Recurrence-free Survival In Patients Research Articles

Circulating Tumor DNA Analysis in Advanced Urothelial Carcinoma: Insights from Biological Analysis and Extended Clinical Follow-up.

To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease. We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors. Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathologic downstaging (HR = 4.7; P = 0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR = 3.4; P = 0.0005) and after RC (HR = 17.8; P = 0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Basal/Squamous (Ba/Sq) subtype and enrichment of epithelial-to-mesenchymal transition and cell cycle-associated gene sets. ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than 5 years follow-up and outperforms pathologic downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.

Multivisceral resection for retroperitoneal liposarcoma-is it worth it? A 20-year single-center experience.

Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. The overall survival rate at 5years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.

Single-Dose Post-Office Fulguration Mitomycin C Instillation Appears to Improve Recurrence-Free Survival in Patients With Low-Grade Noninvasive Bladder Cancer.

Perioperative instillation of mitomycin-C (MMC) has shown effectiveness in reducing the recurrence of low-grade non-muscle invasive bladder cancer (NMIBC). Data is lacking about the impact of single-dose MMC following office fulguration of low-grade urothelial carcinoma. We compared the outcomes of small-volume low-grade recurrent NMIBC in patients treated with office-fulguration - with and without an immediate single-dose instillation of MMC. A retrospective analysis of medical records of patients with recurrent small-volume (≤1 cm) low-grade papillary urothelial cancer who underwent fulguration in a single institution between January 2017 and April 2021 either with or without instillation of post-fulguration MMC (40mg/50 mL). The primary outcome was recurrence-free survival (RFS). Of 108 patients (27% women) who underwent fulguration, 41% received intravesical MMC. The treatment and control groups had similar sex ratio, mean age, mass size, tumor multifocality and or tumor grade. Median RFS was 20 months (95% CI 4-36) in the MMC group and 9 months (95% CI 5-13) in the control group (P=.038). Multivariate Cox regression analysis showed that MMC instillation was associated with longer RFS (OR=0.552, 95% CI 0.320-0.955, P=.034) and multifocality was associated with shorter RFS (OR=1.866, 1.078-3.229, P=.026). A higher rate of grade 1-2 adverse events was observed in the MMC group (18.2%) vs. the control (6.8%, P=.048). No complications grade 3 or higher were observed. A single dose of MMC instilled after office fulguration is associated with longer RFS compared to patients who did not receive MMC after the procedure, with no associated high-grade complications.

Abstract PO-066: Complete pathological response following neoadjuvant chemotherapy and recurrence free survival in patients with p16-positive oropharyngeal cancer

Abstract Introduction: Locoregionally advanced p16+ squamous cell carcinoma of the oropharynx (OPSCC) is most often treated either with primary chemoradiation (CRT) or surgery followed by adjuvant treatment. Surgery alone is often insufficient treatment as adverse features such as extranodal extension, close or positive margins, lymphovascular invasion, or multiple positive lymph nodes are often identified, resulting in the need for adjuvant radiation or CRT. Primary surgery is often not pursued in more advanced cases since surgical pathology may show adverse features requiring adjuvant CRT, resulting in "triple therapy", the effects of which may worsen risk of long-term treatment toxicity. Our institution has demonstrated excellent oncologic and quality of life outcomes using a neoadjuvant chemotherapy (NAC) regimen of cisplatin and docetaxel prior to surgical treatment with TORS and neck dissection. Due to high rates of clinical-to-pathologic downstaging, adjuvant treatment is often avoided entirely. Here, we explore whether the development of a complete pathologic (pCR) response following NAC associates with 2-year recurrence free survival. Methods: A retrospective cohort study of patients receiving neoadjuvant doublet cisplatin and docetaxel followed by surgery (NAC+S) at a single institution between October 2015 and March 2023 was performed and pathologic responses and 2-year recurrence free survival was recorded following IRB exemption. Results: Fifty-four patients with p16+ OPSCC treated with NAC+S were identified. 49 patients (91%) received three cycles of NAC; 5 patients (9%) received two cycles. Comparing clinical staging to pathologic analysis of surgical specimens, 40 of 54 patients (68%) experienced clinical-to-pathologic downstaging after NAC. A pCR was identified in 23 of 54 patients (43%). Of patients that did not develop a pCR, 9 of 31 patients (29%) received adjuvant treatment due to the identification of high-risk pathologic features. Of patients that developed a pCR, 1 of 23 (4%) developed disease relapse within 2 years. Of patients that did not develop a pCR but did not require adjuvant treatment, 2 of 22 (9%) developed disease relapse within 2 years. Of patients that did not develop a pCR but did require adjuvant treatment, 2 of 9 (22%) developed disease relapse within 2 years. A trend toward reduced risk of disease relapse was observed in patients that develop a pCR following NAC compared to those that do not but did not reach statistical significance (1 of 23 relapses with pCR, 4 of 31 relapses without pCR; P>0.05, two-sided Chi-square test). Conclusion: High rates of pCR following NAC were observed in this small retrospective cohort of patients with newly diagnosed p16+ OPSCC despite 84% of patients avoiding any adjuvant treatment. Patients that develop a pCR after NAC trend toward reduced risk of recurrence compared to those that do not. The development of pCR after NAC may be a suitable short-term clinical outcome measure in prospective clinical trials of NAC for patients with newly diagnosed p16+ OPSCC. Citation Format: Alisha R. Pershad, Maxwell Madani, Timothy B. Shaver, Arjun Joshi, Clint T. Allen, Joseph F. Goodman. Complete pathological response following neoadjuvant chemotherapy and recurrence free survival in patients with p16-positive oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-066.

Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. A competing risks survival analysis adjusted for grade, lymphovascular invasion, and stage was performed to assess local recurrence-free survival in patients with penile intraepithelial neoplasia-positive margins and completely negative surgical margins. A negative surgical margin was described in 319 men (85%), whereas penile intraepithelial neoplasia in the surgical margin was found in 59 men (15%). Local recurrence was observed in 30/319 men with a negative surgical margin compared to 11/59 men with penile intraepithelial neoplasia in the surgical margin. Adjusted for T stage and grade, patients with penile intraepithelial neoplasia at the surgical margin had a higher risk to develop a local recurrence than those with a negative surgical margin without penile intraepithelial neoplasia (HR 1.51, 95% CI 1.07-2.12, P = .019). Men with a penile intraepithelial neoplasia-positive surgical margin have an increased risk to experience local recurrence compared to men with a negative surgical margin and should undergo closer surveillance and/or adjuvant treatment.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas

BackgroundThe altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. MethodsWe determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. ResultsDuring the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3–74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02–22.68, P=0.042). ConclusionThere is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence.

143. NEOADJUVANT CHEMORADIOTHERAPY VERSUS CHEMOTHERAPY FOR THE TREATMENT OF LOCALLY ADVANCED ESOPHAGEAL ADENOCARCINOMA IN THE EUROPEAN MULTICENTER ENSURE STUDY

Abstract Background nCT and nCRT are the standard of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated superiority of either approach. This study aimed to compare clinicopathologic, oncologic and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. Methods ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009–2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. Results 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% (P < 0.001), with R0 in 78.2% and 94.2% (P < 0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased (HR 2.73, 95%CI 1.43–5.21, P = 0.002) following nCRT vs nCT. Probability of local recurrence was reduced (OR 0.71, 956% CI 0.54–0.93, P = 0.012), and distant recurrence free survival time reduced (HR 1.18, 95% CI 1.02–1.37, P = 0.023) after nCRT vs nCT, with no difference in OS among all patients (HR 1.10, 95% CI 0.98–1.25, P = 0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median 60.7, 95% CI 49.5–71.8 months, vs 40.8, 95% CI 42.8–53.4, P < 0.001). Conclusion In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence free survival for patients with LAEC, without differences in overall survival. These data support tailored patient-specific decision-making in the overall approach to achieving optimum outcomes in LAEC.

Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer.

Both high 21-gene recurrence score (RS) and high Ki-67 level are poor prognostic factors in patients with estrogen receptor (ER)-positive ERBB2-negative (ER+/ERBB-) breast cancer; however, a discrepancy between the 2 has been noted. Survival differences according to these 2 biomarkers are not well known. To assess the associations between RS and Ki-67 expression and between Ki-67 expression and recurrence-free survival in patients with ER+/ERBB- breast cancer with low RS. This cohort study included women treated for ER+/ERBB2- breast cancer who underwent the 21-gene RS test from March 2010 to December 2020 in 2 hospitals in Korea. Recurrence score and Ki-67 level. A Cox proportional hazards regression model was used to examine the association of Ki-67 with recurrence-free survival (RFS), while a binary logistic regression model was used to examine the association between Ki-67 and secondary endocrine resistance. High Ki-67 expression was defined as 20% or greater, and low genomic risk as an RS of 25 or less. Secondary endocrine resistance was defined as breast cancer recurrence that occurred after at least 2 years of endocrine therapy and during or within the first year after completing 5 years of adjuvant endocrine therapy. A total of 2295 female patients were included (mean [SD] age, 49.8 [9.3] years), of whom 1948 (84.9%) were in the low genomic risk group and 1425 (62.1%) had low Ki-67 level. The median follow-up period was 40 months (range, 0-140 months). The RS and Ki-67 level had a moderate correlation (R = 0.455; P < .001). Of the patients with low Ki-67 level, 1341 (94.1%) had low RS, whereas 607 of 870 patients with high Ki-67 level (69.8%) had low RS. In patients with low RS, the RFS differed significantly according to Ki-67 level (low Ki-67, 98.5% vs high Ki-67, 96.5%; P = .002). Among the 1807 patients with low genomic risk who did not receive chemotherapy, high Ki-67 level was independently associated with recurrence (hazard ratio, 2.51; 95% CI, 1.27-4.96; P = .008). Recurrence after 3 years differed significantly according to Ki-67 level (low Ki-67, 98.7% vs high Ki-67, 95.7%; P = .003), whereas recurrence within 3 years did not differ (low Ki-67, 99.3% vs high Ki-67, 99.3%; P = .90). In addition, Ki-67 was associated with secondary endocrine resistance in patients with low RS who did not receive chemotherapy (odds ratio, 2.49; 95% CI, 1.13-5.50; P = .02). In this cohort study of patients with ER+/ERBB2- breast cancer, a moderate correlation was observed between Ki-67 and RS, and high Ki-67 level in patients with low genomic risk was associated with increased risk of secondary endocrine resistance.

Elevated preoperative plasma D-dimer level was an independent prognostic factor for patients with PDAC after curative resection: a retrospective analysis.

In this study, the relationship between preoperative plasma D-dimer level and overall survival and recurrence free survival were evaluated in patients with curative resection of pancreatic ductal adenocarcinoma. Preoperative plasma D-dimer level of 573 patients with pancreatic ductal adenocarcinoma were collected. The univariate and multivariate Cox hazard models were used to identify independent variables associated with overall survival and recurrence free survival in this study. The Kaplan-Meier method was used to evaluate overall survival and recurrence free survival, and the differences between survival curves were analyzed using the Log-rank test. Continuous variables were presented as $\overline{x}\pm s$, parametric analysis was performed using t-test. Categorical variables were analyzed by means of the chi-square or Fisher's exact test. Based on the analysis for the whole study, the results showed that patients in the elevated plasma D-dimer levels had a tendency to have an elder mean age (58.69±8.32years vs. 63.05±8.44years, P<0.001), larger tumour size ≥4cm (P=0.006), advanced T stage (P=0.024), N stage (P=0.041), Tumor, Node and Metastasis (TNM) stage (P=0.029) and postoperative complications (P=0.042) was more likely occurred. Besides, according to the results of Cox multivariate analysis, elevated preoperative plasma D-dimer level was an independent prognostic factor not only for overall survival (Hazard Ratio (HR):1.430, 95% Confidence Interval (CI) (1.163-1.759), P=0.001) but also for recurrence free survival (HR:1.236, 95% CI (1.018-1.500), P=0.032). In our study, the elevated preoperative plasma D-dimer level may act as an independent prognostic factor for overall survival and recurrence free survival in patients with pancreatic ductal adenocarcinoma after curative resection. Pancreatic ductal adenocarcinoma patients with elevated preoperative plasma D-dimer level had a worse prognosis than those with normal plasma D-dimer level; and the elevated preoperative plasma D-dimer level may imply heavy tumour burden and provide supplementary information regarding disease status.

Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients.

To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P < .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P < .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

Urological procedures performed by gynecologists: Activity profile in a gynecological surgery department, 10-year observation cohort

IntroductionThe proximity of the urinary tract to the female genital tract explains its possible involvement in pelvic gynaecological cancer or deep endometriosis. Surgical treatment is aimed at improving overall survival and recurrence-free survival of patients, as well as restoring normal anatomy and functional integrity depending on the pathology. These operations are accompanied by significant post-operative complications. Thus, the urological procedures performed must be rigorously justified, and the different resection and reconstruction techniques adapted to the pathology and the level of infiltration. ObjectiveTo describe the activity profile, over the last ten years, of a gynaecological surgery department in terms of urological procedures in the management of patients with deep endometriosis and pelvic carcinology. Study designThis is a monocentric retrospective observational study, including all patients who underwent a urological procedure by a gynaecological surgeon only, as part of the management of pelvic gynaecological cancers or deep endometriosis, at the University Hospital Centre (CHU) of Strasbourg, between January 1st 2010 and April 31st 2021. The variables studied were early postoperative complications, the rate of surgical reintervention, operating time, length of hospital stay, the need for peri-operative drainage or transfusion, and post-operative functional disorders. ResultsA total of 86 patients were included, 27 in the pelvic gynaecological cancer group and 59 in the deep endometriosis group. 61.6% of patients received uretero-vesical catheterization, 60.5% partial cystectomy, 10.5% psoic bladder ureteral reimplantation, and 3.5% trans-ileal Bricker skin ureterostomy. The mean operating time was 316 min in the pelvic gynaecological cancer group and 198.9 min in the deep endometriosis group. The average hospital stay was 11.5 days, 22.3 days for patients treated for pelvic cancer and 6.3 days for those treated for endometriosis. The rate of minor post-operative complications was 8.2% of cases, and major post-operative complications 17.4% of cases, the majority of which were in the gynecological cancer group. There were no cases of intra- or early post-operative death. Early postoperative urinary complications affected 14.0% of the total patients, mostly in the gynaecological cancer group with 33.3% of patients, but only 5.1% of patients in the deep endometriosis group. The total reoperation rate within 60 days postoperatively was 15.1%, 40.7% for patients treated for gynaecological cancer and 3.4% for those treated for deep pelvic endometriosis. The rate of reoperations for urinary complications was 11.6% of total patients, or 76.9% of total reoperations. 15 patients received labile blood products intra- or postoperatively, 11 in the pelvic gynaecological cancer group and 4 in the endometriosis group. ConclusionOur overall results appear comparable to those reported in the literature and are particularly satisfactory in terms of post-operative complications after partial cystectomy in the management of deep endometriosis compared to other gynaecological departments. This work encourages us to continue and improve the training of gynaecological surgeons in terms of multidisciplinary surgical procedures, including urological ones, to obtain a global vision of the pathology and to allow an optimal quality of care for the patients.

SYNPO2 upregulation is an unfavorable prognostic factor for nasopharyngeal carcinoma patients.

Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2 expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2 expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2 was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2 expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2 may aid in the development of potential prognostic biomarkers for NPC patients.

MiR-146b-5p regulates the scavenging effect of GPx-3 on peroxide in papillary thyroid cancer cells

BackgroundGlutathione peroxidase (GPx) is an important antioxidant enzyme in thyroid follicular cells. Reduced levels of glutathione peroxidase 3 (GPx-3) expression in papillary thyroid cancer (PTC) are associated with poor prognosis. However, the reason for the decreased expression level of GPx-3 in PTC is unclear. MethodsThe expression of GPx-3 in papillary thyroid carcinoma and adjacent normal tissue (n = 18) was detected by Western blotting. Bioinformatics was used to predict the relationship between the level of GPx-3 and gender, age, lymph node metastasis, stage, BRAFV600E mutation, and recurrence-free survival of patients. The possible upstream microRNAs of GPx-3 were analyzed by bioinformatics tools also. We verified the relationship between GPx-3 and upstream microRNA by dual luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA). ResultsThe protein level of GPx-3 decreased in PTC, and analysis of public database datasets suggests that its decreased expression may be associated with the BRAFV600E mutation. MiR-146b-5p was significantly overexpressed in PTC. The dual luciferase reporter assay verified the effect of miR-146b-5p on 3′-UTR of GPx-3 mRNA. Knockdown of miR-146b-5p in thyroid cancer cell lines TPC-1 and BCPAP increased GPx-3 expression levels, accompanied by an increase in the conversion of glutathione (GSH) to oxidized glutathione (GSSG). ConclusionsIn conclusion, the level of GPx-3 decreases in papillary thyroid carcinoma and impairs intracellular peroxide clearance, due to the inhibitory effect of miR-146b-5p. The accumulation of intracellular peroxides may contribute to the poor prognosis of thyroid cancer.

The impact of sarcopenia on prognosis of patients with pancreatic cancer: A systematic review and meta-analysis.

To summarize recent findings on the association of low skeletal muscle mass and muscle quality with overall survival and recurrence-free survival in patients with pancreatic cancer. A systematic search was conducted using Medline (via PubMed), Embase and Scopus databases for observational studies reporting on the overall survival and recurrence-free survival. Pooled effect sizes were reported as hazards ratio along with 95% confidence intervals. A total of 34 studies were included. Low skeletal muscle index (indicating muscle mass) was associated with poor overall survival (hazards ratio: 1.50; 95% confidence interval: 1.34, 1.67) and lower recurrence-free survival (hazards ratio: 1.28, 95% confidence interval: 1.15, 1.43). Low skeletal muscle attenuation (indicating muscle quality) was associated with poor overall survival (hazards ratio: 1.32; 95% confidence interval: 1.05, 1.66). Recurrence-free survival was similar in patients with low and normal/high skeletal muscle attenuation (hazards ratio: 1.12, 95% confidence interval: 0.89, 1.40). Both low skeletal muscle mass and poor muscle quality are associated with poor long-term survival. Low skeletal muscle index, but not low skeletal muscle attenuation, are associated with poor recurrence-free survival.

Functional Analysis and Clinical Importance of ATP1A1 in Colon Cancer.

Na+/K+-ATPase α1 subunit (ATP1A1) exhibits aberrant expression in various types of cancer. Moreover, its levels in specific tissues are associated with the development of cancer. Nevertheless, the mechanism and signaling pathways underlying the effects of ATP1A1 in colon cancer (CC) have not been elucidated, and its prognostic impact remains unknown. Knockdown of ATP1A1 expression was performed in human CC cell lines HT29 and Caco2 using small interfering RNA. The roles of ATP1A1 in various biological processes of cells (i.e., proliferation, cell cycle, apoptosis, migration, and invasion) were assessed. Microarray analysis was utilized for gene expression profiling. Samples obtained from 200 patients with CC who underwent curative colectomy were analyzed through immunohistochemistry. ATP1A1 knockdown suppressed cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that the upregulated or downregulated gene expression in ATP1A1-depleted cells was related to the extracellular signal-regulated kinase 5 (ERK5) signaling pathway [epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase 5 (MAP2K5), mitogen-activated protein kinase 7 (MAPK7), FOS, MYC, and BCL2 associated agonist of cell death (BAD)]. Immunohistochemical analysis demonstrated a correlation between ATP1A1 expression and pathological T stage (p = 0.0054), and multivariate analysis identified high ATP1A1 expression as an independent predictor of poor recurrence-free survival in patients with CC (p = 0.0040, hazard ratio: 2.807, 95% confidence interval 1.376-6.196). ATP1A1 regulates tumor progression through the ERK5 signaling pathway. High ATP1A1 expression is associated with poor long-term outcomes in patients with CC.

The role of platinum-based antineoplastic drugs and their impact on complete pathological response and prognosis in patients with BRCA-associated triple-negative breast cancer after neoadjuvant treatment: a single institution experience

Background. BRCA-associated triple negative breast cancer (TNBC) is considered one of the most aggressive subtypes of breast cancer with high sensitivity to chemotherapy, which leads to increased interest in finding new treatment options for patients with this subtype of breast cancer. Aim. To determine the role of adding a platinum drug to standard systemic neoadjuvant therapy (NAC) for patients with primary BRCA-associated TNBC with clinical stage T1–3N0–3M0, and to evaluate the effect of platinum-based drugs on recurrence-free survival in patients of this category. Materials and methods. The study included 75 patients diagnosed with primary BRCA-associated TNBC. They were divided into 2 groups depending on the NAC provided, and then they were subdivided depending on the completion of the course of ongoing NAC, the final pathomorphological result and the presence of recurrence. Results. Group I included 48 (64 %) patients who received the AC–T regimen; in group II (n = 27 (36 %)) patients received NAC according to the AC–TCarb regimen. Patients of group II showed a higher frequency of achieving pathological complete response (pCR) compared with patients of group I (73.7 % versus 41.2 %, respectively, p = 0.0433). Taking into account the NAC regimens being carried out, patients of group I had a slightly higher risk of recurrence compared to patients of group II (p = 0.099). Conclusion. In patients with primary BRCA-associated TNBC, the addition of platinum compounds to the systemic NAC resulted in achieving of pCR in 73.7 % cases compared with 41.2 % pCR after the standard anthracycline-taxane NAC, which entails a reduced risk recurrence in this category of patients. Performing a full course of planned NAC has a positive trend in achieving pCR in patients of this category.

B4GALNT1 promotes carcinogenesis by regulating epithelial-mesenchymal transition in hepatocellular carcinoma based on pan-cancer analysis.

β-1,4-N-Acetyl galactosaminyltransferase1 (B4GALNT1) has been reported to play important roles in tumor progression and metastasis. Herein, we investigate the oncogenic roles of B4GALNT1 for hepatocellular carcinoma (HCC) based on immune microenvironment. The Cancer Genome Atlas database and Genotype-Tissue Expression, cBioportal, ImmuCellAI, TIMER2 and other databases were searched to analyze the expression and clinical applications of B4GALNT1 in liver cancer patients. Kaplan-Meier survival analysis, Cox regression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were utilized. Moreover, western blot assay, immune histochemistry staining, Cell Counting Kit-8 (CCK-8) assay, invasion and migration assay were performed to evaluate the function of B4GALNT1 in HCC. B4GALNT1 is overexpressed in 14 tumors, and the mRNA expression levels of B4GALNT1 were remarkably elevated in most tumor types, including HCC. In addition, B4GALNT1 expression was an independent prognostic factor, and a low expression of B4GALNT1 showed a better overall survival and disease-specific recurrence-free survival in patients with HCC. Gene set variation analysis indicated that B4GALNT1 presented a positive correlation with the epithelial-mesenchymal transition (EMT) pathway in HCC. B4GALNT1 expression was closely associated with immune activation genes in the HCC microenvironment. Moreover, B4GALNT1 expression was higher in HCC tissue than that in surrounding tissues. B4GALNT1 promoted the expression of apoptosis-related or EMT-related proteins and then decreased the expression of Bcl-2 and Bcl-xl in HCC cells, suggesting that B4GALNT1 knockdown significantly inhibited the proliferation and invasion of HCC cells. B4GALNT1 may promote HCC development through regulating the EMT pathway, which suggests that B4GALNT1 may serve as a promising predictive biomarker and a potential therapeutic target for HCC.

Retrospective comparison of percutaneous balloon compression and radiofrequency-thermocoagulation in the management of trigeminal neuralgia

PurposeTo compare percutaneous balloon compression (PBC) and radiofrequency thermocoagulation (RFTC) for the treatment of trigeminal neuralgia.MethodsThis was a retrospective single-center analysis of data from 230 patients with trigeminal neuralgia who underwent 202 PBC (46%) and 234 RFTC (54%) from 2002 to 2019. Comparison of demographic data and trigeminal neuralgia characteristics between procedures as well as assessment of 1) initial pain relief by an improved Barrow Neurological Institute (BNI) pain intensity scale of I–III; 2) recurrence-free survival of patients with a follow-up of at least 6 months by Kaplan-Meier analysis; 3) risk factors for failed initial pain relief and recurrence-free survival by regression analysis; and 4) complications and adverse events.ResultsInitial pain relief was achieved in 353 (84.2%) procedures and showed no significant difference between PBC (83.7%) and RFTC (84.9%). Patients who suffered from multiple sclerosis (odds ratio 5.34) or had a higher preoperative BNI (odds ratio 2.01) showed a higher risk of not becoming pain free. Recurrence-free survival in 283 procedures was longer for PBC (44%) with 481 days compared to RFTC (56%) with 421 days (p=0.036) but without statistical significance. The only factors that showed a significant influence on longer recurrence-free survival rates were a postoperative BNI ≤ II (P=<0.0001) and a BNI facial numbness score ≥ 3 (p = 0.009). The complication rate of 22.2% as well as zero mortality showed no difference between the two procedures (p=0.162).ConclusionBoth percutaneous interventions led to a comparable initial pain relief and recurrence-free survival with a low and comparable probability of complications. An individualized approach, considering the advantages and disadvantages of each intervention, should guide the decision-making process. Prospective comparative trials are urgently needed.

Preoperative C-reactive protein-to-albumin ratio as a prognostic factor in biliary tract cancer: A systematic review and meta-analysis.

The preoperative C-reactive protein-to-albumin ratio is a novel inflammation-based prognostic marker in various cancers. However, its prognostic role in biliary tract cancer is unknown. We conducted a systematic review and meta-analysis to evaluate the prognostic value of preoperative C-reactive protein-to-albumin ratio in biliary tract cancer. A systematic search of the literature for studies evaluating the prognostic value of C-reactive protein-to-albumin ratio in patients undergoing surgery for biliary tract cancer was conducted, and a random effects meta-analysis of overall survival and recurrence-free survival was performed. Nine studies with 1292 participants were included. The preoperative C-reactive protein-to-albumin ratio negatively correlated with overall survival (hazard ratio, 2.44 [95% confidence interval: 1.98-2.90]; P < .001) and recurrence-free survival (hazard ratio, 2.73 [95% confidence interval: 2.01-3.70]; P < .001). Subgroup analysis showed that an elevated preoperative C-reactive protein-to-albumin ratio predicted poor overall survival, regardless of the cutoff value, sample size, histological type, and treatment. An elevated preoperative C-reactive protein-to-albumin ratio is significantly associated with poor prognosis in patients undergoing surgery for biliary tract cancer. The C-reactive protein-to-albumin ratio may be an independent prognostic biomarker for overall survival and recurrence-free survival in patients undergoing surgery for biliary tract cancer.

Recurrence free survival in patients with HPV+ head and neck cancer treated with TORS and neck dissection.

e18076 Background: Prior research has demonstrated that delays to initiation of radiation therapy (RT) in the treatment of head and neck squamous cell carcinoma (HNSCC) after surgery result in poorer survival outcomes. However, there is limited data with little long-term follow up to evaluate whether human papilloma virus (HPV) positive primaries undergoing transoral robotic surgery (TORS) and neck dissection (ND) face a similar decrement in recurrence free survival (RFS) and disease specific survival (DSS). Methods: Single center retrospective chart review of patients diagnosed with HPV positive primary nonmetastatic HNSCC who underwent TORS with ND followed by RT with or without Chemotherapy and/or Immunotherapy from 2012-2022 with data collection from December 2022 to February 2023. 248 patients met inclusion criteria and were analyzed for DSS and RFS. Kaplan-Meier survival analysis with Log-rank testing was used to assess the impact of time intervals between diagnosis, TORS, radiation initiation and radiation completion on survival. Univariable and Multivariable Cox proportional hazards regression analysis was performed to identify factors associated with RFS and DSS and adjust for potential confounding variables. Subgroup analysis was completed with high risk (lymph nodes &gt; 4 with extracapsular extension) and low risk population. Results: Median follow-up time was 47.22 months (1452.07 days). Of 248 patients, 17 had a recurrence and 12 died due to disease. In patients who underwent radiation therapy for a time frame (TR1-R2) of 5-7 weeks compared with those who had a shortened or prolonged course of RT, RFS (140.116 months, p-value = .012) and DSS (142.641 months, p-value = .016) were improved. Although time from diagnosis to TORS did not impact RFS (p-value = .195), improved RFS persisted in patients who underwent time from diagnosis to radiation completion (TD-R2) or total treatment package time (TTPT) between 17-20 weeks (109.155 months, 95% CI: 105.276-113.034, p-value = .057) compared to patients with TTPT less than 17 or greater than 20 weeks. When the population is stratified into high risk and low risk groups, patients in the high risk group who underwent Chemotherapy had improved RFS compared to no chemotherapy (HR: 7.19, p-value = .09). On Univariate Analysis, TR1-R2 &lt; 5 weeks and &gt; 7 weeks, TD-R2 &lt; 17 weeks and &gt; 20 weeks, extracapsular extension, smoking history, and age &gt; 70 were associated with increased risk of recurrence. Conclusions: For HPV positive patients with OPSCC undergoing TORS and Neck dissection, time to radiation initiation may not be as critical in improving OS, DSS, and RFS as other patient populations. However, the length of radiation time between 5 to 7 weeks and overall treatment time from 17-20 weeks may improve recurrence free survival and disease specific survival.