Journal of Cancer Research and Clinical Oncology最新文献

Aims: We aimed to describe treatment of lung cancer patients in Germany based on health claims data, focusing particularly on differences by age.

Materials and methods: Using the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population) we identified lung cancer patients diagnosed in 2015-2018 based on a previously developed algorithm and followed them until death, end of continuous insurance or end of 2020. We described initial treatment patterns after diagnosis and survival, stratified among others by age.

Results: We included 42,629 incident lung cancer patients (58% male). Surgery within three months after diagnosis was performed in 36%, 31%, 29% and 18% of patients aged < 50, 50-69, 70-79 and ≥ 80, respectively. Among patients without surgery, systemic therapy was administered in 77%, 72%, 54% and 25% of patients aged < 50, 50-69, 70-79 and ≥ 80, respectively. Monoclonal antibodies were administered in 15-30% of patients across age groups, and 4% to 15% received protein kinase inhibitors. Overall, 21% of patients remained untreated. In the age groups < 50, 50-69, 70-79 and ≥ 80, this proportions was 9%, 12%, 22% and 48%, respectively.

Conclusion: In conclusion, our study provides a comprehensive overview of the therapy of lung cancer patients in Germany and quantitatively demonstrates the considerable differences between age groups. In terms of clinical cancer registration, the results are useful to estimate the completeness of data for the different types of treatment.

Colorectal cancer (CRC) exhibits a substantial morbidity and mortality rate, with its aetiology and pathogenesis remain elusive. It holds significant importance within the tumour microenvironment (TME) and exerts a crucial regulatory influence on tumorigenesis, progression, and metastasis. TAMs possess the capability to foster CRC pathogenesis, proliferation, invasion, and metastasis, as well as angiogenesis, immune evasion, and tumour resistance. Furthermore, TAMs can mediate the prognosis of CRC. In this paper, we review the mechanisms by which natural compounds target TAMs to exert anti-CRC effects from the perspective of the promotional effects of TAMs on CRC, mainly regulating the polarization of TAMs, reducing the infiltration and recruitment of TAMs, enhancing the phagocytosis of macrophages, and regulating the signalling pathways and cytokines, and discuss the potential value and therapeutic strategies of natural compounds-targeting the TAMs pathway in CRC clinical treatment.

Niemann-Pick Type C1 (NPC1) plays a significant role in the development of liver diseases and liver cancer. Our objective was to investigate the involvement of NPC1 in regulating liver cancer development. We observed that high levels of NPC1 expression in tumor tissues from patients with liver cancer were associated with a poor prognosis. Through in vitro experiments, we found that inhibiting NPC1 expression reduced the proliferation, invasion, and migration of liver cancer cells, while also inducing apoptosis in these cells. Additionally, the inhibition of NPC1 led to decreased activation of Wnt/β-catenin signaling. In vivo studies further supported our findings by demonstrating that the suppression of liver cancer cell growth was effectively achieved through the inhibition of NPC1. Overall, our results strongly indicate that the inhibition of NPC1 suppresses liver cancer cell proliferation. Targeting NPC1 is a promising potential therapeutic strategy for liver cancer.

Purpose: Cancer outcome is dependent on multiple predetermining factors including cancer, type of cancer and its related factors. This study aims to investigate the association between COVID-19 & cancer/cancer types, focusing on risk of in-hospital mortality within 30 days of hospitalization of COVID-19 patients with cancer.

Materials and methods: We did a registry (National Clinical Registry for COVID-19) based retrospective observational study including 51,544 patients, of whom 976 were patients with cancer, admitted with COVID-19 between August 2020 and August 2023 across 42 hospitals of India.

Results: Out of 51,544 patients, 976 (1.8%) had cancer. Hematological malignancies made up 15.06% (147 cases), while solid cancers accounted for 29.5% (288 cases), with genitourinary (18.4%, 80 cases), gastrointestinal (15.2%, 49 cases), and lung cancers (10.1%, 34 cases) being the most common. Solid cancers had the highest in-hospital mortality rate at 25%. Survival analysis showed that cancer-related hazards were highest at admission but decreased to levels comparable with other morbidities within nine to ten days. For each cancer type, the hazard was significantly elevated compared to that of the cancer-free (Other Comorbidities and No Comorbiditiy) groups during the initial period of hospitalization. The use of Remdesivir, steroids, and anticoagulants reduced mortality risk, and prior COVID-19 vaccination was protective against mortality across all cancer types.

Conclusion: This study shows that both cancer in general and specific cancer types significantly increase the risk of severe outcomes among SARS-CoV-2-infected patients, especially immediately after hospitalization. The findings highlight the need for close monitoring and personalized interventions for COVID-19 patients with cancer for at least 10 days post-hospitalization, with a more specific high-risk period ranging from 7 to 18 days depending on the type of cancer.

Purpose: Skeletal muscle quality assessment can be performed by cross-sectional imaging. Skeletal muscle density (SMD) identified to be of prognostic relevance of several clinically outcomes in patients with hematological diseases. The purpose of the present study was to establish the effect of SMD on overall survival (OS) and progression-free survival (PFS) in patients with multiple myeloma (MM).

Methods: All patients with MM were retrospectively analyzed between 2009 and 2019. 127 patients were included into the analysis. Whole-body computed tomography (CT) was used to calculate skeletal muscle index (SMI), SMD, albumin-gauge score and intramuscular adipose tissue content (IMAC).

Results: Overall, 28 patients (22.0%) of the patient sample died. In the discrimination analysis muscle density was higher in non-survivors compared to survivors (mean 30.8 ± 12.5 versus 24.1 ± 15.8, p = 0.03) and IMAC was lower in non-survivors (- 0.66 ± 1.8 versus - 0.25 ± 0.21, p = 0.01). These differences, however, were not demonstrated in the logistic regression analysis, which could not show prognostic relevance for the investigated muscle density parameters on PFS or OS.

Conclusion: CT-defined muscle density parameters have no prognostic relevance on survival in patients with MM undergoing autologous stem cell therapy, which was demonstrated in a comprehensive analysis. These results corroborate previous smaller studies that body composition might have a limited role in this tumor entity.

Immune checkpoint inhibitors (ICIs), particularly anti-programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) antibodies, have led to significant progress in lung cancer treatment. However, only a minority of patients have responses to these therapies. Detecting peripheral blood of circulating tumor DNA (ctDNA) allows minimally invasive diagnosis, characterization, and monitoring of lung cancer. ctDNA has potential to be a prognostic biomarker and a predictor of the response to ICI therapy since it can indicate the genomic status and tumor burden. Recent studies on lung cancer have shown that pretreatment ctDNA analysis can detect residual proliferative disease in the adjuvant immunotherapy setting and evaluate tumor burden in patients with metastatic disease. Early ctDNA dynamics can not only predict the clinical outcome of ICI therapy but also help distinguish between pseudoprogression and real progression. Furthermore, in addition to quantitative assessment, ctDNA can also detect genetic predictors of response to ICI therapy. However, barriers still exist in the application of ctDNA analysis in clinical lung cancer treatment. The predictive value of ctDNA in lung cancer immunotherapy requires further identification and resolution of these challenges. This review aims to summarize the existing data of ctDNA analysis in patients receiving immunotherapy for lung cancer, understand the limitations of clinical treatment, and discuss future research directions.

Purpose: To investigate whether neoadjuvant chemotherapy (NACT) increases the incidence of postoperative delirium (POD) in patients with gynecological tumors undergoing radical hysterectomy.

Methods: This study included 60 patients in the neoadjuvant chemotherapy exposure group and 60 in the non-exposure group. Preoperative cognitive function, the incidence of POD and other physiological parameters were assessed on preoperative day 1 (POD-1), postoperative day 1 (POD1), postoperative day 2 (POD2), and postoperative day 3 (POD3). Additionally, preoperative olfactory function was evaluated using an olfactory detection kit on POD-1. The primary outcome was the incidence of POD within three days after surgery.

Results: The incidence of POD was 28.33% in the exposed group and 8.33% in the non-exposed group (P = 0.005). Compared to the non-exposed group, the exposed group had a higher rate of cognitive dysfunction (33.33% vs 13.33%; P = 0.010), and a higher rate of olfactory dysfunction (OD) (25.00% vs 10.00%; P = 0.031). A restricted cubic spline analysis revealed a non-linear relationship between olfactory test scores and Montreal Cognitive Assessment Scale (MoCA) scores (P for overall < 0.001, P for nonlinear = 0.001). Logistic regression identified NACT, mild and moderate cognitive dysfunction, OD, and depression as independent risk factors for POD, with all factors showing significant associations (P < 0.05). The area under the curve (AUC) of OD for predicting POD was 0.783 (95%CI 0.656-0.909).

Conclusions: This single-blind observational study suggests that NACT increases the incidence of POD in patients with gynecological tumors undergoing radical hysterectomy. Moreover, the results indicate that preoperative OD may reflect preoperative cognitive dysfunction, and have predictive value for the incidence of POD.

Purpose: Small cell lung cancer (SCLC) has an extremely poor prognosis. Despite high initial response rates to chemotherapy and modest survival improvements with the addition of immune checkpoint inhibitors (ICI), almost all patients experience relapse and fatal outcomes. Recent genomic insights uncovered extensive molecular heterogeneity in addition to the almost uniform loss of RB1 and TRP53. Additionally, defective DNA mismatch repair (MMR) has recently been described in some SCLC cases. Here, we generated a novel SCLC mouse model capturing MMR deficiency and assessed immunotherapy responses.

Methods: We developed an MMR-deficient genetically engineered mouse model (GEMM) of SCLC by introducing a conditional Msh2 gene, crucial for maintaining MMR integrity, into the standard Rb1^fl/fl;Trp53^fl/fl (RP) model. Genomic characteristics and preclinical therapy responses were evaluated by focusing on overall survival and whole exome sequencing (WES) analyses.

Results: MMR-defective SCLC tumors (Rb1^fl/fl;Trp53^fl/fl;Msh2^fl/fl (RPM)) developed later than tumors in MMR-proficient mice. However, the time from tumor manifestation to death of the affected animals was substantially shortened (median survival 55 days in RP vs. 46.5 days in RPM), indicating increased aggressiveness of MMR-defective tumors. RPM tumors exhibited MMR deficiency, high tumor mutational burden (TMB), and an elevated load of candidate neoantigens, compared to RP lesions (p = 0.0106), suggesting increased immunogenicity. Importantly, the overall survival of RPM animals was significantly improved when exposed to ICI.

Conclusion: We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.

Introduction: The human gut microbiota influence critical functions including the metabolism of nutrients, xenobiotics, and drugs. Gut microbial β-glucuronidases (GUS) enzymes facilitate the removal of glucuronic acid from various compounds, potentially affecting anti-cancer drug efficacy and reactivating carcinogens. This review aims to comprehensively analyze and summarize studies on the role of gut microbial GUS in cancer and its interaction with anti-cancer treatments. Its goal is to collate and present insights that are directly relevant to patient care and treatment strategies in oncology.

Methods: This scoping review followed PRISMA-ScR guidelines and focused on primary research exploring the role of GUS within the gut microbiota related to cancer etiology and anti-cancer treatment. Comprehensive literature searches were conducted in PubMed, Embase, and Web of Science.

Results: GUS activity was only investigated in colorectal cancer (CRC), revealing increased fecal GUS activity, variations in the gut microbial composition, and GUS-contributing bacterial taxa in CRC patients versus controls. Irinotecan affects gastrointestinal (GI) health by increasing GUS expression and shifting gut microbial composition, particularly by enhancing the presence of GUS-producing bacteria, correlating with irinotecan-induced GI toxicities. GUS inhibitors (GUSi) can mitigate irinotecan's adverse effects, protecting the intestinal barrier and reducing diarrhea.

Conclusion: To our knowledge, this is the first review to comprehensively analyze and summarize studies on the critical role of gut microbial GUS in cancer and anti-cancer treatment, particularly irinotecan. It underscores the potential of GUSi to reduce side effects and enhance treatment efficacy, highlighting the urgent need for further research to integrate GUS targeting into future anti-cancer treatment strategies.