Independent Risk Factor For Metastasis Research Articles

Preoperative Clinical and Ultrasonographic Predictors for Aggressive Behaviors in Sporadic Medullary Thyroid Carcinomas.

Objective: To explore the clinical and ultrasonographic predictors for aggressive behaviors preoperatively in sporadic medullary thyroid carcinomas (MTCs). Materials and Methods: The preoperative clinical and ultrasonographic characteristics of patients diagnosed with MTCs between January 2009 and May 2022 were retrospectively reviewed. MTCs were described and categorized according to the American College of Radiology (ACR) thyroid imaging reporting and data system classification by 2 radiologists. Interobserver agreement was evaluated by kappa test. Univariate and multivariate analyses were performed to identify predictors of aggressive behaviors in MTCs. The log-rank test was utilized to compare differences in Kaplan-Meier (K-M) curves for postoperative disease-free survival (PDFS). Results: A total of 120 patients were enrolled in the final study. Male sex was significant risk factor for metastasis, perithyroidal invasion, and lateral cervical lymph node (LCLN) metastasis [odds ratio (OR): 3.109, P = .019; OR: 5.316, P = .018; OR: 5.154 P = .012, respectively]. The kappa values for all ultrasonic characteristics were high (ranged from 0.811 to 0.941). Size, focality, and margin of the nodule were independent risk factors for metastasis, as well as for LCLN metastasis. Whereas margin (P < .001) and a subcapsular location (P = .021) were risk factors for perithyroidal invasion. According to K-M analysis, PDFS of patients differed significantly between groups with/without metastasis (P < .001), groups with/without perithyroidal extension (P < .001) and groups with/without LCLN metastasis (P < .001). Conclusions: Male sex is an independent risk factor for metastasis, perithyroidal invasion, and LCLN metastasis. The large size (≥2.55 cm for metastasis, ≥2.15 cm for LCLN metastasis, respectively), multifocality, and irregular margin of nodules were independent risk factors for both metastasis and LCLN metastasis. Extrathyroidal extension and a subcapsular location were risk factors for perithyroidal invasion. Moreover, patients with metastasis/perithyroidal extension/LCLN metastasis exhibited worse PDFS.

Abstract IA06: Postpartum breast involution informs breast cancer metastasis to the liver

Abstract Young women with breast cancer have disproportionally higher rates of metastasis, and effective treatment strategies are lacking. Our lab has focused on investigating how normal reproductive changes in tissue biology interface with breast cancer metastasis in young patients. These studies identify weaning-induced involution of the breast as a tissue remodeling process similar to wound healing that promotes metastasis in rodent models. Relevance to women is suggested by the fact that a breast cancer diagnosis within 5 years of childbirth is a strong and independent risk factor for metastasis. Further, these studies find that up to 50% of all young onset breast cancer is diagnosed within this high risk postpartum window. This subset of common, young onset breast cancer is referred to as postpartum breast cancer (PPBC). We find that PPBC appears durably altered by involution, as PPBC tumors display involution, metastatic, and treatment resistant molecular signatures. PPBC also specifically associates with increased liver metastases, a metastatic site associated with very poor prognosis. In rodents, we identified a functional link between the mammary gland and the liver, including weaning-induced liver involution. Liver involution is characterized by hepatocyte cell death, fibroblast activation, ECM deposition, and an immune regulatory infiltrate similar to that found in the postpartum involuting breast. In rodent models of breast cancer liver metastasis (BCLM), the involuting liver supports outgrowth of circulating breast cancer cells more than the nulliparous host liver. Evidence for similar liver biology occurring in women is suggested by studies in healthy women, where we find liver volume increase during pregnancy and loss post wean, data consistent with liver involution. In our mouse models of BCLM, the involution metastatic advantage coincided with weaning-induced immune tolerance in the liver. We next targeted the pro-tumor, immune suppressed state of involution with the immune modulatory agent vitamin D. These studies revealed dramatic down regulation of liver metabolism with weaning, including liver cytochrome P450 enzymes, which effectively nullified the protective effect of vitamin D in involution hosts. Combined, these novel findings are anticipated to have implications for sex-specific liver diseases broadly, efficacy of pro-drugs in the postpartum window, and for breast cancer outcomes in young patients. Citation Format: Pepper Schedin. Postpartum breast involution informs breast cancer metastasis to the liver [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr IA06.

The Predictive Value of Conventional Ultrasound Signs Plus Serological Indices for Neck Lymph Node Metastasis in Papillary Thyroid Cancer

The present study aimed to evaluate the predictive value of conventional ultrasound signs and serological indices in the detection of neck lymph node metastasis in papillary thyroid cancer (PTC). A total of 80 patients with PTC scheduled for surgery in our hospital between August 2019 and December 2022 were recruited. Patients with neck lymph node metastasis were categorized as the experimental group, and patients without neck lymph node metastasis were included in the control group. Patients’ ultrasound signs were analyzed, and serological indices were determined. Logistic analysis was performed to determine the risk factors for the development of postoperative neck lymph node metastasis in papillary thyroid cancer, and the receiver operating characteristic (ROC) curve was employed to assess their diagnostic efficiency. Significant differences were observed in the number of lesions, nodule size, calcification, blood flow RI, and PI values comparison between the two arms (P &lt; 0.05), while no significant differences were found in other ultrasound signs (P &gt; 0.05). Patients with neck lymph node metastasis exhibited significantly higher serum concentrations of thyroid stimulating hormone (TSH) and anti-thyroglobulin antibodies (TG-Ab) versus those without metastasis (P &lt; 0.05). Nodule size, number of lesions, and serum TSH level were independent risk factors for metastasis in neck lymph nodes in patients with papillary thyroid cancer (P &lt;0.05). Conventional ultrasound signs, combined with serologic indices, demonstrated the highest diagnostic efficiency for predicting neck lymph node metastasis in patients with papillary thyroid cancer. These findings showed a sensitivity of 0.868, specificity of 0.894, and an area under the ROC curve (AUC) of 0.918. Additionally, the Jorden index was calculated to be 0.761. Analysis revealed that nodule size, number of lesions, and serum TSH concentration were independent risk factors for neck lymph node metastasis in papillary thyroid cancer patients. The combination of conventional ultrasound signs and serologic indices provided a higher diagnostic value compared to using a single diagnostic modality, thus indicating promising clinical benefits.

Predictive nomograms for risk and prognostic factors in metastatic bladder cancer: a population-based study.

Given the poor prognosis of patients with metastatic bladder cancer (MBC), the development of an effective diagnostic and prognostic model is significant in cancer management and for guidance in clinical practice. We acquired data of 23,180 bladder cancer patients from Surveillance Epidemiology and End Results (SEER) database registered from 2010 to 2019. The optimal cut-off value for patient age and tumor size was determined by x-tile software. Independent risk factors for MBC were identified by univariate and multivariate logistic regression analyses and prognosis factors were identified by univariate and multivariate cox regression analyses, and risk and prognostic nomograms were constructed. The accuracy of the nomograms was verified by receiver operating characteristic (ROC) curves, calibration curves, and its clinical utility was determined by decision curve analysis (DCA) curves and clinical impact curves (CIC). Kaplan-Meier (K-M) survival curves further confirmed the clinical validity of the prognostic model. Through logistic regression analyses, we derived that age, histological type, tumor size, T stage, and N stage were independent risk factors for metastasis in bladder cancer patients. By cox regression analyses, age, chemotherapy, histological type, bone, lung and liver metastases were identified as risk factors influencing prognosis of MBC patients. Area under the curve (AUC) of the risk nomogram was 0.80, the AUC values of 1/2/3 years were 0.74/0.71/0.71 in the training group and 0.81/0.77/0.77 in the validation group. Based on calibration curves, DCA curves, CIC and K-M curves, the nomograms were validated with excellent predictive performance and clinical utility for MBC. The nomograms we constructed have perfect predictive accuracy and clinical practicality for MBC patients, enabling clinicians to provide treatment advice and clinical guidance to patients.

Impact of Variant Histology on Oncological Outcomes in Upper Tract Urothelial Carcinoma: Results From the ROBUUST Collaborative Group.

Oncologic implications of variant histology (VH) have been extensively studied in bladder cancer; however, further investigation is needed in upper tract urothelial carcinoma (UTUC). Our study aims to evaluate the impact of VH on oncological outcomes in UTUC patients treated with radical nephroureterectomy (RNU). A retrospective analysis was performed on patients who underwent a robotic or laparoscopic RNU for UTUC using the ROBUUST database, a multi-institutional collaborative including 17 centers worldwide. Logistic regression was used to assess the effect of VH on urothelial recurrence (bladder, contralateral upper tract), metastasis, and survival following RNU. A total of 687 patients were included in this study. Median (IQR) age was 71 (64-78) years and 470 (68%) had organ confined disease. VH was present in 70 (10.2%) patients. In a median follow-up of 16 months, the incidence of urothelial recurrence, metastasis, and mortality was 26.8%, 15.3%, and 11.8%, respectively. VH was associated with increased risk of metastasis (HR 4.3, P <.0001) and death (HR 2.0, P =.046). In multivariable analysis, VH was noted to be an independent risk factor for metastasis (HR 1.8, P =.03) but not for urothelial recurrence (HR 0.99, P =.97) or death (HR 1.4, P =.2). Variant histology can be found in 10% of patients with UTUC and is an independent risk factor for metastasis following RNU. Overall survival rates and the risk of urothelial recurrence in the bladder or contralateral kidney are not affected by the presence of VH.

Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort

Introduction/Aim: Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). Methods: The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. Results: We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). Conclusion: Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.

Level II lateral neck dissection for papillary thyroid carcinoma: A retrospective cohort study

BackgroundFor N1b papillary thyroid carcinoma (PTC) patients, lateral neck dissection encompassing levels Ⅱ-Ⅴ is generally recommended. However, routine level Ⅱ dissection is controversial given the low incidence of metastasis, and potential complications such as increased shoulder syndrome. MethodsRetrospective analysis of consecutive patients with papillary thyroid carcinoma who underwent lateral neck dissection at a single institution from January 2019 to April 2021 was performed. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality and lymph node metastases were examined to evaluate the occurrence of metastatic Level Ⅱ lymph nodes. ResultsOverall and occult level Ⅱ metastases were observed in 51.83% and 34.84% of cN1b PTC patients. Multivariant analysis showed that primary tumor, location of primary tumor and positive level Ⅴ can serve as independent risk factors of metastasis in level Ⅱ. For cN1b PTC patients not suspected of level Ⅱ lymph nodes preoperatively, independent risk factors for predicting occult level Ⅱ metastases may include the location of primary tumor, positive level Ⅲ and positive level Ⅴ. ConclusionA significant number of patients with PTC and lateral neck disease experienced Level Ⅱ metastasis, with the location of primary tumor and multilevel lymph node involvement being the independent risk factors. If the tumor is less than 1 cm and located at lower 2/3 lobe, there is minimal possibility of level Ⅱ lymph node metastasis.

Lung Immune Prognostic Index Could Predict Metastasis in Patients With Osteosarcoma.

BackgroundThe lung immune prognostic index (LIPI), composed of serum lactate dehydrogenase (LDH) and the derived neutrophil to lymphocyte ratio (dNLR), is a novel prognostic factor of lung cancer. The prognostic effect of the LIPI has never been verified in osteosarcoma.MethodsWe retrospectively reviewed the osteosarcoma patients with metachronous metastasis from January 2016 to January 2021 in West China Hospital. We collected and analyzed the clinical data and constructed the LIPI for osteosarcoma. The correlation between the LIPI and metastasis was analyzed according to the Kaplan–Meier method and Cox regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). Univariate analysis and multivariate analysis were conducted to clarify the independent risk factors of metastasis. The nomogram model was established by R software, version 4.1.0.ResultsThe area under the curve (AUC) and best cutoff value were 0.535 and 91, 0.519, and 5.02, 0.594 and 2.77, 0.569 and 227.14, 0.59 and 158, and 0.607 and 2.05 for ALP, LMR, NLR, PLR, LDH, and dNLR, respectively. The LIPI was composed of LDH and dNLR and showed a larger AUC than other hematological factors in the time-dependent operator curve (t-ROC). In total, 184 patients, 42 (22.8%), 96 (52.2%), and 46 (25.0%) patients had LIPIs of good, moderate, and poor, respectively (P < 0.0001). Univariate analysis revealed that pathological fracture, the initial CT report of suspicious nodule, and the NLR, PLR, ALP, and the LIPI were significantly associated with metastasis, and multivariate analysis showed that the initial CT report of suspicious nodule and the PLR, ALP, and LIPI were dependent risk factors for metastasis. Metastatic predictive factors were selected and incorporated into the nomogram construction, including the LIPI, ALP, PLR, initial CT report, and pathological fracture. The C-index of our model was 0.71. According to the calibration plot, this predictive nomogram could accurately predict 3- and 5-year metachronous metastasis. Based on the result of decision curve and clinical impact curve, this predictive nomogram could also help patients obtain significant net benefits.ConclusionWe first demonstrated the metastatic predictive effect of the LIPI on osteosarcoma. This LIPI-based model is useful for clinicians to predict metastasis in osteosarcoma patients and could help conduct timely intervention and facilitate personalized management of osteosarcoma patients.

Abstract 5912: A postpartum breast cancer diagnosis is an independent risk factor for metastasis

Abstract Introduction: A diagnosis of breast cancer after childbirth increases risk for metastasis and death in patients diagnosed at ≤45 years of age [1]. Data to delineate if a postpartum diagnosis is an independent risk factor for breast cancer metastasis remain limited. Here, we addressed this question using early-onset cases available from the Utah Population Database. Methods: This population-based study includes 2,970 women with stage I-III breast cancer, diagnosed at ≤45 years of age between 1996 and 2017. The primary exposures are nulliparity or time between last childbirth and diagnosis of breast cancer. Primary outcomes are distant metastasis and breast cancer-specific death. The Cox proportional hazard model was used to investigate associations between exposures and outcomes adjusting for diagnosis year, age, tumor stage and estrogen receptor (ER) status. Stratified analyses were conducted. Results: Reproductive histories of the breast cancer patients were grouped as nulliparous (n=860), and parous: diagnosed 0-&amp;lt;5 years (n=614), 5-&amp;lt;10 years (n=615) and ≥10 years (n=881) since last childbirth. Through multivariate analyses, we find a breast cancer diagnosis within 5 years postpartum associates with elevated risk for metastasis [(HR)(95%CI)]=1.5(1.2-2.0)] and breast cancer-specific death [HR(95%CI)=1.5(1.1-2.1)] compared to nulliparous cases. Further, for stage I or II cancers that classically have good prognoses, a postpartum diagnosis (0-&amp;lt;5 years) is a dominant feature of increased risk for metastasis [HR(95% CI)]=[1.9 (1.2-2.8)], particularly liver metastasis, and a 2 fold increase in probability of death [HR(95% CI)]=[2.0 (1.2-3.2)]. For women diagnosed with poor prognostic ER- breast cancer, the probability of dying in 0-&amp;lt;5 yrs postpartum group is also ~2 fold compared to nulliparous cases [HR(95% CI)]=[2.3 (1.3-4.1)]. ER+ cases diagnosed 0-&amp;lt;5 yrs postpartum trended towards poor outcomes with marginal significance. Unexpectedly, the proportion of patients progressing to metastasis was the same for ER+ and ER- disease, at 13.2% and 13.5% respectively, with ~3 fold more deaths in women diagnosed with ER+ breast cancer due to increased incidence. Further, we find increased liver metastasis in ER+ patients diagnosed &amp;lt;5 years postpartum, with a full 46% of women who progressed to metastasis having liver as first site of metastasis. Conclusion: This study shows a postpartum diagnosis as an independent risk factor for breast cancer progression and implicates a birth-interval-associated liver biology in the increased liver metastasis observed in this study. Irrespective of ER status, clinical consideration of time between last completed pregnancy and breast cancer diagnosis will increase accuracy of prognosis in young-onset breast cancer patients. 1.Nichols, H.B., et al., Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies. Ann Intern Med, 2018. Citation Format: Zhenzhen Zhang, Solange Bassale, Sonali Jindal, Emily Guinto, Alison Fraser, Tomi Mori, Ken R. Smith, Pepper Schedin. A postpartum breast cancer diagnosis is an independent risk factor for metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5912.

Treatment results and patient characeristics for breast cancer patients older than 70 Years

Objective: The incidence of breast cancer (BC) subtypes varies according to age, and its treatment is more strenuous and requires much more attention in advanced ages. The aim of this study is to investigate patient characteristics and treatment results respectively for patients older than 70 years. Materials and Methods: In this study, we examined 188 elderly BC patients treated in our hospital, at March 2008 - November 2019. Patient characteristics and demographics were investigated from patients’ files retrospectively. Results: Mean age of the patients was 74.3 ± 4 years (All female). The presence of comorbid diseases was 76.1%. Major histology was invasive ductal carcinoma in 72.9% and mostly grade 2 differentiated, and the majority of patients were T2 size (58.5%). Oestrogen receptor (OR) positivity was seen in 83%, Progesterone receptor (PR) positivity in 72.3% of patients and cerb2 positivity in 16.5%. Luminal B (47.9%) was the most common in molecular subgroup analysis. Patients with lymph node involvement (N1 33%; N2, 19.1%; N3, 6.9%) were higher than those without involvement (34%). Surgery type was modified radical mastectomy (MRM) for 51.6%, breast conserving surgery (BCS) for 39.4 % and lumpectomy for 7.4%. In a median follow-up time was 53.9 (9-101) months, local recurrence was seen in 5 (2.7%) patients and distant metastasis was developed in 16 (8.5%) patients. The median overall survival was worse in those with MRM than those with BSC (p=0.006). In multivariate logistic regression analysis, only found that lymph node positivity was an independent risk factor for metastasis (HR; 4.15, 95% CI:1.019-16.933, P=0.047). Conclusion: While it was observed that the most important risk factor for metastasis risk in elderly patients was lymph node positivity; The hormonal status and her2 conditions were not affected in terms of metastasis. It was thought that tumor clinical course and relapse may differ in the elderly population compared to general BC patients.

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.

Suprapancreatic nodal dissection should not be uniformly selected in additional gastrectomy for the patients who diagnosed as pT1b gastric cancer by endoscopic resection

BackgroundSurgery for T1b gastric cancer requires suprapancreatic nodes (SPA nodes) and perigastric nodes (PG nodes), however, SPA nodal dissection can cause pancreatic complications. If endoscopic treatment followed by additional surgery is planned, it may be possible to predict SPA nodal metastasis by analyzing the pathological information of the primary tumor in addition to the clinical findings. MethodsPatients who underwent D1+ or D2 and who were pathologically diagnosed with pT1b were retrospectively analyzed. The stations were divided into the nodes located at the perigastric area (PG nodes; #1–7) and the nodes located at the suprapancreatic area (SPA nodes; #8a-12a). The patients were classified into those with and without metastasis to the SPA nodes. Clinicopathological factors were investigated for their possible association with metastasis to the SPA nodes. ResultsA total of 2017 patients were examined in this study. Metastasis to the SPA nodes was observed in 80 patients (4%). In a multivariate analysis, undifferentiated histology, lower third, and lymphovascular invasion were independent risk factors for metastasis to the SPA nodes. The risk of metastasis to the SPA nodes was <2% in upper/middle tumors of differentiated type with no lymphovascular invasion and in lower tumors of undifferentiated type with no lymphovascular invasion. On the other hand, the risk of metastasis to the SPA nodes was >10% in lower tumors of undifferentiated type with lymphovascular invasion. ConclusionSPA nodal metastasis can be predicted when endoscopic treatment is initially planned. SPA nodal dissection should not be uniformly selected for T1b gastric cancer.

Clinicopathological characteristics and treatment outcomes of luminal B1 breast cancer in Taiwan.

Hormone receptor-positive, human epidermal growth factor receptor II (HER2)-negative luminal B1 breast cancer is associated with a higher risk of disease relapse than luminal A breast cancer. Therefore, we assessed and compared the distant metastasis pattern and clinical outcomes associated with luminal B1 and luminal A breast cancer in an Asian population. In this observational study, we assessed patients with estrogen receptor-positive, HER2-negative breast cancer who underwent surgery from 2009 to 2016. Patients were classified into luminal A or luminal B1 subsets via immunohistochemical analysis. Disease-free survival, post-metastasis survival, and overall survival were estimated; time to disease relapse and patterns of distant metastasis were compared. Risk of relapse and mortality were assessed using Cox proportional hazards model. Patients with luminal B1 breast cancer (n = 677) were significantly younger and had larger tumors and a higher degree of affected axillary lymph nodes, lymphovascular invasion, and tumor necrosis than those with luminal A breast cancer (n = 630). Higher rates of local recurrence and distant metastasis were observed for luminal B1 (both p < 0.05); however, no difference was observed in the specific distant metastatic sites. We observed a significant increase in disease relapse risk in luminal B1 patients compared with that in luminal A (hazard ratio: 2.157, 95% CI: 1.340-3.473, p < 0.05). Patient age, tumor size, stage, lymphovascular invasion, and receiving chemotherapy and hormone therapy were independent risk factors for metastasis and recurrence. Only the luminal B1 subtype (hazard ratio: 5.653, 95% CI: 1.166-27.409, p < 0.05) and stage (hazard ratio: 3.400, 95% CI: 1.512-7.649, p < 0.05) were identified as independent risk factors for post metastatic mortality. Luminal B1 breast cancer has aggressive tumor biology compared with luminal A breast cancer in the follow-up period. However, there was no significant difference in the disease relapse pattern between the groups.

Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.

To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis. We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry. Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2 =18784, p<0.001; χ2 =47.1, p<0.001; χ2 =20, p<0.001). The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.

Expression and Diagnostic Value of tRNA-Derived Fragments Secreted by Extracellular Vesicles in Hypopharyngeal Carcinoma.

ObjectiveTo detect the expression level of tRNA-derived fragments secreted by extracellular vesicles in hypopharyngeal cancer and explore the influence of tRNA-derived fragments on the occurrence of hypopharyngeal cancer and lung metastasis.MethodsAfter high-speed centrifugation, tRNA, which was extracted from the extracellular vesicles of patients with hypopharyngeal cancer and healthy subjects, was sequenced using microarrays. The expression of three differentially expressed tRNAs in hypopharyngeal cancer, healthy subjects, human normal laryngeal epithelial cells and hypopharyngeal cancer line was detected by qRT-PCR. The correlation between the upregulated tRNA, as identified by qRT-PCR, and the clinicopathological features of the non-lung metastatic patients was further analyzed. Finally, the expressions of upregulated tRNA were compared between the non-lung metastatic and lung metastatic patients. The risk factors of hypopharyngeal cancer with lung metastatic were identified by the Cox regression analysis.ResultsBy high-speed centrifugation, extracellular vesicles were extracted successfully. It was found that a variety of tRNAs in the extracellular vesicles from patients with hypopharyngeal cancer by sequencing. qRT-PCR validation indicated that tRF-1:30-Lys-CTT-1-M2 was significantly overexpressed in hypopharyngeal cancer patients and tumor cells, especially in lung metastatic patients. It was indicated that tRF-1:30-Lys-CTT-1-M2 overexpression was closely related to such pathological features as tumor staging, differentiation grade, smoking history and drinking history. According to the Cox regression analysis, stage III–IV, smoking history, drinking history and tRF-1:30-Lys-CTT-1-M2 overexpression were independent risk factors for metastasis of hypopharyngeal cancer.ConclusiontRF-1:30-Lys-CTT-1-M2 was overexpressed in patients with hypopharyngeal cancer and was identified as an independent risk factor for lung metastasis. It can be used as a novel biomarker for the diagnosis and lung metastasis monitoring of hypopharyngeal cancer.

Sonographic predictors of aggressive behavior in medullary thyroid carcinomas

ObjectiveTo identify the clinical and sonographic risk factors for aggressive behavior of Medullary Thyroid Carcinomas (MTCs). Material and methodsThis is a retrospective analysis. The informed consents were waived. Totally, 127 patients were selected from the database. Two radiologists were invited to review the clinical records and ultrasonic images and scored all the cases according to ACR TI-RADS, retrospectively. Kappa test was used to evaluate the consistency between the two reviewers. Logistic regression analysis was carried to identify the risk factors for aggressive behaviors of MTCs. Comparison of survival proportions between different groups were calculated by Kaplan–Meier method and log-rank test. ResultsFemale patients with MTCs were more commonly seen than male (1.7:1), male sex was a risk factor for both metastasis (OR: 4.471, P = 0.001) and perithyroidal invasion (OR = 4.674, P = 0.004). Consistency between the two reviewers were quite high (K value, 0.797–0.988). On sonograms, typical MTCs manifest as hypoechoic (96.9%) solid nodules (94.5%). Sex of patients (P = 0.001), margin (P = 0.003) and focality (P = 0.01) of the nodule were independent risk factors for metastasis, whereas sex of the patients (P = 0.004) and margin (P = 0.000) were independent risk factors for perithyroidal invasion. By Kaplan–Meier analysis, survival proportions different between groups with/without perithyroidal extension (P = 0.000) but not between groups with/without metastasis (P = 0.473). ConclusionHigh frequency ultrasound and TI-RADS were effective methods for preoperative diagnosis of MTC. Sex of the patients and margin of the nodule are common risk factors for both metastasis and perithyroidal invasion. Focality of the tumor is another independent risk factor for metastasis.

BCL6B hypermethylation predicts metastasis and poor prognosis in early-stage hepatocellular carcinoma after thermal ablation.

The aim of this study was to evaluate the role of BCL6B methylation in the progression of early-stage hepatocellular carcinoma (HCC) after thermal ablation. This is a retrospective study and written informed consent was obtained from all patients or their legal guardians. Between October 2008 and December 2013, 73 patients with early-stage HCC within the Milan criteria, who received thermal ablation, were recruited. Based on methylation-specific polymerase chain reaction, the relationship between BCL6B methylation and patient characteristics and prognosis was analyzed using univariate, multivariate, and Kaplan-Meier analysis. The median follow-up period was 56 (8-110) months. For the BCL6B unmethylated group, the 1-, 3- and 5-year metastasis and overall survival (OS) rates after thermal ablation were 10.0%, 10.0%, and 40.0% and 100%, 100% and 90.0%, respectively. The 1-, 3-, and 5-year metastasis and OS rates of the methylated group were 23.8%, 66.7% and 88.9% and 66.2%, 71.4% and 41.3%, respectively. Levels of absolute count lymphocyte, serum cholinesterase and albumin in the BCL6B unmethylated group were higher than those in the methylated group (P = 0.020, 0.000, and 0.009, respectively). Kaplan-Meier analysis revealed that BCL6B methylation was related to metastasis and poor prognosis (P = 0.001 and 0.018, respectively). Univariate analysis revealed that BCL6B methylation was a risk factor for metastasis and poor prognosis (odds ratio [OR]: 5.663; 95% confidence interval [CI], 1.745-18.375, P = 0.004 and OR: 3.734; 95% CI, 1.151-12.110, P = 0.028, respectively). Multivariate analysis revealed that BCL6B methylation was an independent risk factor for metastasis (OR: 3.736; 95% CI, 1.000-13.963,P = 0.05) and not for prognosis (OR: 2.780; 95% CI, 0.835-9.250,P = 0.096). BCL6B methylation could be a valuable prognostic factor for metastasis and poor prognosis in early-stage HCC after thermal ablation, which is an independent risk factor for metastasis. Our findings provide insights for combining ablation and epigenetic therapy for patients with HCC.

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.

Early ultrasonographic tumor regression after linear accelerator stereotactic fractionated photon radiotherapy of choroidal melanoma as a predictor for metastatic spread

Background and purposeDuring extended follow-up (of up to 15 years), approximately fifty percent of patients with choroidal melanoma will develop metastatic disease and eventually die. Thus, continuing research on prognostic factors, early detection and treatment is necessary. Height regression rates both after plaque brachytherapy and proton beam irradiation have been shown to have prognostic value. The purpose of this study was to analyze the influence of early tumor regression rate after treatment of choroidal melanoma with LINAC stereotactic fractionated radiotherapy (SFRT) as an independent risk factor for metastasis. Material and methods256 patients with choroidal melanoma treated with LINAC SFRT were included. Follow-up included standardized echography yielding apical height, smallest and largest basal linear diameter, tumor volume and mean reflectivity. The influence of baseline measurements and of a longitudinal, normalized area under the curve coefficient (NAC) of the latter marker on metastasis risk was assessed. ResultsNAC for tumor thickness at months 3, 6, and 12 had a statistically significant (p < 0.001) non-linear effect on risk of metastasis. Additionally, ultrasonographic baseline tumor dimensions, but not internal reflectivity were found to be statistically significant risk factors for metastasis. ConclusionsOur results demonstrate a non-linear influence of regression rate of choroidal melanoma as independent risk factor of metastatic disease after LINAC SFRT. These prove the clinical experience that, in comparison to rather slow regressions, very quick and very slow early tumor responses to LINAC SFRT are associated with a significantly higher metastasis risk.

TMEM45B is a novel predictive biomarker for prostate cancer progression and metastasis.

It is urgently needed to explore the clinical relevance of TMEM45B expression and Prostate cancer(PCa), and determine the predictive significance of TMEM45B as a biomarker for PCa patients.Patient-derived xenograft (PDX) model of PCa with different metastatic potential (LTL-418, LTL-313B, LTL-313H and LTL-331) were developed. The gene expression microarray of LTL-313H and LTL-313B, which derived from a single PCa patient, was performed to identify the candidate biomarker gene, TMRM45B. MSKCC and TCGA PCa patient cohorts were introduced to analyzed the clinical significance of TMEM45B expression. Quantitative Real-Time PCR (qRT-PCR) revealed that there was a significant increase of TMEM45B expression in high metastatic potential tumor lines LTL-313H and LTL-331 compared with the other two low metastatic potential tumor lines(LTL-418, LTL-313B). In MSKCC PCa cohort, the mRNA level of TMEM45B in patients with metastasis was significantly higher than that in primary PCa (P=0.001) and begin prostate hyperplasia (BPH) patients (P<0.001). In addition, the increased TMEM45B expression was positively related with a higher possibility of biochemical recurrence (P=0.016), distant metastasis occurrence(P<0.001) and overall patient survival (P=0.07). Moreover, TMEM45B expression was considered as an independent risk factor for metastasis of PCa based on multivariate logistic regression. Kaplan-Meier analysis showed that patients with elevated TMEM45B had a shorter biochemical recurrence free survival (RFS). For primary PCa patients, subgroup analysis showed that there was a significant association between TMEM45B expression and clinical features in primary PCa cohort. Meanwhile, cases with elevated TMEM45B were more likely to develop metastasis compared to the normal group among N0 primary PCa patients (P=0.010). Primary PCa patient cohort TCGA was used to validate the results, and an obvious relationship was found between TMEM45B and clinical characteristic of PCa (T/N stage, Gleason score, Recurrence / Progress). Furthermore, a significant poor disease free survival (DFS) was investigated in high-level of TMEM45B patients compared with the other remaining cases (P=0.007). Taken together, the increased expression of TMEM45B appears to be significantly associated with prostate carcinoma progression and metastasis which provide a new prognostic biomarker for predicting metastatic potential of PCa patients, especially for primary PCa.