BMC Cancer最新文献

Background: Pancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study.

Patients and methods: A retrospective analysis of patients' records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included.

Results: The study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013).

Conclusion: Patients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt.

Purpose: Loddo et al. (Br J Cancer 100:959-70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the prognostic potential of specific cell-cycle phenotypes in sarcoma.

Methods: Tissue samples from 128 soft tissue sarcomas were stained for four cell cycle-specific markers: Mcm2, Geminin, Plk1, and H3S10ph. Only primary soft tissue tumors (liposarcoma, leiomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma) were included in the analysis. Any tumor coming from a recurrent or metastatic lesion were excluded from the analysis. Three cell-cycle phenotypes (I, II, III) were derived from marker expression patterns. Prognostic significance was evaluated in a subset of primary soft tissue sarcomas using Cox regression for survival analysis.

Results: Compared to phenotype I, the phenotype III tumors had a decreased 5-year overall survival (HR 6.81 [2.36-19.61]; p =  < 0.001), 5-year disease-free survival (HR 1.07 (1.02-1.18); p = 0.004), and 5-year metastasis-free survival (HR 4.34 [1.58-11.93]; p = 0.004). High expression of Plk1 was associated with decreased 5-year overall survival (HR: 4.04 CI [1.21-6.67; p = 0.02) and 5-year metastasis-free survival (HR: 2.91 CI [1.15-7.37]; p = 0.03). Geminin was also found to have a decreased 5-year overall survival (HR:2.84 CI [1.21-6.67]; p = 0.02). No statistical difference in prognostication were noted between phenotypes and the AJCC system.

Conclusions: We identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system.

Background: Although adequate physical activity has been shown to be beneficial in early breast cancer, evidence in metastatic breast cancer is sparse and contradictory, which could be related to distinct effects of physical activity on the different molecular cancer subtypes. Therefore, we here evaluated the effect of physical activity on progression-free and overall survival (PFS, OS) in metastatic breast cancer, specifically looking at molecular subtypes.

Methods: International Physical Activity Questionnaire (IPAQ) questionnaires, filled out by patients enrolled in the prospective PRAEGNANT registry (NCT02338167; n = 1,270) were used to calculate metabolic equivalent task (MET) minutes, which were subsequently categorized into low (n = 138), moderate (n = 995) or high IPAQ categories (n = 137). Cox regression analyses were used to evaluate the impact of IPAQ categories and its interaction with molecular subtypes on PFS and OS.

Results: Patient and tumor characteristics were equally distributed across IPAQ categories. HER2pos, HRpos and TNBC were present in 23.1%, 65.7% and 11.2% of patients, respectively. IPAQ scores did not have an impact on PFS and OS in addition to established prognostic factors, either overall or in particular molecular subtypes (PFS: p = 0.33 and OS: p = 0.08, likelihood ratio test). Exploratory analyses showed higher overall survival rates for high IPAQ categories compared to low/moderate IPAQ categories in luminal B-like breast cancer.

Conclusions: Self-reported physical activity using the IPAQ questionnaire did not significantly affect PFS or OS in patients suffering from metastatic breast cancer. Nevertheless, some hypothesis-generating differences between molecular subtypes could be observed, which may be interesting to evaluate further.

Objective: Testicular tumor (TT) is a uncommon disease posing serious health problem. There are differences in some aspects between adult and pediatric TT. The study was to compare their differences of clinical and histological characteristics through the analysis of the long-term experiences in TT patients from two institutions.

Materials and methods: The clinical data of hospitalized patients was collected and analyzed retrospectively from January 2014 to January 2024 at a pediatric and an adult institution, respectively. The data included composition, gender, age, initial presentation, tumor size, tumor markers, pathological diagnosis.

Results: A total of 195 hospitalized patients were included. There were 135 children and 60 adult with TT, respectively. Of these children, patients were aged from 1 month to 14 years, with a mean age of 2.32 years. More cases (37.04%) were diagnosed at age younger than 1 years. 69 cases were left-sided, 65 cases were right-side and only 1 case was bilateral. Pediatric TTs mainly included 82 prepubertal teratomas, 37 had prepubertal yolk sac tumors and 3 mixed malignant germ tumors. Testicular surgeries included testicular-sparing surgery (TSS) (n = 73), radical orchiectomy (n = 60), and testicular biopsy (n = 2). There were 24 patients receiving postoperative chemotherapy. Adult TTs mainly contained 17 seminomas, 10 prepubertal teratomas,7 postpubertal teratomas, 6 stromal tumors and 3 embryonal carcinomas. The average age was 34.08 years. There were 29 right-sided, 27 left-sided and 4 bilateral tumors. TSS (n = 26), radical orchiectomy (n = 33), and testicular biopsy (n = 1) were performed in these TT patients. Only 6 patients received postoperative chemotherapy. The most common symptom was a painless scrotal mass at initial diagnosis in both groups. In addition, we found that significant differences were explored between histological type and age, tumor size (P < 0.05). Yolk sac tumor and seminoma were the most common malignant TT in pediatric and adult population, respectively. After two year follow-up, two children with yolk sac tumor and 4 adults with seminoma died of their diseases.

Conclusions: The majority of pediatric cases were benign compared to adult. The most common type was prepubertal teratoma and yolk sac tumor. Pediatric TTs often occurred under the age of 1 year. Seminomas and prepubertal teratomas were commonly found in adult TTs, especially for young adult. We found that pediatric tumor type was associated with age and tumor size. TSS should be considered for benign TTs based on frozen biopsy findings in children.

Background: Non-small cell lung cancer (NSCLC) presents a significant challenge in the medical field due to its high incidence and resistance to chemotherapy. Chemoresistance in NSCLC diminishes treatment efficacy and contributes to poor patient outcomes. Matrine alkaloids have shown promise in reversing chemotherapy resistance in NSCLC by targeting DNA repair mechanisms.

Methods: Utilizing molecular dynamics simulations, we explored the interactions between Matrine alkaloids and DNA repair-related proteins to elucidate their impact on NSCLC cells. In vitro experiments involved treating A549/DDP cells with Matrine alkaloids to evaluate their sensitizing effects on lung cancer cells. Additionally, animal model experiments were conducted to validate the therapeutic potential of Matrine alkaloids in NSCLC treatment.

Results: Our findings demonstrate that Matrine alkaloids disrupt DNA damage repair processes in NSCLC cells, leading to increased sensitivity to chemotherapy. Molecular docking studies revealed the intricate mechanisms by which Matrine alkaloids interact with DNA repair proteins, impacting cell survival and proliferation. Both cell experiments and animal models confirmed the chemosensitizing effects of Matrine alkaloids in NSCLC treatment.

Conclusion: Matrine alkaloids offer a promising avenue for overcoming chemotherapy resistance in NSCLC by interfering with DNA repair pathways. This study lays a solid foundation for future clinical investigations into the potential of Matrine alkaloids as effective therapeutic agents for enhancing NSCLC treatment outcomes.

Background: Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumour. The aim of this study was to investigate the long-term prognosis and its relationship with treatment modalities.

Methods: From March 2014 to June 2024, a total of 234 patients with histologically confirmed hepatic EHE were treated or followed up regularly by our team. The patients' clinical data at the time of diagnosis and initial treatment modalities were retrospectively collected. Kaplan-Meier curves were constructed to determine overall survival (OS). To explore prognostic factors and treatment outcomes, univariable and multivariable Cox proportional hazard models were developed.

Results: A total of 228 patients were ultimately included. The median age of the cohort was 41 years. For all patients, the OS of 1-, 3- and 5-year were 96.2%, 87.9% and 84.9%, respectively. For patients who underwent liver transplantation (LT), the OS of 1- and 3-year were 62.5% and 25%, respectively. No difference was found in the OS between patients who received surgical therapy and those who did not (1-year: 100% vs. 96.9%; 3-year: 90.1% vs. 91.5%; 5-year: 87.2% vs. 88.2%; P = 0.891). In the multivariable analysis, age ≥ 60 years [HR (95% CI): 4.207 (1.266-13.973), P = 0.019], the size of the largest lesion > 10 cm [HR (95% CI): 12.140 (1.419-103.872), P = 0.023] and LT [HR (95% CI): 5.502 (1.343-22.536), P = 0.018] were poor prognostic factors.

Conclusions: Compared with nonsurgical therapy, surgical therapy has no advantage in terms of long-term survival. The role of LT in the management of hepatic EHE should be reevaluated. Age ≥ 60 years and the size of the largest lesion > 10 cm are poor prognostic factors.

Background: There is controversy regarding the optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC). We aimed to address this crucial issue through a frequentist network meta-analysis.

Methods: We conducted a literature database search for randomized controlled trials comparing the following treatment modalities before March 1st, 2023: surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and various combinations of these treatments. Summary data on overall survival (OS) and treatment-related deaths (trDeath) were analyzed using frequentist methods.

Results: Twenty-two randomized controlled trials (RCTs) with 3269 participants were included, covering 17 treatment regimens. In terms of overall survival, surgery followed by adjuvant targeted therapy (S-T), neoadjuvant targeted therapy followed by surgery and adjuvant targeted therapy (T-S-T), and neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy (C-S-C) were relatively more advantageous than other treatment regimens. Overall, S-T is the most likely treatment option to prolong OS, with a 59.8% likelihood, while immunotherapy plus chemotherapy followed by surgery and adjuvant chemotherapy (IC-S-C) demonstrates good safety.

Conclusion: S-T and T-S-T treatments have the greatest potential to be the optimal overall survival treatments for stage IIIA-N2 NSCLC patients with positive driver genes, demonstrating significant clinical application prospects. While for patients with negative driver genes, C-S-C treatments benefit the most. The protocol was registered in the Prospective Register of Systematic Reviews, PROSPERO (CRD42022372711).

Background: Neoadjuvant chemotherapy (NAC) for breast cancer enables pathological complete response (pCR) in patients initially diagnosed with axillary lymph node metastases, potentially obviating the need for axillary lymph node dissection (ALND). Current targeted axillary dissection (TAD) techniques, guided by traditional tissue markers placed prior to NAC, face challenges such as marker loss and high costs. Carbon nanoparticle suspension injection (CNSI) offers a stable and reliable alternative for marking, which could enhance the TAD procedure. This study aims to evaluate the feasibility and accuracy of different TAD strategies using CNSIs and to explore their clinical utility in locally advanced breast cancer.

Methods: This prospective, multicenter, randomized controlled trial will enroll 126 biopsy-proven breast cancer patients with suspicious axillary lymph node metastases (cN1-2a) who achieve ycN0 status following NAC. Participants will be randomized in a 1:1:1 ratio to undergo TAD guided by: [1] conventional tissue clips (CG-TAD); [2] CNSI lymph node marking (CN-LNM); or [3] peritumoral CNSI mapping (PCN-MAP). Primary endpoints include retrieval rate of marked lymph nodes, number of sentinel and marked lymph nodes, concordance rates, and complication rates. Secondary endpoints encompass regional and distant recurrence rates, survival outcomes, surgical duration, postoperative complications, quality of life scores, and margin status in breast-conserving surgery. Statistical analyses will adhere strictly to the CONSORT guidelines.

Discussion: This study aims to evaluate the feasibility and accuracy of CNSI for targeted axillary dissection in breast cancer patients following neoadjuvant chemotherapy and to explore its clinical significance in reducing surgical complications and costs, as well as improving surgical precision.

Trial registration: Clinicaltrials.gov, NCT04744506, Registered 27 December 2020, Updated 24 September 2024. Protocol Version Ver 1.2, 17/9/2024.

Background: Neuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblastoma with different genetic characteristics.

Methods: We enrolled 31 patients with neuroblastoma and collected samples to detect three genetic characteristics. Peripheral blood samples were tested for immune cells and cytokines by fluorescent microspheres conjugated with antibodies and flow cytometry. Event-free survival (EFS) was analyzed using the Kaplan‒Meier method.

Results: Twenty-two patients had genetic aberrations, including MYCN amplification in 6 patients, chromosome 1p deletion in 9 patients, and chromosome 11q deletion in 14 patients. Two genetic alterations were present in seven patients. The EFS was worse in patients with MYCN amplification or 1p deletion than in the corresponding group, whereas 11q deletion was a prognostic factor only in patients with unamplified MYCN. Changes in immune status revealed a decrease in the proportion of T cells in blood, and an increase in regulatory T cells and immunosuppression-related cytokines such as interleukin (IL)-10. The EFS of the IL-10 high-level group was lower than that of the low-level group. Patients with concomitant genetic alterations and a high level of IL-10 had worse EFS than other patients.

Conclusions: Patients with neuroblastoma characterized by these genetic characteristics often have suppressed T cell response and an overabundance of immunosuppressive cells and cytokines in the peripheral blood. This imbalance is significantly associated with poor EFS. Moreover, if these patients show an elevated levels of immunosuppressive cytokines such as IL-10, the prognosis will be worse.

Background: Cancer poses a significant public health challenge in India, making it crucial to predict its future impact for effective healthcare planning. This study forecast cancer incidence, mortality, and disability-adjusted life years (DALYs) in India from 2022 to 2031.

Methods: We extracted age-standardized data on incidence, prevalence, DALYs, and mortality from 1990 to 2021 from the Global Burden of Disease (GBD) study. We used Decadal Average Percentage Change techniques to identify trends in cancer burden over decades and the Autoregressive Integrated Moving Average (ARIMA) method were used for forecasting. The ARIMA (2,2,2) model was identified as the best for predicting cancer incidence, ARIMA (0,3,3) for DALYs, and ARIMA (0,2,2) for mortality.

Results: The cancer incidence rate is expected to rise from 529.40 (95% CI: 525.41-533.38) in 2022 to 549.17 (95% CI: 487.43-610.92) per 100,000 population in 2031. The DALYs rate is projected to decrease from 2001.53 (95% CI: 1964.24-2038.82) in 2022 to 1842.08 (95% CI: 1273.57-2410.60) per 100,000 population in 2031, indicating improvements in cancer burden management. Mortality rates are forecasted to increase slightly, from 71.52 (95% CI: 69.91-73.12) in 2022 to 73.00 (95% CI: 60.88-85.11) per 100,000 population in 2031. Overall, while incidence and mortality rates show a slight upward trend, the DALYs rate is projected to decrease, reflecting potential advancements in cancer management and treatment over the forecast period.

Conclusions: Over the next decade, cancer incidence and mortality are expected to increase in India, highlighting the need for enhanced prevention, early detection, and proper treatment strategies. Despite these increases, the anticipated decrease in DALYs suggests potential advancements in cancer management, warranting further investigation into the drivers of this positive trend and measures to sustain it.