Chinese clinical oncology最新文献

Background: Melanoma stands out as a prevalent instigator of leptomeningeal disease (LMD) within the realm of cancer. Given the poor prognosis accompanying this condition, ongoing trials are exploring a spectrum of treatment modalities in pursuit of more effective interventions. To ascertain the most effective therapeutic strategies, we aim to compare novel treatments against the current standard of care for melanoma-associated LMD.

Methods: A comprehensive search was conducted across multiple databases, including PubMed/Medline, EMBASE, Scopus, ScienceDirect and Web of Science for relevant studies published from January 2014 to September 2024. We included primary research studies, including observational studies, randomised control trials, quasi-experimental design studies, clinical trials, and experimental studies focusing on LMD caused by metastatic melanoma. Data extraction was conducted according to PRISMA guidelines and quality assessment/risk of bias was performed individually using the GRADE method. A network meta-analysis is conducted to evaluate the effects of multiple interventions within the study. Overall survival outcomes were quantified using log hazard ratio. The protocol for this study was registered on PROSPERO (CRD42024529626).

Results: Out of 843 records screened for eligibility, seven carefully chosen studies, meeting our specific inclusion criteria, provided insights into the management of 397 patients grappling with LMD due to metastatic melanoma. These studies vary in design: one observational cohort study with 29 participants, a clinical trial with 25 patients, four retrospective cohort studies ranging from 39 to 190 participants and one experimental study with 24 patients. The chosen studies contain moderate to high risks of bias, with low heterogeneity (I2=13.4%). Immunotherapy with or without targeted therapy is the most effective intervention.

Conclusions: Despite the escalating breakthroughs of treatment options in melanoma-associated LMD, further studies may be imperative to conclusively determine whether the newer therapeutic options yield superior outcomes compared to the current standard of care.

Background: Radiotherapy plus temozolomide followed by adjuvant temozolomide was the standard treatment for high-grade gliomas. This study aimed to explore the effectiveness and safety of the addition of apatinib in patients with high-grade gliomas after surgery.

Methods: In this retrospective cohort study, patients with high-grade glioma [World Health Organization (WHO) grade III or IV] treated with apatinib and concurrent chemoradiotherapy (cCRT) after surgery from October 2017 to February 2021 were reviewed. High-grade glioma patients used cCRT alone in the same period were reviewed as the control group. Progression-free survival (PFS), overall survival (OS), the grade of peritumoral brain edema (PTBE) and safety profiles were recorded. Cox regression analyses were used to determine the associated factors of PFS and OS.

Results: A total of 60 patients with high-grade glioma were reviewed, with 30 patients in the apatinib plus cCRT group and 30 patients in the cCRT group. The median PFS of the apatinib plus cCRT group compared with the cCRT group was 8.53 vs. 7.33 months (P=0.62), and the median OS was 13.70 vs. 14.30 months (P=0.93). Multivariate analysis revealed that only pathological grade was independently associated with PFS [hazard ratio (HR) =4.445, 95% confidence interval (CI): 1.857 to 10.641, P<0.001] and OS (HR =3.737, 95% CI: 1.530 to 9.123, P=0.004). The apatinib plus cCRT also improved PTBE (P=0.001), and decrease the corticosteroids use than cCRT alone (P=0.002). No grade 3 or higher adverse event was observed in both groups.

Conclusions: Post-operative cCRT plus apatinib was feasible for patients with high-grade glioma, with manageable toxicities.

Background: The characteristics of tumor immune microenvironment are important factors affecting the efficacy of immunotherapy, and there are differences in the distribution of tumor-infiltrating lymphocyte (TIL) subsets in different types of tumors. This study aims to compare the distributions of cluster of differentiation (CD) 4+ and CD4+ T cell subsets of TILs and their clinical significance between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).

Methods: The tumor tissues of 78 LUAD and 56 LUSC patients who underwent surgery at The Second Affiliated Hospital of Zhengzhou University between October 2020 and October 2022 were collected, TIL level were detected by pathological observation, and the proportions of CD4+, CD4+ T cell subsets and CD4+/CD4+ ratio in TILs were detected by flow cytometry. These indicators were compared between LUAD and LUSC, and their correlations with clinicopathological characteristics and patient survival were analyzed.

Results: There was no significant difference in the TILs level between LUAD and LUSC (P>0.05). The CD4+/CD4+ ratio in LUSC was lower, and proportion of CD4+ T cells was higher than those in LUAD (all P<0.05). In LUAD, the proportions of CD4+, CD4+ T cells and CD4+/CD4+ were correlated with tumor size or tumor-node-metastasis (TNM) stage, while in LUSC, only the proportions of CD4+ and CD4+ T cells were correlated with tumor size, degree of differentiation or TNM stage. In LUAD patients, higher proportions of CD4+, CD4+ T cells and lower CD4+/CD4+ predicted longer survival, and high CD4+/CD4+ (>1.04) was an independent risk factor for PFS and OS (P<0.05); In LUSC patients, there was no correlation between the proportions of CD4+ T cells, CD4+ T cells and CD4+/CD4+ ratio, and patient prognosis (P>0.05).

Conclusions: There were differences in the distribution and balance of CD4+ and CD4+ TIL subsets between LUAD and LUSC, among which CD4/CD4+ ratio closely affected the prognosis of LUAD patients but had relatively weak prognostic value in LUSC patients due to the restriction of CD4+ T cells.

Background: The recurrence shortly after interventional therapy poses a great challenge in managing malignant central airway obstruction (MCAO). While cryotherapy has shown potential benefits when combined with immunotherapy in lung cancer, its effectiveness for improving local control of malignant central airway tumors is not well understood. This study aims to evaluate the clinical efficacy and safety of combining these strategies.

Methods: A total of 12 patients with MCAO who had been treated with a combination of cryotherapy and immune checkpoint inhibitors (ICIs) were compiled for analysis in a tertiary hospital in Shanghai East Hospital, China. The primary endpoint is the duration of efficacy (DoE) for MACO after the combined therapy, which was defined as the time interval of the airway stayed patency without additional repeated interventional treatment. Secondary endpoints encompassed an assessment of objective response rate, overall survival and the adverse events.

Results: Twelve patients received a combination therapy between January 2021 and December 2023. Median age was 66 years, 91.7% male. Fifty percent were squamous carcinoma. 50.0% had medium to low programmed cell death-ligand 1 (PD-L1) levels. 41.7% patients' performance status scored higher than 2. 91.7% (11/12) of the patients objectively respond to the combined therapy, with a median DoE of 10.0 (95% confidence interval: 3.7-21.7) months. The 6-, 12- and 18-month survival rate was 75.0%, 50.0% and 41.8%, respectively. The most common adverse event was granulation. Other events included mild rash, pneumonitis, and hypothyroidism. No severe procedure-related adverse events occurred.

Conclusions: In patients with endoluminal or mixed MCAO, our findings suggest that combining endobronchial cryotherapy with ICIs may help maintain airway patency, offering a promising preliminary signal for this therapeutic approach.

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) is characterized by higher lymphocytic infiltration, which predicts sensitivity to immunotherapy. However, there are few studies investigating the mechanisms of acquired resistance to programmed cell death protein 1 (PD-1) blockade and its subsequent treatment strategies for EBVaGC.

Case description: We describe the case of a patient with EBVaGC who was initially treated with first-line chemotherapy plus Sintilimab, a fully humanized anti-PD-1 monoclonal antibody, resulting in a near-complete response. However, the acquired resistance to the immunotherapy treatment emerged shortly after consolidating radiotherapy, and subsequent second-line chemotherapy plus Sintilimab proved ineffective, confirming the true acquired resistance to PD-1 blockade. Re-biopsy of the treatment-resistant tumors revealed that a secondary gain-of-function mutation in mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1) E203K had been acquired. Subsequently, the patient received an off-label MEK inhibitor trametinib and achieved a rapid and durable response.

Conclusions: This study highlights the aberrant activation of the mitogen-activated protein kinase (MAPK) pathway as another important mechanism of resistance to immunotherapy. This case provides direct clinical evidence that MEK1 E203K is involved in resistance to immune checkpoint inhibitors (ICIs). Furthermore, for the first time, the MEK inhibitor trametinib has shown promising results in treating tumors with this mutation.

Urothelial carcinoma poses significant challenges in clinical management due to its aggressive nature and high prevalence. While most diagnoses involve localized disease, advanced urothelial carcinoma (aUC) often leads to short overall survival (OS). Historically, platinum-based chemotherapy has been the primary treatment for aUC, although its efficacy is limited. However, recent therapeutic advancements, such as immune checkpoint inhibitors (ICIs) and targeted therapy using antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs), have shown promise in clinical trials, initially among patients who have undergone platinum-based chemotherapy. Recently, phase III clinical trials have assessed the effectiveness of ICIs, ADCs, and TKIs either in combination or as monotherapy in the first line setting for patients with aUC. As a result of this expanding knowledge, the combination of enfortumab vedotin (EV) with pembrolizumab in the front-line scenario became the new standard of care for aUC, demonstrating significant enhancements in OS and progression-free survival compared to platinum-based chemotherapy. Additionally, other ADCs and targeted therapies have exhibited promising efficacy in clinical trials. This review summarizes recent advancements in the treatment landscape of aUC, focusing on the efficacy and safety profiles of ICIs, ADCs, and TKIs, highlighting the evolving standards and promising combination approaches in the management of this challenging malignancy.