Cancer Research and Treatment最新文献

Purpose: Anastomotic leakage (AL) is a severe complication after esophagogastrostomy, yet the classifications of AL and their associated healing times are poorly understood.

Materials and methods: This study retrospectively analyzed 117 cases of AL among 2,728 patients who underwent esophagectomy with circular stapled esophagogastric anastomosis at Tianjin Medical University Cancer Institute and Hospital from January 1, 2019, to March 31, 2024. AL cases were categorized into four types based on the direction of leakage (anterior, right, posterior, and left). The differences in healing times among these four types were analyzed using the log-rank test. A multivariable Cox model was used to identify factors associated with healing time.

Results: The incidence of AL was 4.3% (117/2728), with a median occurrence time of 9 days (Interquartile Range[IQR]: 5) and a median healing time of 56 days (IQR:64). Single cervical ALs accounted for 17.5%, with significantly shorter healing times compared to intrathoracic leaks (33 days vs. 61 days, p=0.018). Right-sided leaks were the most common (49.6%), while left-sided leaks healed faster than right- and posterior-sided leaks (42 days vs. 63 days vs. 70 days, p<0.05). Body Mass Index (BMI), diabetes, and neoadjuvant therapy did not influence healing time. In 117 AL patients, the occurrence of tracheoesophageal fistula (p=0.004) and the placement of trans-fistula reverse drainage tubes (p=0.002) were associated with healing time.

Conclusion: These findings provide valuable insights for clinicians to better understand the mechanisms of AL development and predict the healing times.

Purpose: Immune checkpoint inhibitors (ICIs) have become a standard therapy for metastatic hepatocellular carcinoma (HCC), often as an alternative to tyrosine kinase inhibitors (TKIs). However, safety data combining ICIs with stereotactic ablative radiotherapy (SABR) remain limited. We compared the safety and efficacy of SABR combined with ICIs versus TKIs in patients with extrahepatic metastatic HCC.

Materials and methods: This single-center retrospective study included patients with HCC who received SABR for extrahepatic metastases combined with either TKIs or ICIs within 30 days of SABR between January 2010 and June 2024. Adverse events (AEs; CTCAE v5.0) and oncologic outcomes were evaluated using logistic regression and Cox models.

Results: Among 103 patients with 128 SABR-treated lesions, 72 patients (90 lesions) received SABR+TKI and 31 patients (38 lesions) received SABR+ICI. Acute AEs occurred only in the SABR+TKI group (8.9%), predominantly grade 1. Grade 3 late AEs were rare, occurring in one case in each group, while late AEs of lower grades were more frequent with SABR+ICI (any-grade: 57.9% vs. 25.6%, p<0.001; grade ≥2: 23.7% vs. 8.9%, p=0.024). Multivariable analysis showed borderline increased risk of grade ≥2 late AEs with SABR+ICI (p=0.052). One-year local control, progression-free survival, and overall survival were 76.6%, 35.3%, and 72.3% respectively, with no significant differences between groups.

Conclusion: Metastasis-directed SABR combined with either TKIs or ICIs was generally well tolerated in patients with extrahepatic metastatic HCC, with rare grade 3 late AEs; grade ≥2 late AEs were more frequent with SABR plus ICIs, warranting prospective evaluation.

Purpose: We investigated the associations between smoking, pain expression, opioid use, substance use behaviors, coping strategies, and risk of chemical coping in Korean patients with advanced cancer.

Materials and methods: In this prospective study, 240 patients were enrolled. Demographic and clinical information were obtained from medical records. Smoking status, symptom burden by the Edmonton Symptom Assessment System (ESAS), the Cut down/Annoyed/Guilty/Eye-opener (CAGE) alcoholism questionnaire results, morphine equivalent daily dose (MEDD), tranquilizers and coffee use, coping strategies, and physician-assessed risk of chemical coping and somatization were assessed using questionnaires and interviews.

Results: Of the 240 patients, 49 (20.4%) were current smokers, 104 (43.3%) were former smokers, and 87 (36.3%) were never-smokers. 161 were male (67.1%); 89.4% (144/161) of these men were current or former smokers, while 88.6% (70/79) of women were never-smokers (p<0.001). ESAS pain scores did not differ by smoking status (3.0 vs. 2.9 vs. 2.7, p=0.480), but current smokers had higher MEDD (63.5 mg/day vs. 25.1 mg/day vs. 22.3 mg/day, p=0.015). Current smokers were more often CAGE-positive (32.7% vs. 16.3% vs. 2.3%, p<0.001), heavy coffee drinkers (24.5% vs. 12.5% vs. 0%, p<0.001) and showed a greater physician-assessed risk of chemical coping (26.5% vs. 8.7% vs. 13.8%, p=0.015).

Conclusion: Among Korean patients with advanced cancer, current smokers were more likely to use higher doses of opioids, have positive CAGE results, and drink more coffee. Close monitoring and appropriate management for the possibility of chemical coping or non-medical opioid use will be important in these patients.

Purpose: The aim of this study was to identify subgroups of patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) who may benefit from postoperative radiotherapy (PORT). Particular attention was given to evaluating whether extranodal extension (ENE) influences the therapeutic efficacy of PORT.

Materials and methods: A total of 231 patients with pN2 NSCLC who underwent surgical resection followed by adjuvant chemotherapy at a single institution were analyzed retrospectively. Propensity score matching was performed to compare treatment outcomes according to the receipt of PORT.

Results: Propensity score matching yielded 99 matched pairs of patients with no significant differences in clinical parameters. There were no significant differences in the overall survival (OS; p=0.11) and disease-free survival (DFS; p=0.29) between the PORT and no PORT groups. However, PORT significantly improved the locoregional recurrence (LRR)-free rate (p=0.011), whereas the distant metastasis-free rate was comparable between groups (p=0.64). In subgroup analyses, PORT was associated with improved OS in patients with 1-3 positive N2 lymph nodes (p=0.013) and with significantly improved DFS among patients without ENE (p=0.046) or lymphatic invasion (p=0.032).

Conclusion: Although PORT did not improve OS or DFS in the matched overall cohort, it significantly reduced LRR. Subgroup analyses suggested potential benefits in patients with limited nodal burden and in those without ENE or lymphatic invasion. These findings, however, should be interpreted cautiously given small subgroup sizes and inherent limitations of retrospective design.

Purpose: Molecular biomarker testing is essential for lung cancer management and precision medicine. This study evaluated biomarker testing practices for non-small cell lung cancer across pathology laboratories in South Korea.

Materials and methods: A nationwide survey of 30 pathology laboratories assessed testing policies, biomarker adoption, testing platforms, next-generation sequencing (NGS) implementation, reporting practices, turnaround times (TATs), and perceived challenges.

Results: All institutions routinely performed biomarker testing; 20 (66.7%) employed reflex testing at least in part. Tissue was the primary specimen type, and cytology and liquid biopsy specimens were accepted by 90.0% and 46.7% of institutions, respectively. For non-squamous NSCLC, all institutions tested EGFR, ALK, ROS1, and PD-L1, with additional testing for BRAF (86.7%) and KRAS (80.0%); other actionable targets were rarely tested outside NGS. In squamous NSCLC, PD-L1 was routinely assessed, whereas other drivers were tested less frequently. All institutions performed tissue-based NGS using companion diagnostic (CDx) and/or non-CDx platforms, and liquid biopsy-based NGS was available in 46.7% of institutions. Median TATs were 2-3, 5, 9, 19, and 15 days for immunohistochemistry, polymerase chain reaction, fluorescence in situ hybridization, tissue-based NGS, and liquid biopsy-based NGS, respectively. Reported barriers included limited sample availability, workforce shortages, prolonged TATs, regulatory restrictions, and lack of standardization.

Conclusion: Biomarker testing is widely implemented in South Korea, with increasing integration of NGS. Despite alignment with international recommendations, systemic and policy reforms are needed to harmonize workflows, reduce variability, and optimize precision oncology.

Purpose: Circulating tumor cell (CTC) is a promising minimally invasive biomarker for EGFR-mutant non-small cell lung cancer (NSCLC). However, the rarity of CTCs and limitations in their isolation and molecular characterization hinder their clinical utility, particularly in predicting treatment outcomes. This study evaluates the potential of CTC molecular response to predict treatment efficacy and guide therapy in patients with EGFR-mutant NSCLC undergoing EGFR-tyrosine kinase inhibitors (TKI) therapy.

Materials and methods: Seventy-seven patients with EGFR-mutant NSCLC treated with EGFR-TKIs were enrolled. CTCs were isolated using continuous centrifugal microfluidic technology (CCM-CTCD) and compared with ctDNA and tissue biopsy for EGFR mutation analysis. Patients were categorized as CTC molecular responders or non-responders based on a ≥ 44.4% reduction in CTC count from baseline. Progression-free survival (PFS) and tumor burden changes were evaluated.

Results: CTC responders had significantly longer PFS (46.3 vs. 13.6 months, p=0.007) and greater tumor burden reduction (-37.7% vs. -35.2%, p=0.218) compared to non-responders. The CCM-CTCD demonstrated concordance with the cobas test while exhibiting higher sensitivity for EGFR mutation detection among 46 patients who underwent both tests simultaneously. Mutational discordance among tissue, ctDNA, and CTCs highlighted tumor heterogeneity. CTC profiling complemented traditional methods for identifying genomic alterations and predicting early progression.

Conclusion: CTC analysis using CCM-CTCD shows potential as a biomarker for predicting treatment response and prognosis in EGFR-mutant NSCLC. Stratification by CTC molecular response may inform risk-adapted treatment; however, its clinical utility remains to be established. Prospective studies are warranted to validate these findings and determine the role of CTC-guided decision-making.

Purpose: This phase I/II study aimed to evaluate the tolerability and the organ-sparing effects of continuous positive airway pressure (CPAP) in breast cancer radiotherapy (RT).

Materials and methods: We conducted a prospective, single-institutional trial approved by the Ministry of Food and Drug Safety of South Korea. Patients with breast cancer who received postoperative RT underwent 4D-CT simulation and treatment planning under both free breathing (FB) and CPAP-assisted breathing (WC), with a target pressure of 20 cm H2O. Adverse events (AEs) were evaluated, and dosimetric parameters of organs at risk and heart position change were compared between the FB and WC arms.

Results: Among 20 enrolled patients, four withdrew due to discomfort during simulation. During the trial, no CPAP-related AEs greater than grade 2 were observed. Compared to FB, CPAP reduced the mean heart dose by 33.8% (p < 0.001), as well as V5-V30 for both the left ventricle and left anterior descending artery (all p < 0.05). It also led to significant reductions in V5-V40 and the mean ipsilateral lung dose, including a 4.4% reduction in V20 (all p < 0.001). The heart centroid shifted rightward (4.8 mm), ventrally (8.1 mm), and caudally (16.3 mm) with CPAP, displacing the heart away from the RT field.

Conclusion: CPAP demonstrated both safety and efficacy for breast cancer RT, achieving significant reductions in cardiac and pulmonary radiation exposure. These findings support further investigation of CPAP as a novel respiratory motion management strategy. Future studies are warranted to identify optimal CPAP pressure levels to facilitate broader clinical implementation.

Purpose: Since the FDA approval of ibrutinib in 2012, the treatment landscape for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has undergone a paradigm shift. Nevertheless, the disease remains incurable, posing ongoing clinical challenges. In Korea, these challenges are further compounded by unique characteristics of patients and national healthcare system.

Materials and methods: The multicenter retrospective analysis included 519 patients diagnosed with CLL/SLL between 2006 and 2024 across three major Korean institutions.

Results: The median age at diagnosis was 62 years. Among 267 patients who received first-line therapy, 68.9% (184/267) were treated with immunochemotherapy, 19.4% (52/267) with cytotoxic chemotherapy, and 11.2% (30/267) with a Bruton tyrosine kinase (BTK) inhibitors. Since the Korean approval of ibrutinib in 2016, BTK inhibitor use has steadily increased. Subgroup analyses demonstrated that patients receiving BTK inhibitor-based therapy had more favorable outcomes compared to those treated with immunochemotherapy.

Conclusion: This study provides the most comprehensive real-world reflection of current diagnostic and therapeutic practices in Korea. Through comparative analysis with international data, it offers valuable insights into the limitations of current CLL/SLL care and may inform future strategies to optimize management in the Korean context.

Purpose: The study aims to explore the predictive value of the Ki67 index for everolimus efficacy in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).

Materials and methods: We collected data on 2,518 cancer patients who received everolimus treatment from three cancer centers in China. Their clinicopathologic characteristics were retrospectively collected. A training cohort and a validation cohort were developed.

Results: A total of 300 patients with HR+/HER2- ABC were included in the study, with 200 patients in the training cohort and 100 patients in the validation cohort. When analyzing the Ki67 index from 14% to 50%, only the Ki67 cut-off of 40% was found to be significantly correlated with progression-free survival (PFS) for patients in the training cohort. Multivariate Cox analyses further showed that Ki67 index of 40% (p=0.03) was significantly associated with PFS in patients treated with everolimus. Patients with Ki67 less than 40% had an improved PFS of 7.0 months, significantly better than 4.6 months for patients with Ki67 more than 40% (p=0.03, HR=0.67, 95CI%=0.46-0.97). In the validation cohort, patients with a Ki67 index of less than 40% had a significantly longer PFS of 4.3 months (2.1 months versus 4.3 months, p<0.001, HR=0.29, 95CI%=0.17-0.51).

Conclusion: The Ki67 cut-off value of 40% was identified as an optimal index for predicting the efficacy of everolimus, which may help with the management of everolimus in Chinese patients with HR+/HER2- ABC.

Purpose: To elucidate how Salidroside-loaded, oligopeptide-modified tumor exosomes (Salidroside@T-exo) rewire the PI3K/AKT/mTOR axis to remodel the immune microenvironment (IME) and reverse acquired PD-1 resistance in breast cancer.

Materials and methods: CSC-exosomes were surface-engineered with TMTP1 peptide and electroporated with Salidroside. PD-1-resistant MA782/5s-8101-R cells and an orthotopic mouse model were used. Multi-omics, flow cytometry, ELISA, immunofluorescence, in vivo imaging, and molecular assays examined immune and signaling outcomes.

Results: Salidroside@T-exo restored T-cell IFN-γ and GZMB secretion, suppressed CD8+ T-cell apoptosis, and inhibited p-PI3K/p-AKT/p-mTOR in T cells. CSC migration, invasion, and stemness (OCT4, NANOG, SOX2) were markedly reduced. Tumor growth, Ki-67 index, and CSC frequency dropped while TUNEL-positive cells rose.

Conclusion: Salidroside@T-exo reverses PD-1 blockade resistance by simultaneously inhibiting PI3K/AKT/mTOR signaling in T cells and eradicating breast CSCs, offering a clinically translatable strategy for refractory breast cancer immunotherapy.