Smaller Tumor Size Research Articles

Folic Acid-Targeted Mixed Pluronic Micelles for Delivery of Triptolide

The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA–F-127/F-68–TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA–F-127/F-68–TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA–F-127/F-68–Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA–F-127/F-68–Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA–F-127/F-68–Nr, the fluorescence imaging system showed that FA–F127/F-68–Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA–F-127/F-68–TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA–F-127/F-68–TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA–F-127/F-68–TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA–F-127/F-68–TPL represents a promising antitumor drug delivery system.

Trends and Outcomes of Neoadjuvant Chemotherapy for Clinical Stage T1 Pancreatic Cancer.

Neoadjuvant chemotherapy (NC) for early pancreatic ductal adenocarcinoma (PDAC) remains controversial. We investigate the adoption of NC and its impact on survival in clinical T1 (cT1) PDAC. National Cancer Database (2006-2017) was reviewed for cT1 PDAC. Patients receiving NC and surgery were compared with patients undergoing upfront surgery (US). A total of 5886 patients were included. NC use increased from 4.8% in 2006 to 18.8% in 2017. The NC group (n = 618) versus the US group (n = 5268) had: younger age (66 years vs. 68 years), smaller tumor size (2 cm vs. 2.2 cm), more pancreas head tumors (77% vs. 70.6%), lower lymph-vascular invasion (25.9% vs. 40.6%), and less lymph node positivity (43.6% vs. 54.5%), p < 0.001. Factors associated with receipt of NC were: younger age, recent year of diagnosis, and treatment at an academic program. In the NC group versus the US group, median OS was 35.2 months versus 28.3 months, p < 0.001. Factors associated with improved survival included: well differentiated pathology, R0 surgical margins, and receipt of chemotherapy. In cT1 PDAC, chemotherapy is associated with improved survival. In a surgery-first approach, only 59% of patients receive adjuvant chemotherapy. These data suggest consideration of neoadjuvant therapy for early pancreatic cancer.

Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.

The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies. The study included 15489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database. A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies. The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

Strong Factors to Preserve Breast in Surgery Preferences among Javanese Ethnicities of Breast Cancer Patients.

As breast cancer treatment advances, more breast cancer patients have the option to keep their breasts. This offers them more choices based on their preferences. However, not all eligible patients opt for Breast-Conserving Surgery (BCS) due to various factors. This study aims to examine patient-related factors in the selection of surgical procedures in Javanese breast cancer patients. Between July 2023 to October 2023, the researcher collected data on 407 Javanese ethnic breast cancer patients of stage 1 and stage 2 from the 2018-2022 database. These patients were then divided into 2 groups, those who opted for BCS or breast preservation and those who chose mastectomy without breast reconstruction. Then, data regarding factors that were considered to influence the patients' choice of surgery type were collected. The researchers collected complete data from the 240 respondents. The factors in these 2 groups were then analyzed univariately. Factors that tended to influence were analyzed in a multivariate way. The determined significance level was 0.05. Of the 240 Javanese early breast cancer, 152 (66.2%) who were eligible for BCS, chose mastectomy, and 81 (33.8%) of them chose BCS. The multi-variate data showed that many patients who preferred BCS over mastectomy were in the group with small tumor sizes with OR 2.78 and P 0.01. The second strong factor was the small number of children with OR 2.74 and P 0.01. Other factors that also influenced were the patients' old age, single status, high education, and without neoadjuvant chemotherapy (NAC). Of all the Javanese early breast cancer patients, only 33.8% chose BCS. Factors that supported the choice of BCS were small tumor size, a small number of children, old age, single status, high education, and no NAC. But Tumor size was the strongest factor.

Gliosarcoma: A Multi-Institutional Analysis on Clinical Outcomes and Prognostic Factors.

This study describes oncological outcomes and investigates prognostic factors for patients with gliosarcomas (GSM). Histopathologically confirmed GSM patients who underwent treatment at five European institutions were retrospectively analyzed. We analyzed 170 patients with a median clinical follow-up time of 9.2 months. The majority received surgery (94.1%), postoperative radiotherapy (pRT, 81.8%), and temozolomide (TMZ)-based postoperative chemotherapy (66.5%). The median overall survival (OS) and progression-free survival (PFS) were 12.3 and 6.6 months, respectively. In the multivariable Cox regression analysis (MVA), the following factors were significantly associated with OS: age per year (hazard ratio (HR): 1.03, p < 0.001), subtotal resection (STR) versus biopsy only (HR: 0.15, p = 0.018), gross total resection (GTR) versus biopsy only (HR: 0.13, p = 0.011), pRT versus no pRT (HR: 0.20, p < 0.001), postoperative TMZ-based chemotherapy versus no postoperative chemotherapy (HR: 0.44, p = 0.003), MGMT promoter non-methylated versus methylated (HR: 1.79, p = 0.05), and tumor diameter per cm (HR: 1.15, p = 0.046). For PFS, the following factors were significantly associated in the MVA: GTR versus biopsy only (HR: 0.19, p = 0.026), pRT versus no pRT (HR: 0.36, p = 0.006), postoperative TMZ-based chemotherapy vs. no postoperative chemotherapy (HR: 0.39, p < 0.001), MGMT promoter status unknown versus methylated (HR: 1.69, p = 0.034), and tumor diameter per cm (HR: 1.18, p = 0.016). Sex, primary or secondary GSM, and TP53 mutational status were not significantly associated with OS or PFS. Trimodal therapy comprising surgical resection, pRT and TMZ-based chemotherapy appears to have the most beneficial effect on survival in GSM patients. Smaller tumor size, younger age and methylated MGMT promoters are associated with improved survival. To our knowledge, this is the largest multi-institutional cohort study investigating outcomes and prognostic factors for GSM.

Determinants of tumor necrosis and its impact on outcome in patients with Localized osteosarcoma uniformly treated with a response adapted regimen without high dose Methotrexate– A retrospective institutional analysis

PurposeResponse to neoadjuvant chemotherapy in form of tumor necrosis predicts outcome in osteosarcoma; although response-adapted treatment escalation failed to improve outcome among patients treated with high-dose methotrexate-based (HDMTx) chemotherapy. This study aimed to identify factors predicting tumor necrosis and its impact on survival among patients with non-metastatic osteosarcoma treated with a response-adapted non-HDMTx regimen. MethodsA retrospective single-institutional study was conducted among non-metastatic osteosarcoma patients treated with neoadjuvant therapy between 2004–2019. Patients were treated uniformly with three cycles of neoadjuvant cisplatin/doxorubicin. Post-operatively, patients with favourable necrosis (≥90 %) received 3 cycles of cisplatin/doxorubicin, while patients with poor necrosis (<90 %) received escalated treatment with alternating six cycles of cisplatin/doxorubicin and ifosfamide/etoposide. Propensity score matching (PSM) analyses were conducted to ascertain independent impact of necrosis on event-free survival (EFS) and overall survival (OS). ResultsOf 594 registered osteosarcoma patients, 280 patients (median age 17 years; male 67.1 %) were included for analysis. 73 patients (26.1 %) achieved favourable necrosis. Patients with smaller tumor size (≤10 cm) (aOR = 2.28; p = 0.030), lower serum alkaline phosphatase (≤450 IU/L) (aOR = 2.10; p = 0.035), and who had surgery earlier (<115 days) (aOR = 2.28; p = 0.016) were more likely to have favourable necrosis. On 1:2 PSM analysis, patients not achieving favourable necrosis demonstrated inferior EFS (HR = 2.68; p = 0.003) and OS (HR = 3.42; p = 0.003). ConclusionsPatients of osteosarcoma with smaller tumor, lower serum alkaline phosphatase and earlier surgery are more likely to achieve favourable necrosis. Tumor necrosis independently predicts outcome in osteosarcoma, and response-adapted treatment escalation fails to overcome the adverse impact of poor necrosis in non-HDMTx based regimen.

MITRAL STENOSIS PRESENTATION REVEALING ALARGE LEFT ATRIAL MYXOMA

Introduction: Cardiac myxoma (CM) is the most frequent benign primary cardiac tumor. Around 75% of myxomas originate in the left atrium 20% arise from the right atrium while the remaining 5% are born from both the atria and the ventricle. Atrial myxomas can result in many symptoms: heart failure, systemic or pulmonary embolism, arrhythmias, and conductive disorders, or also constitutional symptoms (such as fever, and weight loss). It largely relies on the tumors size, location, and architecture. It can obstruct the blood flow, mimicking mitral stenosis. The surgical management is the cornerstone of this entity. Case Report: A 63-year-old female with a past medical history of diabetes and arterial hypertension was admitted to our department for palpitations and acute heart failure symptoms.The physical examination revealed an irregular pulse with a tachycardia of 150 bpm. The blood pressure was at 118/80 mmHg. It also revealed lower limb edema, lung crackles, and ascites with a mitral stenosis murmur. EKG showed atrial fibrillation at 150HR . Transthoracic echocardiography found dilated atriums with a large mass in the left atrium causing mitral pseudo stenosis . Discussion: Myxomas are primary cardiac tumors that originate from multipotent mesenchymal cells. They can occur at any age but mostly between 30 and 60 years. The incidence of myxoma in women is 2 to 4 times higher than in men. Clinically, atrial myxomas vary from asymptomatic especially with small tumor size, to non-specific symptoms (dyspnea, lower limb and pulmonary oedema, angina, syncope, and palpitation) and constitutional symptoms such as fever, fatigue, and weight loss. The diagnosis of atrial myxoma based on its presentation is challenging. echocardiography is usually the modality of choice which helps identify the location of the mass whether itÂ’s intra or pericardial, its size, attachment and mobility. Furthermore, it differentiates atrial myxoma from any thrombus or vegetation. Once a presumptive diagnosis of myxoma has been made on imaging studies, prompt resection is required because of the risk of embolization or cardiovascular complications, including sudden death. Conclusion: Myxoma continues to be a significant challenge for emergency physicians due to its non-specific symptoms and overlap with other conditions. The discrepancy between mild symptoms and the serious consequences the condition carries, necessitates high index of suspicion and thorough investigation to timely diagnose it among a long list of differentials.

Clinical Significance of Gross Extrathyroidal Extension to Only the Strap Muscle According to Tumor Size in Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis.

The presence of extrathyroidal extension (ETE) in patients with differentiated thyroid cancer (DTC) serves as a significant prognostic indicator. Consequently, the staging of DTC is categorized into extensive ETE and gross ETE that solely impacts the strap muscles (gross strap muscle invasion [gSMI]). However, there is a lack of sufficient evidence concerning the relationship between gSMI and prognosis, particularly in terms of tumor size. Relevant literature was searched in Medline, Embase, Cochrane Library, and KoreaMed. All procedures were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and carried out by two independent reviewers. The meta-analysis utilized a random-effects model to account for the diversity of the studies. Risk of Bias for Nonrandomized Studies (RoBANS) version 2.0, an evaluation tool for non-randomized studies, was employed to assess the quality of the selected research. Clinical data from observational studies that examined the relationship between the degree of ETE and prognosis were gathered, and a meta-analysis was conducted. Eighteen observational studies were included in this analysis. Subgroup analyses were conducted for each outcome. The findings revealed that the recurrence rate (odds ratio [OR], 2.498), disease-specific mortality (risk ratio [RR], 2.984), overall mortality (RR, 1.361), and lymph node (LN) metastasis (OR, 5.355) were significantly higher in patients with gSMI than in those without ETE. However, when the analysis was restricted to tumors measuring 4 cm or smaller, no significant differences in prognostic outcomes were observed, with the exception of LN metastasis. gSMI negatively impacts prognosis; however, this correlation diminishes with smaller tumor sizes. Thus, a more cautious approach is warranted during the treatment process.

Co-expression of multiple transcription factors is associated with clinical features and endocrine prognosis in growth hormone-secreting pituitary adenomas.

The types of growth hormone-secreting pituitary adenomas are diverse, we have found that there are significant differences in clinical features and prognosis between PIT-1 single-cell spectrum growth hormone adenomas and growth hormone phenotypic polyhormonal adenomas. This study examined a cohort of 193 patients with growth hormone-secreting pituitary adenoma (GHPA), stratifying them into two groups: PIT-1 single transcription factor positive growth hormone adenoma (STF-GHPA) and Multiple transcription factor-positive growth hormone-secreting adenomas (MTF-GHPA). The objective was to compare these two groups' clinical characteristics. Within the MTF-GHPA group, we further subtyped them based on transcription factors to evaluate potential variations in clinical manifestations. Logistic regression analyses were employed to develop a risk factor model for investigating factors influencing hormone remission. There were no statistically significant differences in terms of age, gender, serum GH, and IGF-1 levels between patients diagnosed with MTF-GHPA and STF-GHPA. However, patients with MTF-GHPA exhibited a higher proportion of hypopituitarism compared to those with STF-GHPA. Furthermore, MTF-GHPA were characterized by smaller tumor size and less invasiveness, as indicated by lower Knosp classes. However, patients with MTF-GHPA have a lower rate of hormonal remission (30.8%) and more postoperative complications (31.0%), which means that STF-GHPA (hormonal remission:71.6%; postoperative complications:13.4%) has a better endocrine outcome than MTF-GHPA patients. Between the PIT-1 + SF-1+ and PIT-1 + TPIT+ subtypes within MTF-GHPA, significant differences were also observed in tumor size, endocrine outcomes, and postoperative complications. Risk factors influencing hormonal remission for GHPA included preoperative GH level, primary/recurrent, extent of resection, and transcription factor expression. Co-expression of multiple transcription factors is an important factor associated with clinical behavior and endocrine outcomes in patients with GHPA.

Roles of miR-20a-5p in breast cancer based on the clinical and multi-omic (CAMO) cohort and in vitro studies

MicroRNAs are involved in breast cancer development and progression, holding potential as biomarkers and therapeutic targets or tools. The roles of miR-20a-5p, a member of the oncogenic miR-17-92 cluster, remain poorly understood in the context of breast cancer. In this study, we elucidate the role of miR-20a-5p in breast cancer by examining its associations with breast cancer risk factors and clinicopathological features, and its functional roles in vitro. Tissue microarrays from 313 CAMO cohort breast cancer surgical specimens were constructed, in situ hybridization was performed and miR-20a-5p expression was semiquantitatively scored in tumor stromal fibroblasts, and in the cytoplasm and nuclei of cancer cells. In vitro analysis of the effect of miR-20a-5p transfection on proliferation, migration and invasion was performed in three breast cancer cell lines. High stromal miR-20a-5p was associated with higher Ki67 expression, and higher odds of relapse, compared to low expression. Compared to postmenopausal women, women who were premenopausal at diagnosis had higher odds of high stromal and cytoplasmic miR-20a-5p expression. Cytoplasmic miR-20a-5p was significantly associated with tumor grade. In tumors with high cytoplasmic miR-20a-5p expression compared to low expression, there was a tendency towards having a basal-like subtype and high Ki67. In contrast, high nuclear miR-20a-5p in cancer cells was associated with smaller tumor size and lower odds of lymph node metastasis, compared to low nuclear expression. Transfection with miR-20a-5p in breast cancer cell lines led to increased migration and invasion in vitro. While the majority of our results point towards an oncogenic role, some of our findings indicate that the associations of miR-20a-5p with breast cancer related risk factors and outcomes may vary based on tissue- and subcellular location. Larger studies are needed to validate our findings and further investigate the clinical utility of miR-20a-5p.

Siglec-15 expression in diffuse gliomas and its correlation with MRI morphologic features and apparent diffusion coefficient.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) enhances tumor immune escape and leads to tumor growth. To investigate the expression of Siglec-15 in diffuse gliomas and its correlation with tumor magnetic resonance imaging (MRI) features. This study included 57 patients with gliomas. Morphological MRI features, including the largest tumor diameter, enhancement category, location, calcification, cysts, and hemorrhage, were visually rated. Apparent diffusion coefficient (ADC) values were calculated in tumor region. MRI morphologic features and ADC were compared between patients with positive and negative Siglec-15 expression. Receiver operating characteristic (ROC) curves were further constructed to assess the diagnostic performance. Siglec-15 was expressed in immunocytes, such as macrophages in the peritumoral area. Siglec-15 expression was positive in 20/57 (35.09%) patients, with higher expression in patients with IDH-mutant gliomas and lower grade gliomas. The tumor diameter was significantly smaller in patients with positive Siglec-15 expression than in those with negative expression for all patients (P = 0.017) and for patients with IDH-mutant gliomas (P = 0.020). Moreover, ADC values of the tumor were significantly higher in patients with positive Siglec-15 expression than in those with negative expression for all patients (P = 0.027). The areas under the ROC curve (AUCs) of the diameter and ADC were 0.702 and 0.686, respectively. A combination of these two parameters generated an improved AUC of 0.762. Siglec-15 was expressed in immunocytes such as macrophages in the peritumoral area, with a positive rate of 35.09%. Positive Siglec-15 expression in diffuse gliomas was correlated with smaller tumor size and higher ADC values.

Descriptive Analysis of Common Fusion Mutations in Papillary Thyroid Carcinoma in Hungary

Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto’s disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto’s disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes.

Correlation between White Globe Appearance and Clinicopathologic Characteristics in Early Gastric Cancer.

Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type (differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

Comparison of Patient-Reported Outcomes Between Active Surveillance and Immediate Lobectomy in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Initial Findings from the KoMPASS Cohort.

Background: Patients diagnosed with low-risk papillary thyroid microcarcinoma (PTMC) face the decision between thyroid lobectomy and active surveillance (AS). This study aimed to investigate the factors influencing treatment decisions in low-risk PTMC and to compare the quality of life (QoL) according to the treatment plan. Methods: The multicenter prospective cohort study comparing AS and thyroid lobectomy was conducted. Clinical characteristics were compared between the AS and Lobectomy groups. QoL questionnaires were administered every 6 months in the initial year and annually thereafter. Results: A total of 927 patients (453 in the AS group and 474 in the Lobectomy group) with low-risk PTMC were included in this study. The mean age was 47.4 ± 12.2 years, and 72.2% of the patients were women. Older age (odd ratio [OR] 1.04, confidence interval [CI] 1.02-1.05, p < 0.001), smaller tumor size (OR 0.78, CI 0.69-0.87, p < 0.001), family history of thyroid cancer (OR 1.48, CI 1.03-2.12, p = 0.035), prior awareness of AS (OR 1.53, CI 1.16-2.02, p = 0.003), and higher income (OR 1.79, CI 1.13-2.83, p = 0.013) were significantly associated with a higher likelihood of choosing AS. The median follow-up was 27.3 months (23.9-43.9) in the AS group and 28.7 months (20.4-44.5) in the Lobectomy group. During the follow-up period, the AS group showed significantly better QoL scores compared with the Lobectomy group (β 0.17, CI 0.02-0.33, p = 0.029). Although baseline QoL scores favored the AS group significantly (7.1 ± 1.2 vs. 6.7 ± 1.2, p < 0.001), no significant difference was observed after 12 months (7.2 ± 1.2 vs. 7.1 ± 1.2, p = 0.592). Conclusions: This study demonstrated that age, tumor size, family history of thyroid cancer, awareness of AS, and income were associated with patients' treatment choices. Although the overall QoL scores were significantly higher in the AS group, the QoL became similar between the two groups after 12 months. Clinical Trial Registration: KCT0004935.

Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones.

7161 Similar Progression-Free Survival in Familial Non-medullary Thyroid Cancer and Sporadic Differentiated Thyroid Cancer Patients

Abstract Disclosure: E. Chuki: None. N. Behairy: None. S. Auh: None. A. Makarewicz: None. N. Uttarkar Vikram: None. P. Padmasree: None. C. Cochran: None. S. Gubbi: None. J. Klubo-Gwiezdzinska: None. Background: There is conflicting data on the disease aggressiveness in patients with Familial Non-medullary Thyroid Cancer (FNMTC) as compared with sporadic differentiated thyroid cancer (sDTC). Moreover, limited evidence exists comparing FNMTC and sDTC responsiveness to treatment. Therefore, the goal of this study was to compare response to standard therapy, defined as progression-free survival (PFS), in patients with FNMTC and sDTC. Methods: This was a single-center Institutional Review Board-approved cohort study, including patients diagnosed with FNMTC or sDTC, subjected to standard therapy with a median follow-up of 4.8 years (range 2.1-10 years). Patients with FNMTC were matched to patients with sDTC in a 1:2 ratio using the Ccoptimalmatch package in R based on age, sex, and American Thyroid Association (ATA) risk stratification at presentation. PFS was defined from the date of initial thyroid surgery to the first evidence of progression, assessed by RECIST 1.1 criteria. Demographics, cancer characteristics, and treatment modalities were collected and compared. Kaplan-Meier curves and log-rank tests were employed to assess differences in PFS. SAS 9.4 software was used for analyses, with a p-value set at 0.05. Results: The study consisted of 198 subjects, with 66 patients affected by FNMTC and 132 sDTC cases, aged 43.1±14.3, 69.7% female, 47% low, 45.5% intermediate and 7.6% high ATA risk for recurrence. Within the FNMTC cohort 26 (39.4%) cancer cases were detected by screening. There were no differences in age, sex and ATA risk stratification between the study groups due to exact matching (±1 year for age). No significant differences were observed in histology type (p = 0.49), multifocality (p = 0.59), gross extrathyroidal extension (p = 0.76), or presence of distant metastases (p = 0.09). FNMTC exhibited smaller tumor size at diagnosis (mean 1.2±0.96 vs 1.8±1.5 cm, p &amp;lt; 0.01), and fewer positive lymph nodes (p = 0.02). Initial surgery extent favored more total thyroidectomies in the FNMTC group (p &amp;lt; 0.01), and there was a higher prevalence of repeat neck surgeries in the sDTC group (p = 0.045). There was no difference in utilization of RAI therapy between the groups (p = 0.68). During follow up 15.2% of FNMTC and 12.9% of sDTC patients presented with disease progression. PFS probabilities at 5, 10, 15, 20, and 25 years were similar between both groups (0.8 and 0.85 at 5 years, 0.8 and 0.78 for subsequent years) (p = 0.99). Conclusions: The initial surgical treatment for FNMTC tends to be more extensive than applied in sDTC, despite a smaller tumor size and lower number of metastatic lymph nodes at diagnosis. This strategy could lead to a lower need for repeat neck surgeries. The smaller tumor size at diagnosis of FNMTC might be a result of an active screening of affected families. The similar PFS in patients with FNMTC and sDTC suggests a comparable tumor biology and similar responsiveness to standard therapy. Presentation: 6/3/2024

Rates and predictors of loss to follow-up for sporadic vestibular schwannomas undergoing imaging surveillance.

Imaging surveillance with serial MRI, or a "wait-and-scan" approach, is a management option for patients with small or medium-sized vestibular schwannomas (VSs). Prior publications have indicated no distinct quality of life advantage to upfront treatment compared with initial wait-and-scan management. However, imaging surveillance is dependent on patient adherence to follow-up. In this study, the authors aimed to identify rates and predictors of patient loss to follow-up during wait-and-scan management of sporadic VS. A single-center study was conducted including all patients from 2013 to 2018 who had undergone upfront imaging surveillance of sporadic VS. Patient data were retrospectively obtained from the electronic medical record. Outcomes of interest included loss to follow-up unrelated to death and inconsistent adherence to imaging surveillance recommendations. Logistic regression analyses were conducted to evaluate factors associated with loss to follow-up. Over a 6-year study period, 270 patients underwent initial imaging surveillance of a sporadic VS. The median tumor diameter was 8.6 mm (range 1-28.9 mm). At the time of censoring, 106 patients (39.3%) had received treatment, 157 (58.1%) had been advised to continue follow-up, and 7 (2.6%) had died of non-VS-related causes. In total, 73 patients (27.0%) were completely lost to follow-up prior to the first treatment or death. Additionally, 60 patients (22.2%) missed at least 1 MRI follow-up or imaging follow-up was delayed by more than 1 year. Multivariable logistic regression identified an out-of-state residence (OR 3.05, 95% CI 1.58-5.89, p = 0.0009) and a smaller tumor size (unit OR per 1-mm increase in size, OR 0.88, 95% CI 0.83-0.95, p = 0.0006) to be associated with loss to follow-up. Patients living ≥ 350 miles from the hospital or with tumors ≤ 3 mm at the time of initial clinic evaluation were most likely to be lost to follow-up. Only a smaller tumor size was associated with an increased risk of inconsistent imaging follow-up (unit OR per 1-mm increase in size, OR 0.92, 95% CI 0.87-0.98, p = 0.007). Patients undergoing imaging surveillance of VS are at risk for loss to follow-up and inconsistent imaging surveillance. Patients with smaller tumors or those living farther away from the treating institution are at highest risk for being lost to follow-up.

Association of Hashimoto thyroiditis with papillary thyroid carcinoma and its clinical features – A retrospective study in a tertiary care hospital

Background: Papillary thyroid carcinoma (PTC) is the most widespread endocrine malignancy. Among the several risk factors, Hashimoto thyroiditis (HT) is one of the factors associated with increased incidence of PTC. Both HT and PTC share several epidemiologic features including high prevalence, female predominance, and increased incidence in iodine-sufficient areas. Aims and Objectives: The aim of the study was to assess the incidence of HT and PTC coexistent in endemic population. The study also aimed to determine the association of various prognostic parameters of PTC in patients with coexistent HT. Materials and Methods: This was a retrospective study done from May 2019 to May 2024 over a period of 5 years in a tertiary care hospital of West Bengal. A total of 54 patients with primary PTC who underwent total thyroidectomy with cervical lymph node dissection (LND) were studied. Patients with primary PTC with neck LND and complete medical history were included in this study. Patients with previous thyroidectomy surgery or patients with incidental PTC diagnosed in thyroidectomy specimens done for a benign neoplasm (without LND) were excluded from the study. Results: A total of 54 cases of PTC were studied out of which 23 cases were PTC associated with HT and 31 cases were PTC without HT constituting 42.59% and 57.4%, respectively. PTC associated with HT had a greater incidence in females. In this study, our results showed that PTC with HT had a greater tendency of tumor multifocality, greater mean lymph node size, and increase rate of extranodal tumor extension. At the same time, patients of PTC associated with HT had smaller tumor size and low clinical stage. Conclusion: PTC associated with HT had a female preponderance, larger metastatic lymph node, a tendency for multifocality, and extranodal extension. At the same, they also had smaller tumor size and low clinical stage indicating a complex and controversial effect of HT on PTC.

ECMTrans-net: Multi-Class Segmentation Network Based on Tumor Tissue in Endometrial Cancer Pathology Images

Endometrial cancer has the second highest incidence of malignant tumors in the female reproductive system, and accurate and efficient endometrial cancer pathology image analysis is one of the important research components of computer-aided diagnosis. However, endometrial cancer pathologic images have the challenges of smaller solid tumors, lesion areas varying in morphology, and difficulty distinguishing solid and non-solid tumors, which would impact the accuracy of subsequent pathological analyses. Therefore, an Endometrial Cancer Multi-class Transformer Network (ECMTrans-net) is proposed to improve the segmentation accuracy of endometrial cancer pathology images. On the one hand, an ECM-Attention is proposed, which can sequentially infer attention maps along three separate dimensions: channel, local spatial, and global spatial, and multiply the attention maps and the input feature map for adaptive feature refinement, solving the problems of the small size of solid tumors and similar characteristics of solid tumors to non-solid tumors and further improving the accuracy of segmentation of solid tumors. On the other hand, an ECM-Transformer is proposed, which can fuse multi-class feature information and dynamically adjust the receptive field, solving the issue of complex tumor features. Experiments on the solid tumor endometrial cancer pathological (ST-ECP) dataset show that the ECMTrans-net performs superior to state-of-the-art image segmentation methods, and the average values of Accuracy, MIoU, Precision, and Dice were 0.952, 0.927, 0.931 and 0.901, respectively.

Treatment strategies with electrochemotherapy for limb in-transit melanoma: Real-world outcomes from a European, retrospective, cohort study

BackgroundThis study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM). MethodsWe audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006–2020) within the International Network for Sharing Practices of ECT (InspECT). Results452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1–8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years. ConclusionsAmong patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support.