Aggressive Tumor Research Articles

Immunohistochemical Expression of Human Epidermal Growth Factor Receptor 2 and Ki67 in Apocrine Gland Anal Sac Adenocarcinoma.

Apocrine gland anal sac adenocarcinoma is an aggressive neoplasm, and surgery remains the treatment of choice, although it is controversial in advanced cases. The prognostic factors are not well established. Human Epidermal Growth Factor Receptor 2 (HER2) is a membrane protein related to tumorigenesis, whereas Ki67 is a nuclear protein related to cell proliferation. Both are potential prognostic markers and therapeutic targets. This study aimed to evaluate the expression of HER2 and Ki67 markers in canine apocrine gland anal sac adenocarcinoma. The tumor samples were divided into four groups: largest tumor diameter less than 2.5 cm, largest tumor diameter greater than 2.5 cm, metastatic lymph nodes, and control group of non-neoplastic anal sacs. Each contained 10 samples. Immunohistochemistry was performed to verify the expression of HER2 and Ki67 markers. Positive HER2 staining was observed in 45% of the neoplastic cases and negative HER2 staining in 100% of the control group. The Ki67 expression had a median of 25% in all groups, except for the control group, which had a median of 8%. The HER2 and Ki67 expression was present in apocrine gland anal sac adenocarcinoma, making them potential therapeutic targets. However, it was not possible to determine the clinical value of either marker.

Prognostic factors and nomogram for pulmonary resected high-grade neuroendocrine carcinomas: a 20-year single institutional real-world experience

BackgroundPulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables.MethodsThis retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001–2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools.ResultsMinimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival.ConclusionsWe identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management.

Clinicopathological Impact of FOXM1 and MMP-9 Immunohistochemical Expression in Different Grades of Intracranial Meningioma.

To find predictive biomarkers for recurrence and progression of meningioma. Despite great advances in meningioma treatment, the prognosis remained unfavorable due to the high recurrence rate. In this study, we evaluated the immunohistochemical expression of FOXM1, MMP-9, and Ki67 in 50 cases of intracranial meningioma to detect its potential role in meningioma progression, recurrence, and patients' survival. Strong FOXM1 expression was detected in 20% of the cases and was significantly associated with meningioma grade (P= 0.002) and peritumoral brain edema (PTBE; P<0.001). Strong MMP-9 expression was noted in 32% of the cases and was significantly associated with meningioma grade and PTBE (P<0.001, P<0.001, respectively). High Ki67 was noted in 50% and significantly associated with tumor grade and PTBE (P<0.001, P= 0.002, respectively). The follow-up period revealed that meningiomas with strong FOXM1, strong MMP-9, and high Ki67 expression were associated with tumor recurrence, shorter OS, and recurrence-free survival. Furthermore, up-regulation of FOXM1 and MMP-9 expression had a significant relation with poor clinical response to the therapy (P= 0.010, P= 0. 001, respectively). However, high Ki67 cases were more sensitive to clinical therapy (P= 0.005). Strong FOXM1, strong MMP-9, and high Ki67 in meningiomas indicate highly aggressive tumors with a shortened survival rate, dismal outcome, and high risk of recurrence after the standard protocol of therapy.

Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features.

Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour-associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.

Triptolide and its pro-drug Minnelide target high-risk MYC amplified medulloblastoma in preclinical models.

Most children with medulloblastoma (MB) achieve remission, but some face very aggressive metastatic tumors. Their dismal outcome highlights the critical need to advance therapeutic approaches that benefit such high-risk patients. Minnelide, a clinically relevant analog of the natural product triptolide, has oncostatic activity in both preclinical and early clinical settings. Despite its efficacy and tolerable toxicity, this compound has not been evaluated in MB. Utilizing a bioinformatic dataset that integrates cellular drug response data with gene expression, we predicted that Group 3 (G3) MB, which has a poor five-year survival, would be sensitive to triptolide/Minnelide. We subsequently showed that both triptolide and Minnelide attenuate the viability of G3 MB cells ex vivo. Transcriptomic analyses identified MYC signaling, a pathologically relevant driver of G3 MB, as a downstream target of this class of drugs. We validated this MYC dependency in G3 MB cells and showed that triptolide exerts its efficacy by reducing both MYC transcription and MYC protein stability. Importantly, Minnelide acted on MYC to reduce tumor growth and leptomeningeal spread, which resulted in improved survival of G3 MB animal models. Moreover, Minnelide improved the efficacy of adjuvant chemotherapy, further highlighting its potential for the treatment of MYC-driven G3 MB patients.

Does New WHO 2022 Nomenclature of Pituitary Neuroendocrine Tumors Offer an Extra Edge to the Neurosurgeons for Its Management? A Narrative Review

AbstractThe new World Health Organization nomenclature of pituitary tumors was introduced in the year 2022 after much deliberation. This nomenclature clearly demarcates the anterior lobe (adenohypophyseal), posterior lobe (neurohypophyseal), and hypothalamic tumors. There is also focus on other tumors arising in the sellar region. The nomenclature has also advocated the routine use of immunohistochemistry in describing the pituitary transcription factors that plays a fundamental role in distinguishing the cell lineage of these tumors. However, the nomenclature is complex in understanding due to inclusion of pathological correlates like transcription factors, hormones, biomarkers, and various controversies that have emerged regarding the renaming of pituitary adenomas (PA) as PiTNETs (“Pituitary Neuroendocrine tumors”) because majority of the adenomas are benign and have rare metastatic behavior while classifying them as PiTNETs will create unnecessary misinterpretation of these as aggressive tumors that will lead to apprehension among the patients. The new classification gives deeper insight into the histological picture of the various pituitary tumors but other than contributing to the follow-up strategy and postsurgery management, this classification does not add anything new that could be advantageous for the neurosurgeons in clinical practice and decision making, especially in deciding the plan of action for surgery. Hence, there is need of a more comprehensive, integrated, neuroradiological-based classification with more emphasis on the invasiveness of these tumors that would assist the neurosurgeons in planning the treatment strategy and managing patients of pituitary tumors.

The Protective Role of miR-125b in Hepatocellular Carcinoma: Unraveling Tumor-Suppressive Mechanisms

Abstract: MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene, depending on the context. As a tumor suppressor, miR-125b inhibits HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, a complex network of regulatory mechanisms influences the dysregulation of miR-125b expression in HCC. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.

SRSF9 promotes cell proliferation and migration of glioblastoma through enhancing CDK1 expression

BackgroundGlioblastoma (GBM) is a highly aggressive and prevalent brain tumor that poses significant challenges in treatment. SRSF9, an RNA-binding protein, is essential for cellular processes and implicated in cancer progression. Yet, its function and mechanism in GBM need clarification.MethodsBioinformatics analysis was performed to explore differential expression of SRSF9 in GBM and its prognostic relevance to glioma patients. SRSF9 and CDK1 expression in GBM cell lines and patients’ tissues were quantified by RT-qPCR, Western blot or immunofluorescence assay. The role of SRSF9 in GBM cell proliferation and migration was assessed by MTT, Transwell and colony formation assays. Additionally, transcriptional regulation of CDK1 by SRSF9 was investigated using ChIP-PCR and dual-luciferase assays.ResultsThe elevated SRSF9 expression correlates to GBM stages and poor survival of glioma patients. Through gain-of-function and loss-of-function strategies, SRSF9 was demonstrated to promote proliferation and migration of GBM cells. Bioinformatics analysis showed that SRSF9 has an impact on cell growth pathways including cell cycle checkpoints and E2F targets. Mechanistically, SRSF9 appears to bind to the promoter of CDK1 gene and increase its transcription level, thus promoting GBM cell proliferation.ConclusionsThese findings uncover the cellular function of SRSF9 in GBM and highlight its therapeutic potential for GBM.

Prevalence of Genetic Mutations in Patients with Metastatic Prostate Cancer in a Cohort of Mexican Patients

Background: Prostate cancer is a malignant neoplasm of the male genitourinary system with the highest incidence worldwide. Susceptibility genes related to aggressiveness and prognosis, such as BRCA1/2, ATM, PTEN, have been identified. Currently, reports related to germline mutations in patients with prostate cancer in Latin American populations are very limited or absent. In the Mexican population, reports are also limited, especially in the context of metastatic prostate cancer. Determining the prevalence of these mutations is relevant to predict the potential aggressiveness of tumors and allow the use of targeted therapies, such as PARPi inhibitors. Objective: Determine the prevalence of germline mutations in patients with metastatic prostate cancer and establish their clinical characteristics at diagnosis. Material and Methods: Sixty-nine patients with metastatic PCa underwent testing and genetic analysis using the Comprehensive Multi-Cancer Hereditary Cancer Panel. The prevalence of germline mutations was assessed, and the cohort was divided into two groups for the evaluation and analysis of clinical characteristics between the mutated and non-mutated populations. Results: We identified mutations in 15 out of 69 patients (21.73%), while 54 patients (78.26%) had no mutations. Pathogenic mutations were observed in 15.9% of patients, Variants of Uncertain Significance (VUS) in 34.78%, and 5.79% had both. The most frequent mutations included ATM (11.54%), BRCA1 (11.54%), BRCA2 (7.69%), FANCA (7.69%), and FANCM (7.69%). No statistically significant differences were found in PSA levels, age at diagnosis, and resistance to castration between the two groups. Conclusions: Our study unveiled a mutation rate of 21.73%, marked by a significant prevalence of ATM, FANCA, FANCM, and Variants of Uncertain Significance (VUS). This pattern deviates from findings in other series, underscoring the necessity for improved access to clinical genetic testing in our population.

Delineating the Biomarker Potential and Therapeutic Significance of MicroRNAs in IDH-wildtype Glioblastoma as Defined by the WHO CNS5 Criteria

The World Health Organization (WHO) CNS5 classification, updated in 2021, has brought about a significant transformation in the diagnosis and treatment of IDH-wildtype glioblastoma, a subgroup of aggressive brain tumors. This new system, which incorporates molecular markers alongside traditional tissue analysis, provides a more refined approach that facilitates the identification of distinct glioblastoma subtypes with unique genetic profiles. Examples of these subtypes include IDH-mutant astrocytoma, IDH-mutant and 1p/19q-deleted oligodendroglioma, and IDH-wildtype glioblastoma. Despite advancements in genetics and targeted therapies, the treatment of these malignant tumors remains an ongoing quest. Therefore, the need for more specific diagnostic and therapeutic approaches is undeniable. MicroRNAs (miRNAs) are emerging as molecules that molecular biology has brought to the medical world in this context. These tiny molecules act as master regulators of gene expression and hold immense potential for glioblastoma diagnosis, prognosis prediction, and biomarker development. Recent research has highlighted the potential of miRNAs as therapeutic strategies, attracting scientific interest to this point. This review examines the current relationships of miRNAs in the context of IDH-wildtype glioblastoma within the framework of the WHO CNS5 classification. Utilizing extensive databases, this article investigates the intricate relationship between genetic abnormalities defined in the latest WHO classification and dysregulated miRNAs. By analyzing proposed molecular biomarkers and associated miRNA dysregulation, we aim to pave the way for the development of personalized miRNA-based therapies for this aggressive cancer type.

Knee Extensor Apparatus Reconstruction with Allograft after Patellar Resection: A Case Report

Background: The extensor apparatus of the knee can be thought of a chain that transmits the muscular strength developed by the quadriceps muscles to the proximal tibia. This complex is essential to allow the extension of the tibia over the femur, being essential to provide knee mobility and stability. In case of lesions which irreparably damage the patella, such as a locally aggressive bone tumor, it is necessary to restore both the apparatus’ anatomical continuity and its strength.Case report: A 39-years-old Caucasian man with a history of lung carcinoma developed atraumatic swelling and soreness in his left knee. Imaging evidence reported a degeneration of the left patella. We performed an en bloc resection of the patella and the nearby soft tissues of the extensor apparatus. The resulting gap was fulfilled with a massive allograft consisting of a quadriceps tendon, a patella and a patellar ligament. No complication or local recurrences were observed. At the patient’s latest follow-up, he did not have any extension lag and quadriceps strength was completely restored.Conclusion: Massive allografts can represent a reliable alternative for the reconstruction of the patella and the knee extensor apparatus in orthopedic oncology.

Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.

Tumor-stroma contact ratio - a novel predictive factor for tumor response to chemoradiotherapy in locally advanced oropharyngeal cancer

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package "Spatstat". TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance.Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61).In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.

The Role of Serum Dickkopf1 and CKAP4 Levels in Diagnosing Colorectal Cancer and Measuring the Disease Severity: A Prospective Study.

Background and Objective: Colorectal cancer (CRC) is among the most common types of cancer. Although the disease is treatable in its early stages, five-year survival falls below 20% in the later stages. CEA and CA19-9 are tumor markers used in the diagnosis and follow-up of the disease in clinical practice; however, their diagnostic effectiveness is insufficient. Therefore, the identification of biomarkers that can be easily studied from serum and can diagnose CRC and determine its severity is highly important. In this context, dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are both promising biomarkers. Materials and Methods: Serum DKK1 and CKAP4 levels were measured in 55 patients with CRC and 40 healthy controls. The patients with CRC were divided into groups based on pathological stages and histological differentiation. The serum levels of both proteins in patients with CRC were measured preoperatively and 10 and 30 days postoperatively. Results: Serum DKK1 and CKAP4 were significantly higher in the CRC group than in the healthy controls (p < 0.05). Serum levels of both proteins rose in line with the disease stage and grade but decreased following surgical resection. A positive correlation was observed between tumor diameter and protein blood levels. The diagnostic efficacy of DKK1 and CKAP4 in CRC (approximately 95%) was higher than that of markers such as CEA and CA19-9. Conclusions: The DKK1 and CKAP4 serum values of patients with CRC are promising biomarkers. They can potentially be used in CRC management, namely, in the diagnosis and treatment of tumor response access and in tumor aggressiveness prediction.

Strength of selection in lung tumors correlates with clinical features better than tumor mutation burden

Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist. Strength of selection estimated as the density of missense mutations relative to the density of silent mutations showed only a weak correlation with tumor mutation burden. In the “all histology together” analysis we found that absolute strength of selection was strongly correlated with all clinically relevant features analyzed. In histology-stratified analysis selection was strongest in small cell lung cancer. Selection in adenocarcinoma was somewhat higher compared to squamous cell carcinoma. The study suggests that somatic mutation- based quantifying of directional and absolute selection in individual tumors can be a useful biomarker of tumor aggressiveness.

Epidemiology of undifferentiated sarcomas: A rare entity.

e23571 Background: Undifferentiated Sarcomas (USar), previously known as malignant fibrous histiocytomas, are a group of rare and diverse malignant tumors of mesenchymal origin with a prevalence of 0.08-1 per 100,000. These are aggressive tumors with often high-grade morphology. The diagnosis is made by exclusion of other sarcoma entities upon bone marrow biopsy (criteria listed below). Undifferentiated sarcomas are of four major types, i.e. Pleomorphic, Epithelioid, spindle and round cells. The exact etiology of these sarcomas remains obscure, although many signaling pathways with various genetic alterations may be implicated in their development. The goal of this epidemiologic study is to assist in better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted undifferentiated sarcoma cases diagnosed between 0-90 years of age, using the ICD Code 8805/3. The analysis was stratified age, gender, race, &amp; primary site labeled. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 1680 cases of USar were identified, which were diagnosed between 2000 and 2020. Median age of diagnosis was 59.5 years. 50.54% were males and 49.46% were females. Of these cases, ~64.05% were Caucasians, ~15.18% Hispanics, ~10.48% Asians or Pacific Islanders, ~9.35% Black, and &lt; 1% were Alaskan natives/American Indian and Non-Hispanics of unknown race. Further survival curves were compared based on gender, race and organ system. The average months of survival (MoS) based on gender showed no statistical significance (p value 0.6077). MoS calculated for Whites (28), Blacks (16), Asian &amp; Pacific islanders (1), Alaskan natives &amp; American-Indians (15), &amp; Hispanics (21) (p value &lt; 0.0001). MoS based on involved organ system were compared for: head/face/neck (18), GI tract (10), respiratory tract (4), heart/mediastinum/pleura (9), skin &amp; soft tissue (51), bone (32), breast (30), GU (19), CNS (26), gynecological tract (12) and male reproductive system (29) (p &lt; 0.0001). Conclusions: Undifferentiated Sarcoma accounts for less than 1% of all adult tumors. Only 1680 cases were found in the past twenty years, rendering it one of the rarest seen malignancies. Of the reported data, USar was most commonly observed in Caucasians. Comparing the survival curves also showed that there was no difference in survival based on gender. The highest MoS was seen in undifferentiated sarcomas of skin and soft tissues while respiratory tract tumors had the lowest average survival time. More research and analysis is warranted to understand this lesser known malignancy given its extremely low incidence.

Place of rank ligand inhibitor in giant cell tumour of bone.

e23511 Background: Giant cell tumour of bone (GCTB) is a locally aggressive and osteolytic tumour.The peak incidence is during the third and fourth decades of life. The majority of tumours occur in the metaepiphyseal (end) region of the long bones. Surgical resection is the preferred treatment option, if possible but it is a tumor which always poses progressive problems. Denosumab is indicated in recurrent or unresectable GCTB. Methods: We report a series of 70 patients treated for GCT at the medical oncology department of the CPMC (Algiers) in collaboration with the orthopedics department of Mustapha University Hospital from January 2020 to December 2023. Results: 70 patients ( 50 women and 20 men). The sex ratio is 0.54 The average age is 22 years (11-54 years). Reason for consultation : - Pathological fracture: n = 10 - Pain: n = 30 - Functional impotence: n = 20 - Tumor mass: n = 5 - Concept of trauma: n = 5 Stage of the disease: -Localized: n = 29 -Recurrence: n = 30, -Recurrence + pulmonary metastases: n = 10, -Sarcomatous transformation: n = 1 Type of treatment: -Radiotherapy, n = 1 -Exercised biopsy: n = 10, -Curettage + cementoplasty: n = 50 -Exeresis with osteosynthesis material: n = 8, -Amputation : n = 1 Medical treatment: Denosumab: n = 45 The number of courses with denosumab was between 6 and 55 cycles. Denosumab was administered neoadjuvantly in 10 patients, in 20 patients with reccurence disease, 15 patients in the metastatic phase - In terms of toxicity, we noted moderate hypocalcemia in 3 patients. -Objective responses: 95% ORR, 5 complete radiological responses and 10 partial responses, 20 stable patients and 9 out of 10 patients who received neoadjuvant denosumab were able to operate.Progression Free Survival was 28 months. Conclusions: GCTs are aggressive tumors with intermediate malignancy that should not be underestimated. The treatment is essentially surgical. Denosumab is indicated for both neoadjuvant and adjuvant use, it allows obtaining a clear clinical and radiological improvement.

Longitudinal cell-free DNA characterization by low-coverage whole-genome sequencing in patients undergoing high-dose radiotherapy

Background and PurposeCurrent radiotherapy guidelines rely heavily on imaging-based monitoring. Liquid biopsy monitoring promises to complement imaging by providing frequent systemic information about the tumor. In particular, cell-free DNA (cfDNA) sequencing offers a tumor-agnostic approach, which lends itself to monitoring heterogeneous cohorts of cancer patients. MethodsWe collected plasma cfDNA from oligometastatic patients (OMD) and head-and-neck cancer patients (SCCHN) at six time points before, during, and after radiotherapy, and compared them to the plasma samples of healthy and polymetastatic volunteers. We performed low-pass (on average 7x) whole-genome sequencing on 93 plasma cfDNA samples and correlated copy number alterations and fragment length distributions to clinical and imaging findings. ResultsWe observed copy number alterations in 4/7 polymetastatic cancer patients, 1/7 OMD and 1/7 SCCHN patients, these patients’ imaging showed progression following radiotherapy. Using unsupervised learning, we identified cancer-specific fragment length features that showed a strong correlation with copy number-based tumor fraction estimates. In 4/4 HPV-positive SCCHN patient samples, we detected viral DNA that enabled the monitoring of very low tumor fraction samples. ConclusionsOur results indicate that an elevated tumor fraction is associated with tumor aggressiveness and systemic tumor spread. This information may be used to adapt treatment strategies. Further, we show that by detecting specific sequences such as viral DNA, the sensitivity of detecting cancer from cell-free DNA sequencing data can be greatly increased.

Utility of circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) for prognosis of patients with recurrent high grade glioma.

2010 Background: High-Grade Gliomas (HGGs) are the most aggressive primary brain tumors in adults and molecular characterization is crucial for diagnosis and optimal disease treatment. Due to the eloquent location of many HGGs, upfront or repeat tumor sampling may be sub-optimal. Hence, there is an urgent need to develop alternative, minimally invasive means to obtain diagnostic information and determine the expected clinical behavior. Here we report that circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) can be used to identify disease defining genomic alterations and to track clonal evolution. Additionally, we demonstrate that detection of CSF ctDNA is positively correlated with leptomeningeal disease and overall survival suggesting that CSF ctDNA should be integrated into clinical decision making in the clinic. Methods: Our study includes 313 samples from 253 patients with recurrent glioma treated at Memorial Sloan Kettering Cancer Center who underwent CSF collection for routine clinical care and were sequenced using the MSK-IMPACT targeted clinical sequencing assay (468 and 505 genes). Alterations were classified as oncogenic based on OncoKB. 17% of genomic alterations detected were identified using a secondary bioinformatics analysis, following an informed approach with less stringent mutation calling criteria and Gaussian Mixture Model to call copy number events. CSF ctDNA positivity was determined by the presence of at least one oncogenic disease defining alteration or any shared alteration with the tumor. Results: Within this cohort, we found 193 CSF ctDNA positive (62%) and 120 CSF negative (38%) samples. Of note, CSF ctDNA positivity was the highest amongst histone mutant tumors with 94% CSF ctDNA positivity compared to 56% CSF ctDNA positivity for IDH-WT tumors. We noticed 44% of alterations shared between the tumor and the CSF, additionally, we noted considerable tumor evolution particularly within the growth signaling pathways (e.g. PDGFRA). The majority of the shared alterations were clonal, and we noticed the emergence of new clonal events in the CSF. Conclusions: Our cohort demonstrated that patients with positive CSF ctDNA had a significantly shorter overall survival compared to those who were CSF ctDNA negative (4.83 months vs 11.83 months, HR 2.1, p &lt; 0.001). In tandem with secondary clinical analysis, radiographic findings also correlated with CSF ctDNA positivity. Specifically, the presence of enhancing disease and contact of the tumor with the ventricular space were positively associated with detection of CSF ctDNA. Additionally, CSF ctDNA was associated with positive cytology in 21/21 cases (100%). With our improved bioinformatics pipeline, we hypothesize ctDNA from CSF may be used as a prognostic biomarker for survival, but confirmation requires further validation in a prospective study.

Malignant mesenchymoma: A demographic analysis of the National Cancer Database.

e23556 Background: Malignant mesenchymoma is a rare, aggressive soft tissue tumor characterized by the presence of two or more histologic subtypes of sarcoma. As a result of these characteristics, this cancer has a poor prognosis and a lack of proven treatment options. It may be epidemiologically beneficial to analyze the diagnostic trends to further understand the factors contributing to the disease. This study examines the demographic factors of malignant mesenchymoma, ICD-O-3 Code 8990, through the National Cancer Database (NCDB). Methods: The 2004-2020 NCDB was used for retrospective analysis. 72 patients were identified and their demographic factors such as age, sex, race, Hispanic status, educational attainment, insurance status, facility type and location, distance from facility, and Charlson-Deyo score were analyzed using descriptive statistics. Regression analysis was used to interpret incidence trends. Results: The NCDB contains 72 recorded cases of malignant mesenchymoma from 2004-2020 with an average age at diagnosis of 49.9 ± 21.3 years, with the incidence rate exhibiting variability (R2= 0.1028). Women had a considerably higher diagnosis rate (67%) compared to men (33%). The majority of patients were White (75%), and 11% of patients were Black. Most patients were of non-Hispanic origin (81%). A higher percentage of patients fell into the fourth quartile of income earners (32%) compared to the top three quartiles. A significant portion of patients (26%) did not have a high school degree. The sites with the highest cancer prevalence were the retroperitoneum (10%) and endometrium (10%). A majority of individuals (78%) had Charlson-Deyo comorbidity scores of 0. The size of the tumors ranged from 10.0 to 250.0 mm with an average size of 61.6 ± 67.4 mm. A majority of the patients (72%) underwent surgery at the primary site. Most (96%) patients survived at least thirty days following their primary surgery, with 94% surviving for ninety or more days. The mean survival time was 91.0 months. The cancer’s 2-year, 5-year, and 10-year survival rates were 61.5%, 45.5%, and 43.1% respectively. Conclusions: Based on our searches, this is the first NCDB study on malignant mesenchymoma to address epidemiological gaps in the literature. Most malignant mesenchymoma patients identified as non-Hispanic and White with a primary site of either the retroperitoneum or endometrium. The majority of patients fell into the fourth income quartile, and a significant amount did not have a high school degree. Due to this cancer’s rarity, recent literature exploring the factors contributing to the disease course is scarce. Additional research is necessary to understand how demographics influence the diagnosis, treatment, and long-term outcomes of individuals diagnosed with malignant mesenchymoma.