Presence Of Metastases Research Articles

Treatment tactics for patients with combined kidney tumor and urolithiasis (clinical cases)

Annotation. Global medical literature shows an ever-increasing number of patients suffering from urolithiasis and malignant kidney tumors. The number of patients suffering from both conditions also seems to be on the rise. Correlation and interdependence, as well as the preferable course of treatment for these diseases, remain uncertain. The present study aims to map out treatment strategies for patients presenting with both urolithiasis and kidney tumor. In 2013- 2021 21 patients with urolithiasis and kidney tumor were examined and treated in the SI “Acad. O.F. Vozianov Institute of Urology NAMS of Ukraine”. In 61.9% of cases a tumor and calculi were located unilaterally, in 14.3% contralaterally, and in other 14.3% tumor was comorbid with bilateral urolithiasis. 4.75% of patients had a tumor combined with a stone in the upper third of the ureter on the same side, and 4.75% – in the lower third of the ureter on the opposite side. Depending on the localization of a tumor and a stone, the stage of the oncological process, the presence of metastases, clinical manifestations, etc, different treatment tactics have been employed. Simultaneous removal of a kidney tumor and a stone in case of their ipsilateral location was performed in 52.4% of patients. We prioritized organ-sparing surgery in all cases. 9.52% of patients underwent PNLT before the tumor removal. In 9.52% of patients ureterolith removal was followed by kidney tumor removal. 71.4% of patients underwent successful laparoscopic resection of a tumorous kidney, but in 28.6% of patients, attempts to save the organ failed. So, types of combinations of urolithiasis and kidney tumor can be different, hence, it is necessary to apply individual treatment tactics in each case. If the functional state of a tumorous kidney and technical capacity allow it, organ-sparing surgery is highly advisable.

Adrenal Oligometastatic Malignant Pheochromocytoma: Case Report

is defined by the presence of metastases in non-chromaffin tissue or by the appearance of recurrences. About 40% of cases are genetic. It is therefore important to look for symptoms that suggest a genetic predisposition syndrome, particularly the multiple endocrine neoplasia (MEN). The severity of this cancer is due to its rarity, a common cause of delayed diagnosis. Through the observation of our patient followed for malignant pheochromocytoma for 3 years and became oligometastatic, we would like to present the characteristics of this rare disease and to underline the interest of an optimal as well specific management of the tumor, the oligometastases, and associated complications, passing through experienced multidisciplinary teams.

Minimally Invasive Treatment Options for Hepatic Uveal Melanoma Metastases.

Uveal melanoma is one of the most common primary intraocular malignancies that accounts for about 85% of all ocular melanomas. The pathophysiology of uveal melanoma is distinct from cutaneous melanoma and has separate tumor profiles. The management of uveal melanoma is largely dependent on the presence of metastases, which confers a poor prognosis with a one-year survival reaching only 15%. Although a better understanding of tumor biology has led to the development of novel pharmacologic agents, there is increasing demand for minimally invasive management of hepatic uveal melanoma metastases. Multiple studies have already summarized the systemic therapeutic options available for metastatic uveal melanoma. This review covers the current research for the most prevalent locoregional treatment options for metastatic uveal melanoma including percutaneous hepatic perfusion, immunoembolization, chemoembolization, thermal ablation, and radioembolization.

High-grade Undifferentiated Pleomorphic Sarcoma Presenting as Acquired Lymphangioma Circumscriptum

A previously healthy woman in her 40s presented to the dermatology clinic with a 1-year history of a tender, draining, enlarging mass on the left buttock. Physical examination revealed an extensively indurated hyperpigmented nodule with numerous overlying clustered exophytic verrucous papules on the L medial buttock (see figure 1). Initial skin biopsy of verrucous lesions was notable for lymphangioma with overlying condyloma, D2-40 positive. MRI abdomen and pelvis with contrast demonstrated a left gluteal enhancing subcutaneous soft tissue mass, 10.3 x 8.2 x 8.8 cm in size, overlying and involving the left gluteus maximus, along with satellite nodules present in the medial gluteus maximus and paraspinal muscles, with bilateral pelvic and inguinal adenopathy. Excisional deep tissue biopsy revealed a diagnosis of a high-grade, multifocal spindle and undifferentiated pleomorphic sarcoma. The patient subsequently underwent 4 cycles of neoadjuvant chemotherapy AIM (doxorubicin, iphosphamide, MESNA), followed by radical resection of the left gluteal region, with positive margins, followed by repeat surgical resection and reconstruction with left-sided latissimus dorsi myocutaneous free flap. The patient has now completed radiation therapy.
 Soft tissue sarcoma is a heterogeneous group of rare malignancies of mesenchymal origin, that represents 0.8% of all adult cancers. Prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability1. Herein, we report a novel case of high-grade soft-tissue undifferentiated pleomorphic sarcoma, masquerading as acquired lymphangioma circumscriptum (ALC), as noted on initial skin biopsy of grouped flesh-colored verrucous papules overlying an indurated tender mass. ALC is a lymphatic malformation occurring as sequela to any process which interrupts previously normal lymphatic drainage. As such, subcutaneous lymphatic cisterns are unable to drain completely into the general lymphatic system, resulting in lymphatic dilation and subsequent development of vesicular and papular lesions on the trunk, extremities, and anogenital areas.2 ALC can mimic common infectious growths including molluscum contagiosum and condyloma accuminata, and accordingly be mismanaged. Etiologic causes of ALC including malignancy, and has previously been reported in the setting of cervical carcinoma, vulvar carcinoma, endometrial carcinoma, Hodgkin lymphoma, rhabdomyosarcoma, rectal carcinoma, melanoma, and high-grade penile dysplasia2,3,4. Other etiologic causes can include surgery, trauma, radiation therapy, chronic inflammatory conditions including hidradenitis suppurativa, and inflammatory bowel disease.
 To date, acquired lymphangioma circumscriptum has not been reported in the setting of underlying high-grade pleomorphic soft tissue sarcoma. As such, clinical presence of grouped frogspawn-like or verrucous papules, in an area of tender induration or lymphedema, should prompt a work-up to exclude an underlying malignant etiology as new onset ALC may be masquerading an underlying malignancy.

Clinical and Pathological Features and Gene Expression Profiles of Clinically Aggressive Papillary Thyroid Carcinomas

Papillary thyroid carcinoma (PTC) is considered an indolent neoplasm but it may demonstrate aggressive behavior. We aimed to identify clinical and pathological characteristics and molecular signatures associated with aggressive forms of PTCs. We selected 43 aggressive PTC cases based on the presence of metastases at the time of diagnosis, the development of distant metastasis during follow-up, and/or biochemical recurrence, and 43 PTC patients that were disease-free upon follow-up, matching them according to age, sex, pT, and pN parameters. Twenty-four pairs (a total of 48 cases) and 6 normal thyroid tissues were studied using targeted mRNA screening of cancer-associated genes employing NanoString nCounter® technology. In general, aggressive PTCs showed distinctive clinical and morphological features. Among adverse prognostic parameters, the presence of necrosis and an increased mitotic index were associated with shorter disease-free and overall survivals. Other parameters associated with shorter disease-free or overall survivals include a lack of tumor capsule, the presence of vascular invasion, tumor-infiltrating lymphocytes, fibrosclerotic changes, age > 55 years, and a high pTN stage. Various pathways were differentially regulated in non-aggressive as compared to aggressive PTC, including the DNA damage repair, the MAPK, and the RAS pathways. In particular, the hedgehog pathway was differentially de-regulated in aggressive PTC as compared to non-aggressive PTC cases, being WNT10A and GLI3 genes significantly up- and down-regulated in aggressive PTC and GSK3B up-regulated in non-aggressive PTC cases. In conclusion, our study revealed specific molecular signatures and morphological features in aggressive PTC that may be useful to predict more aggressive behavior in a subset of PTC patients. These findings may be useful when developing novel, tailored treatment options for these patients.

Exploring biomarkers and prognostic factors in uterine carcinosarcoma: An insight into L1CAM, CDX2, p53, and MSI status.

Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers. The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.

Efficacy of avelumab in the treatment of oncourological malignances. Results of registration studies and own experience

Background. In the JAVELIN Bladder 100 trial, 1st line maintenance with avelumab in combination with best supportive care significantly increased (9.2 months) overall survival compared to best supportive care in patients with locally advanced or metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy: 29.7 months versus 20.5 months, respectively. Trial results led to inclusion of avelumab into the international guidelines as a standard of care with the highest level of evidence. Combined therapy with avelumab + axitinib in patients with previously untreated metastatic renal cell carcinoma showed higher progression-free survival and objective response rate compared to sunitinib in all IMDC (International Metastatic Renal Cancer Database Consortium) groups. Avelumab + axitinib is one of the immuno-oncology combinations with proven effectiveness for progression-free survival and objective response rate.Aim. To evaluate the effectiveness of avelumab in treatment of oncological urological diseases in routine clinical practice. Materials and methods. At the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology - branch of the National Medical Research Radiology Center, 12 patients with locally advanced inoperable and metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy in combination with gemcitabine received maintenance avelumab therapy. Median follow-up was 10 months. Primary endpoints were overall survival from the start of avelumab maintenance therapy and safety.Combined therapy with avelumab + axitinib was administered in 18 patients with metastatic renal cell carcinoma. Median follow-up was 9 (3-16) months. Overall survival, progression-free survival, response rate and safety in the overall population and according to IMDC groups were evaluated.Results. At data cut-off (March 2023) with median follow-up of 10 months, overall survival was 100 %, progression-free survival was 66.7 % (among patients who received more than 3 infusions - 100 %). Progression-free survival was higher in patients with tumors of the lower urinary tract compared to upper (72.5 % versus 60 %), complete response to induction platinum-based chemotherapy compared to partial response and stable disease (100 % versus 66.7 %) and presence of metastases in the lymph nodes only compared to visceral and bone metastases (100 % versus 66.7 %). Adverse events were observed in 4 (66.7 %) patients.Among 18 patients who received avelumab + axitinib, complete response was observed in 2 (11.1 %) patients, partial response in 6 (33.3 %) patients, stable disease in 9 (50 %) patients, disease progression in 1 (5.6 %) patient. Response to therapy was observed in patients of all prognosis groups; for large (&gt;5 cm) metastases in the lungs, soft tissues, lymph nodes and bones response was observed 3 months after treatment start. Overall survival for this follow-up duration was 100 %, progression-free survival was 96.4 ± 11.2 %. Adverse events were observed in 8 (44.4 %) patients, and in 6 (75 %) of them they were grade I—II and did not require infusion regimen correction or axitinib dose reduction.Conclusion. Avelumab maintenance therapy in the 1st line is the standard of care for patients with locally advanced and metastatic urothelial cancer without disease progression during 1st line platinum-based chemotherapy. Maintenance therapy allows to achieve better overall survival and progression-free survival irrespective of the choice of platinum regimen (cisplatin or carboplatin), response to platinum-based chemotherapy, number of chemotherapy cycles, tumor localization and advancement.Experience of the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology confirms results of the JAVELIN Bladder 100 trial on the effectiveness of avelumab maintenance therapy in routine clinical practice. Combination drug therapy with avelumab and axitinib in patients with metastatic renal cell carcinoma is an effective and safe treatment method which allows to achieve fast objective response and has good tolerability in patients irrespective of IMDC group or metastasis location. Effectiveness and favorable safety profile of avelumab + axitinib combination were proven in the context of routine clinical practice.

Formulation and validation of a baseline prognostic score for osteosarcoma treated uniformly with a non-high dose methotrexate-based protocol from a low middle income healthcare setting: a single centre analysis of 594 patients.

The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol. A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability. 594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell's c-indices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively. The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival.

Is Bone Marrow Aspiration and Biopsy of Clinical Importance in the Initial Staging of Extraskeletal Ewing Sarcoma?

Extraskeletal Ewing sarcoma are rare tumors within the Ewing sarcoma family. Initial staging studies for extraskeletal Ewing sarcoma historically have included imaging and bone marrow aspiration and biopsy (BMAB). However, recent studies on Ewing sarcoma of bone have questioned the utility of BMAB in the initial staging of patients, but no studies of which we are aware have evaluated the role of BMAB in extraskeletal Ewing sarcoma. We suspected that BMAB was of low diagnostic yield in patients with extraskeletal Ewing sarcoma and exposed patients to potential morbidity without an impact on their clinical course. Is BMAB a useful test in the staging of extraskeletal Ewing sarcoma? Between January 1996 and December 2021, our institution evaluated 109 patients with a listed diagnosis of extraskeletal Ewing sarcoma. Those patients were retrospectively reviewed for this study. Of those, we considered patients with biopsy-confirmed diagnosis of extraskeletal Ewing sarcoma. Biopsy was performed based on institutional protocols, with all diagnoses assigned by a board-certified pathologist. Based on that criteria, 96% (105 of 109) were eligible. An additional 18% (20 of 109) were excluded because records of their initial diagnostic and staging workup were not available. This left 78% (85 of 109) for analysis. Of those, 52% (44 of 85) were male. The average age was 32 ± 16 years. Primary tumor locations included extremities in 26% (22 of 85), paraspinal in 20% (17 of 85), chest in 19% (16 of 85), retroperitoneum in 13% (11 of 85), intraabdominal in 12% (10 of 85), intrapelvic in 7% (6 of 85), and head or neck in 4% (3 of 85). Initial diagnostic and staging information, including the use of PET-CT, bone scan, CT chest, and BMAB, was collected. Metastatic disease at the time of presentation or during follow-up was noted. The utility of BMAB was determined by the rate of positive tests in those undergoing BMAB during the initial staging process. Descriptive statistical analysis was sufficient to address the study question, and therefore no comparative statistics were performed. BMAB was obtained during the initial staging process in 64% (54 of 85) of patients. This BMAB was negative in all 54 patients, including those with known metastatic disease. Diagnosing metastatic disease in extraskeletal Ewing sarcoma is important as the presence of metastases at diagnosis adversely affects prognosis. The routine use of BMAB in the staging process of extraskeletal Ewing sarcoma is of low diagnostic yield. BMAB is unlikely to diagnose metastatic involvement even in patients with known metastases to bone. We do not have enough data to suggest whether other modalities, such as PET-CT, might be more useful. Similar studies should be pursued to determine the utility of the remainder of staging modalities in patients with extraskeletal Ewing sarcoma to elucidate the most efficient and effective staging protocol. Level III, diagnostic study.

An Australian experience using Tc-PSMA SPECT/CT in the primary diagnosis of prostate cancer and for staging at biochemical recurrence after local therapy.

Technetium 99 prostate-specific membrane antigen(Tc-PSMA) single-photon emission computed tomography/computed tomography (SPECT/CT) has the potential to provide greater accessibility globally thangallium 68(Ga)-PSMA positron emission tomography (PET)/CT but has not been studied as extensively in primary diagnosis, staging, or relapse of prostate cancer (PC). We instituted a novel SPECT/CT reconstruction algorithm using Tc-PSMA and established a database to prospectively accumulate data on all patients referred with PC. This study extracts data on all patients referred over a 3.5-year period with the primary aim of comparing the diagnostic accuracy of Tc-PSMA and multiparametric magnetic resonance imaging (mpMRI) in the primary diagnosis of PC. The secondary aim was to assess the sensitivity of Tc-PSMA in detecting disease with relapse after either radical prostatectomy or primary radiotherapy. A total of 425 men referred for primary staging (PS) of PC and 172 men referred with biochemical relapse (BCR) were evaluated. We evaluated diagnostic accuracy and correlations between Tc-PSMA SPECT/CT, magnetic resonance imaging(MRI), prostate biopsy, prostate-specific antigen (PSA), and age in the PS group and positivity rates at different PSA levels in the BCR group. Taking the biopsy's grade according to the International Society of Urological Pathologyprotocol as a reference, the sensitivity (true positive rate), specificity (true negative rate), accuracy (positive and negative predictive value), and precision (positive predictive value) for Tc-PSMA in the PS group were 99.7%, 83.3%, 99.4%, and 99.7%, respectively. Comparison rates for MRI in this group were 96.4%, 71.4%, 95.7%, and 99.1%. We found moderate correlations between Tc-PSMA uptake in the prostate and biopsy grade, the presence of metastases, and PSA. In BCR, the Tc-PSMA positive rates were 38.9%, 53.2%, 62.5%, and 84.6% at PSA levels of <0.2, 0.2 to <0.5, 0.5 to <1.0, and > 1.0 ng/mL respectively. We have shown that Tc-PSMA SPECT/CT using an enhanced reconstruction algorithm has a diagnostic performance similar to Ga-PSMA PET/CT and mpMRI in an everyday clinical setting. It may have some advantages in cost, sensitivity for primary lesion detection, and the ability for intraoperative localization of lymph nodes.

Associated Factors of Red Blood Cell Alloimmunization among Solid Cancer Patients in Teaching Hospital in Malaysia

Background: Alloimmunization is a known complication following repeated red blood cell transfusions. However, the associated factors of RBC alloimmunization are different among blood recipient groups. This study aimed to determine the associated factors of red blood cell alloimmunization among solid cancer patients in Hospital USM. Material and Methods: This cross-sectional study involved 322 adult solid cancer patients screened for red cell alloantibodies in our centre from October 2016 until February 2019. The clinical and transfusion data were obtained from the patient’s medical record and laboratory information system (My Transfusi). The multiple logistic regression was used for analysis of potential associated factors of red blood cells alloimmunization, and p-value of less than 0.050 was considered statistically significant. Results: The patient’s mean age was 52.0 years old, with the majority were Malays (91.0%) and females (61.2%). The most common cancers were breast (32.3%) followed by gastrointestinal (16.8%) and head and neck (14.3%). The presence of metastases (adjusted OR=13.53, p=0.017), numbers of packed red cell transfusions (adjusted OR=1.12, p= 0.015), and blood group A (adjusted OR=7.45, p=0.003) were the associated factors of alloimmunization. Conclusions: Solid cancer patients with metastases, received a higher number of packed red cell transfusions, and blood group A were at higher risk for alloimmunization. Strategies to provide phenotype RBC should focus on this type of patient to prevent red blood cells alloimmunization in solid cancer patients. Bangladesh Journal of Medical Science Vol. 22 No. 02 April’23 Page : 379-384

Serum total oxidant and anti-oxidant status in children with cancer.

Oxidative stress has a potential role in carcinogenesis. Anti-oxidant enzymes have a neutralizing effect on both cancer initiation and progression. We aimed to assess the oxidant and anti-oxidant levels of pediatric cancer patients and to compare the levels in healthy controls. The study involved 105 pediatric cancer patients (40 undergoing chemotherapy, 65 survivors) and 40 healthy children. The serum total oxidant status (TOS) and total anti-oxidant status (TAS) were measured. The oxidative stress index was significantly lower in pediatric cancer patients compared to the levels in the controls (0.20 ± 0.07 vs. 0.26 ± 0.10; P = 0.001). The mean serum TAS level was significantly higher in patient groups compared to the level in the control (1.87 ± 0.48 vs. 1.63 ± 0.32 mmol/L, P = 0.001). The TAS level of children with cancer in survivors was also found to be significantly higher compared to the levels in the control group (1.85 ± 0.45 vs. 1.63 ± 0.32 mmol/L, P = 0.005). Radiotherapy, surgery, relapsed disease, presence of metastases, and receiving enteral nutritional support caused no change in the TAS/TOS level. It has been revealed for the first time that the serum total anti-oxidant level was high in children undergoing chemotherapy and the survivor group as well. Moreover, the oxidative stress index was low in children with cancer. Longitudinal prospective studies are needed to reveal the alterations in oxidant status among children with cancer.

Abstract 4394: Feasibility analysis of querying EHR databases for cancer clinical trial criteria

Abstract Background: In order to enroll patients for clinical trials (CT), it is common to run queries in clinical databases using CT eligibility criteria as filters and specifications. However, CT eligibility criteria are often unavailable as discrete data fields, which can interfere with CT recruitment. The purpose of this study was to identify the most commonly needed eligibility criteria that are specified in cancer CT to investigate whether and how they could be found in clinical databases. Design: We examined the data elements needed for the trial eligibility criteria that would be used in queries for all the Breast, Gastrointestinal, Genitourinary, Head and Neck, and Cutaneous Cancer treatment trials open for enrollment across our health system. We then performed a sort-rank exercise for these eligibility criteria terms. Results: The analysis included 33 trials and 12 data elements. Table 1 shows the number of times each eligibility criterion appeared in the 33 CTs and its feasibility for an EHR query. The data elements that appeared most frequently were Organ/Cancer Site (100%), Tumor Morphology (66.7%), Presence of Metastases (51.5%), TN Staging (39.4%), and Days Since Diagnosis (24.2%). Of these, only Organ/Cancer Site and Days Since Diagnosis were accessible as structured datapoints in our clinical databases. Conclusions: The lack of feasibility for EHR query is likely due to the fact that healthcare information is generally stored in a discrete, structured form as a means of completing care transactions (drug orders or laboratory values) and ensuring billing compliance (ICD and outpatient CPT codes). This presents a critical challenge when data are required for CT enrollment, quality assurance metrics, and prospective and retrospective clinical research. Health systems—and by extension, their patients—would benefit from investing in structured data schemas involving AJCC staging, tumor morphology, and presence of metastases. Eligibility criteria with corresponding number of appearances in CTs and feasibility for EHR query Eligibility criterion Number of trials with each criterion Feasibility for EHR query Organ/Cancer Site 33 (100%) Accessible (ICD codes very detailed for site and used consistently for purpose of billing) Tumor Morphology 22 (66.7%) Not accessible (Code have not been created in ICD system, SNOMED is not widely adopted, not needed for billing) Presence of Metastases 17 (51.5%) Not accessible (Not coded consistently, coded in ICD as a “secondary” malignancy but generally does not affect billing) TN Staging 13 (39.4%) Not accessible (Not coded in ICD system) Days Since Diagnosis 8 (24.2%) Accessible (Structured data captured for purpose of initial transaction) Tumor Markers and Other Lab Results 4 (12.1%) Accessible (Structured data captured by laboratory instrument for purpose of initial transaction) Immunohistochemical Biomarkers 4 (12.1%) Not accessible (Pathologist assessment documented as narrative text) History of Systemic Therapy 3 (9.1%) Accessible (NDC drug code captured with initial order in order to complete the initial transaction) Feasibility of Resection 3 (9.1%) Not accessible (Surgeon assessment documented as narrative text) Disease progression 3 (9.1%) Not accessible (Radiologist assessment documented as narrative text) Surgical Procedure 2 (6.1%) Accessible as CPT codes for outpatient surgeries as needed for billing. Not accessible for inpatient surgeries where billing is capitated as a single fee for entire hospitalization based on disease related groups Margins 2 (6.1%) Not accessible (Pathologist assessment documented as narrative text) Citation Format: Dylan J. Cooper, Joseph Herman, Nalan Yurtsever, Sergio Garza, Daniel A. King, Yonah Ziemba. Feasibility analysis of querying EHR databases for cancer clinical trial criteria. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4394.

Abstract 2395: A bioluminescent probe for detection and imaging of heparanase enzymatic activity

Abstract Cancers of all types have been shown to overexpress the carbohydrate-processing enzyme heparanase during angiogenesis and invasion, and this enzymatic activity correlates positively with tumor stage and the presence of metastases. While detection of heparanase enzymatic activity holds potential for cancer diagnosis and staging, no probe has been achieved for in vivo systems. We have recently developed fluorogenic heparanase probes for single-step detection of in vitro heparanase enzymatic activity, drastically simplifying the detection of heparanase activity. The modular chemistry allows us to extend the utility further to improve the sensitivity of in vitro heparanase activity detection and enable in vivo detection. Thus, we have developed a bioluminescent heparanase probe, which upon activation by heparanase produces a substrate of firefly luciferase, a standard reporter enzyme for in vivo monitoring of tumor progression. This probe will be validated in multi-well assays of heparanase activity, and applied in real-time correlation of heparanase activity and tumor progression in, fLuc+ tumors in animal models. These studies hold promise in enabling highly sensitive detection of heparanase activity both in vitro and in vivo, and in allowing future research of real-time monitoring of heparanase activity with the tumor progression. Citation Format: Johnathan Somers, Kelton Schleyer, Jun Liu, Zhishen Wang, Arjun Kafle, Lina Cui. A bioluminescent probe for detection and imaging of heparanase enzymatic activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2395.

Abstract 5174: PEGylated liposomal doxorubicin improves oral cancer response to radio-immunotherapy

Abstract Introduction: The immunosuppressive tumor microenvironment (TME) in oral cancer inhibits response to conventional treatment (surgery +/- chemoradiotherapy) and check-point inhibitor (αPD1) immunotherapy. The chemotherapeutic agent doxorubicin and its PEGylated liposomal nanoparticle formulation (PLD) have been shown to target myeloid derived suppressor cells (MDSCs) in the TME. In this preclinical work, we investigated whether PLD improves response to radio-immunotherapy in a highly aggressive and immunologically ‘cold’ oral cancer model. Experimental Procedure: Studies were performed in the MOC2 syngeneic mouse model of oral cancer. Mice were randomized to one of seven treatment groups: αPD1, Radiation (XRT), αPD1+XRT, PLD, PLD+αPD1, PLD+XRT, PLD+αPD1+XRT. High-resolution nanoparticle contrast-enhanced computed tomography (nCECT) imaging was performed, and whole-body T2-weighted magnetic resonance imaging (MRI) used to monitor primary tumor response and development of metastases. Response evaluation criteria in solid tumors (RECIST) were used to evaluate treatment outcomes. Results: Tumors in all non-PLD groups were treatment resistant and grew progressively, consistent with the immunologically ‘cold’ MOC2 model. In contrast, all PLD groups showed tumor regression with 25-38% complete responders (CR) and 12-88% partial responders (PR) while all animals in non-PLD groups showed progressive disease (PD). MR imaging identified a high incidence of regional and distant metastases in the non-PLD groups while the PLD groups showed decreased regional and no distant metastases (Table 1). Presence of metastases was confirmed by nCECT imaging and histopathological analysis. Conclusion: PLD improved response to radio-immunotherapy in a highly aggressive immunologically ‘cold’ mouse model of oral cancer while simultaneously preventing disease progression and metastasis. Citation Format: Laxman Devkota, Rohan Bhavane, Andrew Badachhape, Ratna Veeramachaneni, Renuka Menon, Prajwal Bhandari, Sofia Cortes, Fabio Henrique Brasil Da Costa, Ketan Ghaghada, Simon Young, Andrew G. Sikora, Ananth V. Annapragada. PEGylated liposomal doxorubicin improves oral cancer response to radio-immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5174.

Prognostic Value of β-Catenin and L1CAM Expressions in Type I Endometrial Carcinoma.

The aim of this study is to evaluate the expression of β-catenin and L1CAM in the type I of Endometrial Carcinoma. This study was an analytical study with a cross-sectional design using 49 samples of type I Endometrial Carcinoma. Immunohistochemical method was used to evaluate the expression of β-catenin and L1CAM related to two significant prognostic parameters i.e., lymphovascular space invasion (LVSI) and metastases event of type I Endometrial Carcinoma samples. From all samples collected, based on the presence of LVSI, there were 17 cases (34.7%) with LVSI and 32 (65.3%) no LVSI. Among them, there were 13 cases that included lymph node or omental samples in type I Endometrial Carcinoma, 5 (38.5%) cases of metastasis, and 8 (61.5%) cases that did not metastasize. The statistical results showed that there was a significant correlation between β-catenin and L1CAM expressions examined from tumor cells with lymphovascular space invasion and the presence of metastases in the type I Endometrial Carcinoma (p <0.05). This study suggest that the positive expression of β-catenin together with L1CAM can participate in the development of tumor cells in type I Endometrial Carcinoma, in its ability to involve lymphovascular space invasion, and metastases to other sites. Our results indicate that both of β-catenin and L1CAM are prominent biomarkers for the prognosis of type I Endometrial Carcinoma.

Exérèse fascio-cutanée d’un dermatofibrosarcome de Darier-Ferrand du flanc droit

Darrier-Ferrand dermatofibrosarcoma (DFSC) is the most common cutaneous sarcoma. It generally affects subjects with an average age of 40years, without gender or race predominance. It is a tumour characterised by a slow evolution and local aggressiveness. The reasons for consultation are pain, pruritus or rapidly progressive evolution. There are no specific imaging studies for this tumour. The diagnosis of certainty is based on immunohistochemistry with positive CD34 labelling. Treatment is surgical based on wide excision. This is an observation of a patient operated in our department for the initial diagnosis of cutaneous leiomyosarcoma of the right flank that rapidly increased in volume to 10cm in sixmonths. A large fasciocutaneous excision was performed. The postoperative course was simple. In our patient, this lesion occurred on an old burn scar. This notion of skin trauma preceding the appearance of DFSC is reported in 10 to 20% of cases. The rapid increase in volume was the reason for consultation. The diagnosis of DFSC could only be made on definitive analysis of the surgical specimen, which showed positive immunostaining for CD34. The occurrence of metastases, although rare, confers a survival of no more than twoyears. The prognostic factors depend on the quality of the surgical excision, the presence of metastases and certain locations (head, neck), which make the surgery particularly mutilating. Only long-term monitoring attests to definitive cure, given the frequency of recurrence. DFSC is a rare and slowly evolving tumour. Wide surgical excision should be attempted in most cases. In inoperable cases, the use of targeted therapies (IMATINIB) has led to complete cures in some cases.

Sporadic pancreatic neuroendocrine neoplasms: A retrospective clinicopathological and outcome analysis from a Latvian study group.

Although pancreatic neuroendocrine neoplasms (PNEN) are rare, there has been a constant increase in incidence. Furthermore, PNEN present unique clinical behaviors and long-term survival can be expected even in the presence of metastases as compared with ductal adenocarcinoma of the pancreas. Determining the best therapeutic approach and proper timing of therapy requires knowledge of reliable prognostic factors. Therefore, the aim of this study was to explore clinicopathological features, treatment, and survival outcomes of patients with PNEN based on Latvian gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) registry data. Patients with confirmed PNEN at Riga East Clinical University Hospital and Pauls Stradins Clinical University Hospital, between 2008 and 2020, were retrospectively analyzed. Data were collected and included in EUROCRINE, an open-label international endocrine surgical registry. In total, 105 patients were included. The median age at diagnosis was 64 years (IQR 53.0-70.0) for males and 61 years (IQR 52.5-69.0) for females. In 77.1% of patients, tumors were hormonally nonfunctional. Among those with functioning PNEN, 10.5% of patients presented with hypoglycemia and were diagnosed with insulinoma, 6.7% of patients presented with symptoms related to carcinoid syndrome; 30.5% of patients showed distant metastases at the time of diagnosis, and surgery was performed in 67.6% of patients. Notably, for five patients with nonfunctional PNEN <2 cm, a "watch and wait" approach was used; none of the patients developed metastatic disease. The median length of hospital stay was 8 days (IQR 5-13). Major postoperative complications were found in 7.0% of patients, and reoperation was conducted for 4.2% of patients, due to postpancreatectomy bleeding (2/71) and abdominal collection (1/71). The median follow-up period was 34 months (IQR 15.0-68.8). The OS at the last follow-up was 75.2% (79/105). The observed 1-, 5- and 10-year survival rates were 87.0, 71.2 and 58.0, respectively. Seven of the surgically treated patients had tumor recurrence. The median time of recurrence was 39 months (IQR 19.0-95.0). A univariable Cox proportional hazard analysis provided evidence that a nonfunctional tumor, a larger tumor size, the presence of distant metastases, a higher tumor grade, and the tumor stage were strong, negative predictors of OS. Our study represents the general trends of clinicopathological features and treatment of PNEN in Latvia. For PNEN patients, tumor functionality, size, distant metastases, grade, and stage may be useful to predict OS and must be confirmed in further studies. Furthermore, a "surveillance" strategy might be safe for selected patients with small asymptomatic PNEN.

Clinical Features and Outcomes of Patients with Pancreaticobiliary Malignancies in Los Angeles County and Their Association with CA 19-9 Levels

We retrospectively collected data on patients with biopsy-confirmed PBMs and stratified patients into categories based on their CA 19-9 level at diagnosis. Survival curves were estimated for patients in each of the three aforementioned CA 19-9 groups using the Kaplan-Meier method and compared using a Cox proportional hazards regression model. Of the 283 patients identified, 23 (8.1%) had low, 70 (24.7%) had normal, and 190 (67.1%) had elevated CA 19-9 levels. After controlling for sex, age, BMI, the presence of metastases at the time of diagnosis, and treatment with curative intent, the hazard ratio for death in the elevated CA 19-9 group compared to the low CA 19-9 group was 1.993 (95% CI 1.089-3.648; p = 0.025). The elevated CA 19-9 level compared to the low CA 19-9 level and the presence of metastases were associated with an increased hazard of death, while treatment with curative intent was associated with a decreased hazard of death.

The role and place of transanal endoscopic resections in rectal cancer

The aim of the work is to improve the algorithm of intraoperative diagnosis of rectal cancer metastasis in order to optimize surgical intervention and reduce the number of intraoperative and postoperative complications. Materials and methods. 184 operated patients with rectal cancer (RC) were divided into 2 groups: group 1 – patients with stage I RC (T1–2N0M0), and group 2 – stage II RC (T3N0M0), who underwent intraoperative detection and examination of sentinel lymph nodes. The volume and surgical approach depended on the stage and the presence of metastases (MTS). The average period of postoperative observation was 12–60 months, taking into account early (purulent-septic complications, bleeding, intestinal perforation) and late (recurrent rectal cancer) complications. Results. The patients of group 1 had no MTS lesions of the sentinel lymph nodes, the surgical intervention was limited to transanal microsurgery due to this fact. Among the complications were the following: bleeding – 2.2 %; intraoperative perforation of the intestinal wall – 5.6 %. No purulent-septic cases, no recurrences of rectal cancer were detected. In group 2, 36 (38.3 %) out of 94 patients had MTS detected intraoperatively in the sentinel lymph nodes which required a low anterior rectal resection with total mesorectumectomy. Among the complications was bleeding – 6.3 %. No intraoperative perforations of the intestinal wall and no purulent-septic complications were detected. Recurrence of rectal cancer was detected in 12 (12.8 %) patients. Conclusions. Performing transanal endoscopic resections in patients with stage I RC and especially stage II RC is possible only under the conditions of mandatory intraoperative staining and urgent histological examination of the sentinel lymph nodes. The extent of the surgical intervention is determined on the operating table based on urgent histological examination results. When MTS lesions of the mesorectal sentinel lymph nodes are detected, the operation should be continued with mandatory mesorectumectomy.