BMC Cancer最新文献

Purpose: The impact of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on muscle mass in individuals with advanced lung cancer has yet to be fully delineated. This study aimed to examine the dynamics of skeletal muscle mass during EGFR-TKIs targeted therapy, elucidate its clinical relevance, and explore the potential mechanisms.

Methods: We retrospectively recruited 104 patients with EGFR-mutant advanced lung adenocarcinoma who received icotinib or afatinib as first-line treatment. Skeletal muscle changes were assessed by abdominal CT obtained before and during treatment with EGFR-TKIs. The mean interval (± SD) between two CT scans was 109 days (± 16 days). Targeted panel sequencing of tumor tissue was used to detect genetic alterations. Functional enrichment analysis of genes interacting with EGFR-TKIs and muscle loss was performed to elucidate the potential toxicological mechanisms.

Results: A total of 42 (40.4%) patients experienced muscle loss during targeted therapy. Genetic analysis indicated muscle loss group had a higher proportion of MDM2 amplification and PIK3CA alterations (p = 0.011 & p = 0.045, respectively).Patients with baseline low muscle density and experienced ≥ Grade 2 diarrhea had higher rate of muscle loss (p = 0.005 & p < 0.001, respectively). Multivariate analysis revealed that muscle loss was independently associated with shorter PFS (hazard ratio [HR] 1.86, 95% confidence interval [CI]: 1.09 ∼ 3.18; p = 0.023). Besides, we found genes associated with icotinib, afatinib and muscle loss were significantly enriched in MAPK signaling pathway and calcium signaling pathway.

Conclusions: This study highlights the high prevalence and detrimental impact of muscle loss during EGFR-TKIs treatment.

Introduction: Obese patients with penile cancer may have more advanced disease. This study evaluated the association of obesity with penile cancer and the risk of lymph node metastases in patients who underwent inguinal lymphadenectomy.

Methods: We retrospectively reviewed the charts of 197 penile cancer (PC) patients from January 2000 to December 2011. Seventy underwent inguinal lymphadenectomy. For this subgroup, chi-square analysis evaluated the correlations of sociodemographic, clinical, and pathological variables with the presence of positive inguinal lymph nodes. Patients were divided into normal weight, overweight, and obese categories according to body mass index (BMI). The mean numbers of positive and resected lymph nodes were compared for each BMI category.

Results: The percentage of overweight men in the Brazilian population and among patients with PC was 52.6% and 42.8%, respectively. For patients who underwent lymphadenectomy, the mean BMIs were 25.9 ± 6. Most patients were white, married, had a lower education level, and had no history of smoking. Partial penectomy was the most frequently performed surgery; lymphovascular invasion occurred in 45.7%, and lymph node metastasis occurred in 52.9% of cases. The mean numbers of resected and positive lymph nodes for normal weight, overweight, and obesity were 21.1 and 2.2, 23.3 and 2.2, and 16.8 and 1.5, respectively.

Conclusion: Overweight and obesity were less frequently seen in patients with PC than in the Brazilian population. BMI was not a risk factor for developing lymph node metastasis; the only predictive factor for lymph node metastasis was the presence of lymphovascular invasion.

Background: The association between the oral pathogen Porphyromonas gingivalis (PG) and the gut microbiota in colorectal cancer (CRC) patients has been explored with inconsistent results. This study aims to systematically assess this potential association.

Materials and methods: A systematic review was conducted across three databases (Pubmed, Embase and Web of Science) from inception up to January 2023 and updated until November 2024. Inclusion criteria were observational studies examining PG in the microbiota of adults with CRC compared to healthy controls. Exclusion criteria were studies without control group of healthy individuals, other designs or without full-text access. Two reviewers independently selected and extracted data following a pre-registered protocol. Disagreements were resolved by consensus or with a third reviewer. Risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale (NOS). Results were summarized with a flow diagram, tables, and narrative descriptions. Meta-analysis was not feasible, so Fisher's method for combining p-values and the sign test were used as alternative integration methods.

Results: Finally, 18 studies, with 23 analysis units were included, providing a total sample of 4,373 participants (48.0% cases and 52.0%controls), 38.2% men and 61.8% women, with a similar distribution among cases and controls. The mean (SD) age of cases was 63.3 (4.382) years old and 57.0 (7.753) years for controls. Most of the studies analyzed the presence of PG in feces (70.0%) collected before colonoscopy (55.0%) and were classified with good quality (70.0%) in the RoB assessment. Results suggested an effect (Fisher's test, p = .000006) with some evidence towards a positive association of PG in CRC patients compared to healthy controls (Sign test, p = .039).

Conclusions: Results of the systematic review suggest that PG is associated with the microbiota of CRC patients. Lack of information to calculate the effect size prevented the performance of a meta-analysis. Future research should aim for standardized protocols and statistical approaches.

Funding: No funding was received for this work.

Systematic review registration: The research protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 2023 (registration number: CRD42023399382).

Background: Pemetrexed is a key treatment for non-small-cell lung cancer (NSCLC), and its usage is increasing. However, owing to treatment-related fatality in a patient with severe renal impairment observed during an initial clinical trial, such patients were excluded from further studies. Consequently, data on the safety and efficacy of pemetrexed in these patients are limited. This study aimed to assess the use of pemetrexed in this patient group in a clinical setting.

Methods: We conducted a retrospective analysis of patients with lung cancer treated with pemetrexed at Kyoto University Hospital from April 2008 to April 2023. The patients were categorized into two groups: those who received pemetrexed with platinum derivatives (n = 349) and those who received pemetrexed alone (n = 142). Both groups were further divided into creatinine clearance (CCr) > 45 and ≤ 45 mL/min subgroups, and safety and efficacy were compared between the subgroups. The correlation between renal impairment and adverse events was evaluated through chi-square test. Univariate and logistic regression analyses were used to identify the independent risk factors for severe adverse events (SAEs) related to renal impairment. We also analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test.

Results: A significant increase in the incidence of grade 3 or higher anemia was observed in the CCr ≤ 45 mL/min subgroups of both the platinum-concomitant and pemetrexed-alone groups (p = 0.03 and p < 0.01, respectively). No significant differences were observed in other SAEs. Multivariate analysis showed that baseline hemoglobin levels were an independent predictor of grade 3 or higher anemia across both treatment groups, alongside a baseline CCr ≤ 45 mL/min in the pemetrexed-alone group. No significant differences were observed in the overall response rate, PFS, or OS between the CCr > 45 and CCr ≤ 45 mL/min subgroups in either treatment group.

Conclusions: Although severe anemia was more common in patients with renal impairment, the efficacy of treatment did not differ, indicating that pemetrexed remains a viable treatment option for this population with proper management.

Symptom severity and complexity have considerable impact on a patient's cancer care journey. This study describes symptom scores of radiotherapy patients across their radiotherapy care trajectory and factors associated with symptom complexity. Patients who received radiotherapy at a single tertiary cancer center, who also completed at least one symptom-reporting questionnaire, the Edmonton Symptom Assessment Scale- Revised (ESAS-r) between October 1, 2019 and April 1, 2020 were included in this retrospective analysis. Symptom assessment time points were pre-treatment, start and end of radiation treatment and post-treatment follow-up. Mean ESAS-r scores for individual symptoms were descriptively analyzed by assessment timing and tumour group. We calculated a symptom complexity score for each ESAS-r measurement, using a validated algorithm, and assigned overall symptom complexity as low, moderate or severe. We modelled the association between assessment timing, and tumor group, with symptom complexity using Generalized Estimating Equations (GEE). The study cohort consisted of 1,632 patients who completed 2,519 ESAS-r questionnaires. Patients with lung and H&N cancers reported higher mean symptom scores compared to other tumour groups. Patients at the start of treatment had significantly lower odds of having a more severe symptom complexity, compared with patients pre-treatment (OR = 0.77, 95% CI = 0.64-0.93). Patients with H&N and lung cancer and patients prior to starting radiation may benefit most from increased symptom support and management.

Background: There have been previously reported associations between the gut microbiota, immune cells, and colorectal cancer; however, the specific mechanisms underlying these relationships remain largely unexplored and require further research. Therefore, in this study, we aimed to unravel the interactions between the gut microbiota, immune cells, and colorectal cancer.

Methods: The analysis used genome-wide association study (GWAS) data encompassing 207 microbial taxa and 205 functional pathways and data on 731 immune cell phenotypes. Colorectal cancer data on 6 581 cases and 463 421 controls were sourced from the Integrative Epidemiology Unit Open GWAS Project. Univariate inverse-variance weighted Mendelian randomization analysis was used to identify gut microbial taxa associated with colorectal cancer. Mediation analysis was used to identify the mediating role of specific immune cells in the link between gut bacteria and colorectal cancer.

Results: Univariate inverse-variance weighted Mendelian randomization analysis revealed that several microbial taxa from the Actinobacteria and Firmicutes phyla were significantly associated with colorectal cancer. Coriobacteriaceae (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.72-0.97), Sutterellaceae (OR: 0.88, 95% CI: 0.78-0.99), Eggerthella (OR: 0.91, 95% CI: 0.84-0.99), Coriobacteriales (OR: 0.84, 95% CI: 0.72-0.97), Collinsella aerofaciens (OR: 0.85, 95% CI: 0.74-0.99), and Ruminococcus bromii (OR: 0.91, 95% CI: 0.83-0.99) were negatively associated with colorectal cancer, whereas Lactobacillales (OR: 1.11, 95% CI: 1.03-1.20), Veillonella (OR: 1.08, 95% CI: 1.01-1.15), and Bifidobacterium bifidum (OR: 1.05, 95% CI: 1.00-1.09) were positively associated with colorectal cancer. Mediation analysis revealed that in the causal pathway from Collinsella aerofaciens to colorectal cancer, CD127 on CD28⁺ CD45RA^- CD8br and human leukocyte antigen (HLA) DR on CD33^- HLA DR⁺, mediated 11.30% and - 6.52% of the effect, respectively, and that in the causal pathway from Ruminococcus bromii to colorectal cancer, IgD^- CD38dim %lymphocyte mediated - 14.80% of the effect.

Conclusions: These results highlight the potential of gut microbiota and immune cell phenotypes as novel treatment strategies for colorectal cancer.

Background: Female breast cancer (FBC) is a well-known public health issue worldwide. However, male breast cancer (MBC), though rare, may be overlooked by both public health authorities and clinicians. Both diseases exhibit similarities, and understanding their behavior over time is crucial to grasping their annual impact on many citizens. Furthermore, analyzing if medical personnel are well allocated and influence disease outcomes in a limited setting such as the Public Health System (PHS) is of utmost importance.

Methods: This ecological study utilized secondary data from 2008 to 2020 to explore the relationship between the number of doctors per 100,000 inhabitants and mortality from FBC and MBC in Brazil. All data were sourced from Brazil's PHS. Mortality rates were analyzed by age and standardized according to the World Health Organization's population figures. The number of physicians was calculated per 100,000 inhabitants. A linear regression analysis was performed using a stepwise selection/backward elimination approach.

Results: Between 2008 and 2020, Brazil recorded 195,969 breast cancer-related deaths among adults, including 2,220 male victims. The majority of these deaths occurred in the Southeast region among patients older than 50 years. Although both MBC and FBC demonstrated increasing trends over the study period, no correlation was found between the number of physicians and mortality rates for MBC. Conversely, an increase in primary care physicians over the years was positively correlated with mortality rates for FBC (p < 0.05). In addition, the number of physicians in the PHS (β = -0.163; 95% CI: -0.240 to -0.085; p = 0.002), oncologists (β = -0.507; 95% CI: -0.881 to -0.134; p = 0.015), and radiotherapists (β = -6.402; 95% CI: -12.357 to -0.446; p = 0.039) all showed an inverse association with FBC mortality.

Conclusions: The increasing trends in FBC and MBC underscore the need for urgent monitoring. Lower FBC mortality correlates with higher numbers of physicians and specialized care, highlighting the critical role of healthcare workforce capacity and the strategic allocation of specialized personnel in enhancing patient outcomes.

Background: Survival prediction accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in extra-nodal natural killer/T-cell lymphoma (ENKTL) is controversial. This study aimed to evaluate the prognostic value of ¹⁸F-FDG PET/CT parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), and to develop a new prognostic model for ENKTL.

Methods: We analyzed 390 ENKTL patients with comprehensive clinical and survival data. All patients received asparaginase-based chemotherapy with or without radiotherapy, or radiotherapy alone. Metabolic tumor volume (MTV) was calculated using a 41% SUVmax threshold, and TLG was computed as MTV multiplied by the average SUV. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves and compared with log-rank tests. Optimal cut-off values were determined using the Youden' index. Cox regression analysis identified significant prognostic factors. A nomogram predicting 1-, 3-, and 5-year survival was developed and validated using the C-index and calibration curves. Statistical significance was set at p < 0.05.

Results: Of the 390 patients, 262 (67.2%) were included in the training set and 128 (32.8%) in the validation set. ¹⁸F-FDG PET-CT parameters with cutoff values of SUVmax > 12.8, TMTV > 16.4 cm³, and TLG > 137.0, were significantly associated with poorer OS (p = 0.009) and PFS (p = 0.003). Multivariable Cox regression identified the following as independent predictors of worse OS: age > 60 years (HR = 1.923, 95% CI: 1.001-3.693), presence of B symptoms (HR = 1.861, 1.132-3.059), ECOG score ≥ 2 (HR = 2.076, 1.165-3.699), extranodal involvement ≥ 2 sites (HR = 2.349, 1.384-3.988), bone marrow involvement (HR = 4.884, 2.137-11.163), SUVmax > 12.8 (HR = 2.226, 1.260-3.930), and TMTV > 16.4 cm³ (HR = 1.854, 1.093-3.147). The new prognostic model achieved a C-index of 0.772 for OS and 0.750 for PFS in the training set, and 0.777 for OS and 0.696 for PFS in the validation set. Area under the curve (AUC) values for 1-, 3-, and 5-year OS were 0.841, 0.804, and 0.767 in the training set, and 0.718, 0.786, and 0.893 in the validation set. Risk stratification divided patients into four groups with significant differences in survival (p < 0.001).

Conclusion: SUVmax, TMTV, and TLG are independent prognostic factors in ENKTL. Our new model, which integrates ¹⁸F-FDG PET/CT metrics with clinical data, enhances survival prediction and may support personalized treatment strategies, though further validation is required.