Histological Type Research Articles

The correlation between Ki 67 and Oncotype Dx on HR+, HER2- early breast cancer management: Insights of molecular testing.

e12546 Background: Elevated Ki-67 expression serves as an indicator of tumoral proliferation in breast cancer (BC) and is used in Ecuador for survival estimation, recurrence risk assessment, and guiding chemotherapy decisions. The Oncotype DX Breast Recurrence Score (ODX RS) is a validated 21-gene assay for hormone receptor-positive, HER2-negative invasive BC. It predicts chemotherapy benefits and the risk of distant recurrence over 10 years and is a mortality indicator. ODX RS has the potential to reduce the need for chemotherapy, alleviate financial burdens, and enhance clinical outcomes. Despite conflicting evidence on the significance of Ki-67 in the ODX RS, there is a lack of exploration within Latin populations. This study aims to compare the correlation of immunohistochemical (IHC) measured Ki-67 to the ODX RS in the Ecuadorian population. Methods: A retrospective analysis included women with early BC who underwent ODX RS testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3/N0-N1a); IHC estrogen receptor (ER) positive; HER2 negative; and availability of tumor size, grade, lymph node status, and Ki67 proliferation index data. Exclusion criteria: patients with recurrent BC, incomplete pathology, or lacking IHC data. Patients were categorized into low (≤5%), intermediate (6%–29%), and high Ki67 expression groups (≥30%). Using the statistical software SPSS, the correlation between ODX scores and Ki-67 expression was analyzed using Pearson’s correlation coefficient. For risk stratification groups, Spearman's correlation was employed. Results: Among 77 patients undergoing Oncotype DX testing, 64 (with a mean age of 55) met the inclusion criteria. Eighty-six percent of cases were invasive ductal carcinomas (IDC). Seventeen percent exhibited low Ki-67 expression, 61% intermediate, and 20% high. No statistically significant correlation was found between IHC Ki-67 expression and ODX RS (r=0.051; p=0.69), neither when stratified by categories (r=0.086; p=0.50). A subanalysis based on risk categories showed 82% correspondence in the low Ki-67 group, 18% in the intermediate group, and 31% in the high Ki-67 group. No significant correlation was observed when stratified by histological types (invasive ductal carcinoma and invasive lobular carcinoma), nor by sample origin (core biopsy, excisional biopsy). Conclusions: There was no correlation between IHC Ki-67 expression and ODX risk scores in this study involving Ecuadorian patients. Our findings emphasize that IHC Ki-67 expression should not be the sole determinant for guiding therapeutic decisions and predicting recurrence in early breast cancer.[Table: see text]

Preoperative and postoperative platelet-lymphocyte ratio as a prognostic marker for patients with soft tissue sarcoma treated with curative resection.

e23568 Background: In cancer development and progression, systemic inflammation has been implicated. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. In this study, we explored the prognostic relevance of initial and postoperative systemic inflammatory markers (neutrophil -lymphocyte ratio, platelet -lymphocyte ratio) on relapse-free survival (RFS) and overall survival (OS) in patients with soft -tissue sarcoma (STS) who underwent curative resection. Methods: We included a total of 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital (Daegu, Korea,) between 2004 and 2018. Kaplan-Meier curves and RFS and OS were calculated using multivariate Cox proportional models. Results: The median age of the patients was 55 years (range 27 - 86) and the ratio of male-to-female ratio was approximately 1:1. A total of 67 (75.3%) patients demonstrated a high initial neutrophil-lymphocyte ratio(NLR) (≥4.1) and 65 (75.3%) showed a high initial platelet-lymphocyte ratio(PLR) (≥231). After curative resection, the number of patients with high NLR and PLR was 16(18.0%) and 17 (29.3%). In both the NLR and PLR groups, including the postoperative NLR and postoperative PLR subgroups, no significant differences were observed in terms of age, sex, histologic type, tumor site, tumor size, tumor depth, or American Joint Committee on Cancer staging when stratified into high and low subgroups. In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (hazard ratio[HR]: 2.120; 95% confidence interval[CI]: 1.021 - 4.883, p = 0.017) and OS (HR: 5.073; 95% CI: 1.731 - 14.87, p = 0.003). Patients with a high PLR (PLR > 231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was significantly associated with a decreased RFS (HR: 3.921; 95% CI: 1.738 - 8.845, p = 0.001) and OS (HR: 5.702; 95% CI: 1.099 -29.576, p = 0.038). Conclusions: The present results suggest that the preoperative and postoperative PLR ratio can be used as a cost- effective prognostic marker for oncologic outcomes in patients with STS who underwent surgery.

Unveiling inequalities: An analysis of treatment disparities of primary gallbladder neuroendocrine tumors by race, ethnicity, and socioeconomic status from the National Cancer Database.

e16385 Background: Gallbladder neuroendocrine tumors (NETs) are exceedingly rare tumors and carry a poor prognosis. Racial/ethnic disparities and socioeconomic status have been known to influence cancer treatment and outcomes. This study explores racial/ethnic and socioeconomic disparities in treatment patterns of primary gallbladder NETs, focusing on factors affecting receipt of chemotherapy and multimodal therapy. Methods: We analyzed primary gallbladder NETs patients using the National Cancer Database (NCDB) from 2004 to 2020. Racial groups were divided into White and Black categories, and then those groups were further divided into Hispanic White, non-Hispanic White, Hispanic Black, and non-Hispanic Black categories according to ethnicity. We considered socioeconomic factors, tumor histology, and facility type. Logistic regression was used to determine the odds of receiving chemotherapy and multimodality therapy. The significance of disparities was determined using odds ratio (OR) and p-value. Results: Of 1,195 primary gallbladder NET patients, 59% (708 patients) underwent surgery. These patients had a median age of 65 years, with a female majority (64%) and predominantly White ethnicity (73.6%). Insurance coverage varied, with 48.9% having Medicare and 35.6% private insurance, while 3.9% were uninsured and 8.6% were covered by Medicaid. The study highlighted key factors affecting the receipt of surgery. Notably, racial disparities were apparent, with Black patients less likely to receive surgery compared to White patients (OR: 0.52; P < .001). Furthermore, patients with typical carcinoid tumors were markedly more likely to receive surgery than those with other histology (OR: 10.93; P < .001). The type of treatment facility was influential, with patients in Academic/Research Programs more likely to receive surgery (OR: 0.41; P < .001) than those in Community Cancer Programs. Conclusions: This study highlights racial and socioeconomic disparities in chemotherapy and multimodality therapy for gallbladder NETs, with Black, uninsured, and Medicaid-insured patients less likely to receive treatment. These findings call for targeted policy and healthcare reforms to ensure equitable access and outcomes for all patients with this condition. [Table: see text]

Correlation of ADC values of adult brain tumors with the diagnosis and pathological grade: A cross-sectional multicenter study.

Brain tumors are common, requiring physicians to have a precise understanding of them for accurate diagnosis and treatment. Considering that various histological tumor types present different cellularity, we conducted this research to examine the role of apparent diffusion coefficient (ADC) values in the differential diagnosis and pathologic grading of brain tumor types. In this cross-sectional study, we gathered pathology reports of histological samples of adult brain tumors. The tissue sample of brain tumors were examined histologically by a pathologist. The magnetic resonance imaging data of these patients were interpreted by a neuroradiologist. The measured ADC values and ADC ratios were calculated. Standard mean ADC values were expressed as 10- 6 mm2/s. The findings were compared according to the histological diagnosis of each tumor. Sixty-eight patients were included in the study: 34 (50%) were male, and 34 (50%) were female. The average age of the patients was 51.69 + 16.40 years. In the examination of tumor type, 16 (23.5%) were astrocytoma, 9 (13.2%) were oligodendroglioma, 20 (29.4%) were glioblastoma, 4 (5.9%) were medulloblastoma, and 19 (27.9%) were metastatic tumors. the average value of ADC was statistically significantly different according to the pathological type of tumor (p < 0.001). The two-by-two comparison of average ADC among tumor types revealed significant differences, except for oligodendroglioma and glioblastoma (p-value = 0.87) and glioblastoma and medulloblastoma (p-value = 0.347). The average value of ADC and ADC ratio was statistically significantly different according to the pathological grade of the tumor (p < 0.001). In the two-by-two comparison of average ADC between all pathological grades of the tumor showed a significance difference except for Grade I and Grade II (p-value = 0.355). The mean value of ADC and ADC ratio for glioblastoma and metastatic tumors showed no significant difference. The assessment of brain tumor grade through ADC examination will help to estimate prognosis and devising suitable therapeutic strategies.

Safety and preliminary efficacy of EIK1001 in combination with atezolizumab in participants with advanced solid tumors.

2618 Background: Immune checkpoint inhibitors (ICIs) relieve immunosuppression of tumor-reactive T cells and enhance antitumor immune response; however, not all patients benefit and some become refractory. EIK1001 is a Toll-like receptor (TLR)7/8 agonist that stimulates myeloid and plasmacytoid dendritic cells, activating immune and inflammatory responses. This dual activity provides another pathway, distinct from effects on checkpoint proteins, to enhance antitumor T-cell activity alone or in combination with ICIs. Methods: Study BDB001-102 was a Phase 1, open-label, dose-escalation/expansion study of EIK1001 combined with atezolizumab (comb Rx). Enrollment criteria included participants (pts) ≥ age 18 with confirmed, RECIST-measurable advanced solid tumors. Primary study objectives included safety and tolerability, and secondary objectives included evaluation of dose-limiting toxicities, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy by RECIST 1.1. During dose escalation, pts received a range of doses of EIK1001 (QW IV) in combination with atezolizumab (1200 mg Q3W). Results: Forty-one pts (median age 65 years [range = 32 to 79]) with multiple, distinct histological tumor types and a median of 3 prior Rx regimens were enrolled. Overall, a total of 28/41 (68.3%) receiving EIK1001 + atezolizumab experienced a treatment-related adverse event (TRAE). Of these, 4/41 (9.8%) experienced a ≥ Grade 3 TRAE, including fatigue, nausea, hyponatremia, and lymphedema. Only 1/41 (2.4%) experienced manageable cytokine release syndrome. There were no deaths due to TRAEs. Of the efficacy-evaluable pts (n = 37), complete response (CR) or partial response (PR) was observed for 3/37 (8.1%). Disease control (including CR, PR, or stable disease) was observed in 19/37 (51.4%). The median duration of response (DOR) was 13 months (range = 10 to 27). One responder was PD-L1 negative yet had a &gt; 12-month DOR; another had a history of prior anti-PD-1 Rx yet experienced a 10-month DOR on comb Rx. EIK1001 PK was linear and dose-proportional, and was not affected by combination with atezolizumab. Conclusions: Overall, EIK1001 was well-tolerated with a manageable safety profile and showed encouraging preliminary efficacy across several tumor types in combination with atezolizumab. Responses were observed even in pts not anticipated to respond to atezolizumab monotherapy. Further development of EIK1001 is underway. Clinical trial information: NCT04196530 .

Advancing drug development by leveraging microdissection for proteogenomic analysis of histological sections.

e14660 Background: Combining laser capture microdissection (LCM) with proteogenomics in cancer research offers a targeted way to way to explore the intricate interactions between the tumor microenvironment and tumor cells proper. For immuno-oncology (IO) research, this is especially important, since improvements in the predictability of patient response to IO-based drugs is greatly needed. An improved understanding of the spatial relationships involving tumor cells, stromal cells, blood supply and immune cell interactions may help to inform drug development and improve the indicators of success for IO-based drug regimens. Methods: From fresh frozen tissue, LCM is used to isolate and obtain distinct histological cell types. Nucleic acids and proteins are extracted from captured cells for in-depth multi-modality molecular profiling assays. This includes multiple genomic modalities and a customized solution-based mass spectrometry proteomics approach for samples or specimens with a limited amount of tissue. Results: Optimizing the analysis of minute tissue quantities from LCM captured cells is challenging. Following the isolation of nucleic acids, DNA sequencing can be performed for the discovery and analysis of actionable mutations, copy number variation, and methylation profiles. RNA-seq may be performed for gene expression. Regarding genomic-based studies, commercial kits are often utilized for these steps due to their general availability, rapid innovation, and the robust performance of these products. However, this kit-based adaptive approach is not true for proteomics. There remains a need for highly sensitive proteomic methods targeting small-sized samples. Our novel proteogenomics approach is focused around a customized enhanced liquid chromatography mass spectrometry (LC-MS) analysis of micro-scale and/or nano-scale tissue sections. This is achieved with a silver-stained one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) approach developed for LC-MS analysis of fresh-frozen tissue specimens obtained via LCM. This includes an in-gel digestion method adjusted and specifically designed to maximize the proteome coverage from amount-limited LCM samples to better facilitate in-depth molecular profiling. Conclusions: A proteogenomic approach is reported that is utilizing amount limited tissue quantities from microdissected fresh frozen tissue. The methodology may also be applicable to other types of specimens having limited nucleic acids, protein quantity, and/or sample volume.

Safety and preliminary efficacy of EIK1001 in combination with pembrolizumab in participants with advanced solid tumors.

2521 Background: Immune checkpoint inhibitors (ICIs) relieve immunosuppression of tumor-reactive T cells and enhance antitumor immune response; however, not all patients benefit and some become refractory. EIK1001 is a Toll-like receptor (TLR)7/8 agonist that stimulates myeloid and plasmacytoid dendritic cells, activating immune and inflammatory responses. This dual activity provides another pathway, distinct from effects on checkpoint proteins, to enhance antitumor T-cell activity alone or in combination with ICIs. Methods: Study BDB001-101 was a Phase 1, open-label, dose-escalation/expansion study of EIK1001 as either monotherapy (mono Rx; previously reported) or combined with pembrolizumab (comb Rx). Enrollment criteria included participants (pts) ≥ age 18 with confirmed, RECIST-measurable advanced solid tumors. Primary study objectives included safety and tolerability, and secondary objectives included evaluation of dose-limiting toxicities, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy by RECIST 1.1. During comb Rx dose escalation, pts received a range of doses of EIK1001 (QW IV) in combination with pembrolizumab (200 mg Q3W). Results: Fifty-one pts (median age 67 [range 33 to 86]) with multiple, distinct histological tumor types and with a median of 3 prior Rx regimens were enrolled. Overall, a total of 42/51 (82.4%) comb Rx pts experienced a treatment-related adverse event (TRAE). A total of 9/51 (17.7%) experienced a ≥ Grade 3 TRAE, including fatigue, cytokine release syndrome (CRS), hemiparesis, hypertension, joint range of motion reduced, muscular weakness, pancreatitis, rash (maculopapular), skin plaque, and stomatitis. Overall, 5/51 (9.8%) experienced manageable CRS, with only 1 discontinuation due to CRS. There were no deaths due to TRAEs. Of the efficacy-evaluable pts (n = 50), complete response (CR) or partial response (PR) was observed for 7/50 (14.0%), including 3 CR and 4 PR. Disease control (including CR, PR, or stable disease) was observed in 24/50 (48.0%). The median duration of response was 10 months (range = 4 to 32 months). Responses were observed in pts with prior anti-PD-1 exposure as well as in those with low or negative PD-L1 tumor expression. EIK1001 PK was linear and dose-proportional, and combination with pembrolizumab did not affect EIK1001 PK. Conclusions: Overall, EIK1001 was well-tolerated with a manageable safety profile and showed encouraging preliminary efficacy across several tumor types in combination with pembrolizumab. Responses were observed even in heavily pretreated patients not anticipated to respond to pembrolizumab monotherapy. Further development of EIK1001 is underway. Clinical trial information: NCT03486301 .

Origin associated with heterogeneity amongst Hispanic patients with breast cancer in the United States.

e23077 Background: There are over 50 million self-identifying Hispanics in the United States. This, however, represents a heterogenous population variably affected by an array of determinants of health, including race and insurance status. We used a national registry to investigate for significant differences in outcomes of Hispanic patients with breast cancer in the United States by country of origin. Methods: We identified a cohort of Hispanic patients in the United States with breast cancer for which origin was documented using the 2004-2019 National Cancer Database (NCDB) dataset. The NCDB delineates the following specific origins: Puerto Rico, Mexico, Cuba, South or Central America (excluding Brazil), or the Dominican Republic. We performed multivariate logistic regression modeling to identify whether origin was a significant predictor of advanced cancer staging at diagnosis (AJCC stage III or IV), adjusting for age, race, receptor subtype, histology, grade, insurance status, and facility type. Consequently, we used Cox Regression survival modeling to investigate whether overall survival (OS) differed by Hispanic origin after adjusting for stage at diagnosis and other confounders of survival: age, race, stage at diagnosis, receptor subtype, and systemic therapy received. Results: Of the identified n = 60,438 Hispanic patients with breast cancer in the United States: n = 26,800 (44.3%) had Mexican, n = 9,792 (16.2%) had Puerto Rican, n = 5,283 (8.8%) had Cuban, n = 14,381 (23.8%) had South/Central American, and n = 4,172 (6.9%) had Dominican Republic origins. After adjusting for the aforementioned covariates, we found that origin was a significant predictor of staging at diagnosis (p &lt; 0.001). Patients originally from Mexico were more likely to be diagnosed at advanced stages compared to patients from Puerto Rico (OR 1.31; 95% CI, 1.18-1.46; p &lt; 0.001). We also identified that origin was a significant predictor of overall survival in this cohort even when controlling for various confounders, including stage at diagnosis. Compared to patients from Puerto Rico, patients from Central/South America (HR 0.78, 95% CI 0.70-0.88, p &lt; 0.001) and patients from the Dominican Republic (HR 0.77, 95% CI 0.65-0.92, p = 0.003) exhibited significantly improved overall survival. There was no statistically-significant survival difference between patients from Mexico and patients from Puerto Rico. Conclusions: This real-world analysis showed that, for Hispanic individuals living in the US with breast cancer, origin is significantly associated with outcomes even after accounting for other known determinants of health. We suggest that region of origin should be studied further as a potential determinant of outcomes in patients with cancer.

Genomic profile in Mexican women with early-stage breast cancer using Mammaprint+Blueprint assay: A retrospective study.

e12541 Background: Genomic assays have facilitated the decision-making of using chemotherapy and hormone therapy when incorporated into the care of patients with early-stage breast cancer. Mammaprint+Blueprint have been validated as a prognostic tool in cohorts around the world. However, to date, there hasn’t been a study that addresses the use of these assays on a large Mexican population and the description of clinical characteristics associated with genomic risk. Methods: We conducted a multicenter, retrospective, descriptive study from 2012 to 2023, including women who underwent surgery, aged ≥ 18 years with tumor size less than 5 cm, hormone receptor-positive evaluated through immunochemistry (IHC), 0 to 1-3 positive lymph nodes, in early stages (I-II), who underwent the Mammaprint+Blueprint at 20 institutions in Mexico. The primary goal was to describe the clinical and genomic characteristics of these patients and calculate the discordance rate between clinical risk and genomic risk. Results: This study included 1,673 patients, with a mean age of 57 ± 11 years. Of these, 649 (39%) were classified as high-risk, and 1,024 (61%) as low-risk through MammaPrint. A discordance rate of 49% was observed in the initially clinically classified high-risk group, which was reclassified as genomic low-risk through MammaPrint. On the other hand, 33% of patients in the clinically low-risk group were reclassified as genomic high-risk. The most common molecular subtype identified through Blueprint was Luminal A (61%), and the most prevalent histologic type was ductal (79%). The predominant tumor size stage was T1 (70%), with the majority presenting with no infiltrating lymph nodes at the testing time (N0, 88%). The most common tumor grade was 2 (65%) and the proliferation rate, assessed through Ki-67, was ≥ 20% in 43% of the patients. Conclusions: Our study showed a high rate of discordance between clinical and genomic risk, a rate of 49% between clinical high-risk and genomic high-risk patients, highlighting the importance of these assays in the decision-making of breast cancer patients. This represents the first cohort to evaluate MammaPrint+BluePrint in a Latin American population. A noteworthy result was identifying a significant proportion of our cohort as low-risk through genomic assay, sparing them from the toxic effects and expenses associated with chemotherapy. Using the combined insights from MammaPrint+BluePrint along with clinical factors provides a more complete basis for predicting prognosis and benefit from specific treatments. Finally, these assays emerge as a valuable tool, particularly in middle-income countries, offering a means to improve the accurate allocation of resources in the care of their population. Due to the retrospective nature of our study, its limitations are being addressed prospectively to evaluate survival rates, distant metastasis, and recurrent cancer.

Evaluation of biomarkers of response in patients with breast cancer with BRCA 1/2 pathogenic variants treated with PARP inhibitors.

e15188 Background: Several prospective studies highlight the pivotal role of PARP inhibitors (PARPi) in treating BRCA-associated breast cancers (BC), demonstrating a significant overall response rate (ORR) of up to 60% in advanced BC patients with BRCA 1/2 germline pathogenic variants (PV). Despite their clinical efficacy, the factors predicting PARPi response, the mechanisms of resistance to PARPi, and the clinical strategies to overcome these challenges are still unknown. The aim of this study is to establish tissue microarrays (TMA) from primary breast tumor tissue from BC patients with BRCA1/2 PVs who were treated with PARPi and identify biomarkers of PARPi resistance. Methods: Stage 4 BC patients with BRCA 1/2 PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2023 were identified using our database. Available patient tissue samples were obtained from institutional tumor banks. TMA from breast tumor tissue created and evaluated by our collabrating pathologists for expression of biomarkers:Wee-1, MRE, BP1,and c-Myc. Clinical and tumor characteristics analyzed included:Age at diagnosis, treatment details, tumor characteristics including histological type, hormonal receptor status, Her-2/Neu status, grade, Ki-67 and clinical outcome. Descriptive statistics, the Fisher exact test, and the log rank test were used to report patient characteristics and outcomes. Here we report on initial TMA construct and biomarker analysis. Results: So far TMA from 12 patients treated with PARPi were succesfully constructed. Patient characteristics include: Median age of 36.5 years (29-57). Nine (75%) and 3 (25%) patients had BRCA1 and BRCA2 mutations, respectively. All patients had invasive ductal carcinoma and 9 (75%) had triple negative BC. Most patient (75%) had high nuclear grade BC and median Ki-67 was 75 (15-90). In 11 evaluable patients, the ORR was 72.7%. The median OS was 383.6 months (95% CI 62.5-383.6) and median PFS was 31.5 months (95% CI 10.8-NE). No significant difference in biomarker expression was observed between PARPi-responders and non-responders (Table1). Conclusions: This report presents unique data on novel predictive biomarkers of response and evaluates the evidence for potential biomarkers. Further analysis on a larger TMA cohort is ongoing. [Table: see text]

Effect of screening with a pan-TRK immunohistochemistry-based algorithm on NTRK fusion detection rates.

e15135 Background: Rearrangements in the NTRK1, NTRK2, and NTRK3 genes are clinical actionable and predictive of response to TRK kinase inhibitors in solid tumors. Their detection in clinical practice is a priority, but their low prevalence (0.25-1%) poses a diagnostic challenge. In this study, we describe our immunohistochemical-based and cost-effective approach for NTRK rearrangements detection. Methods: We implemented a comprehensive NTRK testing approach at a reference center that combined clinical criteria (e.g., iodine therapy-resistant thyroid cancer); molecular biomarkers (e.g., non-small-cell lung carcinoma negative for driver alterations, colorectal carcinoma with deficient MMR and/or microsatellite instability); and histopathological criteria (identifying tumor subtypes associated with NTRK fusions, such as breast secretory carcinoma). Automated immunohistochemistry (Ventana BenchMark ULTRA IHC/ISH System) using the antibody pan-TRK (Ventana, EPR17341) was used as a screening tool. Positive results were confirmed through molecular techniques, including Next Generation Sequencing, NGS (Oncomine Focus Assay, Thermo Fisher, based on DNA and RNA) and/or FISH (NTRK3 break-apart probe, Zytovision). Results: We evaluated 172 patients (99 female/73 male), with a mean age of 52 years (SD 23.8). Eighteen (18) patients with neoplasms expressing TRK proteins were identified. Confirmatory studies using NGS identified fusions in 7 cases. In instances of poor RNA quality, FISH techniques (NTRK3) were employed, confirming the findings in an additional 3 patients. Overall prevalence of NTRK fusions was 5.8%. Histological types included the following tumor types: Thyroid carcinoma, 4 patients (one medullary and 3 papillary carcinomas, two of them in the pediatric population); soft tissue sarcomas, 3 patients (2 corresponding to infantile fibrosarcoma and a soft tissue provisional entity, "NTRK-rearranged spindle cell neoplasm”); secretory carcinoma of the breast, one patient; secretory carcinoma of the salivary gland, one patient; colorectal carcinoma, one patient, with a deficient MMR phenotype. NTRK3 gene fusions were found in 10 patients, (6 fusions with ETV6 detected by NGS and 3 detected by FISH), and NTRK1 fusion in 1 case (fusion with LMNA detected by NGS). The positive predictive value of pan-TRK immunohistochemistry as a screening tool was 0.55. Conclusions: In our experience, the comprehensive screening approach based on morphological and clinical/ molecular inclusion criteria, along with the use of immunohistochemical techniques (pan-TRK antibody), significantly enhances the detection rate of NTRK fusions (5.8% vs. 0.25-1%). Additionally, FISH provides a valuable tool in samples with poor RNA quality. This approach allows for a reduction in the impact of costly testing, such as NGS, on the healthcare system.

Clinical, Pathological and Immunohistochemical Characteristics of Patients with Primary Testicular Lymphoma Undergoing Orchiectomy: A Systematic Review and Meta-Analysis.

Primary testicular lymphoma (PTL) is a rare and aggressive malignant tumour with no specific clinical symptoms. Large-scale evidence-based medical evidence to guide preoperative diagnosis is lacking at present. This study aimed to analyse the clinical, pathological and immunohistochemical characteristics of patients with PTL undergoing testicular resection surgery. Literature on the clinical characteristics of patients with PTL undergoing orchiectomy was retrieved from databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data. The search covered all available records from the inception of these databases until December 31, 2023. Data extraction was followed by a meta-analysis using Stata 15.0 software. A total of 22 articles and 475 cases of PTL were included. The meta-analysis revealed that 58.1% of patients with PTL undergoing orchiectomy were under 60 years old, and 41.9% were 60 years or older. The lesion is mostly located on the right side (55.1%). Common symptoms included testicular swelling and falling swelling (91.3%), hydrocele testis (31.0%) and testicular pain (23.0%). Ann Arbor stages I-IV accounted for 53.3%, 16.7%, 14.8% and 15.7%, respectively. Diffuse large B-cell lymphoma (DLBCL) cases were higher at 95.5% than NK/T-cell lymphoma cases at 8.2%. Amongst DLBCL cases, 69.3% were non-germinal centre B-cell (GCB) subtype, and 27.6% were GCB subtype. Immunohistochemistry markers showed 95.9% CD3 negative, 94.9% CD10 negative, 94.4% CD20 positive, 88.4% multiple myeloma oncogene-1 (MUM-1) negative, 73.6% B-cell lymphoma-6 (BCL-6) negative and 66.5% BCL-2 positive. Laboratory findings indicated that 70.4% of patients had a tumour proliferating cell nuclear antigen (Ki67) index of ≥80%, 36.0% had increased serum lactate dehydrogenase level and 22.9% had increased serum β2-microglobulin level. PTL is rare, and it often occurs in elderly male patients. Common symptoms include testicular swelling and falling swelling, and the common histological type is DLBCL. Diagnosis should be based on histopathological characteristics and immunohistochemical examination.

The Coexistence of Occult (Latent) Thyroid Cancer and Multinodular Goiter After Total Thyroidectomy: A Retrospective Study.

Introduction Multinodular goiter (MNG) is a common thyroid disorder characterized by the presence of multiple nodules within the thyroid gland. While most cases of MNG are benign, there is a risk of malignancy, particularly in nodules with certain features. The coexistence of occult (latent) thyroid cancer within MNG presents diagnostic and management challenges, underscoring the need for comprehensive investigation and treatment strategies. Objective The objective of this retrospective study is to investigate the prevalence of occult thyroid carcinoma in non-toxic MNG following total thyroidectomy. Materials and methods The study population consisted of 412 patients who underwent total thyroidectomy between 2004 and 2022 at the Second Surgical Department of the 424 General Military Hospital of Education in Thessaloniki. Data collection included patients' demographic characteristics, surgical indications for thyroidectomy, and histopathological examination findings. Initial data were available for all 412 patients, while sufficient information was present for 319 individuals, with a subset of 271 undergoing total thyroidectomy due to non-toxic MNG. Out of the aforementioned group, 253 cases were histologically confirmed as MNG. Subsequently, a statistical analysis was conducted concerning age, gender, the association of MNG with malignancy, and other thyroid disorders. Results Out of the total 412 thyroidectomies performed, 271 patients remained for statistical analysis and study. Among them, 253 patients had histologically confirmed MNG. Among the histological findings, 38 cases (14.02%) were identified with occult carcinoma within MNG. The predominant histological type was papillary thyroid carcinoma (PTC), comprising 93.3% of cases. Additionally, 18 patients (6.64%) were diagnosed with MNG, Hashimoto's thyroiditis (HT), and malignancy concurrently. Conclusions The coexistence of occult thyroid carcinoma within MNG underscores the importance of vigilant evaluation and management strategies in patients undergoing total thyroidectomy. These findings emphasize the need for comprehensive preoperative assessment and postoperative surveillance to detect and address occult thyroid cancer, thereby optimizing patient care and outcomes.

Investigation of racial disparities in hepatocellular carcinoma and rates of liver transplant: A SEER 2000-2020 study.

e13754 Background: Hepatocellular carcinoma (HCC) most commonly occurs in patients with pre-established liver disease and is occurring with increasing incidence and mortality across the United States while disproportionately affecting all US racial/ethnic minority populations. Surgical resection or liver transplant is the preferred treatment for HCC if patient is a surgical candidate and offers the best chance to cure HCC. Previous literature analysis of HCC racial disparities using the Surveillance, Epidemiology, and End Results (SEER) database between the years 1998 and 2012 has been reported, however recent data has not yet been investigated to compare trends. Methods: The SEER database was used to identify 134,212 patients diagnosed with HCC between 2000 and 2020 in the US. Patients with HCC were identified using the ICD-0-3 primary site code C220 and histologic type codes 8170, 8172, 8173, 8174, and 8175. Patient race was categorized as White, Black, American Indian/Alaska Native, Asian or Pacific Islander, and Unknown based on SEER coding scheme. Racial disparities were then determined using chi-squared testing. Results: Patients with reported Unknown race or American Indian/Alaska Native had the greatest increase in proportion of new HCC diagnoses when comparing the years 2016-2020 to 2000-2005. Across all races, the average age at diagnosis was between 60-69 and males were more likely than females to be diagnosed with HCC. Those with Unknown race were more likely to present with Tumor grade I. American Indian/Alaskan Native patients were more likely to be reported as unstaged for HCC and also more likely to have surgery recommended, but not performed for an unknown reason. American Indian/Alaskan Native patients were less likely to receive liver transplant. Patients with Unknown race were more likely to be alive or dead of other cause and less likely to be dead from HCC diagnosis. When comparing this data to previously reported data from 1998-2012, there is an increase in proportion of patients having unstaged HCC especially in the American Indian/Alaskan Native cohort. Conclusions: Native American Indian/Alaskan Native patients continue to have significantly decreased rate of liver transplant (p&lt;0.001) compared to White patients (24.24% vs 30.31%). Previous rates reported 4.4% vs 5.5%.

Real-world data of cancer-associated venous thromboembolism in a tertiary-care hospital in India.

e23298 Background: Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with various malignancies. Anticoagulation is crucial for preventing and treating thrombosis associated with cancer. However, its use faces challenges due to increased risks of bleeding, recurrent thrombosis and complexities in dosing, particularly in patients with concurrent comorbidities. Prophylactic anticoagulation is under-utilized and the cost of low- molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. Methods: It was an ambispective observational study. All the cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in north India between 2018 and 2023 were analysed. Patient demographics, disease-related and treatment-related parameters were collected and analysed. The study was approved by the Institute Ethics Committee. Results: A total of 1312 patients attended the thrombosis clinic during study period, of which 139 (10.59%) cases were Cancer-associated VTE. The median age was 48 years and 61.2% were female. Most of VTE (54.6%) occurred within 6 months of cancer diagnosis and only 7% occurred after 3 years. Gynaecological malignancies (25.18%) and adenocarcinomas (21.58%) were the most common site and histological type of cancer respectively. Common risk factors observed for VTE development were: active cancer (80.3%), active chemotherapy (36.7%), cancer surgery (15.1%). Lower limb thrombosis was the most commonly seen type (46%), while abdominal and pulmonary thrombosis were seen in 17% and 7.9% respectively. Out of total patients, 124 (89.2%) patients received anticoagulation. Low molecular weight heparin (LMWH) was used as an initial anticoagulation in majority (52.41%) and direct oral anticoagulant (DOACs) was used as long term anticoagulation in 54% of patients. In 26 patients, anticoagulation was interrupted, the major reasons being bleeding and thrombocytopenia. There was no significant difference in frequency of bleeding with use of different anticoagulants (P = 0.48). Conclusions: Most cases of cancer associated VTE occur shortly after cancer diagnosis. Prophylactic anticoagulation is still underutilized in our patients with cancer. Early suspicion and prompt treatment can improve quality of life in such patients.

Retroperitoneal sarcoma: a 10-year follow-up analysis using hospital-based cancer registry data in Japan.

We sought clinical characteristics, survival outcomes, and prognostic factors for overall survival of retroperitoneal sarcoma in Japan. A Japanese hospital-based cancer registry database with a pivotal 10-year follow-up was used to identify and enroll patients, registered from 106 institutions, diagnosed with retroperitoneal sarcoma in 2008-2009. Treating hospitals were divided by hospital care volume; high-volume hospitals and low-volume hospitals were defined as ≥4 and<4 cases/year, respectively. A total of 91 men and 97 women were included, with a median age of 64years. The most common histological type was liposarcoma in 101 patients, followed by leiomyosarcoma in 38 patients. The 5-year and 10-year overall survival rates were 44.1 and 28.3%. The majority of patients (n=152, 80.9%) were treated at low-volume hospitals. High-volume hospital patients had higher 10-year overall survival rates than low-volume hospital patients (51.2% vs 23.2%, P=0.026). Multivariate analysis revealed age over 60years, treatment in low-volume hospitals and chemotherapy were independent predictors of unfavorable survival while treatment with surgery was an independent predictor of favorable survival. The possibility of surgical removal was suggested to be the most important prognostic factor for retroperitoneal sarcoma. Better survival was shown in patients treated at high-volume hospitals in our series.

Supersulfide metabolome of exhaled breath condensate for diagnostic biomarkers of esophageal cancer.

e15027 Background: The early estimate and detection of esophageal cancer (EC) is essentially required for continuous esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examination is sometimes invasive, which may cause somehow limited clinical application and compliance. Also, the traditional blood tumor marker is unsuitable for a cancer screening. In recent years, the energy production by sulfur respiration in hypoxic environments in cancer tissues is getting spotlighted in tumor biology. The current study is aimed to evaluate usefulness of sulfur containing compounds as new biomarkers for EC by using blood samples and exhaled breath condensate (EBC) that can be readily obtained in a non-invasive fashion. Methods: Fifty EC patients were included in the study between June 2021 and September 2021. EBC and plasma samples were collected before starting any medicinal remedy including medication, chemotherapy, radiation, surgery, and endoscopic and dentistry maneuvers. Thirty healthy controls were recruited if they did not have any cancer history, surgery and aged over 50s preferred age for esophageal cancer. All samples were stored at -80℃ immediately after appropriate preparation until the following inspection. Then, sulfur metabolome analysis using LC-MS/MS was performed to see the difference of metabolic profile between the two groups. We used Student t tests for comparing two groups, and one -way ANOVA test for more than two groups, with significance set at P&lt;0.05. To evaluate the diagnostic value of some metabolites, ROC curves and the AUC were calculated. Results: The supersulfide metabolic profiles were remarkably different between EC patients and controls. Especially, cysteine persulfide (CysSSH) was significantly increased in both EBC and plasma of the EC patients. The sensitivity and specificity of CysSSH in EBC were 60% and 96%, respectively, with an AUC of 0.71. The sensitivity and specificity of CysSSH in plasma were 49% and 96%, respectively, with an AUC of 0.73. In addition, homocysteine persulfide (HomoCysSSH) in plasma showed more significant difference than CysSSH and was able to distinguish EC patients from healthy subjects with AUC of 0.93 (sensitivity, 89%; specificity, 96%). The level of HomoCysSSH was correlated with that of CysSSH in EBC. The subgroup analysis for histological subtypes and tumor progression showed that both two metabolites were increased in EC patients regardless of histological type and disease’ progression. In particular, the amount of homoCysSSH in plasma was statistically higher in early-stage EC than that of controls (p&lt;0.0001). Conclusions: Supersulfides like CysSSH and HomoCysSSH could be potential biomarkers for detecting EC. Cysteine persulfide from EBC may serve as a valuable non-invasive biomarker with similar detectable ability compared with several biomarkers of blood samples that are currently reported.

Assessing response and adherence to neoadjuvant treatment in soft tissue sarcomas of the extremities.

e23559 Background: The standard treatment for large, intermediate, and high-grade extremity soft tissue sarcoma (ESTS) involves surgery and radiotherapy. The addition of chemotherapy has improved oncological outcomes, such as reduced recurrence and prolonged survival. However, the relationship between neoadjuvant treatment and tumor response in ESTS is not well understood. Pathological evaluation of viable tumor cells after treatment is an indicator of tumor response, yet the proportion of viable tumor cells remains high, particularly in high-risk sarcomas. Combining radiotherapy with chemotherapy may enhance the response of tumor cells. Objective: This study aims to evaluate the effects of neoadjuvant chemotherapy (NCT) and chemoradiotherapy (CRT) on patients with high-risk ESTS and to determine its impact on the pathological response. Methods: We enrolled adult patients with high-risk ESTS (SARCULATOR OS &lt; 60%) at a single center in Latin America. The study was designed to analyze the pathological response in patients with high-risk sarcomas who underwent neoadjuvant CRT and resection and to correlate these responses with various variables. The treatment response was evaluated using the EORTC–STBSG criteria. Results: Thirty-four patients were recruited, with a median age of 44 years (IQR 23-74). Fifty-two percent had T3 tumors (mean size 18 cm), and 79.4% were diagnosed at stage III. The predominant histological subtypes were synovial sarcoma (35.3%) and dedifferentiated liposarcoma (29.4%). The most used NCT regimen was doxorubicin/ifosfamide (84.4%), with 62.5% receiving a dosage intensity of Q4W, affected by overcapacity, and 25% received Q3W. Concurrent CRT was administered to 64.7% of patients, with a median delay to onset of 36 days due to overcapacity (43.5%). Only 79.4% completed three preoperative cycles of treatment. As for the response, 41.2% had an EORTC-E response, and 17.6% had an EORTC-D response. Grade 3 neutropenia and anemia occurred in 17.2% and 8.8% of patients, respectively. Disease progression during NCT was observed in six patients. No significant difference was found in the pathological response between the Q4W and Q3W dosage intensities (p = 0.62). Conclusions: The impact of NCT on pathological responses was not significantly high, which may be due to the predominant histological type in our series. The main cause of treatment delay at our center was due to overcapacity; however, this did not influence the pathological response relative to dose intensity. Additional follow-up assessments are required to determine the influence on relapse-free and overall survival based on the response after preoperative CRT.

Retrospective study on the profile of patients undergoing intraoperative radiotherapy with INTRABEAM for breast cancer treatment at a Brazilian cancer center.

e12538 Background: Conservative breast therapy combined with adjuvant radiotherapy has been the preferred treatment for early-stage breast cancer for many decades. Considering that most breast cancer recurrences occur near the original tumor site, partial breast radiotherapy has become an alternative for patients in this scenario, allowing for a single-dose radiation application directly to the tumor site. This technique has advantages such as reducing local toxicity and improving the quality of life for treated patients, in addition to decreasing the waiting time for radiotherapy treatment in developing countries like ours. Our case series is the largest in Latin America to date, and we believe that reporting the results of our experience will be valuable for the scientific community and aid in treatment decision-making in low- and middle-income countries. Methods: This is a retrospective study based on data from the medical records of 209 patients with early-stage breast cancer undergoing conservative surgery and intraoperative radiotherapy at A.C. Camargo Cancer Center (São Paulo, Brazil) from 2016 to 2023. Results: In our cohort, 88.5% of tumors were invasive ductal carcinomas. The majority were T1b (41.8%), had histological grade 2 (45.4%), nuclear grade 2 (62.7%), and showed no axillary involvement (87.6%). All patients received intraoperative radiotherapy in a single dose of 20 Gy radiation at the tumor site with a voltage of 50 kV. In our study, 17.7% of patients required additional external radiotherapy due to postoperative histopathological findings inconsistent with treatment indication criteria, including 35.3% for micrometastasis and 32.4% for nodal macrometastasis, 10.8% for narrow or compromised margins, 10.8% for histological types not covered in the final report, 2.7% for multifocality, 2.7% for extensive ductal carcinoma in situ, 2.7% for negative progesterone receptor, and 2.7% for the presence of lymphatic vascular invasion. The average follow-up time for patients was 36 months. The local recurrence rate was 0.5%. Conclusions: The results of this study support established data indicating the efficacy of intraoperative radiotherapy in early-stage breast cancer treatment. Therefore, for carefully selected patients, this technique with should be considered as a treatment option. We will continue to follow this patient cohort to identify the occurrence of late recurrences and publish long-term follow-up data.

Phase I summary of the HB0025 efficacy and safety to the heavily pretreated non-small cell lung cancer (NSCLC) population.

e14600 Background: HB0025 is a recombinant humanized bispecific molecule built on IgG1 that targets the human programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF, VEGF-A, VEGF165). Here we present the NSCLC results in Phase 1 study. Methods: This ongoing, open-label, multicenter, dose escalation and dose expansion, phase 1 trial to evaluate the safety and efficacy of HB0025 for pts with advanced solid tumors. HB0025 is administered intravenously every 14 days (Q2W). Response was evaluated by RECIST v.1.1 every 8 weeks. Results: As of Dec 25, 2023, 12 (7M/5F) NSCLC pts have received HB0025 at doses of 3mg/kg (n=1), 6mg/kg (n=2), 10mg/kg (n=2), 12mg/kg (n=1), 20mg/kg (n=5), 30mg/kg (n=1). Overall, the median age was 61.5 years, the median number of prior treatment lines was 4. The histologic types include squamous cell (Sq)-NSCLC (2 pts) without EGFR/ALK mutation and non- squamous cell (Nonsq)-NSCLC (10 pts), among of Nonsq-NSCLC 9 pts carrying EGFR/ALK mutation. The 3 pts with EGFR/ALK wild-type gene fail to prior anti-PD-1 treatment, 9 pts with EGFR/ALK gene mutation fail to prior TKI therapy. Among the 12 pts having imaging tumor assessment, the ORR was 25% and DCR was 66.7%, which included 3 partial responses (PR) ,5 stable disease (SD), and 4 progressive disease (PD) according to RECIST v1.1.For the 2 Sq-NSCLC pts, one pt achieved PR with 3mg/kg HB0025 treatment, the other pt achieved SD. For the10 Nonsq-NSCLC pts, there were 2 PR (20mg/kg and 30mg/kg treatment, respectively), 4 SD and 4 PD. Till the report date, the PR status and HB0025 treatment are ongoing to 3 PR pts, which includes 1 Sq-NSCLC pt, and 2 Nonsq-NSCLC pts which one pt doesn’t carry EGFR/ALK mutation. The Sq-NSCLC pt whose maximum tumor regression is 60% achieves PR after 4 cycles of treatment, and the duration of response (DOR) is more than 22 months. The one Nonsq-NSCLC pt whose maximum tumor regression is 74% achieves PR after 2 cycles of treatment, and the DOR is more than 11 months. The other Nonsq-NSCLC pt whose tumor regression is 32% achieves PR after 4 cycles of treatment, and the DOR is more than 2 months. Among the 5 SD pts, 1 Sq-NSCLC pt’s progression-free survival (PFS) is more than 14 months and continusous, 2 Nonsq-NSCLC pts’ PFS is more than 6 months and ongoing. For the 12 pts, 11 pts (91.7%) experienced a treatment related adverse events (TRAEs). The most common TRAEs included proteinuria (50%, 6/12), lymphocyte count decrease (50%, 6/12), blood bilirubin increased (33.3%, 4/12), and blood pressure increased (33.3%, 4/12). TRAEs ≥ grade 3 occurred in 2 (16.7%) pts. No TRAE leading to discontinuation and death. Conclusions: HB0025 monotherapy showed an acceptable safety profile and promising anti-tumor activity for prior heavily treated NSCLC, no matter in TKI-resistant population with EGFR/ALK mutation or population failed to anti-PD-1 treatment. Now Phase II studies of combination chemotherapy are ongoing. Clinical trial information: NCT04678908 .