Metastatic Neoplasia Research Articles

Diagnostic elucidation between primary sweat gland or breast cancer metastasis: case report of mucinous carcinoma of the scalp

Introduction: primary malignant neoplasms of the apocrine glands are rare, accounting for less than one percent of all primary malignant skin lesions. Cutaneous apocrine carcinoma presents characteristics similar to those of cutaneous metastases from breast carcinoma, which makes its diagnostic differentiation very difficult. Objective: the objective of this case report was to demonstrate the difficulty in differentiating the diagnosis between the tumor mentioned being primary to the sweat gland or being a metastasis of breast carcinoma. Methods: this is a descriptive, retrospective study with a qualitative approach, in the form of a clinical case report, carried out based on the records available in the patient’s medical records. Data were collected regarding the patient’s previous history, current history, diagnostic hypotheses, treatments performed, and complementary exams performed. Result: the authors describe the case of an 86-year-old patient who was diagnosed with mucinous carcinoma in a recurrent lesion on the scalp and describe the difficulties encountered and the resources used to elucidate the diagnosis between whether this was a primary adnexal tumor of the sweat gland of the skin or metastatic neoplasia of the breast. Conclusion: the pathologist’s resources alone are not sufficient to reach a differential diagnosis between primary mucinous carcinoma of the skin and cutaneous metastasis of a primary mucinous carcinoma of the breast, requiring an extensive correlation with clinical data and imaging exams for a better diagnostic conclusion regarding the primary site of the neoplasia.

Effector Functions of Dendritic Cells in Cancer: Role of Cytotoxicity and Growth Inhibition.

The tumor microenvironment plays a critical role in modulating immune responses associated with tumorigenesis, tumor progression, and metastasis. Dendritic cells (DC) play a key role in preventing and progression of metastatic neoplasia by driving and restoring dysfunctional immune systems and obliterating immunosuppression, thus obstructing tumor evasion. In this review, we will discuss the functions of tumor-infiltrating DC in anti-tumor resistance, prevention of tumor recurrence, and immunosuppression. We will also describe DC metabolism, differentiation, and plasticity, which are essential for its function. Cancers like Lymphomas may be able to corrupt immune surveillance by reducing natural killer cell numbers. Thus, interactions between lymphoma and DC with reference to cytotoxicity may be an important event, likely to be mediated via activation with interferon-γ (IFN-γ) and Toll like receptors (TLR) ligands. Mechanisms of DC-mediated cytotoxicity and the role of apoptosis and death receptors, including the role played by nitric oxide, etc., are of immense significance. We will also look into the molecular mechanisms in the tumor microenvironment, reduced drug sensitivity, and tumor relapse, as well as methods for combating drug resistance and focusing on immunosuppressive tumor networks. We will address how DC mediated cytotoxicity in combination with drugs affects tumor growth and expansion in relation to checkpoint inhibitors and regulatory T cells. Innovative approaches for therapeutic modulation of this immunosuppressive adoptive DC immunotherapy will be highlighted, which is necessary for future personalized therapeutic applications.

Lingual neoplasia in nonhuman primates: Description of five cases and a literature review.

Documentation of lingual tumors is scarce in nonhuman primates. Through a multi-institutional retrospective study we compile cases of primary and metastatic neoplasia in non-human primates. We describe five cases of lingual neoplasia. Three cases are primary lingual tumors: chondro-osteoblastic lipoma in a howler monkey, squamous cell carcinoma, and fibroma in two baboons. We describe two cases of metastatic lymphoma in the tongue in rhesus macaques. A literature review of published lingual neoplasia in nonhuman primates is included in this manuscript. Lingual neoplasia is seldom reported in non-human primates.

Systemic treatment of patients with metastatic neuroendocrine Neoplasia

Due to the complexity and heterogeneity of metastatic NEN an interdisciplinary expert team should be involved in an individualized treatment strategy. SSA is the mainstay of antisecretory treatment in most functioning tumors. In antiproliferative intention SSA are first line treatment in receptor positive low proliferative NET. In intestinal metastatic disease PRRT is best established second line treatment. Further options are Everolimus (labeled) and tyrosine kinase inhibitors (off-label). Everolimus is the only approved drug for antiproliferative treatment in patients with metastatic lung NET, whereas in pancreatic NET more therapeutic options are available (SSA, chemotherapy, PRRT, Sunitinib, Everolimus) without a standard of best sequence. In patients with metastatic NEC standard first line treatment (platinum + etoposide) has not changed for decades and new treatment options for this fatal disease are urgently needed. Benefit of immunotherapy is limited to a small subset of patients - new combinations are under investigation. This review summarizes the standard of care, criteria of treatment selection and new developments for systemic therapy in patients with metastatic NEN.

PALC-02. PALLIATIVE RADIOTHERAPY FOR HAEMOSTASIS IN CHILDREN WITH CEREBRAL METASTATIC HAEMORRHAGE

Abstract BACKGROUND Among children, bleeding from brain metastases is rare. Bleeding could be caused by: cancer, treatments and chemotherapy/other drugs such as Bevacizumab, NSAIDs and anticoagulants. We report a case of brain RT after metastases bleeding. METHODS A 14-years-old boy with a negative previous medical history presented to the Emergency Department with seizures and loss of consciousness. Full-body CT scan revealed brain and renal haemorrhages and a right testicular lesion. Serum βhCG was 223,773 mIU/mL. Neurosurgical bleeding control and right orchiectomy were performed: the histopathology revealed a metastatic mixed non-seminomatous germ cell neoplasia of the testis. First-line chemotherapy (4 cycles of Cisplatin/Etoposide/Ifosfamide) and second-line treatments (Paclitaxel/Ifosfamide/Cisplatin and Gemcitabine/Paclitaxel/Oxaliplatin) were performed. Suddenly, he presented with left-sided hyposthenia and partial left hemibody seizure. CT scan revealed 2 haemorrhagic brain lesions, one in each hemisphere. Surgery was not feasible. We started anti-oedema and anti-epileptic therapy, and whole brain RT (WBRT, 36 Gy/12 fx, BEDα/β= 10 Gy= 46.8 Gy). After 5 days from the start, RT had a 7-day stop because of acute oedema and clinical deterioration. Fourth-line chemotherapy was administered with CarboPEB (1st of further 4 cycles), and then WBRT was restarted. At the end of WBRT a stereotactic RT boost to both the haemorrhagic lesions was delivered (20 Gy/10 fx, BEDα/β= 10 Gy= 24.0 Gy). As of today, eight months after the end of therapy, the patient is free from disease and βhCG is negative. CONCLUSION Palliative RT in children is a non-conventional indication, but potentially effective at providing rapid haemostasis, especially in selected cases (surgery not feasible/contraindicated, adult-type histologies, …) and it is ensuring a good tumor control and low-grade acute toxicities. Hypofractionation is suggested to balance patient comfort and treatment effectiveness, especially when life expectancy is short. The optimal RT schedule, dose and fractionations need to be further investigated.

Oncological Disease in Metastatic Breast Neoplasia and Palliative Care: A Review

Oncological Disease in Metastatic Breast Neoplasia and Palliative Care: A Review

Metastatic Neoplasms to the Breast.

When the clinical presentation is related to the metastatic mass and a radiologically solitary tumor focus is detected, especially in cases where clinical information is not taken into account or is insufficient, if a possible metastatic neoplasia is not kept in mind then it is possible to evaluate the tumor as a primary breast neoplasm. In this study, it is aimed to present our cases of non-hematopoietic metastatic neoplasms and to evaluate the clinicopathological features that may aid in distinguishing metastatic from primary neoplasms. This study includes cases diagnosed with metastatic non-hematopoietic breast neoplasm in breast resection materials in our center, between the years 2010-2023. All cases were analyzed retrospectively by evaluating clinicopathological features. Of the 15 subjects included in the study, 11 (73%) were female and 4 (27%) were male. The mean age of the patients were 46.9 ranged from 22 to 63 years. The most frequent metastatic malignancy was carcinoma (60%), followed by melanoma (33%) and sarcoma (7%). Of the 9 patients with metastatic carcinoma, the primary tumor originated from the lungs in 4, from gastrointestinal system in 2, female genital tract in 2, and kidney in 1 patient. Sarcoma diagnosis was given in a single patient and the histology was a leiomyosarcoma originating from kidney. A careful histomorphological and immunohistochemical evaluation and a detailed examination of the clinicoradiological data are critical to establish the right course in patient management, treatment plan and to correctly predict the prognosis.

PROSPECTIVE POSTMORTEM ASSESSMENT OF THE INCIDENCE OF MAMMARY NEOPLASIA IN CHIMPANZEES (PAN TROGLODYTES).

When evaluating the last 25 yr of morbidity and mortality from adult chimpanzees managed within the Association of Zoo and Aquarium Chimpanzee Species Survival Plan® for North American zoos, only two female chimpanzees were diagnosed with mammary neoplasia: one incidentally antemortem and one with a terminal metastatic neoplasia. When comparing this observation of prevalence of mammary neoplasia to humans, a substantial disparity is apparent. Mammary neoplasia is the second most common cancer in adult female humans, with a lifetime risk of 1:8 in the United States. The reason for the disparity between humans and chimpanzees, as closely related species, is unknown. The true prevalence in chimpanzees may be higher than currently noted, because routine examination of mammary tissue in chimpanzees is generally less complete than for other tissues postmortem, and antemortem assessment is generally limited to mammary palpation. This study was performed on intact, bilateral mammary glands harvested at postmortem examination of adult female chimpanzees (n = 7) from six institutions. With mammography, complete histopathologic sectioning, and genetic evaluation, the risk of mammary neoplasia was evaluated more thoroughly than during a typical postmortem exam in zoo populations during 2017-2019. No chimpanzees in the study were diagnosed with mammary neoplasia. Overall, this study supports the previous impression that chimpanzees do not develop mammary neoplasia at a similar rate as humans, even when comparable diagnostic modalities for evaluation are used.

Циторедуктивне хірургічне лікування гігантського метастазу колоректального раку в яєчник. Клінічний випадок

Purpose - to present and analyze the case of surgical treatment of a patient with secondary giant adenocarcinoma of the right ovary. It is presented a clinical case of a giant metastasis of colorectal cancer to the ovary in a 48-year-old woman, measuring 30×20×15 cm, weighing about 9 kg, which occupied almost the entire volume of the abdominal cavity, pushing the stomach and intestines under the diaphragm with compression of the intestines, right ureter and the presence of ascites with a volume of 1.5 liters. A right-sided hemicolectomy with lymphodissection was performed, and an end-to-end ileotransversoanastmosis was applied. A right adnexectomy, extirpation of the uterus, omentectomy were performed. During the immunohistochemical study, membrane-cytoplasmic expression of cytokeratin (CK) 20 and nuclear expression of CDX2 were revealed. CDX2 is a defining marker for the diagnosis of adenocarcinoma of the gastrointestinal tract, as well as for the differentiation of primary and metastatic ovarian carcinomas. The patient has a lack of expression of receptors for estrogen and CK7 and positive nuclear expression of CDX2, which indicates metastasis of colorectal adenocarcinoma to the ovary. According to the results of the histological examination, which were of decisive importance, the origin of the tumor was determined and, accordingly, the patient’s diagnosis - the tumor of the cecum is G2 adenocarcinoma with germination into the serous membrane, metastases to the right ovary and regional lymphatic nodes 10 out of 10, and areas of tumor growth in the mesentery. Conclusions. In the case of detection of an ovarian neoplasm, the differential diagnosis of primary and secondary tumors is extremely important. Reproductive age at the time of presentation should not interfere with the diagnosis of primary or secondary ovarian malignancy. Metastases of primary colorectal cancer in the ovaries can manifest as pelvic tumors, so preoperative examination of the gastrointestinal tract and removal of the ovarian tumor with immunohistochemical examination is the leading option for choosing an appropriate treatment strategy. Immunohistochemical study of cytokeratin expression markers CK7, CK20 are appropriate for the differential diagnosis of synchronous cancer of the cecum and ovary, and CDX2 protein is a defining marker for the diagnosis of adenocarcinoma of the gastrointestinal tract and for distinguishing between primary and metastatic ovarian carcinomas. Cytoreductive surgery appears to be an important treatment option for metastatic ovarian neoplasia to improve prognosis. A multidisciplinary approach remains key in further examination, determination of the main diagnosis and development of an optimal treatment strategy. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Hidden colon adenocarcinoma diagnosed from mouth metastasis: case report and literature review

BackgroundWe report an unusual case of metastatic colon adenocarcinoma to the maxilla as an initial clinical sign of the disease, this being the second case reported in the palate. In addition, we show an extensive review of the literature, with clinical cases of adenocarcinoma with metastasis to the mouth.Case presentationAn 80-year-old man complained of “swelling on the palate” with a 3-week evolution time. He reported suffering from constipation and high blood pressure. The intraoral examination revealed a pedunculated, red, and painless nodule on the maxillary gingiva. Under the diagnostic hypotheses of squamous cell carcinoma and malignant neoplasm of the salivary gland, an incisional biopsy was performed. Microscopically, the columnar epithelium was observed forming papillary areas, neoplastic cells with prominent nucleoli, hyperchromatic nuclei, atypical mitotic figures, and mucous cells, being positive for CK 20, suggesting the provisional diagnosis of metastatic adenocarcinoma, probably of gastrointestinal origin. The patient was submitted to endoscopy and colonoscopy exams, and a lesion in the sigmoid region of the colon was observed. After a colon biopsy, a moderately differentiated adenocarcinoma was confirmed, establishing the final diagnosis of metastatic neoplasia of colon adenocarcinoma to the oral lesion. The literature review revealed 45 clinical cases of colon adenocarcinoma with metastasis to the oral cavity. To the best of our knowledge, it is the second case on the palate.ConclusionsColon adenocarcinoma with metastasis to the oral cavity is rare but should be included in the differential diagnosis of neoplasms of the oral cavity, even when there are no known primary tumors in some cases, and this may be the first indication of the presence of a tumor.

ODP390 Metastatic Gestational Trophoblastic Neoplasia Masquerading as Thyroid Storm in a Girl with Molar Pregnancy and Hyperthyroidism

Abstract The Case Patient is a 16-year-old female with molar pregnancy, admitted for D&C, referred for hyperthyroidism, concern for thyroid storm. A month prior, she presented with heavy vaginal bleeding, morning sickness. Ultrasound showed blighted ovum. HCG was significantly elevated, 668,123 mIU/mL. TSH was low at 0. 01 mIU/L, Free T4 elevated 2.3 ng/dL. No family history of thyroid dysfunction. She was for was noted to have respiratory distress, hypoxia, and tachycardia in the 120s post-operatively. LFTs normal, no fever, jaundice or CNS manifestations. Chest CT showed bilateral lower lobe localized pulmonary edema concerning for trophoblastic fluid embolism vs thyroid storm. BWPS = 40. She was placed on PTU, beta blockade, Lugol's iodine, and hydrocortisone. Repeat chest CT showed diffuse pulmonary nodules consistent with gestational trophoblastic neoplasm (GTN). No other metastasis on further imaging (chest, abdomen, pelvis, brain). Clinical status improved, FT4 normalized 5 days after starting treatment. TRAbs negative. She was discharged on Methimazole and Atenolol, which were eventually discontinued. HCG levels significantly decreased after D&C but remained detectable on follow-up. Endocervix/uterine curettage showed intraplacental choriocarcinoma arising within a complete hydatidiform mole. She is followed by Oncology and currently undergoing chemotherapy. Discussion HCG-mediated hyperthyroidism include gestational transient thyrotoxicosis, hyperemesis gravidarum, and trophoblastic hyperthyroidism (TH). Due to significant homology between TSH and the beta-subunit of HCG, HCG can cause hyperthyroidism. 2-60% of women with trophoblastic disease may have symptomatic hyperthyroidism at time of diagnosis which can be severe. Patients with GTN (choriocarcinoma in our case) have a higher likelihood of TH, as HCG exceeds 100,000 mIU/mL. Choriocarcinoma is the most aggressive type of GTN characterized by vascular invasion and widespread metastases, of which the most common sites are vagina and lungs. Patients with pulmonary metastasis my present with respiratory distress, chest pain, cough or hemoptysis. Our patient was initially thought to have impending thyroid storm mainly from findings of pulmonary edema, respiratory distress, tachycardia, and precipitant history (D&C), and was managed as such while further workup was being undertaken. Realization that the initial chest CT findings of pulmonary edema were actually related to multiple pulmonary nodules and GTN made thyroid storm less likely. Hyperthyroidism typically resolves with decreasing HCG levels in TH. Indeed, our patient no longer needed ATD once her HCG levels subsided s/p D&C. Conclusion One of the most common sites of metastasis in GTN is the lungs. An acute presentation of respiratory distress and pulmonary findings on chest imaging upon simultaneous discovery of TH may complicate management as thyroid storm needs to be considered. Although a higher index of suspicion for metastatic GTN should be made in this situation, a conservative management approach of treating for possible impending thyroid storm until definitive diagnosis has been established is prudent. Presentation: No date and time listed

Toxoplasma gondiimimicking metastatic neoplasia in a senior indoor‐only cat

AbstractAn 11‐year‐old cat presented for a 1‐week history of dyspnoea. The cat had a history of allergies that were being managed on cyclosporine. Physical examination revealed an increased respiratory rate and effort, and the cat was oxygen dependent. Thoracic radiographs revealed a severe diffuse nodular pulmonary pattern, suggestive of metastatic neoplasia. An abdominal ultrasound was performed to evaluate for a primary mass or evidence of disseminated disease. A 4.3 × 2.2 cm ileocolic mass was noted. Fine‐needle aspirates of the intestinal mass were poorly exfoliative.Toxoplasma gondiititres were performed (IgM <1:20 and IgG >1:20,480). Fine‐needle aspirates of the pulmonary nodules revealed neutrophilic and macrophagic inflammation with large numbers of 2–4 µm, crescent‐shaped organisms, consistent withToxoplasma gondii. Cyclosporine was discontinued and clindamycin was prescribed. The cat was discharged 3 days later. Repeat imaging revealed resolution of the pulmonary and intestinal lesions. Clinical cure was achieved.

Tumor-Infiltrating Dendritic Cells: Decisive Roles in Cancer Immunosurveillance, Immunoediting, and Tumor T Cell Tolerance.

The tumor microenvironment plays a key role in progression of tumorigenesis, tumor progression, and metastasis. Accumulating data reveal that dendritic cells (DCs) appear to play a key role in the development and progression of metastatic neoplasia by driving immune system dysfunction and establishing immunosuppression, which is vital for tumor evasion of host immune response. Consequently, in this review, we will discuss the function of tumor-infiltrating DCs in immune cell signaling pathways that lead to treatment resistance, tumor recurrence, and immunosuppression. We will also review DC metabolism, differentiation, and plasticity, which are essential for metastasis and the development of lung tumors. Furthermore, we will take into account the interaction between myeloid cells and DCs in tumor-related immunosuppression. We will specifically look into the molecular immune-related mechanisms in the tumor microenvironment that result in reduced drug sensitivity and tumor relapse, as well as methods for combating drug resistance and focusing on immunosuppressive tumor networks. DCs play a crucial role in modulating the immune response. Especially, as cancer progresses, DCs may switch from playing an immunostimulatory to an inhibitory role. This article’s main emphasis is on tumor-infiltrating DCs. We address how they affect tumor growth and expansion, and we highlight innovative approaches for therapeutic modulation of these immunosuppressive DCs which is necessary for future personalized therapeutic approaches.

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

IntroductionTumor immunotherapy is a key therapeutic paradigm for the treatment of several malignancies. However, in metastatic lung cancer, classical immunotherapy regimes are ineffective due to regulatory T cell (Treg)-related immunosuppression and tumor relapse.MaterialsTo address this issue, we designed specific biocompatible Treg-targeted nanocarriers (NCs) as a model of immune-based nanotherapy, in order to target Treg-related immunosuppression in the lung tumor microenvironment. This is achieved through the combination of Dasatinib and Epacadostat integrated into biodegradable nanosomes which can inhibit and reverse Treg-supporting immunosuppression. Flow cytometry and immunofluorescence analysis, PET/CT scan, PTT/PA imaging and the Balb/c tumor model were used to explore the anti-tumor effect of Treg-targeted NCs both in vitro and in vivo.ResultsFindings reveal that NC treatment triggered substantial tumor cell apoptosis and drastically decreased tumor volume followed by downregulation of Ki-67 antigen expression, respectively. Drug circulation time was also increased as shown by biodistribution analysis accompanied by greater accumulation in lung and peripheral tissues. Intratumoral Th1 cytokines’ expression was also increased, especially TNF-A, IL-12 by 42%, and IL-6 by 18% compared to PBS treatment. In addition, the presence of mature CD80+/CD86+dendritic cells (DCs) revealed T cell enrichment and a decline in MDSC infiltration and myeloid subsets. Interestingly, a significant decline of Gr/CD11b myeloid cell population in blood and tissue samples was also observed. This immune activation can be attributed to the enhanced PTT efficiency and tumor targeting ability of the nanospheres which under near infrared (NIR) exposure can prompt highly efficient tumor ablation. We also demonstrated their therapeutic efficacy against 4T1 metastatic breast cancer model. Additionally, the photothermal therapy in combination with PD-L1 checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors.DiscussionOverall, our findings present a novel nano-enabled platform for the inhibition of Treg-dependent immunosuppression in NSCLC and provide a novel nanotherapeutic strategy for the treatment of metastatic neoplasia.

Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is a leading cause of death from cancer worldwide. Tumor markers like carbohydrate antigen 19-9 (CA 19-9) have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy.AIMTo delineate the phenotype of normal CA 19-9 PDAC according to clinical features, disease staging and prognosis as compared with high CA 19-9 PDAC cases.METHODSWe performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition. Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL. We performed a comparison between the two groups with regard to demographic and clinical data, biomarkers, tumor staging and 6-mo survival.RESULTSAltogether 111 patients were recruited with 29 having documented normal CA 19-9 (< 37 U/mL). In the CA 19-9 negative group of patients, 20.68% had elevated levels of both CEA and CA 125, 13.79% for CA 125 only whilst 17.24% for CEA only. The two groups had similar demographic characteristics. Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases (76.83% vs 55.17%), while smoking was slightly more prevalent in the latter group (28.04% vs 31.03%). Tumors over 2 cm were more frequently seen in the positive CA 19-9 group, reflecting a higher proportion of locally advanced and metastatic neoplasia (87.7% vs 79.3%). Six-month survival was higher for the negative CA 19-9 group (58.62% vs 47.56%).CONCLUSIONElevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology, high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases. CEA and CA 125 can be adjunctive useful markers for PDAC, especially in CA 19-9 negative cases.

ArTisaN trial protocol: a single Centre, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs)

BackgroundNeuroendocrine neoplasias (NENs) are a rare type of malignancy that arise from the cells of the neuroendocrine system. Most patients present with advanced, unresectable disease, typically with metastases to the liver. The presence of liver metastases dictates prognosis and there has been a number of studies investigating therapies that reduce the burden of liver disease. Selective Internal Radiation Therapy (SIRT) allows the delivery of targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. Here, we describe the design and rationale of ArtTisaN, a phase II study to assess efficacy and tolerability of SIRT using TheraSpheres for the management of liver metastases secondary to NENs.MethodsTwenty-four eligible participants will be recruited to receive SIRT with TheraSpheres. The primary objective is to determine the objective response rate to treatment, defined as the rate of best overall response in the treated liver volume. In addition, total hepatic response and overall response will be assessed according to RECIST 1.1. The second co-primary objective is to determine the incidence of adverse and serious adverse device events. The secondary objectives are progression free survival, overall survival and quality of life. Additional exploratory objectives include investigation of circulating biomarkers of response and identification of a radiomic signature of response.DiscussionThis trial will provide prospective evidence on the efficacy of SIRT using TheraSpheres for the management of liver metastases.Trial registrationNCT04362436.

Artisan trial protocol: A single center, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs).

e16208 Background: Patients(pts) with NENs present with advanced, unresectable disease, with liver metastases. Liver metastases dictates prognosis. SIRT allows targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. ArTisaN is a phase II study assessing efficacy and tolerability of SIRT using TheraSpheres for management of liver metastases secondary to NENs. Methods: Pts with liver dominant NENs will receive up to 2 TheraSphere treatments. Pts will be followed until disease progression for up to 2-years. Primary endpoints: objective response rate (ORR) within the treated liver volume, incidence of adverse events. Secondary endpoints: progression-free survival (PFS), overall (OS) and quality of life (EORTC QLQ-C30 and QLQ-GI.NET21). Assuming ORR 40%, sample size 24 patients-95% confidence interval will extend 20% in either direction. Results: 13 pts completed therapy: 69% female, primary site: 23% pancreatic, 31% small bowel. Grade: 54%-1, 46% - 2. 69% had previously received more than one line of systemic therapy including 7 who had previously received peptide receptor radiotherapy. 92% received bilobar treatment-average dose 2.49GBq administered. Hepatic ORR-69%. Grade 3 treatment related events occurred in 2 patients–1 ischaemic limb and 1 radiation induced hepatitis. Quality of life-maintained across all parameters. At the time of analysis, 5 pts had progressed, 3 had extrahepatic progression. Median PFS was 15.4 months (95%CI 11.5-19.4) and median OS was 18.5months (95%CI 7.4-29.6). Conclusions: Theraspheres is a safe and effective therapy for the management of patients with liver dominant disease from NENs. Clinical trial information: NCT04362436.

Retrospective evaluation of canine primary, multicentric, and metastatic intraocular neoplasia.

To provide an updated characterization of the prevalence of primary, multicentric, and metastatic intraocular tumors in the canine patient. Medical records databases from 4 veterinary referral hospitals were reviewed from 1999 to present to identify dogs with a diagnosis of intraocular neoplasia histopathologically confirmed following enucleation or necropsy. One hundred seventy-two dogs with 173 intraocular neoplasms met the inclusion criteria. Primary intraocular neoplasms were the most common tumors in the study (128); the two most common types were melanocytic neoplasia (90), followed by iridociliary neoplasia (33). There were 28 cases of intraocular involvement secondary to round cell neoplasia, with 18 cases of lymphoma, seven histiocytic sarcomas, and three undifferentiated round cell neoplasms. There were 17 cases of metastatic intraocular neoplasia, with hemangiosarcoma being the most common (9). The majority of intraocular tumors in dogs arise from the ocular tissues. However, the eye may also be involved in patients with multicentric neoplasia, and, less commonly, as a site for metastatic disease. Ocular screening for patients with multicentric neoplasia should be considered during staging, and ocular signs should be viewed with suspicion in dogs with neoplasia in other sites.

Role of 68Ga-DOTATOC PET/CT in Insulinoma According to 3 Different Contexts: A Retrospective Study.

The aim of this study was to assess the performance of 68Ga-DOTATOC PET/CT in the detection and extension of insulinomas according to 3 different contexts: sporadic benign, sporadic metastatic, and multiple endocrine neoplasia type 1 (MEN1). The data of 71 adult patients who underwent 68Ga-DOTATOC PET/CT for suspected or confirmed sporadic insulinoma, suspicion of insulinoma in the context of MEN1, follow-up of metastatic insulinoma, or suspicion of recurrence of insulinoma were retrospectively analyzed. Pathological examination or strong clinical and biological findings were used as standards of truth. For the assessment of a confirmed sporadic insulinoma in 17 patients, the sensitivity of SR-PET was 75%, including 2 patients for whom metastatic lesions had been revealed by SR-PET. For 35 patients with a suspicion of insulinoma, the sensitivity was 39%. In 10 patients followed up for metastatic insulinoma, the sensitivity was 100%. For 5 patients with a history of MEN1, interpretation of SR-PET was difficult, as 3 of them presented with multiple pancreatic uptake foci. The global sensitivity of SR-PET in all insulinomas excluding those with a MEN1 story was 64% (100% for metastatic insulinomas, 62% for benign insulinomas), with a specificity of 89%. 68Ga-DOTATOC PET/CT is a useful examination tool for the assessment of insulinomas in selected contexts, with very high performance for the detection and extension workup of metastatic insulinomas and high specificity for the detection of sporadic benign insulinomas. The examination should be completed with GLP-1 receptor PET when it is negative or in a MEN1 context.

Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms.

There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p=0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51months (PTR group 10.9% and non-PTR group 16.2%, p=0.403). Multivariate analysis revealed age<60years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p=0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73months, p=0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.