BACKGROUND: The present study aimed to investigate physicians\' perspectives on the diagnosis and treatment decisions for patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutations in a real-world setting in China using an online questionnaire.
METHODS: This study was performed via the CAPTRA-Lung collaboration between December 9, 2022 and March 6, 2023. The questionnaire was distributed digitally to physicians around China and was comprised of three sections: basic characteristics of surveyed physicians, diagnosis and treatment status of NSCLC patients with the EGFR exon20ins-mutation, and physicians\' perspectives on treatment options. Physicians who treat more than 10 patients with advanced NSCLC every month and who have treated patients with advanced EGFR exon20ins-mutant NSCLC in the past six months were involved in this study.
RESULTS: A total of 53,729 questionnaires were distributed and 390 valid ones were collected. The EGFR mutation test was performed in 80.9% and 59.9% of patients receiving first-line or second-line therapy and beyond (hereinafter \"second-line\")therapy, respectively. In terms of treatment options, chemotherapy plus antiangiogenic therapy was the most common treatment option (30.0% of patients in first-line settings; 25.0% of patients in second-line settings), and a certain proportion of patients received novel EGFR exon20ins-targeted agents (including tyrosine kinase inhibitors [TKIs] and bispecific antibodies) in first- or second-line settings, which accounted for 11.9% and 15.7% of all treated patients, respectively. Additionally, physicians reported the highest satisfaction score for the efficacy and safety of targeted agents. Most physicians believed that EGFR exon20ins-targeted TKIs represented the most promising treatment option (80.2% in first-line treatment and 73.3% in second-line treatment). Among several novel agents under study, sunvozertinib has received the highest recognition for efficacy and safety.
CONCLUSIONS: This study investigated the current diagnosis and treatment status and physicians\' perspective, of patients with EGFR exon20ins-mutant NSCLC. The results highlight significant unmet clinical needs in this subgroup of patients. EGFR exon20ins-targeted TKIs were recognized as the most promising treatment regimen and may benefit more patients considering their awareness and acceptance of targeted therapy.

UNASSIGNED: Transarterial chemo(embolization) is preferred for treating unresectable hepatocellular carcinoma (uHCC); however, because of emerging immune-targeted therapies, its efficacy is at stake. This systematic review pioneers to evaluate the clinical efficacy and safety of transarterial chemo(embolization) combined with immune-targeted therapy for uHCC patients.
UNASSIGNED: PubMed, Embase, and Cochrane Library were searched for studies comparing immune-targeted therapy with or without transarterial chemo(embolization) until 31 May 2024. The complete response (CR) rate, objective response rate (ORR), and disease control rate (DCR) were considered to be the primary outcomes calculated for the clinical outcomes of transarterial chemo(embolization) combined with immune-targeted therapy, along with progression-free survival (PFS) and overall survival (OS). The incidence of treatment-related severe adverse events was set as the major measure for the safety outcome.
UNASSIGNED: Sixteen studies, encompassing 1,789 patients receiving transarterial chemo(embolization) plus immune-targeted therapy and 1,215 patients receiving immune-targeted therapy alone, were considered eligible. The combination of transarterial chemo(embolization) and immune-targeted therapy demonstrated enhanced outcomes in CR (OR = 2.12, 95% CI = 1.35-3.31), ORR (OR = 2.78, 95% CI = 2.15-3.61), DCR (OR = 2.46, 95% CI = 1.72-3.52), PFS (HR = 0.59, 95% CI = 0.50-0.70), and OS (HR = 0.51, 95% CI = 0.44-0.59), albeit accompanied by a surge in ALT (OR = 2.17, 95% CI = 1.28-3.68) and AST (OR = 2.28, 95% CI = 1.42-3.65). The advantages of additional transarterial chemo(embolization) to immune-targeted therapy were also verified in subgroups of first-line treatment, intervention techniques, with or without extrahepatic metastasis, Child-Pugh grade A or B, and with or without tumor thrombus.
UNASSIGNED: The combination of transarterial chemo(embolization) and immune-targeted therapy seems to bolster local control and long-term efficacy in uHCC, albeit at the expense of hepatic complications.
UNASSIGNED: http://www.crd.york.ac.uk/PROSPERO/, identifier 474669.

This review discusses the topic of prevention of brain metastases from the most frequent solid tumor types, i.e., lung cancer, breast cancer and melanoma. Within each tumor type, the risk of brain metastasis is related to disease status and molecular subtype (i.e., EGFR-mutant non-small cell lung cancer, HER2-positive and triple-negative breast cancer, BRAF and NRAF-mutant melanoma). Prophylactic cranial irradiation is the standard of care in patients in small cell lung cancer responsive to chemotherapy but at the price of late neurocognitive decline. More recently, several molecular agents with the capability to target molecular alterations driving tumor growth have proven as effective in the prevention of secondary relapse into the brain in clinical trials. This is the case for EGFR-mutant or ALK-rearranged non-small cell lung cancer inhibitors, tucatinib and trastuzumab-deruxtecan for HER2-positive breast cancer and BRAF inhibitors for melanoma. The need for screening with an MRI in asymptomatic patients at risk of brain metastases is emphasized.

UNASSIGNED: Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC).
UNASSIGNED: To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs).
UNASSIGNED: Retrospective cohort study.
UNASSIGNED: Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs.
UNASSIGNED: We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively.
UNASSIGNED: Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7-58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was -0.4 months (95% CI: -0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: -0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: -1.6 months; 95% CI: -2.4 to -0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: -0.9 months; 95% CI: -1.7 to -0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP.

Systemic treatment of metastatic colorectal cancer (mCRC) has improved considerably over the past 20 years. First- and second-line combinations of 5FU, oxaliplatin, and irinotecan, with or without anti-angiogenic and/or anti-EGFR antibodies, were approved shortly after the turn of the millennium. Further triumphs were not seen for almost 10 years, until the approval of initially regorafenib and shortly after trifluridine/tipiracil. A growing understanding of tumor biology through molecular profiling has led to further treatment options. Here, we review the most recent clinical data for late-line treatment options in mCRC, focusing on randomized trials if available. We include recommendations for options in unselected patients and therapies that should only be offered in patients with distinct tumor profiles (e.g., BRAF mutations, KRAS G12C mutations, HER2 amplification, deficient MMR, or NTRK gene fusions).

The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.

Based on its absence in normal tissues and its role in tumorigenesis and tumor progression, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of N6-methyladenosine (M6A) on RNA, represents a putative valuable and specific target for some cancer therapy. In this study, we performed bioinformatic analysis and immunohistochemistry (IHC) to find that IGF2BP3 was highly expressed in tumor epithelial cells and fibroblasts of ovarian cancer (OC), and was associated with poor prognosis, metastasis, and chemosensitivity in OC patients. In particular, we discovered that knockdown IGF2BP3 expression inhibited the malignant phenotype of OC cell lines by decreasing the protein levels of c-MYC, VEGF, CDK2, CDK6, and STAT1. To explore the feasibility of IGF2BP3 as a therapeutic target for OC, a small molecular AE-848 was designed and screened by molecular operating environment (MOE), which not only could duplicate the above results of knockdown assay but also reduced the expression of c-MYC in M2 macrophages and tumor-associated macrophages and promoted the cytokine IFN-γ and TNF-α secretion. The pharmacodynamic models of two kinds of OC bearing animals were suggested that systemic therapy with AE-848 significantly inhibited tumor growth by reducing the expression of tumor-associated antigen (c-MYC/VEGF/Ki67/CDK2) and improving the anti-tumor effect of macrophages. These results suggest that AE-848 can inhibit the growth and progression of OC cells by disrupting the stability of the targeted mRNAs of IGF2BP3 and may be a targeted drug for OC treatment.

暂无摘要。

Breast cancer (BC) in elderly women is an increasing health issue due to demographic changes. BC tends to present later and may receive less than standard treatment options. More often, BC in elderly patients is endocrine-positive (HR+). The treatment of elderly patients with metastatic BC (mBC) represents a therapeutic challenge. In recent years, the treatment landscape of patients that are HR+/Her2-negative has changed due to the introduction in clinical practice of new targeted drugs, which have improved patient outcomes. Elderly patients are a small percentage of all patients enrolled in clinical trials and, to date, there are no standardized guidelines that define the best treatment option for this patient population. This can lead to undertreatment or overtreatment, impacting patient morbidity and mortality. Geriatric Assessment tools to tailor the treatment in elderly patients are underused because they are long and difficult to apply in a busy routine clinical practice. For all these reasons, there is an urgent need to produce data about the best treatment for elderly patients with HR+ mBC. Herein, we report data from randomized clinical trials and real-world evidence on the therapeutic options for HR+ Her2-negative mBC elderly patients and explore future treatment directions.