Asia-Pacific journal of clinical oncology最新文献

Trastuzumab deruxtecan (T-DXd) is a third-generation, HER2-targeting antibody-drug conjugate that has been shown to significantly prolong overall survival, compared with standard chemotherapy, when used to treat patients who have "HER2-low" (HER2 immunohistochemistry [IHC] score 1+; or HER2 IHC 2+ plus in situ hybridization-negative) unresectable or metastatic breast cancer and who have received prior chemotherapy in the metastatic setting or developed disease recurrence during, or within 6 months of completing, adjuvant chemotherapy. The broad aims of this paper are: (a) To draw attention to some of the challenges associated with identifying whether patients have HER2-low metastatic breast cancer (mBC), in an environment where healthcare professionals have previously only needed to determine whether mBC is HER2-positive and therefore likely to respond to traditional HER2-targeted therapies; and (b) to indicate, where possible, what might be done to help overcome specific challenges in this regard. Advice regarding the management of specific T-DXd-related side effects of interest, including interstitial lung disease and pneumonitis, left ventricular dysfunction and emesis, is also offered.

Aim: Primary mediastinal germ cell tumors (PMGCTs), a rare subset of extragonadal GCTs, exhibit heterogeneous prognoses depending on histological subtype. Limited prospective clinical studies exist due to their rarity. This study analyzed therapeutic efficacy and prognostic factors for PMGCT patients.

Methods: We retrospectively analyzed PMGCT patients treated at Peking University Cancer Hospital (2009-2024). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier curves and log-rank tests. Cox regression identified prognostic factors.

Results: Among 37 patients (the median age: 30; 35 males and two females), nine had seminomas, and 28 had non-seminomas. All patients received chemotherapy, 21 received mediastinal radiotherapy, and 10 underwent surgery. The 1-, 2-, 3-, and 5-year OS rates were 92%, 81%, 73%, and 73%, respectively. The median PFS for the first-line treatment (84% received bleomycin, etoposide, and cisplatin [BEP] regimen) was 9.1 months (95% confidence interval [CI] 4.6-13.5). Seminoma patients showed superior outcomes vs. non-seminoma: PFS (not reached [NR] vs. 4.2 months, p < 0.001) and OS (NR vs. 29.5 months, p = 0.008). In non-seminoma patients, demonstrated significant tumor reduction post-first-line therapy correlated with prolonged PFS (p < 0.001). Cox regression indicated non-seminoma patients who received mediastinal radiotherapy had significantly longer OS (hazard ratio [HR] 5.943, 95% CI 1.077-32.791; p = 0.041).

Conclusions: The BEP regimen, which was effective in testicular GCTs, demonstrates activity in PMGCTs. Seminomas showed superior therapeutic effect and survival compared to non-seminomas. For non-seminomas, the first-line response might predict PFS, and mediastinal radiotherapy might provide additional survival benefits. These findings highlight histology-driven prognostic stratification for PMGCTs and multimodal management for primary mediastinal non-seminoma GCTs.

Skin adverse events (AEs) frequently accompany all types of anticancer treatments. The type and course of these skin AEs with different cancer treatments have been described and may be considered to generally have a similar pattern in differing world regions. However, some populations, including Asian populations, may have presentations that vary somewhat based on skin sensitivity and other factors. Education of both healthcare professionals and patients about how to identify, prevent, and manage these skin AEs is imperative in this era when not only is cancer on the rise but also there are longer life expectancies due to new, improved treatment approaches. Maintaining a good quality of life is a key target in oncology management, and skin AEs can have a profound effect on patient comfort, patient self-image, and psychological ability to cope. Today, proactive skincare regimens, including dermocosmetics, can be put in place to minimize potential for AEs. If skin AEs occur, dermocosmetics may be employed alone or to augment the effects of medical treatments. Optimally, cancer patients should be managed by a multidisciplinary team with knowledge of skin and treatment-related AEs. This publication discusses how recent international guidance on best-practices use of dermocosmetics can be adapted to the North Asia region (China, Hong Kong, Japan, Republic of Korea, and Taiwan).

Here, we utilized advanced bioinformatics approaches alongside experimental validation to identify key prognostic biomarkers and potential immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Our findings highlight distinct differences in the immune and molecular environments between primary and brain metastatic NSCLC. Brain metastases exhibited higher proportions of cancer stem cells (CSCs), reduced infiltration of B and T cells, and a greater immune escape potential, contributing to diminished responsiveness to ICIs. Specifically, Tregs, with the highest immune checkpoint activity, emerged as critical mediators of immune suppression, offering potential therapeutic targets. Pseudotime analysis revealed that Tcm and Tregs are at the terminal stages of T cell differentiation, with immune checkpoint gene expression reflecting dynamic shifts in immune response regulation. Machine learning models revealed that TNFRSF8, CD160, and TNFSF9 are survival-associated biomarkers. Immunofluorescence confirmed significant upregulation of TNFRSF8, CD160, and TNFSF9 in lung cancer tissues, particularly in brain metastasis, underscoring their involvement in tumor progression and immune evasion. The identification of TNFRSF8, CD160, and TNFSF9 as key prognostic biomarkers emphasizes their potential as ICIs in brain metastatic NSCLC. These findings provide insights into the immune landscape of both primary and metastatic NSCLC and highlight novel therapeutic avenues, including combinatorial strategies targeting immune evasion mechanisms and tumor-specific pathways in brain metastasis. Our study suggests that tailored approaches, integrating immune checkpoint inhibition with other targeted strategies, could improve the efficacy of immunotherapy in brain metastatic NSCLC.

Objective: This study aimed to classify patients with gastric cancer (GC) based on neutrophil extracellular trap (NET)-related gene expression and to develop a prognostic risk score model.

Methods: Utilizing data from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) cohort, we performed univariate Cox regression analysis followed by K-means clustering to stratify GC samples into two NET-related subtypes (C1 and C2), and then the survival analysis and immune cell infiltration analysis were performed between these subtypes. Next, to further investigate the prognostic significance of NET-related features, we developed a risk score model using LASSO Cox regression analysis, and survival analysis was then conducted.

Results: Ten prognostic NET-related genes were identified, distinguishing two GC subtypes; compared with the C1 subtype, the C2 subtype demonstrated significantly poorer clinical outcomes. Furthermore, the C2 subtype exhibited elevated TIDE scores, along with enhanced infiltration of immunosuppressive cell populations, including regulatory T cells, macrophages, and myeloid-derived suppressor cells (MDSCs). Next, we constructed a six-gene risk score model (MPO, BST1, IL6, KCNJ15, SELP, and ELANE) derived from the aforementioned 10 NET-related genes. This risk score model may serve as an independent prognostic indicator for GC patients, with the high-risk group showing markedly reduced survival rates. Notably, the poor-prognosis C2 subtype was associated with a higher risk score compared to the C1 subtype.

Conclusion: NET-related genes are useful for categorizing GC samples into different subtypes and potentially playing significant roles in forecasting prognosis and guiding immunotherapy in GC. Furthermore, the six-gene risk model may aid in personalized prognosis prediction for GC patients.

Aim: Clinical evidence on disease characteristics and outcomes of retroperitoneal sarcoma (RPS) remains limited. Although eribulin was approved for soft tissue sarcomas in Japan in 2016, real-world data on its use for advanced RPS are scarce. We investigated treatment patterns and survival outcomes of patients with RPS, with a particular focus on those receiving eribulin.

Methods: The database included 118 patients pathologically diagnosed with RPS between January 2000 and August 2025. Clinicopathologic data, including inflammation/nutrition markers and survival outcomes, were analyzed.

Results: Among them, 102 (86%) underwent surgical resection of the primary tumor, with a median recurrence-free survival of 20 months and a median overall survival of 9.2 years. Well-differentiated liposarcoma, dedifferentiated liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma were the most frequent histologic subtypes. Non-well-differentiated liposarcoma histology, Stage IIIA-IIIB, lower C-reactive protein-albumin-lymphocyte index, and higher modified neutrophil-platelet score were associated with poor postoperative prognosis. Of 44 patients with unresectable RPS who received systemic therapy, 23 (52%) were treated with eribulin. In this group, complete response, partial response, and stable disease rates were 4.3%, 26%, and 35%, respectively. The most common adverse events were decreased neutrophil count (40%), peripheral neuropathy (30%), and dysgeusia (20%). Multivariate analysis showed that non-use of eribulin and undifferentiated pleomorphic sarcoma were independently associated with worse survival in unresectable disease.

Conclusion: We separately described outcomes and treatment patterns of patients with resectable and unresectable RPS. Our findings suggest that eribulin should be considered a treatment option for unresectable RPS in clinical practice.

Objective: Ovarian cancer (OC) is the most prevalent cause of death among gynecologic malignancies. Astragalus polysaccharides (APS) possess antitumor activity in OC. We explored the mechanism of APS regulating ferroptosis and malignant progression of ovarian cancer cells (OCCs) via the MAPK/ERK pathway.

Methods: A2780 OCCs were cultured in vitro and initially treated with varying concentrations of APS (0, 50, 100, 200, 500, 1000 µg/mL) for 24 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was assessed to establish a dose-response curve, and the IC50 value (121.7 µg/mL) was calculated to determine the optimal concentration of APS for subsequent experiments. A2780 OCCs were treated with APS, a ferroptosis inhibitor ferrostatin-1, and the MAPK/ERK pathway activator C16-PAF for 24 h. Cell proliferation, invasion, and migration were assessed by CCK-8, Transwell, and wound healing assays. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), 4-hydroxynonenal (4-HNE), and Fe²⁺ in cells, the release of lactate dehydrogenase (LDH), and phosphorylated (p)-ERK1/2, ERK1/2, and GPX4 proteins were determined using kits and Western blot.

Results: APS treatment suppressed expression levels of p-ERK1/2, ERK1/2, and GPX4 proteins, increased ROS, MDA, and Fe²⁺ in the cells, as well as LDH release, promoted ferroptosis, and repressed invasion, proliferation, and migration. Further treatment with ferroptosis inhibitor ferrostatin-1 upregulated GPX4 protein level, diminished LDH release and MDA, ROS, and Fe²⁺ levels in OCC, and enhanced cell malignant biological behaviors. APS promoted OCC ferroptosis by inactivating the MAPK/ERK pathway. The MAPK/ERK pathway activation partially reversed APS-induced suppression on OCC malignant biological behaviors.

Conclusion: APS intensified OCC ferroptosis by repressing the MAPK/ERK pathway and abated cell proliferation, invasion, and migration, thereby limiting malignant progression.

Introduction: The Pharmaceutical Benefits Scheme (PBS) provides affordable access to cancer treatments in Australia. Not all cancer treatments are available on the PBS. Access to non-PBS-listed cancer treatments can occur through Compassionate Access Programs (CAPs). This retrospective review describes cancer treatments used via CAPs in a Metropolitan Cancer Centre in Australia.

Methods: Patients with solid organ malignancies who had received drugs via compassionate access between 2017 and 2024 were identified via pharmacy and hospital medical records. Patients with hematological malignancies or who accessed drugs through out-of-pocket funding were excluded. CAPs were grouped into cost-share/co-pay and cost-free programs.

Results: Of 228 cases, 148 (64.9%) received the drug cost-free, and 80 (35.1%) were on a cost-share/co-pay program. A total of 110 (48.2%) patients received the CAP drug as their first therapy. The median number of previous therapies before receiving CAP drug was 1 (range: 0-4). The median duration between diagnosis and use of CAP drug was 5.1 months (range: 0.2-96.0). The median and mean duration of CAP drug use were 5.2 and 10.3 months, respectively (range: 0.03-96.0). A total of 53 programs provided 40 drugs from 18 companies. Six drugs had both cost-share/co-pay and cost-free programs. The drug with the most patients was pertuzumab (n = 43), followed by nivolumab (n = 27) and durvalumab (n = 21). Fourteen patients accessing non-oral drugs via cost-share/co-pay programs ultimately did not receive any free drugs.

Conclusion: There is an increasing prevalence of novel drug use via CAPs across all types of cancers with promising impacts on patient outcomes.

We report an 83-year-old woman with severe concomitant pathology who underwent surgery for colon cancer, with recurrent bleeding from the tumor, and subcompensated intestinal stenosis. After right-sided hemicolectomy with regional lymph node dissection, the disease was staged as pIIIC, and a translocation of the NTRK1 (Neurotrophic Tyrosine Receptor Kinase) gene was detected. The patient required adjuvant treatment, given the high risk of disease progression, but due to her severe concomitant pathology, chemotherapy was contraindicated. Adjuvant therapy with larotrectinib was recommended given NTRK gene translocation. According to examination data after three months, there was no progression. Following this, the patient decided to stop larotrectinib. Subsequently, disease progression was detected in the form of abdominal carcinomatosis, after which larotrectinib was resumed. At the time of this clinical case report, therapy is ongoing for 21 months without any signs of further disease progression. This study demonstrates the efficacy and safety of larotractinib as both adjuvant therapy and first-line therapy in a complex clinical case of colon cancer against the background of severe concomitant pathology, when chemotherapy is contraindicated.

Background: BNIP3 is a crucial gene involved in mitophagy that modulates mitochondrial and cellular homeostasis. However, there is limited research examining its biological regulation. The current study investigates the expression of BNIP3 in breast cancer, and its relationship with hypoxia and immune response.

Methods: BNIP3 expression and its effect on clinical prognosis was assessed using TCGA database. Immunohistochemistry was used to identify the expression of BNIP3 in 50 cases of invasive breast carcinomas. Gene expression of BNIP3 was assessed in breast cancer cell lines exposed to hypoxia. The expression levels of BNIP3 were correlated with multiple clinicopathologic variables, HIF-1α and NF-κB (p65). The association between BNIP3 and cancer immune infiltration was investigated using the TIMER database.

Results: In breast cancer, an overexpression of BNIP3 has been substantially linked to a poor survival rate. Immunohistochemical analysis showed a repression of BNIP3 in patient samples tested. An increase in the gene expression of BNIP3 was observed in breast cancer cell lines exposed to hypoxic conditions. Our results demonstrate a positive correlation between expression of BNIP3 and the expression of hypoxia and immune response markers, as well as the lobular subtypes of invasive breast cancer.

Conclusion: According to the study findings, BNIP3 expression is lower in breast cancer and may influence the prognosis and play a role in immune modulation. Our findings suggest that hypoxia and immune response regulate the expression of BNIP3 in breast cancer. Hence the results signify the importance of BNIP3 as a prognostic marker in breast tumor progression.