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Background/Aim: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance. Patients and Methods: This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes. Results: The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan–Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC. Conclusion: This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010–2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population. [ABSTRACT FROM AUTHOR]

The study compared disease-specific survival rates between primary penile melanoma (PPM) and melanoma in other cutaneous sites using the SEER database. PPM patients had higher rates of regional and distant stages of disease, tumor ulceration, and thicker Breslow depths compared to other sites. Univariate analysis showed that PPM had significantly poorer disease-specific survival rates, with a multivariate analysis indicating a higher risk of disease-specific mortality for PPM patients. The study highlights the need for early detection and education on melanoma in atypical sites to improve outcomes for PPM patients. [Extracted from the article]

Abstract Killer cell lectin-like receptor B1 (KLRB1) is implicated in cancer progression and immunity. In this study, we aimed to evaluate the expression levels of KLRB1 in lung adenocarcinoma (LUAD) and analyze the relationship between KLRB1 expression levels, LUAD progression, and the tumor immune microenvironment. KLRB1 levels in LUAD were analyzed using data from the TCGA and XENA databases. Additionally, the diagnostic values of KLRB1 were analyzed in patients with LUAD. Survival and meta-analyses were employed to investigate the relationship between KLRB1 levels and other prognostic factors in patients with LUAD. Bioinformatics and cellular experiments were used to understand the functions and mechanisms of KLRB1. In addition, correlation analysis was used to investigate the relationship between KLRB1 levels and the immune microenvironment in LUAD. Reduced KLRB1 expression in LUAD was found to positively correlate with tumor size, distant metastasis, pathological stage, age, overall survival, diagnostic value, and disease-specific survival in patients with LUAD (P

Introduction: Extraocular sebaceous carcinoma (SC), particularly those outside the head and neck region, is rare and not well-described. Purpose: This study aimed to explore the epidemiology and identify the prognostic factors of non-head and neck SC, describe the possible relevant factors of distant metastasis, and provide implications for distant metastasis screening. Methods: Data from the 17 registries in the Surveillance, Epidemiology, and End Results database were retrospectively collected for patients with SC outside the head and neck from 2000 through 2020. Overall survival (OS) and diseasespecific survival (DSS) were the primary endpoints. Survival analysis was conducted through Kaplan-Meier curves, and multivariate analysis was carried out using Cox proportional hazard models. Results: A total of 1,237 patients with SC outside the head and neck were identified. The mean age at diagnosis of the entire patient cohort was 67.7 years (30 to 90+ years), and the mean tumor size was 2.2 cm (0.1-16 cm). Patients with distant disease experienced the lowest OS (mean, 29.5 months) than those with localized disease and regional disease (p < 0.0001). Multivariate analysis revealed that age, tumor size, and stage were independent determinants of OS; age, stage, and primary site were independent determinants of DSS. Tumor grade and lymph node status had less prognostic value for survival. Undifferentiated tumors have a trend toward distant metastasis, especially those at the primary site of the trunk. Conclusion: The prognosis of the non-head and neck SC is excellent, while the survival of distant disease is very poor. Distant metastasis screening can be considered for undifferentiated tumors, especially those located in the trunk region with large tumor sizes. [ABSTRACT FROM AUTHOR]

Abstract Background The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. Methods Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. Results A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P

Background: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. Methods: Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. Results: A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites. Conclusion: This large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to analyze the survivals and clinicopathological features of epithelial ovarian cancer (EOC) in younger age patients and to determine the impact of age on survival. Methods: EOC patients aged =40 years were matched to patients aged >40 years at a 1:4 ratio. Disease-specific survival (DSS), progression-free survival (PFS), and clinicopathological and treatment features were compared between patients aged =40 and >40 years. Results: A total of 763 EOC patients were reviewed. During a median follow-up period of 41 (range, 1-195) months, EOC patients aged =40 and >40 years did not show any statistically significant difference in median DSS (120 versusversus 84.7 months; hazard ratio, 0.78; 95% confidence interval, 0.58, 1.06); however, the median PFS was better in patients aged =40 years (median PFS not reached versusversus 41 months; HR, 0.65; 95% CI, 0.5, 0.85). Age =40 years was an independent favorable prognostic factor for DSS at 3 years after diagnosis. In contrast, younger age was an independent poor prognostic factor prior to this time point. EOC patients aged =40 years exhibited a significantly higher rate of early-stage disease, a higher proportion of mucinous subtype, and lower cancer antigen-125 level. Conclusion: Overall, EOC patients in the younger age group were associated with more favorable prognostic factors and showed better PFS, but not DSS, than those in the older age group. Younger age was identified as an unfavorable prognostic factor within 3 years of diagnosis and became a favorable prognostic factor after 3 years. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent animal studies have shown a correlation between environmental temperature and tumor growth. Based on these studies, we hypothesized that esophageal cancer and gastric cancer patients living in warmer climates have improved survival as compared to patients living in colder climates. We conducted a study using the SEER (Surveillance, Epidemiology, and End Results) database and analyzed the cancer outcomes with the county-level average annual temperature in which those patients resided. We analyzed 17,408 esophageal cancer and 20,533 gastric cancer patients. We noted for the first time that higher environmental temperatures were associated with significant improvements in survival in patients with esophageal and gastric cancers. Further confirmatory population-based studies as well as mechanistic-bench studies are needed to support our findings. Background: Cold stress suppresses antitumor response in animal models, leading to tumor growth. Recent studies have also shown a negative correlation between the average annual temperature (AAT) and cancer incidence. We hypothesized that esophageal cancer (EC) and gastric cancer (GC) patients living in warmer climates have improved survival outcomes than those living in colder climates. Methods: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database from 1996 to 2015. We retrieved the National Centers for Environmental Information data to calculate the county-level AAT. Cox multivariate regression models were performed to measure the association between temperature (measured continuously at diagnosis and in 5-degree increments) and OS/DSS, adjusting for variables. All associations were compared at a significance level of 0.05. The OS and DSS were summarized using Kaplan–Meier methods. All statistics were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Results: A total of 17,408 EC patients were analyzed. The average age of the cohort was 65 years, 79% of which were males and 21% were females. Of them, 61.6% had adenocarcinoma, and 37.6% were squamous. After adjusting for covariates, patients in regions with an AAT > 53.5 °F had an 11% improvement in OS [HR 0.89 (95% CI 0.86–0.92), p < 0.0001] and 13% in DSS [HR 0.87 (95% CI 0.84–0.90), p < 0.0001]. When the temperature was analyzed in 5 °F increments, with each increment, there was a 3% improvement in OS [HR 0.97 (95% CI 0.96–0.98), p < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95–0.97), p < 0.0001]. Subgroup analysis of squamous and adenocarcinoma showed similar results. These findings were validated in 20,553 GC patients. After adjusting for covariates, patients in regions with an AAT > 53.5 had a 13% improvement in OS [HR 0.87 (95% CI 0.85–0.90), p < 0.0001] and 14% in DSS [HR 0.86 (95% CI 0.83–0.89), p < 0.0001]. When analyzed in 5 °F increments, with each increment, there was a 4% improvement in OS [HR 0.96 (95% CI 0.952–0.971), p < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.945–0.965), p < 0.0001]. Conclusion: We showed for the first time that higher environmental temperatures are associated with significant improvements in OS and DSS in patients with gastro-esophageal cancers, notwithstanding the limitations of a retrospective database analysis. Further confirmatory and mechanistic studies are required to implement specific interventional strategies. [ABSTRACT FROM AUTHOR]

Prior multiinstitutional studies demonstrate that patients diagnosed with melanoma during the Coronavirus Disease 2019 (COVID-19) pandemic presented with more advanced melanomas. To further characterize patients diagnosed with melanoma during the COVID-19 pandemic. Retrospective population-based cohort study of the Surveillance, Epidemiology, and End-Results (SEER) registry of patients diagnosed with cutaneous melanoma from 2018-2020. Patients diagnosed with melanoma in 2020 were more likely to have increased Breslow depth, more ulceration, nodular tumors, and more advanced stage at diagnosis despite less treatment delays. Patients tended to be from wealthier, more urban areas. Primary surgical treatment was more likely to be with Mohs surgery. Diagnosis in the year 2020 was not correlated with overall or disease specific survival. This is a retrospective cohort review and limited by short follow-up times, which could affect survival outcomes. There was a 15.5% drop in melanoma diagnosis in 2020 compared to prior years, which could relate to delayed presentation. Patients diagnosed with melanoma in 2020 tended to have thicker, more ulcerated, and more advanced tumors, but this was not associated with survival. Further studies are needed to characterize outcomes for patients diagnosed with melanoma during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Objective: This study assessed positive lymph node ratio (LNR) as a prognostic marker for patients with pyriform sinus cancer. Methods: The present study retrospectively analyzed 101 patients with pyriform sinus cancer to determine the association of LNR with recurrence-free survival (RFS) and disease-specific survival (DSS). Results: The patients were followed up for a median duration of 28 months (range: 6–196 months). The number of median dissected lymph nodes (LNs) was 41, and the number of median positive LNs was three. The receiver operating characteristic curve revealed an LNR cut-off value of 8.6%. Lymphovascular invasion (LVI) or perineural invasion (PNI) (P = 0.001), thyroid gland invasion (TGI, P = 0.000), positive LNs >4 (P = 0.036), and LNR >8.6% (P = 0.008) were significantly associated with poor RFS, and LVI or PNI (P = 0.005), tumor pT3/T4 stage (P = 0.028), positive LNs >4 (P = 0.033), TGI (P = 0.001), and LNR >8.6% (P = 0.003) were significantly associated with poor DSS. The multivariate analysis revealed that LVI or PNI (P = 0.010), TGI (P = 0.000), and LNR >8.6% (P = 0.022) were independent predictors for poor RFS, while tumor pT3/T4 stage (P = 0.049), TGI (P = 0.015), and LNR >8.6% (P = 0.001) were independent predictors for poor DDS. Conclusion: LNR and other clinicopathological data can be used to predict the RFS and DSS of pyriform sinus cancer patients.

Purpose: To explore the risk factors for lymph node metastasis (LNM) and establish nomograms for predicting survival outcomes and assessing individual risk in patients with LNM and hypopharyngeal squamous carcinoma (HSCC). Methods: Clinical data of patients with HSCC were retrospectively reviewed. The study's primary endpoints were overall survival (OS) and disease-specific survival (DSS). Nomograms were established based on Cox regression analyses. The accuracy and calibration ability of the nomograms were evaluated using the C-index, area under the curve, calibration curves, and decision curve analysis. Results: Overall, 2888 patients were enrolled, and the LNM rate was 74.2%. Age ≤ 60 years, male sex, unmarried status, pyriform sinus location, grade III–IV, tumor larger than 4 cm, and advanced T stage increased the risk of LNM. In addition, LNM was a negative prognostic factor for OS and DSS. Ten variables were identified and incorporated into nomograms to estimate OS and DSS. Our nomograms outperformed the traditional staging system in training and validation cohorts. Patients were stratified into risk subgroups based on the OS- and DSS-nomogram scores. Patients in the high-risk subgroup had a higher risk of death and disease-specific mortality than those in the low- and intermediate-risk subgroups. Conclusions: LNM worsens the prognosis of HSCC. This study identified the independent prognostic factors for HSCC with LNM and developed satisfactory OS- and DSS-monogram to provide individual prediction and risk classification for patients with this diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Most cutaneous squamous cell carcinomas (cSCC) have a good prognosis, there is a small group where metastasis and death occur and the evaluation of this risk is still cause for controversy. Tumour budding is a pattern of histological invasion that is an emerging risk factor in other solid tumours. Objective: To examine the association between tumour budding and other known high‐risk predictors in cSCC. In addition, the impact of tumour budding on overall survival (OS) and disease‐specific survival (DSS) was analysed. Method: Retrospective study. It included patients with a diagnosis of non‐genital cSCC by excisional biopsy at a university hospital, between 2010 and 2020. A pathologist re‐analysed their histological slides and evaluated budding. Univariate and multivariate analyses were made to study the associations. Results: 156 cSCC biopsies were found, and positive tumour budding was found in 13.5%. This correlated with worse DSS and OS. On univariate analysis, budding was correlated with the diameter, thickness of the tumour, histological grade, level of invasion, perineural and lymphovascular invasion, previous radiotherapy, recurrent tumours and lymph node metastasis (LNM). Multivariate analysis: tumour budding was associated with poorly differentiated tumours, prior radiotherapy and LNM. Conclusion: An association was found between tumour budding and most known risk factors in cSCC. We found findings that indicate that the presence of tumour budding is associated with a worse prognosis in terms of LNM, OS and DSS. This supports the results of previous work which has suggested that budding could be related to high‐risk cSCC. [ABSTRACT FROM AUTHOR]

Increased disease-specific mortality has been observed among patients with local recurrence (LR) from uveal melanoma (UM), but the underlying mechanism is unknown. The purpose of this study was to determine if copy number alterations of chromosomes 3 and/or 8q, at the time of diagnosis, increase the incidence of LR and if disease-specific mortality among patients with LR depends on the chromosome status of the primary tumor. Retrospective cohort study. The study included 239 consecutive patients with primary UM (choroidal or ciliary body) treated with Ruthenium-106 (Ru-106) brachytherapy from January 2009 to December 2019 at a single national referral center. Cox regression modeling and Kaplan–Meier analyses were used to assess the effect of the status of chromosomes 3 and 8q on the incidence of LR and disease-specific mortality after the event of LR. Multistate models were used to illustrate the probabilities over time of patients being alive and disease-free, alive with LR, dead from UM metastases, or dead from other causes split on the status of chromosomes 3 and 8q. Incidence of LR and disease-specific mortality. Local recurrence was observed in 42 patients (16%). Overall incidence of LR was not affected by aberrations of chromosomes 3 and/or 8q (P = 0.87). Although LR occurred earlier in patients with aberrations of chromosomes 3 and/or 8q compared with patients with a normal copy number of chromosomes 3 and 8q, the median time from primary diagnosis to LR was 1.6 years (interquartile range [IQR], 1.0–2.0) and 3.2 years (IQR, 2.1–5.0), respectively. Cox regression found LR to be an independent risk factor for disease-specific mortality (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5–5.0) among all patients, but multistate models demonstrated a low risk of disease-specific death among patients with normal chromosomes 3 and 8q status, even after an LR. Copy number alterations of chromosome 3 and/or 8q in the primary UM did not increase the overall incidence of LR. However, the development of an LR enhanced the risk of disease-specific mortality among patients with copy number alterations of chromosomes 3 and/or 8q. Even after an LR, disease-specific mortality remained low among patients with normal copy numbers of chromosomes 3 and 8q. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

Backgrounds: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. In this study, we aim to construct a prognostic nomogram that integrates the clinical features and treatment options to predict disease-specific survival (DSS). Methods: A total of 713 patients diagnosed with LCNEC were from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010–2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010–2018. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA). Additionally, we conducted a subgroup analysis of data available in the external cohort that may impact prognosis but was not recorded in the SEER database. Results: Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group, respectively. Moreover, the calibration curves for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all Area Under Curve (AUC) > 0.8). DCA exhibited the favorable clinical applicability of the nomogram in the prediction of LCNEC survival. A risk classification system was built which could perfectly classify LCNEC patients into high-, medium- and low-risk groups (p < 0.001). The survival analysis conducted on the West China Hospital cohort indicated that whole brain radiation therapy (WBRT), prophylactic cranial irradiation (PCI), surgical procedures, tumor grade, Ki-67, and PD-L1 expression were not significantly associated with DSS. Conclusion: This study has effectively developed a prognostic nomogram and a corresponding risk stratification system, which demonstrate promising potential for predicting the DSS of patients with LCNEC. [ABSTRACT FROM AUTHOR]

This study assessed positive lymph node ratio (LNR) as a prognostic marker for patients with pyriform sinus cancer. The present study retrospectively analyzed 101 patients with pyriform sinus cancer to determine the association of LNR with recurrence-free survival (RFS) and disease-specific survival (DSS). The patients were followed up for a median duration of 28 months (range: 6–196 months). The number of median dissected lymph nodes (LNs) was 41, and the number of median positive LNs was three. The receiver operating characteristic curve revealed an LNR cut-off value of 8.6%. Lymphovascular invasion (LVI) or perineural invasion (PNI) (P = 0.001), thyroid gland invasion (TGI, P = 0.000), positive LNs >4 (P = 0.036), and LNR >8.6% (P = 0.008) were significantly associated with poor RFS, and LVI or PNI (P = 0.005), tumor pT3/T4 stage (P = 0.028), positive LNs >4 (P = 0.033), TGI (P = 0.001), and LNR >8.6% (P = 0.003) were significantly associated with poor DSS. The multivariate analysis revealed that LVI or PNI (P = 0.010), TGI (P = 0.000), and LNR >8.6% (P = 0.022) were independent predictors for poor RFS, while tumor pT3/T4 stage (P = 0.049), TGI (P = 0.015), and LNR >8.6% (P = 0.001) were independent predictors for poor DDS. LNR and other clinicopathological data can be used to predict the RFS and DSS of pyriform sinus cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: To describe a local radio-oncological treatment for patients with prostate cancer that metastasized to either the lymph nodes or distant regions. Methods and materials: We included 133 patients with prostate cancer that displayed either distant metastases (DM) or lymph node metastases alone (NM) and were treated between 2004 and 2019. All patients underwent computed tomography and a bone scan or 18F- or prostate-specific membrane antigen-targeted positron emission tomography. Patients received local external beam radiation therapy to the prostate to achieve local control (60–81.4 Gy to the prostate, and 45–50.4 Gy to pelvic lymph nodes), with either the 3D conformal (4-field box) or volumetric modulated arc therapy technique. A urologist prescribed additional therapy. Results: We included 51 patients with DM and 82 patients with NM. The mean follow-up was 42 months for all patients. The groups were similar in T stage, initial prostate-specific antigen, histology, androgen deprivation therapy, age, treatment techniques, and prescribed doses, but different in lymph node inclusion and follow-up times. In the NM and DM groups, the 5‑year biochemical recurrence-free rates were 52% and 24%, respectively (p < 0.0001); the 5‑year disease-specific survival rates were 92% and 61%, respectively (p = 0.001); and the 5‑year OS rates were 77% and 48%, respectively (p = 0.01). The groups had similar acute and late gastrointestinal and genitourinary side effects, except that late genitourinary side effects occurred significantly more frequently in the NM group (p = 0.01). Conclusions: DM was associated with significantly worse outcomes than NM. The long-term survival of patients with metastatic prostate cancer was low. [ABSTRACT FROM AUTHOR]

Background: The purpose of this retrospective study was to investigate the prognosis of patients with oral cavity cancer with positive margin (PM) or close margin (CM) divided into pN− and pN+ groups. Methods: The evaluated endpoints were local control and disease‐specific survival (DSS) rates. Results: Higher T classification, lymphovascular space invasion (LVSI), and older age were significant risk factors for DSS in the pN− groups. On the other hand, extranodal extension, multiple lymph node metastases, and LVSI were significant risk factors for DSS in the pN+ groups. Among the CM pN+ patients, no significant differences in the 3‐year DSS were observed between the only surgery (51.9%) and adjuvant groups (53.2%). Conclusions: Higher T classification and LVSI are high‐risk features more than PM or CM in the pN− groups for DSS. However, further prospective studies are needed to demonstrate the usefulness of adjuvant treatment in patients with PM or CM. [ABSTRACT FROM AUTHOR]

Skull base chordoma is a rare and locally destructive malignancy which presents unique therapeutic challenges. While achieving gross total resection (GTR) confers the greatest survival advantage, the role of adjuvant radiotherapy (RT) for patients who receive GTR remains unclear in the absence of prospective trials. Here, we aim to assess the effect of RT on survival outcomes in skull base chordoma patients who receive GTR by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Patients with diagnostic, primary site, and resection codes specific for chordoma, skull base, and GTR, respectively, were queried in the SEER database (2000–2018). Kaplan-Meier curves (log-rank test) were constructed and Cox proportional hazards models were used to assess survival outcomes. A total of 115 skull base chordomas undergoing GTR were identified, of which 37 (32%) received no RT and 78 (68%) received RT. Median follow-up was 55.00 months (range: 0.00–227.00). Overall survival (OS) of patients with GTR was 85% and 70% at 5 and 10 years, respectively. Multivariate Cox proportional hazard analysis among chordoma patients undergoing GTR found age ≥65 (P < 0.01) was associated with poorer OS outcomes. RT appeared to trend toward offering benefit in terms of OS in patients after GTR, however this did not achieve statistical significance in the adjusted model (HR = 0.51, CI = 0.23–1.16, P = 0.09). When comparing, disease-specific survival was also not improved in patients undergoing RT (HR = 0.58, CI = 0.23–1.46, P = 0.25). It remains unclear whether RT after GTR of chordoma improved survival outcomes among SEER database patients. [ABSTRACT FROM AUTHOR]

BackgroundPapillary thyroid cancer (PTC) is the fastest increasing cancer in the United States; incidence increases with age. It generally has a favorable prognosis but may behave more aggressively in older patients. This study aims to describe national treatment patterns for low-risk PTC in older adults.Materials and methodsThe Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients ≥66 y treated for clinical T1N0M0 PTC between 1996 and 2011. Multivariable logistic regression was used to identify factors associated with extent of surgery (total thyroidectomy versus lobectomy) and radioactive iodine (RAI) administration. Cox proportional hazards modeling was used to estimate the effect of treatment type on disease-specific survival (DSS).ResultsThree thousand two hundred and fourteen patients met inclusion criteria; 77.6% were women, median age was 72 y, and mean tumor size was 0.7 cm. 42.7% had preoperatively diagnosed PTC (versus incidental). 65.4% underwent total thyroidectomy, 29.0% lobectomy, and 5.6% lobectomy followed by completion thyroidectomy; 33.4% received postoperative RAI. Five- and 10-year DSS were 98.9% and 98.3%, respectively. After adjustment, larger tumor size (1.1-2 cm), multifocality, and a preoperative PTC diagnosis were associated with greater odds of undergoing more extensive surgery and receiving RAI (P  0.05).ConclusionsMost older adults with PTC underwent total thyroidectomy and a third received RAI; neither treatment improved DSS. In the growing elderly population, less extensive interventions for PTC may reduce morbidity and improve quality of life while preserving an excellent prognosis.

PurposeTo examine the California Cancer Registry (CCR) for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance in California patients.Patients and methodsThe CCR was queried for bladder cancer cases in California from 1988 to 2012. The primary outcome was disease-specific survival (DSS), defined as the time interval from date of diagnosis to date of death from bladder cancer. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors.ResultsA total of 72,452 cases were included (74.5% men, 25.5% women). The median age was 72 years (range, 18-109 years). The racial distribution among the patients was 81% white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% from other races. In black patients, tumors presented more frequently with advanced stage and high grade. Medicaid patients tended to be younger and had more advanced-stage, higher-grade tumors compared to patients with Medicare or managed care (P < .0001). Kaplan-Meier analysis demonstrated significantly poorer 5-year DSS in black, low SES, and Medicaid patients (P < .0001). When controlling for stage, grade, age, and gender, multivariate analysis revealed that black race (DSS hazard ratio = 1.295; 95% confidence interval, 1.212-1.384), low SES (DSS hazard ratio = 1.325; 95% confidence interval, 1.259-1.395), and Medicaid insurance (DSS hazard ratio = 1.349; 95% confidence interval, 1.246-1.460) were independent prognostic factors (P < .0001).ConclusionAn analysis of the CCR demonstrated that black race, low SES, and Medicaid insurance portend poorer DSS. These findings reflect a multifaceted socioeconomic and public health conundrum, and efforts to reduce inequalities should be pursued.

Abstract Background Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. Methods A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. Results 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50–1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50–1.50; P = 0.76) was observed with no PORT. Conclusions PORT isn’t necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

Abstract Background Tumor size assessment by MRI is central for staging uterine cervical cancer. However, the optimal role of MRI-derived tumor measurements for prognostication is still unclear. Material and methods This retrospective cohort study included 416 women (median age: 43 years) diagnosed with cervical cancer during 2002–2017 who underwent pretreatment pelvic MRI. The MRIs were independently read by three radiologists, measuring maximum tumor diameters in three orthogonal planes and maximum diameter irrespective of plane (MAXimaging). Inter-reader agreement for tumor size measurements was assessed by intraclass correlation coefficients (ICCs). Size was analyzed in relation to age, International Federation of Gynecology and Obstetrics (FIGO) (2018) stage, histopathological markers, and disease-specific survival using Kaplan–Meier-, Cox regression-, and time-dependent receiver operating characteristics (tdROC) analyses. Results All MRI tumor size variables (cm) yielded high areas under the tdROC curves (AUCs) for predicting survival (AUC 0.81–0.84) at 5 years after diagnosis and predicted outcome (hazard ratios [HRs] of 1.42–1.76, p

Objectives: Tumor satellites are defined as islands of tumor cells completely separated from the border of the main tumor. They are believed to be a sign of aggressive disease. Our goal was to investigate the association between tumor satellites and outcome in patients with oral squamous cell carcinoma. Materials and Methods: A retrospective analysis of all patients treated for oral squamous cell carcinoma at a university‐affiliated tertiary care center between 2010 and 2018 was performed. Data collected included demographics, clinical and pathological features including tumor satellites, staging, treatment modalities, and outcomes. Results: A total of 144 patients were included. The mean age of all patients was 63.5 and 50.7% were males. The mean follow‐up time was 40.5 months. Seventeen patients (11.8%) had tumor satellites. These patients had a higher rate of involved margins, peri‐neural invasion, lympho‐vascular invasion, and extra‐nodal extension. Tumor, nodal and overall classification were significantly more advanced in patients with satellites. Disease‐specific and overall survival rates were significantly lower among satellites patients (28.7% vs. 59.7% and 28.7% vs. 54.9%, respectively). Conclusions: Tumor satellites are associated with several adverse features and advanced locoregional disease. Patients with satellites should be treated aggressively with a combination of surgery aimed at achieving free surgical margins and adjuvant treatment, as they have a worse prognosis compared with patients without satellites. Further prospective studies are mandatory to consolidate the importance of adjuvant treatment in these patients. Level of Evidence: 3 Laryngoscope, 133:336–343, 2023 [ABSTRACT FROM AUTHOR]

Objective: Differentiated thyroid cancer (DTC) is associated with an excellent prognosis, but patients with distant metastatic DTC have a 10-year disease-specific survival (DSS) of just 50%. The incidence of distant metastatic DTC has steadily increased in the United States since the 1980s. The aim of this study was to examine trends in survival and treatment for patients with distant metastatic DTC. Methods: In this population-based, retrospective cohort study, patients with distant metastatic DTC were identified from the Surveillance, Epidemiology, and End Results-13 cancer registry program. Multivariable logistic and Cox regression analyses were used to examine factors associated with DSS and management. Annual percentage changes in treatment patterns were calculated using log-linear regression. Results: During 1992–2018, 1991 patients (69.7% white, 58.0% female, 47.5% aged ≥65 years) were diagnosed with distant metastatic DTC. Papillary thyroid cancer was the most common histological type (74.5%). While the 10-year DSS for overall DTC increased over time (95.4% for patients diagnosed in 1992–1998, 96.6% in 1999–2008, and 97.3% in 2009–2018; p < 0.01), 10-year DSS for DTC with distant metastases did not change (50.2%, 47.3%, and 52.4%, respectively; p = 0.48). Ten-year DSS rates were reduced for patients aged ≥65 years (28.1%), patients undergoing nonsurgical treatment with external beam radiation therapy and/or systemic therapy (6.0%), and patients undergoing no/unknown treatment (32.8%). On multivariable analysis, oncocytic carcinoma, age 65–79 and ≥80 years, male sex, node-positive disease, larger tumor size, nonsurgical treatment, and no/unknown treatment were associated with increased risk of thyroid cancer death. Between 1992 and 2018, the rate of nonsurgical treatment increased, on average, 1.3% per year (1992–1998: 22.9% vs. 2009–2018: 25.6%; p = 0.03), and the rate of patients receiving no/unknown treatment increased 1.9% per year (1992–1998: 11.3% vs. 2009–2018: 15.6%; p = 0.01). Patients aged 65–79 and ≥80 years were more likely than younger patients to receive nonsurgical management or no/unknown treatment. Conclusion: Patients diagnosed with distant metastatic DTC have experienced no improvement in DSS over the past three decades. An increasing proportion of patients diagnosed with distant metastatic DTC are receiving nonsurgical treatment or no/unknown treatment over time; the proportion was highest among the oldest patients. [ABSTRACT FROM AUTHOR]

Objective Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4 subclassification. Methods Patients with SCC of the EAC who underwent curative treatment from 2002 to 2021 at our hospital were retrospectively reviewed. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS), were analyzed. To clarify the surgical indication for advanced-stage tumors, we proposed the T4 subclassification. Results In the 46 patients included in the study, 8 patients had T1 tumors, 10 had T2 tumor, 5 had T3 tumors, and 23 had T4 tumors. The 5-year DSS with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS (p = 0.23 and 0.13, respectively). Patients with far-advanced-stage (T4b) tumors were significantly associated with shorter DSS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors (p = 0.007 and 0.03, respectively). Conclusion The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors. [ABSTRACT FROM AUTHOR]

The prognosis of oral squamous cell carcinoma (OSCC) with posterior invasion is poor. We examined whether the pterygomandibular raphe (PMR) is useful for the diagnosis of invasion and determination of surgical methods. Of 390 patients with OSCC treated surgically at our hospital between June 2009 and June 2020, 80 patients with posterior invasion were included in the study. Preoperative magnetic resonance imaging was used to classify the lesions into three types: non-contact with PMR (non-contact type), contact with PMR (contact type), and invasion beyond PMR (invasion type). We compared the local control, recurrence, and survival rates of each of the three types. The invasion type showed a significantly higher recurrence rate than the non-contact type (P < 0.001) and contact type (P = 0.018). Overall survival rate comparisons showed that the invasion type had significantly worse prognosis than the non-contact (P = 0.004) and contact types (P = 0.041). OSCCs with posterior invasion beyond the PMR showed a poor treatment outcome and, therefore, should be treated with caution. The initial surgery is especially important and must ensure local control. This study indicates that the PMR is an important criterion for surgical method determination and that invasion beyond the PMR is a predictor of local recurrence and poor prognosis. [ABSTRACT FROM AUTHOR]

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale.

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms with a potential to metastasize in 10–30% of cases. Several risk models have been designed to predict tumor behavior at the pleura and extrapleural sites. Intrabdominal SFTs primarily involving the gastrointestinal tract (SFTGI) and liver (SFTL) are rare. We analyzed a series of SFTGI and SFTL to describe the clinicopathologic features and evaluate prognostic factors. The cohort included 33 males and 25 females, with a median age of 58.5 years and a mean tumor size of 15.6 cm. Patients with SFTL were predominantly older females compared to patients with SFTGI. By univariate analysis, high mitotic count (> 4/10 HPF), tumor size, tumor necrosis, and nuclear pleomorphism were associated with both disease-specific survival (DSS) and metastasis-free survival (MFS) (p < 0.05). Tumor location (SFTL vs. SFTGI) also predicted MFS (p = 0.026). Only very high mitotic count (> 9/10 HPF) predicted local recurrence-free survival (LFS, p = 0.001). Further analysis showed that all adverse histologic parameters (necrosis, hypercellularity, pleomorphism) correlated with high mitotic grade (> 4/10 HPF) (p < 0.05). On multivariate analysis, only mitosis predicted DSS (p = 0.023), MFS (p = 0.01), and LFS (p = 0.017). Validation of the 3 risk models (mDemicco, Salas, Pasquali) showed variable associations with DSS, MFS, and LFS, while a simplied 3-tiered risk model based on mitosis (0–4, 5–9, > 9/10 HPF) performed well in predicting all risks. Our results suggest that prognostication of SFTs is mainly associated with mitotic activity, supporting the use of mitosis (> 4 and/or > 9/10 HPF) for tumor grading and risk stratification at specific locations. [ABSTRACT FROM AUTHOR]

BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single-institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan-Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive-year overall survival (OS) was 49%. Five-year disease-free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation-27 [ACE-27] scale; HR 3.76; 95% confidence interval [CI] 1.56-9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74-4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.

Background: Frailty as a common geriatric syndrome can affect the clinical outcomes in patients with gastric cancer. However, the impact of frailty on survival and readmission patients with gastric cancer has not been wellcharacterised. Objectives: To investigate the impact of frailty on survival and readmission in patients with gastric cancer undergoing gastrectomy by conducting a meta-analysis. Methods: Eligible studies were identified by searching the PubMed, Web of Science, Cochrane Library, and Embase databases until 2 September 2022. Observational studies that evaluated the value of frailty in predicting adverse outcomes in gastric cancer patients undergoing gastrectomy were included. The outcomes of interest were overall survival, disease-specific survival (death from gastric cancer), and readmission. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were pooled to calculate the association of frailty with adverse outcomes. Results: Eight studies reported on nine articles with 2,792 patients with gastric cancer were included. A fixed-effect meta-analysis indicated that frailty was associated with a reduced in-hospital overall survival (HR 2.08; 95% CI 1.46-2.95), long-term overall survival (HR 1.84; 95% CI 1.37-2.47), and diseasespecific survival (HR 1.94; 95% CI 1.34-2.83). In addition, frailty was associated with increased risk of readmission within 1 year (HR 3.63; 95% CI 1.87-7.06). Conclusions: Frailty was associated with a reduced overall survival and diseasespecific survival and an increased risk of readmission in patients with gastric cancer undergoing gastrectomy. Frail status may play an important role in the risk stratification of gastric cancer after gastrectomy. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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). Results: 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. Conclusion: Time to recurrence, extranodal extension, and higher T stage were independent prognosis predictors in OSCC. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest None disclosed.

Objective: For patients with clinical nodal-negative (cN0) maxillary oral squamous cell carcinoma (MOSCC), neck dissection (ND) and clinical observation are the main two management strategies for the neck. However, the indications corresponding to these two options remain controversial. This study aimed to elucidate the clinical factors affecting ND treatment and to identify clinical characteristics of the population that may benefit from ND based on a retrospective analysis of cN0 MOSCC patient data from the Surveillance, Epidemiology, and End Results (SEER) database., Methods: 8846 MOSCC patients were identified in the SEER database from 2000 to 2020. The Kaplan-Meier method was utilized to examine overall survival (OS) and disease-specific survival (DSS), while the hazard ratio (HR) was estimated using the stepwise multivariate Cox regression model. Furthermore, multi-subgroup analyses of DSS and OS were performed to compare ND and No ND., Results: We included 2,512 cN0 MOSCC patients. Basic survival analysis and Cox regression modeling showed that ND was an independent prognostic factor that promoted DSS and OS. Additional subgroup analyses revealed that the primary site and T-stage might influence the efficacy of ND modality. Moreover, patients with T3/T4 stage of upper gingival squamous cell carcinoma (UGSCC) (DSS p = 0.009, OS p = 0.004), hard palate squamous cell carcinoma (HPSCC) (DSS p = 0.001, OS p < 0.001), and soft palate squamous cell carcinoma (SPSCC) (p = 0.029) showed a better survival benefit with ND in OS and DSS. Nonetheless, no differences were observed in OS and DSS between ND and No ND at the T1/T2 stage of the abovementioned primary tumor sites. Additionally, the DSS outcomes for T1/T2 stage upper lip squamous cell carcinoma (ULSCC) patients were significantly worse in the ND group than in the No ND group (p = 0.018). However, no significant differences were noted in OS (p = 0.140) as well as OS (p = 0.248) and DSS (p = 0.627) for T1/T2 and T3/T4 patients, respectively., Conclusion: Active surveillance might be a feasible strategy for managing all T-staged ULSCC as well as early-stage (T1/T2) UGSCC, SPSCC, and HPSCC, provided regular and meticulous follow-up is performed. Hence, concurrent ND is recommended for patients with intermediate to advanced (T3/T4) stage UGSCC, SPSCC, and HPSCC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background and Objective: Cutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival., Materials and Methods: All cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated., Results: A total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort., Conclusions: Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients' survival and was closely associated with tumor skin involvement and stage IIB., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background/aim: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance., Patients and Methods: This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes., Results: The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC., Conclusion: This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To reveal a novel pathological feature: heterotypic neutrophil-intumor structure (hNiT) first discovered in patients with oropharyngeal squamous cell carcinoma (OPSCC), to analyze the prognostic role of hNiT in OPSCC patients and to explore the role of p16 in the formation of hNiT structures. Methods: Clinically, 197 patients were enrolled. Clinicopathological information was extracted and analyzed. All pathologic sections made from primary tumors were re-evaluated by immunohistochemistry and immunostaining. In vitro, we cocultured OPSCC cell line SCC-15 with neutrophils to form hNiT structures, which were then subject to fluorescence staining. By RNAi and overexpression techniques, we investigated the role of CDKN2A in the formation of hNiTs. We validated the two techniques by qPCR and Western Blot. Results: The hNiT as a novel pathological feature was first discovered in the tissues of OPSCC. The FNiT was significantly associated with tumor stage, disease stage, p16 and tumor grade. A total of 119 patients died of the disease, and the 5-year disease-specific survival (DSS) rate was 36%. The median survival time was 52.6 months. In patients with an FNiT<0.5%, the 5-year DSS rate was 40%; in patients with an FNiT>=0.5%, the 5-year DSS was 28%, and the difference was significant (p=0.001). Cox model analysis showed that FNiT along with disease stage, p16 and tumor grade was an independent prognostic factor for DSS. Immunostaining results of p16 expression showed hNiT formation was negatively correlated to p16 in OPSCC as well as in the hNiT formation assays in vitro indicated by fluorescent staining. Function assays of CDKN2A implied that reduce CDKN2A promoted the formation of hNiT while elevated CDKN2A impeded the hNiT formation. Conclusion: The hNiT as a novel pathological feature is associated with the adverse prognosis of OPSCC patients with p16 inhibiting the formation of hNiT structures. [ABSTRACT FROM AUTHOR]

Introduction: Among industrialized countries, endometrial cancer is a common malignancy with generally an excellent outcome. To personalize medicine, we ideally compile as much information as possible concerning patient prognosis prior to effecting an appropriate treatment decision. Endometrial cancer preoperative risk stratification (ENDORISK) is a machine learning-based computational Bayesian networks model that predicts lymph node metastasis and 5-year disease-specific survival potential with percentual probability. Our objective included validating ENDORISK effectiveness in our patient cohort, assessing its application in the current use of sentinel node biopsy, and verifying its accuracy in advanced stages. Methods: The ENDORISK model was evaluated with a retrospective cohort of 425 patients from the University Hospital Brno, Czech Republic. Two hundred ninety-nine patients were involved in our disease-specific survival analysis; 226 cases with known lymph node status were available for lymph node metastasis analysis. Patients were included undergoing either pelvic lymph node dissection (N = 84) or sentinel node biopsy (N =70) to explore the accuracy of both staging procedures. Results: The area under the curve was 0.84 (95% confidence interval [CI], 0.77-0.9) for lymph node metastasis analysis and 0.86 (95% CI, 0.79-0.93) for 5-year disease-specific survival evaluation, indicating quite positive concordance between prediction and reality. Calibration plots to visualize results demonstrated an outstanding predictive value for low-risk cancers (grades 1-2), whereas outcomes were underestimated among high-risk patients (grade 3), especially in disease-specific survival. This phenomenon was even more obvious when patients were subclassified according to FIGO clinical stages. Conclusions: Our data confirmed ENDORISK model's laudable predictive ability, particularly among patients with a low risk of lymph node metastasis and expected favorable survival. For high-risk and/or advanced stages, the ENDORISK network needs to be additionally trained/improved. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary metastasectomy (PM) is often performed in sarcoma patients with resectable oligo-metastases in the lungs. Although there have been several studies on PM for sarcomas, few have analyzed only soft tissue sarcomas (STSs) arising in the trunk wall and extremities, and many of these studies are older. Therefore, it would be of interest to confirm the outcomes of PM for STS in recent years, when systemic treatment has advanced, in accordance with the latest WHO classification. In the present study, we investigated our recent results of PM for STSs arising in the trunk and extremities, and analyzed the prognostic factors and safety of PM. Although there is no evidence from prospective randomized controlled trials to support this practice, pulmonary metastases of sarcomas are often treated surgically if they are resectable. The purpose of this retrospective study was to evaluate the prognostic factors and outcome of pulmonary metastasectomy (PM) for soft tissue sarcomas (STSs) arising in the trunk wall and extremities in 66 consecutive patients. Prognostic factors associated with disease-specific survival after PM were evaluated using univariate and multivariate analyses. The patients included 38 men and 28 women, with a median age of 49 years. The median disease-specific survival after PM was 48 months, and the 5-year survival rate was 45%. No major perioperative complications occurred. Disease-free interval (<12 months), size of largest lung lesion (≥20 mm), and non-curative resection were independent prognostic factors in multivariate analysis. PM was effective in selected patients with pulmonary metastases from STSs arising in the trunk wall and extremities. Disease-free interval, maximum size of metastases, and resectability were identified as prognostic factors. [ABSTRACT FROM AUTHOR]

To assess the predictive value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition , and histologic features for outcomes and metastasis patterns in conjunctival melanoma (CM). Retrospective, single-center cohort study. Eighty-three patients with CM were treated at Shanghai Ninth People's Hospital between 2000 and 2021. We reviewed the clinical and histologic parameters and used Kaplan–Meier survival curves and Cox proportional hazards regression models for risk factor analyses. Time to nodal/distant metastasis, disease-specific survival, metastatic pattern, and metastatic site. At presentation, 5 patients (6%) had clinical tumor (cT)1 disease, 34 patients (41%) had cT2 disease, and 44 patients (53%) had cT3 disease. Four patients (5%) had nodal metastasis (N1), and none had distant metastasis (M1). During follow-up, 12 patients (14%) developed nodal metastasis, 29 patients (35%) developed distant metastasis, and 26 patients (31%) died of disease. The brain, liver, and lung were common distant metastasis sites. Higher cT category was associated with increased risks of distant metastasis (P < 0.001) and disease-specific death (P = 0.002). The separate analysis of primary and recurrent tumors at presentation showed that the patients with cT3 tumors had a higher risk of distant metastasis than those with cT2 tumors. Greater tumor thickness, ulceration, and the presence of regression were correlated with distant metastasis. Previously unreported mutations were detected in the tumor suppressor genes FAT atypical cadherin 4 (FAT4) and spleen associated tyrosine kinase (SYK). Among the 29 patients who developed distant metastasis, we analyzed 2 patterns of metastasis: Eleven patients (38%) developed nodal metastasis before distant metastasis, and 18 patients (62%) developed distant metastasis without previously known nodal metastasis. The patients with cT3 tumors were more likely to follow the latter metastasis pattern (P = 0.02). Conjunctival melanoma presented with mostly advanced stages and high rates of distant metastasis in the current Chinese cohort. This study confirmed the prognostic value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, for Chinese patients. Histologic features, such as tumor thickness and ulceration, should be emphasized when assessing prognosis and guiding the treatment of CM. Prognostic value of AJCC T category was associated with increased risks of distant metastasis and disease-specific death, Greater tumor thickness, and, ulceration, and the presence of regression were correlated with distant metastasis. Patients with cT3 tumors were more likely to develop distant metastasis without prior nodal metastasis. [ABSTRACT FROM AUTHOR]

Background: Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. Methods: A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. Results: 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50–1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50–1.50; P = 0.76) was observed with no PORT. Conclusions: PORT isn't necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed. [ABSTRACT FROM AUTHOR]

Background: Tumor size assessment by MRI is central for staging uterine cervical cancer. However, the optimal role of MRI-derived tumor measurements for prognostication is still unclear. Material and methods: This retrospective cohort study included 416 women (median age: 43 years) diagnosed with cervical cancer during 2002–2017 who underwent pretreatment pelvic MRI. The MRIs were independently read by three radiologists, measuring maximum tumor diameters in three orthogonal planes and maximum diameter irrespective of plane (MAXimaging). Inter-reader agreement for tumor size measurements was assessed by intraclass correlation coefficients (ICCs). Size was analyzed in relation to age, International Federation of Gynecology and Obstetrics (FIGO) (2018) stage, histopathological markers, and disease-specific survival using Kaplan–Meier-, Cox regression-, and time-dependent receiver operating characteristics (tdROC) analyses. Results: All MRI tumor size variables (cm) yielded high areas under the tdROC curves (AUCs) for predicting survival (AUC 0.81–0.84) at 5 years after diagnosis and predicted outcome (hazard ratios [HRs] of 1.42–1.76, p < 0.001 for all). Only MAXimaging independently predicted survival (HR = 1.51, p = 0.03) in the model including all size variables. The optimal cutoff for maximum tumor diameter (≥ 4.0 cm) yielded sensitivity (specificity) of 83% (73%) for predicting disease-specific death after 5 years. Inter-reader agreement for MRI-based primary tumor size measurements was excellent, with ICCs of 0.83–0.85. Conclusion: Among all MRI-derived tumor size measurements, MAXimaging was the only independent predictor of survival. MAXimaging ≥ 4.0 cm represents the optimal cutoff for predicting long-term disease-specific survival in cervical cancer. Inter-reader agreement for MRI-based tumor size measurements was excellent. [ABSTRACT FROM AUTHOR]

BackgroundThis study aims to compare the seventh and eighth editions of the American Joint Commission on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, node, metastasis staging system for patients with papillary thyroid cancer (PTC) in two national patient cohorts.MethodsAdult PTC patients undergoing surgery were selected from the Surveillance, Epidemiology and End Results (SEER) program (2004-2012) and the National Cancer Database (2004-2012). Staging criteria for the seventh and eighth AJCC/UICC editions were applied separately to each cohort. Survival probabilities were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to estimate the association of stage with survival in both settings. The Akaike information criterion was used to assess model performance.ResultsAbout 23% of patients were downstaged from the seventh to the eighth edition in SEER, while 24% were downstaged in the National Cancer Database. Disease-specific survival (DSS) and overall survival (OS) were significantly related to stage at diagnosis when using both the seventh and eighth editions of the AJCC/UICC staging system (p

IntroductionAmong industrialized countries, endometrial cancer is a common malignancy with generally an excellent outcome. To personalize medicine, we ideally compile as much information as possible concerning patient prognosis prior to effecting an appropriate treatment decision. Endometrial cancer preoperative risk stratification (ENDORISK) is a machine learning–based computational Bayesian networks model that predicts lymph node metastasis and 5-year disease-specific survival potential with percentual probability. Our objective included validating ENDORISK effectiveness in our patient cohort, assessing its application in the current use of sentinel node biopsy, and verifying its accuracy in advanced stages.MethodsThe ENDORISK model was evaluated with a retrospective cohort of 425 patients from the University Hospital Brno, Czech Republic. Two hundred ninety-nine patients were involved in our disease-specific survival analysis; 226 cases with known lymph node status were available for lymph node metastasis analysis. Patients were included undergoing either pelvic lymph node dissection (N = 84) or sentinel node biopsy (N =70) to explore the accuracy of both staging procedures.ResultsThe area under the curve was 0.84 (95% confidence interval [CI], 0.77–0.9) for lymph node metastasis analysis and 0.86 (95% CI, 0.79–0.93) for 5-year disease-specific survival evaluation, indicating quite positive concordance between prediction and reality. Calibration plots to visualize results demonstrated an outstanding predictive value for low-risk cancers (grades 1–2), whereas outcomes were underestimated among high-risk patients (grade 3), especially in disease-specific survival. This phenomenon was even more obvious when patients were subclassified according to FIGO clinical stages.ConclusionsOur data confirmed ENDORISK model’s laudable predictive ability, particularly among patients with a low risk of lymph node metastasis and expected favorable survival. For high-risk and/or advanced stages, the ENDORISK network needs to be additionally trained/improved.

ObjectiveTo reveal a novel pathological feature: heterotypic neutrophil-in-tumor structure (hNiT) first discovered in patients with oropharyngeal squamous cell carcinoma (OPSCC), to analyze the prognostic role of hNiT in OPSCC patients and to explore the role of p16 in the formation of hNiT structures.MethodsClinically, 197 patients were enrolled. Clinicopathological information was extracted and analyzed. All pathologic sections made from primary tumors were re-evaluated by immunohistochemistry and immunostaining. In vitro, we cocultured OPSCC cell line SCC-15 with neutrophils to form hNiT structures, which were then subject to fluorescence staining. By RNAi and overexpression techniques, we investigated the role of CDKN2A in the formation of hNiTs. We validated the two techniques by qPCR and Western Blot.ResultsThe hNiT as a novel pathological feature was first discovered in the tissues of OPSCC. The FNiT was significantly associated with tumor stage, disease stage, p16 and tumor grade. A total of 119 patients died of the disease, and the 5-year disease-specific survival (DSS) rate was 36%. The median survival time was 52.6 months. In patients with an FNiT=0.5%, the 5-year DSS was 28%, and the difference was significant (p=0.001). Cox model analysis showed that FNiT along with disease stage, p16 and tumor grade was an independent prognostic factor for DSS. Immunostaining results of p16 expression showed hNiT formation was negatively correlated to p16 in OPSCC as well as in the hNiT formation assays in vitro indicated by fluorescent staining. Function assays of CDKN2A implied that reduce CDKN2A promoted the formation of hNiT while elevated CDKN2A impeded the hNiT formation.ConclusionThe hNiT as a novel pathological feature is associated with the adverse prognosis of OPSCC patients with p16 inhibiting the formation of hNiT structures.

Abstract Background Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Very few studies have presented data on pleomorphic liposarcoma specifically, often including a limited number of cases and short-term follow-up. As a result, the survivorship and prognostic characteristics of this tumor remain incompletely identified. Study design and setting Cross-sectional analysis of the Surveillance Epidemiology and End Results database (1996–2015). Results Overall survival for the entire series was 54% (95% confidence interval [CI], 49–58%) and 40% (95% CI, 35–45%) at 5 and 10 years, respectively. Disease-specific survival for the entire series was 60% (95% CI, 56–65%) and 53% (95% CI, 48–58%) at 5 and 10 years, respectively. Patients who survived 10 years or more were more likely to die of events unrelated to pleomorphic liposarcoma. Univariate and multivariate analysis demonstrated that not receiving cancer-directed surgery was an independent poor prognostic factor. Older age (≥ 65 years old) was associated with worse overall survival but not disease-specific survival. Tumor stage and radiotherapy showed different impact on survival depending on tumor size. In comparison to localized staged tumors, regional stage only predicts poor survival in patients with tumor size less than 5 cm, while distant stage is an independent worse prognosis factor. Radiotherapy only benefits patients with tumor size larger than 10 cm. These results were confirmed in competing risk analysis. Conclusion Survival rates of patients with pleomorphic liposarcoma has not changed over the past 20 years. Patients with distant stage have poor prognosis; regional stage indicates worse survival in patients with tumor size less than 5 cm. Receiving surgery could prolong the survival, while radiotherapy only benefits patients with large tumor size (> 10 cm). Older age is associated with poor overall survival but not disease-specific survival. Routine patient surveillance following initial diagnosis should at least be 10 years for pleomorphic liposarcoma.

Background: The aim of this study was to derive and validate a decision tree model to predict disease-specific survival after curative resection for primary cholangiocarcinoma (CCA). Method: Twenty-one clinical characteristics were collected from 482 patients after curative resection for primary CCA. A total of 289 patients were randomly allocated into a training cohort and 193 were randomly allocated into a validation cohort. We built three decision tree models based on 5, 12, and 21 variables, respectively. Area under curve (AUC), sensitivity, and specificity were used for comparison of the 0.5-, 1-, and 3-year decision tree models and regression models. AUC and decision curve analysis (DCA) were used to determine the predictive performances of the 0.5-, 1-, and 3-year decision tree models and AJCC TNM stage models. Results: According to the fitting degree and the computational cost, the decision tree model derived from 12 variables displayed superior predictive efficacy to the other two models, with an accuracy of 0.938 in the training cohort and 0.751 in the validation cohort. Maximum tumor size, resection margin, lymph node status, histological differentiation, TB level, ALBI, AKP, AAPR, ALT, γ-GT, CA19-9, and Child-Pugh grade were involved in the model. The performances of 0.5-, 1-, and 3-year decision tree models were better than those of conventional models and AJCC TNM stage models. Conclusion: We developed a decision tree model to predict outcomes for CCA undergoing curative resection. The present decision tree model outperformed other clinical models, facilitating individual decision-making of adjuvant therapy after curative resection. [ABSTRACT FROM AUTHOR]

Background: Primary small cell breast carcinoma (SCBC) is an uncommon malignancy with highly invasive behavior. The aim of this study was to find out more about the incidence, clinicopathologic characteristics and identify potential prognostic factors of SCBC. Methods: Data of patients with primary diagnosis of SCBC between 1975 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence after adjustment for age and percentage change per year in incidence were calculated. Disease-specific survival (DSS) and overall survival (OS) were analyzed among these SCBC patients identified from the SEER database. The whole cohorts were randomized into training and validation cohorts as ratio of 7: 3. Cox regression analysis was performed to determine predictors of survival with the training cohorts. Predictive models were constructed with training cohorts, and nomogram validation was performed using receiver operating characteristic curves, concordance indices and calibration curves in both training and validation cohorts. Results: 323 SCBC patients were enrolled finally during the research period. The overall incidence after adjustment for age between 1990 and 2018 was 0.14 per million per year, and the prevalence of the incidence has plateaued. Most of these tumors were poorly differentiated or undifferentiated. The most prevalent presenting stage was Stage II. Patients identified in this study were randomly divided into training (n = 226) and testing (n = 97) cohorts. Multivariate Cox proportional hazards model showed that chemotherapy, surgery and stage were important predictors of DSS and OS. Conclusion: SCBC is considered an infrequent breast neoplasm with aggressive characteristics. Tumor stage is associated with poor prognosis. Combination of surgery and chemotherapy is the main treatment for SCBC. [ABSTRACT FROM AUTHOR]