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Typical Pulmonary Carcinoid (TPC) is defined by its slow growth, frequently necessitating surgical intervention. Despite this, the long-term outcomes following tumor resection are not well understood. This study examined the factors impacting Overall Survival (OS) in patients with TPC, leveraging data from the Surveillance, Epidemiology, and End Results database spanning from 2000 to 2018. We employed Lasso-Cox analysis to identify prognostic features and developed various models using Random Forest, XGBoost, and Cox regression algorithms. Subsequently, we assessed model performance using metrics such as Area Under the Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA). Among the 2687 patients, we identified five clinical features significantly affecting OS. Notably, the Random Forest model exhibited strong performance, achieving 5- and 7-year AUC values of 0.744/0.757 in the training set and 0.715/0.740 in the validation set, respectively, outperforming other models. Additionally, we developed a web-based platform aimed at facilitating easy access to the model. This study presents a machine learning model and a web-based support system for healthcare professionals, assisting in personalized treatment decisions for patients with TPC post-tumor resection. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 70–80% of patients with epithelial ovarian cancer (OC) experience peritoneal metastasis. Identification of mesothelial-to-mesenchymal transition (MMT) in the peritoneum may guide the accurate treatment and follow-up of patients with advanced OC. The aim of this study was to evaluate whether MMT took place in primary OC biopsies. We suggest the identified mesothelial-derived carcinoma-associated fibroblasts in primary tumors could impact the clinical progression of patients with OC. Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread. [ABSTRACT FROM AUTHOR]

Objective: When the clinical presentation is related to the metastatic mass and a radiologically solitary tumor focus is detected, especially in cases where clinical information is not taken into account or is insufficient, if a possible metastatic neoplasia is not kept in mind then it is possible to evaluate the tumor as a primary breast neoplasm. In this study, it is aimed to present our cases of non-hematopoietic metastatic neoplasms and to evaluate the clinicopathological features that may aid in distinguishing metastatic from primary neoplasms. Material and Methods: This study includes cases diagnosed with metastatic non-hematopoietic breast neoplasm in breast resection materials in our center, between the years 2010–2023. All cases were analyzed retrospectively by evaluating clinicopathological features. Results: Of the 15 subjects included in the study, 11 (73%) were female and 4 (27%) were male. The mean age of the patients were 46.9 ranged from 22 to 63 years. The most frequent metastatic malignancy was carcinoma (60%), followed by melanoma (33%) and sarcoma (7%). Of the 9 patients with metastatic carcinoma, the primary tumor originated from the lungs in 4, from gastrointestinal system in 2, female genital tract in 2, and kidney in 1 patient. Sarcoma diagnosis was given in a single patient and the histology was a leiomyosarcoma originating from kidney. Conclusion: A careful histomorphological and immunohistochemical evaluation and a detailed examination of the clinicoradiological data are critical to establish the right course in patient management, treatment plan and to correctly predict the prognosis. [ABSTRACT FROM AUTHOR]

Yuqing Bu,1,* Junye Wen,2,* Fayan Wang,1,3 Shibo Dong,4 Liya He,1 Yang Li,1,5 Jinlong Liang,1,3 Hongzhen Zhang1,3,5 1Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 3Department of Medicine, Hebei North University, Zhangjiakou, Hebei Province, 075000, People’s Republic of China; 4Department of Imaging, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 5Department of Medicine, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongzhen Zhang, Email hongzhenzhang456@sohu.comAbstract: This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII–VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII–VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient’s survival time was 16 months.Keywords: synchronous tumor, liver tumor, primary tumor, small cell neuroendocrine carcinoma, hepatocellular carcinoma

Simple Summary: Rhabdoid meningiomas are a rare subtype of (per definition) grade 3 meningiomas of unknown cause, with a heterogeneous clinical course and higher recurrence rates, even among tumors undergoing complete surgical removal, for whom early postoperative radiotherapy may favor local control of the disease and prolonged survival. Here, we compared the clinical, biological and genetic features (at diagnosis and in sequential tumor recurrences) of recurrent vs. non-recurrent rhabdoid meningiomas in a retrospective series of 15 patients with a long follow-up. Recurrent RM showed a higher genetic instability at diagnosis associated with multiple chromosomal losses involving chromosomes 1p, 14q, 18 and 22. Non-recurrent RM were genetically less complex tumors which more frequently showed extensive losses at chromosome 19p and/or 19q, together with gains of chromosomes 20 and 21. Comparison of paired primary vs. recurrent tumor samples of recurrent RM revealed additional losses of chromosomes 16q and 19p, together with gains of chromosomes 1q and 17q. Of note, focal chromosome gains at 17q22 were exclusively found in women with recurrent RM who died, although survival differences did not reach statistical significance. Rhabdoid meningiomas (RM) are a rare meningioma subtype with a heterogeneous clinical course which is more frequently associated with recurrence, even among tumors undergoing-complete surgical removal. Here, we retrospectively analyzed the clinical-histopathological and cytogenetic features of 29 tumors, from patients with recurrent (seven primary and 14 recurrent tumors) vs. non-recurrent RM (n = 8). Recurrent RM showed one (29%), two (29%) or three (42%) recurrences. BAP1 loss of expression was found in one third of all RM at diagnosis and increased to 100% in subsequent tumor recurrences. Despite both recurrent and non-recurrent RM shared chromosome 22 losses, non-recurrent tumors more frequently displayed extensive losses of chromosome 19p (62%) and/or 19q (50%), together with gains of chromosomes 20 and 21 (38%, respectively), whereas recurrent RM (at diagnosis) displayed more complex genotypic profiles with extensive losses of chromosomes 1p, 14q, 18p, 18q (67% each) and 21p (50%), together with focal gains at chromosome 17q22 (67%). Compared to paired primary tumors, recurrent RM samples revealed additional losses at chromosomes 16q and 19p (50% each), together with gains at chromosomes 1q and 17q in most recurrent tumors (67%, each). All deceased recurrent RM patients corresponded to women with chromosome 17q gains, although no statistical significant differences were found vs. the other RM patients. [ABSTRACT FROM AUTHOR]

Background: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. Methods: A total of 30 ESCC patients with lymph node positive (IIB‐IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551‐tumor‐targeted DNA sequencing and 289‐immuno‐oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. Results: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One‐year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse‐free survival (univariate, HR: 5.39, 95% CI: 1.67–17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79–30.23, p = 0.006). Transcriptomic results showed non‐relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN‐α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF‐α/NF‐κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). Conclusion: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes‐positive ESCC. [ABSTRACT FROM AUTHOR]

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Venous thromboembolism and postoperative bleeding are complications of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this systematic review was to summarize current knowledge on the effect of cytoreductive surgery with HIPEC on coagulation and fibrinolysis within 10 days after surgery. Studies were identified in PubMed, Embase, and Web of Science on December 12, 2022. Data on biomarkers of coagulation and fibrinolysis measured preoperatively up to the 10th postoperative day were extracted. Among 15 included studies, 13 studies reported markers of primary hemostasis. Eleven studies found reduced platelet count following cytoreductive surgery with HIPEC and two studies reported reduced platelet function. Twelve studies reported impaired secondary hemostasis until postoperative day 10 indicated by prolonged international normalized ratio, prothrombin time, and activated partial thromboplastin time. Fibrinogen was decreased in three studies from preoperative to postoperative day 3 switching to increased levels until postoperative day 10. In accordance, three studies found reduced maximum amplitude and maximum clot firmness by thromboelastography/thromboelastometry (ROTEM/TEG) on the first postoperative day indicating impaired clot strength. Four studies demonstrated increased d-dimer, factor (F) VIII, and thrombin generation during the 10 postoperative days. Four studies investigated fibrinolysis by ROTEM/TEG and plasminogen activator inhibitor-1 (PAI-1) after cytoreductive surgery with HIPEC reporting contradictive results. In conclusion, a decrease in platelet count and subtle changes in secondary hemostasis were found following cytoreductive surgery with HIPEC. Data on the effect of cytoreductive surgery with HIPEC on fibrinolysis are sparse and this needs to be further investigated. [ABSTRACT FROM AUTHOR]

Background: The optimal surgical technique for managing external ear melanoma and its corresponding prognosis remain areas lacking comprehensive data. In this retrospective study were patients treated with a cartilage-sparing excision of melanoma of the external ear. The primary objectives are to evaluate local control rates, overall survival, and disease-specific survival. Methods: After conducting a structured review encompassing surgical methodologies and survival rates, a clinical retrospective analysis was undertaken involving patients treated from 2011 to 2022. The treatment approach across all cases involved cartilage-sparing resection followed by wound closure utilizing primary closure or split/full-thickness skin grafting for reconstruction. Statistical analysis was conducted employing the Kaplan–Meier survival analysis. Results: Superficial spreading melanoma represents the predominant histological subtype observed. In all cases, patients underwent cartilagesparing resection of the tumor. Among them, 9 patients underwent simultaneous sentinel lymph node biopsy during resection, all of which yielded negative results. Subsequent to treatment, 1 patient experienced local recurrence after 9 months, while another presented with locoregional recurrence in a lymph node after 15 months. No instances of distant metastasis were recorded within the patient cohort. The local control rate was 92.86%, the overall survival 100% and the disease-specific survival 100%. The average follow-up was 41 months. Conclusion: The outcomes regarding local control rate, overall survival, and disease-specific survival underscore the efficacy of cartilage-sparing resection as a viable treatment modality, particularly for early-stage melanoma cases. These results not only highlight the significance of achieving tumor-free margins but also emphasize the importance of attaining aesthetically satisfactory outcomes. Consequently, cartilage-sparing resection emerges as an acceptable therapeutic approach for managing melanoma of the external ear, offering promising prospects for patients in terms of both medical and cosmetic considerations [ABSTRACT FROM AUTHOR]

Abstract Objective Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment. Methods We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC–MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison. Results We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor. Conclusion We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.

Objective: Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment. Methods: We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC–MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison. Results: We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor. Conclusion: We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases. [ABSTRACT FROM AUTHOR]

Abstract Background The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. Methods A total of 30 ESCC patients with lymph node positive (IIB‐IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551‐tumor‐targeted DNA sequencing and 289‐immuno‐oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. Results The primary tumors exhibited a higher mutation burden than lymph nodes (p

Background. Breast cancer ranks first in the structure of cancer morbidity and mortality. Involvement of a large number of regional lymph nodes is considered a poor prognostic outcome. The mechanisms of development of lymphogenous metastasis in general and common in particular are not fully understood. Integrins are involved in the metastatic process by mediating tumor cell invasion and adhesion to vascular endothelium. Aim. To study the role of integrins in lymphogenous metastasis. Materials and methods. The study included 72 patients diagnosed with invasive breast carcinoma of no special type who underwent surgical treatment on the basis of the cancer research institute national research medical center. The average age reached 51.2 years. In accordance with the indications and morphological data, the patients underwent antitumor treatment. The tissue of the primary tumor obtained by trepanbiopsy. Histological and immunohistochemical examination was carried out according to the standard method. In primary tumor cells, the presence or absence of cytoplasmic or membrane/cytoplasmic colocalization of CD61 (Integrin beta 3), CD104 (Integrin beta 4), CD51 (Integrin alpha-V) expression was assessed. When statistically processing the results, Fisher's test and one-way regression analysis were used. Results. In the N3 group, the frequency of cytoplasmic expression of CD 61 was higher at the trend level (40.9 and 18%; p=0.074). In the group of patients with N3, positive cytoplasmic expression of CD104 (37.5 and 15.0%; p=0.029) and membrane and cytoplasmic colocalization (52.6 and 15.1%; p=0.004) were more often detected. In the group with N1 and N2, membrane and cytoplasmic colocalization of CD104 expression was less common (15.8 and 54.7%; p=0.006). When studying the expression frequency of CD51 integrin, no significant differences were found depending on the severity of lymphogenous metastasis. Conclusion. Expression of CD104 in primary tumor cells is strongly associated with widespread lymphogenous metastasis. Studies of the role of integrins in the development of lymphogenous metastasis are promising for predicting the prevalence of this process in the preoperative period and for searching for methods of influencing the tumor.

Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread.

Simple Summary: Uveal melanoma (UM) is the most common eye tumor in adults. It is associated with dismal survival once metastasized. The treatment landscape has changed over the last years for the primary tumor, and new therapeutic options are being investigated for metastatic UM. However, it remains unclear if patients diagnosed in recent decades have a better survival compared to patients diagnosed in earlier decades. In this study, we use national data from patients diagnosed in the Netherlands between 1989 and 2019. We show that survival improvement was not related to the period of diagnosis but related to the treatment of the eye tumor with radiotherapy (for overall survival and cancer-specific survival) and female gender (for overall survival). Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. Methods: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants' cause of death. Two time periods (1989–2004, 2005–2019) were compared with descriptive statistics. Kaplan–Meier and (multivariate) Cox proportional hazard models were used to assess changes over time for overall survival (OS) and cancer-specific survival (CSS). Results: In total, 5036 patients were analyzed with a median age of 64.0 years at the time of diagnosis. The number of patients increased over time. In the first (1989–2004) and second (2005–2019) period, 32% versus 54% of the patients received radiotherapy (p < 0.001). The median FU time was 13.4 years. The median OS of the first and second periods was 9.5 (95% CI 8.7–10.3) versus 11.3 years (95% CI 10.3–12.3; p < 0.001). The median CSS was 30.0 years (95% CI NA) in the first period and not reached in the second period (p = 0.008). In multivariate analysis (MVA), female gender (HR 0.85; 95% CI 0.79–0.92, p < 0.001) and radiotherapy treatment (HR 0.73; 95% CI 0.64–0.83, p < 0.001) were associated with better OS. Radiotherapy treatment (HR 0.74; 95% CI 0.61–0.90, p = 0.002) was also associated with better CSS. The period of diagnosis was not associated with OS or CSS. Conclusions: In this study of patients with primary UM, there was a shift to the diagnosis of smaller tumors, possibly due to stage migration. There was also an increase in eye-preserving treatments over time. OS and CSS were modestly improved in the second time period; however, the time period was not associated with OS or CSS in multivariate analyses. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a humanized anti-carcinoembryonic antigen monoclonal antibody conjugated to a PEGylated near-infrared dye, that targets and brightly labels human CRC tumors in metastatic orthotopic mouse models. The hT84.66-M5A (M5A) monoclonal antibody was conjugated with a polyethylene glycol (PEG) chain that incorporated a near infrared (NIR) IR800 dye to establish M5A-IR800 Sidewinder (M5A-IR800-SW). Nude mice with CRC orthotopic primary tumors and liver metastasis both developed from a human CRC cell line, were injected with M5A-IR800-SW and imaged with the Pearl Trilogy Imaging System. M5A-IR800-SW targeted and brightly labeled CRC tumors, both in primary-tumor and liver-metastasis models. M5A-IR800-SW at 75 μg exhibited highly-specific tumor labeling in a primary-tumor orthotopic model with a median tumor-to-background ratio of 9.77 and in a liver-metastasis orthotopic model with a median tumor-to-background ratio of 7.23 at 96 h. The precise labeling of the liver metastasis was due to lack of hepatic accumulation of M5A-IR800-SW in the liver. M5A-IR800-SW provided bright and targeted NIR images of human CRC in orthotopic primary-tumor and liver-metastasis mouse models. The results of the present study suggest the clinical potential of M5A-IR800-SW for fluorescence-guided surgery including metastasectomies for CRC. The lack of hepatic NIR signal is of critical importance to allow for precise labeling of liver tumors. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis (BM) is a serious neurological complication of cancer of different origins. The value of deep learning (DL) to identify multiple types of primary origins remains unclear. Purpose: To distinguish primary site of BM and identify the best DL models. Study Type: Retrospective. Population: A total of 449 BM derived from 214 patients (49.5% for female, mean age 58 years) (100 from small cell lung cancer [SCLC], 125 from non‐small cell lung cancer [NSCLC], 116 from breast cancer [BC], and 108 from gastrointestinal cancer [GIC]) were included. Field Strength/Sequence: A 3‐T, T1 turbo spin echo (T1‐TSE), T2‐TSE, T2FLAIR‐TSE, DWI echo‐planar imaging (DWI‐EPI) and contrast‐enhanced T1‐TSE (CE T1‐TSE). Assessment: Lesions were divided into training (n = 285, 153 patients), testing (n = 122, 93 patients), and independent testing cohorts (n = 42, 34 patients). Three‐dimensional residual network (3D‐ResNet), named 3D ResNet6 and 3D ResNet 18, was proposed for identifying the four origins based on single MRI and combined MRI (T1WI + T2‐FLAIR + DWI, CE‐T1WI + DWI, CE‐T1WI + T2WI + DWI). DL model was used to distinguish lung cancer from non‐lung cancer; then SCLC vs. NSCLC for lung cancer classification and BC vs. GIC for non‐lung cancer classification was performed. A subjective visual analysis was implemented and compared with DL models. Gradient‐weighted class activation mapping (Grad‐CAM) was used to visualize the model by heatmaps. Statistical Tests: The area under the receiver operating characteristics curve (AUC) assess each classification performance. Results: 3D ResNet18 with Grad‐CAM and AIC showed better performance than 3DResNet6, 3DResNet18 and the radiologist for distinguishing lung cancer from non‐lung cancer, SCLC from NSCLC, and BC from GIC. For single MRI sequence, T1WI, DWI, and CE‐T1WI performed best for lung cancer vs. non‐lung cancer, SCLC vs. NSCLC, and BC vs. GIC classifications. The AUC ranged from 0.675 to 0.876 and from 0.684 to 0.800 regarding the testing and independent testing datasets, respectively. For combined MRI sequences, the combination of CE‐T1WI + T2WI + DWI performed better for BC vs. GIC (AUCs of 0.788 and 0.848 on testing and independent testing datasets, respectively), while the combined MRI approach (T1WI + T2‐FLAIR + DWI, CE‐T1WI + DWI) could not achieve higher AUCs for lung cancer vs. non‐lung cancer, SCLC vs. NSCLC. Grad‐CAM helped for model visualization by heatmaps that focused on tumor regions. Data Conclusion: DL models may help to distinguish the origins of BM based on MRI data. Evidence Level: 3 Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have revealed that primary tumor resection (PTR) surgery could improve prognosis in some solid tumors. Thus, we aimed to investigate whether patients with stage IVB cervical carcinoma can benefit from PTR surgery and who can benefit. Methods: We extracted and obtained data on patients with stage IVB cervical carcinoma from the SEER database from 2010 to 2017 and classified them into two groups: the surgery and the non-surgery group. The overall survival (OS) and cancer-specific survival (CSS) of the two groups were compared before and after propensity score matching (PSM). The independent prognostic variables were identified using univariate and multivariate Cox regression analyses. Then, the model was established to select the optimal patients to receive PTR surgery using multivariate logistic regression. Results: After PSM, the study included 476 cervical carcinoma (stage IVB) patients, of whom 238 underwent PTR surgery. Compared to the non-surgery group, the surgery group's median OS and median CSS were both longer (median OS: 27 months vs. 13 months, P < 0.001; median CSS: 52 months vs. 21 months, P < 0.001). The model showed no organ metastasis, adenocarcinoma, G1/2, and chemotherapy were more supportive of performing PTR surgery. The calibration curves and DCA showed that the model had high predictive accuracy and excellent clinical applicability. Finally, the "surgery benefit" group had the OS that was approximately four times better than "surgery non-benefit" group. Conclusion: PTR surgery can potentially improve the prognosis of patients with cervical carcinoma at stage IVB. The model could probably select optimal candidates and provide a new perspective on individualized treatment. [ABSTRACT FROM AUTHOR]

Background and goals: Gastric outlet obstruction (GOO) usually occurs at the pylorus or the duodenum through primary gastric, duodenal, or pancreatic tumors. However, metastatic GOO is relatively rare. Although self-expandable metal stent (SEMS) placement is often performed as an alternative and practical palliative approach for primary GOO, there are few reports of metastatic GOO treatment with SEMS. This study aimed to investigate the efficacy, safety, stent patency, and complications of SEMS for treating primary and metastatic GOO. Methods: The data of 42 patients with GOO who received SEMS from November 2016 to April 2022 were reviewed retrospectively. Patients were divided into primary group (n = 25) and metastatic group (n = 17) according to the cause of GOO. The rates of technical and clinical success, stent patency, and complications were compared between the two groups. Results: The overall technical and clinical success rates were 97.9% and 93.5%, respectively. The total SEMS implantation time was 48.2 ± 33.5 (10.0–140.0) minutes. The primary technical success rate was 100.0% in both primary and metastatic groups, and the primary clinical success rate was 96.0% (24/25) in the primary group vs 88.2% (15/17) in the metastatic group (P = 0.350). After reintervention, the secondary technical success rate was 100.0% (27/27) in the primary group vs 95.0% (19/20) in the metastatic group (P = 0.330); and the secondary clinical success rate was 96.3% (26/27) in the primary group vs 89.5% (17/19) in the metastatic group (P = 0.367). No serious complications, such as gastrointestinal perforation, stent migration, bleeding, or aspiration pneumonia, were observed in these patients. Conclusions: SEMS under fluoroscopic guidance is an effective and safe treatment for primary and metastatic GOO. The etiology of obstruction did not influence stent patency or complications. Therefore, stent implantation is recommended for patients with metastatic GOO caused by multiple peritoneal metastases to improve their quality of life. [ABSTRACT FROM AUTHOR]

Rhabdoid meningiomas (RM) are a rare meningioma subtype with a heterogeneous clinical course which is more frequently associated with recurrence, even among tumors undergoing-complete surgical removal. Here, we retrospectively analyzed the clinical-histopathological and cytogenetic features of 29 tumors, from patients with recurrent (seven primary and 14 recurrent tumors) vs. non-recurrent RM (n = 8). Recurrent RM showed one (29%), two (29%) or three (42%) recurrences. BAP1 loss of expression was found in one third of all RM at diagnosis and increased to 100% in subsequent tumor recurrences. Despite both recurrent and non-recurrent RM shared chromosome 22 losses, non-recurrent tumors more frequently displayed extensive losses of chromosome 19p (62%) and/or 19q (50%), together with gains of chromosomes 20 and 21 (38%, respectively), whereas recurrent RM (at diagnosis) displayed more complex genotypic profiles with extensive losses of chromosomes 1p, 14q, 18p, 18q (67% each) and 21p (50%), together with focal gains at chromosome 17q22 (67%). Compared to paired primary tumors, recurrent RM samples revealed additional losses at chromosomes 16q and 19p (50% each), together with gains at chromosomes 1q and 17q in most recurrent tumors (67%, each). All deceased recurrent RM patients corresponded to women with chromosome 17q gains, although no statistical significant differences were found vs. the other RM patients.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3–130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa. [ABSTRACT FROM AUTHOR]

Simple Summary: In de novo metastatic luminal breast cancer, there remains an urgent need to fill the knowledge gap about which molecular mechanisms drive de novo metastatic disease. This study is the first to explore the transcriptomic profile and tumor microenvironmental differences at baseline of patients with ER+/HER2− de novo metastatic luminal breast cancer compared to patients with early (non-metastatic) luminal breast cancer to determine which aspects of the tumor microenvironment of de novo luminal breast cancer are altered and obtain perspective of the molecular mechanisms underlying breast cancer metastasis. Background: The molecular mechanisms underlying the de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials and Methods: Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/−, HER2−), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical–pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n = 32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 × 10 µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR; deconvolution was performed using CIBERSORTx to assess immune cell fractions. A paired Wilcoxon test was used to compare dnMBC and eBC groups and corrected for the false discovery rate. Results: Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that the CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusions: Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Microwave ablation (MWA) is becoming an effective therapy for inoperable pulmonary metastases from colorectal cancer (CRC). However, it is unclear whether the primary tumor location affects survival after MWA. OBJECTIVE: This study aims to investigate the survival outcomes and prognostic factors of MWA based on different primary origins between colon and rectal cancer. METHODS: Patients who underwent MWA for pulmonary metastases from 2014 to 2021 were reviewed. Differences in survival outcomes between colon and rectal cancer were analyzed with the Kaplan-Meier method and log-rank tests. The prognostic factors between groups were then evaluated by univariable and multivariable Cox regression analyses. RESULTS: A total of 118 patients with 154 pulmonary metastases from CRC were treated in 140 MWA sessions. Rectal cancer had a higher proportion with seventy (59.32%) than colon cancer with forty-eight (40.68%). The average maximum diameter of pulmonary metastases from rectal cancer (1.09 cm) was greater than that of colon cancer (0.89 cm; p = 0.026). The median follow-up was 18.53 months (range 1.10 – 60.63 months). The disease-free survival (DFS) and overall survival (OS) in colon and rectal cancer groups were 25.97 vs 11.90 months (p = 0.405), and 60.63 vs 53.87 months (p = 0.149), respectively. Multivariate analyses showed that only age was an independent prognostic factor in patients with rectal cancer (HR = 3.70, 95% CI: 1.28 – 10.72, p = 0.023), while none in colon cancer. CONCLUSIONS: Primary CRC location has no impact on survival for patients with pulmonary metastases after MWA, while a disparate prognostic factor exists between colon and rectal cancer. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of cancer patient mortality. Metastasis suppressors are genes that, upon reexpression in metastatic tumor cells to levels observed in their nonmetastatic counterparts, significantly reduce metastasis without affecting the growth of the primary tumor. Analysis of > 30 metastasis suppressors revealed complex mechanisms of action that include multiple signaling pathways, transcriptional patterns, posttranscriptional regulatory mechanisms, and potential contributions of genomic stability. Clinical testing of strategies to re-establish a validated metastasis suppressor pathway in tumors is best directed to the adjuvant setting, with the goal of inhibiting the outgrowth of occult micrometastases. [ABSTRACT FROM AUTHOR]

Purpose: Compared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa). Methods: A retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3-4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression. Results: The SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS =8, and tPSA >20 ng/ml and GS=8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT. Conclusion: 99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Metastases to the breast (intramammary metastases, IM) from extramammary malignancies (EM) are uncommon. As prognosis is poor, timely diagnosis is key to direct patients towards appropriate treatment. We will review recent literature regarding the epidemiology, presentation, and diagnosis of IM. Recent Findings: IM commonly present as palpable masses, with imaging findings often based on hematogenous versus lymphatic spread. While many IM are diagnosed with a history of EM, IM may also be the first presentation of distant metastatic disease. In most cases, immunohistochemical testing is required to differentiate between primary breast cancer (PBC) and IM. Summary: Recent research, focused on immunohistochemical markers, can guide diagnosticians in differentiating IM from PBCs. Key factors to consider when diagnosing any breast mass include a prior history of cancer, imaging characteristics, histologic findings that are atypical for PBCs, and the immunohistochemical profile of each lesion. [ABSTRACT FROM AUTHOR]

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Tran Manh Hung,1 Thi Phuong Thao Tran2 1Department of Surgery, Bach Mai Hospital, Hanoi, Vietnam; 2Center for Population Health Sciences, Hanoi University of Public Health, Hanoi, VietnamCorrespondence: Tran Manh Hung, Department of Surgery, Bach Mai Hospital, Hanoi, Vietnam, Tel +84-912-157-095, Email tranmanhhungngoaibm@gmail.comPurpose: Hepatic angiosarcoma is very rare malignancy and more common in men than in women. To date, only a few female cases of liver angiosarcoma have been reported. Here, we report a female case of liver angiosarcoma, first detected in Vietnam, with a high malignancy stage, rapid progression, and poor prognosis.Case Presentation: A 61-year-old woman was admitted to the Bach Mai Hospital with fatigue, anorexia, weight loss, and severe pain in the right upper quadrant for 2 weeks prior. Clinical examination detected a firm 4-cm hepatomegaly below the right costal margin and grade I splenomegaly. Abdominal ultrasonography and CT revealed diffuse lesions in the entire liver parenchyma, spreading to the spleen, while MRI showed signs of bone metastasis. Blood tests showed elevated transaminase enzymes, especially Gamma Glutamyl Transferase 501 U/L; thrombocytopenia; no anemia; and other tumor markers such as AFP, CEA, and CA19-9 were within normal limits. On CT images, the dots and nodules in the liver and spleen appeared hyperenhanced in the arterial phase and washout in the venous phase. The results of both histopathology and immunohistochemistry showed liver angiosarcoma. Surgery and radiation were not indicated due to the suspicion of bone metastasis. Chemotherapy with doxorubicin at a dose of 60 mg/m2 and intravenous infusion once every 21 days was administered. Unfortunately, during the first dose of chemotherapy with doxorubicin, side effects appeared. Since the disease developed continuously and uncontrollably, the patient was subsequently exhausted, anemic, presented peritoneal fluid, and eventually died of intra-abdominal bleeding.Conclusion: For the diagnosis of liver angiosarcoma, ultrasound-guided liver biopsy could be applied for safe and effective histopathology, and selective embolization of the hepatic artery is necessary to prevent bleeding complications. The disease has a very poor prognosis, and if chemotherapy does not respond, the patient can die within six months of diagnosis.Keywords: liver angiosarcoma, primary tumor, hepatectomy, case report

Approximately 6% of metastatic breast cancers arise de novo. While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic. [ABSTRACT FROM AUTHOR]

Mutations in tumor suppressor p53 protein can occur at different phases of malignant transformation and affect the patient's prognosis. This study aimed to evaluate the expression of mutant p53 protein in Iranian patients with the primary and recurrence oral squamous cell carcinoma (OSCC). This retrospective cross-sectional study conducted on a group of patients with the primary OSCC (n=122) and the control subjects with oral noncancerous reactive lesions (n=80). Immunohistochemistry was performed with the DO-7 monoclonal antibody against p53 protein, and samples with =10% immunostaining were considered positive. Statistical analyses were carried out using SPSS. Positive staining for p53 was observed in none of the control subjects and 57.4% (70 of 122) of the primary OSCC patients (p<0.0001, OR=107.69, 95%CI=6.49-179.0). The p53 immunopositivity had no significant differences between males and females (54.2% vs. 62%, p=0.390), but significantly different between those aged below and over 50 years (p<0.0001, OR=4.52, 95%CI=1.07-12.05). During followup, OSCC recurrence occurred in 104 patients, but the phenotype of the mutant p53 protein in patients who relapsed was the same as in matched primary tumors (p=0.763). Risk of recurrence had no significant differences between p53-positive and p53-negative cases (p=0.953), males and females (p=0.263), and age below and over 50 years (p=0.223). Despite its confirmed diagnostic value, the immunoexpression of the p53 mutant protein in OSCC in cancer recurrence was the same as in the primary tumor. However, further studies with a larger sample size and longer follow-up are needed to confirm or change our conclusions. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To explore the feasibility of differentiating three predominant metastatic tumor types using lung computed tomography (CT) radiomics features based on supervised machine learning.Materials and Methods: This retrospective analysis included 252 lung metastases (LM) (from 78 patients), which were divided into the training (n = 176) and test (n = 76) cohort randomly. The metastases originated from colorectal cancer (n = 97), breast cancer (n = 87), and renal carcinoma (n = 68). An additional 77 LM (from 35 patients) were used for external validation. All radiomics features were extracted from lung CT using an open-source software called 3D slicer. The least absolute shrinkage and selection operator (LASSO) method selected the optimal radiomics features to build the model. Random forest and support vector machine (SVM) were selected to build three-class and two-class models. The performance of the classification model was evaluated with the area under the receiver operating characteristic curve (AUC) by two strategies: one-versus-rest and one-versus-one.Results: Eight hundred and fifty-one quantitative radiomics features were extracted from lung CT. By LASSO, 23 optimal features were extracted in three-class, and 25, 29, and 35 features in two-class for differentiating every two of three LM (colorectal cancer vs. renal carcinoma, colorectal cancer vs. breast cancer, and breast cancer vs. renal carcinoma, respectively). The AUCs of the three-class model were 0.83 for colorectal cancer, 0.79 for breast cancer, and 0.91 for renal carcinoma in the test cohort. In the external validation cohort, the AUCs were 0.77, 0.83, and 0.81, respectively. Swarmplot shows the distribution of radiomics features among three different LM types. In the two-class model, high accuracy and AUC were obtained by SVM. The AUC of discriminating colorectal cancer LM from renal carcinoma LM was 0.84, and breast cancer LM from colorectal cancer LM and renal carcinoma LM were 0.80 and 0.94, respectively. The AUCs were 0.77, 0.78, and 0.84 in the external validation cohort.Conclusion: Quantitative radiomics features based on Lung CT exhibited good discriminative performance in LM of primary colorectal cancer, breast cancer, and renal carcinoma. [ABSTRACT FROM AUTHOR]

PurposeCompared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa).MethodsA retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3–4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression.ResultsThe SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P

Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. Methods: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants’ cause of death. Two time periods (1989–2004, 2005–2019) were compared with descriptive statistics. Kaplan–Meier and (multivariate) Cox proportional hazard models were used to assess changes over time for overall survival (OS) and cancer-specific survival (CSS). Results: In total, 5036 patients were analyzed with a median age of 64.0 years at the time of diagnosis. The number of patients increased over time. In the first (1989–2004) and second (2005–2019) period, 32% versus 54% of the patients received radiotherapy (p < 0.001). The median FU time was 13.4 years. The median OS of the first and second periods was 9.5 (95% CI 8.7–10.3) versus 11.3 years (95% CI 10.3–12.3; p < 0.001). The median CSS was 30.0 years (95% CI NA) in the first period and not reached in the second period (p = 0.008). In multivariate analysis (MVA), female gender (HR 0.85; 95% CI 0.79–0.92, p < 0.001) and radiotherapy treatment (HR 0.73; 95% CI 0.64–0.83, p < 0.001) were associated with better OS. Radiotherapy treatment (HR 0.74; 95% CI 0.61–0.90, p = 0.002) was also associated with better CSS. The period of diagnosis was not associated with OS or CSS. Conclusions: In this study of patients with primary UM, there was a shift to the diagnosis of smaller tumors, possibly due to stage migration. There was also an increase in eye-preserving treatments over time. OS and CSS were modestly improved in the second time period; however, the time period was not associated with OS or CSS in multivariate analyses.

BackgroundPrimary atrial tumors are relatively rare and predominantly benign. However, some atrial tumors may be malignant and are associated with poor outcome. Currently, it is hard to determine the malignance of atrial tumors by preoperative clinical presentation or by echocardiography. We aimed to report the difference in the clinical characteristics of patients with benign and malignant atrial tumor.MethodsThis was a single-center retrospective study. A total of 194 patients with primary atrial tumor admitted to our center between 2012 and 2021 were included. The clinical characteristics of patients with benign and malignant tumor were compared.ResultsBenign and malignant tumor accounted for 93% (n = 180) and 7% (n = 14) of the total patients, respectively. Malignant atrial tumor tended to occur in younger patients (P

Approximately 6% of metastatic breast cancers arise de novo. While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic.

Simple Summary: Local radiation treatment of the main tumors in patients with synchronous metastatic illness has traditionally only been used for palliative purposes. The management of patients with de novo metastatic cancer is undergoing a revolution with the advent of new systemic therapies enabling longer overall survival with enhanced quality of life. Numerous studies have looked into the potential survival advantage of treating localized primary tumors at the oligometastatic or oligopersistent stage. In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of the concept of oligometastatic and oligopersistent diseases, the advent of new systemic therapies enabling longer overall survival with an enhanced quality of life, a better understanding of the biologic history of metastatic spread, and technical advances in radiation therapy are revolutionizing the management of patients with de novo metastatic cancer. The prognosis of these patients has been markedly improved and many studies have investigated the survival benefits from the local treatment of various primary tumors in cases of advanced disease at the time of diagnosis or in the case of oligopersistence. This article provides an update on the place of irradiation of the primary tumor in cancer with synchronous metastases, and discusses its interest through published or ongoing trials. [ABSTRACT FROM AUTHOR]

Background: Depth of Invasion ≥ 4 mm, T stage and primary site with more than 20% chances for occult metastasis are currently the accepted indications for elective neck dissection. Nodal metastasis decreases survival by 50%. ENE further reduces the prognosis. Dissection of level IIb lymph nodes in clinically N0 neck does not improve survival. Methods: A total of 320 patients were evaluated. Binary and multiple logistic regression and chi-square test were used for data analysis. ROC curve with Youden's J index was used to set up a cutoff value for DOI. The predictor variables were site, size, grading and depth of invasion of primary tumor. Incidence of level IIb metastasis and ENE were the outcomes. Results: The study revealed a significant association and risk stratification between primary tumor characteristics with the occurrence of ENE. The cutoff value for DOI predicting ENE was 12.5 mm. Tumors of the oral tongue were an independent risk factor for level IIb metastasis. Discussion: Size of primary tumor, DOI, tumors of the mandibular alveolus and poor grading are independent risk factors for ENE. Isolated metastasis to level IIb rarely occurs in the absence of concomitant level IIa metastasis. Size, DOI and grading were significantly associated with level IIb metastasis. However, only tumors of the oral tongue were independent risk factor. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic neoplasias (GTN) are malignant neoplasms that occur in pregnant or recently pregnant women. Choriocarcinoma (CCA) is a highly aggressive and rare GTN, and cases outside the female genital tract are commonly seen as secondary manifestations of gynecologic disease. In this paper, we describe the case of a 40 years-old female patient with a primary pulmonary CCA who was surgically treated and for whom the confirmation of the primary origin of the tumor was possible using a DNA short tandem repeat genotyping. Distinction between gestational and non-gestational trophoblastic neoplasia is crucial as they require different therapeutic approach and have different prognoses. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases are the most common brain tumor in adults and are associated with poor prognosis. The propensity of different solid tumors to metastasize varies greatly, with lung, breast, and melanoma primary tumors commonly leading to brain metastases, while other primaries such as prostate rarely metastasize to the brain. The molecular mechanisms that predispose and facilitate brain metastasis development are poorly understood. In this review, we present the current data on the genomic landscape of brain metastases that arise from various primary cancers and also outline potential molecular mechanisms that drive the formation of distant metastases in the brain. Targeted therapies for cancers have improved primary tumor response rates, but concomitantly, brain metastases (BM) have become the most common brain tumors in adults and are associated with a dismal prognosis of generally less than 6 months, irrespective of the primary cancer type. They most commonly occur in patients with primary breast, lung, or melanoma histologies; however, they also appear in patients with other primary cancers including, but not limited to, prostate cancer, colorectal cancer, and renal cell carcinoma. Historically, molecular biomarkers have normally been identified from primary tumor resections. However, clinically informative genomic alterations can occur during BM development and these potentially actionable alterations are not always detected in the primary tumor leading to missed opportunities for effective targeted therapy. The molecular mechanisms that facilitate and drive metastasis to the brain are poorly understood. Identifying the differences between the brain and other extracranial sties of metastasis, and between primary tumors and BM, is essential to improving our understanding of BM development and ultimately patient management and survival. In this review, we present the current data on the genomic landscape of BM from various primary cancers which metastasize to the brain and outline potential mechanisms which may play a role in promoting the formation of the distant metastases in the brain. [ABSTRACT FROM AUTHOR]

Following radical surgery, patients may suffer a relapse. It is important to identify such patients so that therapy tactics can be modified appropriately. Existing stratification schemes do not display the probability of recurrence with enough precision since locally advanced prostate cancer (PCa) is classified as high-risk but is not ranked in greater detail. Between 40 and 50% of PCa cases belong to the TMPRSS2-ERG subtype that is a sufficiently homogeneous group for high-precision prognostic marker search to be possible. This study includes two independent cohorts and is based on high throughput sequencing and qPCR data. As a result, we have been able to suggest a perspective-trained model involving a deep neural network based on both qPCR data for mRNA and miRNA and clinicopathological criteria that can be used for recurrence risk forecasts in patients with TMPRSS2-ERG-positive, locally advanced PCa (the model uses ALDH3A2 + ODF2 + QSOX2 + hsa-miR-503-5p + ISUP + pT, with an AUC = 0.944). In addition to the prognostic model's use of identified differentially expressed genes and miRNAs, miRNA–target pairs were found that correlate with the prognosis and can be presented as an interactome network. [ABSTRACT FROM AUTHOR]

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-β signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-β1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre - ; Tgfb1 fl/fl mice, HCC orthotopic models established on Pf4cre + ; Tgfb1 fl/fl mice showed reduced TGF-β1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-β1. Clinically, higher platelet count correlated with increased TGF-β1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-β1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis. • Platelet releasate drives HCC cell EMT and invasion through autophagy. • Platelets trigger HCC cell autophagy via TGF-β1 mediated AMPK/mTOR pathway activation. • Platelets promote cancer cell EMT in primary tumor and HCC metastasis via releasing TGF-β1 to tumor microenvironment. • Higher platelet count correlates with increased TGF-β1, autophagy and EMT in primary tumor of HCC patients. [ABSTRACT FROM AUTHOR]

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3–130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

Background: The molecular mechanisms underlying the de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials and Methods: Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/−, HER2−), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical–pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n = 32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 × 10 µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR; deconvolution was performed using CIBERSORTx to assess immune cell fractions. A paired Wilcoxon test was used to compare dnMBC and eBC groups and corrected for the false discovery rate. Results: Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that the CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusions: Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.