Decrease In Disease-free Survival Research Articles

Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas.

To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher's exact, Log-Rank Mantel Cox and Cox regression were performed. In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (p = 0.035) and mean MSH6 expression was significantly higher than MSH2 (p = 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (p = 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06). Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.

The Impact of DAXX, HJURP and CENPA Expression in Uveal Melanoma Carcinogenesis and Associations with Clinicopathological Parameters.

Uveal melanomas (UMs) represent rare malignant tumors associated with grim prognosis for the majority of patients. DAXX (Death Domain-Associated Protein), HJURP (Holliday Junction Recognition Protein) and CENPA (Centromere Protein A) proteins are implicated in epigenetic mechanisms, now in the spotlight of cancer research to better understand the molecular background of tumorigenesis. Herein, we investigated their expression in UM tissues using immunohistochemistry and explored possible correlations with a multitude of clinicopathological and survival parameters. The Cancer Genome Atlas Program (TCGA) was used for the investigation of their mRNA levels in UM cases. Nuclear DAXX expression correlated with an advanced T-stage (p = 0.004), while cytoplasmic expression marginally with decreased disease-free survival (DFS) (p = 0.084). HJURP nuclear positivity also correlated with advanced T-status (p = 0.054), chromosome 3 loss (p = 0.042) and increased tumor size (p = 0.03). More importantly, both nuclear and cytoplasmic HJURP immunopositivity correlated with decreased overall survival (OS) (p = 0.011 and 0.072, respectively) and worse DFS (p = 0.071 and 0.019, respectively). Lastly, nuclear CENPA overexpression was correlated with presence of irido-corneal angle involvement (p = 0.015) and loss of chromosome 3 (p = 0.041). Nuclear and cytoplasmic CENPA immunopositivity associated with decreased OS (p = 0.028) and DFS (p = 0.018), respectively. HJURP and CENPA mRNA overexpression exhibited strong association with tumor epithelioid histology and was linked to worse prognosis. Our results show the compounding role of DAXX, HJURP and CENPA in UM carcinogenesis, designating them as potential biomarkers for assessing prognosis and possible targets for novel therapeutic interventions.

A 10-Year Retrospective Cohort Study of Endometrial Cancer Outcomes and Associations with Lymphovascular Invasion: A Single-Center Study from Germany.

This 10-year retrospective cohort study at a single-center clinic in Germany aimed to analyze the outcomes of endometrial cancer patients and explore the impact of lymphovascular invasion (LV) on patient outcomes and disease-free survival (DFS). Identifying correlations among demographic data, tumor characteristics, treatment modalities, and survival outcomes could enhance patient management and improve survival rates. The study encompassed patients diagnosed and treated for endometrial cancer from January 2010 to December 2020. Clinical and pathological data were extracted from medical records for 311 patients, focusing on variables such as age, histological type, tumor grade, type of surgical treatment, and adjuvant therapies. Survival analysis was conducted using the Kaplan-Meier method and multivariate Cox proportional hazard models to identify factors independently associated with survival. The study demonstrated that lymphovascular invasion significantly impacted survival outcomes on Kaplan-Meier analysis (log-rank p-value = 0.0058). Patients with LV showed a marked decrease in DFS compared to those without LV invasion, with a median DFS of 3.2 years and a hazard ratio of 2.18 (95% CI: 1.56-3.04, p < 0.001). Furthermore, high-grade tumors and p53 positivity were strongly associated with reduced DFS, with hazard ratios of 1.93 (p = 0.001) and 2.11 (p < 0.001), respectively. Patients with distant metastasis exhibited the most significant decline in survival, with a hazard ratio of 5.56 (95% CI: 2.45-10.18, p < 0.001). Despite comprehensive surgical and adjuvant therapies, these high-risk factors dictated poorer outcomes. The presence of lymphovascular invasion, high-grade tumors, and genetic markers like MSI and p53 are pivotal in predicting the course of endometrial cancer. This study underscores the necessity for aggressive management strategies in patients exhibiting these high-risk features to potentially improve prognosis and survival outcomes. The findings advocate for enhanced therapeutic strategies tailored to the biological behavior of the tumor, thereby aiming to elevate the overall survival rates for women diagnosed with endometrial cancer.

Prognostic Significance of Circulating and Disseminated Tumor Cells in Breast Cancer Patients before and after Adjuvant Chemotherapy.

Despite the advances in treatment, breast cancer (BC) remains a major cause of death in women. This study aims to evaluate the prognostic significance of detecting circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in paired peripheral blood (PB) and bone marrow (BM) samples obtained both before and after adjuvant chemotherapy from patients with operable BC. In this experimental study, from 160 patients with primary BC, we collected 160 PB and BM samples before and we could be able to collect PB and BM samples from 100 of them after adjuvant chemotherapy. The expression level of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin 1 (MGB1), mucin 2 (MUC2) and trefoil factor 1 (TFF1) mRNAs in the PB/BM samples were analyzed by quantitative real-time polymerase chain reaction (PCR). Multivariate Cox regression analyses indicated that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvant chemotherapy was an independent factor for prognosis associated with decreased diseasefree survival (DFS). Patients with tumor cells detected in both PB and BM and patients with persistent detection of tumor cells before and after chemotherapy had worse outcomes compared to those with tumor cells detected in one or neither of the compartments. This study suggests that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvant chemotherapy could be an independent predictor of DFS in operable BC patients.

Long-term consequences of positive surgical margin after partial nephrectomy for renal cell carcinoma: multi-institutional analysis.

The aim of the study was to determine the impact of positive surgical margins (PSM) after PN on very long-term recurrence in a contemporary cohort. Patients who underwent PN for a localized renal tumour were included. Patients were stratified according to the presence of PSM. Data on patients' characteristics, the tumour, the peri- and postoperative events were collected. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method and compared by the log-rank test. Sensitivity analyses using weighted propensity score analysis was performed to account for potential selection biases arising from the nonrandom allocation of patients to different groups. A total of 1115 patients were included in the study. The incidence of PSM was 5.4% (n = 61). The median follow-up time was 51months for the PSM group and 61months for the NSM group (p = 0.31). Recurrence rates were significantly higher in the PSM group (13%, n = 8) compared to the NSM group (7%, n = 73) (p = 0.05). This resulted in a significant reduction in DFS in the PSM group (p = 0.004), particularly pronounced in patients with clear cell renal cell carcinoma. Additionally, OS was significantly lower in the PSM group (p < 0.01). Propensity score analysis confirmed a decrease in DFS for the PSM group (p = 0.05), while there was no significant difference in OS between the two groups (p = 0.49). In this retrospective multicenter study, PSM impact on oncological outcomes, increasing recurrence, but no difference in OS was observed post-adjustment for biases.

The Impact of BRCA1 Expression on Survival Status in Ovarian Serous Carcinoma of Egyptian Patients.

The present study aimed to investigate the impact of BRCA1 protein expression on the patients' outcome of ovarian serous carcinoma, and its correlation with different clinicopathologic features. Immunohistochemistry with BRCA1 was done for 80 cases of ovarian serous carcinoma that had a positive family history. Correlation with clinico-pathologic variables and patients' outcomes was investigated. BRCA1 expression was detected in 61.2% of the studied cases. A significant relation with patients' age, tumor grade and tumor stage was found (P<0.05). Also, there was a significant decrease in disease free survival (DFS) & overall survival (OS) in the positive BRCA1 group. Metastasis, recurrence, residual disease, and mortality rate showed significantly higher figures in patient with BRCA1 expression (P<0.05). Positive BRCA1 expression had proven to be associated with advanced stage & grade of tumors, as well as worsened prognostic survival parameters (metastasis, recurrence, residual disease, and mortality) in patients with ovarian serous carcinoma.

Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors

BackgroundTo compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT).MethodsBased on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan–Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years.ResultsWe included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150–2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255–2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057–2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185–1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347–2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761).ConclusionR-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (<3 cm) Nonfunctional Pancreatic Neuroendocrine Tumors?

A proposed grading scheme for predicting recurrence in medullary thyroid cancer based on the Ki67 index and metastatic lymph node ratio.

The Ki67 index and lymph node ratio (LNR) have been proposed as components of alternative pathological classification schemes, but the most appropriate classification for patients with medullary thyroid cancer (MTC) remains unknown. The aim of the present study was to examine the usefulness of a new grading system combining the Ki67 index and LNR as a predictor of prognostic and disease-free survival (DFS) in MTC. We conducted a retrospective study of patients with MTC who were registered at Sun Yat-sen University Cancer Center, Guangzhou, P. R. China from June 2003 to October 2021. The DFS rates were assessed using risk-adjusted Cox proportional hazard regression modeling to explore the relationship among pathological features, nutritional status and DFS. The Ki67 index (cutoff value: 5% and 10%) and LNR (cutoff value: 0.2 and 0.3) were combined to create a new grading system. In total, 101 matched patients were assessed. The integrated grading system showed better separation of Kaplan Meier (KM) curves for DFS. As the grading stage progressed, there was a significant stepwise decrease in DFS, which was better than Ki67, LNR and N staging alone. According to the grading system, the high-risk group had a worse prognosis. The proposed grading scheme demonstrated a better prognostic performance in MTC patients than the Ki67, LNR and N staging alone. However, larger scale studies are needed to further verify our findings.

Clinicopathological and survival profile of patients with salivary gland myoepithelial carcinoma: A systematic review.

In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with myoepithelial carcinoma (MC) of the salivary glands. MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma", "malignant myoepithelioma", and "salivary glands". Only primary salivary glands MC that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias. Forty-three studies (comprising data from 71 cases) met the inclusion criteria. The patients having MC showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%) (49.3%). Clinically, the MC presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p=0.010) and solid growth pattern (p=0.003) were related to decreased disease-free survival (DFS). Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments (surgery, radiation therapy with/without chemotherapy) showed a longer DFS (p=0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1% respectively. Salivary gland MC is a rare salivary cancer with no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower DFS. Overall, salivary gland MC presented low recurrence and metastasis rates.

PROGNOSTIC FACTORS FOR LYMPH NODE INVOLVEMENT, DISEASEFREE SURVIVAL AND OVERALL SURVIVAL IN PENILE CANCER

Background Penile Cancer (PC) is a rare neoplasm. The most important PC prognostic factor is inguinal lymph node (ILN) involvement (pN+). Inguinal lymphadenectomy (ILND) is the most accurate method for ILN staging. Due to high morbidity and quality of life impairment, alternative staging modalities have been researched. This epidemiological study aims to assess risk factors to determine prognosis in PC patients. A retrospective review was Methods conducted on 84 PC patients. Mean age was 58.68 (12.98) years. Thirty-Eight (45.3%) patients underwent ILND. The main reasons were primary tumor staging (pT2 and up) and palpable nodes (cN+) in physical examination. For pN+ risk, cN+, tumor inltration of penile body, dartos, spongios Results um and corpora cavernosa, as well as perineural and lymph vascular invasion (LVI) were signicant. For recurrence and metastasis, cN+, penile body invasion, LVI, corpora cavernosa invasion and pN+ showed statistical signicance. In overall survival (OS) evaluation, cN+, LVI, penile body, dartos, spongiosum and corpora cavernosa invasion, pT and pN+ presented worst prognosis. In multivariate analysis, cN+ was a risk factor for pN+. Cox regression analysis was also performed. Factors that decreased disease-free survival (DFS), were cN+, penile body, dartos or corpora cavernosa invasion and pN+. When applied to OS, cN+, penile body invasion, LVI, dartos invasion, pT and pN+ were related to worst survival. Most patients (67.5%) stayed disease free. Recurrence was more common on ILN (14.3%). When metastatic (10.7%), mortality was 55.6%. Conclusion This study conrmed several risk factors for pN+, DFS and OS on PC patients.

A nomogram for predicting the HER2 status of circulating tumor cells and survival analysis in HER2-negative breast cancer.

In breast cancer patients with HER2-negative tumors (tHER2-), HER2-positive CTCs (cHER2+) were associated with promising efficacy of HER2-targeted therapy, but controversy has persisted over its prognostic effect. We developed a model including clinicopathologic parameters/blood test variables to predict cHER2 status and evaluated the prognostic value of cHER2+ in tHER2- patients. cHER2+ was detected, blood test results and clinicopathological characteristics were combined, and a nomogram was constructed to predict cHER2 status in tHER2- patients according to logistic regression analysis. The nomogram was evaluated by C-index values and calibration curve. Kaplan-Meier curves, log-rank tests, and Cox regression analyses were performed to evaluate the prognostic value of cHER2 status. TNM stage, white blood cells (WBCs), neutrophils (NEUs), uric acid (UA), De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)], and high-density lipoprotein (HDL) were found to be associated with cHER2 status in tHER2- patients in univariate logistic regression analysis, in which UA and De Ritis ratio remained significant in multivariate logistic regression analysis. A model combining these six variables was constructed, the C-index was 0.745 (95% CI: 0.630-0.860), and the calibration curve presented a perfect predictive consistency. In survival analysis, patients of the subgroups "with cHER2+/UA-low" (p = 0.015) and "with cHER2+/De Ritis ratio - high" (p = 0.006) had a significantly decreased disease-free survival (DFS). Our nomogram, based on TNM stage, WBC, NEU, UA, De Ritis ratio, and HDL, may excellently predict the cHER2 status of tHER2- patients. Incorporation with UA and De Ritis ratio may enhance the prognostic value of cHER2 status.

Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials.

Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis. We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors. Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes. In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma.

To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC). We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery. Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n= 51) was 39.2% (95% confidence interval [CI]: 25.3%-53.1%), and for patients with a low expression (n= 59), it was 63.6% (95% CI: 51.1%-76.1%) (p= 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p= 0.086). In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

ROCC/GOG-3043: A randomized non-inferiority trial of robotic versus open radical hysterectomy for early-stage cervical cancer.

TPS5605 Background: Minimally invasive surgery (MIS) is associated with improved perioperative safety outcomes, but, in 2018, the Laparoscopic Approach to Cervical Cancer (LACC) trial, a non-inferiority study comparing laparoscopic versus open radical hysterectomy for early stage cervical cancer, reported significantly worse disease-specific (DSS) and overall survival (OS) in the MIS group. Criticisms of the LACC trial include lack of proper preoperative imaging and assessment, use of transcervical uterine manipulators, and lack of proper tumor containment leading to peritoneal contamination. Subsequent retrospective studies have reported conflicting results. Given the potential benefit of MIS, the ROCC trial seeks to address the limitations of the LACC trial. Methods: ROCC is a multi-center, prospective, randomized, non-inferiority trial. The primary objective is to determine whether robotic-assisted (RBT) radical hysterectomy is not inferior to abdominal (OPEN) approach with respect to 3-year disease-free survival (DFS). Secondary objectives include DSS, OS, patterns of recurrence, peri- and postoperative complications, long-term morbidity, impact on patient-reported outcome (PRO) measures and development of lower extremity lymphedema (LEL). Key inclusion criteria include patients with histologically confirmed adenocarcinoma, squamous cell, and adenosquamous cell carcinoma of FIGO 2018 stage IA2-IB2. All patients must have a preoperative pelvic MRI confirming that the cervical tumor is &lt; 4 cm in size, no obvious evidence of extracervical extension and no nodal or other regional metastasis. Intraoperatively, the use of transcervical uterine manipulators is not allowed and specific detailed surgical techniques for proper tumor containment is required. Photographic evidence of specimen with tumor contained is mandated. We estimate the 3-year DFS to be 92% in the control (OPEN) arm. If the DFS does not differ by more than 7% and the one-sided 95% CI does not cross the non-inferiority boundary, then the RBT arm will be deemed non-inferior. 840 patients will be enrolled (420 per arm, 89 events total), which provides 90% power to exclude an absolute decrease in DFS by 7% (HR &lt; = 1.375) with a log-rank test for non-inferiority with a one-sided alpha of 0.05. The primary analysis will be conducted in all randomized patients (ITT). Given the LACC findings of worse oncologic outcomes with MIS, a formal DSMC will conduct periodic reviews of safety including two planned formal interim analyses for futility (harm) after accrual of 370 and 640 patients using an aggressive Lan-DeMets beta-spending function similar to a Pocock boundary. Results of this trial may be practice changing and will either support or refute the findings of the LACC trial. The study is currently activating sites for enrollment. Clinical trial information: NCT04831580.

Prognostic impact of early treatment discontinuation and early oxaliplatin discontinuation in patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer: an ACCENT/IDEA pooled analysis of 11 trials.

11 Background: Six months of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) remains a standard in high-risk stage III patients. Early treatment discontinuation (ETD) could worsen the prognosis. In addition, there is current lack of data on the prognostic impact of early oxaliplatin only discontinuation (EOD). Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC who participated in 11 relevant clinical trials of the ACCENT and IDEA databases, where patients were planned to receive 6 months of adjuvant fluoropyrimidine plus oxaliplatin (FOLFOX or CAPOX). ETD was defined as discontinuation of treatment before 75% of cycles of chemotherapy. EOD was defined as discontinuation of oxaliplatin only, while continuing the fluoropyrimidine, before 75% of cycles of oxaliplatin. Association between ETD/EOD and overall survival (OS) and disease-free survival (DFS) was assessed by Cox model adjusted for prognostic factors. Results: ETD analysis included 10,444 patients (FOLFOX n = 7,033; CAPOX n = 3,411), with 20.9% of patients with ETD (17.8% with FOLFOX and 27.2% with CAPOX, p &lt; 0.001). Out of 7,243 patients, 18.8% experienced EOD (17.4% FOLFOX versus 21.4% with CAPOX, p &lt; 0.001). Compared to patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, older, with higher ECOG-PS ≥ 1, and in addition for ETD, a Body Mass Index (BMI) &lt; 18.5 kg/m2. In multivariate analyses, ETD was associated with a decrease in DFS and OS in the overall population (HR: 1.40 95%CI 1.23-1.58, p &lt; 0.001 and HR: 1.51 95%CI 1.31-1.74, p &lt; 0.001, respectively). The same pattern was present with FOLFOX and CAPOX regimen, and also in low-risk and high-risk groups for each regimen with the exception of the CAPOX regimen in the low-risk group for DFS and OS. By contrast, EOD was not associated with reduced DFS or OS in the overall population (HR: 1.10 95%CI 0.77-1.58, p = 0.6 and HR: 0.97 95%CI 0.62-1.52, p = 0.9, respectively), in the low-risk group (HR: 0.97 95%CI 0.56-1.66, p = 0.9 and HR: 0.97 95%CI 0.51-1.82, p = 0.9, respectively) and high-risk group (HR: 1.22 95%CI 0.74-2.02, p = 0.4 and HR: 1.05 95%CI 0.53-2.08, p = 0.9, respectively) and for all subgroups of regimen. Conclusions: In patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III CC, ETD was associated with a decrease in DFS and OS. By contrast, EOD was not significantly associated with poorer outcomes. In case of relevant neurotoxicity during a 6 months schedule, these data are not in favor of continuing oxaliplatin beyond 75% of planned cycles of adjuvant chemotherapy, and demonstrate that fluoropyrimidines remain the cornerstone of adjuvant chemotherapy in localized CC.

Acidic Urine Is Associated With Poor Prognosis of Upper Tract Urothelial Carcinoma.

PurposeTo assess the prognostic role of acidic urine (low urine pH) in upper tract urothelial cancer (UTUC).Materials and MethodsWe reviewed patients enrolled in Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Upper Tract Urothelial Cancer (SUPER-UC-UTUC) who underwent surgical resection from March 2016 to December 2020 in Seoul National University Hospital (SNUH). Patients with non-urothelial cancer or those who are in condition at end-stage renal disease were excluded. Acidic urine was defined as urine pH ≤ 5.5.ResultsA total of 293 patients with a mean age of 70.7 ± 9.5 years were enrolled in this study. Pre-operative laboratory results showed a mean estimated glomerular filtration rate (eGFR) of 64.1 ± 19.2 mL/min/1.73m2 and a mean urine pH of 5.86 ± 0.66. Patients were subdivided into low (pH ≤ 5.5) and high (pH > 5.5) urine pH for comparison. As a result, all variables were comparable except for the T stage, which was significantly higher in the low urine pH group (p = 0.017). Cox regression analysis was performed to assess the clinical impact of acidic urine on patient survival. Multivariate Cox regression analysis revealed that tumor multifocality (HR 2.07, p = 0.015), higher T stage (HR 1.54, p = 0.036), lymphovascular invasion (HR 1.69, p = 0.033), eGFR < 60 mL/min per 1.73 m2 (HR 1.56, p = 0.017), and acidic urine (HR 1.63, p < 0.01) independently decreased disease-free survival (DFS), while multifocality (HR 9.50, p < 0.01), higher T stage (HR 9.51, p = 0.001) and acidic urine (HR 10.36, p = 0.004) independently reduced the overall survival (OS).ConclusionsAcidic urine is independently associated with reduced DFS and OS in UTUC. Acidic urine contributing to acidic environment may promote acquisition of agressive behavior of UTUC.

Genetic Variant of CXCR1 (rs2234671) Associates with Clinical Outcome in Perihilar Cholangiocarcinoma

Background: Perihilar cholangiocarcinoma (pCCA) is a rare primary liver malignancy. Even in patients amenable to surgery, outcomes are often dismal. Here, we aimed to identify prognostic markers for patient outcomes by analyzing functionally relevant single-nucleotide polymorphisms (SNPs) in genes with a role in tumor inflammation and angiogenesis. We analyzed 11 polymorphisms in the inflammation-angiogenesis axis (VEGF, EGF, EGFR, IL-1b, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A, and COX2 genes) for their prediction of tumor recurrence and survival in pCCA patients undergoing surgery in a curative intent. Methods: Samples were obtained from 111 patients with pCCA undergoing liver resection in curative intent. DNA was extracted and analyzed using polymerase chain reaction-restriction fragment length polymorphism protocols and correlated with patients’ outcomes. Results: Out of the assessed variants, only the CXCR1 (also: interleukin-8-receptor alpha – IL-8RA) +860C>G heterozygous polymorphism (rs2234671) was associated with decreased disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) (18/111 (16.2%), median DFS 14 months, log-rank p = 0.007; median CSS 31 months, log-rank p = 0.007; and median OS 6 months, log-rank p = 0.002), compared to the GG genotype (92/111 (82.9%), median DFS 55 months, median CSS 63 months, and median OS 33 months). In the multivariate analysis, +860C>G remained an independent prognostic factor for DFS (adjusted p = 0.008), CSS (adjusted p = 0.001), and OS (adjusted p = 0.001). Conclusion: Genetic variant of CXCR1 +860C>G may serve as a molecular marker for DFS, CSS, and OS in patients undergoing curative-intent surgery for pCCA, indicating that the analysis of SNPs in genes involved in immune-mediated angiogenesis may help to identify patient subgroups at high risk for dismal oncological and overall outcome.

Is Completion Thyroidectomy Necessary in Patients with Papillary Thyroid Carcinoma who Underwent Lobectomy?

Background/Objectives: Although thyroid lobectomy recently is considered as sufficient for low-risk papillary thyroid carcinoma (PTC), completion thyroidectomy is required due to the insufficiency of the preoperative evaluation. The aim of this study was to investigate recurrence rate and disease free survival depending on the gross extrathyroidal extension (gETE) or the number of metastatic lymph node identified in patients with PTC.Materials &amp; Methods: We assessed 3373 patients with PTC who underwent lobectomy at Seoul St. Mary’s Hospital (Seoul, Korea) between January 2009 and December 2014. Clinicopathological characteristics and long-term surgical outcomes were retrospectively analyzed through complete chart reviews. The mean follow-up duration was 97.1 ± 21.4 months.Results: The rate of recurrence was higher in gETE group (1.8% vs. 6.0%, p=0.004), leading to decreased disease free survival in Kaplan-Meier analysis (log-rank p&lt;0.001). N1 group (n=1389) was analyzed into two groups whether the number of positive nodes is more than 5 or less. For the group of the more metastatic nodes, the recurrence rate higher compared to the other group (3.0% vs. 9.3%, p&lt;0.001). DFS was longer in the group that had lesser metastatic nodes (log-rank p&lt;0.001). However, in terms of N1 group over 1cm (n=492), No statistical difference was observed according to the number of positive lymph nodes (4.5% vs. 9.1%, p=0.092)Conclusion: When it comes to node positive PTC, Despite the number of positive lymph nodes was over 5, follow-up with no further surgery can be an option.

Potential Clinical Value of 5-Hydroxytryptamine Receptor 3C as a Prognostic Biomarker for Lung Cancer.

Ion channels and pumps not only regulate membrane potential, ion homeostasis, and electric signaling in excitable cells but also contribute to cell proliferation, migration, apoptosis, and differentiation. Channel proteins and ion pumps can form macromolecular complexes with signaling molecules, including growth factors and cell adhesion molecules. Serotonin (5-hydroxytryptamine (5-HT)) promotes the proliferation of various cancer cell types mediated through the activation of the 5-HT receptor (HTR). Only HTR3 is a ligand-gated ion channel. However, the role of the HTR3 family of HTRs in lung cancer has not been adequately evaluated. We evaluated the relationship between the HTR3 family of HTRs and lung cancer patients' survival using Kaplan–Meier analyses and examined the expression levels of target proteins using immunohistochemistry. In this study, we found that HTR3C was amplified with high frequency in lung cancer patients, and HTR3C protein expression levels were significantly associated with lymph node metastasis and distant metastasis in lung cancer tissues. Survival analysis using the log-rank test demonstrated a decrease in disease-free survival (DFS) and overall survival (OS) rates among the high-level HTR3C expression group compared with the low-level HTR3C expression group. We also evaluated the risk factors associated with lung cancer. The univariate and multivariate analyses of DFS and OS showed that HTR3C expression was a significant predictor of patient outcomes. Taken together, these data demonstrated that HTR3C expression levels were associated with poor DFS and OS in lung cancer patients, indicating that HTR3C can serve as a useful predictive biomarker for lung cancer.