Increased Tumor Size Research Articles

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer

ObjectiveThe primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we...

Incidence and Prognostic Implications of Lymphovascular Invasion in Node-Negative Pancreatic Neuroendocrine Tumors: Results From the US Neuroendocrine Study Group.

Despite the well-known prognostic role of lymph node metastasis (LNM) in pNETs, less is known about the importance of lymphovascular invasion (LVI) among patients with these tumors. Patients undergoing pancreatectomy for pNET between 2002 and 2020 were identified in the US Neuroendocrine Tumor Study Group database. Cox regression analysis was utilized to identify the impact of LVI on recurrence-free survival (RFS) among patients with node-negative pNET. Among 853 patients who underwent resection for pNET, 214 patients (25.1%) had LNM, while 116 (13.6%) and 523 individuals (61.3%) were LVI + N0 and LVI - N0, respectively. The overall incidence of LVI among patients with N0 pNET was 18.1%; the incidence of LVI increased with increasing tumor size and Ki-67 levels (size < 2 cm and Ki-67 < 3%: 5.5%; size < 2 cm and Ki-67 ≥ 3%: 17.2%; size ≥ 2 cm and Ki-67 < 3%: 22.2%; size ≥ 2 cm and Ki-67 ≥ 3%: 43.1%, p < 0.001). Five-year RFS was highest among patients with LVI - N0 disease followed by individuals with LVI + N0 and N+ pNETs (92.8% vs. 61.6% vs. 58.3%, p < 0.001). On multivariable analysis, the presence of LVI on pathology remained independently associated with almost 2.5 times higher hazards of recurrence (HR 2.47, 05% CI 1.44-4.24) among individuals with N0 pNETs. The incidence of LVI varied according to tumor size and Ki-67. LVI was associated with a higher likelihood of recurrence among individuals who underwent formal pancreatic resection for N0 pNETs. LVI is an important prognostic indicator among patients with node-negative pNETs.

Macrofollicular subtype of papillary thyroid carcinoma: Ultrasonographic findings and clinical implications.

The macrofollicular subtype of papillary thyroid cancer (MFS-PTC) is a rare subtype often leading to a challenging diagnosis. To evaluate the ultrasonographic (US) features and clinical implication of MFS-PTC. Records of 14 patients histologically diagnosed with MFS-PTC at our institution over a period of 16 years were retrospectively reviewed. Preoperative US features, Bethesda categories determined by fine-needle aspiration (FNA) or core needle biopsy (CNB), and final pathology were assessed in all patients with MFS-PTC. Of the 14 MFS-PTC cases, most nodules were noted as smooth marginated, solid or predominantly solid isoechoic on US and were categorized as low suspicion in 12 cases and intermediate suspicion in 2 cases. The median tumor size was 1.2 cm (range, 0.6-5.6 cm). Of 11 cases that underwent FNA or CNB, 4 (36.4%) with Bethesda category II or III underwent the follow-up because of benign-looking appearance on US and benign results in subsequent CNBs. However, the patients underwent delayed surgery (31.3 months, range 12-41 months) because of serially increased tumor size. Seven patients diagnosed with Bethesda type IV, V, and VI subsequently underwent surgery. Gross extrathyroidal extension into subcutaneous fat tissue and lateral lymph node metastasis were noted in a patient who underwent follow-up. No distant metastases or recurrence was detected. MFS-PTC is representative of a benign sonographic appearance of PTC subtypes. Tumor growth on serial US images is the only suspicious finding for MFS-PTC because FNA or CNB is often false negative.

Glutamate Transport Proteins and Metabolic Enzymes are Poor Prognostic Factors in Invasive Lobular Carcinoma.

Invasive Lobular Carcinoma (ILC) is a subtype of breast cancer characterized by distinct biological features, and limited glucose uptake coupled with increased reliance on amino acid and lipid metabolism. Our prior studies highlight the importance of glutamate as a key regulator of ILC tumor growth and therapeutic response. Here we examine the expression of four key proteins involved in glutamate transport and metabolism - SLC3A2, SLC7A11, GPX4, and GLUD1/2 - in a racially diverse cohort of 72 estrogen receptor-positive (ER+) ILC and 50 ER+ invasive ductal carcinoma, no special type (IDC/NST) patients with primary disease. All four proteins are associated with increased tumor size in ILC, but not IDC/NST, with SLC3A2 also specifically linked to shorter overall survival and the presence of comorbidities in ILC. Notably, GLUD1/2 expression is associated with ER expression in ILC, and is most strongly associated with increased tumor size and stage in Black women with ILC from our cohort and TCGA. We further explore the effects of GLUD1 inhibition in endocrine therapy-resistant ILC cells using the small-molecule inhibitor R162, which reduces ER protein levels, increases reactive oxygen species, and inhibits oxidative phosphorylation. These findings highlight a potentially important role for glutamate metabolism in ILC, particularly for Black women, and position several of these glutamate-handling proteins as potential targets for therapeutic intervention in ILC.

Simulating the impact of tumor mechanical forces on glymphatic networks in the brain parenchyma.

The brain glymphatic system is currently being explored in the context of many neurological disorders and diseases, including traumatic brain injury, Alzheimer's disease, and ischemic stroke. However, little is known about the impact of brain tumors on glymphatic function. Mechanical forces generated during tumor development and growth may be responsible for compromised glymphatic transport pathways, reducing waste clearance and cerebrospinal fluid (CSF) transport in the brain parenchyma. One such force is solid stress, i.e., growth-induced forces from cell hyperproliferation and excess matrix deposition. Because there are no prior studies assessing the impact of tumor-derived solid stress on glymphatic system structure and performance in the brain parenchyma, this study serves to fill an important gap in the field. We adapted a previously developed Electrical Analog Model using MATLAB Simulink for glymphatic transport coupled with Finite Element Analysis for tumor mechanical stresses and strains in COMSOL. This allowed simulation of the impact of tumor mechanical force generation on fluid transport within brain parenchymal glymphatic units-which include perivascular spaces, astrocytic networks, interstitial spaces, and capillary basement membranes. We conducted a parametric analysis to compare the contributions of tumor size, tumor proximity, and ratio of glymphatic subunits to the stress and strain experienced by the glymphatic unit and corresponding reduction in flow rate of CSF. Mechanical stresses intensify with proximity to the tumor and increasing tumor size, highlighting the vulnerability of nearby glymphatic units to tumor-derived forces. Our stress and strain profiles reveal compressive deformation of these surrounding glymphatics and demonstrate that varying the relative contributions of astrocytes vs. interstitial spaces impact the resulting glymphatic structure significantly under tumor mechanical forces. Increased tumor size and proximity caused increased stress and strain across all glymphatic subunits, as does decreased astrocyte composition. Indeed, our model reveals an inverse correlation between extent of astrocyte contribution to the composition of the glymphatic unit and the resulting mechanical stress. This increased mechanical strain across the glymphatic unit decreases the venous efflux rate of CSF, dependent on the degree of strain and the specific glymphatic subunit of interest. For example, a 20% mechanical strain on capillary basement membranes does not significantly decrease venous efflux (2% decrease in flow rates), while the same magnitude of strain on astrocyte networks and interstitial spaces decreases efflux flow rates by 7% and 22%, respectively. Our simulations reveal that solid stress from growing brain tumors directly reduces glymphatic fluid transport, independently from biochemical effects from cancer cells. Understanding these pathophysiological implications is crucial for developing targeted interventions aimed at restoring effective waste clearance mechanisms in the brain. This study opens potential avenues for future experimental research in brain tumor-related glymphatic dysfunction.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation.

Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.

Potential predictor of prognosis in breast carcinoma: Tumor budding

ABSTRACT Background: Breast cancer is the most common cancer in women, with invasive breast carcinoma of no special type (IBC-NST) accounting for the majority of cases. Aim: This study aimed to evaluate the relationship between tumor budding (TB), which is the earliest histological indicator of tumor spread and represents epithelial–mesenchymal transition, and prognostic factors as well as the effect of TB on survival in patients with IBC-NST, thereby demonstrating its potential prognostic value. Materials and Methods: This study included 278 cases of breast resection diagnosed with IBC-NST from 2014 to 2019. Total tumor buds were counted in 10 high-power fields of a hematoxylin and eosin–stained section with the most infiltrative area at 400× magnification. The cutoff value for TB was obtained using receiver operating characteristic analysis for mortality and recurrence risk; this cutoff value was used to classify TB into two categories: low and high grades. The relationship between TB and prognostic factors and the effect of TB on the survival of patients were investigated. Results: This study revealed a statistically significant relationship between high-grade TB and increased tumor size, advanced pathological primary tumor (pT) category, lymph node metastasis, lymphatic invasion, blood vessel invasion, increased recurrence, and mortality as well as reduced overall and disease-free survival. Conclusion: TB in breast carcinomas may have significant predictive value for prognosis. It emerges as a simple, reproducible, and cost-effective histological marker. With the standardization of evaluation criteria, TB may be readily integrated into routine pathological examination, thereby increasing its value in clinical patient management.

Comparative prognosis analysis of ovarian squamous cell carcinoma versus serous carcinoma: Insights from the SEER database.

The aim of this study was to identify survival rates and potential prognostic factors of ovarian squamous cell carcinoma (OSCC), offering valuable insights for clinical decision making. Leveraging the Surveillance, Epidemiology, and End Results (SEER) database, we selected 11 078 serous carcinoma (SC) patients and 198 OSCC patients based on predetermined criteria diagnosed from 2000 to 2020. We compared the overall survival (OS) and cancer-specific survival (CSS) before and after propensity score matching (PSM) in two groups. Prognostic differences were also compared between OSCC and SC groups at different stages. Univariate and multivariate Cox regression analyses were performed to investigate the impact of clinical and pathologic variables on the survival of patients with OSCC. Finally, we developed and validated a nomogram predictive model. OSCC tumors exhibited distinct characteristics, being relatively larger, more frequently unilateral, and better differentiated than SC tumors. After PSM, Kaplan-Meier analysis revealed significantly lower survival rates for OSCC patients in Stages IIB-IV, while Stages IA-IC displayed comparable survival. Independent risk factors for OSCC patients included advanced age, single marital status, higher tumor stage, and increased tumor size. Conversely, higher median household income and chemotherapy emerged as independent protective factors. Our predictive model and nomogram accurately forecasted patient survival rates in both SEER and internal validation datasets. OSCC patients face significantly poorer prognosis than their SC counterparts, except in the very early stages. Higher median household income was associated with better OSCC survival.

Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.

Primary liver cancer is an increasing problem worldwide and is associated with significant mortality. A popular method of modeling liver cancer in mice is plasmid hydrodynamic tail vein injection (HTVI). However, plasmid-HTVI models rarely recapitulate the chronic liver injury which precedes the development of most human liver cancer. We sought to investigate how liver injury using thioacetamide contributes to the pathogenesis and progression of liver cancer in two oncogenic plasmid-HTVI-induced mouse liver cancer models. Fourteen-week-old male mice received double-oncogene plasmid-HTVI (SB/AKT/c-Met and SB/AKT/NRas) and then twice-weekly intraperitoneal injections of thioacetamide for 6 weeks. Liver tissue was examined for histopathological changes, including fibrosis and steatosis. Further characterization of fibrosis and inflammation was performed with immunostaining and real-time quantitative PCR. RNA sequencing with pathway analysis was used to explore novel pathways altered in the cancer models. Hepatocellular and cholangiocellular tumors were observed in mice injected with double-oncogene plasmid-HTVI models (SB/AKT/c-Met and SB/AKT/NRas). Thioacetamide induced mild fibrosis and increased alpha smooth muscle actin-expressing cells. However, the combination of plasmids and thioacetamide did not significantly increase tumor size, but increased multiplicity of small neoplastic lesions. Cancer and/or liver injury up-regulated profibrotic and proinflammatory genes while metabolic pathway genes were mostly down-regulated. We conclude that the liver injury microenvironment can interact with liver cancer and alter its presentation. However, the effects on cancer development vary depending on the genetic drivers with differing active oncogenic pathways. Therefore, the choice of plasmid-HTVI model and injury agent may influence the extent to which injury promotes liver cancer development.

ESR Essentials: response assessment criteria in oncologic imaging-practice recommendations by the European Society of Oncologic Imaging.

Assessing the response to oncological treatments is paramount for determining the prognosis and defining the best treatment for each patient. Several biomarkers, including imaging, can be used, but standardization is fundamental for consistency and reliability. Tumor response evaluation criteria have been defined by international groups for application in pharmaceutical clinical trials evaluating new drugs or therapeutic strategies. RECIST 1.1 criteria are exclusively based on unidimensional lesion measurements; changes in tumor size are used as surrogate imaging biomarkers to correlate with patient outcomes. However, increased tumor size does not always reflect tumor progression. The introduction of immunotherapy has led to the development of new criteria (iRECIST, Level of Evidence (LoE) Ib) that consider the possibility that an increase in disease burden is secondary to the immune response instead of progression, with the new concept of Unconfirmed Progressive Disease (a first progression event which must be confirmed on follow-up). Specific criteria were devised for HCC (mRECIST, LoE IV), which measure only enhancing HCC portions to account for changes after local therapy. For GIST treated with imatinib, criteria were developed to account for the possible increase in size reflecting a response rather than a progression by assessing both tumor size and density on CT (Choi, LoE II). This article provides concise and relevant practice recommendations aimed at general radiologists to help choose and apply the most appropriate criteria for assessing response to treatment in different oncologic scenarios. Though these criteria were developed for clinical trials, they may be applied in clinical practice as a guide for day-to-day interpretation. KEY POINTS: Response evaluation criteria, designed for use in clinical trials, might serve as a surrogate biomarker for overall survival. RECIST 1.1 defines measurable and non-measurable disease among which target lesions and non-target lesions are selected at baseline as reference for follow-ups. Some therapies and/or cancers require the use of different criteria, such as iRECIST, mRECIST, and Choi criteria.

Overactivation of Signal Transducer and Activator of Transcription 3 in Canine Hepatocellular Carcinoma and Its Prognostic Significance.

Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), which is related to anti-apoptosis, cellular proliferation, invasion and migration of tumours, has prognostic significance in malignant tumours in humans as well as in canine melanoma. However, the significance of pSTAT3 in canine liver tissues has not yet been evaluated. This study's objective was to compare its expression in canine normal, non-neoplastic hepatic disease and hepatocellular carcinoma (HCC) tissues by immunohistochemical analysis. Furthermore, the association between pSTAT3 immunostaining and clinicopathological factors was investigated. Overall, 68 canine liver tissues, including 10 normal liver tissues, 30 non-neoplastic hepatic disease tissues and 28 HCC tissues were examined, revealing distinct differences in pSTAT3 immunostaining among the groups. (p < 0.001). Additionally, high pSTAT3 immunostaining was significantly associated with increased tumour size (5 > cm) (p = 0.041), and metastasis (p = 0.046). Furthermore, Kaplan-Meier survival curve analysis revealed a correlation between high pSTAT3 immunostaining and poor disease-free survival (p = 0.013) and overall survival (p = 0.011). These findings suggest that overactivation of STAT3 is associated with poor prognosis in canine HCC. Therefore, pSTAT3 is considered a potential prognostic marker and therapeutic target for canine HCC.

The Impact of DAXX, HJURP and CENPA Expression in Uveal Melanoma Carcinogenesis and Associations with Clinicopathological Parameters.

Uveal melanomas (UMs) represent rare malignant tumors associated with grim prognosis for the majority of patients. DAXX (Death Domain-Associated Protein), HJURP (Holliday Junction Recognition Protein) and CENPA (Centromere Protein A) proteins are implicated in epigenetic mechanisms, now in the spotlight of cancer research to better understand the molecular background of tumorigenesis. Herein, we investigated their expression in UM tissues using immunohistochemistry and explored possible correlations with a multitude of clinicopathological and survival parameters. The Cancer Genome Atlas Program (TCGA) was used for the investigation of their mRNA levels in UM cases. Nuclear DAXX expression correlated with an advanced T-stage (p = 0.004), while cytoplasmic expression marginally with decreased disease-free survival (DFS) (p = 0.084). HJURP nuclear positivity also correlated with advanced T-status (p = 0.054), chromosome 3 loss (p = 0.042) and increased tumor size (p = 0.03). More importantly, both nuclear and cytoplasmic HJURP immunopositivity correlated with decreased overall survival (OS) (p = 0.011 and 0.072, respectively) and worse DFS (p = 0.071 and 0.019, respectively). Lastly, nuclear CENPA overexpression was correlated with presence of irido-corneal angle involvement (p = 0.015) and loss of chromosome 3 (p = 0.041). Nuclear and cytoplasmic CENPA immunopositivity associated with decreased OS (p = 0.028) and DFS (p = 0.018), respectively. HJURP and CENPA mRNA overexpression exhibited strong association with tumor epithelioid histology and was linked to worse prognosis. Our results show the compounding role of DAXX, HJURP and CENPA in UM carcinogenesis, designating them as potential biomarkers for assessing prognosis and possible targets for novel therapeutic interventions.

Did the Coronavirus Disease 2019 (COVID-19) Pandemic Cause a Delay in the Diagnosis of Breast Cancer Patients?

Introduction The coronavirus disease 2019 (COVID-19) outbreak, first reported in Wuhan, China, in December 2019, quickly hit the world in just one month, causing a global public health emergency. We aimed to investigate whether the COVID-19 pandemic caused a delay in the hospital admissions of breast cancer patients and diagnosis of breast cancer, thus increasing the tumor size and the stage of the disease. Materials and methods Included in the study were patients who underwent breast cancer surgery between 01/03/2019 and 01/03/2020 (pre-COVID-19, first period) and between 01/03/2020 and 01/03/2021 (post-COVID-19, second period). Three hundred and seventy patients with enough details were included, and details were analyzed retrospectively. Tumor characteristics of pre-COVID-19 breast cancer patients were compared with the tumor characteristics of post-COVID-19 breast cancer patients. Demographics, preoperative diagnosis, tumor properties, surgical procedure (breast-conserving surgery, modified radical mastectomy, simple mastectomy, skin-sparing mastectomy), tumor size, total lymph node number, metastatic lymph node number, locally advanced disease, metastatic disease, and neoadjuvant therapy were evaluated. Results The mean tumor size increased significantly in the post-COVID-19 primary surgery group (p=0.005). There is no significant relationship between the pre-COVID-19 and post-COVID-19 period and pT in the neoadjuvant received group (p>0.05). The presence of pT2+pT3+pT4 was statistically significantly higher in the post-COVID-19 primary surgery group (p=0.001). The mean value of metastatic lymph nodes dissected between pre-COVID-19 and post-COVID-19 primary surgery groups increased significantly (p=0.010). Pericapsular extension was higher in the post-primary surgery group (p=0.002). Conclusion During the COVID-19 outbreak, breast cancer patients have difficulty accessing healthcare services and hesitate to apply to hospitals to fear contracting the COVID-19 disease. This situation has led to delays in diagnosing breast cancer patients, increased tumor size and pT grade, increased number of metastatic lymph nodes, pericapsular extension, and the resulting disease often appearing in advanced sizes and stages.

LINC00518: a key player in tumor progression and clinical outcomes.

Long non-coding RNAs (lncRNAs), defined as RNA molecules exceeding 200 nucleotides in length, have been implicated in the regulation of various biological processes and the progression of tumors. Among them, LINC00518, a recently identified lncRNA encoded by a gene located on chromosome 6p24.3, consists of three exons and is predicted to positively regulate the expression of specific genes. LINC00518 has emerged as a key oncogenic lncRNA in multiple cancer types. It exerts its tumor-promoting effects by modulating the expression of several target genes, primarily through acting as a sponge for microRNAs (miRNAs). Additionally, LINC00518 influences critical signaling pathways, including the Wnt/β-catenin, JAK/STAT, and integrin β3/FAK pathways. Elevated levels of LINC00518 in tumor tissues are associated with increased tumor size, advanced clinical stage, metastasis, and poor survival prognosis. This review provides a comprehensive summary of the genetic characteristics, expression patterns, biological functions, and underlying mechanisms of LINC00518 in human diseases.

Association of circulating tumor DNA with patient prognosis in surgically resected renal cell carcinoma.

Despite complete resection, 20%-50% of patients with localized renal cell carcinoma (RCC) experience recurrence within 5 years. Accurate assessment of prognosis in high-risk patients would aid in improving outcomes. Here we evaluate the use of circulating tumor DNA (ctDNA) in RCC using banked samples and clinical data from a single institution. The cohort consisted of 45 RCC patients (≥pT1b) who underwent complete resection. The presence of ctDNA in plasma was determined using a personalized, tumor-informed ctDNA assay (Signatera RUO, Natera, Inc.). Relationships with outcomes and other relevant clinical variables were assessed. The median follow-up was 62 months. Plasma ctDNA was detected in 18 out of 36 patients (50%) pre-operatively and was associated with increased tumor size (mean 9.3 cm vs. 7.0 cm, P < .05) and high Fuhrman grade (60% grades III-IV vs 27% grade II, P = .07). The presence of ctDNA, either pre-operatively or at any time post-operatively, was associated with inferior relapse-free survival (HR = 2.70, P = .046; HR = 3.23, P = .003, respectively). Among patients who were ctDNA positive at any time point, the sensitivity of relapse prediction was 84% with a PPV of 90%. Of note, ctDNA positivity at a post-surgical time point revealed a PPV of 100% and NPV of 64%. The lack of ctDNA detection at both time points yielded an NPV of 80%. Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies.

Utilization of neoadjuvant therapy for localized gastric gastrointestinal stromal tumors and the association with survival

BackgroundFor gastric gastrointestinal stromal tumors (GISTs), neoadjuvant imatinib is most often reserved for tumors near the gastroesophageal junction, multivisceral involvement, or limited metastatic disease. Whether localized gastric GISTs benefit from neoadjuvant therapy (NAT) remains unknown. We sought to examine factors associated with NAT utilization for localized gastric GISTs and evaluate implications on survival. MethodsThe National Cancer Database identified patients with localized gastric GISTs treated with NAT (2010–2020), excluding tumors extending beyond the gastric wall, located in the cardia, or with metastatic disease. Multivariable logistic regression assessed characteristics of NAT use. After 1:1 propensity score matching, Kaplan-Meier methods and multivariable Cox regression assessed overall survival (OS). ResultsOf 7203 patients, 762 (10.6%) received NAT followed by resection. On multivariable analysis, increasing tumor size was associated with NAT use (<2.0 cm vs 2.0–5.0 cm [odds ratio {OR}, 2.03; 95% CI, 1.19–3.47; P = .010] vs >5 cm [OR, 16.87; 95% CI, 10.02–28.40; P < .001]). After propensity score matching, 1506 patients remained. Median OS for NAT was 46.0 months vs 43.0 months for resection (P = .059), which was independently predictive of improved survival on multivariable analysis (hazard ratio [HR], 0.89; 95% CI, 0.80–0.99; P = .041). Subgroup analysis by tumor size showed no survival differences for tumors <2.0 cm or from 2.0 to 5.0 cm. Median OS was higher for tumors > 5.0 cm treated with NAT (NAT, 45.4 months [IQR, 29.5–65.9] vs upfront resection, 42.3 months [IQR 26.9–62.8]) and associated with improved survival on multivariable analysis (HR, 0.88; 95% CI, 0.78–0.99; P = .040). ConclusionAlthough patients who received NAT had improved survival, this was primarily due to tumors >5.0 cm. Expanding NAT selection criteria to include localized gastric GISTs >5.0 cm may improve outcomes and warrants investigation through clinical trials.

Cystic vestibular schwannoma – a subgroup analysis from a comparative study between radiosurgery and microsurgery

Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still, there has not been a direct comparative study comparing both SRS and SURGERY effectiveness in cystic VS. This retrospective bi-center cohort study aims to analyze the management of cystic VS compared to solid VS in a dual center study with both microsurgery (SURGERY) and stereotactic radiosurgery (SRS). Cystic morphology was defined as presence of any T2-hyperintense and Gadolinium-contrast-negative cyst of any size in the pre-interventional MRI. A matched subgroup analysis was carried out by determining a subgroup of matched SURGERY-treated solid VS and SRS-treated solid VS. Functional status, and post-interventional tumor volume size was then compared. From 2005 to 2011, N = 901 patients with primary and solitary VS were treated in both study sites. Of these, 6% showed cystic morphology. The incidence of cystic VS increased with tumor size: 1.75% in Koos I, 4.07% in Koos II, 4.84% in Koos III, and the highest incidence with 15.43% in Koos IV. Shunt-Dependency was significantly more often in cystic VS compared to solid VS (p = 0.024) and patients with cystic VS presented with significantly worse Charlson Comorbidity Index (CCI) compared to solid VS (p < 0.001). The rate of GTR was 87% in cystic VS and therefore significantly lower, compared to 96% in solid VS (p = 0.037). The incidence of dynamic volume change (decrease and increase) after SRS was significantly more common in cystic VS compared to the matched solid VS (p = 0.042). The incidence of tumor progression with SRS in cystic VS was 25%. When comparing EOR in the SURGERY-treated cystic to solid VS, the rate for tumor recurrence was significantly lower in GTR with 4% compared to STR with 50% (p = 0.042). Tumor control in cystic VS is superior in SURGERY, when treated with a high extent of resection grade, compared to SRS. Therapeutic response of SRS was worse in cystic compared to solid VS. However, when cystic VS was treated surgically, the rate of GTR is lower compared to the overall, and solid VS cohort. The significantly higher number of patients with relevant post-operative facial palsy in cystic VS is accredited to the increased tumor size not its sole cystic morphology. Cystic VS should be surgically treated in specialized centers.

GCT-26. INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION TO EMBRYONAL RHABDOMYSARCOMA

Abstract BACKGROUND Non-germinomatous germ cell tumors (NGGCT) constitute 35%- 45% of intracranial germ cell tumors. Growing teratoma syndrome has been observed in patients with NGGCTs after starting chemotherapy. While growing teratomas are typically benign, this process can rarely involve malignant transformation and result in poor prognosis. We present the case of a patient with pineal NGGCT and growing teratoma syndrome with malignant transformation to embryonal rhabdomyosarcoma. CASE REPORT A 13-year-old male presented with headaches and vision changes. An MRI brain demonstrated a 26 x 25 x 19 mm (AP X TR X CC) mixed solid and cystic pineal mass with no evidence of metastatic disease. Due to elevated alpha fetoprotein levels in the serum and cerebrospinal fluid, he was diagnosed with intracranial NGGCT. Treatment was initiated with alternating cycles of Carboplatin/Etoposide and Ifosfamide/Etoposide. After 2 cycles of chemotherapy, a complete biochemical response was noted but MRI showed increased tumor size (presumed growing teratoma syndrome). The patient underwent complete tumor resection. Histology showed embryonal rhabdomyosarcoma as a somatic malignancy arising in a mature teratoma. Further molecular characterization revealed somatic NF1 and KRAS pathogenic mutations that are consistent with the primary diagnosis. Methylation profiling, however, did not exhibit a match with any known malignancies. Continued complete response was noted following two additional chemotherapy cycles. The patient is planned for six total chemotherapy cycles followed by high-dose craniospinal radiation with boost to the primary tumor. CONCLUSIONS Malignant transformation is a rare phenomenon in NGGCT. There is no standard of care for these patients. Further studies are needed to define ideal therapy for this patient population.

Histological pattern of tumor inflammation and stromal density correlate with patient demographics and immuno-oncologic transcriptional profile in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignancy, with emerging interest in the characterization of its tumor microenvironment. Herein, we present a comprehensive histological analysis of OSCC stromal density and inflammation and their relationship with patient demographics, clinicopathologic features and immuno-oncologic signatures. Eighty-seven completely excised OSCC tissues were prospectively collected and scored for histopathologic inflammatory subtypes [HIS]-inflamed (INF), immune-excluded (IE) and immune-desert (ID), peritumoral stromal inflammation (PTSI), and peritumoral stromal fibrosis (PTSF). Scoring of inflammation was complemented by Semaphorin 4D immunohistochemistry. NanoString differential gene expression (DGE) analysis was conducted for eight OSCC cases representative of the inflammatory and stromal subtypes and the demographic groups. PTSF correlated with male gender (p = 0.0043), smoking (p = 0.0455), alcohol consumption (p = 0.0044), increased tumor size (p = 0.0054), and advanced stage (p = 0.002). On the contrary, PTSI occurred predominantly in females (p = 0.0105), non-drinkers (p = 0.0329), and small tumors (p = 0.0044). Transcriptionally, decreased cytokine signaling, and oncogenic pathway activation were observed in HIS-IE. Smokers and males displayed decreased global immune-cell levels and myeloid-cell predominance. Our work describes OSCC stromal and inflammatory phenotypes in correlation with distinct patient groups and DGE, highlighting the translational potential of characterizing the tumor microenvironment for optimal patient stratification.

Updated endometrial cancer FIGO staging: the role of MRI in determining newly included histopathological criteria.

Endometrial cancer (EC) is among the prevalent malignancies in gynecology, showing an increasing occurrence and mortality rate. The updated 2023 FIGO staging integrates both histopathological and molecular analyses, which significantly impact the prognosis and treatment approaches. This research aims to examine the effectiveness of MRI in identifying essential histopathological tumor features, including histological subtype, grade, and lymphovascular space invasion. A total of 106 patients diagnosed with EC from February 2018 to December 2023 underwent preoperative pelvic MRI. Surgical procedures followed ESMO guidelines, with histopathological assessments using FIGO 2009 criteria. Two radiologists independently evaluated MRI images, measuring maximum tumor size, minimum tumor ADC value (using a free-hand ROI technique), and ADC tumor/myometrium ratio. MRI findings were compared with histopathological data. Peritoneal implant presence and tumor size exhibited significant differences between endometrioid adenocarcinoma (EAC) and non-endometrioid endometrial carcinoma (NEEC), with p values of < 0.001 and 0.003, respectively. Significant differences in age, tumor size, ADC tumor, and ADC tumor/myometrium between low-grade and high-grade tumors were observed, with p values of < 0.001, 0.004, 0.006, and 0.011, respectively. Increased tumor size, reduced ADC tumor, ADC tumor/myometrium, and pelvic peritoneal implant presence were significantly associated with LVSI, with p values of < 0.001, 0.001, 0.002, and 0.001, respectively. The AUC values for tumor size, ADC tumor, and ADC tumor/myometrium were 0.842, 0.781 and 0.747, respectively, in distinguishing between low and high-grade endometrial tumors. Similarly, obtained AUC values for predicting LVSI were 0.836, 0.719, and 0.696, respectively. Our study emphasizes MRI's role in predicting tumor characteristics such as histological subtype, grade, and LVSI based on updated FIGO criteria. By highlighting the potential of MRI, this research contributes to our comprehension of improving diagnostic and clinical management for EC. Further multicenter studies are warranted to validate these findings and establish MRI's role in EC management.