Significant Difference In Overall Survival Research Articles

Unraveling molecular signatures and prognostic biomarkers in glioblastoma: a comprehensive study on treatment resistance and personalized strategies

BackgroundGlioblastoma (GBM) is a highly aggressive primary brain tumor with limited treatment success and poor prognosis. Despite surgical resection and adjuvant therapies, GBM often recurs, and resistance to radiotherapy and temozolomide presents significant challenges. This study aimed to elucidate molecular signatures associated with treatment responses, identify potential biomarkers, and enhance personalized treatment strategies for GBM.MethodsWe conducted a comprehensive analysis using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The GEO dataset (GSE206225) was used to identify differentially expressed genes (DEGs) between radiation-sensitive/resistant and temozolomide-sensitive/resistant GBM samples. TCGA data were utilized for subsequent analyses, including Lasso-Cox regression, risk score model construction, Kaplan–Meier survival analysis, and gene set enrichment analysis (GSEA). Hub genes were identified through survival analysis, and a gene prognostic nomogram was developed. Additionally, validation of the three-gene risk signature through multiple external cohorts and validation of protein expression levels were performed.ResultsDEG analysis identified 111 genes associated with chemoradiotherapy resistance, providing insights into the complex landscape of GBM treatment response. The risk score model effectively stratified patients, showing significant differences in overall survival and progression-free survival. GSEA offered a deeper understanding of pathway activities, emphasizing the intricate molecular mechanisms involved. NNAT, IGFBP6, and CYGB were identified as hub genes, and a gene prognostic nomogram demonstrated predictive accuracy.ConclusionThis study sheds light on the molecular intricacies governing GBM treatment response. The identified hub genes and the gene prognostic nomogram offer valuable tools for predicting patient outcomes and guiding personalized treatment strategies. These findings contribute to advancing our understanding of GBM biology and may pave the way for improved clinical management.

Mid-term follow-up results of neoadjuvant sintilimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma.

The study was conducted in order to investigate whether neoadjuvant immunotherapy combined with chemotherapy can bring survival benefits to patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) in the real world. We retrospectively analysed patients with locally advanced resectable ESCC who underwent surgery at the Jining First People's Hospital from April 2020 to April 2022. Based on their medical history, the enrolled patients were divided into a neoadjuvant immunochemotherapy plus surgery group (nICT group) and a surgery-only group (S group). Primary endpoints were the two-year overall survival (OS) and disease-free survival (DFS) rates. Secondary endpoints were the safety and efficacy of neoadjuvant immunochemotherapy for patients with locally advanced esophageal cancer, and compared the surgery and postoperative outcomes between the two groups. A total of 47 patients in the nICT group and 73 patients in the S group were included for further analysis, the stage of the nICT group was more advanced than that of the S group. In the group nICT, 8 patients (17%) achieved the complete pathological response (pCR), 29 patients (61.7%) achieved major pathological response (MPR), including 6 patients (12.8%) with a primary tumor achieving pCR but had residual tumor cells in the lymph nodes (pT0N+), and the treatment-related AES was manageable. The surgery and postoperative outcomes were comparable in both groups. The two-year OS and DFS rates for the nICT group were 91.5% and 85.5% respectively, while those for the S group were 71.2% and 68.5%, and Kaplan-Meier survival analysis and log-rank test revealed significant differences in DFS and OS between the two groups. Patients who achieved MPR in the nICT group showed better DFS and OS, while the Three-cycle subgroup did not exhibit any survival benefit compared to the Two-cycle subgroup. Neoadjuvant sintilimab combined with chemotherapy has promising efficacy and safety in the treatment of locally advanced resectable ESCC. The treatment modality has the potential to become a standard therapy for locally advanced resectable ESCC.

Comparative analysis of the safety and feasibility of laparoscopic and open approaches for right anterior sectionectomy

Laparoscopic hepatectomy has minimally invasive advantages, but reports on laparoscopic right anterior sectionectomy (LRAS) are rare. Herein, we try to explore the benefits and drawbacks of LRAS by comparing it with open right anterior sectionectomy (ORAS). Between January 2015 and September 2023, 39 patients who underwent LRAS (n = 18) or ORAS (n = 21) were enrolled in the study. The patients’ characteristics, intraoperative details, and postoperative outcomes were compared between the two groups. No significant differences in the preoperative data were observed between the two groups. The LRAS group had significantly lesser blood loss (P = 0.019), a shorter hospital stay (P = 0.045), and a higher rate of bile leak (P = 0.039) than the ORAS group. There was no significant difference in the operative time (P = 0.156), transfusion rate (P = 0.385), hospital expenses (P = 0.511), rate of other complications, postoperative white blood cell count, and alanine aminotransferase and aspartate aminotransferase levels between the two groups (P > 0.05). Beside, there was no significant difference in disease-free survival (P = 0.351) or overall survival (P = 0.613) in patients with hepatocellular carcinoma between the two groups. LRAS is a safe and feasible surgical procedure. It may be preferred for lesions in the right anterior lobe of the liver.

Vulnerability in Colorectal Cancer: Adjusted Gross Income and Geography as Factors in Determining Overall Survival in Colorectal Cancer: A Single-Center Study Across a Broad Income Inequality in an American Context.

Introduction: Regional differences in socioeconomic status (SES) are well known, and we believe that the use of geocoding (zip code) can facilitate the introduction of targeted interventions for underserved populations. This is a single-center, retrospective analysis of data extracted from the cancer registry at the Capital Health Cancer Center in Pennington, N. The Capital Health Cancer Center in central New Jersey primarily serves two counties, catering to a diverse patient population from a wide range of socioeconomic backgrounds. Methods: We abstracted 1269 consecutive cases of colorectal cancer (CRC) diagnosed and treated between 2000 and 2019 from the Cancer Registry of the Capital Health Cancer Center (CHCC). Using the definition of SES based on previously published work, and zip codes (geocoding), we created four SES levels. We stratified our subjects according to their stage at diagnosis, age at diagnosis, race, and ethnicity. The primary outcome variable was overall survival (OS). Results: There was a statistically significant difference in OS based on SES, with the highest overall survival (OS) in the high-SES group (47 months) and the shortest OS in the low and mid-low-SES groups (40.4 and 30 months, respectively). Subjects living in high-SES areas were predominantly white (88.2%) and diagnosed at a later age (mean of 68.9 years of age) compared to individuals who lived in a low-SES area, who were predominantly non-white (72.6%) and diagnosed somewhat earlier in life (65.1 years of age). White people were diagnosed later in life (70.9 years of age) compared to non-white populations, including Black (66.5), Asian (61.7), and Hispanic (58.5) (p = 0.001) populations, but this did not lead to a significant difference in OS (p = 0.56). Stage at diagnosis was a significant predictor of OS, but was unrelated to SES (p = 0.066). A Cox proportional hazard ratio (HR) model showed that the risk of dying from colorectal cancer decreases with a higher socioeconomic status (SES). Those from mid-high-SES backgrounds had a 19% lower risk (HR 0.81), and those from high-SES areas had a 45% lower risk (HR 0.55) compared to individuals from low-SES areas. Conclusions: The vulnerability of patients with CRC in central New Jersey is a complex issue, influenced by many different variables. Our results indicate that SES is the most critical factor affecting OS after being diagnosed with CRC.

Clinical features of vulvar and vaginal malignant melanomas and the effects of immune checkpoint inhibitors in Japanese patients: a single-center, retrospective cohort study.

Vulvar and vaginal melanomas (VVMs) are rare malignancies, but they are relatively more common among Asian women. This makes the collection of data on VVMs in this population crucial. Moreover, no cohort studies have examined and compared the effects of immune checkpoint inhibitors (ICIs) on VVM in Asian women. Therefore, we aimed to investigate the clinical characteristics of VVMs in Japanese women and the effects of ICI treatment. This single-center, retrospective cohort study included patients who were histologically diagnosed with VVM at our hospital between March 2005 and December 2023. The Kaplan-Meier analysis was used to compare the prognosis of vulvar melanoma (VuM) and vaginal melanoma (VaM) throughout entire treatments and compare the efficacies of ICIs and conventional chemotherapies in VVM. In total, 28 women with VuM (n = 14) and VaM (n = 14) were included. There were no significant differences in overall survival (OS) [median OS: not reached (95% confidence interval (CI), 13.2-NA) vs. 30.2 months (95% CI, 23.2-NA), log-rank test, P = 0.456] between the VuM and VaM groups. The progression-free survival (median progression-free survival: 14.7 vs. 5.2 months, P = 0.002) and OS (median OS: 33.8 vs. 7.2 months, P < 0.001) were significantly better for the ICI-treated group than for the conventional chemotherapy-treated group in VVM. The prognosis of patients with VVM improved significantly with the advent of ICI, demonstrating the importance of ICI in the treatment of VVM.

A real-world study: third-line treatment options for metastatic colorectal cancer.

Numerous third-line treatment options exist for colorectal cancer. This study aims to assess the efficacy and safety of third-line therapies, including TKIs (fruquintinib, regorafenib) combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab, in patients with refractory microsatellite stable metastatic colorectal cancer who have progressed or are intolerant following standard first- and second-line treatments. This retrospective analysis collected data from patients with microsatellite stable advanced colorectal adenocarcinoma, diagnosed through histopathology and treated at Henan Provincial Cancer Hospital from May 2019 to April 2023. We compared the efficacy and safety of fruquintinib combined with PD-1 inhibitors, regorafenib combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab. Among 60 eligible patients with refractory microsatellite stable metastatic colorectal adenocarcinoma, 29 (48.3%) received fruquintinib combined with PD-1 inhibitors, 15 (25%) received regorafenib combined with PD-1 inhibitors, and 16 (26.7%) received trifluridine/tipiracil combined with bevacizumab. The average follow-up period was 12.6 months (ranging from 2.3 to 37.6 months). After third-line treatment, the overall objective response rate (ORR) was 8.6%, and the disease control rate (DCR) was 78.6%. The median overall survival (OS) for the regorafenib, fruquintinib, and trifluridine/tipiracil groups was 19.2 months, 14.0 months, and 16.2 months, respectively, with no statistically significant differences observed. However, there were statistically significant differences in progression-free survival (PFS); the median PFS for the regorafenib group was 6.3 months, for the fruquintinib group was 4.2 months, and for the trifluridine/tipiracil group was 5.4 months. Pairwise comparisons indicated that the PFS for the regorafenib group was similar to that for the trifluridine/tipiracil group, both of which were superior to the fruquintinib group. Cox univariate regression analysis revealed that the presence of liver and peritoneal metastases was associated with PFS in third-line treatment. In the third-line treatment of colorectal cancer, regorafenib combined with PD-1 inhibitors and trifluridine/tipiracil combined with bevacizumab showed superiority over fruquintinib combined with PD-1 inhibitors in terms of PFS, but no statistically significant difference in OS was noted among the three groups.

Clinical and pathological characteristics of HR+ breast cancer with HER2 low and HER2(0) expression: exploring endocrine therapy sensitivity.

The clinical significance of human epidermal growth factor receptor 2 (HER2) low and HER2(0) expression in hormone receptor-positive (HR+) breast cancer patients remains uncertain. This study aimed to explore the clinical and pathological characteristics, prognosis, and endocrine therapy (ET) sensitivity among HR+ breast cancer patients with HER2 low and HER2(0) expression. We conducted a retrospective analysis of 390 HR+, HER2-negative breast cancer patients who underwent radical surgery at The First Affiliated Hospital of Bengbu Medical University between December 2014 and December 2017. HER2 status was classified per ASCO/CAP 2018 guidelines: tumors with an immunohistochemistry (IHC) score of 0 were defined as HER2(0), and those with a score of 1+ or 2+ with negative FISH for ERBB2 gene amplification were categorized as HER2 low. Clinical and pathological characteristics, ET sensitivity, and survival outcomes were analyzed. Primary endpoints included disease-free survival (DFS) and overall survival (OS), with ROC curve analysis employed to determine prognostic thresholds. Of the 390 HR+ breast cancer patients, 32.6% had HER2(0) expression [HER2(0) cohort] and 67.4% had HER2 low expression (HER2-low cohort). Most baseline characteristics were balanced between the two cohorts, and the HER2(0) cohort had significantly worse DFS and OS than the HER2-low cohort (both P<0.05). Within the same pN stage (pN0-2), patients with HER2 low expression had a better prognosis (all P<0.05). But at pN3, patients had worse survival outcomes (P=0.003). Patients with the IHC score >4 had significantly better OS (P<0.001) and DFS (P=0.003). No significant difference in OS and DFS was observed in the IHC score ≤4 group between cohorts (both P>0.05), whereas in the IHC score >4 group, the HER2-low cohort had better OS (P<0.001) and DFS (P=0.01). Patients with HER2 low expression have distinct clinical characteristics and a better prognosis compared to those with HER2(0) expression. Our study provides further real-world evidence for personalized treatment of breast cancer patients.

Clinical characteristics and prognostic analysis of metachronous bilateral breast carcinoma: a retrospective study based on propensity score matching.

To investigate clinical characteristics, treatment, outcomes, and prognostic risk factors of metachronous bilateral breast carcinoma (MBBC) and provide a theoretical basis for clinical management of MBBC. This was a retrospective study. From January 1, 2010 to March 31, 2022, a total of 23,010 patients with breast cancer underwent surgical treatment at the Breast Center of the Fourth Hospital of Hebei Medical University, including 386 patients with MBBC. Propensity score matching (PSM) was performed on MBBC patients and unilateral breast cancer (UBC) patients in a 1:1 ratio, and 210 UBC patients and 210 MBBC patients were finally matched. Clinical medical records of all patients were collected, including age of onset, family history of breast cancer, tumor size, lymph node status, TNM stage, mode of surgery, menstruation, pathological type, immunohistochemical (IHC) typing, treatment, disease-free survival (DFS), and overall survival (OS). The result showed that age of onset of the second primary cancer (SPC) was significantly older than that of the first primary cancer (FPC) (P = 0.024). Baseline data from MPPC patients showed that the tumor size of FPC was significantly larger than that of SPC (P = 0.043), and the proportion of PR ( +) in FPC is significantly higher than that in SPC (P = 0.045). Among MBBC patients with FPC for estrogen receptor (ER) or progesterone receptor (PR) ( +) and Her-2 (-), clinical characteristics and treatment results showed that the proportion of PR ( +) in the drug-resistant group was significantly lower than that in the non-drug-resistant group. The 2-year OS rate of SPC in the drug-resistant group was significantly shorter than those of the non-drug-resistant group (78.9% vs 100%, P < 0.05). The result of PSM-based comparison between MBBC patients and UBC patients showed significantly lower proportion of MBBC patients with SPC received chemotherapy compared to UBC patients (P = 0.026), and there was no significant difference in OS and DFS between SPC course of MBBC patients and UBC patients (P > 0.05). The univariate analysis showed that high TNM stage was a risk factor for death and disease progression in MBBC patients, with the risk of death in stage III MBBC patients being about 5 times higher than that in stage I MBBC patients (HR = 4.97, 95%CI = 1.42-17.31, P = 0.012), and the risk of disease recurrence being about 3.5 times higher than that in stage I MBBC patients (HR = 3.55, 95%CI = 1.07-11.81, P = 0.039). In summary, this study presented clinical characteristics, treatment options, and outcomes of MBBC patients and patients with MBBC who were resistant to endocrine therapy have a worse SPC survival prognosis. The course of SPC in MBBC patients was similar to that of UBC in terms of prognosis and survival, which suggested that SPC can be treated according to UBC treatment regimen. High TNM stage was a prognostic risk factor for SPC patients.

Comparison of Sublobar Resection and Proton Therapy for Early-Stage Non-small Cell Lung Cancer.

For early-stage lung cancer, sublobar resection (SLR) is an alternative to lobectomy, which is the standard treatment. Recently, proton therapy (PT) is being increasingly used, even in patients with operable lung cancer, as an attractive alternative to conventional radiation therapy. Thus, we performed propensity score matching (PSM) to compare the outcomes of SLR and PT in patients with early-stage non-small cell lung cancer (NSCLC). A total of 202 patients with histologically confirmed clinical stage 0 or I peripheral NSCLC who underwent SLR or PT at our institution between July 2013 and December 2021 were included in the study. PSM was performed to adjust for confounding effects. PSM generated a cohort of 104 patients who were treated with SLR (n = 52) or PT (n = 52). We observed no significant differences in overall survival (OS) (P = .77), cause-specific survival (P = .43), recurrence-free survival (RFS) (P = .35), local tumor control (P = .51), regional lymph node tumor control (P = .99), and distant tumor control (P = .37). The 5-year OS and 5-year RFS were 85.2% and 73.7%, respectively, in the SLR group and 83.4% and 70.2%, respectively, in the PT group. This study demonstrated no significant differences in the prognosis or tumor control efficacy between SLR and PT in patients with histologically confirmed clinical stage 0 or I peripheral NSCLC. Further studies are warranted to clarify the comparative effectiveness of SLR and PT across various patient risk strata.

Adjuvant rituximab and elevated intratumoural CD8 expression are associated with sustained disease control after radiotherapy in a randomised trial of systemic therapy in early-stage follicular lymphoma

We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies. Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT+CVP). From 2006 rituximab was added to IFRT+CVP (IFRT+R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively). Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR]=0.60, 95% CI=0.37-0.98, p=0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR=0.44, 95% CI=0.16-1.18, p=0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p=0.045). PFS of IFRT+R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT+CVP) was superior (HR=0.36, 95% CI=0.13-0.82, p=0.013). Amongst PET-staged patients, PFS differences between IFRT+R-CVP vs. IFRT were maintained (HR=0.38, 95% CI=0.16-0.89, p=0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR=0.45, 95% CI=0.26-0.79, p=0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p=0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p=0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease. Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL. Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

Efficacy and safety of preoperative intravenous iron versus standard care in colorectal cancer patients with iron deficiency anemia: a systematic review and meta-analysis.

Anemia, particularly iron deficiency (ID) anemia, is common in colorectal cancer (CRC) patients, affecting up to 58% of individuals. This study aimed to compare the effectiveness and safety of preoperative intravenous iron (IVI) with standard care (no iron or oral iron) in CRC patients with ID anemia. A systematic search across multiple databases identified studies comparing IVI versus no iron or oral iron in CRC patients with ID anemia. Pooled data were analyzed for changes in hemoglobin (Hb) levels, need for red blood cell transfusions (RBCT), overall mean number of transfused RBC units, overall survival (OS), disease-free survival (DFS), and complications. The authors analyzed data from 11 studies with 2024 patients and found that IVI significantly increased Hb levels at crucial time points: preoperative (MD=1.17, 95% CI [0.95-1.40], P<0.01), postoperative day one (MD=1.32, 95% CI [0.89-1.76], P<0.01), hospital discharge (MD=0.76, 95% CI [0.28-1.24], P=0.002), and 30 days postoperative (MD=1.57, 95% CI [1.27-1.87], P<0.01). IVI significantly decreased the overall need for RBCT, particularly in the postoperative period (RR=0.69, 95% CI [0.52-0.92], P=0.01). It also reduced the mean number of transfused RBC units, total complications, and wound dehiscence. However, there were no significant differences in total death, hospital stay, infections, paralytic ileus, OS, or DFS. Preoperative IVI significantly increased Hb levels at critical time points and markedly reduced the overall need for RBCT, complications, and wound dehiscence. To further validate these findings and ensure robust conclusions, more well-designed randomized controlled trials are warranted.

Comparison of Microwave and Radiofrequency Ablation for the Treatment of Small- and Medium-Sized Hepatocellular Carcinomas in a Prospective Randomized Trial

Purpose To compare the therapeutic response and clinical outcome of CT-guided percutaneous microwave (MWA) and radiofrequency ablation (RFA) for the treatment of small- and medium-sized HCC. Materials and Methods In this prospective trial, 50 patients with HCC were randomly assigned to MWA or RFA treatment. MRI was performed 24 h before and after ablation and subsequently in 3-month intervals. Ablation volumes, ablation durations, adverse events (AE), technique efficacy, technical success, local tumor progression (LTP), disease-free survival (DFS), intrahepatic distant recurrence (IDR), and overall survival (OS) rates were evaluated. Results The mean ablation volume was 66.5 cm³ for MWA and 29.2 cm³ for RFA (p &lt; 0.01). The mean ablation durations for MWA and RFA were 11.2 ± 4.0 min and 16.3 ± 4.7 min, respectively (p &lt; 0.01). Six mild AEs were documented (p &gt; 0.05). All treatments had a technical success rate and a technique efficacy rate of 100 % (50/50, p = 1.00). LTP within 2 years occurred in 1/25 (4 %) in the MWA group and in 4/25 (16 %) in the RFA group (p = 0.06). IDR within 2 years was 8/25 (32 %) for MWA and 14/25 (56 %) for RFA (p &lt; 0.05). The median DFS was 24.5 months and 13.4 months for MWA and RFA, respectively (p = 0.02). The 1-, 2-, 3-year OS rates were 100 %, 80 %, 72 % in the MWA group and 72 %, 64 %, 60 % in the RFA group, respectively (p ≥ 0.14). Conclusion The clinical outcome after MWA or RFA for HCC treatment was very similar with no significant differences in LTP or OS. However, MWA shows a trend toward better DFS with fewer IDRs than RFA. Key Points

Long-term Outcomes of Prostate Capsule-Sparing and Nerve-Sparing Radical Cystectomy With Neobladder: A Propensity Score-Matched Comparison.

This study aimed to compare and analyze the feasibility and long-term efficacy of prostatic capsule-sparing (PCS) and nerve-sparing (NS) radical cystectomy in the treatment of bladder cancer. From June 2004 to December 2021, our institution treated and followed 145 patients who underwent radical cystectomy with neobladder reconstruction for over a year. These patients were divided into 2 groups: PCS (n=74) and NS (n=71). To minimize potential biases, 1:1 propensity score matching was utilized to compare oncological outcomes, functional outcomes, and complications between the groups. Additionally, Kaplan-Meier analysis and the log-rank test were used to evaluate survival differences between the PCS and NS groups. The median follow-up durations for PCS and NS were 155 and 122 months, respectively. After adjusting for propensity scores, a total of 96 patients (48 in each group) were included for further analysis. Kaplan-Meier curves showed no statistically significant differences in metastasis-free probability (P=0.206), cancer-specific survival (P=0.091), and overall survival (P=0.208). The daytime urinary control (UC) rate at 3, 6, and 12 months postoperatively was 72.9%, 91.7%, and 97.9% in the PCS group and 47.9%, 79.2%, and 91.7% in the NS group, respectively (P=0.012, P=0.083, and P=0.362). The nocturnal UC rate was 54.2%, 85.4%, and 95.8% in the PCS group, and 31.3%, 60.4%, and 83.3% in the NS group, respectively (P=0.023, P=0.006, and P=0.091). Regarding erectile function recovery, 62.5% of patients in the PCS group and 22.9% in the NS group returned to preoperative levels (P<0.001). PCS outperformed NS in restoring UC and sexual function and did not affect oncological outcomes. However, PCS was associated with a higher risk of complications linked to bladder-neck obstruction.

Oncological outcomes of patients with muscle-invasive bladder cancer treated with trimodal strategy: A French multicentric study

PurposeTrimodal therapy, an organ-sparing alternative, may be proposed for selected patients with muscle-invasive bladder cancer instead of radical cystectomy. In this multicentre retrospective study, we aimed to assess the oncological outcomes of patients who had trimodal therapy for a muscle-invasive bladder cancer. Materials and methodsSeventy-three patients from four centres treated who had trimodal therapy (maximal transurethral resection of bladder tumour and concomitant chemoradiotherapy) for localized muscle-invasive bladder cancer were included. Patients meeting the optimal trimodal therapy eligibility criteria as per the European Association of Urology guidelines were identified. Overall survival, recurrence-free survival and cancer-specific survival were assessed using the Kaplan–Meier method. The cumulative incidence of recurrence was estimated using the Kalbfleisch–Prentice method. ResultsMedian overall survival was 27.0 months (95 % confidence interval [CI]: 20.3–58.3 months), 5-years overall-, cancer-specific- and recurrence-free survival rates were 37.5% (95 % CI: 25.5–49.5 %), 60 % (95 % CI: 48.3–72.0 %), and 17.9 % (95 % CI: 9.3–28.8 %), respectively. There was no significant difference in 5-year overall survival and recurrence-free survival between the trimodal therapy-eligible and non-eligible patients (hazard ratio [HR]: 1.38, P=0.30 and HR: 0.96, P=0.90, respectively). The univariate analysis did not reveal any significant prognostic factors associated with recurrence-free or overall survival. ConclusionTrimodal therapy offers encouraging specific survival, the prognosis remains poor. Our study highlights the low number and high frailty of patients to whom trimodal therapy is offered in clinical practice.

Comparison of proximal gastrectomy with tubular esophagogastric anastomosis and total gastrectomy with Roux-en-Y reconstruction in the treatment of adenocarcinoma of the esophagogastric junction of Siewert type II/III at stage II

BackgroundTubular anastomosis is commonly used in proximal gastrectomy; however, its use in stage II esophagogastric conjugate cancer is currently unclear. In this study, we investigated the short- and long-term clinical outcomes of Siewert II/III adenocarcinoma of the esophagogastric junction after modified proximal gastrectomy with tubular esophagogastric anastomosis compared with total gastrectomy with Roux-en-Y reconstruction.MethodsWe collected the clinical data of patients who underwent proximal gastrectomy tubular esophagogastric anastomosis (PG-TEA) and total gastrectomy Roux-en-Y reconstruction (TG-RY) from October 2015 to October 2018. The clinical characteristics, postoperative quality of life, nutritional status, and long-term survival outcomes of the two groups were compared.ResultsThere were 43 patients in the PG-TEA group and 80 patients in the TG-RY group, and there was no significant difference between the baseline data of the groups. The operation time of the PG-TEA group was shorter, there was less intraoperative bleeding, and the feeding time was earlier, which was conducive to postoperative recovery. Reflux esophagitis was more evident in the PG-TEA group than in the TG-RY group, and there was no significant difference in the incidence of anastomotic ulcers or other complications. Three months after surgery, the nutritional status of the PG-TEA group was better than the TG-RY group. By the 6th postoperative month, there was no significant difference between the two groups. Regarding quality of life, the PG-TEA group was superior to the TG-RY group in terms of diarrhea and dumping syndrome. In addition, the PG-TEA group had higher satisfaction with daily life and higher-quality meals. There was no significant difference in overall survival between the two groups.ConclusionsProximal gastrectomy tubular gastroesophageal anastomosis is a surgical procedure for stage II Siewert type II and III AEG. It achieves similar clinical outcomes to those after total gastrectomy and can be further applied in the clinic.

Treatment patterns and clinical outcomes of resectable central non-small cell lung cancer patients undergoing sleeve lobectomy: a large-scale, single-center, real-world study.

In the treatment of central-type non-small cell lung cancer (NSCLC), sleeve lobectomy (SL) has emerged as the surgical treatment of choice over pneumonectomy (PN). This retrospective study evaluates the clinical profiles and prognostic elements impacting survival and recurrence rates in patients who underwent SL. We retrospectively analyzed 288 patients who underwent SL from January 2010 to December 2023. Survival analysis was performed using the Kaplan-Meier method, and survival curves were subsequently drawn. Factors predicting SL outcomes were investigated through univariate and multivariable Cox regression analyses. Univariate and multivariable analyses consistently demonstrated significant variations in overall survival (OS) and disease-free survival (DFS) among subgroups receiving neoadjuvant therapy (NT), which also stood out as independent prognostic factors. Patients undergoing NT showed enhanced OS [hazard ratio (HR) =0.4652, 95% confidence interval (CI): 0.3042-0.7116, P=0.004] and DFS (HR =0.5182, 95% CI: 0.3243-0.8279, P=0.01). Earlier pT stages were associated with better prognosis (P<0.05). Significant differences in both OS and DFS were noted across pN stages, with earlier stages indicating improved prognosis; this was a significant independent factor for DFS (P<0.001). Similar significant trends were observed across pathological Tumor-Node-Metastasis (pTNM) stages, with earlier stages linked to better outcomes. Additionally, body mass index (BMI) was identified as an independent prognostic factor for both OS and DFS. Clinical T stage independently influenced DFS. No significant prognostic disparities were observed in other clinical characteristics (P>0.05). NT significantly improves the prognosis for NSCLC patients undergoing SL. Pathological staging is proven to be more indicative of prognosis than clinical staging. Understanding the staging of lymph nodes (LNs) is crucial for predicting the long-term recurrence risk in patients with NSCLC who undergo SL treatment. Mediastinal and hilar LN dissection is especially important in minimizing this risk and improving prognosis.

In-field prostate cancer recurrence following radical prostatectomy and salvage radiation.

To define the natural history, patterns of recurrence and treatment modalities for local prostate cancer (PCa) recurrence following radical prostatectomy (RP) and radiation therapy (RT), and to investigate factors that could predict metastasis-free survival (MFS) in this unique patient population. We queried a prospectively maintained PCa registry to identify men developing in-field recurrence (IFR) following RP and RT from 2008 to 2021 at a single institution. IFR was defined as biopsy-proven recurrent PCa or the presence of persistent positron emission tomography-avid lesions in the prior radiation field without evidence of metastasis. Cox regression was conducted to determine predictors of MFS. Kaplan-Meier methods were used to calculate MFS, cancer-specific survival (CSS) and overall survival (OS) for patients in three primary therapy categories: cryoablation, androgen deprivation therapy (ADT) alone, and surveillance. Of 4575 patients from our registry, 108 (2.3%) with IFR were identified. The median (interquartile range [IQR]) time to IFR from salvage treatment was 78 (50-126) months. A total of 29 patients (26%) were managed with cryoablation, 23 (21%) with ADT, and 28 (25%) with surveillance. The median (IQR) follow-up was 76 (48-100) months. There were no statistically significant differences in MFS (P = 0.67) or OS (P = 0.07) among the three primary treatment cohorts. Patients treated with ADT or cryoablation had longer CSS compared to patients managed with surveillance (P = 0.047). We found that IFR may present years after completion of primary treatment for PCa. While curative management strategies may be attempted, local and distant metastatic recurrence is common and often requires systemic therapy.

Causal-inferring and molecular-docking yield new targets for malignant melanoma therapy.

To obtain the causal related genes through Mendelian randomization and to screen the therapeutic drugs for malignant melanoma. Using Mendelian randomization, the causal relationship between genes and melanoma patients was calculated based on clumped genetic instruments extracted from genome-wide association studies. Prognostic significance of potential target genes was evaluated using survival information of patients with skin cutaneous melanoma in The Cancer Genome Atlas. In the Comparative Toxicogenomics Database (CTDbase), therapeutic drugs acting on target genes were screened amongst the interactions of medical and experimental evidence. Finally, considering the absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics of drugs, available drugs and their transformation structures are generated. The binding ability of receptor-ligand was evaluated by the molecular docking of target gene crystal structure with drug-like chemicals. As a result, three potential target genes LYZ, C1QB and BTN3A2, were negatively associated with melanoma patients, and showed significant difference (Logrank P value < 0.05) in overall survival and/or progression-free interval. A total of 183 unique interactive drug-like chemicals from CTDbase were obtained by the keywords of target genes. Through assessment of ADMET properties and binding ability of receptor-ligand, 15 antagonists and 25 agonists of matched drug-like chemicals showed therapeutic effects on target genes. On the basis of causal relationship, docking score and ADMET evaluation, these hit targets and drug-like compounds yield new directions for the development of potent therapeutic agents in melanoma patients.

Identification of genetic and immune mechanisms linking preeclampsia and endometrial cancer: a prognostic model for survival and treatment response

Preeclampsia (PE) and endometrial cancer (EC) are two distinct conditions that share common genetic and molecular mechanisms involving immune dysregulation, endothelial dysfunction, and angiogenesis. This study aimed to investigate the potential genetic links between PE and EC, identify key prognostic genes, and develop a risk model to predict overall survival in EC patients. We conducted comprehensive genetic and molecular analyses, revealing significant overlaps in immune and angiogenic pathways between PE and EC. Through LASSO regression and multivariate Cox analysis, we identified five core prognostic genes—FSTL3, PRSS23, IGFBP4, MYDGF, and TSC22D3—that were used to construct a risk model. This model effectively stratified EC patients into high- and low-risk groups, with significant differences in overall survival. Patients in the low-risk group exhibited better 1-, 3-, and 5-year survival outcomes and had higher immune cell infiltration and expression of immune checkpoint-related genes, indicating a more favorable tumor microenvironment. Additionally, the analysis showed that these genes are also implicated in the pathogenesis of PE, highlighting potential shared molecular mechanisms. Our findings suggest that these PE-related genes may serve as valuable prognostic biomarkers for EC and could lead to improved prognostic tools and personalized treatment strategies for EC patients.

Long-term outcomes of induction chemotherapy followed by concurrent chemoradiotherapy and adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective study.

Nasopharyngeal carcinoma (NPC) is a prevalent form of head and neck cancer, particularly in specific regions with a higher incidence. The optimal treatment strategy for locally advanced NPC (stage III and IVA, LA-NPC) involves various combinations of induction chemotherapy (IC), concurrent chemoradiotherapy (CCRT), and adjuvant chemotherapy (AC), each with distinct advantages. This one institutional study aims to retrospectively analysis the efficacy and clinical outcomes of IC with CCRT (IC+CCRT), CCRT with AC (CCRT+AC), and the comprehensive approach of IC followed by CCRT and subsequently AC (IC+CCRT+AC) in the management of LA-NPC. A total of 352 LA-NPC patients were included: 173 accepted IC+CCRT, 60 received CCRT+AC, and 119 underwent IC+CCRT+AC. The primary endpoints including overall survival (OS) and progression-free survival (PFS), were assessed using the Kaplan-Meier method and log-rank test. The median follow-up was 61.2 months (1-216 months). There was no significant difference in 5-year OS and PFS between IC group and no IC group, extending the observation time to 90 months, the OS and PFS were significantly better in IC group than no IC group (OS: 76% vs. 70%,P<0.05; PFS: 76% vs. 71%, P<0.05). Patients with 1, 2, or 3 cycles of IC had higher 5-year OS and PFS than those with more than 3 cycles (1-4 cycles IC OS: 89% vs. 87% vs. 88% vs. 79%, P<0.05; 1-4 cycles IC PFS: 87% vs. 85% vs. 85% vs. 70%, P<0.05). NP regimen demonstrated higher OS and PFS than TP, PF, and TPF regimens (OS: 95% vs. 82% vs. 85% vs. 71%, P<0.05; PFS: 93% vs. 83% vs. 81% vs. 80%, P<0.05). The 5-year OS and PFS were significantly better in AC group than no AC group (OS: 82% vs. 72%, P<0.05; PFS: 81% vs. 69%, P<0.05). In the AC group, there was no differential effect of chemotherapy cycles and chemotherapy regimens on patients' OS and PFS. In the ThNh group, patients receiving IC+CCRT+AC had higher OS and PFS compared to those receiving IC+CCRT, with no significant difference in the rest (OS: 85% VS 66% P<0.05; PFS: 78% VS 62%, P<0.05). CCRT combined with IC or AC could benefit LA-NPC patients. The IC+CCRT +AC regimen was most beneficial for NPC patients with later T and N stages.