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Background: Tumor neoantigen peptide-based vaccines, systemic immunotherapies that enhance antitumor immunity by activating and expanding antigen-specific T cells, have achieved remarkable results in the treatment of a variety of solid tumors. However, how to effectively deliver neoantigens to induce robust antitumor immune responses remains a major obstacle. Results: Here, we developed a safe and effective neoantigen peptide delivery system (neoantigen-ferritin nanoparticles, neoantigen-FNs) that successfully achieved effective lymph node targeting and induced robust antitumor immune responses. The genetically engineered self-assembled particles neoantigen-FNs with a size of 12 nm were obtained by fusing a neoantigen with optimized ferritin, which rapidly drainage to and continuously accumulate in lymph nodes. The neoantigen-FNs vaccine induced a greater quantity and quality of antigen-specific CD8+ T cells and resulted in significant growth control of multiple tumors, dramatic inhibition of melanoma metastasis and regression of established tumors. In addition, no obvious toxic side effects were detected in the various models, indicating the high safety of optimized ferritin as a vaccine carrier. Conclusions: Homogeneous and safe neoantigen-FNs could be a very promising system for neoantigen peptide delivery because of their ability to efficiently drainage to lymph nodes and induce efficient antitumor immune responses. [ABSTRACT FROM AUTHOR]

Background: Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. Methods: One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. Discussion: SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. Trial registration: Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023). [ABSTRACT FROM AUTHOR]

Background The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. Materials and Methods This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. Results Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. Conclusion Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care. [ABSTRACT FROM AUTHOR]

Background: Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer. Methods: A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity. Results: PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed. Conclusion: In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors. [ABSTRACT FROM AUTHOR]

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577–1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216–1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion: A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI. [ABSTRACT FROM AUTHOR]

To compare clinical characteristics and survival outcomes of patients with multiple renal cell carcinoma versus single renal cell carcinoma. Develop a prognostic model for predicting prognosis in patients with multiple tumors and analyze prognostic factors. Patients with primary multiple renal cell carcinoma were selected from the Surveillance, Epidemiology, and End Results database (2004–2015). They were divided into single-tumor and multiple-tumor groups. Survival analysis was conducted using the Kaplan–Meier method and log-rank test. A Cox regression model was used to identify potential prognostic factors. A total of 19,489 renal cell carcinoma cases were included, with 947 in the multiple-tumor group and 18,542 in the single-tumor group. The multiple-tumor group had lower cancer-specific survival (P = 0.03, HR = 1.431). Cox regression identified risk factors for the multiple-tumor group including number of tumors, gender, combined summary stage, T stage, N stage, tumor size, and type of surgery. The predicted probabilities showed acceptable agreement with the actual observations at 3-, 5-, and 8-years area under the curve values in both the training and validation cohorts (0.831 vs. 0.605; 0.775 vs. 0.672; and 0.797 vs. 0.699, respectively). Compared with single renal cell carcinoma, multiple renal cell carcinoma is associated with decreased cancer-specific survival. Additionally, we identified several prognostic factors including the number of tumors, T stage, tumor size, and type of surgery. These findings offer valuable insights for selecting appropriate treatment strategies for patients diagnosed with multiple renal cell carcinomas. [ABSTRACT FROM AUTHOR]

Background: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. Methods: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan–Meier method. Results: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. Conclusion: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria. [ABSTRACT FROM AUTHOR]

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients' samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions. [ABSTRACT FROM AUTHOR]

To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup. [Display omitted] • Patients with single curatively treated HCC account for 20% of LT candidates. • In these patients, LT can be safely delayed without hampering pre/post-LT outcomes. • This strategy has the potential to redirect spared organs to patients in urgent need. • The DELTA-HCC study supports extension of a delayed strategy to other LT programs. [ABSTRACT FROM AUTHOR]

Therapy‐induced senescence can regulate both the innate and adaptive immune systems, thereby affecting therapeutic efficacy. Bleomycin is a major component of combined chemotherapy regimens, utilized for the treatment of multiple tumors, whereas pulmonary toxicity severely restricts its clinical benefits. As a member of the bleomycin family, boningmycin (BON) exhibits potent anticancer activity with minimal pulmonary toxicity, making it a potential alternative to bleomycin. Low concentrations of BON can induce senescence, but the impact of BON‐induced senescence on anticancer immunity remains unclear. This study investigates the effects of BON‐induced senescence on PD‐L1 expression and the underlying mechanisms in human cancer cells. Firstly, the elevation of PD‐L1 protein during BON‐induced senescence was confirmed by a senescence β‐galactosidase staining assay, detection of the senescence‐associated secretory phenotype (SASP), western blot and flow cytometry in human lung cancer NCI‐H460 cells and breast cancer MDA‐MB‐231 cells. Subsequently, it was shown that the increase in PD‐L1 protein is mediated by SASP, as evidenced by the use of conditional media, knockdown of cyclic GMP‐AMP synthase and inhibition of stimulator of interferon genes. Ultimately, it was demonstrated that SASP‐mediated PD‐L1 up‐regulation is dependent on the activation of the JAK/STAT pathway through the use of specific inhibitors and siRNAs. These findings clarify the impact of BON‐induced senescence on PD‐L1 expression and may contribute to the optimization of the therapeutic efficacy of bleomycin‐related compounds and the clinical transformation of BON. [ABSTRACT FROM AUTHOR]

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with a high propensity for local invasion and recurrence. Although it is a rare event, the occurrence of multiple tumors in a single patient raises a diagnostic dilemma, as metastatic disease should be differentiated from multiple primary malignant events. In more than 90% of DFSP, a pathogenic t(17;22) translocation leads to the expression of COL1A1::PDGFB fusion transcripts. Karyotype analysis, fluorescence in situ hybridization, and RT‐PCR can be useful ancillary studies in detecting this characteristic rearrangement, and sequencing of the fusion transcript can be used to support a clonal origin in metastatic and multifocal disease. However, previous reports have demonstrated variable sensitivity of these assays, in part due to the high sequence variability of the COL1A1::PDGFB fusion. Here, we report a patient who developed two distinct DFSP tumors over the course of 7 years. Chromosomal microarray analysis identified distinctive genomic alterations in the two tumors, supporting the occurrence of multiple primary malignant events. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of multiple primary cancers (MPCs) among 96,174 cancer patients at the Korea Cancer Center Hospital (KCCH) from 2003 to 2022 was 2.3%. Breast cancer (15.7%) was the most common primary cancer, with lung cancer (15.2%) being the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years, decreasing for third and fourth primary cancers (2.1 years and 1.6 years, respectively). Lymphoma had the highest relative risk (2.1) for developing MPCs. Specific primary cancers showed significant associations with subsequent cancers, informing future research and management strategies. Rising cancer survival rates have led to an increased risk of multiple primary cancers (MPCs). Data on MPCs in South Korea are limited. This study aimed to address incidence and clinical characteristics of MPCs in a single cancer center in Korea during a 20-year period. We retrospectively analyzed 96,174 cancer patients at the Korea Cancer Center Hospital between 2003 and 2022, identifying 2167 patients with metachronous MPCs based on Surveillance, Epidemiology, and End Results SEER criteria. We categorized patients by cancer type (15 major solid cancer groups and 3 major hematologic cancer groups), including pathological diagnosis, assessed latency periods, and relative risks (RRs) for developing MPCs. The overall MPC incidence was 2.3%. Breast cancer (15.7%) was the most common primary cancer, and lung cancer (15.2%) was the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years. Decreasing latency periods for third and fourth primary cancers were observed (2.1 years and 1.6 years, respectively). Most cancers maintained their dominant pathological type despite notable changes in the prevalence of specific pathologies for certain types of second primaries. Lymphoma showed the highest RR (2.1) for developing MPCs. Significant associations were found between specific primary and subsequent cancers, including breast–ovary, thyroid–breast, stomach–pancreas, colorectal–head and neck, lung–prostate, and lymphoma–myeloid neoplasms. These findings contribute to a better understanding of MPC occurrence. They can inform future research on their etiology and development of improved management strategies. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex (MHC) could serve as a potential biomarker for tumor immunotherapy, however, it is not yet known whether MHC could distinguish potential beneficiaries. Single‐cell RNA sequencing datasets derived from patients with immunotherapy were collected to elucidate the association between MHC and immunotherapy response. A novel MHCsig was developed and validated using large‐scale pan‐cancer data, including The Cancer Genome Atlas and immunotherapy cohorts. The therapeutic value of MHCsig was further explored using 17 CRISPR/Cas9 datasets. MHC-related genes were associated with drug resistance and MHCsig was significantly and positively associated with immunotherapy response and total mutational burden. Remarkably, MHCsig significantly enriched 6% top‐ranked genes, which were potential therapeutic targets. Moreover, we generated Hub-MHCsig, which was associated with survival and disease-special survival of pan-cancer, especially low-grade glioma. This result was also confirmed in cell lines and in our own clinical cohort. Later low-grade glioma-related Hub-MHCsig was established and the regulatory network was constructed. We provided conclusive clinical evidence regarding the association between MHCsig and immunotherapy response. We developed MHCsig, which could effectively predict the benefits of immunotherapy for multiple tumors. Further exploration of MHCsig revealed some potential therapeutic targets and regulatory networks. [ABSTRACT FROM AUTHOR]

Background: Fibroblast activation protein (FAP), a cell surface serine protease, plays roles in tumor invasion and immune regulation. However, there is currently no pan-cancer analysis of FAP. Objective: We aimed to assess the pan-cancer expression profile of FAP, its molecular function, and its potential role in head and neck squamous cell carcinoma (HNSC). Methods: We analyzed gene expression, survival status, immune infiltration, and molecular functional pathways of FAP in The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) tumors. Furthermore, to elucidate the role of FAP in HNSC, we performed proliferation, migration, and invasion assays post-FAP overexpression or knock-down. Results: FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them. In the context of immune infiltration, FAP expression negatively correlated with CD8+ T-cell infiltration in five tumor types and positively with regulatory T-cell infiltration in four tumor types. Our enrichment analysis highlighted FAP's involvement in the PI3K-Akt signaling pathway. In HNSC cells, FAP overexpression activated the PI3K-Akt pathway, promoting tumor proliferation, migration, and invasion. Conversely, FAP knockdown showed inhibitory effects. Conclusion: Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC. [ABSTRACT FROM AUTHOR]

Double primary malignancy though uncommon, we often encounter in our clinical practice. The lung malignancy is known to cause left vocal cord paralysis. Bilateral abductor paralysis secondary to adenocarcinoma of the lung with concurrent basal cell carcinoma of the face is not common. Proper counseling and timely management are needed in these cases of multiple primary malignancies. Early evaluation in all cases of hoarseness can help in early diagnosis and management. [ABSTRACT FROM AUTHOR]

The ubiquitination-mediated protein degradation exerts a vital role in the progression of multiple tumors. NEDD4L, which belongs to the E3 ubiquitin ligase NEDD4 family, is related to tumor genesis, metastasis and drug resistance. However, the anti-tumor role of NEDD4L in esophageal carcinoma, and the potential specific recognition substrate remain unclear. Based on public esophageal carcinoma database and clinical sample data, it was discovered in this study that the expression of NEDD4L in esophageal carcinoma was apparently lower than that in atypical hyperplastic esophageal tissue and esophageal squamous epithelium. Besides, patients with high expression of NEDD4L in esophageal carcinoma tissue had longer progression-free survival than those with low expression. Experiments in vivo and in vitro also verified that NEDD4L suppressed the growth and metastasis of esophageal carcinoma. Based on co-immunoprecipitation and proteome analysis, the NEDD4L ubiquitination-degraded protein ITGB4 was obtained. In terms of the mechanism, the HECT domain of NEDD4L specifically bound to the Galx-β domain of ITGB4, which modified the K915 site of ITGB4 in an ubiquitination manner, and promoted the ubiquitination degradation of ITGB4, thus suppressing the malignant phenotype of esophageal carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: This reassessment of the findings from our phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate–high-risk prostate cancer in the absence of androgen deprivation therapy due to patient refusal, with a median follow-up of 6.5 years. Our primary focus is on analyzing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade ≥ 2, both genitourinary and gastrointestinal. Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate–high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25–74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17–76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate–high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent. [ABSTRACT FROM AUTHOR]

Evidence shows stereotactic ablative body radiotherapy (SABR) is used as a non-invasive ablative therapy in the treatment of multisite oligometastatic (OM) and oligoprogressive (OP) diseases originating from metastatic breast cancer. This study aims to report the treatment outcomes and to investigate what factors that are prognostic in terms of local control, progression-free survival (PFS) and overall survival (OS) in patients receiving SABR for extracranial OM and OP diseases originating from metastatic breast cancer. A retrospective review on treatment records of patients with OM and OP from metastatic breast cancer who underwent SABR at a single was carried out. SABR was performed with daily image-guided radiotherapy (IGRT) using a dedicated robotic SABR machine. Local control, PFS and OS were calculated using Kaplan-Meier statistics and the post-treatment toxicity data was scored following the CTCAE v4.0 protocol. Univariate and multivariate Cox regression tests were used in the subgroup analysis of prognostic factors on PFS and OS including patients' age, types of follow-up imaging (staging CT only vs whole-body MR/PET), metastases status (OM vs OP), primary breast cancer tumour grade, hormone receptors (ER/PR/HER2) status, change of systemic treatments at SABR, number of metastases, SABR treatment sites and doses. 56 metastatic breast cancer patients (38 patients with OM and 18 patients with OP) were involved in this retrospective review. The median follow-up was 35.6 months (range 4.0–132.9 months). The estimated local control at 1 , 2 and 5 years were 90.9%, 88.7% and 88.7%, respectively. The estimated median PFS was 19.2 months (95%CI 10.3–28.1 months); the PFS at 1, 2 and 5 years were 63.3%, 44.4% and 33.2%. The estimated OS at 1, 2 and 5 years were 98.0%, 91.9% and 74.3%, respectively with the estimated median OS of 105.1 months (95%CI 51.5–158.7 months). The vast majority of patients tolerated the treatment well with the commonest acute side effects as grade 1 fatigue. There were no statistically significant factors found in OS regression analysis. The types of follow-up imaging, metastases status, oestrogen receptor status, and number of metastases for SABR were statistically significant factors (p < 0.05) in the multivariate Cox regression analysis on PFS. There are limited studies published on the efficacy and post-treatment toxicities of metastatic breast cancer OM and OP SABR with adequate length of follow-up. This study confirmed that SABR was a safe, non-invasive treatment option for patients with extracranial OM and OP diseases originated from primary breast cancer in terms of the acceptable post-treatment toxicities. • This study reported SABR treatment outcomes for multisite OM and OP diseases originating from metastatic breast cancer • It showed modest local control and post-treatment toxicities on the SABR of extracranial OM and OP from metastatic breast cancer. • The types of follow-up imaging, OM vs OP, oestrogen receptor status, and number of metastases for SABR can be used as PFS prognostic factors. [ABSTRACT FROM AUTHOR]

Background: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. Methods: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM). Results: Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6–16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC. Conclusion: Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort. [ABSTRACT FROM AUTHOR]

The diagnosis of breast cancer through MicroWave Imaging (MWI) technology has been extensively researched over the past few decades. However, continuous improvements to systems are needed to achieve clinical viability. To this end, the numerical models employed in simulation studies need to be diversified, anatomically accurate, and also representative of the cases in clinical settings. Hence, we have created the first open-access repository of 3D anatomically accurate numerical models of the breast, derived from 3.0T Magnetic Resonance Images (MRI) of benign breast disease and breast cancer patients. The models include normal breast tissues (fat, fibroglandular, skin, and muscle tissues), and benign and cancerous breast tumors. The repository contains easily reconfigurable models which can be tumor-free or contain single or multiple tumors, allowing complex and realistic test scenarios needed for feasibility and performance assessment of MWI devices prior to experimental and clinical testing. It also includes an executable file which enables researchers to generate models incorporating the dielectric properties of breast tissues at a chosen frequency ranging from 3 to 10 GHz, thereby ensuring compatibility with a wide spectrum of research requirements and stages of development for any breast MWI prototype system. Currently, our dataset comprises MRI scans of 55 patients, but new exams will be continuously added. [ABSTRACT FROM AUTHOR]

Background: The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. Methods: We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. Results: A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)‐CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. Conclusion: Routine chest CT is needed for breast cancer patients before surgery, and PET‐CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer. [ABSTRACT FROM AUTHOR]

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with a high, lifetime risk of a broad spectrum of cancers caused by pathogenic germline TP53 mutations. Numerous different germline TP53 mutations have been associated with LFS, which has an exceptionally diverse clinical spectrum in terms of tumor type and age of onset. Our patient has developed six asynchronous tumors to date: a phyllode tumor of the breast, a pheochromocytoma, a rosette-forming glioneuronal tumor (RGNT), an adrenocortical carcinoma (ACC), a ductal carcinoma of the breast, and a thymoma. The occurrence of such a number of rare tumors is sporadic even among in the population of patients living with cancer predisposition syndromes. In this instance, the omission of pretest genetic counseling and thorough family tree analysis prior to selecting the test led to the oversight of an underlying TP53 likely pathogenic mutation (classified as Class 4). This emphasizes the necessity for such counseling to prevent overlooking crucial genetic information. Neglecting this step could have had profound implications on the patient's treatment, particularly considering the early onset and occurrence of multiple tumors, which typically raise suspicion of a hereditary component. The implications for family members must be considered. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome (LS) is an autosomal dominant multi-organ cancer syndrome with a high lifetime risk of cancer. The number of cumulative colorectal adenomas in LS does not generally exceed ten, and removal of adenomas via routine screening minimizes the cancer burden. However, abnormal phenotypes may mislead initial diagnosis and subsequently cause suboptimal treatment. Aim: Currently, there is no standard guide for the care of multiple colorectal adenomas in LS individuals. We aimed to shed insight into the molecular features and reasons for multiplicity of adenomas in LS patients. Methods: We applied whole exome sequencing on nine adenomas (ten samples) and three assumed primary carcinomas (five samples) of an LS patient developing the tumors during a 21-year follow-up period. We compared the findings to the tumor profiles of two additional LS cases ascertained through colorectal tumor multiplicity, as well as to ten adenomas and 15 carcinomas from 23 unrelated LS patients with no elevated adenoma burden from the same population. As LS associated cancers can arise via several molecular pathways, we also profiled the tumors for CpG Island Methylator Phenotype (CIMP), and LINE-1 methylation. Results: All tumors were microsatellite unstable (MSI), and MSI was present in several samples derived from normal mucosa as well. Interestingly, frequent frameshift variants in RNF43 were shared among substantial number of the tumors of our primary case and the tumors of LS cases with multiple tumors but almost absent in our control LS cases. The RNF43 variants were completely absent in the normal tissue, indicating tumor-associated mutational hotspots. The RNF43 status correlated with the mutational signature SBS96. Contrary to LS tumors from the reference set with no elevated colorectal tumor burden, the somatic variants occurred significantly more frequently at C>T in the CpG context, irrespective of CIMP or LINE-1 status, potentially indicating other, yet unknown methylation-related mechanisms. There were no signs of somatic mosaicism affecting the MMR genes. Somatic variants in APC and CTNNB1 were unique to each tumor. Conclusion: Frequent somatic RNF43 hot spot variants combined with SBS96 signature and increased tendency to DNA methylation may contribute to tumor multiplicity in LS. [ABSTRACT FROM AUTHOR]

Background: Tumor microenvironment actually reduces antitumor effect against the immune attack by exclusion of CD8+T cells. Progranulin (PGRN) is a multifunctional growth factor with significant pathological effects in multiple tumors; however, its role in immunity evasion of breast cancer (BCa) is not completely understood. Methods: We depleted GRN (PGRN gene) genetically in mice or specifically in PY8119 murine BCa cell line, and mouse models of orthotopic or subcutaneous transplantation were used. Chimeric mice-deficient of PGRN (Grn−/−) in bone marrow (BM) compartment was also generated. Association of PGRN expression with chemokine production or BCa development was investigated by histological and immunological assays. Results: We found PGRN was involved in exhaustion of cytotoxic CD8+T cell in BCa with the increasing expressions of M2 markers and intercellular cell adhesion molecule-1 (ICAM-1) on macrophages. Specifically, ablation of PGRN in PY8119 cells reduced tumor burden, accompanied by the infiltrating of cytotoxic CD8+T cells into tumor nests. Moreover, our result revealed that blockade of PD-1 in PGRN-depleted tumors exhibited better antitumor effect in vivo and significantly decreased tumor burden. Conclusion: These findings suggest that inhibition of PGRN may act as a potential immune-therapeutic strategy by recovering infiltration of CD8+T cell in BCa tissue and thereby enhancing the response to anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Objectives: Contrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS). Materials and methods: Consecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS. Results: This study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p =.02). Nonperipheral washout (p =.006), markedly low apparent diffusion coefficient value (p =.02), intratumoral arteries (p =.01), and width of the main portal vein (p =.03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p =.02). Multiple tumors (p =.048) and radiologically-evident cirrhosis (p <.001) were the only predictors for L-RFS. Conclusion: Twelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs. Clinical relevance statement: The prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models. Key Points: • Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival. • Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival. • Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (PNETs) represent 1–2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. Methods: This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. Results: Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence. Conclusion: This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: Equine melanomas are a common problem in clinical practice. Although a known issue in the equestrian world, there is still some lack of knowledge about various aspects of the disease. Due to the misconception that these tumors do not cause problems, there is a tendency to leave them to be treated at a later date. However, there is still little evidence regarding the effect of time on these tumors. This work aimed to study the clinical and histological differences between tumors excised sooner and later. In this retrospective study, information regarding 34 horses and 42 tumors was analyzed. According to the results, tumors with delayed excision were statistically more likely to acquire larger dimensions (p = 0.038) and be malignant (p = 0.035). Furthermore, delayed excision was also associated with a higher number of tumors (p = 0.011), since horses with a tumor for more than 6 years often had multiple tumors. With this study, we conclude that delayed excision has clinical and histological consequences for equine melanoma, highlighting the importance of surgical removed at an early stage, when excision is easier, preventing future complications. Equine melanomas are a common neoplasm in gray horses. However, scientific knowledge about their progression over time is quite scarce. Some owners and veterinarians still believe that early intervention is not necessary, stating that tumors evolve very slowly and intervention could worsen the animal's condition. This work aims to identify clinical and histological differences that may exist between equine melanomas with different excision intervals (time between tumor detection and surgical excision). A total of 42 tumors (13 benign and 29 malignant) from 34 horses were included in this study. There was a statistically significant association between excision interval and tumor size (p = 0.038), with tumors excised later being significantly larger than the ones excised sooner. The excision interval was also statistically associated with the number of tumors (p = 0.011), since the horses that carried a tumor for longer seemed to be prone to have multiple tumors. Furthermore, there was an association between excision interval and malignancy (p = 0.035), with tumor excised later being fives times more likely to be malignant. This study provides evidence of delayed excision's effect on the progression of equine melanomas. Additionally, it reinforces the importance of the early excision of these tumors. [ABSTRACT FROM AUTHOR]

Introduction: The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. Method: We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. Results: In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. Conclusions: The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have revealed increasing evidence that the long noncoding RNA bladder cancer associated transcript 1 (LncRNA BLACAT1) plays an essential role in the emergence of different malignancies. This meta-analysis aimed to evaluate the prognostic significance of LncRNA BLACAT1 in various cancers. Methods: Six electronic databases (PubMed, Embase, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese WanFang database) were comprehensively searched for relevant studies. The analysis of overall survival (OS) and clinicopathological characteristics was conducted. Results: Nineteen studies with 1,559 patients were eventually eligible to be included in this meta-analysis. High expression level of LncRNA BLACAT1 was identified to be linked with shorter OS (HR: 2.02, 95% CI: 1.66-2.46, p < 0.001) and PFS (HR: 2.424, 95% CI: 1.827-3.020, p < 0.001) in cancer patients as opposed to low expression levels. Subgroup analysis showed that analysis model (multivariate or univariate), cut-off value (mean or median), sample size (more or fewer than 100), and cancer type had little effect on OS in multiple tumors. Moreover, high LncRNA BLACAT1 expression was associated with positive lymph node metastasis (HR: 2.29, 95% CI: 1.66-3.16, p < 0.00001), advanced clinical stage (HR: 2.29, 95% CI: 1.65-3.19, p < 0.00001) and worse differentiation status (HR: 0.58, 95% CI: 0.37-0.92, p = 0.02), compared to low LncRNA BLACAT1 expression. Conclusion: The findings highlight that high LncRNA BLACAT1 expression might be detrimental and induce a worse prognosis for cancer patients. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with 10–40% of cases involving portal vein tumor thrombosis (PVTT), leading to poor outcomes and a short survival. The effectiveness of PVTT treatment in patients with HCC is still controversial. Methods: This prospective dual-center study cohort comprised 60 patients with HCC and PVTT who underwent PVR-EPRFA-ST using a novel intravascular radiofrequency system followed by vascular stent placement across the PVTT stenosed segment under fluoroscopy guidance. Results: PVR-EPRFA-ST was technically and clinically successful in 54/60 (90%) and 37/54 (68.5%) patients, respectively. The mean tumor size, PVTT length, post-ablation luminal diameter, and median duration of the recanalized PV patency were 8.6 ± 3.4 cm, 4.1 ± 2.1 cm, 10.3 ± 1.8 mm, and 13.4 months. Higher technical and clinical success rates were associated with a longer survival (177 ± 17.3 days, HR: 0.3, 95%CI 0.12–0.71, p = 0.04; and 233 ± 18.3 days, HR: 0.14, 0.07–0.27, p < 0.001). A shorter survival was associated with Child–Pugh C (HR: 2.7, p = 0.04), multiple tumors (HR: 1.81, p = 0.03), and PVTT length (HR: 1.16, p = 0.04). Conclusions: PVR-EPRFA-ST was feasible and effective for the treatment of selected patients with PVTT, especially in patients with Child–Pugh A/B, single tumors, or a shorter PVTT length. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) play regulatory roles in the biological processes of multiple tumors, colorectal cancer (CRC) included. Our previous study probed the impact of circ_0007385 on CRC cell malignant behaviors, while the underlying mechanism remains obscure. In this work, the potential mechanism of hsa_circ_0007385 in CRC was probed. Functional experiments were implemented for probing the function of hsa_circ_0007385 in CRC. Further analysis revealed the relation between hsa_circ_0007385 and miRNAs. A xenograft mouse model was implemented for probing the influence of hsa_circ_0007385 on CRC growth and metastasis in vivo. Hsa_circ_0007385 was up-regulated in CRC. Hsa_circ_0007385 positively regulated its host gene mediator of cell motility 1 (MEMO1). Hsa_circ_0007385 silencing inhibited CRC progression. Hsa_circ_0007385 and MEMO1 bond to miR-485-3p/miR-543/miR-337-3p, and these three miRNAs were lowly expressed in CRC, and negatively modulated by hsa_circ_0007385. Hsa_circ_0007385 functioned as an oncogene in CRC in a miR-485-3p/miR-543/miR-337-3p- or MEMO1-dependent manner. Hsa_circ_0007385 promoted CRC progression via modulating miR-485-3p/miR-543/miR-337-3p/MEMO1 axis. Thus, circ-MEMO1 might be a promising therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

ABSTRACT The frequency of ovarian neoplasms in dogs is low, and these tumors are often underdiagnosed mainly due to nonspecific clinical signs. Multiple ovarian tumors are rarely described in dogs and can be of primary or secondary origin. Lymphomas, in turn, are among the most common malignant neoplasms in dogs, with a variable clinical course. This report describes a case of multiple concomitant ovarian tumors and a multicentric lymphoma in a dog, diagnosed histologically and confirmed by immunohistochemistry. The right and left ovaries and mesenteric lymph node of a 14-year-old mixed breed female dog were received for histopathological evaluation. Histologically, a multicentric small to intermediate cell lymphoma was diagnosed in the lymph node and both ovaries, in addition to a bilateral granulosa cell tumor and papillary adenocarcinoma in one of the ovaries. Immunohistochemistry determined the diagnosis of multicentric peripheral T-cell lymphoma. Coexisting ovarian tumors are rarely described in the literature but can occur. This is the first report of these three neoplasms occurring concomitantly in the same organ. Therefore, clinicians and pathologists should be aware of this possibility when evaluating ovaries.

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting > 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers. [ABSTRACT FROM AUTHOR]

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research. [ABSTRACT FROM AUTHOR]

To investigate the significance of perioperative hepatitis B virus (HBV) DNA changes for predicting recurrence in patients with HBV-related hepatocellular carcinoma (HCC) undergoing liver resection (LR). From 2013 to 2020, 241 patients with HBV-related HCC who underwent LR in five Hallym university-affiliated hospitals were enrolled. The serum HBV DNA level, together with other clinicopathological variables, was analyzed for association with HCC recurrence. Preoperatively, 99 patients had undetectable HBV DNA and 142 had detectable viral levels. Of those with detectable viral levels, 72 rapidly progressed to undetectable levels within 3 mo after LR (Rapid group), and 70 showed persistently detectable levels (Nonrapid group). The Rapid group had a better recurrence-free survival (RFS) rate than the Nonrapid group (1-y, 3-y RFS = 75.4%, 57.3%, versus 54.7%, 39.9%, respectively, P = 0.012). In the subgroup analysis, the Rapid group had a better RFS rate in early stages (1-y, 3-y RFS = 82.6%, 68.5%, versus 62.8%, 45.8%, respectively, P = 0.005); however, the RFS rates between the two groups were comparable in the advanced stage (1-y, 3-y RFS = 61.1%, 16.7% versus 45.5%, 22.7%, respectively, P = 0.994). Among the 142 patients with preoperatively detectable HBV DNA, persistently detectable HBV DNA within 3 mo postoperatively (hazard ratio [HR] = 1.7, P = 0.022), large tumor size (HR = 2.7, P < 0.001), multiple tumors (HR = 3.2, P < 0.001), and microvascular invasion (HR = 1.7, P = 0.028) were independent risk factors for RFS in multivariate analysis. Rapidly undetectable HBV DNA after LR is associated with a better prognosis for recurrence in patients with HCC. Therefore, appropriate treatment and/or screening may be necessary for patients who do not return to undetectable HBV DNA after LR. [ABSTRACT FROM AUTHOR]

Angiosarcomas originating from the gastrointestinal tract are rare but highly aggressive tumors with poor prognosis. These tumors can be misdiagnosed as benign and malignant gastrointestinal tract lesions. The definitive histological diagnosis of angiosarcomasis made by pathologists based on immunohistochemical analysis demonstrating cluster of differentiation 31 (CD31), factor VIII-related antigen (FVIIIRAg), erythroblast transformation specific related gene (ERG), and cluster of differentiation 34 (CD34). Angiosarcomas are treated with a single or multimodality approach that may include resection, radiotherapy, chemotherapy, and palliative care, depending on the stage of disease and the condition of the patient. No matter the treatment option, metastasis and death rates are substantially highin patients with angiosarcoma. In this context, a 59-year-old male with synchronous double primary angiosarcoma arising from the gastric and rectum who presented with the complaint of abdominal pain and distention to the outpatient clinic is presented in this case report, along with a brief literature review. [ABSTRACT FROM AUTHOR]

This study reports the first case of fibropapillomatosis (FP) in the green turtle Chelonia mydas that has been successfully diagnosed and treated in Colombia. Worldwide, FP has reached epizootic proportions as it has been reported in marine turtles of tropical and subtropical waters, and in severe cases, it reduces the probability of survival. Treatment has been elusive as multiple surgical excisions are needed due to tumor recurrence. In this case, one green turtle with multiple tumors was diagnosed by histopathology and molecular detection of the chelonid herpesvirus 5 (ChHV5) by means of amplification and sequencing of the DNA polymerase (DNApol) gene. Two separate treatments that consisted of autogenous vaccines and surgical excisions were applied; the first one had a partial success as one out of the tumors treated reappeared after 3 months post-treatment. Treatment 2 consisted of an autogenous vaccine enriched with adjuvants and applied at increasing doses, after which, the tumor significatively decreased in size and was surgically removed. At the end of the 6 months followup period, no tumor recurrence was observed, and the turtle was in apparent optimal health conditions. These findings, although limited, suggest a possible treatment that might help to contain this epizootic problem. [ABSTRACT FROM AUTHOR]

Background: Whether the value of PD‐L1 expression from metastatic sites to predict the efficacy of immune checkpoint blockade (ICB)‐based treatment is equivalent to that from a primary tumor is uncertain. This study aimed to compare the utility of PD‐L1 TPS from a primary lung tumor and metastatic sites to predict the overall response rate (ORR) of first‐line ICB‐based treatment. Methods: This study included 249 patients with advanced non‐small cell lung cancer (NSCLC) who received first‐line ICB‐based treatment. All subjects underwent PD‐L1 testing prior to ICB‐based treatment and were divided into two cohorts corresponding to the different biopsy sites: lung primary site‐sampled cohort (PT cohort, n = 167) and metastatic site‐sampled cohort (MT cohort, n = 82). Results: There was no statistical significance in PD‐L1 TPS distribution between the two cohorts (p = 0.742). PD‐L1 TPS ≥50% was also related to high ORR compared with PD‐L1 < 50% in the PT cohort (34.3% vs. 14.1%, p = 0.004). In contrast, ICB‐based therapy could bring comparable ORR (35.1% vs. 33.3%, p = 0.871) in the MT cohort regardless of PD‐L1 TPS status (≥50%, or <50%). As supported, when the cutoff value of TPS was selected as 50%, it was suggested that PT‐related PD‐L1 was the independent predictor of ORR (OR 2.870, 95% CI: 1.231–6.694, p = 0.015) rather than MT‐related PD‐L1 (OR 0.689, 95% CI: 0.236–2.013, p = 0.495). Furthermore, ROC proved that PT‐related PD‐L1 expression manifested a better AUC of 0.621 (p = 0.026) than that of MT‐related PD‐L1 (AUC = 0.565, p = 0.362). Conclusion: Compared with PT‐related PD‐L1 expression, MT‐related PD‐L1 expression showed limited value in predicting ORR in patients with advanced NSCLC receiving ICB‐based therapy. It was concluded that even patients with low MT‐related PD‐L1 expression could benefit from ICB‐based therapy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to elucidate the patterns of recurrence of hepatocellular carcinoma and to analyze factors that can predict recurrence after complete response to radioembolization. Materials and Methods: A total of 289 consecutive patients who underwent radioembolization for the treatment of hepatocellular carcinoma at a single tertiary center were retrospectively reviewed. Baseline characteristics were collected and compared between the group showing complete response and the group showing noncomplete response. Data on recurrence status, time to recurrence, and the patterns of recurrence among the patients who showed radiologic complete response were collected. The group that maintained complete response and the group that experienced recurrence were compared, and the risk factors affecting recurrence were evaluated by logistic regression analysis. Results: The complete response rate was 24.9% (73/289). Age, sex, tumor markers, maximum tumor diameter, multiplicity, presence of vascular invasion, and target radiation dose were significantly different between the complete response and noncomplete response groups. The recurrence rate after complete response was 38.4% (28/73), and 67.9% (19/28) of recurrences occurred by 8 months after complete response. Eight patients who underwent resection/transplantation after complete response experienced no recurrence. Multiple tumors and a lower target radiation dose were independent risk factors of recurrence after complete response in the multivariate logistic regression. Conclusion: Hepatocellular carcinoma recurrence following complete response after radioembolization is not uncommon and frequently occurs within 1 year after complete response. Multiple tumors and a lower target radiation dose may be risk factors for recurrence. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular carcinoma is the second most prevalent histological subtype of breast cancer after invasive duct carcinoma, with a reported increased incidence in the last two decades. It often presents with challenging imaging characteristics that lower the sensitivity of mammography in their detection and delineation of their extent. Moreover, an increased risk of having synchronous lesions in the same or opposite breast was reported in cases with invasive lobular carcinoma. This obviates the need for other imaging modalities, specifically contrast-enhanced imaging modalities, to improve early detection as well as allow precise determination of the extent of the disease. Our aim in this study was to compare the diagnostic performance of contrast-enhanced digital mammography and dynamic contrast-enhanced magnetic resonance imaging (MRI) in the local staging of invasive lobular carcinoma regarding the size, extensions, multiplicity and bilaterality. Methods: This study included 46 female patients with pathologically proven invasive lobular carcinoma. They underwent full-field digital mammography with a complementary ultrasound examination, contrast-enhanced digital mammography, and dynamic contrast-enhanced MRI. The findings encountered by the three imaging modalities were evaluated independently, and the results were compared with final histopathology. Results: In the current study, dynamic contrast-enhanced MRI study was the most sensitive modality in the detection of the index lesion, synchronous ipsilateral and contralateral lesions and achieved a sensitivity of 100% in each analysis as compared to contrast-enhanced digital mammography, which achieved a sensitivity of 97.8%, 85.7% and 80%, respectively. Regarding the assessment of the lesion extent to the surroundings, there was a tendency to overestimation by MRI examination. Conclusions: Although dynamic contrast-enhanced MRI is the most sensitive imaging modality for detecting the index lesion, multiplicity and bilaterality, contrast-enhanced digital mammography achieved comparable overall accuracy. Regarding the locoregional staging of invasive lobular carcinoma, there was a tendency for relative overestimation by MRI examination. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian metastasis of colorectal cancer is known to have a poor prognosis. This study aimed to elucidate the characteristics of patients who underwent oophorectomy for ovarian metastasis from colorectal cancer. Methods: This retrospective study included 16 patients who underwent oophorectomy for colorectal cancer metastasis to the ovary from January 2004 to December 2017. Improvement in patient's symptoms and pre- and postoperative changes in various nutritional and inflammatory indicators were assessed. Survival analysis and identification of prognostic factors were conducted with a median follow-up of 40.7 (5–109) months. Results: Of 16 patients, 12 had (75%) synchronous and 4 (25%) had metachronous metastasis. Fourteen patients were symptomatic but symptoms resolved postoperatively. Thirteen patients (81.3%) had ascites and 5 (31.3%) had pleural effusion on preoperative computed tomography that disappeared after surgery in all cases. The median value of prognostic nutritional factor was significantly increased postoperatively (36.0 [preoperatively] vs. 47.5, p < 0.0001). The median (interquartile range) values for lymphocyte-C-reactive protein ratio were 715.2 (110–2,607) preoperatively and 6,095.2 (1,612.3–14,431.8) postoperatively (p = 0.0214). The median survival of the entire cohort was 60.4 months. The 3-year survival rates for R0 + R1 and R2 cases were 83% and 24% (p = 0.018), respectively. Univariate analysis showed that R2 resection and low postoperative lymphocyte-C-reactive protein ratio were associated with poor prognosis. Conclusions: Oophorectomy for ovarian metastasis from colorectal cancers was safely performed. It improved the patients' symptoms and nutritional status and may result in improved prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has notably improved the 5-year survival in colorectal cancer (CRC) patients with peritoneal metastases (PM). This study investigated recurrence patterns and survival outcomes in patients with synchronous versus metachronous PM following complete CRS+HIPEC. Among 310 patients studied from June 2006 to December 2020, the recurrence rate was 79.7%, and sites were most frequently isolated peritoneal and multifocal recurrence. Recurrence locations did not differ between synchronous and metachronous PM groups. Notably, patients with metachronous PM had a shorter disease-free survival compared to synchronous PM (9.4 vs. 12.5 months, p = 0.01); however, the overall survival was similar. Despite frequent recurrence, especially at extraperitoneal sites, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3–12.1) vs. 12.5 months (95% CI: 11.2–13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2–46.8) vs. 40.8 months (95% CI: 28.8–46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 2 is a hereditary disease with predisposition to the development of multiple tumors of the central and peripheral nervous system. The disease is characterized by significant variability in the clinical picture; the number of neoplasms, their location, and growth rate largely determine the severity of the course. However, assessing the rate of tumor growth requires the availability of a consistent series of instrumental studies conducted within a certain time range, which is not always available at the time of initial treatment. In this study, on the basis of quantitative (age of onset, age of examination) and qualitative (large number of intracranial tumors, large number of spinal tumors, severity of neurological symptoms, mosaic status of the genetic variant) characteristics, an alternative classification of clinical subtypes of neurofibromatosis type 2 was developed. We have revealed statistically significant differences (p-value = 0.037) in the representation of Halliday prognostic classes between the groups identified using the proposed classification, which allows us to suggest the possibility of integrating this approach into clinical practice. [ABSTRACT FROM AUTHOR]

The best-known etiologies of hyperinsulinemic hypoglycemia are insulinoma, non-insulinoma pancreatogenous hypoglycemic syndrome, autoimmune processes, and factitious hypoglycemia. In 2009, a disease not associated with classic genetic syndromes and characterized by the presence of multiple pancreatic lesions was described and named insulinomatosis. We present the clinical and pathologic features of four patients with the diagnosis of insulinomatosis, aggregated new clinical data, reviewed extensively the literature, and illustrated the nature and evolution of this recently recognized disease. One of our patients had isolated (without fasting hypoglycemia) postprandial hypoglycemia, an occurrence not previously reported in the literature. Furthermore, we reported the second case presenting malignant disease. All of them had persistent/recurrent hypoglycemia after the first surgery even with pathology confirming the presence of a positive insulin neuroendocrine tumor. In the literature review, 27 sporadic insulinomatosis cases were compiled. All of them had episodes of fasting hypoglycemia except one of our patients. Only two patients had malignant disease, and one of them was from our series. The suspicion of insulinomatosis can be raised before surgery in patients without genetic syndromes, with multiple tumors in the topographic investigation and in those who had persistent or recurrent hypoglycemia after surgical removal of one or more tumors. The definitive diagnosis is established by histology and immunohistochemistry and requires examination of the "macroscopically normal pancreas." Our case series reinforces the marked predominance in women, the high frequency of recurrent hypoglycemia, and consequently, a definitive poor response to the usual surgical treatment. [ABSTRACT FROM AUTHOR]

Multiple primary lung cancers (MPLCs) are becoming more and more common and these patients can benefit from minimally invasive surgery. Here, we report a case of a patient diagnosed with synchronous MPLCs who underwent bilateral thoracoscopic pulmonary resections in a two‐stage strategy, and achieved a good surgical outcome and high quality of life. A 66‐year‐old female was found to have one major ground‐glass nodule (GGN) in the right upper lobe and eight minor GGNs in the left upper and lower lobes. The patient underwent right upper lobe resection and systematic mediastinal lymph node dissection via single‐utility port thoracoscopic surgery in September 2018. Pathology was lepidic predominant adenocarcinoma pT1bN0M0, IA2. Regular high‐resolution computed tomography examination during 36 months after right upper lobectomy showed gradually increasing diameter and solid component of multiple GGNs in left lung. The patient underwent thoracoscopic multiple pulmonary resections using an intraoperative localization technique in a hybrid operating room in October 2021 and all eight nodules in the left lung were resected. Two segmentectomies and four wedge resections were performed, and the pathological results of the eight nodules included four adenocarcinomas, three adenocarcinomas in situ, and one alveolar epithelial hyperplasia. The two operations were successful with no intra‐ or postoperative 90‐day complications. During more than 20 months of follow‐up after the second operation, the patient had well recovered pulmonary function and physical status with a Karnofsky performance status score of 90 and no local recurrence or metastasis. A two‐stage surgical strategy for synchronous MPLCs is therefore feasible. The surgical strategy, timing of intervention, and extent of pulmonary resection should be individually designed according to the location and characteristics of each nodule. Intraoperative localization of small GGNs is very important to ensure that all nodules are completely and accurately resected during the operation. [ABSTRACT FROM AUTHOR]

Introduction: It is clinically challenging to infer the phylogenetic relationship between different tumor lesions of patients with multiple synchronous lung cancers (MSLC), whether these lesions are the result of independently evolved tumor or intrapulmonary metastases. Methods: We used the Illumina X10 platform to sequence 128 stage I lung cancer samples collected from 64 patients with MSLC. All samples were analyzed for mutation spectra and phylogenetic inference. Results: We detected genetic aberrations within genes previously reported to be recurrently altered in lung adenocarcinoma including, EGFR, ERBB2, TP53, BRAF, and KRAS. Other putative driver mutations identified were enriched in RTK‐RAS signaling, TP53 signaling, and cell cycle. Also, we found some interesting cases, two cases that carried EGFR L858R and T790M co‐mutation in one tumor and another tumor with only EGFR 19del, and 1 case with two KRAS hotspots in the same tumor. Due to the short follow‐up time and early stage, further investigation is needed to determine whether this unique mutation profile will affect their progression‐free survival (PFS) and overall survival (OS). Regarding genetic evolution analysis among 64 tumor samples, 50 of them display distinct mutational profiles, suggesting these are independently evolved tumors, which is consistent with histopathological assessment. On the other hand, six patients were identified to be intrapulmonary metastasis as the mutations harbored in different lesions are clonally related. Conclusion: In summary, unlike intrapulmonary metastases, patients with MSLC harbor distinct genomic profiles in different tumor lesions, and we could distinguish MSLC from intrapulmonary metastases via clonality estimation. [ABSTRACT FROM AUTHOR]

Case: Glomus tumors of the hand are rare tumors that occur predominantly in the subungual region. Though multicentric glomus tumors have been reported in the subungual region involving the nailbed, monostotic multiple intraosseous glomus tumors have not been reported so far. We report a case of a 36 year-old woman who presented with a 5-year history of intermittent thumb pain, aggravated with exposure to cold or pressure. A glomus tumor of the thumb was excised, but symptoms returned 3 months later. She ultimately underwent curettage with bone grafting of a recurrent glomus tumor at the same site, and has been free of symptoms for 1.5 years. Conclusion: Intraosseous glomus tumors may present as multiple synchronous lesions. This, to the best of our knowledge, is the first case report of monostotic multiple intraosseous glomus tumors. [ABSTRACT FROM AUTHOR]

Objects: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. Methods: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. Results: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2‐3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0‐1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. Conclusions: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative 18F-FDG PET/CT is valuable in detecting colon lesions not visualized by conventional workup, especially in patients with incomplete colonoscopy. 18F-FDG PET/CT highlights distant metastases but exhibits limitations for N staging. The quantitative analysis of 18F-FDG uptake in the primary tumor did not reveal any association with recurrence or disease-free survival, adding no prognostic information. We analyzed whether preoperative 18F-FDG PET/CT adds to conventional primary staging in patients with presumed non-metastatic colonic cancer (CC). The prognostic role of 18F-FDG uptake in the primary tumor was evaluated after a mean follow-up of 15 years. Patients with a new diagnosis of presumed localized CC were prospectively enrolled and underwent presurgical 18F-FDG PET/CT. For each colon lesion, SUVmax, SUVpeak, TLG, and MTV were assessed and tested as prognostic factors. Forty-eight patients were included. Post-surgery pathology identified a total of 103 colon lesions, including 58 invasive adenocarcinomas, 4 in situ adenocarcinomas, 3 adenomas with high-grade dysplasia, and 38 adenomas with low-grade dysplasia. Per lesion sensitivity, specificity, positive (PPVs) and negative predictive values (NPVs) for colonic primary tumor detection were 78%, 97%, 98%, and 73% for conventional workup, and 94%, 87%, 92%, and 89% for 18F-FDG PET/CT. Only sensitivity was significantly different between 18F-FDG PET/CT and conventional workup. PET detected an additional ten pathological colonic lesions in seven patients. SUVmax, SUVpeak, and TLG showed significant differences between invasive adenocarcinomas, in situ adenocarcinomas, and high-grade dysplasia compared to low-grade dysplasia. There was a statistically significant difference between pT1-pT2 and pT3-pT4 adenocarcinomas. On patient-based analysis, sensitivity, specificity, PPV, and NPV for nodal staging were 22%, 84%, 44%, and 65% for CECT, and 33%, 90%, 67%, and 70% for 18F-FDG PET/CT, without a statistically significant difference. PET/CT also identified unknown metastatic spread and one synchronous lung cancer in four patients. Overall, 18F-FDG PETCT had an additional diagnostic value in 11 out of 48 patients (23%). 18F-FDG uptake of the primary tumor did not predict nodal or distant metastases. The difference in disease-free survival categorized by median SUVmax, SUVpeak, TLG, and MTV was not significant. Finally, preoperative 18F-FDG PET/CT is valuable in detecting potential colon lesions not visualized by conventional workups, especially in cases of incomplete colonoscopy. It effectively highlights distant metastases but exhibits limitations for N staging. Mainly due to the relatively small sample size, the quantitative analysis of 18F-FDG uptake in the primary tumor did not reveal any association with recurrence or disease-free survival, adding no significant prognostic information. [ABSTRACT FROM AUTHOR]

Simple Summary: Synchronous bilateral breast cancers are uncommon. While metastatic staging guidelines in patients with unilateral cancer are established, the indication for metastatic staging in patients with bilateral breast cancers remains unclear. This study aimed to retrospectively determine if all synchronous bilateral breast cancer patients need metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. In our study, negative nodal status was predictive for negative metastatic staging results at diagnosis in patients with synchronous bilateral breast cancers. Nodal status alone, however, may not detect all cases with systemic metastasis. Hence, symptoms of systemic metastasis and metastatic nodal status could be used to determine the subgroup of synchronous bilateral invasive cancer patients who require metastatic staging. This finding could be validated in larger studies. Background: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. Methods: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging. Results: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients. Conclusions: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies. [ABSTRACT FROM AUTHOR]