval, -0.035 to -0.002).

Conclusion: The result shows that consistency of interest can be a protective factor against suicidality by reducing psychological distress.

Purpose: The molecular classification of breast cancer is crucial for effective treatment. The emergence of digital pathology has ushered in a new era in which weakly supervised learning leveraging whole-slide images has gained prominence in developing deep learning models because this approach alleviates the need for extensive manual annotation. Weakly supervised learning was employed to classify the molecular subtypes of breast cancer.

Materials and methods: Our approach capitalizes on two whole-slide image datasets: one consisting of breast cancer cases from the Korea University Guro Hospital (KG) and the other originating from The Cancer Genomic Atlas dataset (TCGA). Furthermore, we visualized the inferred results using an attention-based heat map and reviewed the histomorphological features of the most attentive patches.

Results: The KG+TCGA-trained model achieved an area under the receiver operating characteristics value of 0.749. An inherent challenge lies in the imbalance among subtypes. Additionally, discrepancies between the two datasets resulted in different molecular subtype proportions. To mitigate this imbalance, we merged the two datasets, and the resulting model exhibited improved performance. The attentive patches correlated well with widely recognized histomorphologic features. The triple-negative subtype has a high incidence of high-grade nuclei, tumor necrosis, and intratumoral tumor-infiltrating lymphocytes. The luminal A subtype showed a high incidence of collagen fibers.

Conclusion: The artificial intelligence (AI) model based on weakly supervised learning showed promising performance. A review of the most attentive patches provided insights into the predictions of the AI model. AI models can become invaluable screening tools that reduce costs and workloads in practice.

Purpose: This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics.

Materials and methods: This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex.

Results: The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types.

Conclusion: Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.

Purpose: This study aimed to develop a magnetic resonance imaging (MRI)-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space, and poorly differentiated patterns.

Materials and methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, maximum standardized uptake value on FDG PET/CT, and the mean apparent diffusion coefficient value on diffusion-weighted image, were considered together to build prediction models for high-risk pathologic features.

Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The magnetic resonance (MR)-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p < 0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p < 0.001), worse 4-year disease-free survival (p < 0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC, 0.860 and 0.907, respectively).

Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.

Materials and methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.

Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.

Conclusion: TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: To investigate the clinical outcomes of stereotactic body radiation therapy (SBRT) in patients with large uveal melanoma (UM).

Materials and methods: We conducted a retrospective review of 64 consecutive patients with UM treated with Cyberknife at Yonsei Cancer Center from September 2015 to October 2021. The median radiation dose was 60 Gy (range 48-64 Gy) administered in four fractions every alternate day. The local failure-free rate (LFFR), distant metastasis-free rate (DMFR), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to analyze the predictive factors affecting survival outcomes and the factors associated with vision loss.

Results: The median tumor diameter and height were 11.5 mm and 8.4 mm, respectively. After a median follow-up of 32.1 months (range 4.9-89.9), the 3-year LFFR, DMFR, PFS, and OS were 89.5%, 70.5%, 65.5%, and 89.4%, respectively. Enucleation was performed in 13 (20.3%) patients, with three cases attributed to disease progression. A larger tumor diameter was associated with significantly worse DMFR (HR=1.35, p=0.015) and OS (HR=1.49, p=0.026) in the multivariate analysis. Regarding visual prognosis, 41 (64.1%) patients had baseline visual acuity ≥20/200, but only 4 (6.3%) patients maintained visual acuity ≥20/200 by the final follow-up. Initial visual acuity ≥20/40 (HR 0.45, p=0.030) was the single favorable significant factor predicting visual retention ≥20/200 in multivariate analysis.

Conclusion: SBRT using CyberKnife demonstrated a comparable local control rate to that observed in historical studies for patients with large UM. Distant metastasis and treatment-related ocular toxicity remain the limitations of this treatment.

Purpose: This study aimed to evaluate the clinical impact of main tumor resection on long-term survival compared with pleural biopsy alone in patients with lung adenocarcinoma who were intraoperatively diagnosed with pleural metastasis.

Materials and methods: A total of 176 patients with adenocarcinoma who had unexpected pleural metastasis detected during surgery from 2002 to 2021 were retrospectively analyzed. Each surgeon decided whether to perform main tumor resection or pleural biopsy alone.

Results: The patients were grouped based on the surgical approaches: main tumor resection (Resection group; n=83) and pleural biopsy only (O&C group; n=93). The Resection group had better overall survival (OS, 10-year survival: 27.9% vs. 9.4%; median survival: 68.3 vs. 36.6 months; p<0.01) and locoregional progression-free survival (10-year survival: 12.5% vs. 7.1%; median survival: 19.6 vs. 10.6 months; p<0.01) than the O&C group. Similar results were found for OS in patients who received tyrosine kinase inhibitors (TKIs) as first-line therapy (10-year survival: 49.2% vs. 15.0%; median survival: 72.2 vs. 45.4 months; p=0.03), patients who did not undergo TKIs treatment (10-year survival: 29.4% vs. 9.2%; median survival: 82.4 vs. 23.8 months; p<0.01), and patients with positive target gene mutation (10-year survival: 31.7% vs. 10.1%; median survival: 72.2 vs. 33.7 months; p<0.01). In multivariate analysis, pleural biopsy only (hazard ratio, 1.73; p=0.04) was a significant predictor of OS.

Conclusion: Main tumor resection can improve survival in patients with lung adenocarcinoma who had unexpected pleural metastasis during operation.

Purpose: Platinum-based chemotherapy is the standard treatment for advanced urothelial carcinoma (aUC). Switch maintenance therapy after first-line (1L) treatment may delay disease progression. This study evaluated pemetrexed as switch maintenance therapy versus observation in aUC patients without disease progression after initial chemotherapy.

Materials and methods: Eligible aUC patients who did not progress after 4-6 cycles of cisplatin or carboplatin-based chemotherapy were randomized 1:1 to receive maintenance pemetrexed (500 mg/m2 IV every 3 weeks, up to 16 cycles) or observation. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety.

Results: The trial was closed early due to slow accrual after avelumab approval. From October 2016 to December 2022, 97 patients were randomized to pemetrexed (n=49) or observation (n=48). The median age was 69 years (range: 43-90) and 66 (range33-82), respectively, with 63% and 73% of patients being male, respectively. The median PFS was 6.0 months (95% CI, 3.4-8.5) with pemetrexed versus 2.3 months (1.8-2.7) with observation (p=0.044, HR 0.64; 95% CI, 0.41-0.99). The median OS was 18.1 months (95% CI, 6.9-29.4) for pemetrexed and 17.9 months (16.1-19.7) for observation (p=0.913, HR 1.03; 95% CI, 0.61-1.73). Common adverse events in the pemetrexed group included anemia (30%), fatigue (18%), and neutropenia (12%), primarily grade 1 or 2.

Conclusion: The PREMIER trial showed that switch maintenance pemetrexed significantly prolonged PFS in aUC patients post-1L platinum-based chemotherapy, with a favorable safety profile. Further studies on combination maintenance therapies are warranted.

Purpose: This study examined the roles of nuclear factor erythroid 2-related factor 2 (NRF2) and programmed death ligand 1 (PD-L1) in colon carcinogenesis, underscoring on sex and differences in tumor location.

Materials and methods: A total of 378 participants were enrolled from Seoul National University Bundang Hospital: 88 healthy controls (HC), 139 patients with colorectal adenoma (AD), and 151 patients with colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (PCR), methylation-specific PCR, and immunohistochemistry (IHC) were performed utilizing tumor samples from patients and normal mucosa in the HC group.

Results: NRF2 mRNA expression was higher in the CRC group than in the HC and AD groups, with decreased NRF2 methylation in the AD and CRC groups. NRF2 protein expression, as evaluated by IHC, increased in the AD and CRC groups relative to that in the HC group. PD-L1 protein expression was remarkably higher in the CRC group than in the HC and AD groups. These patterns were consistent in both males and females. In sex- and CRC location-specific analyses, NRF2 methylation was lower in female than in male patients with CRC. NRF2 protein expression was significantly higher in females, particularly in patients with right-sided CRC. Moreover, females exhibited increased PD-L1 mRNA expression compared to males in the AD group, and PD-L1 mRNA levels were higher in females with right-sided CRC than in those with cancer at other locations.

Conclusion: Differences in NRF2 and PD-L1 expression indicate site-specific colon carcinogenesis based on sex, particularly in females with right-sided CRC.

Purpose: Fentanyl, a highly lipophilic opioid, was developed as a sublingual fentanyl tablet (SFT) for the management of breakthrough cancer pain (BTcP), and its efficacy and safety were confirmed in a randomized, controlled study. We investigated the effectiveness and safety of SFT administered to alleviate BTcP in a real-world setting.

Materials and methods: In this prospective, open, single-cohort study, conducted in 13 referral hospitals in South Korea, opioid-tolerant cancer patients receiving around-the-clock opioids for persistent cancer pain were enrolled if the individual had BTcP ≥ 1 episode/day during the preceding week. The primary outcome was the SFT titration success rate.

Results: Among 113 patients evaluated for effectiveness, 103 patients (91.2%) had a successful titration of SFT, with an effective dose range between 100 µg and 400 µg. The most frequent dose was 100 µg, administered to 65.0%, 72.1%, and 81.8% of the patients at Week 1, 4, and 12, respectively. The proportion of patients achieving the personalized pain goal assessed in the first week was 75.2%. The mean change in pain intensity measured with a numeric rating scale at 30 and 60 minutes after taking SFT was -2.57 and -3.62, respectively (p<0.0001 for both). The incidence rate of adverse events related to SFT among 133 patients included for safety evaluation was 9.0% (12/133), which included vomiting (3.0%), nausea (2.3%), and headache (1.5%).

Conclusion: In a real-world setting, SFT provides rapid and effective analgesia in BTcP, even at the lowest dose (100 μg), and the safety profile was acceptable.