Disease-specific Survival Outcomes Research Articles

Better Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma.

Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer. TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes. Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival. However, better outcomes were not observed when assessing anti-viral CDR3s representing cytomegalovirus, influenza A, or Sars-CoV-2. Due to previous occurrences of the occasional misdiagnoses of lymphoma as ovarian cancer, the frequency of anti-EBV CDR3s in lymphoma patients was determined. These frequencies were relatively high, particularly for diffuse large B-cell lymphoma. These findings (i) underscore the potential value of anti-EBV immune responses in terms of patient outcomes; (ii) raise questions about the potential value of anti-EBV immunotherapies; and (iii) support further inquiry into the relationship between EBV infection and previously reported cases of ovary-resident lymphoma.

Delving into female breast cancer: Distinct disease-specific survival outcomes between invasive lobular and ductal carcinomas revealed by propensity score matching

Purpose The difference in prognosis between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) is still controversial in the academic community. Resolving this controversy can help to more accurately determine patients’ prognosis, provide further personalized treatment, alleviate unnecessary psychological burden for some patients, and provide direction for further fundamental research. Patients and methods A retrospective cohort study was conducted using the SEER Research Plus Data 8 Registries, Nov 2021 sub (1978–2019), including female breast cancer patients diagnosed with ILC or IDC between 2010 and 2015. Univariate and multivariate Cox regression analyses were performed, and key covariates affecting prognosis were selected. Propensity score matching (PSM) was employed to match patients, and balance tests were conducted to evaluate covariate distribution. Disease-specific survival (DSS) differences between the matched IDC and ILC groups were compared. Results Following PSM, the covariate differences between the IDC and ILC groups were significantly reduced. The survival analysis revealed a significantly better prognosis for the IDC group than the ILC group (Log-rank test p < 0.001), with a 28.0% increased risk observed in the ILC group. Conclusion This study provides evidence supporting the existence of significant differences in prognosis between IDC and ILC patients after rigorous matching. The IDC group displayed a significantly better prognosis than the ILC group. Notably, these findings have implications for personalized treatment in clinical practice and contribute to the ongoing academic debate on survival differences between IDC and ILC. However, further research is needed to investigate the biological mechanisms, gene expression, and signaling pathway disparities between IDC and ILC, aiming to provide more targeted guidance for clinical decision-making.

Improved disease-specific survival in lentigo maligna treated with Mohs surgery over wide local excision: a retrospective cohort analysis.

Lentigo maligna (LM), a subtype of melanoma in situ, typically occurs on sun-damaged skin of the head and neck in older men. Using the SEER database, the aim of this study was to compare disease-specific survival (DSS) outcomes between patients treated with wide local excision (WLE) and Mohs micrographic surgery (MMS), finding – on multivariable analysis – that MMS demonstrated improved 5- and 10-year DSS rates and a lower disease-specific mortality risk than WLE. Our findings highlight a potential DSS benefit of MMS for treating LM, although further research is required to confirm these findings and explore factors influencing treatment choices.

Disease-specific survival outcomes for patients after locoregional treatment for ductal carcinoma in situ: observational cohort study.

Breast-conserving surgery alone, breast-conserving surgery with adjuvant radiation treatment, and mastectomy are guideline-concordant treatments for ductal carcinoma in situ. The aim of this study was to compare survival outcomes between these treatment options. A stratified random sample of patients diagnosed with pure ductal carcinoma in situ between 2008 and 2014 was selected from 1330 sites in the USA. Data on diagnosis, treatment, and follow-up were abstracted by local cancer registrars. Population-averaged marginal estimates of disease-specific survival and overall survival for breast-conserving surgery alone, breast-conserving surgery with radiation treatment, and mastectomy were obtained by combining sampling and overlap weights. A total of 18 442 women were included, with a median follow-up of 67.8 (interquartile range 46.1-93.5) months. A total of 35 women died from breast cancer, at a median age of 62 (interquartile range 50-74) years. Population-averaged 8-year rates of disease-specific survival were 99.6% or higher for all treatment groups, with no significant differences between groups (breast-conserving surgery alone versus breast-conserving surgery with radiation treatment, HR 1.19 (95% c.i. 0.29 to 4.85); and mastectomy versus breast-conserving surgery with radiation treatment, HR 1.74 (95% c.i. 0.53 to 5.72). There was no difference in overall survival between the patients who underwent a mastectomy and the patients who underwent breast-conserving surgery with radiation treatment (HR 1.09 (95% c.i. 0.83 to 1.43)). Patients who underwent breast-conserving surgery alone had lower overall survival compared with the patients who underwent breast-conserving surgery with radiation treatment (HR 1.29 (95% c.i. 1.00 to 1.67)). This survival difference vanished for all but one subgroup, namely patients less than 65 years (HR 1.86 (95% c.i. 1.15 to 3.00)). There was no statistically significant difference in disease-specific survival between women operated with breast-conserving surgery alone, breast-conserving surgery with radiation treatment, or mastectomy for ductal carcinoma in situ. Given the low absolute risk of disease-specific mortality, these results provide confidence in offering individualized locoregional treatment without fear of compromising survival.

Prognosing post-treatment outcomes of head and neck cancer using structured data and machine learning: A systematic review.

This systematic review aimed to evaluate the performance of machine learning (ML) models in predicting post-treatment survival and disease progression outcomes, including recurrence and metastasis, in head and neck cancer (HNC) using clinicopathological structured data. A systematic search was conducted across the Medline, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological characteristics and performance metrics of studies that developed and validated ML models were assessed. The risk of bias was evaluated using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Out of 5,560 unique records, 34 articles were included. For survival outcome, the ML model outperformed the Cox proportional hazards model in time-to-event analyses for HNC, with a concordance index of 0.70-0.79 vs. 0.66-0.76, and for all sub-sites including oral cavity (0.73-0.89 vs. 0.69-0.77) and larynx (0.71-0.85 vs. 0.57-0.74). In binary classification analysis, the area under the receiver operating characteristics (AUROC) of ML models ranged from 0.75-0.97, with an F1-score of 0.65-0.89 for HNC; AUROC of 0.61-0.91 and F1-score of 0.58-0.86 for the oral cavity; and AUROC of 0.76-0.97 and F1-score of 0.63-0.92 for the larynx. Disease-specific survival outcomes showed higher performance than overall survival outcomes, but the performance of ML models did not differ between three- and five-year follow-up durations. For disease progression outcomes, no time-to-event metrics were reported for ML models. For binary classification of the oral cavity, the only evaluated subsite, the AUROC ranged from 0.67 to 0.97, with F1-scores between 0.53 and 0.89. ML models have demonstrated considerable potential in predicting post-treatment survival and disease progression, consistently outperforming traditional linear models and their derived nomograms. Future research should incorporate more comprehensive treatment features, emphasize disease progression outcomes, and establish model generalizability through external validations and the use of multicenter datasets.

Neck dissection of cN0 maxillary oral squamous cell carcinoma: A study based on SEER database

ObjectiveFor 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. Methods8846 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. ResultsWe 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. ConclusionActive 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.

Prognostic factors and clinical survival outcome in patients with primary mediastinal diffuse large B-cell lymphoma in rituximab era: A population-based study.

The goal of this study was to investigate the clinical characteristics, prognostic variables, and survival of patients with primary mediastinal diffuse large B cell lymphoma (PMBCL) in the rituximab era. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PMBCL patients diagnosed between 2000 and 2019. The Kaplan-Meier (K-M) technique and log-rank test were used to assess overall survival (OS) and disease-specific survival (DSS). The independent prognostic variables for OS and DSS were identified using univariate and multivariate Cox regression analysis. Nomograms were created to predict survival prospects according to identified prognostic indicators. Totally, 841 patients were enrolled with PMBCL. One-year, 5-year, and 10-year OS rates were 93.99%, 85.04%, and 81.76%, and the corresponding DSS rates were 95.27%, 87.37%, and 85.98%. The results of multivariate Cox regression analysis demonstrated that age, years of diagnosis, Ann arbor staging, and chemotherapy were independent prognostic factors for survival. Nomograms designed exclusively for PMBCL were created to forecast the likelihood of 1-year, 5-year, and 10-year OS and DSS, respectively. The Harrell concordance index (C-index) for the nomograms predictions of OS and DSS were 0.704 and 0.733, respectively, which showed the established model harboring powerful and accurate performance. The present study revealed that incidence of PMBCL has been consistently rising over the last 20 years. Simultaneously, survival rates have improved tremendously. Rituximab based immunochemotherapy has emerged as an effective treatment option, leading to enhanced OS and DSS outcomes. Furthermore, the nomograms specifically developed for PMBCL have demonstrated robustness and accuracy in forecasting OS and DSS rates at 1, 5, and 10 years. These predictive tools can be valuable for clinicians in accurately estimating prognosis and establishing personalized treatment plans and follow-up protocols.

Survival outcomes of malignant peripheral nerve sheath tumors (MPNSTs) with and without neurofibromatosis type I (NF1): a meta-analysis

IntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs.MethodsAn electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest.ResultsA total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication.ConclusionNF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.

The effect of radioactive iodine (RAI) on disease-specific survival in differentiated thyroid cancer (DTC): A study of 96,557 patients.

e18095 Background: The use of RAI in the treatment of DTC of various stages and risk levels is widespread. However, its efficacy continues to be a subject of debate, particularly with regard to low-risk patients. Some studies have found significant differences in RAI's ability to decrease recurrence and distant metastasis, while others have not. Thus, we conducted this study to evaluate the effect of RAI on disease-specific survival (DSS) in patients with DTC without distant metastasis. Methods: Data were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between the years 2000 and 2018. Patients who have distant metastatic, tumor size ≥200 mm, receiving chemotherapy or any type of radiation other than RAI were excluded. Only patients with total thyroidectomy as surgical procedure were included. These patients were classified into three groups based on their histology: classical papillary thyroid carcinoma (C-PTC), follicular type variant carcinoma (FV-PTC), and follicular thyroid cancer (FTC). T-tests and chi-square tests were employed to compare variables, while the Cox proportional hazards model was utilized to assess the effect of RAI on DSS, presenting adjusted hazard ratios and confidence intervals. Results: The study population consisted of 96,557 patients, with 59,460 classified as having C-PTC, 31,583 as FV-PTC, and 5,489 as FTC. Most patients were female (78.6%), and the mean age was 45.8 years. 80.5% of the patients were white. The mean tumor size was 19.4 mm, with FTC tumors having a larger mean size of 34.8 mm. About a third of cases had an extrathyroidal extension. FV-PTC had the most favorable survival outcome with a 5-year DSS of 97.9%, followed by C-PTC (97.1%) and then FTC (96.9%). RAI was administered to 61.2% of FTC cases, 53.2% of C-PTC cases, and 52.1% of FV-PTC cases. In both FV-PTC and C-PTC, patients who received RAI had significantly better long-term survival than those who underwent surgery alone. The multivariable analysis confirmed that RAI had a more favorable prognosis in FV-PTC (HR = 0.68, 95%CI: 0.61 to 0.77, p&lt;0.001) and C-PTC (HR = 0.60, 95%CI: 0.54 to 0.67, p&lt;0.001), but did not result in improved DSS in FTC (HR = 0.87, 95%CI: 0.70 to 1.09, p = 0.226). There was a survival difference between the three histological subtypes in the overall cohort (p&lt;0.001), even after matching baseline characteristics (p = 0.019). Conclusions: Our results showed that RAI administration was statistically associated with improved long-term DSS outcomes in FV-PTC and C-PTC histological subtypes, but not in FTC. However, a careful interpretation of these results is needed as the survival benefit was less than 3% in all cohorts, it might be clinically insignificant. This study was the first to examine all histological types of DTC using a large sample size. There is a need for a randomized trial to confirm the efficacy of RAI in FTC treatment.

Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation.

This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.

Jumonji domain-containing protein RIOX2 is overexpressed and associated with worse survival outcomes in prostate cancers.

Histone demethylase RIOX2 was cloned as a c-Myc downstream gene involved in cell proliferation and has been implicated as an oncogenic factor in multiple tumor types. Its expression profiles and correlation with disease progression in prostate cancers are unknown. Transcriptomic profiles of Jumanji domain-containing protein genes were assessed using multiple public expression datasets generated from RNA-seq and cDNA microarray assays. RIOX2 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Gene expression profiles were analyzed using the bioinformatics software R package. Western blot assay examined androgen stimulation on RIOX2 protein expression in LNCaP cells. Among 35 Jumanji domain-containing protein genes, 12 genes were significantly upregulated in prostate cancers compared to benign compartments. COX regression analysis identified that the ribosomal oxygenase 2 (RIOX2) gene was the only one significantly associated with disease-specific survival outcomes in prostate cancer patients. RIOX2 upregulation was confirmed at the protein levels using immunohistochemical assays on prostate cancer tissue sections. Meanwhile, RIOX2 upregulation was associated with clinicopathological features, including late-stage diseases, adverse Gleason scores, TP53 gene mutation, and disease-free status. In castration-resistant prostate cancers (CRPC), RIOX2 expression was positively correlated with AR signaling index but negatively correlated with the neuroendocrinal progression index. However, androgen treatment had no significant stimulatory effect on RIOX2 expression, indicating a parallel but not a causative effect of androgen signaling on RIOX2 gene expression. Further analysis discovered that RIOX2 expression was tightly correlated with its promoter hypomethylation and MYC gene expression, consistent with the notion that RIOX2 was a c-Myc target gene. The Jumanji domain-containing protein RIOX2 was significantly overexpressed in prostate cancer, possibly due to c-Myc upregulation. RIOX2 upregulation was identified as an independent prognostic factor for disease-specific survival.

Neck management of pathological N1 oral squamous cell carcinoma: a retrospective study

This study was performed to compare the effects of neck dissection procedures on the prognosis of patients with pathological N1 (pN1) oral squamous cell carcinoma (OSCC), analyse factors affecting the prognosis, and provide a neck management strategy for clinical N1 (cN1) oral cancer. The study patients were divided into two groups according to the neck dissection: a selective neck dissection (SND) group (n = 85) and a radical or modified radical neck dissection (RND/MRND) group (n = 22). There was no statistically significant difference in recurrence rates at local, regional, and distant sites between the SND and RND/MRND groups. The 5-year overall survival was 68.3% for SND and 65.2% for RND/MRND patients (P = 0.590), while the 5-year disease-specific survival was 70.4% for SND and 75.7% for RND/MRND patients (P = 0.715). Histological grade and postoperative radiotherapy were independent predictors of the outcome for SND patients. For histological grade II/III cases, 5-year overall survival (P = 0.004) and disease-specific survival (P = 0.002) outcomes differed significantly between patients treated with and without postoperative radiotherapy, with worse survival for patients not treated with radiotherapy. Therefore, SND appears appropriate for cN1 OSCC patients, and postoperative radiotherapy is recommended for those with histological grade II or III tumours.

Impact of surgical management of upper tract urothelial cancer in octogenarians: A population-based study.

Upper tract urothelial carcinoma (UTUC) is an aggressive disease with a high progression rate. The standardmanagement for this disease is nephroureterectomy. Nephron sparing nonradical surgery is an alternative therapeutic approach. In men with limited life expectancy, the potential harm of UTUC progression must be weighed against surgical morbidity and mortality, and thus, more conservative approaches may be selected. This study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized UTUC. A search was conducted in the Surveillance, Epidemiology, and End Results database for patients older than 80 years who were diagnosed with localized (T1-2N0M0) cancer in the renal pelvis or ureter as the only malignancy from 2004 to 2015. Patients were divided into 3 therapeutic groups: no surgery, local intervention (ie, local tumor excision or segmented ureterectomy), and radical surgery (nephroureterectomy). Demographic and cancer-related parameter data were collected. Logistic regression analysis was conducted to investigate predictors for surgical treatment. Kaplan-Meier curves and Cox regression were used to analyze survival outcomes. Data from 774 patients were analyzed, including 205 in the no-surgery group, 181 in the local intervention group, and 388 in the radical surgery group. Older, African American patients with T1 stage disease were less likely to receive surgical treatment. Among surgically treated patients, renal pelvic tumors, and high-grade and T2 stage disease were associated with radical resection. Surgically treated patients had a longer median overall survival (OS) than in those treated nonsurgically (13, 35, and 47 months in no-surgery, local intervention, and radical surgery groups, respectively; p < 0.001). Although surgically treated patients demonstrated higher 5-year OS (8.8% [no surgery], 23.2% [local intervention], and 23.5% [radical surgery], p < 0.001) and 5-year disease-specific survival (DSS) (41.0%[no surgery], 69.1%[local intervention], and 72.9%[radical surgery]; p < 0.001) than in those treated nonsurgically, no significant differences were found between the local intervention and radical surgery groups (p > 0.05). Based on multivariate Cox regression analysis, surgical treatments, including both nonradical and radical resection, were independently associated with improved OS and DSS after controlling for age, marital status, tumor grade, and radiation status. Patients older than 80 years with localized UTUC who undergo surgery demonstrate longer survival. Radical and nonradical resections seemto have similar OS and DSS outcomes. Thus, when clinically indicated in this population, a more conservative surgical approach may be reasonable.

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.

Extensive resection improves overall and disease-specific survival in localized anorectal melanoma: A SEER-based study.

BackgroundAnorectal melanoma is a rare tumor with a dismal prognosis. The only promising treatment for anorectal melanoma is surgery, either extensive resection (ER) or local excision (LE). However, the optimal extent of resection is still controversial. The purpose of this study was to investigate whether the survival outcomes of anorectal melanoma at different stages are influenced by the surgical approaches (LE or ER) using the National Institute of Health's Surveillance, Epidemiology, and End Results Program (SEER) database.MethodsThe Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients treated for anorectal melanoma (2000–2018). Overall survival (OS) and disease-specific survival (DSS) outcomes were compared for the two surgical approaches (ER or LE) stratified by stage (localized, regional and distant).ResultsA total of 736 patients were included in the study. Details of previous surgical procedures were available for 548 of the study patients: 360 (65.7%) underwent LE, and 188 (34.3%) underwent ER. In localized cases, 199 underwent LE, and 48 underwent ER. The OS (median 45 vs. 29 months, 5-year rate 41.7% vs. 23.4%) and DSS (median 66 vs. 34 months, 5-year rate 51% vs. 30.7%) of patients undergoing ER were significantly better (p = 0.009 and 0.041, respectively) than those who received LE. Multivariate analysis showed that the type of surgery was an independent prognostic factor for both OS and DSS. Among the regional cases, 89 cases had LE, and 96 cases had ER. Patients with regional disease who underwent ER had no significant differences in OS (23 vs. 21 months; p = 0.866) or DSS (24 vs. 24 months; p = 0. 907) compared to patients who underwent LE. In distant cases, 72 cases had LE, and 44 cases had ER. Patients with metastatic disease who had ER also had similar OS (median 11 vs. 8 months; p = 0.36) and DSS (median 11 vs. 8 months; p = 0.593) to those who underwent LE.ConclusionExtensive resection can improve the long-term prognosis of localized anorectal melanoma compared to local excision, but the prognosis of the two surgical techniques is comparable in both regional patients and distant patients.

Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer

BackgroundIn the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC).AimTo validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina.MethodsRetrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems.ResultsReclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%).ConclusionIn this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.

A Novel Combined Tumor Budding-Poorly Differentiated Clusters Grading System Predicts Recurrence and Survival in Stage I-III Colorectal Cancer.

Tumor budding (TB) and poorly differentiated clusters (PDCs) are powerful prognostic factors in colorectal cancer (CRC). Despite their morphologic and biological overlap, TB and PDC are assessed separately and are distinguished by an arbitrary cutoff for cell cluster size. This cutoff can be challenging to apply in practice and its biological significance remains unclear. We developed a novel scoring system that incorporates TB and PDC into a single parameter ("Combined Score"; CS), eliminating the need for such cutoffs and allowing the prognostic value of PDC to be captured alongside TB. In a cohort of 481 stage I-III CRC resections, CS was significantly associated with American Joint Committee on Cancer (AJCC) stage, T-stage, N-stage, histologic grade, tumor deposits, lymphovascular invasion, and perineural invasion ( P &lt;0.0001). In addition, CS was significantly associated with decreased 5-year recurrence-free survival, overall survival, and disease-specific survival ( P &lt;0.0001). TB and PDC showed similar associations with oncologic outcomes, with hazard ratios consistently lower than for CS. The association between CS and oncologic outcomes remained significant in subgroup analyses stratified by AJCC stage, anatomic location (rectum/colon) and neoadjuvant therapy status. On multivariable analysis, CS retained its significant association with oncologic outcomes ( P =0.0002, 0.005, and 0.009) for recurrence-free survival, disease-specific survival, and overall survival, respectively. In conclusion, CS provides powerful risk stratification in CRC which is at least equivalent to that of TB and PDC assessed individually. If validated elsewhere, CS has practical advantages and a biological rationale that may make it an attractive alternative to assessing these features separately.

Health Insurance Coverage and Survival Outcomes among Nasopharyngeal Carcinoma Patients: A SEER Retrospective Analysis.

Objectives Insurance coverage plays a critical role in head and neck cancer care. This retrospective study examines how insurance coverage affects nasopharyngeal carcinoma (NPC) survival in the United States using the Surveillance, Epidemiology, and End Results (SEER) program database. Design, Setting, and Participants A total of 2,278 patients aged 20 to 64 years according to the International Classification of Diseases for Oncology (ICD-O) codes C11.0-C11.9 and ICD-O histology codes 8070-8078 and 8080-8083 between 2007 and 2016 were included and grouped into privately insured, Medicaid, and uninsured groups. Log-rank test and multivariable Cox's proportional hazard model were performed. Main Outcome Measures Tumor stage, age, sex, race, marital status, disease stage, year of diagnosis, median household county income, and disease-specific survival outcomes including cause of death were analyzed. Results Across all tumor stages, privately insured patients had a 59.0% lower mortality risk than uninsured patients (hazard ratio [HR]: 0.410, 95% confidence interval [CI]: [0.320, 0.526], p < 0.01). Medicaid patients were also estimated to have 19.0% lower mortality than uninsured patients (HR: 0.810, 95% CI: [0.626, 1.048], p = 0.108). Privately insured patients with regional and distant NPC had significantly better survival outcomes compared with uninsured individuals. Localized tumors did not show any association between survival and type of insurance coverage. Conclusion Privately insured individuals had significantly better survival outcomes than uninsured or Medicaid patients, a trend that was preserved after accounting for tumor grade, demographic and clinicopathologic factors. These results underscore the difference in survival outcomes when comparing privately insured to Medicaid/uninsured populations and warrant further investigation in efforts for health care reform.

Optimal Threshold of Neutrophil-Lymphocyte Ratio and its Association with Survival Outcome Among Patients with Head and Neck Cancer in the United States

<h3>Purpose/Objective(s)</h3> Given the role of inflammation in cancer progression, neutrophil-lymphocyte ratio (NLR) from peripheral blood has been suggested as a read-out of systemic inflammation and a prognostic marker in several solid malignancies. However, optimal threshold for NLR in North American head and neck cancer patients remains unclear. We performed an observational cohort study to determine the optimal NLR threshold as a prognostic biomarker for survival outcomes. <h3>Materials/Methods</h3> A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent radiation therapy from January 2005 to April 2021. A threshold for NLR was determined by Cox proportional hazard model for OS using restricted cubic splines (RCS), and patients were then stratified into two cohorts by above versus below the model-derived threshold for their NLR. Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze overall survival (OS) and disease-specific survival (DSS) outcomes. Logistic MVA was performed to identify variables associated with elevated NLR. To reduce selection bias, propensity score matching was used based on nearest neighbor method in a 1:1 ratio without replacements. <h3>Results</h3> A total of 753 patients were included for analysis. Median follow up was 29.7 months (interquartile range 17.8-57.8). Cox MVA using RCS showed a threshold of NLR at 4.82, with worsening OS in a continuous fashion without plateau as NLR increases. High NLR above 4.82 was associated with worse OS (adjusted hazards ratio [aHR] 1.73, 95% confidence interval [CI] 1.26-2.37, p<0.001) and DSS (aHR 1.77, 95% CI 1.22-2.56, p=0.003). Similar findings were noted in 103 matched pairs (OS: aHR 1.85, 95% CI 1.19-2.90, p=0.007; DSS: aHR 1.91, 95% CI 1.11-3.28, p=0.02). On logistic MVA, patients were more likely to have high NLR if they had a higher T staging (adjusted odds ratio [aOR] 1.75, 95% CI 1.14-2.73, p=0.01), but less likely if they had a good performance status (aOR 0.45, 95% CI 0.29-0.69, p<0.001). Among 466 patients with available HPV data, high NLR was not associated with OS (aHR 1.38, 0.89-2.15, p=0.15) and DSS (aHR 1.15, 95% CI 0.67-1.97, p=0.62). <h3>Conclusion</h3> High NLR based on a model-derived threshold was associated with worse survival. Patients with significant primary disease burden and poor performance status were more likely to have high NLR. Further studies would be warranted to investigate the role of such prognostic marker to identify patients at risk to tailor interventions.

LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma

ObjectivesTo investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC). MethodsThe Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R “clusterProfiler” package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins. ResultsLHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins. ConclusionLHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction.