Independent Predictor Of Disease-specific Survival Research Articles

The Prognostic Utility of the Metastatic Lymph Node Ratio and the Number of Regional Lymph Nodes Removed from Patients with Small Bowel Adenocarcinomas.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

Quantification of perineural invasion in pancreatic ductal adenocarcinoma: proposal of a severity score system.

Perineural invasion (PNI) is a common feature in pancreatic ductal adenocarcinoma (PDAC) and correlates with an aggressive tumor behavior already at early stages of disease. PNI is currently considered as a "present vs. absent" feature, and a severity score system has not yet been established. The aim of the present study was thus to develop and validate a score system for PNI and to correlate it with other prognostic features. In this monocentric retrospective study, 356 consecutive PDAC patients (61.8% upfront surgery patients, 38.2% received neoadjuvant therapy) were analyzed. PNI was scored as follows: 0: absent; 1: the presence of neoplasia along nerves < 3mm in caliber; and 2: neoplastic infiltration of nerve fibers ≥ 3mm and/or massive perineural infiltration and/or the presence of necrosis of the infiltrated nerve bundle. For every PNI grade, the correlation with other pathological features, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed. Uni- and multivariate analysis for DFS and DSS were also performed. PNI was found in 72.5% of the patients. Relevant trends between PNI score and tumor differentiation grade, lymph node metastases, vascular invasion, and surgical margins status were found. The latter was the only parameter statistically correlated with the proposed score. The agreement between pathologists was substantial (Cohen's K 0.61). PNI severity score significantly correlated also with decreased DFS and DSS at univariate analysis (p < 0.001). At multivariate analysis, only the presence of lymph node metastases was an independent predictor of DFS (HR 2.235 p < 0.001). Lymph node metastases (HR 2.902, p < 0.001) and tumor differentiation grade (HR 1.677, p = 0.002) were independent predictors of DSS. Our newly developed PNI score correlates with other features of PDAC aggressiveness and proved to have a prognostic role though less robust than lymph nodes metastases and tumor differentiation grade. A prospective validation is needed.

Nomograms for predicting survival in patients with HER2 negative breast cancer.

e12528 Background: It is increasingly recognized that there is considerable heterogeneity in HER2-negative breast cancer. The clinicopathological characteristics differed between HER2-low and HER2-0 breast cancer evaluated by immunohistochemistry (IHC) or in situ hybridization (ISH). HER2-low breast cancer may benefit from novel antibody-drug conjugates. However, the immunohistochemical agreement of HER2-low is poor. We aimed to construct nomograms to predict the survival of HER2-negative breast cancer and to evaluate the effects of HER2 on survival at the RNA transcript level. Methods: A retrospective analysis was performed on breast cancer patients who were evaluated HER2-negative by IHC or ISH in the TCGA database. Univariate and multivariate cox regression analysis was used to evaluate whether the HER2 RNA transcript level and clinical parameters were independent predictors for overall survival (OS), progression-free survival (PFS), and Disease-Specific Survival (DSS), and nomograms were generated for the prediction of 1-, 2-, 3-, 5-year OS, PFS, and DSS based on significant parameters. Survival curves were drawn using the Kaplan-Meier methods to compare mortality outcomes according to HER2 RNA transcript level (75% vs. 25%). Results: A total of 769 HER2-negative patients were included in the analysis. The median age of patients was 56 years (range 26-30), and the majority were White (80.3%). Univariate and multivariate cox regression analysis showed that age, pN_stage, and pM_stage were independent predictors for OS, but HER2 was not. The C-index of a nomogram based on these three parameters was 0.723 (95%CI, 0.6555-1). HER2, pT_stage, pN_stage, and pM_stage were analyzed as independent predictors of PFS. HER2, pN_stage, and pM_stage were independent predictors of DSS. The C-indexes of established nomograms were 0.734 (95%CI, 0.672-1) and 0.775 (95%CI, 0.686-1) respectively. PFS and DSS were significantly better for patients with high HER2 RNA transcript levels (PFS, log-rank p = 0.00446, HR = 0.352; DSS, log-rank p = 0.0119, HR = 0.247). Conclusions: In the TCGA database, the HER2 RNA transcript level was an independent predictor for PFS and DSS in HER2-negative breast cancer. Stratification of patients at the RNA level can help clinicians optimize treatment for HER2-negative breast cancer.

Histopathologic Grading Is of Prognostic Significance in Primary Angiosarcoma of Breast: Proposal of a Simplified 2-tier Grading System.

Despite a wide spectrum of clinical presentations, including primary or secondary, most angiosarcomas are considered high grade. One exception is primary breast angiosarcoma, where historically, histologic grading has shown to predict outcome using the Rosen 3-tier system. However, more recent studies have challenged this concept suggesting that even in this specific clinical context angiosarcomas should be considered high grade. This study aimed to critically reevaluate the impact of histologic grade in a clinically uniform cohort managed at a single institution using a newly proposed grading system. Our study included 49 primary breast angiosarcomas diagnosed during 1994 to 2022 (median follow-up: 33mo), classified as low grade (29%), intermediate grade (20%), and high grade (51%), based on mitotic count, extent of solid components, and necrosis. At last follow-up, 22% patients developed locoregional recurrences, 63% distant metastases, and 47% patients died of disease. As patients with low and intermediate-grade angiosarcomas had relatively similar outcomes, our cohort was further analyzed using a 2-tier system (low grade and high grade). Targeted-DNA next-generation sequencing (505 cancer gene panel) performed in 11 cases found KDR mutations in 78% and PIK3CA mutations in 44% of high-grade lesions. Histologic grade, by either 3-tier or 2-tier grading systems, had a strong impact on survival, with the 2-tier system being an independent predictor of disease-specific survival and overall survival. Based on 2-tier system, the 5-year overall survival was 38% for high-grade angiosarcoma and 74% for low-grade angiosarcoma. PIK3CA mutations alone or concurrent with KDR alterations were identified in angiosarcomas with worse prognosis.

Cervical squamous cell carcinoma of unknown primary: Oncological outcomes and prognostic factors.

Cervical squamous cell carcinoma of unknown primary (SCCUP) is a rare entity within head and neck cancer and both treatment regimens as well as identified potential predictors for oncological outcomes vary between published series. In this study, we evaluated oncological outcomes and identified potential prognostic factors for outcome. This retrospective monocentric cohort study includes 82 SCCUP patients diagnosed and treated between January 2000 and June 2021. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) were evaluated. The Cox proportional hazards model was used to analyze the prognostic effect of patient and tumor characteristics on oncological outcomes. Five year OS, DSS, DFS and LRFS were respectively 53.9%, 72.2%, 68.9% and 67.3%. The p16 status was evaluated in 55 patients with 40% being p16 positive. On univariable analysis, p16 negative SCCUPs had significantly worse survival and recurrence rates in the presence of clinical extranodal extension (cENE) (OS: p=0.0013, DSS: p=0.0099, DFS: p=0.0164, LRFS: p=0.0099) and radiological extranodal extension (rENE) (OS: p=0.0034, DSS: p=0.0137, DFS: p=0.0167, LRFS: p=0.0100). In p16 positive SCCUP patients, rENE had a significantly negative prognostic effect on DFS (p=0.0345) and LRFS (p=0.0367). Total group multivariate analysis identified rENE as an independent negative predictor for all oncological outcomes. The "number of positive lymph nodes" was a second independent predictor for DSS (p=0.0257) and DFS (p=0.0435). We report favorable oncological outcomes, comparable to previously published results. Although the presence of rENE seems associated with poor oncological outcomes, the differential effect of clinical, radiological and pathological ENE in both p16 positive and negative subgroups remain to be elucidated by further prospective research.

FDG PET/CT Maximum Tumor Dissemination to Predict Recurrence in Patients with Diffuse Large B-Cell Lymphoma.

We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL).We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL). Patients who underwent FDG PET/CT for initial staging and treatment response evaluation of DLBCL were reviewed retrospectively. Baseline Dmax, maximum standardized uptake value, total summation of all metabolic tumor volumes (tMTV), and total summation of all total lesion glycolysis (tTLG) were measured. The treatment response was evaluated at the interim and end of first-line treatment (EOT) using the Deauville score (DS). FDG PET/CT parameters and other clinical factors including sex, age, serum lactate dehydrogenase (LDH) level, stage, performance status, and the International Prognostic Index (IPI) were analyzed to identify factors prognostic of the time to progression (TTP) and disease-specific survival (DSS). A total of 63 patients were included. Univariate survival analysis identified Dmax (> 275mm), tMTV (> 180mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) as significant predictors of poor TTP. Serum LDH level (> 640IU/L), IPI (≥ 4), tMTV (> 180mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) were significant predictors of DSS. After multivariate survival analysis, Dmax (P = 0.008) and EOT DS (P = 0.005) were independent predictors of TTP. EOT DS was an independent predictor of DSS (P = 0.029). Dmax at the time of diagnosis and the EOT response assessed by FDG PET/CT provide useful prognostic information additive to the IPI in patients with DLBCL.

Recurrence Risk Stratification for Women with FIGO Stage I Uterine Endometrioid Carcinoma Who Underwent Surgical Lymph Node Evaluation

<h3>Purpose/Objective(s)</h3> To estimate the recurrence risk based on the number of prognostic factors in women with FIGO stage I uterine endometrioid carcinoma (EC) in a large cohort of patients who underwent surgical staging including surgical lymph node evaluation (SLNE) and were managed with no adjuvant therapy. <h3>Materials/Methods</h3> We queried our in-house prospectively maintained uterine cancer database for patients with FIGO stage I EC underwent surgical staging including SLNE between 1/1990-12/2020. Patients with synchronous ovarian and breast cancer diagnosis were excluded as well as those who received adjuvant therapy of any form. Patient's demographics and pathologic variables were analyzed. We used multivariate analysis (MVA) with Stepwise Model Selection to determine risk factors for 5-year recurrence-free survival (RFS). Study population was then stratified based on the number of risk factors identified (0, 1 or 2). The resultant groups were compared for RFS, disease-specific survival (DSS) and overall survival (OS) using log-rank test and Kaplan-Meier curves. Additionally, independent predictors of DSS and overall OS were estimated. <h3>Results</h3> 706 patients were identified who met our inclusion criteria with a median age of 60 years (range, 30-93) and a median follow-up of 120 months. All patients had at least pelvic SLNE with a median number of examined lymph node (LN) of 8 (range, 1-66): 66 patients (11%) had a sentinel LN sampling and 43% had paraaortic SLNE. 639 patients (91%) were stage IA and lymphovascular space invasion (LVSI) was detected in 6% (n=41). Recurrence was diagnosed in 44 patients (6%). Independent predictors of 5-year RFS include age ≥ 60 years (<i>p</i>=0.038), grade 2 vs. 1 (<i>p</i>=0.003), and grade 3 vs 1 (<i>p</i><0.001). 5-year RFS for group-0 (age < 60 years and grade 1) was 98% vs. 92% for group-1 (either: age ≥ 60 years or grade 2/3) vs 84% for group-2 (both: age ≥ 60 years and grade 2/3), respectively (<i>p</i><0.001). 5- year DSS for the three groups was (100% vs 98% vs 95%, <i>p</i>=0.012) and 5-year OS was (98% vs 90% vs 81%, <i>p</i><0.001), respectively. On MVA, stage IB vs IA was deterministic for DSS (<i>p</i>=0.02); whereas age ≥ 60 years (p<0.001) and grade 3 vs grade 1 (<i>p</i>=0.004) were predictors for worse OS. <h3>Conclusion</h3> In patients with stage I endometrioid carcinoma who had surgical staging including SLNE and no adjuvant therapy, only age ≥ 60 years and high tumor grade were independent predictors of cancer recurrence and hence can be used to quantify individualized recurrence risk. Surprisingly, LVSI was not an independent prognostic factor in this study cohort with SLNE.

Outcomes after Definitive Treatment for Cutaneous Angiosarcomas of the Face and Scalp: Re-Evaluating the Role of Combined Modality Treatment

<h3>Purpose/Objective(s)</h3> Cutaneous angiosarcomas of the face and scalp are rare soft tissue tumors with locally aggressive malignant potential. Previous studies have shown that combined modality treatment (CMT) of surgical resection and adjuvant radiation therapy (RT) improves outcomes. We sought to update our experience with long-term outcomes in patients with cutaneous angiosarcoma of the face and scalp treated with definitive intent. <h3>Materials/Methods</h3> We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic cutaneous angiosarcoma of the face and scalp between 1962 and 2019, with a majority (69%) since 2000. All patients received definitive local treatment either with surgery, RT, or CMT. The Kaplan-Meier method was used to estimate actuarial overall survival (OS), disease-specific survival (DSS) and local control (LC). Multivariable analyses were conducted using Cox proportional hazards model. <h3>Results</h3> Median follow-up for all patients was 33 months. Of the 143 patients, the majority were male (n=109, 76%) and had a primary lesion on the scalp (n=87, 61%). Median age was 70 years at diagnosis (IQR 64-76). Slightly less than half (n=59, 41%) of patients had multifocal disease at diagnosis, and 20 (14%) presented with nodal involvement. CMT was the most common treatment approach (n=69, 48%), followed by RT alone (n=50, 35%) and surgery alone (n=24, 17%). Forty-three percent of patients (n=61) had a local relapse, resulting in a 5-yr LC of 51%. On univariable analysis 5-yr LC was significantly worse in patients with tumors >5 cm at diagnosis (19% vs 59% <5cm, p=0.01), those with multifocal disease at presentation (35% vs 59% unifocal, p<0.005), and those treated with single modality therapy (SMT) (29% vs 75% CMT, p<0.005). These factors all remained significantly associated with poorer LC on multivariable analysis (>5cm HR 2.30 [1.27-4.16], multifocal disease HR 1.95 [1.10-3.43], SMT HR 3.74 [2.01-6.96]). The 5-yr OS and DSS were 45% and 56%, respectively. When evaluating factors associated with DSS, tumor size >5 cm (HR 2.15 [95%CI 1.20-3.88]), multifocal disease at presentation (HR 1.80 [1.02-3.18]), primary site other than the scalp (HR 0.53 [0.29-0.99]), and the use of SMT (HR 2.95 [1.59-5.50]) emerged as independent predictors of DSS. The presence of multifocal disease and large tumor size were also associated with worse OS on both univariate and multivariable analyses (HR 1.59 [1.02-2.50], HR 2.00 [1.21-3.31], respectively). The use of chemotherapy was not associated with any outcome. <h3>Conclusion</h3> Large tumor size (>5 cm) and the presence of multifocal disease are negative prognostic factors in patients presenting with cutaneous head and neck angiosarcomas. With longer follow-up, our data continues to suggest that primary local therapy consisting of CMT improves LC and DSS outcomes for these patients and should remain standard of care when feasible.

Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy

BackgroundThe decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas. ObjectivesWe aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs. MethodsThis single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis. ResultsAfter excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group. ConclusionsIn patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.

Prognostic Advantages of Individual Additional Interventions After Lenvatinib Therapy in Patients with Advanced Hepatocellular Carcinoma

BackgroundIncreasing number of patients with advanced hepatocellular carcinoma (HCC) has recently achieved salvage interventions after introduction of new biologic agents, while there are insufficient data to determine if such additional intervention(s) after treatment with newer biologic agents are truly advantageous for patients with advanced HCC. MethodsThe clinical records of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were extensively reviewed and the prognostic advantages of individual additional treatments after lenvatinib treatment were investigated through a regression analysis considering time-dependent covariates. ResultsMultivariate analysis revealed that R0 resection or curative-intent radiofrequency ablation (RFA) (hazard ratio [HR], 0.07; 95% CI, 0.01–0.32), transarterial chemoembolization or transarterial infusion therapy (HR, 0.39; 95% CI, 0.19–0.81), and subsequent line of systemic therapy (HR, 0.25; 95% CI, 0.10–0.63) were associated with improved disease-specific survival (DSS), while R2 resection or palliative-intent RFA showed no correlation with DSS. The best response during lenvatinib therapy, nutritional status, plasma des-gamma-carboxyprothrombin level, a baseline CT enhancement pattern, and BCLC stage were also selected as independent predictors for DSS. Among the various treatments performed after lenvatinib therapy, R0 resection also showed clear prognostic advantage in both progression-free survival (HR, 0.30; 95% CI, 0.16–0.58) and time-to-treatment failure (HR, 0.08; 95% CI, 0.02–0.39), suggesting that successful conversion to surgery may prolong survival outcomes through prolonged cancer-free interval in advanced HCC. ConclusionsAdditional intervention(s)/treatment(s) after lenvatinib therapy for advanced HCC may have prognostic advantage in strictly selected populations. Successful conversion to curative resection may offer survival benefit with acceptable clinical outcomes.

Prognostic Role of Systemic Inflammatory Markers in Patients Undergoing Surgical Resection for Oral Squamous Cell Carcinoma.

Background: A high platelet–lymphocyte ratio (PLR) is a marker of systemic inflammation and, together with the neutrophil–lymphocyte ratio (NLR), is associated with poor outcomes in several cancers. We investigated the prognostic value of PLR and other systemic inflammatory markers, such as NLR, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), in oral squamous cell carcinoma (OSCC) patients undergoing surgical resection. Methods: We derived PLR, NLR, SII, and SIRI from a retrospective chart review of 269 consecutive OSCC patients. The complete blood count examined in the immediate preoperative period was used to compute PLR, NLR, SII, and SIRI. We analyzed the relationship between these systemic inflammatory markers and the clinicopathologic characteristics, disease-specific survival (DSS), and progression-free survival (PFS) of patients. Results: In the univariate analysis, high PLR and SII were significantly associated with worse DSS and PFS (all p < 0.05). In the multivariate analysis, PLR (HR 2.36, 95% CI 1.28–4.36 for DSS; HR 1.80, 95% CI 1.06–3.06 for PFS) was an independent predictor of survival outcomes. When PLR was analyzed as a continuous variable, the relationship between the outcome and preoperative PLR was not monotonically linear. In the subgroup analysis, PLR was more strongly associated with DSS and PFS in patients who were male, had stage III/IV OSCC, or had lymph node metastasis. Conclusion: Our data suggest that in OSCC patients, the pretreatment PLR is an independent predictor of DSS and PFS. The PLR is a readily available biomarker that will improve prognostication and risk stratification in OSCC.

Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma

BackgroundPheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence of metastases. MethodsThis retrospective study included 582 patients with PPGLs and 57 with HNPGLs. DSS was assessed according to age, location and size of tumours, recurrent/metastatic disease, genetics, plasma metanephrines and methoxytyramine. ResultsAmong all patients with PPGLs, multivariable analysis indicated that apart from older age (HR = 5.4, CI = 2.93–10.29, P < 0.0001) and presence of metastases (HR = 4.8, CI = 2.41–9.94, P < 0.0001), shorter DSS was also associated with extra-adrenal tumour location (HR = 2.6, CI = 1.32–5.23, P = 0.0007) and higher plasma methoxytyramine (HR = 1.8, CI = 1.11–2.85, P = 0.0170) and normetanephrine (HR = 1.8, CI = 1.12–2.91, P = 0.0160). Among patients with HNPGLs, those with metastases presented with longer DSS compared to patients with metastatic PPGLs (33.4 versus 20.2 years, P < 0.0001) and only plasma methoxytyramine (HR = 13, CI = 1.35–148, P = 0.0380) was an independent predictor of DSS. For patients with metastatic PPGLs, multivariable analysis revealed that apart from older age (HR = 6.2, CI = 3.20–12.20, P < 0.0001), shorter DSS was associated with the presence of synchronous metastases (HR = 4.9, CI = 2.78–8.80, P < 0.0001), higher plasma methoxytyramine (HR = 2.4, CI = 1.44–4.14, P = 0.0010) and extensive metastatic burden (HR = 2.1, CI = 1.07–3.79, P = 0.0290). ConclusionsDSS among patients with PPGLs/HNPGLs relates to several presentations of the disease that may provide prognostic markers. In particular, the independent associations of higher methoxytyramine with shorter DSS in patients with HNPGLs and metastatic PPGLs suggest the utility of this biomarker to guide individualized management and follow-up strategies in affected patients.

Utility of RGNEF in the Prediction of Clinical Prognosis in Patients with Rectal Cancer Receiving Preoperative Concurrent Chemoradiotherapy.

Rectal cancer is a heterogeneous malignancy with different clinical responses to preoperative concurrent chemoradiotherapy (CCRT). To discover the significant genes associated with CCRT response, we performed data mining of a transcriptomic dataset (GSE35452), including 46 rectal cancer patients who received preoperative CCRT and underwent standardized curative resection. We identified ARHGEF28 as the most significantly upregulated gene correlated with resistance to CCRT among the genes related to Rho guanyl-nucleotide exchange factor activity (GO:0005085). We enrolled 172 patients with rectal cancer receiving CCRT with radical surgery. The expression of ARHGEF28 encoded protein, Rho guanine nucleotide exchange factor (RGNEF), was assessed using immunohistochemistry. The results showed that upregulated RGNEF immunoexpression was considerably correlated with poor response to CCRT (p = 0.018), pre-CCRT positive nodal status (p = 0.004), and vascular invasion (p < 0.001). Furthermore, high RGNEF expression was significantly associated with worse local recurrence-free survival (p < 0.0001), metastasis-free survival (MeFS) (p = 0.0029), and disease-specific survival (DSS) (p < 0.0001). The multivariate analysis demonstrated that RGNEF immunoexpression status was an independent predictor of DSS (p < 0.001) and MeFS (p < 0.001). Using Gene Ontology enrichment analysis, we discovered that ARHGEF28 overexpression might be linked to Wnt/β-catenin signaling in rectal cancer progression. In conclusion, high RGNEF expression was related to unfavorable pathological characteristics and independently predicted worse clinical prognosis in patients with rectal cancer undergoing CCRT, suggesting its role in risk stratification and clinical decision making.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study

ObjectiveEndometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding...

Does macroscopic extrathyroidal extension to the strap muscles alone affect survival in papillary thyroid carcinoma?

BackgroundMacroscopic extrathyroidal extension to structures adjacent to the thyroid gland is one of the most important predictors of survival in papillary thyroid carcinoma. However, the prognostic significance of macroscopic extrathyroidal extension to strap muscles alone is unknown. The aim of this study is to determine the impact on survival in patients with macroscopic extrathyroidal extension to strap muscles alone compared to those with no macroscopic extrathyroidal extension and macroscopic extrathyroidal extension involving other adjacent structures. MethodsAfter institutional review board approval, adult papillary thyroid carcinoma patients were identified from an institutional database of 6,259 patients undergoing initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients were classified as having no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, or macroscopic extrathyroidal extension to other adjacent structures. Disease-specific survival was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A P value < .05 was considered statistically significant and significant factors were used in a Cox proportional hazard model to predict disease-specific survival. ResultsThere were 5,880 patients included in the analysis; 5,485 patients (93.3%) in the no macroscopic extrathyroidal extension group, 179 (3.0%) in the macroscopic extrathyroidal extension to strap muscles alone group and 216 (3.7%) in the macroscopic extrathyroidal extension involving other adjacent structures group. With a median follow-up of 64 months, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 98.9%, 95.7%, and 83.7%, respectively (P < .0001). In the ≥55-year-old cohort, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 97.6%, 89.3%, and 68.1%, respectively (P <.0001). After controlling for pathological nodal stage and distant metastasis stage, extent of extrathyroidal extension remained an independent predictor of disease-specific survival; patients with macroscopic extrathyroidal extension to strap muscles alone had a 3.3-fold increased likelihood of a disease-specific death compared to no macroscopic extrathyroidal extension patients (hazard ratio 3.294; 95% confidence interval 1.076–10.086, P < .0368). ConclusionIn our study, patients aged ≥55 years with papillary thyroid carcinoma and macroscopic extrathyroidal extension to strap muscles alone appear to have an increased likelihood of a disease-specific death compared to patients with no macroscopic extrathyroidal extension.

Long-Term Survivors after Upfront Resection for Pancreatic Ductal Adenocarcinoma: An Actual 5-Year Analysis of Disease-Specific and Post-Recurrence Survival.

Data on long-term actual survival in patients with surgically resected pancreatic ductal adenocarcinoma (PDAC) are limited. The aim of this study was to evaluate the actual 5-year disease-specific survival (DSS) and post-recurrence survival (PRS) in patients who underwent pancreatectomy for PDAC. Data from patients who underwent upfront surgical resection for PDAC between 2009 and 2014 were analyzed. Exclusion criteria included PDAC arising in the background of an intraductal papillary mucinous neoplasm and patients undergoing neoadjuvant therapy. All alive patients had a minimum follow-up of 60 months. Independent predictors of PRS, DSS, and survival >5 years were searched. Of the 176 patients included in this study, 48 (27%) were alive at 5years, but only 20 (11%) had no recurrence. Median PRS was 12months. In the 154 patients after disease recurrence, independent predictors of shorter PRS were total pancreatectomy, G3 tumors, early recurrence (<12months from surgery), and no treatment at recurrence. Median DSS was 36 months. Independent predictors of DSS were CA19-9 at diagnosis >200U/mL, total pancreatectomy, N+ status, G3 tumors and perineural invasion. Only the absence of perineural invasion was a favorable independent predictor of survival >5years. More than one-quarter of patients who underwent upfront surgery for PDAC were alive after 5years, although only 11% of the initial cohort were cancer-free. Long-term survival can also be achieved in tumors with more favorable biology in an upfront setting followed by adjuvant chemotherapy.

Prognostic Impact of Loss of SETD2 in Clear Cell Renal Cell Carcinoma.

To evaluate the prognostic impact of immunohistochemical expression of SETD2 in patients with clear cell renal cell carcinoma (ccRCC). A total of 662 patients with primary or metastatic ccRCC were evaluated. Two genitourinary pathologist reviewed all of the cases for uniform reclassification and determined the selection of the most representative tumor areas for construction of the tissue microarray (TMA). SETD2 nuclear staining showed that 101 areas (15.3%) had negative expression, and 561 areas (84,7%) had positive expression of SETD2. The protein expression of SETD2 was associated with clinical stage (P < .001), pathological stage (P < .001), tumor size (P < .001), perinephric fat invasion (P < .001), Eastern Cooperative Oncology Group status (P=.004), surgery type (P < .001), International Society of Urologic Pathologists grade (P < .001), and tumor necrosis (P < .001). SETD2 influenced disease-specific survival (DSS) and overall survival (OS). DSS rates in patients with positive and negative expression of SETD2 were 90.2% and 58.4%, respectively (P < .001). OS rates in patients with positive and negative expression of SETD2 were 87% and 55.4%, respectively (P < .001). In a multivariate Cox analysis, low SETD2 expression was an independent predictor of DSS (hazard ratio [HR], 1.690; 95% confidence interval [CI], 1.0582.700; P=.031) and OS (HR, 1.641; 95% CI, 1.039-2.593; P=.037). Our study showed that the negative expression of SETD2 was associated with a worse prognosis, and it was an independent predictor of survival in patients with ccRCC. We believe that the protein expression of SETD2 is an important biomarker in the management of patients with ccRCC.

Time to Recurrence Associated With Poor Prognosis in Japanese Oral Squamous Cell Carcinoma Patients.

Recurrence in oral squamous cell carcinoma (OSCC) is not rare. Due to lack of studies assessing characteristics of recurrent OSCC, including time to recurrence and outcomes, we sought to investigate its characteristics, time to recurrence, and outcomes in Japanese OSCC patients. This study was a nonrandomized retrospective cohort study in a tertiary referral centre. It included 208 (117 men and 91 women) patients with recurrent oral cancer who underwent major curative surgery in the Department of Oral and Maxillofacial Surgery at Kobe University Hospital between January 1999 and April 2017. The outcomes were disease-specific survival (DSS) and overall survival (OS). In multivariable Cox proportional hazards analysis, the time to recurrence (hazard ratio [HR] 3.55, 95% confidence interval [CI] 1.69-6.63; P = 0.001), extranodal extension (ENE, HR 2.72, 95% CI 1.51-4.89; P = 0.001), and high T stage (HR 2.00, 95% CI 1.01-3.97; P = 0.046) were independent predictors of DSS. The time to recurrence (HR 3.29, 95% CI 1.82-5.96; P < 0.001) and ENE (HR 2.64, 95% CI 1.52-4.56; P = 0.001) were independent predictors of OS. Time to recurrence, extranodal extension, and higher T stage were independent prognosis predictors in OSCC.

Vacuolar Membrane ATPase Activity 21 Predicts a Favorable Outcome and Acts as a Suppressor in Colorectal Cancer.

Extracellular and/or intracellular manipulation of pH in tumor may have noticeable potential in cancer treatment. Although the assembly factor genes of V0 domain of the V-ATPase complex are required for intracellular pH homeostasis, their significance in colorectal cancer (CRC) remains largely unknown. Here, we used bioinformatics to identify the candidates from known assembly factor genes of the V0 domain, which were further evaluated by immunohistochemistry (IHC) in CRC and adjacent normal specimens from 661 patients. Univariate and multivariate Cox analyses were used to evaluate factors contributing to prognosis. The effects of variations in the expression of VMA21 on tumor growth were assessed in vitro and in vivo. Of five known assembly factors, only VMA21 showed differential expression between CRC and adjacent normal tissues at both mRNA and protein levels. Patients with high VMA21 expression had higher differentiation grade and longer disease-specific survival (DSS) at stages I–III disease. High VMA21 expression in tumors was also an independent predictor of DSS (hazard ratio, 0.345; 95% confidence interval, 0.123–0.976), with covariates included TNM stage and differentiation grade. VMA21 overexpression decreased CRC growth, whereas VMA21 knockdown increased CRC growth in vitro and in vivo. VMA21 expression suppresses CRC growth and predicts a favorable DSS in patients with stage I-III disease.

Malignant tumours of temporomandibular joint

BackgroundMalignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed.MethodsA retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973–2016).ResultsData for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P < 0.05). In the multivariate survival analysis, age > 44 years and AJCC stage III and IV were associated with poor DSS.ConclusionMTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient’s age and AJCC stage was independent predictor of DSS.