Risk Factors For Distant Metastasis Research Articles

Distinct characteristics of distant metastasis in early-onset gastric cancer patients compared to late-onset patients: An observational study.

Presently, there is limited understanding of the features of distant metastasis in early-onset gastric cancer (GC). To explore these disparities, a retrospective study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was undertaken. The SEER database was utilized to extract patient data, and multivariate logistic regression analysis was employed to identify the risk factors associated with distant metastasis and liver metastasis. Propensity score matching (PSM) was used to compare the occurrence of liver metastasis among patients based on their age at diagnosis. The study included 2684 early-onset GC patients and 33,289 late-onset GC patients. Preliminary data analysis indicated that early-onset GC patients exhibited more aggressive characteristics such as poor cell differentiation, advanced T stage, and a higher incidence of distant metastasis, excluding liver metastasis. Multivariate logistic regression analysis identified younger age as an independent risk factor for distant metastasis, along with T stage, lymph node metastasis (LNM), and tumor size (>3 cm). Another regression analysis revealed that younger age, diffuse type, and female gender were protective factors against liver metastasis. Through PSM, 3276 early-onset GC patients were matched with an equal number of late-onset GC patients, revealing that patients with early-onset GC had fewer instances of liver metastasis but a higher prevalence of distant metastasis. Our findings suggest that early-onset serves as a protective factor against liver metastasis in GC, while it poses a risk for distant metastasis, likely influenced by the increased prevalence of diffuse-type GC in early-onset patients.

Abstract PO4-01-09: The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer

Abstract Backgrounds: We previously reported an analysis of the impact of adjuvant endocrine therapy (ET) for patients with ER+ and HER2- T1a/bN0M0 breast cancer (BC) at ASCO 2023 (Abstract #538). For the whole cohort, adjuvant ET significantly reduced distant metastases, but the absolute overall survival (OS) difference was small. The presence of medical comorbidities related to treatment toxicity and the estimated life-expectancy differ based on age, affecting the clinical impact of ET. There may be settings where comorbidities result in a sufficiently short, expected OS such that the benefit of ET will not outweigh risk. In multivariate analysis, age (<55 vs >55) was not an independent risk factor for distant metastasis. Here we evaluate the impact of adjuvant ET for ER+/HER2- T1a/bN0M0 breast cancer by age-specific subgroups, focusing on younger (< 40) and older (>65) population. Methods: This is a multicenter retrospective cohort study that evaluated the impact of adjuvant ET for patents with ER+/HER2- T1a/bN0M0 BC who underwent primary breast cancer surgery between 2008 and 2012 in 47 institutes of the Japan Clinical Oncology Group (JCOG). We analyzed distant metastatic-free survival (DMFS) and OS using Kaplan-Meier estimates with log-rank test in patients treated with and without ET in each of three age-specific subgroups (<40, 41-64 and 65> years of age). Results: Median follow-up was 9.2 years; the median age of the entire cohort was 55 years. Of 4756 eligible patients, 417 patients were age 65 (1025 (82%) with ET and 227 (18%) without ET). Of all 3989 (84%) patients with ET (2053 (51%) with Tamoxifen, 2142 (54%) with Aromatase inhibitor, 595 (15%) with LH-RH analog and 76 (2%) with others, includes duplicates). In the < 40 subgroup, 9-year DMFS was 97.2% with ET and 91.0% without ET (p=0.023) and 9-year OS was 97.8% with ET and 97.0% without ET (p=0.954). In the > 65 subgroup), 9-year DMFS was 92.6% with ET and 84.0% without ET (p< 0.01) and 9-year OS was 93.8% with ET and 84.9% without ET (p< 0.01). In those aged 41-64, no significant difference was observed in both 9-year DMFS and OS between patients with and without ET (p=0.328 and p=0.731, respectively) See Table for details. Conclusions: Adjuvant endocrine therapy was associated with improved distant metastatic-free survival in the younger (<40) and older (>65) population in this large Japanese dataset and was associated with improved overall survival in those >65. Our findings suggest clinically relevant benefit from ET in both younger and older unselected patients with very small ER+ BC. The lack of benefit in patients aged 41-64 is likely due to individual tumor and treatment factors, which will be evaluated and described in detail at the meeting. Table. The 9-year DMFS and OS of each age-specific three subgroups. *They are analyzed by using Kaplan-Meier estimates with log-rank test between patients treated with and without ET. Citation Format: Yuko Takahashi, Shinsuke Sasada, Naoto Kondo, Hiroya Hashimoto, Kaori Terata, Kumiko Kida, Yasuaki Sagara, Yoichi Naito, Keisei Anan, Takayuki Ueno, Akihiko Suto, Chizuko Kanbayashi, Mina Takahashi, Rikiya Nakamura, Toshiyuki Ishiba, Michiko Tsuneizumi, Seiichiro Nishimura, Yukinori Ozaki, Akihiko Shimomura, Takehiko Sakai, Tsuguo Iwatani, Hideo Shigematsu, Kenji Tamura, Tomomi Fujisawa, Takashi Hojo, Fumitaka Hara, Tadahiko Shien, Hiroji Iwata. The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-09.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Risk factors, prognostic factors, and nomograms for distant metastasis in patients with diagnosed duodenal cancer: A population-based study.

Duodenal cancer is one of the most common subtypes of small intestinal cancer, and distant metastasis (DM) in this type of cancer still leads to poor prognosis. Although nomograms have recently been used in tumor areas, no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer. To develop and evaluate nomograms for predicting the risk of DM and personalized prognosis in patients with duodenal cancer. Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM. Two novel nomograms were established, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A total of 2603 patients with duodenal cancer were included, of whom 457 cases (17.56%) had DM at the time of diagnosis. Logistic analysis revealed independent risk factors for DM in duodenal cancer patients, including gender, grade, tumor size, T stage, and N stage (P < 0.05). Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM, including age, histological type, T stage, tumor grade, tumor size, bone metastasis, chemotherapy, and surgery (P < 0.05). The accuracy of the nomograms was validated in the training set, validation set, and expanded testing set using ROC curves, calibration curves, and DCA curves. The results of Kaplan-Meier survival curves (P < 0.001) indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer. The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM, potentially enhancing clinical decision-making.

Comparison of metastasis and prognosis between early-onset and late-onset hepatocellular carcinoma: A population-based study

BackgroundWhile hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. MethodsInformation of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan–Meier curve and log-rank test. ResultsIn total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan–Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. ConclusionIn this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

Nuclear Localization of Yes-Associated Protein Is Associated With Tumor Progression in Cutaneous Melanoma

Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, western blotting, viability assays, wound healing assays, verteporfin treatment, and xenograft assays were conducted using melanoma cell lines B16F1 and B16F10 subjected to YapS127A transfection and siYap knockdown. Nuclear YAP localization was identified in 63 tumors (45.0%) and was more frequent than cytoplasmic YAP in acral lentiginous and nodular subtypes (P = .007). Compared with cytoplasmic YAP melanomas, melanomas with nuclear YAP had higher mitotic activity (P = .016), deeper invasion (P < .001), and more frequently metastasized to lymph nodes (P < .001) and distant organs (P < .001). Patients with nuclear YAP melanomas had poorer disease-free survival (P < .001) and overall survival (P < .001). Nuclear YAP was an independent risk factor for distant metastasis (hazard ratio: 3.206; 95% CI, 1.032-9.961; P = .044). Proliferative ability was decreased in siYapB16F1 (P < .001) and siYapB16F10 (P = .001) cells and increased in YapS127AB16F1 (P = .003) and YapS127AB16F10 (P = .002) cells. Cell cycle analysis demonstrated relative G1 retention in siYapB16F1 (P < .001) and siYapB16F10 (P < .001) cells and S retention in YapS127AB16F1 cells (P = .008). Wound healing assays showed that Yap knockdown inhibited cell invasion (siYapB16F1, P = .001; siYapB16F10, P < .001), whereas nuclear YAP promoted it (YapS127AB16F, P < .001; YapS127AB16F1, P = .017). Verteporfin, a direct YAP inhibitor, reduced cellular proliferation in B16F1 (P = .003) and B16F10 (P < .001) cells. Proliferative effects of nuclear YAP were confirmed in xenograft mice (P < .001). In conclusion, nuclear YAP in human melanomas showed subtype specificity and correlated with proliferative activity and proinvasiveness. It is expected that YAP becomes a useful prognostic marker, and its inhibition may be a potential therapy for melanoma patients.

High-risk histopathologic features in local advanced conjunctival melanoma.

To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

Value of the NF-κB signalling pathway and the DNA repair gene PARP1 in predicting distant metastasis after breast cancer surgery

The DNA repair gene PARP1 and NF-κB signalling pathway affect the metastasis of breast cancer by influencing the drug resistance of cancer cells. Therefore, this study focused on the value of the DNA repair gene PARP1 and NF-κB pathway proteins in predicting the postoperative metastasis of breast cancer. A nested case‒control study was performed. Immunohistochemical methods were used to detect the expression of these genes in patients. ROC curves were used to analyse the predictive effect of these factors on distant metastasis. The COX model was used to evaluate the effects of PARP1 and TNF-α on distant metastasis. The results showed that the expression levels of PARP1, IKKβ, p50, p65 and TNF-α were significantly increased in the metastasis group (P < 0.001). PARP1 was correlated with IKKβ, p50, p65 and TNF-α proteins (P < 0.001). There was a correlation between IKKβ, p50, p65 and TNF-α proteins (P < 0.001). ROC curve analysis showed that immunohistochemical scores for PARP1 of > 6, IKKβ of > 4, p65 of > 4, p50 of > 2, and TNF-α of > 4 had value in predicting distant metastasis (SePARP1 = 78.35%, SpPARP1 = 79.38%, AUCPARP1 = 0.843; Sep50 = 64.95%, Spp50 = 70.10%, AUCp50 = 0.709; SeTNF-α = 60.82%, SpTNF-α = 69.07%, AUCTNF-α = 0.6884). Cox regression analysis showed that high expression levels of PARP1 and TNF-α were a risk factor for distant metastasis after breast cancer surgery (RRPARP1 = 4.092, 95% CI 2.475–6.766, P < 0.001; RRTNF-α = 1.825, 95% CI 1.189–2.799, P = 0.006). Taken together, PARP1 > 6, p50 > 2, and TNF-α > 4 have a certain value in predicting breast cancer metastasis, and the predictive value is better when they are combined for diagnosis (Secombine = 97.94%, Spcombine = 71.13%).

Diagnostic and prognostic risk factors analysis for distant metastasis in melanoma: a population-based study.

We aimed to develop tools that could predict the occurrence of distant metastases in melanoma and its prognosis based on clinical and pathological characteristics. We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database of melanoma patients diagnosed between 2010 and 2019. Logistic analyses were performed to identify independent risk factors associated with distant metastasis. Additionally, multivariate Cox analyses were conducted to determine independent prognostic factors for patients with distant metastasis. Two nomograms were established and evaluated with the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Furthermore, we performed a retrospective analysis of melanoma with distant metastasis from our institute between March 2018 and June 2022. Of the total 19 396 melanoma patients, 352 (1.8%) had distant metastases at the time of diagnosis. The following clinical and pathological characteristics were identified as independent risk factors for distant metastasis in melanoma: N stage, tumor size, ulceration, mitosis, primary tumor site, and pathological subtype. Furthermore, tumor size, pathological subtype, and radiotherapy were identified as independent prognostic factors. The results of the training and validation cohorts' ROC curves, calibration, DCA, and Kaplan-Meier survival curves demonstrate the effectiveness of the two nomograms. The retrospective study results from our center supported the results from the SEER database. The clinical and pathological characteristics of melanoma can predict a patient's risk of metastasis and prognosis, and the two nomograms are expected to be effective tools to guide therapy decisions.

A PET/CT radiomics model for predicting distant metastasis in early-stage non–small cell lung cancer patients treated with stereotactic body radiotherapy: a multicentric study

ObjectivesStereotactic body radiotherapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are unfit for surgery. Some patients may experience distant metastasis. This study aimed to develop and validate a radiomics model for predicting distant metastasis in patients with early-stage NSCLC treated with SBRT.MethodsPatients at five institutions were enrolled in this study. Radiomics features were extracted based on the PET/CT images. After feature selection in the training set (from Tianjin), CT-based and PET-based radiomics signatures were built. Models based on CT and PET signatures were built and validated using external datasets (from Zhejiang, Zhengzhou, Shandong, and Shanghai). An integrated model that included CT and PET radiomic signatures was developed. The performance of the proposed model was evaluated in terms of its discrimination, calibration, and clinical utility. Multivariate logistic regression was used to calculate the probability of distant metastases. The cutoff value was obtained using the receiver operator characteristic curve (ROC), and the patients were divided into high- and low-risk groups. Kaplan-Meier analysis was used to evaluate the distant metastasis-free survival (DMFS) of different risk groups.ResultsIn total, 228 patients were enrolled. The median follow-up time was 31.4 (2.0-111.4) months. The model based on CT radiomics signatures had an area under the curve (AUC) of 0.819 in the training set (n = 139) and 0.786 in the external dataset (n = 89). The PET radiomics model had an AUC of 0.763 for the training set and 0.804 for the external dataset. The model combining CT and PET radiomics had an AUC of 0.835 for the training set and 0.819 for the external dataset. The combined model showed a moderate calibration and a positive net benefit. When the probability of distant metastasis was greater than 0.19, the patient was considered to be at high risk. The DMFS of patients with high- and low-risk was significantly stratified (P < 0.001).ConclusionsThe proposed PET/CT radiomics model can be used to predict distant metastasis in patients with early-stage NSCLC treated with SBRT and provide a reference for clinical decision-making.Plain language summaryIn this study, the model was established by combining CT and PET radiomics signatures in a moderate-quantity training cohort of early-stage NSCLC patients treated with SBRT and was successfully validated in independent cohorts. Physicians could use this easy-to-use model to assess the risk of distant metastasis after SBRT. Identifying subgroups of patients with different risk factors for distant metastasis is useful for guiding personalized treatment approaches.

Organ-preservation in rectal cancer: What is at risk when offering watch and wait for a clinical complete response? Data from 2 international registries in rectal cancer.

7 Background: Organ-preservation has become an attractive alternative to total mesorectal excision (TME) among patients with rectal cancer following neoadjuvant therapy. Patients who achieve a clinical complete response (cCR) are currently offered watch-and-wait (WW) without immediate resection. Nearly 30% of these patients will develop local regrowth usually within 3 years from initial decision to WW. While salvage resection is frequently feasible, keeping the primary tumor in situ (despite clinically undetectable) may contribute to the risk for development of subsequent distant metastases (DM). The aim of the present study is to compare the risk of DM between patients with local regrowth (LR) after WW (undetectable residual disease) and patients with near-complete pathological response managed by TME at time of reassessment of response. Methods: Data from patients with rectal cancer following neoadjuvant therapy entered a prospective international database (IWWD) with cCR managed by WW and subsequent LR were compared to patients managed by TME from a prospectively maintained national registry (VIKINGO project). Near-complete response was defined at the presence of ≤10% residual cancer cells in the resected specimen. Primary endpoint was DM-free survival at 3 years from decision to WW or TME. Cox-logistic regression was performed to search for predictors of DM development. Kaplan-Meier curves were used to compare DM-free survival between groups based on statistically significant features found at multivariate analysis (p≤0.05) using log-rank test. Results: 508 patients with LR were compared to 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among local regrowths (22.8% vs. 10.2%,; p≤0.001). Independent risk factors for DM included LR (versus TME at reassessment; p=0.001), ypT3-4 status (p=0.016) and ypN+ status (p=0.001) at the time of surgery. 3yr-DM-free survival was significantly worse for patients with local regrowth (75% vs. 87%; p=0.001). When stratified for pathological stage, patients with local regrowth did significantly worse through all stages ypT1-2N0 (p&lt;0.001); ypT3-4N0 (p=0.009) and ypTanyN+ (p&lt;0.001). Conclusions: Development of LR following WW is a significant and independent risk factor for subsequent DM. Final pathological stage is also a risk factor for subsequent DM. Patients with local regrowth have a higher risk for subsequent DM development than patients managed by TME at restaging irrespective of final ypT and ypN status. Leaving the primary undetectable tumor in situ until development of local regrowth may result in worse oncological outcomes. Future studies incorporating organ-preservation strategies should focus on the subsequent risk of DM among patients who eventually develop local regrowth as one of clinically relevant primary endpoints.

Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study

Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. A retrospective study. Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Risk Factors for Distant Metastasis in T3 T4 Rectal Cancer.

Distant metastasis is the leading cause of death in patients with rectal cancer. This study aims to comprehensively analyze the risk factors of distant metastasis in T3 T4 rectal cancer using magnetic resonance imaging (MRI), pathological features, and serum indicators. The clinicopathological data of 146 cases of T3 T4 rectal cancer after radical resection from January 2015 to March 2023 were retrospectively analyzed. Pre- and postoperative follow-up data of all cases were collected to screen for distant metastatic lesions. Univariate and multivariate Logistic regression methods were used to analyze the relationship between MRI features, pathological results, serum test indexes, and distant metastasis. Of the 146 included patients, synchronous or metachronous distance metastasis was confirmed in 43 (29.4%) cases. The patients' baseline data and univariate analysis showed that mrEMVI, maximum tumor diameter, mr T Stage, pathological N stage, number of lymph node metastasis, cancer nodules, preoperative serum CEA, (Carcinoembryonic antigen) and CA199 were associated with distant metastasis. In the multiple logistic regression model, mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter, and preoperative serum CEA were identified as independent risk factors for distant metastasis: mrEMVI [odds ratio (OR) = 3.06], pathological N stage (OR = 6.52 for N1 vs N0; OR = 63.47 for N2 vs N0), preoperative serum CEA (OR = 0.27), tumor maximum diameter (OR = 1.03), number of lymph nodes metastasis (OR = 0.62). And, the receiver operating characteristic (ROC) curve was plotted and the area under the curve was calculated (area under the curve [AUC) = 0.817, 95% CI = 0.744-0.890, P < .001]. mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter and preoperative serum CEA are the independent risk factors for distant metastasis in T3 T4 rectal cancer. A comprehensive analysis of the risk factors for distant metastasis in rectal cancer can provide a reliable basis for formulating individualized treatment strategies, follow-up plans, and evaluating prognosis.

Machine learning based on SEER database to predict distant metastasis of thyroid cancer.

Distant metastasis of thyroid cancer often indicates poor prognosis, and it is important to identify patients who have developed distant metastasis or are at high risk as early as possible. This paper aimed to predict distant metastasis of thyroid cancer through the construction of machine learning models to provide a reference for clinical diagnosis and treatment. Data on demographic and clinicopathological characteristics of thyroid cancer patients between 2010 and 2015 were extracted from the National Institutes of Health (NIH) Surveillance, Epidemiology, and End Results (SEER) database. Our research used univariate and multivariate logistic models to screen independent risk factors, respectively. Decision Trees (DT), ElasticNet (ENET), Logistic Regression (LR), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Multilayer Perceptron (MLP), Radial Basis Function Support Vector Machine (RBFSVM) and seven machine learning models were compared and evaluated by the following metrics: the area under receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), sensitivity(also called recall), specificity, precision, accuracy and F1 score. Interpretable machine learning was used to identify possible correlation between variables and distant metastasis. Independent risk factors for distant metastasis, including age, gender, race, marital status, histological type, capsular invasion, and number of lymph nodes metastases were screened by multifactorial regression analysis. Among the seven machine learning algorithms, RF was the best algorithm, with an AUC of 0.948, sensitivity of 0.919, accuracy of 0.845, and F1 score of 0.886 in the training set, and an AUC of 0.960, sensitivity of 0.929, accuracy of 0.906, and F1 score of 0.908 in the test set. The machine learning model constructed in this study helps in the early diagnosis of distant thyroid metastases and helps physicians to make better decisions and medical interventions.

Risk factor analysis of distant metastases in patients with primary medullary thyroid cancer: a population-based study.

Medullary thyroid carcinoma has a high rate of recurrence and distant metastasis. The aim of this study was to investigate the risk factors for distant metastasis in patients with primary medullary thyroid carcinoma. Patients diagnosed with primary medullary thyroid cancer between 2010 and 2015 were enrolled using the Surveillance, Epidemiology, and End Results (SEER) database. Patient demographics and tumor clinicopathological features were evaluated to identify potential risk factors for distant metastasis in patients with primary medullary thyroid cancer. Univariate and multivariate logistic regression analyses were used to determine independent risk factors for distant metastasis in patients with primary medullary thyroid carcinoma. All statistical analyses were performed using SPSS statistical software (version 27.0). A two-tailed P < 0.05 was considered statistically significant. We collected 685 patients with primary medullary thyroid carcinoma, 40 of whom (5.84%) developed distant metastases. Univariate logistic regression analysis showed that except marital status, age, sex, race, pT stage, N stage, multifocal and capsular infiltration were significantly correlated with distant metastasis of medullary thyroid carcinoma. Multivariate logistic regression analysis showed that patients aged ≤ 18years or > 55years, Black race, higher pT stage and N stage were independent risk factors for distant metastasis of medullary thyroid carcinoma. This study found that ≤ 18years or > 55years, black race, higher pT stage and N stage were significantly associated with distant metastasis of medullary thyroid cancer. This is important for clinicians to identify patients at high risk of distant metastasis in a timely manner.

Development and Validation of Nomograms to Predict Risk and Prognosis in Salivary Gland Carcinoma Patient with Distant Metastases.

Background: Salivary gland carcinoma (SGC) patients with distant metastasis (DM) are rare, and understanding this disease is insufficient. Nomograms can predict the prognostic probability of patients, while few studies have examined diagnostic and prognostic factors in SGC patients with DM. The purpose of this study was to establish and validate the risk and prognostic nomograms of SGC patients with DM. Methods: Based on the SEER database, we analyzed the data of SGC patients between 2004 and 2015. Logistic regression analyses and Cox proportional hazards regression analyses were used to identify risk and prognostic factors for DM in SGC patients. Based on the Akaike information criterion (AIC) value and likelihood ratio test, the best-fitting model was selected to build risk and prognostic nomograms, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) survival curves. ROC curves were also used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system. Results: 7418 SGC patients were included in the study, and 307 (4.14%) of them were diagnosed with DM. This study identified that there are variables (age ≥ 80, no-parotid gland primary site, histologic type of mucoepidermoid carcinoma and squamous cell carcinoma, T stage ≥ T2, N staged ≥ N1, histologic grade ≥ III, and tumor size ≥ 41 mm) associated with the occurrence of DM in SGC patients. Therefore, we constructed diagnostic and prognostic nomograms after incorporating these variables. ROC curves illustrated the better predictive efficacy of 2 nomograms over the AJCC staging system. DCA curves, calibration curves, and K-M survival curves showed that 2 nomograms can accurately predict the occurrence and prognosis of DM among SGC patients in training and validation sets. Conclusion: It was shown that the nomograms were highly discriminative in predicting the diagnosis and prognosis of SGC patients with DM, and could identify high-risk patients, thereby providing SGC patients with individualized treatment plans.

Incidence, risk factors, and a prognostic nomogram for distant metastasis in endometrial cancer: A SEER-based study.

To evaluate the metastatic pattern, identify the risk factors, and establish a nomogram for predicting prognosis of endometrial cancer (EC) with distant metastasis. A retrospective cohort study of women diagnosed with EC was conducted according to the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2017. Multivariate logistic analysis and Cox analysis were performed to identify the risk factors in promoting distant metastasis and predictors associated with overall survival (OS) in this particular subpopulation. A nomogram was then constructed and validated by the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. A total of 2799 cases of distant metastasis in EC patients were identified, with an overall incidence rate of 3.74% from 2010 to 2017. Black race, unmarried status, non-endometrioid histologic types, and grade IV were significant risk factors for distant metastasis in EC patients. Meanwhile, race, histology, grade, metastasis status, surgery, lymphadenectomy, and chemotherapy were identified as independent prognostic factors for OS. A nomogram to predict 1-, 3-, and 5-year OS was established, and presented favorable accuracy and clinical applicability. Patients were further divided into high- and low-risk groups according to the model. The nomogram was developed as a highly accurate, individualized tool to better predict the prognosis of EC patients with distant metastasis, which would help clinicians to identify high-risk patients, and adjust and tailor their treatment strategies.

Risk factors for distant metastasis of Chondrosarcoma in the middle-aged and elderly people.

Chondrosarcoma is the second most common primary bone malignancy with the highest incidence in middle-aged and elderly people, where distant metastasis (DM) still leads to poor prognosis. The purpose of this study was to construct a nomogram for studying the diagnosis of DM in middle-aged and elderly patients with chondrosarcoma. Data on chondrosarcoma patients aged ≥ 40 years diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The data were divided into a training set and an internal validation set according to a 7:3 ratio, and the training set data were screened for independent risk factors for DM in chondrosarcoma patients using univariate and multivariate logistic regression analysis. The screened independent risk factors were then used to build a nomogram. In addition, data from 144 patients with chondrosarcoma aged ≥ 40 years diagnosed in a tertiary hospital in China from 2012 to 2021 were collected as the external validation set. The results were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis in the training set, internal validation set, and external validation set. A total of 1462 middle-aged and elderly patients with chondrosarcoma were included, and 92 (6.29%) had DM at the time of diagnosis. Independent risk factors for DM in middle-aged and elderly patients with chondrosarcoma included being married (OR: 2.119, 95% CI: 1.094-4.105), histological type of dedifferentiated chondrosarcoma (OR: 1.290, 95% CI: 1.110-1.499), high-grade tumor (OR: 1.511, 95% CI: 1.079-2.115), T3 stage (OR: 4.184, 95% CI: 1.977- 8.858), and N1 staging (OR: 5.666, 95% CI: 1.964-16.342). The area under the receiver operating characteristic curve (AUC) was 0.857, 0.820, and 0.859 in the training set, internal validation set, and external validation set, respectively. The results of the calibration curve and decision curve analysis also confirmed that the established nomogram could accurately predict DM in middle-aged and elderly patients with chondrosarcoma. Married, histological type of dedifferentiated chondrosarcoma, high-grade tumor, T3 stage, and N1 stage are independent risk factors for DM in middle-aged and elderly chondrosarcoma patients, and clinicians should see more attention.

Prediction of liver and lung metastases in patients with early-onset colorectal cancer by nomograms based on heterogeneous and homogenous risk factors.

Identifying the risk factors for distant metastasis in early-onset colorectal cancer (EOCRC) is crucial for elucidating its etiology and facilitating preventive treatment. This study aims to characterize the variability in EOCRC incidence and discern both heterogeneous and homogeneous risk factors associated with synchronous liver, lung, and hepato-lung metastases. This study included patients with EOCRC enrolled in the SEER database between 2010 and 2015 and divided patients into three groups by synchronous liver, lung, and hepato-lung metastases. Each group of patients with different metastasis types was randomly assigned to the development and validation cohort in a ratio of 7:3. Logistic regression was used to analyze the heterogeneous and homogenous risk factors for synchronous liver, lung, and hepato-lung metastases in the development cohort of patients. Nomograms were built to calculate the risk of metastasis, and the receiver operating characteristic (ROC) curve and calibration curve were used to quantitatively evaluate their performance. A total of 16,336 eligible patients with EOCRC were included in this study, of which 17.90% (2924/16,336) had distant metastases. The overall incidences of synchronous liver, lung, and hepato-lung metastases were 11.90% (1921/16,146), 2.42% (390/16,126), and 1.50% (241/16,108), respectively. Positive CEA values before treatment, increased lymphatic metastases, and deeper invasion of intestinal wall were positively correlated with three distant types of metastases. On the contrary, the correlation of age, ethnicity, location of primary tumor, and histologic grade among the three types was inconsistent. The ROC curve and calibration curve proved to have fine performance in predicting distant metastases of EOCRC. There are significant differences in the incidence of distant metastases in EOCRC, and related risk factors are heterogeneous and homogenous. Although limited risk factors were incorporated in this study, the established nomograms indicated good predictive performance.

Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia.

Despite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited. Medical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated. DM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001). Higher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC.