Oncology最新文献

Introduction: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival.

Methods: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade.

Results: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS.

Conclusion: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

In this study, clinical trials were generalized, summarized, and meta-analyzed to evaluate correlations between artificial sweeteners (ASs) and colorectal cancer (CRC). PubMed, Web of Science, Embase (Ovid platform), MEDLINE, and the Cochrane Library databases were searched from inception until July 24, 2023. The association between AS exposure and CRC incidence was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). STATA software (version 12.0) was used to perform the meta-analysis. Ten studies (three case-control studies and seven cohort studies) involving 711,537 participants were identified. Results showed that the intake of ASs reduced the incidence of CRC (OR = 0.93, 95% CI = [0.87-0.99]) and was not significantly associated with mortality (OR = 0.93, 95% CI = [0.83-1.05]). Subgroup analyses showed that low doses of ASs were associated with lower CRC incidence (OR = 0.90, 95% CI = [0.83-0.99]), and medium/high doses were not associated with CRC incidence (OR = 1.11, 95% CI = [0.93-1.33]; OR = 0.89, 95% CI = [0.79-1.00], respectively). Moreover, low, medium, and high exposures were not associated with an increased risk of mortality due to CRC (OR = 0.95, 95% CI = [0.80-1.14]; OR = 0.99, 95% CI = [0.88-1.11]; OR = 0.93, 95% CI = [0.71-1.21], respectively). The results of our meta-analysis showed that a low intake of ASs may be associated with a lower risk of CRC.

Background: Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies.

Methods: We searched all the relevant studies in PubMed, Embase, and Cochrane Library databases. We also reviewed abstracts of relevant conferences to prevent omissions. The meta-analysis was performed using Stata version 16.0.

Results: CRT combined with immunotherapy can improve progression-free survival (PFS) (hazard rate [HR]: 0.60, 95% confidence interval [CI, 0.55-0.60) and overall survival (OS) (HR: 0.59, 95% CI, 0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5-52.7%) and 71.3% (95% CI, 67.3-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95% CI, 51.0-70.3%) and 77.4% (95% CI, 73.2-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95% CI, 31.3-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95% CI, 31.9-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95% CI, 5.0-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95% CI, 3.1-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95% CI, 2.9-7.3%).

Conclusions: Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Background: Total neoadjuvant therapy (TNT) is a new strategy combining neoadjuvant therapy and chemotherapy to enhance tumor shrinkage and systemic control. Its effectiveness remains debated.

Objectives: This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess TNTs impact and provide high-quality evidence for rectal cancer treatment decisions.

Method: We searched China National Knowledge Infrastructure, VIP Database, Wanfang Database, China biomedical literature database, PubMed database, Embase database, and The Cochrane Library for RCTs comparing TNT with neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. The included trials were screened and assessed for quality based on inclusion and exclusion criteria, and meta-analysis was performed using RevMan 5.3 software.

Results: A total of 11 RCTs reported in 14 articles, with 1,624 cases in the TNT group and 1,541 cases in the CRT group. The results of the meta-analysis showed that compared with the CRT group, the TNT group had a higher pathological complete response rate (risk ratio [RR] = 1.65, 95% confidence interval [CI]: [1.40, 1.94], p < 0.00001), higher T0 downstaging rate (RR = 1.51, 95% CI: [1.29, 1.77], p < 0.00001), higher 3-year overall survival (hazard ratio [HR] = 0.81, 95% CI: [0.67, 0.98], p = 0.03), and higher 3-year disease-free survival (HR = 0.82, 95% CI: [0.70, 0.95], p = 0.008). However, there was no statistically significant difference between the two groups in terms of R0 resection rate (RR = 1.02, 95% CI: [0.99, 1.05], p = 0.14), sphincter preservation rate (RR = 0.94, 95% CI: [0.88, 1.01], p = 0.12), anastomotic leakage rate (RR = 1.42, 95% CI: [0.85, 2.38], p = 0.18), and grade 3 or higher adverse events (RR = 1.21, 95% CI: [0.95, 1.54], p = 0.13).

Conclusions: In the treatment of locally advanced rectal cancer, TNT offers greater survival benefits compared to neoadjuvant CRT and does not significantly increase the incidence of adverse events. However, further data and studies with long-term outcomes are still required.

Background: Viral infections remain a significant problem for patients with chronic myeloid leukemia (CML) who undergo stem cell transplants (SCTs). These infections often result from the reactivation of latent viruses. However, our understanding of the risk of viral reactivation in CML patients who have not undergone SCT is limited, and there is a scarcity of data on this topic. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML as it is highly successful and has transformed the prognosis of patients with CML. However, TKI may be associated with an increased risk of infections.

Summary: We have performed a literature search for publications related to viral infections and their reactivations in patients with CML using PubMed, Scopus, and Google Scholar for the period 2001-2022. The population consisted of patients over 18 years old with a diagnosis of CML and no history of bone marrow transplantation. In an analysis of 41 patients, with 25 males and 16 females, M:F ratio of 1.56:1, and a median age of 50. Age ranged from 22 to 79 years. Most patients with reported viral infections or reactivations were in the chronic phase (CP) of CML, with 22 patients (76%) in the CP, 6 patients (21%) in the accelerated phase, and 1 patient (3%) in the blast phase. Most cases with reported outcomes responded to treatment for CML; only one had refractory disease and 8 cases (32%) had major molecular response. Imatinib was the most used TKI in 31 patients (77%). The most reported viral reactivations were herpes zoster in 17 cases (41%), followed by hepatitis B reactivation in 15 cases (37%).

Key messages: This review sheds light on the importance of having a hepatitis B serology checked before starting TKI therapy and close monitoring for viral infections and reactivations in patients with CML.

Introduction: Cancers in general, and specifically lung cancer, continue to have low patient survival rates when the patient is at an advanced stage when diagnosed. It appears that the local environment, especially fibroblasts and their signaling molecules, tends to induce metastasis, increase cancer cell resistance to treatment, and aid in tumor growth rates. Since 3-D models quickly become too complex and/or expensive and therefore rarely leave the lab they are developed in, it is interesting to develop a 2-D model that more closely mimics clustered tumor formation and bulk interaction with a surrounding fibroblast environment.

Methods: In the present study, we utilize an off-the-shelf stereolithography 3-D printer, standard use well plates, magnets, and metallic tubes to create a customizable 2-D co-culture system capable of being analyzed quantitatively with staining and qualitatively with standard fluorescent/brightfield microscopy to determine cancer-fibroblast interactions while also being able to test chemotherapeutic drugs in a high-throughput manner with standard 96-well plates.

Results: Comparisons from monoculture and co-culture growth rates show that the presence of fibroblasts allows for significantly increased growth rates for H460 cancer. Additionally, the viability of cancer cells can be quantified with simple cell staining methods, and morphology and cell-cell interactions can be observed and studied.

Discussion: The high throughput model demonstrates that boundary condition changes can be observed between cancer cells and fibroblasts based upon the different chemotherapeutics that have been administered.

Introduction: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC).

Methods: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed.

Results: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D' = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30-0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15-0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29-0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10-5).

Conclusion: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.

Introduction: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC.

Methods: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 GC cases. We also performed functional analysis using GC-derived cell lines.

Result: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (p < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells.

Conclusion: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype.

Introduction: It is unclear whether a lower lobe origin is a risk factor for early recurrence of non-small cell lung cancer (NSCLC) in patients who underwent pulmonary resection.

Methods: The risk factors for early recurrence, defined as recurrence occurring within 1 year after surgery, were analyzed in 476 patients with NSCLC who underwent pulmonary resection without wedge resection.

Results: The proportion of men, Brinkman's index, carcinoembryonic antigen levels, and the maximum standardized uptake value (SUVmax) were significantly higher in patients with early recurrence than in those without early recurrence. Furthermore, the rates of lower lobe origin, extended resection beyond lobectomy, lymphatic invasion, vascular invasion, and advanced-stage disease were significantly higher in patients with early recurrence. Age (odds ratio [OR] = 4.46, p < 0.01), SUVmax (OR = 5.78, p = 0.02), a lower lobe origin (OR = 3.06, p = 0.01), and pathological stage (OR = 3.34, p = 0.01) were risk factors for early recurrence in multivariate analysis. Furthermore, only early recurrence (OR = 3.34, p = 0.01) was a risk factor for overall survival in multivariate analysis, and overall survival outcomes and prognoses significantly differed between patients with and without early recurrence (p < 0.01).

Conclusion: Age, SUVmax, a lower lobe origin, and pathological stage are risk factors for early recurrence. These results suggest that for patients with NSCLC who underwent pulmonary resection, SUVmax and a lower lobe origin are important for deciding the indication for adjuvant chemotherapy in addition to pathological stage.