Therapeutic Advances in Medical Oncology最新文献

Brain metastases (BM) are the most common intracranial malignancies. They are responsible for death as well as impairment of quality of life and cognitive function. In some cases, BMs can cause intracranial hemorrhage, which is not only responsible for the acute onset of either a new focal neurological deficit or worsening of a preexisting focal deficit but also poses a new challenge in treatment planning and clinical management. The aim of this study was to evaluate the available treatment modalities and their efficacy in hemorrhagic brain metastases (HBMs) with special attention to radiotherapy. In this review, we searched PubMed, BMJ, NCBI, Springer, BMC Cancer, Cochrane, and Google Scholar for articles containing data on the diagnosis and treatment of patients with HBMs, excluding the pediatric population. Treatment strategies consist of neurosurgery, whole brain radiotherapy, and stereotactic techniques (fractionated stereotactic radiosurgery (fSRS)/stereotactic radiosurgery (SRS)). Although the optimal treatment strategy for HBMs has not been established, we found no convincing evidence that radiotherapy, especially fSRS/SRS, is contraindicated in HBMs. We concluded that fSRS/SRS is a promising option for patients with HBM, particularly when surgical intervention poses risks.

Background: Immunotherapy blocking programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has revolutionized the treatment of extensive-stage small-cell lung cancer (SCLC), but only with limited real-world efficacy data; evidence from immunotherapy for other pulmonary neuroendocrine carcinoma (PNEC) is scarce.

Objective: The purpose of this study is to evaluate the efficacy of receiving PD-1/PD-L1 inhibitors in patients with advanced PNEC and explore factors related to survival prognosis, providing clues for treatment for patients with advanced PNEC.

Methods: In all, 203 patients with advanced PNEC who received PD-1/PD-L1 inhibitors between January 2019 and December 2021 were retrospectively analyzed. Kaplan-Meier curves were constructed for progression-free survival (PFS) and overall survival (OS).

Results: For the 203 patients, the objective response rate (ORR) was 48.3%, the disease control rate (DCR) was 83.3%, the median PFS (mPFS) was 6.0 months, and the median OS (mOS) was 13.1 months. Among them, the histology was 166 SCLC, 13 large-cell neuroendocrine carcinoma, and 24 other unspecified PNEC. Histologically, no significant difference was observed in PFS (p = 0.240) or OS (p = 0.845). In first-line (1L) treatment (N = 125), patients received chemoimmunotherapy and had an ORR of 64.8%, DCR of 92.0%, mPFS of 6.6 months, and mOS of 14.9 months. In second-line (2L) or later-line setting, the ORR, DCR, mPFS, and mOS were 21.8%, 69.2%, 4.4, and 9.4 months; immunotherapy plus small-molecule antiangiogenic agents showed significantly greater PFS than immunotherapy monotherapy or chemoimmunotherapy (6.4 vs 1.4 vs 3.7 months, p = 0.041). Patients without liver metastasis had superior PFS (7.0 vs 5.1 months, p < 0.001) and OS (19.2 vs 9.6 months, p < 0.001) than those with liver metastasis.

Conclusion: In clinical practice, PD-1/PD-L1 inhibitors are effective in patients with advanced PNEC, regardless of the pathological histology. The efficacy of 1L immunochemotherapy is worthy of recognition, and the addition of small-molecule antiangiogenic agents to immunotherapy in 2L or later-line treatment provides a better survival trend.

Design: Retrospective study.

Background: Plasma Epstein-Barr virus (EBV) DNA has been identified as a significant prognostic marker for nasopharyngeal carcinoma (NPC), yet there is limited research on the prognosis of NPC patients with negative EBV DNA.

Objectives: We explore the prognostic value of comprehensive immune-inflammatory and nutritional indicators to offer personalized treatment recommendations and prognosis predictions for non-metastatic NPC patients with negative EBV DNA.

Design: This was a retrospective study.

Methods: This study retrospectively analyzed 257 non-metastatic NPC patients with negative EBV DNA between January 2015 and December 2019. The Kaplan-Meier survival curves evaluated survival endpoints, and group discrepancies were assessed with log-rank tests. Principal component analysis (PCA) reduced data dimensionality. Univariate and multivariate Cox regression analyses identified significant prognostic variables. Risk stratification was performed based on recursive partitioning analysis (RPA). A robust prognostic model was constructed by nomogram and evaluated by calibration curves, decision curves, and the time-dependent area under the curve analysis.

Results: PCA was employed to compute the immune-inflammation index (III) and nutrition index (NI). Multivariate Cox regression analysis revealed lactate dehydrogenase, III, and NI as significant prognostic variables for overall survival (OS). Utilizing RPA, we stratified the risk into three categories: low-risk group (low III + high NI), middle-risk group (low III + low NI), and high-risk group (high III). Both the middle- (p = 0.025) and high-risk groups (p < 0.001) exhibited poorer OS compared with the low-risk group. The nomogram model exhibited superior predictive accuracy compared to tumor lymph node metastasis stage alone (C-index: 0.774 vs 0.679).

Conclusion: Our study validated the prognostic significance of III and NI in non-metastatic NPC patients with negative EBV DNA. Additionally, a clinical risk stratification was constructed to offer valuable insights into the individualized treatment of these patients.

Circulating tumor cells (CTCs) are tumor cells that slough off the primary lesions and extravasate into the bloodstream. By forming CTC clusters and interacting with other circulating cells (platelets, NK cells, macrophage, etc.), CTCs are able to survive in the circulatory system of tumor patients and colonize to metastatic organs. In recent years, the potential of CTCs in diagnosis, prognostic assessment, and individualized therapy of various types of tumors has been gradually explored, while advances in biotechnology have made it possible to extract CTCs from patient blood samples. These biological features of CTCs provide us with new insights into cancer vulnerabilities. With the advent of new immunotherapies and personalized medicines, disrupting the heterotypical interaction between CTCs and circulatory cells as well as direct CTCs targeting hold great promise. Pancreatic cancer (PC) is one of the most malignant cancers, in part because of early metastasis, difficult diagnosis, and limited treatment options. Although there is significant potential for CTCs as a biomarker to impact PC from diagnosis to therapy, there still remain a number of challenges to the routine implementation of CTCs in the clinical management of PC. In this review, we summed up the progress made in understanding biological characteristics and exceptional technological advances of CTCs and provided insight into exploiting these developments to design future clinical tools for improving the diagnosis and treatment of PC.

Background: Programmed cell death protein 1 ligand 1 (PD-L1) expression alone may not be the optimal predictor of immunotherapy (IO) efficacy in advanced non-small cell lung cancer (NSCLC). Evaluation of circulating immune signatures using mass cytometry is a promising technique for predicting IO response and prognosis. The utility of circulating immune signatures for efficacy prediction after IO in advanced NSCLC remains to be elucidated.

Objectives: To assess the feasibility of circulating immune cells and cytokines in predicting tumor response to IO in advanced NSCLC.

Design: A prospective observational study.

Methods: To investigate dynamic changes in immune signatures, blood specimens were prospectively collected from patients with NSCLC at baseline and following chemotherapy (C/T) and/or IO. Mass cytometry and enzyme-linked immunosorbent assay were used to characterize immune signatures and cytokine patterns to identify correlations between immune profiles and treatment efficacy.

Results: The study enrolled 45 patients. The proportion of circulating natural killer (NK) cells and CD8⁺ T cells significantly increased after IO alone treatment. Cell levels of PD-1⁺CD8⁺ T cells, PD-1⁺CD4⁺ T cells, TIM-3⁺CD8⁺ T cells, LAG-3⁺ NK cells, and LAG-3⁺CD8⁺ T cells significantly decreased in patients with treatment response to IO alone. Tumor necrosis factor-alpha (TNF-α) levels significantly increased after IO alone treatment. Patients with high PD-1⁺CD8⁺ T cells before IO alone treatment had lower overall survival (OS) compared to those with low levels. Patients with high LAG-3⁺CD8⁺ T cells before chemotherapy plus immunotherapy treatment had lower OS compared to those with low levels.

Conclusion: Responses to IO in NSCLC were correlated with declines in specific exhausted T cells, suggesting that IO may exert therapeutical efficacy by decreasing circulating exhausted T cells, which were associated with poorer survival, while also increasing TNF-α. These results highlight the prognostic value of monitoring changes in circulating exhausted T cells to predict IO response and survival outcomes in advanced lung cancer.

Background: Several tyrosine kinase receptors inhibitors (TKIs) have demonstrated antiproliferative effects in well-differentiated neuroendocrine tumors (NETs). We aimed to summarize and appraise the current evidence of the efficacy of TKIs in patients with different types of NETs.

Methods: We performed a systematic review of clinical trials of TKIs in patients with advanced gastroenteropancreatic or lung NETs (PROSPERO registration number: CRD42024507379). Population characteristics, efficacy, and safety results were summarized by type of NET.

Results: Twenty-eight studies were eligible, totaling 2284 patients. While sunitinib remains the only Food and Drug Administration-approved TKI in patients with NETs (for patients with pancreatic well-differentiated NETs), recent placebo-controlled randomized trials have demonstrated improved response rates and progression-free survival for patients with progressive and pre-treated well-differentiated pancreatic (cabozantinib or surufatinib) or gastrointestinal (GI) NETs (pazopanib, cabozantinib, or surufatinib). There is limited evidence to support the use of a TKI in patients with lung or grade 3 NETs. The toxicity associated with TKIs follows a class effect, with a significant proportion of patients experiencing fatigue, hypertension, and hand-foot skin reactions.

Conclusion: TKIs are effective therapies in patients with pancreatic or GI well-differentiated NETs and should be part of the therapeutical sequencing of these patients.

Background: The emergence of new antileukemic drugs, including Bruton tyrosine kinase inhibitors (BTKis), phosphoinositide 3-kinase inhibitors (PI3Kis), and B-cell lymphoma 2 antagonists (BCL-2a), has significantly improved the outcomes for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Despite advances in treatment efficacy, the comprehensive safety profile of these novel agents versus traditional chemotherapy and immunotherapy has not been adequately explored, and there have been few direct comparisons.

Objectives: This study aimed to compare the safety profiles of novel therapeutic agents, chemotherapy, and immunotherapy in patients with relapsed/refractory CLL using a Bayesian network meta-analysis (NMA).

Methods: A systematic literature review was conducted to identify randomized clinical trials on relapsed/refractory CLL. The search encompassed major medical databases (MEDLINE, Embase, and CENTRAL) and gray literature, with the aim to integrate the findings into a Bayesian NMA framework for safety outcome assessment.

Design: Systematic literature review with Bayesian NMA.

Results: The systematic search identified 14 randomized trials that formed networks for the comparison of safety outcomes. No differences were shown between therapies in terms of overall adverse events (AEs). However, bendamustine + rituximab had a more favorable safety profile for grade ⩾3 AEs when compared with ibrutinib (risk ratio 0.62 (95% credible interval 0.40-0.86)), acalabrutinib (0.69 (0.45-0.94)), zanubrutinib (0.64 (0.42-0.91)), and venetoclax + rituximab (0.87 (0.79-0.96)). The frequency of grade ⩾3 AEs, serious AEs, and treatment discontinuations and deaths due to AEs was comparable between acalabrutinib, zanubrutinib, and venetoclax + rituximab. There were no significant differences in the safety profiles regarding hematological events, events affecting the quality of life, and infections for most comparisons of venetoclax + rituximab with BTKis. Among BTKi-specific events, zanubrutinib was associated with a higher risk of hypertension (2.96 (1.74-5.16)) and bleeding (1.38 (1.06-1.81)) than acalabrutinib. No differences in the risk of atrial fibrillation were found between acalabrutinib and zanubrutinib (1.56 (0.74-3.34)).

Conclusion: Our findings showed that venetoclax + rituximab, acalabrutinib, and zanubrutinib have acceptable safety profiles, which indicates that they may be the preferred therapeutic options in the setting of relapsed/refractory CLL.

Trial registration: PROSPERO CRD42022304330.

Background and objectives: To evaluate the prognostic value of an integrated model consisting of tumour response to induction chemotherapy (IC) and gross tumour volume (GTV) after IC in nasopharyngeal carcinoma (NPC) and elucidate optimal cumulative cisplatin dose (CCD) in concurrent chemoradiotherapy (CCRT) for different subgroups.

Design and methods: This retrospective study enrolled 896 patients with NPC diagnosed from 2010 to 2017 receiving IC plus radiotherapy. The primary endpoint was disease-free survival (DFS). Cut-off points for GTV were combined with IC response to develop an integrated model. Propensity score matching (PSM) was used to adjust for potential confounders. Survival outcomes and acute toxicity were compared between the different CCD groups.

Results: Unsatisfactory IC response and large GTV after IC were correlated with poor survival outcomes; the AUC increased to 0.668 when these factors were incorporated. The integrated model classified patients into three groups. After PSM, radiotherapy alone and CCRT demonstrated similar efficacy in the low-risk group (complete response (CR)/partial response (PR) and GTV <68 cm³ after IC). In the intermediate-risk group (CR/PR but GTV ⩾68 cm³), CCD of >200 mg/m² and 101-200 mg/m² increased the 5-year DFS rates (83.7% vs 81.1% vs 65.3%, p = 0.042). In the high-risk group (stable disease/progressive disease and any GTV), the use of different CCDs did not result in significantly different survival outcomes (p = 0.793). Additionally, high CCD was significantly associated with increased incidence of grade 1-4 acute toxicity.

Conclusion: The integrated model incorporating IC response and GTV after IC demonstrates satisfactory value in risk stratification and the potential to guide individualised decision-making in CCD selection. Balancing toxicity and efficacy, RT alone seems to be the optimal treatment for patients in low-risk groups and 200 mg/m² might be the optimal dose for intermediate-risk groups. Moreover, increasing CCD does not benefit patients in high-risk groups, and treatment options for these patients require further consideration.

The assessment of response to therapy in prostate cancer (PCa) patients is an ongoing, open issue. Prostate-specific antigen has limitations, especially in advanced metastatic PCa, which often displays intratumor variability in terms of response to therapy. Conventional imaging (i.e. computerized tomography and bone scan) is of limited use for its low sensitivity and specificity. Positron-emission tomography (PET) with prostate-specific membrane antigen (PSMA) demonstrated higher sensitivity and specificity, and novel PSMA-based criteria have been recently proposed for treatment response, with promising results in different scenarios, from chemotherapy to radioligand therapy. PSMA-based criteria have been found to outperform the current RECIST 1.1 and Prostate Cancer Working Group 3 frameworks in describing the behavior of PCa, precisely assessing tumor phenotypes through molecular-imaging-derived parameters. This review critically explores the current evidence about the role of PSMA PET/computed tomography in the assessment of treatment response.

Background: Many studies show that camrelizumab combination therapy can significantly improve progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC). However, the time of camrelizumab to market is short, and there is no systematic evaluation of camrelizumab-based comprehensive treatment of NSCLC.

Objectives: To systematically evaluate the efficacy and safety of camrelizumab in comprehensively treating NSCLC.

Design: A systematic review and meta-analysis.

Data sources and methods: Databases, including PubMed, Web of Science, Embase, and Cochrane, were searched by computer before August 2023 based on Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and reports on the efficacy and safety of camrelizumab-based treatment for NSCLC were collected, and RevMan 5.4 software was employed for meta-analysis finally.

Results: Totally, 5 RCTs, 2 cohort studies, and 12 single-arm studies were included. The meta-analysis results revealed that, compared with the treatment without camrelizumab, the camrelizumab-based combination treatment considerably extended the OS (hazard ratio (HR) = 0.60, 95% confidence interval (CI): (0.44-0.82), p < 0.01), PFS (HR = 0.42, 95% CI: (0.28-0.63), p < 0.01), and event-free survival (EFS) (HR = 0.55, 95% CI: (0.44-0.68), p < 0.01). The median objective response rate in single-arm studies was 41% (95% CI: 28%-53%), and the disease control rate was 84% (95% CI: 78%-89%). Furthermore, in terms of the occurrence of grades 3-5 adverse events, the incidence of neutropenia was lower in the camrelizumab combination group than in the control group, while the incidence of leukopenia and rash was higher than in the combination group, and no significant difference was revealed in the incidence of other adverse events. Among single-arm studies, the incidence of grades 3-5 adverse events did not exceed 10%.

Conclusion: Treatment combined with camrelizumab can effectively prolong OS, PFS, and EFS in NSCLC patients with good safety, camrelizumab combined with chemotherapy is an effective treatment option for NSCLC patients.