Risk Factors For Metastatic Disease Research Articles

Is cribriform pattern in prostate biopsy a risk factor for metastatic disease on 68Ga-PSMA-11 PET/CT?

Cribriform growth pattern (CP) in prostate cancer (PCa) has been associated with different unfavourable oncological outcomes. This study addresses if CP in prostate biopsies is an independent risk factor for metastatic disease on PSMA PET/CT. Treatment-naive patients with ISUP GG ≥ 2 staged with 68Ga-PSMA-11 PET/CT diagnosed from 2020 to 2021 were retrospectively enrolled. To test if CP in biopsies was an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT, regression analyses were performed. Secondary analyses were performed in different subgroups. A total of 401 patients were included. CP was reported in 252 (63%) patients. CP in biopsies was not an independent risk factor for metastatic disease on the 68Ga-PSMA PET/CT (p = 0.14). ISUP grade group (GG) 4 (p = 0.006), GG 5 (p = 0.003), higher PSA level groups per 10ng/ml until > 50 (p-value between 0.02 and > 0.001) and clinical EPE (p > 0.001) were all independent risk factors. In the subgroups with GG 2 (n = 99), GG 3 (n = 110), intermediate-risk group (n = 129) or the high-risk group (n = 272), CP in biopsies was also not an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT. If the EAU guideline recommendation for performing metastatic screening was applied as threshold for PSMA PET/CT imaging, in 9(2%) patients, metastatic disease was missed, and 18% fewer PSMA PET/CT would have been performed. This retrospective study found that CP in biopsies was not an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT.

Lack of radiosensitivity predicts poor disease specific survival in myxoid liposarcoma.

Compared to other sarcomas, myxoid liposarcoma (ML) is known to be radiosensitive, with improved oncologic outcomes. Although these tumors "shrink" following radiotherapy, there is a paucity of data examining the degree of radiosensitivity and oncologic outcome. The purpose of the study was to evaluate pre- and postradiotherapy tumor volume to determine if size reduction impacts outcome. We reviewed 62 patients with ML undergoing surgical resection combined with preoperative radiotherapy, with pre- and postradiotherapy MRI. This included 34 (55%) males, with a mean age of 47 ± 14 years. All tumors were deep to the fascia, and 12 (19%) patients had tumors with a >5% round-cell component. The mean volume reduction was 54% ± 29%. Compared to patients with >25% volume reduction, patients with reduction ≤25% had worse 10-year disease specific survival (86% vs. 37%, p < 0.01), in addition to an increased risk of metastatic disease (HR 4.63, p < 0.01) and death due to disease (HR 4.52, p < 0.01). Lack of volume reduction is a risk factor for metastatic disease and subsequent death due to disease in patients with extremity ML treated with combined preoperative radiotherapy and surgery. This data could be used to stratify patients for adjuvant therapies and follow-up intervals.

P035 - Is cribriform pattern in biopsy a risk factor for metastatic disease on 68Ga-PSMA-PET/ CT?

P035 - Is cribriform pattern in biopsy a risk factor for metastatic disease on 68Ga-PSMA-PET/ CT?

1505P Risk factors for metastatic disease at presentation with synovial sarcoma

Synovial sarcoma is a rare soft tissue neoplasm that usually occurs in the arms and legs, but it can occur in all parts of the body and across all ages. There are differences in management and outcomes for patients who have localized disease compared with distant spread at the time of diagnosis. The purpose of this study was to examine potential risk factors predictive of metastatic disease at presentation.

Risk factors and outcomes for patients with pancreatic cancer undergoing surgical exploration without resection due to metastatic disease: A national cohort study

BackgroundUnresectable disease is sometimes diagnosed during surgery in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to identify preoperative risk factors for metastatic disease diagnosed at surgical exploration and to investigate and compare survival in resected and non-resected patients. MethodsPatients were identified from the Swedish National Pancreatic and Periampullary Cancer Registry 2010-2018. Predictors of metastatic disease were evaluated with a multivariable logistic regression model, and survival was evaluated with Kaplan-Meier estimates and log-rank tests. ResultsIn total, 1938 patients with PDAC were scheduled for surgery. An unresectable situation was diagnosed intraoperatively in 399 patients (20.6%), including 234 (12.1%) with metastasized disease. Independent risk factors for metastasis were involuntary weight loss (OR = 1.72; 95% CI: 1.27-2.33) and elevated carbohydrate antigen 19-9 (CA19-9) (35-599 U/mL, OR = 1.79, 95% CI: 1.11-2.89; ≥ 600 U/mL, OR = 3.24, 95% CI: 2.04-5.17). Overall survival was lower among patients with metastasized disease than that among patients with a resectable tumor (P < 0.001). ConclusionsInvoluntary weight loss and an elevation of CA19-9 are preoperative risk factors for diagnosing metastasized disease during surgical exploration.

Risk Factors and Outcomes for Metastatic Pancreatic Cancer Diagnosed during Planned Pancreaticoduodenectomy - A National Cohort Study

Introduction: Unresectable disease is unfortunately quite often diagnosed during surgery in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to identify preoperative risk factors for metastatic disease diagnosed at surgical exploration and to investigate and compare survival in resected and nonresected patients. Methods: Patients were identified from the Swedish National Pancreatic and Periampullary Cancer Registry 2010-2018. Predictors of metastatic disease were evaluated with a multivariable logistic regression model, and survival was evaluated with Kaplan-Meier estimates and log-rank tests. Results: In total, 1938 patients with PDAC were scheduled for surgery. An unresectable situation was diagnosed intraoperatively in 399 patients (20.6%), including 234 (12.1%) with metastasized disease. Independent risk factors for metastasis were involuntary weight loss (OR 1.95, 95% CI 1.44-2.63) and elevated CA 19-9 (CA 19-9 35-599 kE/L: OR 2.49, 95% CI 1.49-4.13 and CA 19-9 ≥ 600 kE/L: OR 5.26 95% CI 3.13-8.83). Overall survival was lower among patients with metastasized disease than among patients with a resectable tumor (p<0.001). Conclusion: Involuntary weight loss and an elevation of CA 19-9 are preoperative risk factors for diagnosing metastasized disease during surgical exploration. As expected survival is severely impaired.

Pathological predictors of metastatic disease in testicular non-seminomatous germ cell tumors: which tumor-node-metastasis staging system?

Pathological risk factors for metastatic disease in patients with testicular non-seminomatous germ cell tumors are debated. The tumor-node-metastasis (TNM) classification eighth edition for testicular cancers includes divergent versions, by the International Union Against Cancer (UICC) and by the American Joint Committee for cancer (AJCC). We investigated pathological predictors of metastatic disease at presentation in 219 non-seminomatous germ cell tumors with reference to both classifications. Age, tumor size, percentage of embryonal carcinoma, lymphovascular invasion, invasion of stromal rete testis, hilar soft tissue, epididymis, spermatic cord, and tunica vaginalis, as well as tumor at spermatic cord margin, were assessed and correlated with clinical stage at presentation. Of the 219 NSGCT cases, 151 (69%) were clinical stage I, 68 (31%) were clinical stage II/III. On univariate analysis, tumor size (P = 0.028), percentage of embryonal carcinoma (P = 0.004), lymphovascular invasion (P = 0.001), stromal rete testis invasion (P = 0.001), hilar soft tissue invasion (P = 0.010), epididymis invasion (P = 0.010), direct spermatic cord invasion (P = 0.001), and tumor at spermatic cord margin ((P = 0.009) were associated with higher clinical stage. On multivariate analysis, lymphovascular invasion (P = 0.003), tumor size (P = 0.005), percentage of embryonal carcinoma (P = 0.005), stromal rete testis invasion (P = 0.008) remained significant. A tumor size of 6 cm and an embryonal carcinoma percentage of 70% were the significant cut-off values. We conclude that in addition to lymphovascular invasion, stromal rete testis invasion, tumor size, and embryonal carcinoma percentage are strong predictors of metastatic disease at presentation and their inclusion should be considered in any future TNM revision. Further, our results support the changes in the AJCC TNM eighth edition as invasion of the epididymis and hilar soft tissue were both univariately significant.

Risk factors and treatment outcomes of 239 patients with testicular granulosa cell tumors: a systematic review of published case series data

PurposeTesticular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes.MethodsWe conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level.ResultsFrom 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission.ConclusionJuvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.

Management of Appendiceal Neuroendocrine Tumors: Metastatic Potential of Small Tumors.

Appendiceal neuroendocrine tumors (ANETs) are rare neoplasms usually discovered incidentally during appendectomy. ANETs < 2cm were thought to have no metastatic potential, and this dogma has driven management. Our aim is to evaluate the metastatic potential of ANETs < 2cm. A retrospective review was performed in a series of patients with ANETs who presented to our tertiary referral center from 1998 to 2019. Demographics, tumor characteristics, treatment, and clinical outcomes were evaluated. In total, 114 patients were included. Median follow-up was 3.3years (range, 21days-15years). At last follow-up, 34 (30%) patients had positive regional lymph nodes and 20 (18%) patients had metastatic disease. Of the 20 patients with metastatic disease, 11 (55%) had primary ANETs < 2cm. Patient age > 40years at diagnosis and ANETs with serosal invasion, lymphovascular invasion, intermediate tumor grade, or positive lymph nodes were features significantly more likely to present with metastatic disease. We found no difference in the rate of lymph node positivity, metastatic disease, or overall survival when patients were stratified by tumor size or type of resection (appendectomy vs. right hemicolectomy). On multivariate analysis, patients with metastatic disease at diagnosis had worse overall survival (HR = 24.4, p = 0.008). In our cohort, tumor size was not a significant risk factor for metastatic disease or worse outcome as many patients with ANETs < 2cm developed metastatic disease. Appendectomy alone was sufficient surgical management for most ANETs. Patients with risk factors for metastatic disease, regardless of primary ANET size, should be evaluated thoroughly and counseled for further management and surveillance.

Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas.

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours with a hereditary background in over one-third of patients. Mutations in succinate dehydrogenase (SDH) genes increase the risk for PPGLs and several other tumours. Mutations in subunit B (SDHB) in particular are a risk factor for metastatic disease, further highlighting the importance of identifying SDHx mutations for patient management. Genetic variants of unknown significance, where implications for the patient and family members are unclear, are a problem for interpretation. For such cases, reliable methods for evaluating protein functionality are required. Immunohistochemistry for SDHB (SDHB-IHC) is the method of choice but does not assess functionality at the enzymatic level. Liquid chromatography-mass spectrometry-based measurements of metabolite precursors and products of enzymatic reactions provide an alternative method. Here, we compare SDHB-IHC with metabolite profiling in 189 tumours from 187 PPGL patients. Besides evaluating succinate:fumarate ratios (SFRs), machine learning algorithms were developed to establish predictive models for interpreting metabolite data. Metabolite profiling showed higher diagnostic specificity compared to SDHB-IHC (99.2% versus 92.5%, p = 0.021), whereas sensitivity was comparable. Application of machine learning algorithms to metabolite profiles improved predictive ability over that of the SFR, in particular for hard-to-interpret cases of head and neck paragangliomas (AUC 0.9821 versus 0.9613, p = 0.044). Importantly, the combination of metabolite profiling with SDHB-IHC has complementary utility, as SDHB-IHC correctly classified all but one of the false negatives from metabolite profiling strategies, while metabolite profiling correctly classified all but one of the false negatives/positives from SDHB-IHC. From 186 tumours with confirmed status of SDHx variant pathogenicity, the combination of the two methods resulted in 185 correct predictions, highlighting the benefits of both strategies for patient management. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Sertoli Cell Tumors of the Testes: Systematic Literature Review and Meta-Analysis of Outcomes in 435 Patients.

Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs' clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes. Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected. Of the 435 patients included, only one (<1%) showed local recurrence after testis-sparing surgery (TSS). Three patients underwent adjuvant retroperitoneal lymphadenectomy. Fifty patients presented with metastases, located in the retroperitoneal lymph nodes (76%), lungs (36%), and bones (16%); median time to recurrence was 12 months. Risk factors for metastatic disease included age, tumor size, necrosis, tumor extension to the spermatic cord, angiolymphatic invasion, and mitotic index. Patients with metastases had a median life expectancy of 20 months. In six patients, metastasectomy resulted in complete remission. Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission. Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.

Surgical resection for duodenal neuroendocrine neoplasia: Outcome, prognostic factors and risk of metastases

BackgroundClinical management of duodenal neuroendocrine neoplasms (dNEN) is controversial. The aim of this study was to assess the outcome of surgical management and to identify risk factors for metastatic disease. MethodsPatients undergoing surgery for dNEN were retrospectively analysed. Clinicopathologic features, perioperative outcome and survival were assessed. A literature review with focus on risk factors for metastatic disease was additionally performed. Results24 patients were identified. Out of 22 patients presenting with their primary tumour, 20 patients underwent curative resection and 18 patients received curative resection with systematic lymphadenectomy. 17 patients underwent formal oncological resection. Surgical mortality was 1 out of 24 patients. The 5-year overall survival rate was 67% in the entire cohort, 71% in patients undergoing resection for their primary tumour, 72% for patients undergoing curative resection with systematic lymphadenectomy, 75% for pN0 and 70% for pN1 tumours. Lymph node metastases were identified in 15 patients undergoing systematic lymphadenectomy, including 9 of 14 patients with tumours smaller than 2 cm, and 6 of 10 patients with G1 tumours. Literature review confirmed a high risk of metastases in small (58%) or G1 (24%) tumours. Tumour grade and angioinvasion were significantly associated with overall and disease-free survival. ConclusionEven well differentiated or small dNEN harbour a considerable risk of metastases. These data challenge the concepts of surveillance, local resection and endoscopic management for dNEN based on size and grading. Angioinvasion was identified as a strong negative predictor of overall and disease-free survival in dNEN.

Pathological risk factors for metastatic disease at presentation in testicular seminomas with focus on the recent pT changes in AJCC TNM eighth edition

Management of clinical stage (CS) 1 testicular seminoma is controversial. Treatment choice is based on a number of pathological risk factors. However, they have been inconsistently associated with risk of metastatic disease. The eighth edition of the American Joint Committee on Cancer Tumor-Node-Metastasis staging system has separated pT1a and pT1b tumors according to a 3-cm size cutoff and upstaged invasion of hilar soft tissue and epididymis as pT2. We investigated pathological predictors of metastatic disease at presentation in 332 testicular seminomas. Age, tumor size, invasion of vessels, hilar soft tissue, rete testis, epididymis, spermatic cord, tunica vaginalis and tumor at spermatic cord margin were assessed and correlated with CS at presentation. A total of 290 (87%) tumors were CS 1; 42 (13%) were CS 2/3. Median patient age of CS 1 was 36 years (20-81); that of CS 2/3 was 36 years (26-63). Mean tumor size of CS 1 was 38 mm (5-95 mm); that of CS 2/3 was 54 mm (8-95 mm). On univariate analysis, lymphovascular invasion (P = .044), epididymal invasion (P = .009) and tumor size (P = .0001) were associated with higher CS. On multivariate analysis, tumor size (P = .0001) and epididymis invasion (P = .023) remained significant. Optimal tumor size cutoff was 4.25 cm. We conclude that tumor size and epididymal invasion are the strongest predictors of metastatic disease at presentation. The results validate changes in American Joint Committee on Cancer Tumor-Node-Metastasis staging eighth edition but suggest a tumor size of 4 cm as better cutoff value.

Cartilage oligomeric matrix protein in patients with osteoarthritis is independently associated with metastatic disease in prostate cancer.

Metastatic prostate cancer has a 5-year survival rate of 30%. Identifying predictors of metastasis outcome could potentially reduce patient mortality. The objective of this study was to determine whether osteoarthritis had an impact on outcomes of prostate cancer including death, local recurrence and/or metastasis and to determine whether cartilage oligomeric matrix protein was involved. We performed a retrospective case-control study of patients with prostate cancer with and without the diagnosis of osteoarthritis and completed immunohistochemistry (IHC) analysis of prostate (n=20) and lymph node (n=7) surgical specimens. We evaluated death, local recurrence and metastatic disease by various IHC biomarkers including prostate specific membrane antigen (PSMA), cartilage oligomeric matrix protein (COMP), CD31, and Ki-67.Our model identified osteoarthritis as an independent risk factor for metastatic disease (OR 5.24, 95% CI 1.49 - 18.41). Most notably, when joint arthroplasty was included in the model, osteoarthritis was no longer an independent risk factor for this outcome (p=0.071). IHC demonstrated that those with osteoarthritis, had greater expression of COMP in the prostate samples (mean 23.9% vs 5.84%, p<0.05) but not of Ki-67, CD31, or PSMA. This study identified and quantified increased metastatic disease in patients with osteoarthritis. Also, patients with osteoarthritis expressed increased COMP levels in the prostate and most likely in distant lymphatic nodes. Moreover, our findings suggest that joint arthroplasty may affect the ability of osteoarthritis to promote metastasis, which could impact treatment protocols and survival outcomes of the most common cause of cancer-related death (metastasis) in the United States.

Risk factors for detectable metastatic disease at presentation in Ewing sarcoma – An analysis of the SEER registry

BackgroundEwing family of tumors (EFT) represents the second-most common primary bone malignancy in children and adolescents. Approximately 25% of patients have radiographically detectable metastatic disease at presentation and experience poorer five-year survival, yet risk factors for metastatic disease at presentation are poorly characterized. We sought to study patient characteristics associated with metastatic disease upon presentation for patients with EFT. MethodsWe identified EFT cases in the Surveillance, Epidemiology, and End Results Program (SEER) registry from 2004 to 2012. Using univariate analyses and multivariable logistic regression, we explored the relationship between demographic and clinical factors and the presence of detectable metastatic disease at presentation. ResultsAmong 870 EFT cases, 35% (n = 304) presented with detectable metastatic disease. These patients were commonly older (>24 years: 28% vs 19%, p = 0.002) and had a primary tumor site in the axial skeleton (56% vs 44%, p < 0.001). After adjusting for all covariates, compared to patients <11 years, those >24 years old faced a two-fold increase in the odds of metastatic disease (OR = 1.99, 95% CI: 1.17–3.38). Axial (OR = 2.31, 95% CI: 1.58–3.37) and “other” (OR = 2.35, 95% CI: 1.15–4.81) tumor locations had more than twice the likelihood of presenting with metastatic disease, compared to extremity tumor sites. Increasing tumor size conferred up to a three-fold increase in odds of metastatic disease (pTrend <0.001). ConclusionsAdvanced age, axial tumor location, and increasing tumor size are associated with increased odds of detectable metastatic disease upon presentation with EFT. Although these characteristics are not modifiable, they provide objective factors that may inform patient counseling of metastatic risk.

Social determinants of stage IV anal cancer and the impact of pelvic radiotherapy in the metastatic setting.

Anal cancer is a relatively rare malignancy, and a minority of patients present with metastatic disease in the United States. The National Cancer Database (NCDB) was used to identify factors associated with metastatic disease at presentation and evaluate the role of pelvic radiotherapy in these patients. The NCDB was queried for patients with squamous cell cancer of the anus diagnosed between 2004 and 2013. Patients were stratified by clinical stage at diagnosis, and a binary logistic regression model was created to identify factors associated with metastatic disease at diagnosis. A secondary metastatic cohort was generated and a multivariable Cox proportional hazards model was created to identify factors associated with improved survival. To validate findings, propensity‐score matching was performed to generate a 1:1 paired dataset stratified by receipt of pelvic radiotherapy. The primary analysis cohort consisted of 28,500 patients. Facility location, male gender, and lack of insurance were confirmed as independent risk factors for metastatic disease. The metastatic cohort consisted of 1264 patients. Multivariable analysis confirmed female sex, possession of a private or Medicare insurance plan, pelvic radiotherapy, and chemotherapy as independent predictors of improved survival. A propensity‐score matched cohort of 730 patients was generated. The median survival was 17.6 months in patients who received radiotherapy versus 14.5 months in those who did not (P < 0.01). In this cohort, male gender and lack of insurance were associated with metastatic disease at presentation. Furthermore, a significant benefit was associated with the use of pelvic radiotherapy. Future prospective research is warranted to confirm these findings.

Socioeconomic measures influence survival in osteosarcoma: an analysis of the National Cancer Data Base

BackgroundWhile previous studies have identified low socioeconomic status as a risk factor for metastatic disease in patients with high-grade osteosarcoma, the influence of socioeconomic status on overall survival remains unclear. The present study aims to investigate the relationship between survival and socioeconomic status in patients with high-grade conventional osteosarcoma. MethodsThe National Cancer Data Base (NCDB) was queried from 1998-2012 to identify all patients <40years of age with a diagnosis of high-grade conventional osteosarcoma. A total of 3,503 patients were identified that met inclusion and exclusion criteria. Univariate relationships were investigated using Kaplan-Meier survival analysis and associated log-rank tests in order to determine patient, socioeconomic, tumor, and treatment variables associated with overall survival. Multivariate analysis was performed to determine independent predictors of survival. ResultsIn order of decreasing magnitude, metastatic disease (Hazard Ratio [HR] 3.28, 95% Confidence Interval [CI] 2.82-3.82), primary site in the pelvis or spine (HR 2.15, 95% CI 1.79-2.59), positive surgical margins (HR 1.82, 95% CI 1.46-2.27), tumor size >8cm (HR 1.47, 95% CI 1.24-1.74), age ≥18 years (HR 1.30, 95% CI 1.14-1.48), lowest quartile of composite socioeconomic status (HR 1.23, 95% CI 1.02-1.51), and Medicaid insurance (HR 1.18, 95% CI 1.02-1.38) were predictors of decreased survival at 5 years. ConclusionTreating providers should be aware that some of their patients may have challenges unrelated to their diagnosis that make timely presentation, adherence to treatment, and continued close surveillance difficult. This investigation suggests that socioeconomic variables influence overall survival for osteosarcoma in the United States, although not as dramatically as established tumor- and treatment-related risk factors.

ASSESSMENT OF THE RISK OF METASTASIS IN PATIENTS WITH ENDOMETRIAL CARCINOMA

Endometrial cancer can be detected early, and it is considered a disease with good prognosis. In some patients, it may have an aggressive course with an unfavorable outcome. The reason for lethal outcome may be the progression and metastasis of malignant disease as well as common comorbidities in this group of patients. The aim of the study was to define the risk factors for metastasis in patients with endometrial carcinoma. The study is a retrospective one. It included 200 patients with endometrial carcinoma. Several parameters were recorded: patient's age, histological type of the tumor, grade of disease, stage of disease at the time of the initiation of treatment, applied therapy and the emergence of local recurrence and distant metastases. Standard statistical procedures were used: Student's t-test, analysis of variance, univariate and multivariate Cox regression analysis. Quantitative statistical analysis was carried out on the computer. Estimation was performed using SPSS software version 10.0 and StatCalc program of EPI-INFO software package version 6. The appearance of metastatic disease in 200 patients with endometrial cancer was monitored. Metastatic disease was registered in 76 patients (38.2%). The percentage of patients with metastases is proportional to the stage of the disease and is 74.1% for stage I, 60% for stage II, and 25.8% for stage III. All patients with stage IV had metastatic disease at the time of the diagnosis. Patients with metastases have significantly higher risk of lethal outcome. Risk factors for metastatic disease are: older age, higher stage of disease, suboptimal cytoreduction, deep myometrial invasion, use of adjuvant chemotherapy.

Is malignant nodule topography an additional risk factor for metastatic disease in low-risk differentiated thyroid cancer?

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. In recent decades, the incidence has been increasing, largely due to increased detection of patients with low-risk or very low-risk DTC. According to European Thyroid Association and American Thyroid Association guidelines, radioiodine (RAI) thyroid remnant ablation is not indicated in very low-risk patients, while its role is still debated in low-risk patients. Accordingly, risk stratification of DTC patients is pivotal when deciding for or against RAI ablation. Presently, risk stratification is based on pTNM staging integrated with clinical parameters. The aim of our study was to evaluate the relationship between location of malignant thyroid nodules within the thyroid gland and the presence of loco-regional and/or distant metastases in patients with pT1a-pT1b DTCs. We reviewed the records of 246 patients (214 women, 32 men; female-to-male ratio 6.7:1) affected by unifocal DTC ≤ 2 cm, who had undergone RAI thyroid remnant ablation (activity ranged 555-4588 MBq) after levothyroxine withdrawal or after recombinant human TSH (rhTSH) stimulation. The majority of the patients (91.5%) were affected by papillary thyroid carcinoma. Metastases were discovered by posttreatment whole-body scintigraphy in 29 out of 246 (11.8%) patients. In patients with metastases, malignant thyroid nodules were located in the right lobe (14/123, 11.4%), left lobe (7/95, 7.4%), and isthmus (8/27, 29.6%). The prevalence of metastases was significantly higher in patients with DTC located in the isthmus, compared to other sites (χ(2) = 9.6, p = 0.002). Our data show for the first time that a location of a thyroid cancer in the isthmus is an additional risk factor for RAI avid metastatic disease in pT1a-pT1b DTC patients, regardless of the presence or absence of other risk factors.

Silencing of UCHL1 by CpG promoter hyper-methylation is associated with metastatic gastroenteropancreatic well-differentiated neuroendocrine (carcinoid) tumors.

Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined. Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index. Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p < 0.001). Hypermethylation of the UCHL1 promoter was commonly observed among metastatic primary tumors and metastases (those with the lowest UCHL1 expression) but not among localized tumors (p < 0.001). Poor staining (<50 %) for UCHL1 was observed in 27 % of localized tumors compared with 87 % of metastatic tumors (p = 0.001). The presence of <50 % staining for UCHL1 was 88 % sensitive and 73 % specific for identifying metastatic disease. In contrast, there was no association between Ki-67 index and metastatic disease. In multivariable analysis, only UCHL1 staining <50 % [odds ratio (OR) 24.5, p = 0.035] and vascular invasion (OR 38.4, p = 0.03) were independent risk factors for metastatic disease at the time of initial surgery. Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.