Disease-specific Survival In Patients Research Articles

Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy

PurposeFNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients.MethodsWe determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III–IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis.ResultsThere were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5–49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2–100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71–22.06).ConclusionFNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12094-022-02870-3.

Tropomyosin Is Potential Markers for the Diagnosis and Prognosis of Bladder Cancer.

Objective To investigate the correlation between tropomyosin (TM) and clinical characteristics of bladder cancer. In addition, the relationship between TM and immune cell infiltration in bladder cancer was further analyzed. Methods Based on The Cancer Genome Atlas (TCGA) database, the relationship between TM expression and clinicopathological features in bladder cancer was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the value of TM as a diagnostic marker for bladder cancer. Univariate and multivariate Cox regression was used to analyze the independent factors affecting the prognosis of patients with bladder cancer. The relationship between TM and immune cell infiltration was analyzed. Results ROC curve showed that TPM1, TPM2, and TPM3 had significant diagnostic ability (AUC was 0.845, 0.848, and 0.873, respectively). The high expression of TPM1 and TPM2 is associated with poor overall and disease-specific survival in patients with bladder cancer (P < 0.05). Multivariate Cox analysis showed that age and TPM1 were independent prognostic factors. The expression levels of TPM1, TPM2, TPM3, and TPM4 in low grade bladder cancer were lower than those in high grade bladder cancer (P < 0.05). TPM1 and TPM2 are positively correlated with the infiltration of macrophages and NK cells in bladder cancer. TPM3 is positively associated with Th2. TPM4 is positively correlated with Th1 cells, macrophages, and neutrophils (P < 0.05). Conclusions TPM1 and TPM2 are effective markers for the diagnosis of bladder cancer. TPM1 is an independent prognostic factor for bladder cancer. TM is also associated with the infiltration of various immune cells in bladder cancer. TM may have influenced the development of bladder cancer through immune inhibition.

The GPR35 expression pattern is associated with overall survival in male patients with colorectal cancer.

G protein-coupled receptor 35 (GPR35) is involved in the carcinogenesis; however, limited data exist on its relevance for overall survival (OS) and disease-specific survival (DSS) in patients with cancer. We have examined The Cancer Genome Atlas dataset to check the relations between GPR35 expression pattern and OS or DSS of patients with colorectal cancer (CRC). The performed analysis showed a negative association between positive GPR35 expression Z score and OS in males, which remains statistically significant in advanced stages of colon (COAD) and rectal (READ) adenocarcinoma combined. These findings suggest the prognostic value of early testing of GPR35 in male patients with an increased risk of CRC development and warrant further clinical confirmation.

Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases

Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p < 0.001 for G2 vs G1), as well as patient age at diagnosis > 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.

High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer.

BACKGROUNDColorectal cancer (CRC) is often associated with elevated platelet count (> 400 × 109/L), known as thrombocytosis. The role of CD40 ligand (CD40L), a member of the tumor necrosis factor family, is controversial in CRC. Circulating CD40L is higher in CRC, but its relationship with disease staging and local and distant metastasis is not clear. Although most of the circulating CD40L is produced by platelets, no previous study investigated its relationship with CRC-related thrombocytosis.AIMTo investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.METHODSA total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study. Anamnestic data including comorbidities and histopathological data were collected. Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor. Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay, while plasma interleukin-6 was measured via electrochemiluminescence immunoassay. Patient follow-ups were terminated on January 31, 2021.RESULTSPlasma CD40L of CRC patients was tendentiously higher, while platelet count (P = 0.0479), interleukin-6 (P = 0.0002), and thrombopoietin (P = 0.0024) levels were significantly higher as opposed to the control subjects. Twelve of the 106 CRC patients (11.3%) had thrombocytosis. Significantly higher CD40L was found in the presence of distant metastases (P = 0.0055) and/or thrombocytosis (P = 0.0294). A connection was found between CD40L and platelet count (P = 0.0045), interleukin-6 (P = 0.0130), and thrombocytosis (P = 0.0155). CD40L was constant with the course of CRC, and all baseline differences persisted throughout the whole study. Both pre- and postoperative elevated platelet count, CD40L, and interleukin-6 level were associated with poor overall and disease-specific survival of patients. The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.CONCLUSIONCD40L levels of CRC patients do not change with the course of the disease. The CD40L level is strongly correlated with platelet count, interleukin-6, thrombocytosis, and the presence of distant metastases.

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

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

Nicotinamide N-methyltransferase expression in squamous cell carcinoma of the vulva

The molecular pathways involved in the development of vulvar squamous cell carcinoma (SCC) cancer are not completely known. Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme associated with tumorigenesis and metastasis in a variety of cancers. Its role in vulvar cancer has not been studied, previously. Vulvar SCC, high and low grade squamous intraepithelial lesions (SILs) and benign squamous hyperplasia were analysed immunohistochemically. The mean staining score for vulvar SCC was significantly higher than the score for vulvar squamous hyperplasia (p<.001). The mean relapse-free survival for patients with low and high NNMT expression was 41.4 months (95% CI: 25.6–57.2) and 19.8 months (95% CI: 3.0–36.6), respectively (p=.035). The mean disease-specific survival for patients with low and high NNMT expression was 75.8 months (95% CI: 57.5–94.2) and 27.8 months (95% CI 12.2–43.4), respectively (p=.015). Although quite preliminary, this study showed that NNMT expression was elevated in vulvar SCC compared to benign and premalignant lesions. Additionally, elevated NNMT expression was associated with poor survival. Impact Statement What is already known on this subject? Nicotinamide N-methyltransferase (NNMT) is a methyltransferase, associated with tumour progression, spread and poor prognosis in a variety of cancers. Its upregulation can lead to DNA hypomethylation, which can in turn result in the activation of proto-oncogenes and deactivation of tumour suppressor genes. What do the results of this study add? Although quite preliminary, this study showed that NNMT expression was elevated in vulvar SCC compared to benign and premalignant lesions. Additionally, elevated NNMT expression was associated with poor survival. What are the implications of these findings for clinical practice and/or further research? NNMT has been regarded as a potential target of cancer therapy and its role in vulvar cancer has not been studied, previously. This is the first study to investigate the expression of NNMT in vulvar cancer and associate NNMT elevation with poor survival. NNMT can further be investigated as a possible target of vulvar cancer therapy.

Validation of the Memorial Sloan Kettering Gastric Cancer Post-Resection Survival Nomogram: Does It Stand the Test of Time?

The Memorial Sloan Kettering Cancer Center (MSK) nomogram combined both gastroesophageal junction (GEJ) and gastric cancer patients and was created in an era from patients who generally did not receive neoadjuvant chemotherapy. We sought to reevaluate the MSK nomogram in the era of multidisciplinary treatment for GEJ and gastric cancer. Using data on patients who underwent R0 resection for GEJ or gastric cancer between 2002 and 2016, the C-index of prediction for disease-specific survival (DSS) was compared between the MSK nomogram and the American Joint Committee on Cancer (AJCC) 8th edition staging system after segregating patients by tumor location (GEJ or gastric cancer) and neoadjuvant treatment. A new nomogram was created for the group for which both systems poorly predicted prognosis. During the study period, 886 patients (645 gastric and 241 GEJ cancer) underwent up-front surgery, and 999 patients (323 gastric and 676 GEJ) received neoadjuvant treatment. Compared with the AJCC staging system, the MSK nomogram demonstrated a comparable C-index in gastric cancer patients undergoing up-front surgery (0.786 vs 0.753) and a better C-index in gastric cancer patients receiving neoadjuvant treatment (0.796 vs 0.698). In GEJ cancer patients receiving neoadjuvant chemotherapy, neither the MSK nomogram nor the AJCC staging system performed well (C-indices 0.647 and 0.646). A new GEJ nomogram was created based on multivariable Cox regression analysis and was validated with a C-index of 0.718. The MSK gastric cancer nomogram's predictive accuracy remains high. We developed a new GEJ nomogram that can effectively predict DSS in patients receiving neoadjuvant treatment.

Predicting Disease-Specific Survival for Patients With Primary Cholangiocarcinoma Undergoing Curative Resection by Using a Decision Tree Model.

BackgroundThe 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).MethodTwenty-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.ResultsAccording 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.ConclusionWe 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.

Temporal Bone Squamous Cell Carcinoma: Molecular Markers Involved in Carcinogenesis, Behavior, and Prognosis: A Systematic Review

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a poor prognosis in advanced cases. The dismal outcome of advanced TBSSC cases is largely due to the cancer’s local aggressiveness and the complex anatomy of this region, as well as to persistent pitfalls in diagnosis and treatment. Molecular changes occur in malignancies before any morphological changes become visible, and are responsible for the disease’s clinical behavior. The main purpose of this critical systematic review is to assess the level of knowledge on the molecular markers involved in the biology, behavior, and prognosis of TBSCC. A search (updated to March 2022) was run in PubMed, Scopus, and Web of Science electronic databases without publication date limits for studies investigating molecular markers in cohorts of patients with primary TBSCC. The search terms used were: “temporal bone” OR “external auditory canal” OR “ear”, AND “cancer” OR “carcinoma” OR “malignancy”. We preliminarily decided not to consider series with less than five cases. Twenty-four case series of TBSCC were found in which different analytical techniques had been used to study the role of several biomarkers. In conclusion, only very limited information on the prognostic role of molecular markers in TBSCC are currently available; prospective, multi-institutional, international prognostic studies should be planned to identify the molecular markers involved in the clinical behavior and prognosis of TBSCC. A further, more ambitious goal would be to find targets for therapeutic agents able to improve disease-specific survival in patients with advanced TBSCC.

Incidence and survival trends in patients with primary tonsillar lymphoma: a large population-based study.

This study aims to reveal changes in the incidence and prognosis of patients with tonsillar lymphoma on a population level. The incidence, clinicopathological, and prognostic data of tonsillar lymphoma patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The Join-point software and R packages were utilized to analyze the annual percentage changes (APCs) and survival outcomes. The incidence of primary tonsillar lymphoma increased from 0.1204 per 100,000 person-years (95% CI, 0.0680-0.1962) in 1983 to 0.2158 (95% CI, 0.1675-0.2740) in 2015 with an APC of 1.20. When classified by decades, both cancer-specific survival (CSS) and overall survival (OS) improved with time. The 2006-2015 decade showed the highest rate of CSS and OS. Nevertheless, for disease-specific survival (DSS), the difference was not significant between 1996-2005 and 2006-2015 decades. The main cause of mortality among this cohort was heart diseases. Three nomograms were constructed to predict OS, CSS, and DSS for patients with primary tonsillar lymphoma, respectively. Histological subtype made the most contribution to poor prognosis in OS-predicting and CSS-predicting nomograms. While, for DSS, age at diagnosis made the most contribution to poor outcomes. The incidence of primary tonsillar lymphoma has increased in the past decades. The OS and CSS rates of tonsillar lymphoma improved continuously, while there was no significant improvement in DSS in the past decades. These changes indicated an improved management of tonsillar lymphoma with newer therapeutic agents and the need of multi-disciplinary treatments to offset the future burden of noncancer diseases.

Prognostic Value of a Modified Albumin-Bilirubin Score Designed for Patients with Esophageal Squamous Cell Carcinoma After Radical Resection.

The albumin-bilirubin (ALBI) score was originally developed to assess the severity of liver dysfunction in patients with hepatocellular carcinoma and has subsequently been used as a prognostic marker for that disease. Here, we examined the value of the preoperative ALBI score as a prognostic marker for patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. We retrospectively analyzed data from 449 patients who underwent curative resection for ESCC. The ALBI score was calculated as (log10 serum bilirubin [μmol/l] × 0.66) + (serum albumin [g/l] × - 0.0852). Receiver operating characteristic curve analysis was used to define a preoperative modified ALBI (mALBI) score for patient stratification. Of the 449 ESCC patients, 232 and 217 were assigned to mALBI Grade 1 or Grade 2 groups based on preoperative ALBI scores of ≤ - 3.33 or > - 3.33, respectively. Preoperative mALBI grade was significantly associated with age, excessive alcohol consumption, squamous cell carcinoma antigen level, and clinical disease stage. The mALBI Grade 2 group had significantly shorter disease-specific and recurrence-free survival than the mALBI Grade 1 group. Multivariate analysis demonstrated that mALBI Grade 2 was an independent prognostic factor for disease-specific survival (hazard ratio 1.86, 95% confidence interval 1.18-2.93, P = 0.0074). In most subgroup analyses, mALBI Grade 2 was associated with a greater risk of disease-specific death. mALBI grade serves as a simple and useful prognostic marker for disease-specific survival in patients with ESCC after radical esophagectomy.

Do older patients with stage IB non-small-cell lung cancer obtain survival benefits from surgery? A propensity score matching study using SEER data

BackgroundSurgical resection is the preferred treatment for Stage IB non-small cell lung cancer (NSCLC), but one-third of patients still do not receive surgery, which might be due to the lack of robust and dedicated studies on the outcomes of surgical treatment in older patients with stage IB NSCLC. This study aims to investigate whether older patients with stage IB NSCLC benefit from surgery. MethodsData of patients with NSCLC were downloaded from the SEER (Surveillance, Epidemiology, and End Results) database classifications were converted from the 7th edition staging system to the 8th edition staging system, and older patients (aged ≥65 years at diagnosis) with stage IB NSCLC were included. The propensity score matching (PSM) method was used to balance the distribution proportions of clinical characteristics between the surgery and no surgery groups. ResultsAfter 1:1 propensity score matching, the distribution proportions of clinical characteristics were balanced between the surgery and no surgery groups (all P > 0.05). The overall and disease-specific survival rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (both P < 0.001). Furthermore, subgroup analysis showed that receiving surgery was a protective factor for overall survival and disease-specific survival of patients in all clinical character-related subgroups. Ultimately, univariate and multivariate Cox regression analyses showed that sex, tumor size, tumor grade, and tumor classification were independent prognostic factors for overall and disease-specific survival in patients undergoing surgery. ConclusionsOlder patients with Stage IB NSCLC can benefit significantly from surgical treatment after eliminating confounding factors, which is expected to provide strong medical evidence for surgical treatment.

Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma.

Simple SummaryHead and neck cancer (HNC) is the sixth most common cancer worldwide, with a general prognosis of 50% disease-specific survival (DSS). The subgroup of oropharyngeal (OP) cancers are of interest because HPV infection is one of several causative agents and carries favorable prognosis. Influxes of inflammatory cells into tumors may vary with prognosis. T lymphocytes are important regarding specific immune defense. Within the immune system T regulatory cells (Foxp3 positive) co-governs this process. We have therefore primarily studied levels of Foxp3 (+) cells in malignant tumors from 170 patients related to prognosis of the patients. Higher levels of T lymphocyte Foxp3 (+) cells predicted better 5-year DSS. This case was unique relative to age, gender, TNM stage, and HPV infection; but more so among tumor HPV (+) than HPV (−) patients. The results encourage further study into the use of immune-based therapy in HNC patients.Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (−) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (−) patients.

Systematic review and validation of clinical models predicting survival after oesophagectomy for adenocarcinoma.

Oesophageal adenocarcinoma poses a significant global health burden, yet the staging used to predict survival has limited ability to stratify patients by outcome. This study aimed to identify published clinical models that predict survival in oesophageal adenocarcinoma and to evaluate them using an independent international multicentre dataset. A systematic literature search (title and abstract) using the Ovid Embase and MEDLINE databases (from 1947 to 11 July 2020) was performed. Inclusion criteria were studies that developed or validated a clinical prognostication model to predict either overall or disease-specific survival in patients with oesophageal adenocarcinoma undergoing surgical treatment with curative intent. Published models were validated using an independent dataset of 2450 patients who underwent oesophagectomy for oesophageal adenocarcinoma with curative intent. Seventeen articles were eligible for inclusion in the study. Eleven models were suitable for testing in the independent validation dataset and nine of these were able to stratify patients successfully into groups with significantly different survival outcomes. Area under the receiver operating characteristic curves for individual survival prediction models ranged from 0.658 to 0.705, suggesting poor-to-fair accuracy. This study highlights the need to concentrate on robust methodologies and improved, independent, validation, to increase the likelihood of clinical adoption of survival predictions models.

Cost-Effectiveness of Follow-Up Ultrasound for Incidental Thyroid Nodules on CT.

BACKGROUND. Thyroid nodules are common incidental findings on CT. Existing professional society recommendations, based primarily on expert opinion, advise follow-up ultrasound for nodules above size cutoffs in patients of all ages. OBJECTIVE. The purpose of this study was to use a simulation model to evaluate the cost-effectiveness of current recommendations and of other age- and size-based follow-up strategies for thyroid nodules incidentally detected on CT. METHODS. By using a simulation model with 1,000,000 adults with nodules measuring 40 mm or less that have no suspicious features, we evaluated size cutoffs from 5 to 25 mm in patients younger than an age maximum from 25 to 65 years, as well as follow-up versus no follow-up for patients above the age maximum. For each strategy, patient survival was determined by disease-specific and baseline mortality rates and surgical mortality. Costs and quality-adjusted life years (QALYs) were tabulated. A probabilistic sensitivity analysis was performed with varying model parameters. RESULTS. All cost-effective strategies recommended no follow-up for patients above the age cutoffs (which varied from 25 to 65 years). In the base-case simulation, 10 strategies were cost-effective at a willingness-to-pay threshold of $100,000/QALY. Of these, the strategy yielding the highest QALYs was follow-up for patients under 60 years old with nodules 10 mm or larger and no follow-up for patients 60 years old or older, with an incremental cost-effectiveness ratio of $50,196/QALY (95% CI, $39,233-67,479). In the probabilistic sensitivity analysis, if the 10-year disease-specific survival of patients with untreated cancer was more than 94% of patients with treated cancer, then no follow-up for any nodules was optimal. CONCLUSION. Follow-up ultrasound for thyroid nodules incidentally detected on CT is likely not cost-effective in older patients. Follow-up for most thyroid nodules in younger patients may be cost-effective. CLINICAL IMPACT. Future societal recommendations may account for the limited benefit of obtaining follow-up for incidental thyroid nodules on CT in older patients.

Implications of Satellitosis or In-transit Metastasis in Cutaneous Squamous Cell Carcinoma

Unlike Merkel cell carcinoma and melanoma, satellitosis or in-transit metastasis (S-ITM) is not incorporated into the current cutaneous squamous cell carcinoma (CSCC) staging systems. It is important to determine if the clinical outcomes of S-ITM are relevant to prognosis for patients with CSCC. To evaluate the association of S-ITM with clinical outcomes in patients with CSCC and to determine its prognostic implications. A dual-institution (Cleveland Clinic and Brigham and Women's Hospital) database was queried for patients who were treated for CSCC in 2010 to 2020. Patients who were node-negative and had S-ITM-the presence of dermal lesions between the primary tumor and first-echelon lymphatic nodal basins at any point in the disease course-were identified. Subcohorts of patients with T3N0 tumors, T4N0 tumors (bone invasive), N1 to 3, and M1 disease were identified for comparison. The American Joint Committee on Cancer staging system was used to define cancer stages. Data were analyzed from January 15 to March 31, 2021. Pairwise comparison of CSCC recurrence and disease-specific survival in patients with and without S-ITM was performed using Cox proportional hazard modeling. Kaplan-Meier and Fine-Gray competing risk methods were used to estimate disease-specific survival and CSCC recurrence, respectively. In a total of 518 patients with CSCC, S-ITM was present in 72 (13.9 %) patients (median age [range], 73.9 [31.6-95.8] years; 59 [82%] men; 69 [96%] White non-Hispanic individuals; 25 [35%] patients with immunosuppression) who were node-negative. The subcohorts were composed of 341 patients with T3N0 cancer, 36 with T4N0, 70 with N1 to 3, and 19 with M1 disease. Pairwise comparisons between disease levels using Cox proportional hazard model demonstrated lower cumulative incidence of CSCC recurrence rates in the T3N0 (HR, 0.21; 95% CI, 0.14-0.30; P < .001) and T4N0 (HR, 0.36; 95% CI, 0.19-0.68; P = .001) cohorts compared with the S-ITM cohort. No significant difference was observed between patients who were node-positive and those with S-ITM (HR, 0.74; 95% CI, 0.48-1.14; P = .16). The 5-year disease-specific survival rates were 76% for T3N0, 64% for T4N0, 41% for S-ITM, and 39% for N1 to 3. Compared with the S-ITM cohort, DSS was significantly higher in the T3N0 (HR, 0.23; 95% CI, 0.15-0.35; P < .0001) and T4N0 (HR, 0.37; 95% CI, 0.19-0.76; P = .01) cohorts, and not significantly different in the node-positive (HR, 0.77; 95% CI, 0.84-3.93; P = .30) and metastatic cohorts (HR, 1.81; 95% CI, 0.84-3.93; P = .13). This multi-institutional cohort study found that patients with CSCC and S-ITM appear to have clinical outcomes comparable to those of patients who are node-positive, and an increased risk of recurrence and worse survival compared with patients who have T3 and T4 disease. These outcomes are similar to those observed for Merkel cell carcinoma and melanoma. Given that S-ITM may be a powerful prognostic factor, it should be incorporated into clinical staging systems.

Clinical characteristics of undifferentiated pleomorphic sarcoma of bone and the impact of adjuvant chemotherapy on the affected patients: a population-based cohort study.

Clinical characteristics of undifferentiated pleomorphic sarcoma of bone are not elucidated. Herein, we clarify its clinical features and analyze the efficacy of adjuvant chemotherapy in patients with undifferentiated pleomorphic sarcoma of bone. Prognostic factors and estimated disease-specific survival in 247 patients with primary undifferentiated pleomorphic sarcoma of bone were identified from a registry in Japan. The effect of adjuvant chemotherapy was evaluated in localized resectable cases, and the characteristics of the two groups treated with or without chemotherapy were adjusted using propensity score matching. The 5-year disease-specific survival rates were 47.4% in the entire cohort and 56.4 and 16.9% in the M0 and M1 groups, respectively. Multivariate disease-specific survival analysis revealed that metastasis on initial presentation and age≥65years were poor prognostic factors. Overall, 132 localized and resectable primary lesions were extracted. Adjuvant chemotherapy administration was a favorable prognostic factor (hazard ratio: 0.43, P=0.04), and it significantly prolonged disease-specific survival compared with no adjuvant chemotherapy (5-year disease-specific survival: 78.8% vs. 51.8%, P=0.008). Adjuvant chemotherapy prolonged disease-specific survival in patients with tumor size <8cm (5-year disease-specific survival: 100% vs. 54.6%, P=0.02); however, its efficacy decreased in those with tumor size ≥8cm (5-year disease-specific survival: 68.7% vs. 42%, P=0.09). After propensity score matching, adjuvant chemotherapy was significantly associated with good disease-specific survival (P=0.02). Metastasis in the initial presentation was the poorest prognostic factor. On evaluating localized and resectable cases only, adjuvant chemotherapy significantly improved disease-specific survival, although its effect decreased in cases with large tumors.

Is Overweight Related to the Prognosis of Octogenarians with Lung Cancer?

This study aimed to determine outcomes and prognostic factors associated with octogenarians who underwent pulmonary resection for lung cancer. From 2009 to 2018, 76 octogenarians who underwent pulmonary surgery for lung cancer were enrolled in this study. We divided them into two groups, namely overweight and non-overweight, and investigated their clinicopathological characteristics and outcomes. Disease-specific survival (DSS) rates were determined using Kaplan-Meier curves. Univariate and multivariate analyses were performed to identify prognostic factors. Although perioperative morbidity and mortality in octogenarians were not significantly different between the two groups, the long-term prognosis of the overweight group was significantly worse than that of the non-overweight group. The 3-year DSS rate was 56.5%. The median observation period after surgery was 37.5 (8.9-112.3) months for the entire cohort postoperatively. Kaplan-Meier curves showed that being overweight (body mass index ≥ 25) was associated with worse survival rates in all pathological stages (0 to III) and stage 0/I (DSS, p = 0.036 and p = 0.003, respectively). Multivariate analysis identified overweight as an unfavorable prognostic factor for DSS in patients with stage 0/I lung cancer (hazard ratio 2.240, 95% confidence intervals 1.052-4.564, p = 0.037). Overweight is an independent risk factor, especially in pathological stage 0/I lung cancer. Indications for surgery should be carefully considered in elderly patients with obesity. However, owing to the limitations of this retrospective single-center study, future studies involving multiple institutions are required to confirm our findings.

Redefining Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma.

Perineural invasion (PNI) negatively affects disease-specific survival in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC). We aim to analyze the prognostic implications of PNI-related features. Retrospective cohort study. Academic tertiary care hospital. Retrospective chart review was performed on 104 patients diagnosed with HNcSCC between January 2011 and October 2019 who underwent resection, parotidectomy, and neck dissection with more than 1 year of follow-up. PNI was classified as incidental (identified on histopathology alone) or clinical (present on radiography and/or physical exam). Primary outcome measures were overall survival and disease-free survival (DFS). Kaplan-Meier analysis, logistic regression, and Cox regression were performed. The overall 5-year DFS was 57.9%. Sixty-one patients had PNI. On histopathology, 28 lesions showed complete nerve encirclement, 10 involved >5 nerves, and 12 involved named nerves. Patients with facial weakness (P = .026) and positive margins (P = .0029) had a higher likelihood of histopathologic PNI, and positive margins retained significance on multivariable analysis (P = .0079). Worse DFS was seen in patients with PNI (P = .004), advanced tumor stage (P = .049), positive margins (P = .014), and >5 nerves involved (P = .0061). Furthermore, histopathologic PNI was a predictor of DFS (hazard ratio [HR], 3.07; 95% CI, 0.33-1.38; P = .0061) overall and in the clinical PNI cohort (HR, 3.43; 95% CI, 1.65-7.10; P = .00091). DFS was significantly worse in patients with PNI, facial nerve weakness, advanced T stage, positive margins, and multiple nerve involvement. Further characterization of PNI features may help improve prognostic predictions and identify patients who may benefit from more aggressive treatment.