ARID1A deficiency associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes predicts a good prognosis of endometrial carcinoma

BackgroundARID1A alterations have been detected in 40% of endometrial carcinomas (ECs) and are associated with loss of its expression. The role of ARID1A in tumorigenesis and development is complex, and the prognostic role in EC remains controversial. Hence, it is of great significance to confirm the role of ARID1A in EC.MethodsA total of 549 EC patients (cohort A) from TCGA were evaluated to explore the prognostic role of ARID1A. NGS was performed for 13 EC patients (cohort B), and expression of ARID1A, CD3, CD8 and mismatch repair (MMR) proteins in 52 patients (cohort C) from our center was determined by immunohistochemistry (IHC). The Kaplan–Meier method was used to perform survival analyses.ResultsARID1A alterations were detected in 32% of EC patients and correlated with good disease-free survival (DFS, P = 0.004) and overall survival (OS, P = 0.0353). ARID1A alterations were found to co-occur with MMR-related gene mutations and correlated with higher PD-L1 expression. Patients concomitantly harboring ARID1A alterations and MMR-related gene mutations had the best prognosis (DFS: P = 0.0488; OS: P = 0.0024). A cohort from our center showed that ARID1A deficiency was an independent prognostic factor and predicted longer recurrence-free survival (P = 0.0476). ARID1A loss was associated with a tendency toward MSI-H (P = 0.0060). ARID1A alterations and expression loss were associated with a higher abundance of CD3+ (P = 0.0406) and CD8+ (P = 0.0387) T cells.ConclusionARID1A alterations and expression loss are tightly associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes, which might contribute to the good prognosis of EC.     

Efficacy of cascade-primed cell infusion as an adjuvant immunotherapy with concurrent chemotherapy for patients with non–small-cell lung cancer: A retrospective observational study with a 5-year follow-up

BackgroundClinical studies have shown the efficacy of combination therapy for various malignancies. In this study, the characteristics, safety and feasibility of use of cascade-primed (CAPRI) cells for the combination treatment of non–small-cell lung cancer (NSCLC) were evaluated both in vitro and in vivo.MethodsSixty-five patients with stage II–IV NSCLC were recruited. Of these patients, 31 patients received CAPRI cell therapy combined with chemotherapy (CAPRI group), and the other 34 patients constituted the control group and received chemotherapy alone. This study primarily aimed to evaluate the overall survival (OS), progression-free survival (PFS), short-term responses and treatment efficacy.ResultsCD83, CD1a, CD80 and CD86 marker levels were significantly upregulated in CAPRI cells. Interferon-γ expression levels were highest in CD3⁺CD8⁺ cells (33.77% ± 4.40%). Furthermore, interleukin-2 levels were highest in CD3⁺CD56⁺ cells (26.73% ± 6.63%), whereas perforin expression levels were similar in CD3⁺CD8⁺ and CD3⁺CD56⁺ cells. Furthermore, CAPRI cells had a better anti-tumor potential in CD3⁺CD56⁺ cells and displayed the highest expression levels of CD107a to H460 and A549 cell lines. The 5-year OS was significantly greater in the CAPRI group than in the control group (P = 0.008), and the PFS of two groups exhibited a significant difference (P = 0.007). Median OS (48 versus 31.6 months; P = 0.004) and PFS (48 versus 36.4 months; P = 0.016) differed between these two groups. Moreover, treatment-associated toxicities were mild and well-tolerated by patients with NSCLC.ConclusionCAPRI cell therapy potentially prolongs the survival of patients with NSCLC when combined with chemotherapy.     

Prospective study of adoptive activated αβT lymphocyte immunotherapy for refractory cancers: development and validation of a response scoring system

Background aimsThis prospective clinical study aimed to determine the efficacy and prognostic factors of adoptive activated αβT lymphocyte immunotherapy for various refractory cancers. The primary endpoint was overall survival (OS), and the secondary endpoint was radiological response.MethodsThe authors treated 96 patients. Activated αβT lymphocytes were infused every 2 weeks for a total of six times. Prognostic factors were identified by analyzing clinical and laboratory data obtained before therapy.ResultsMedian survival time (MST) was 150 days (95% confidence interval, 105–191), and approximately 20% of patients achieved disease control (complete response + partial response + stable disease). According to the multivariate Cox proportional hazards model with Akaike information criterion–best subset selection, sex, concurrent therapy, neutrophil/lymphocyte ratio, albumin, lactate dehydrogenase, CD4:CD8 ratio and T helper (Th)1:Th2 ratio were strong prognostic factors. Using parameter estimates of the Cox analysis, the authors developed a response scoring system. The authors then determined the threshold of the response score between responders and non-responders. This threshold was able to significantly differentiate OS of responders from that of non-responders. MST of responders was longer than that of non-responders (317.5 days versus 74 days). The validity of this response scoring system was then confirmed by internal validation.ConclusionsAdoptive activated αβT lymphocyte immunotherapy has clinical efficacy in certain patients. The authors’ scoring system is the first prognostic model reported for this therapy, and it is useful for selecting patients who might obtain a better prognosis through this modality.     

The predictive efficacy of tumor mutation burden in immunotherapy across multiple cancer types: A meta-analysis and bioinformatics analysis

PurposeTo explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs).MethodsWe systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients’ OS between the non-ICIs group and meta-analysis results.ResultsOf 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31–3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64–2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21–0.28; P < 0.001) and PFS (HR = 0.38; 95% CI: 0.34–0.42; P < 0.001). Furthermore, compared with non-ICIs group from the TCGA database, immunotherapy can improve OS in some cancer types with high TMB and better prognosis, including colorectal cancer, gastric cancer, lung cancer, melanoma and pan-cancer.ConclusionTMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. If there is a standard for TMB assessment and cut-off, it could improve the management of different cancers.     

The Performance and Reproducibility of Late-Night Salivary Cortisol Estimation by Enzyme Immunoassay for Screening Cushing Disease

ObjectiveOur study aimed to establish a local reference range for late-night salivary Cortisol (LNSC) using enzyme immunoassay (EIA) and to study the intra-individ-ual reproducibility of LNSC.MethodsProspective study involving 30 healthy subjects (HS) with body mass index (BMI) < 25 kg/m², 37 obese/overweight subjects (OS) with BMI > 25 kg/m² and 28 patients with Cushing disease (CD). Salivary sampling was performed on 2 consecutive nights and assayed by EIA. The reference range was established using LNSC values of HS, and receiver operating characteristic (ROC) curves were used to determine diagnostic cutoffs.ResultsThe mean LNSC level of CD was significantly higher than HS and OS (CD: 16.96 ± 9.11nmol/L, HS: 1.30 ± 0.95 nmol/L, and OS 1.21 ± 0.78 nmol/L). A cutoff of 2.92 nmol/L differentiated CD from HS with 100% sensitivity and 96.7 % specificity, and a cutoff of 5.04 nmol/L yielded a specificity of 100% with a sensitivity of 96.4% to distinguish CD from OS. There was more intra-individual variability in HS (55%) than in CD (49%) and OS (22%). There was no difference in the sensitivity and specificity derived from the ROCs using day 1 values or the higher of the 2 LNSCs.ConclusionsIn our cohort, we found that LNSC assayed by EIA showed good sensitivity and specificity to screen patients suspected to have CD. Although intra-individual variability was significant, it did not hamper the diagnostic performance of the test. (Endocr Pract. 2015; 21:158-164)     

Sarcopenia and a 5-mRNA risk module as a combined factor to predict prognosis for patients with stomach adenocarcinoma

BackgroundSarcopenia is an important factor affecting the prognostic outcomes in adult cancer patients. Gastric cancer is considered an age-related disease and is one of the leading causes of global cancer mortality. We aimed to establish an effective age-related model at a molecular level to predict the prognosis of patients with gastric cancer.MethodsTCGA STAD (stomach adenocarcinoma) and NCBI GEO database were utilized in this study to explore the expression, clinical relevance and prognostic value of age-related mRNAs in stomach adenocarcinoma through an integrated bioinformatics analysis. WGCNA co-expression network, Univariate Cox regression analysis, LASSO regression and Multivariate Cox regression analysis were implemented to construct an age-related prognostic signature.ResultsAs a result, sarcopenia is not only an unfavorable factor for OS (overall survival) in patients with tumor of gastric (HR: 1.707, 95%CI: 1.437–2.026), but also increases the risk of postoperative complications in patients with gastric cancer (OR: 2.904, 95%CI: 2.150–3.922). A panel of 5 mRNAs (DCBLD1, DLC1, IGFBP1, RNASE1 and SPC24) were identified to dichotomize patients with significantly different OS and independently predicted the OS in TCGA STAD (HR = 3.044, 95%CI = 2.078–4.460, P < 0.001).ConclusionThe study provided novel insights to understand STAD at a molecular level and indicated that the 5 mRNAs might act as independent promising prognosis biomarkers for STAD. Sarcopenia and the 5-mRNA risk module as a combined factor to predict prognosis may play an important role in clinical diagnosis.     

Revealing the link between macrophage in microenvironment of osteosarcoma and poor prognosis by utilizing the Integrated analysis

Objectives:Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown.Methods:To investigate the function of immune cells in osteosarcoma, we provided a text-based GMT (Gene Matrix Transposed) file in which each line defines one of lm22 with their markers. We used STRING to draw DEG’s PPI network and selected hub genes and modules. Then, survival analysis was conducted to hub genes. We identified 10,390 common genes, and identified 218 DEGs based on the combined t-value and Z scores.Results:The KEGG and GSEA enrichment analysis showed that macrophages are significantly activated in osteosarcoma. PPI network analysis revealed that hub gene CD163 molecule. We found that the expression of CD163 was negatively associated with the OS of osteosarcoma patients. These results suggest that macrophages are a risk factor in patients with osteosarcoma.Conclusions:This study has systematically validated results of the studies carried out previously and filled up the gap in the field of OS on large-scaled meta-analysis. In addition, for the hub gene (CD163) and the macrophage cell capable of being used as a novel biomarker in promoting early diagnosis and development of therapeutic approaches.     

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients.MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses.ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%.ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Higher serum sPD-L1 levels after radiotherapy indicate poor outcome in hepatocellular carcinoma patients

BackgroundOur preclinical research reveals that radiotherapy (RT) promoted PD-L1 upregulation in tumor tissues and that higher PD-L1 after RT worsened the prognosis through immunosuppression. We sought to validate our experimental results in clinical cohorts and promote clinical application.Patients and methodsIn cohort 1, formalin-fixed paraffin-embedded samples were obtained from 46 HCC patients, 23 of whom received preoperative RT and the other 23 received direct surgery. A prospectively collected database contained 122 HCC patients treated with liver RT were enrolled in cohort 2. Blood samples were taken a day before and two weeks after RT. Patients in cohort 2 were further divided into two groups, exploration (73 patients) and validation (49 patients) groups.ResultsIn cohort 1, RT increased the expression of PD-L1 in tumor tissues (p = 0.001), and PD-L1 levels were associated with decreased cytotoxic T-cell infiltration and a trend toward poor prognosis (p = 0.14). Moreover, PD-L1 expression in tumor tissue positively correlated with soluble (s) PD-L1 in serum (R = 0.421, p = 0.046). Then, in cohort 2, we revealed RT increased sPD-L1 in serum (p < 0.001), which was associated with the number of circulating CD8+ T cells (R = -0.24, p = 0.036), indicating poor survival. Furthermore, patients with higher rate of sPD-L1 increase after RT have better treatment response (p < 0.001), PFS (p = 0.032) and OS (p = 0.045).ConclusionHigher post-RT serum sPD-L1, which may potentiate immune suppression effects, indicates a poor prognosis for HCC patients treated with RT.     

Oxidative stress evaluation in patients with chronic Chagas disease

IntroductionChagas disease (CD), caused by protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease that affects millions of people worldwide. The parasite clearance by the immune cells is accomplished by the activation of inflammation and production of reactive oxygen species, including nitric oxide (NO) that can lead to tissue injury and DNA damage. On the other hand, to balance the oxidative environment and decrease free radicals, there is an antioxidant system composed of enzymes and vitamins. The aim was to evaluate oxidative stress parameters in symptomatic and asymptomatic patients with Chagas disease.MethodsParticipants were divided into three groups: indeterminate CD (asymptomatic, n = 8), CD with cardiac/digestive involvement (symptomatic, n = 14), and Control healthy individuals (n = 20). The following parameters were analyzed: DNA damage, NO serum levels, hydrophilic antioxidant capacity (HAC) and vitamin E.ResultsSymptomatic patients showed increased DNA damage and NO levels and lower HAC and vitamin E levels compared to asymptomatic patients and control subjects.ConclusionsIt is possible to conclude that CD patients with clinical symptoms have higher oxidative stress, characterized by increased DNA damage and NO levels, and reduced antioxidant capacity and vitamin E levels.     

Clinical effect and safety of dendritic cell–cytokine-induced killer cell immunotherapy for pancreatic cancer: a systematic review and meta-analysis

BackgroundAlthough promising results have recently been reported using dendritic cells (DCs) and cytokine-induced killer cells (CIKs) to treat pancreatic cancer (PC), its clinical effect and safety are associated with some controversy, and lack sufficient evidence. Here, we conducted a meta-analysis of 21 clinical trials to better evaluate the efficacy of DC-CIK immunotherapy in clinical practice to treat PC.MethodsPubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data Knowledge Service Platform (WANFANG Data) were searched to identify clinical trials that used DC-CIK immunotherapy for PC. Meta-analysis was performed using RevMan 5.3 and Stata 12.0.ResultsA total of 21 clinical trials involving 1549 patients were included. Compared with traditional treatment, DC-CIK immunotherapy improved and increased the clinical indices such as complete remission, partial remission, overall response rate, disease control rate, overall survival (0.5-y OS, 1-y OS, 1.5-y OS, 2-y OS and 3-y OS), interferon γ and CD3+, CD4+, CD4+/CD8+ and CD3+CD56+ lymphocyte. Additionally, DC-CIK immunotherapy reduced stable disease, progression disease, mortality, CD8+, CD4+CD25+CD127 low lymphocyte and interleukin-4. Furthermore, it showed a low incidence of adverse reactions (22%).ConclusionIn contrast to traditional therapy, DC-CIK immunotherapy not only shows improved short-term effect, long-term effect and immunologic function, but also reduces mortality and negative immunoregulatory index, and shows mild adverse reactions. This is the first study to evaluate the clinical effect and safety of DC-CIK immunotherapy for PC, and it indicated that DC-CIK immunotherapy may be suitable for patients with advanced PC or intolerance to radiotherapy and chemotherapy.     

Gankyrin promotes osteosarcoma tumorigenesis by forming a positive feedback loop with YAP

BackgroundAlthough gankyrin has been identified as a vital regulator of tumorigenesis, its role and regulatory mechanism in osteosarcoma (OS) remain unclear.MethodsQRT-PCR, western blot and IHC staining were conducted to detect the expression of gankyrin in OS. Pearson’s χ² test was adopted to examine the associations between gankyrin expression and clinicopathologic characteristics. Kaplan-Meier method was used to investigate the relationship between gankyrin expression and overall survival of patients with OS. Next, a series of in vitro and in vivo assays were performed to determine the positive feedback loop between gankyrin and YAP in OS.ResultsWe first reported that gankyrin is upregulated in human OS specimens and cell lines and predicts OS progression and poor prognosis. Furthermore, we demonstrated that gankyrin protects miR-200a-mediated yes-associated protein (YAP) downregulation through p53 and establishes a positive feedback loop to regulate YAP signaling in U2OS and MG63 cells. Intriguingly, gankyrin interacts with YAP to promote OS cell growth in vitro. In addition, our results showed that gankyrin promotes OS tumor growth and regulates YAP levels in vivo. Notably, we also observed a positive correlation between gankyrin and YAP expression in human OS tissues, and co-upregulation of gankyrin and YAP indicated a poor prognosis.ConclusionsOur results identify that gankyrin acts as an oncogene in OS by forming a positive feedback loop with YAP, and disrupting the gankyrin-YAP regulation may be beneficial for controlling OS tumorigenesis.     

Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy

PurposeThe aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health.MethodsVascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated.ResultsThe volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status.ConclusionIt was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.     

Establishment and validation of lncRNA-related prognostic signatures in cholangiocarcinoma

BackgroundThe prognosis of CCA is extremely poor, making it one of the most lethal cancers. Therefore, there is a need to elucidate the pathogenic mechanisms of CCA. In this study, we aimed at identifying lncRNA-related prognostic signatures for CCA through bioinformatics analysis and further validated their functions in CCA tumorigenesis and progression.MethodsThe RNA-seq data of CCA were downloaded from public databases. Differentially expressed lncRNAs (DElncRNAs) were screened. Then, candidate OS- and DFS-related DElncRNAs were selected through Kaplan–Meier survival analysis. Furthermore, LASSO regression was performed to establish the OS and DFS signatures, respectively. Multivariate COX models and nomograms for overall survival (OS) and disease-free survival (DFS) were established based on OS/DFS signature and clinical data. Hub lncRNAs were identified and enrichment analyses were performed to explore their potential functions. Finally, in vitro and in vivo models were used to validate the effects of the hub lncRNAs in CCA tumorigenesis and progression.ResultsA total of 925 DElncRNAs were selected, of which six candidate OS-related lncRNAs and 15 candidate DFS-related lncRNAs were identified. The OS and DFS signatures were then established using four lncRNAs, respectively. We found that the OS signature and vascular invasion were independent risk factors for the OS of CCA, while the DFS signature, vascular invasion, and CA19–9 were independent risk factors for the DFS of CCA. Then, nomograms were established to achieve personalized CCA recurrence and death prediction. Furthermore, our study uncovered that MIR4435-2HG and GAPLINC might play crucial roles in CCA progression and be selected as hub lncRNAs. GO and KEGG enrichment analyses revealed that the two hub lncRNAs were closely related to CCA tumorigenesis. Finally, we demonstrated that MIR4435-2HG and GAPLINC can stimulate CCA proliferation and migration in vitro and in vivo.ConclusionsThe established OS and DFS signatures are independent risk factors for OS and DFS of CCA patients, respectively. MIR4435-2HG and GAPLINC were identified as hub lncRNAs. In vitro and in vivo models revealed that MIR4435-2HG and GAPLINC can prompt CCA progression, which might be novel prognostic biomarkers and therapeutic targets for CCA.     

Evaluation of the prognostic value of lymphadenectomy for low-grade serous ovarian cancer: A case-control multicenter retrospective study

BackgroundThe prognostic value of lymphadenectomy in low-grade serous ovarian cancer (LGSOC) remains uncertain.Materials and methodsA retrospective analysis of 155 patients with LGSOC who underwent surgery over a ten-year period (2011–2020) was performed. The propensity score matching (PSM) algorithm was performed between the lymphadenectomy and no lymphadenectomy groups, and Kaplan-Meier analyses were conducted to evaluate clinical prognosis. Finally, univariate and multivariate Cox proportional hazards regression analyses were performed to analyze high-risk factors associated with clinical prognosis.ResultsIn the pre-PSM cohort, 110 (71.0%) patients underwent lymphadenectomy. Of these, 54 (34.8%) experienced recurrence, and 27 (17.4%) died. There were statistical differences in disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016) in the post-PSM cohort. In the subgroup analysis, there were no statistically significant differences in DFS (P = 0.449) or OS (P = 0.167) in the FIGO I/II cohort. However, in the FIGO III/IV cohort, DFS (P = 0.011) and OS (P = 0.046) were statistically different between the two groups. Age > 50 years, FIGO stage III/IV, and suboptimal cytoreductive surgery were risk factors associated with prognosis. In the lymphadenectomy group, the histological status of pelvic lymph nodes had no significant effect on DFS (P = 0.205) or OS (P = 0.114).ConclusionLymphadenectomy was associated with DFS and OS, particularly in patients with advanced LGSOC patients. Age > 50 years, advanced FIGO stage III/IV, and suboptimal cytoreductive surgery were high-risk factors associated with clinical prognosis in patients with LGSOC.     

Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis

BackgroundCirculating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma.ObjectivesTo describe the clinical prognostic value of ctDNA for melanoma patients.MethodsSearched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS).ResultsA total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22–3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98–3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19–4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77–4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48–15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36–10.33, p < 0.001).ConclusionInvestigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.     

Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma

AimEvaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy.BackgroundAnemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes.Materials and MethodsRetrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively.ResultsA total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016).ConclusionsIn this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.