Presence Of Distant Metastases Research Articles

Male breast cancer: a 20-year multicenter experience

Aim: Male breast cancer (MBC) is a rare disease and accounts for approximately 1% of breast cancer. Treatment is largely extrapolated from female breast cancer due to lack of data in MBC. However, there are distinct features of MBC that warrant different treatment approach. We aim to better characterize the risk factors, clinicopathologic features, treatment and outcome of MBC patients from six hospitals across Steward Healthcare Network. Materials & methods: A total of 107 men with breast cancer were identified from the respective cancer registry at Steward and 64 patients were included with complete medical records. Their clinical, histopathological and treatment records were retrospectively reviewed. Kaplan–Meier method was used to determine the 5, 10 year overall survival (OS) rate and relapse free survival rate and Cox Regression test was used to assess the association between patient outcome and age at diagnosis, metastasis status at time of diagnosis, tumor size, nodal involvement and use of chemotherapy. Results: Of these 64 patients, median age at diagnosis was 68 years, majority of patients were white, 13 patients had family history of breast or ovarian cancer (20.3%), four patients tested positive for BRCA2 (6.25). Majority of patients presented painless breast lump. A total of 59 patients (92.2%) had invasive ductal carcinoma, and 31 patients (48.4%) had lymph node involvement at time of diagnosis. A total of 62 patients (96.8%) had M0 disease at time of diagnosis. About 97% of patients had estrogen receptor (ER) positive cancer. Most patients underwent mastectomy (87.5%), 35 patients (54.6%) received adjuvant radiation therapy, 19 patients (30%) received adjuvant chemotherapy and 96.7% of patients received adjuvant hormonal therapy. The median follow-up was 71.5 months (range 6–250 months), 5-year survival rate was 86.9% (95% CI: 74.5–93.6%), 5-year relapse free survival rate was 89.9% (95% CI: 77.4–95.7%) and 10-year survival rate was 58.1% (95% CI: 41.0–71.8%). The presence of distant metastasis at the time of initial diagnosis was the only factor associated with shorter OS (hazard ratio: 22.54, p < 0.0001). Conclusion: Majority of MBC patients present with palpable breast mass and the tumors are almost exclusively hormone receptor positive. Majority of patients present without distant metastasis and received surgical therapy; however, only a small subset of patients received breast conserving surgery for T1 tumor. Almost all patients received adjuvant hormonal therapy. OS and relapse free survival in our cohort is similar to historic reports in female breast cancer.

Notch1-Jagged1 Signaling Pathway in Oral Squamous Cell Carcinoma: Relation to Tumor Recurrence and Patient Survival

BACKGROUND: Dysregulated Jagged1/Notch1 signaling has been implicated in a variety of carcinomas, but little is known about the expression and possible role of Jagged1 and Notch1 in patients with oral squamous cell carcinoma (OSCC). AIM: We set out to examine the clinical significance of Notch1 and Jagged1 expression in OSCC. METHODS: Specimens were obtained from 44 patients who underwent surgical resection of primary OSCC. Immunostaining was done for Notch1 and Jagged1. The utilized markers’ expressions were analyzed in respect to 3 years overall survival (OS) and disease-free survival (DFS). RESULTS: Poor prognosis was significantly associated with high Notch1 expression, high Jagged1 expression, advanced TNM clinical stage (III and IV), presence of distant metastasis, presence of nodal involvement, large-sized tumors (≥4 cm), presence of lymphovascular invasion, higher grade carcinomas, high Notch1 and Jagged1 coexpression, and carcinomas aroused from tongue and palate. Notch1, Jagged1, histologic grade, and tumor site were the independent predictors of DFS, while Jagged1 expression, histologic grade, and tumor site were the independent predictors of 3 years OS. CONCLUSION: Our findings imply that either high levels of Notch1 or Jagged1 expression, or combined combination of both are related with poor prognostic outcomes.

Risk of venous thromboembolism in patients with pancreatic cancer

Venous thromboembolism (VTE) is often diagnosed in patients with pancreatic cancer, resulting in increased morbidity and mortality. Objective: to study the relationship between clinical characteristics and hemostatic disorders in patients with pancreatic cancer and determine their role in predicting VTE. Material and Methods. The study included 246 patients with pancreatic cancer. Pancreatic ductal adenocarcinoma was diagnosed in 91.9 % of patients. In most patients (68.3 %), the tumor was localized in the head of the pancreas; 45.9 % of patients had stage IV disease at diagnosis (T1–4N0–2M1); 31.7 % of patients manifested jaundice at diagnosis. A small proportion of patients (17.5 %) received chemotherapy, and 28 % of patients underwent surgery. Within the 12-month follow-up period, the frequency of VTE was 15.4 %. Clinical characteristics and hemostasis parameters were retrospectively compared in patients with VTE and without VTE diagnosed during the follow-up period. Results. The risk of developing VTE in cancer patients was higher with a larger tumor size and the presence of distant metastases. The initial high level of D-dimers increased the risk of VTE during the frst 12 months of diagnosis. In a multivariate analysis, the elevated level of D-dimers was a signifcant risk factor for VTE. Conclusions. The tumor size, advanced tumor stage (stage IV), and elevated levels of D-dimer in patients with pancreatic cancer are of prognostic signifcance for VTE. The study of hemostasis parameters (D-dimer) can help identify patients at risk of developing VTE, who are advised to take anticoagulant therapy with low hemorrhagic risk.

Imaging of Uveal Melanoma—Current Standard and Methods in Development

Simple SummaryUveal melanoma is the most prevalent intraocular tumor in adults, derived from melanocytes; the liver is the most common site of its metastases. Due to troublesome tumor localization, different imaging techniques are utilized in diagnostics, i.e., fundus imaging (FI), ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), or fundus autofluorescence (FAF). Specialists eagerly use these techniques, but sometimes the precision and quality of the obtained images are imperfect, raising diagnostic doubts and prompting the search for new ones. In addition to analyzing the currently utilized methods, this review also introduces experimental techniques that may be adapted to clinical practice in the future. Moreover, we raise the topic and present a perspective for personalized medicine in uveal melanoma treatment.Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, a biopsy followed by a pathological exam is used only in certain cases. Therefore, an early and noninvasive diagnosis is essential to enhance patients’ chances for early treatment. We reviewed imaging modalities currently used in the diagnostics of uveal melanoma, including fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), as well as positron emission tomography/computed tomography (PET/CT) or magnetic resonance imaging (MRI). The principle of imaging techniques is briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities are explained. We describe UM imaging innovations, show their current usage and development, and explain the possibilities of utilizing such modalities to diagnose uveal melanoma in the future.

Thyroid Lymphoma: Case Series Review.

Primary thyroid lymphoma (PTL) is a rare malignancy accounting for about 5% of all thyroid malignancies and less than 2% of extra-nodal lymphomas. Diffuse B-cell lymphoma is the most common pathological subtype of PTL. This is a retrospective review of all patients diagnosed with thyroid lymphoma in our hospital during the period from 2011 to 2021. All patients had clinical, radiological, and pathological evaluation. We have followed up these patients since diagnosis till now. Eight patients were included in our review. Four patients were males and four were females. Mean age at diagnosis was 63 ± 32years of age. Diagnosis was confirmed only with tissue histology. Six patients had stage IIE disease and two had stage IVE disease. Four patients had disease related mortality. Of the other four patients, two had chemotherapy (RCHOP) and one had local radiotherapy; all achieved complete remission, and the last one had hemithyroidectomy to relieve airway compression and still under treatment. Primary thyroid lymphoma is rare malignancy of the thyroid gland. Advanced stage and age at the time of diagnosis, the presence of compression manifestations, large tumor mass, and presence of distant metastasis, all are poor prognostic criteria. Our knowledge of the disease pathology, diagnosis, and management is still limited and more research studies are required.

P-221 Prognostic value of CD3+CD8+ T lymphocytes in advanced and metastatic PDAC

T cells traffic into the tumor microenvironment, and exhibit cytotoxicity against tumor cells. Infiltration by cytotoxic CD3+CD8+ lymphocytes is associated with increased OS and DFS in PDAC (Orhan, 2020). There are some studies reflecting the prognostic value of circulating CD3+CD8+ cells in other cancer localisations. The proliferation potential of circulating CD8+ T cells was found to be a significant predictor for PFS in small cell lung cancer (An, 2019). The positive correlation between high CD3+CD8+ T cells and clinical results indicated the role in the prognosis of gastric cancer patients (He, 2017). We conduct one institution clinical trial to evaluate the prognostic and predictive value of different T lymphocyte subsets and other cells in the peripheral blood in patients with PDAC. A cohort of 105 pts with advanced inoperable and metastatic PDAC was evaluated in this analysis. All patients undergoing systemic treatment in our institution and who signed informed consent were enrolled in the study. All patients were treated with mFOLFIRINOX or gemcitabine regimen for the 1st line. Blood samples were collected for analysis of T cell subsets, including CD19, CD3+ CD56+, CD8+ CD57+, CD3+ CD57+, CD3, CD3+ CD4+, CD3+ CD8+, CD3+ CD4- CD8, CD3- CD56+ CD16+, CD3- CD56+ CD16-, CD4+ CD25+ CD127+/-, CD4+ FOXP3+, CD8+ CD25+ CD127+/-, CD8+ FOXP3+ T cells by flow cytometry at initial diagnosis before chemotherapy. Results were estimated according to the age, sex, differentiation grade, presence of distant metastasis, number of metastatic sites, presence of ascites, body mass index, CA 19-9 values, chemotherapy regimen received, number of lines given after disease progression. Univariate Cox regression was used and survival curves were analyzed using the Kaplan–Meier method. There was a strong relationship between the presence of distant metastasis, the number of metastatic sites with PFS in our cohort. OS in addition to that was strongly associated with age, CA 19-9 level, number of following treatment lines. A quantity of circulating CD3+CD8+ cytotoxic T lymphocytes measured before treatment was found to be of prognostic value for both PFS (p=0.046) and OS (p= 0.031). Patients with higher than median 424,19 cells/MCL value demonstrated significantly better PFS and/or OS in the whole cohort as well as in the mFOLFIRINOX arm (p=0.037 for OS), in staging groups 4 (p=0,04 for PFS p=0.016 for OS) and 3 (p=0,049 for PFS) and G2 differentiation (p=0.03 for OS) arm. In gemcitabine arm and G3 tumors, low and high CD3+CD8+ survival differences didn‘t stand out. Lymphocyte count and CD3- CD56+CD16- T lymphocyte values before treatment also impact PFS but not OS. No other subset values at 1st visit and changes in means between 1st visit and 2nd visit 2 months later revealed an impact on PFS and OS. The positive correlation between high CD3+CD8+ T cells and clinical outcome may show its‘ prognostic significance in advanced and metastatic pancreatic cancer patients and together with other well-known biomarkers, it could help in clinical decision making.

Comparison of the results of treatment of patients with unrespectable NSCLC in the framework of clinical trials and in real world practice using pseudo-randomization.

e21049 Background: Local and international recommendations for anticancer treatment are formed and changed based on the results of clinical trials. A feature of most clinical trials is the strict criteria used to select “safe” patients without severe comorbidities. In real world practice, significant portion of patients do not meet all of these criteria (32%) [ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586241/ ], which raises a significant question about the consistency of treatment results demonstrated in studies with data obtained in routine clinical practice (RCP). The purpose of this work was to compare the results of treatment of patients with unrespectable NSCLC receiving first-line drug therapy in RCP and in the framework of international clinical trials using the method of pseudo-randomization (propency score analysis). Methods: The current analysis included 344 patients with inoperable NSCLC who received first-line drug therapy as part of RCP and 90 patients included in various non-TKI clinical trials irrespectively of IO use 2018-2019.Firstly, a direct comparison of performance indicators was done (progression-free survival) using the Kaplan-Meier method for all patients included in the study.At the second stage, in order to eliminate the influence of the imbalance of prognostic factors, a regression analysis was carried out. To form balanced cohorts, we used the propensity score matching analysis.The propensity to progression was assessed using logistic regression analysis in each individual patient, taking into account the basic clinical characteristics: age, gender, ECOG, histological form, regional lymph nodes, presence of distant metastases (mts), stage of the disease, mts of the lung parenchyma, liver mts, pleural mts, bone lesions, adrenal mts, mts lesions of distant lymph nodes, mts lesions of other areas, mts lesions of the brain, number of metastasis zones, components of the first-line therapy regimen. Patients of both arms treatment were matched in a 1:1 ratio based on their progression propensity score in increments of 0.15.After matching two homogeneous groups of patients were formed: 83 in the RCP group and 84 in the clinical trial therapy group. Results: In a direct comparison of the results of the treatment, progression-free survival in the group of patient who underwent treatment in clinical trials was significantly higher than within the RCP (6.4 months 95% CI 5.9–6.9 vs. 13.3 months 95% CI 8.1–18.5; log rank p < 0.000).propensity score matching analysis showed a significantly longer time to progression in the clinical trials group of 13.3 months, 95% CI 8.3-18.3 versus 6.3 months. 95% CI 4.8-7.7; log rank p < 0.000. Conclusions: Results obtained in clinical trial are substantially better than seen in RCP, this should be taken into consideration when extrapolating new research findings.

Factors Influencing the Outcome of Head and Neck Cancer of Unknown Primary (HNCUP).

Background: This study on patients with head and neck cancer of unknown primary (HNCUP) assesses the impact of surgical and non-surgical treatment modalities and the tumour biology on the oncological outcome. Methods: A total of 80 patients with HNCUP (UICC I–IV) were treated with simultaneous neck dissection followed by adjuvant therapy, between 1 January 2007 and 31 March 2020. As the primary objective, the influence of treatment modalities on the overall survival (OS), the disease-specific survival (DSS) and the progression-free survival (PFS) were analysed in terms of cox regression and recursive partitioning. The tumour biology served as secondary objectives. Results: The 5-year OS for the entire cohort was 67.7%, (95% CI: 54.2–81.2%), the 5-year DSS was 82.3% (72.1–92.5%) and the 5-year PFS was 72.8% (61.8–83.8%). Cox regression revealed that patients undergoing adjuvant radiotherapy only had a four times higher risk to die compared to patients receiving chemoradiation therapy (HR = 4.45 (1.40; 14.17), p = 0.012). The development of distant metastases had a significantly negative impact on OS (HR = 8.24 (3.21–21.15), p < 0.001) and DSS (HR = 23.79 (6.32–89.56), p < 0.001). Recursive portioning underlined the negative influence of distant metastases on OS (3.2-fold increase in death probability) and DSS (4.3-fold increase in death probability), while an UICC stage of IVb increased the risk for further progression of the disease by a factor of 2. Conclusions: The presence of distant metastases as well as adjuvant treatment with radiation without concomitant chemotherapy, were among others, significant predictors for the overall survival of HNCUP patients, with distant metastases being the most significant predictor.

High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer.

BACKGROUNDColorectal cancer (CRC) is often associated with elevated platelet count (> 400 × 109/L), known as thrombocytosis. The role of CD40 ligand (CD40L), a member of the tumor necrosis factor family, is controversial in CRC. Circulating CD40L is higher in CRC, but its relationship with disease staging and local and distant metastasis is not clear. Although most of the circulating CD40L is produced by platelets, no previous study investigated its relationship with CRC-related thrombocytosis.AIMTo investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.METHODSA total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study. Anamnestic data including comorbidities and histopathological data were collected. Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor. Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay, while plasma interleukin-6 was measured via electrochemiluminescence immunoassay. Patient follow-ups were terminated on January 31, 2021.RESULTSPlasma CD40L of CRC patients was tendentiously higher, while platelet count (P = 0.0479), interleukin-6 (P = 0.0002), and thrombopoietin (P = 0.0024) levels were significantly higher as opposed to the control subjects. Twelve of the 106 CRC patients (11.3%) had thrombocytosis. Significantly higher CD40L was found in the presence of distant metastases (P = 0.0055) and/or thrombocytosis (P = 0.0294). A connection was found between CD40L and platelet count (P = 0.0045), interleukin-6 (P = 0.0130), and thrombocytosis (P = 0.0155). CD40L was constant with the course of CRC, and all baseline differences persisted throughout the whole study. Both pre- and postoperative elevated platelet count, CD40L, and interleukin-6 level were associated with poor overall and disease-specific survival of patients. The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.CONCLUSIONCD40L levels of CRC patients do not change with the course of the disease. The CD40L level is strongly correlated with platelet count, interleukin-6, thrombocytosis, and the presence of distant metastases.

Magnetic resonance imaging in terms of observation of patients after transanal resections of rectal tumors

Purpose of the study. Was to study the results of magnetic resonance imaging (MRI) of the patients with malignant neoplasms (MN) of the rectum after transanal full‑layer resection of the tumor.Materials and methods. MRI images of the pelvis of 25 patients with rectal cancer after organ–preserving surgical treatment in the volume of full‑layer excision of the tumor for the period from 2015 to 2020 of the MRI department of the A. Tsyb Medical Radiological Research Centre, the Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; 13 patients received additional treatment in the volume of chemoradiotherapy and brachytherapy; 13 patients underwent dynamic studies to assess the process after treatment.The MRI picture was evaluated by T2‑WI in three planes and DWI with an ADC map in the pelvic region and aimed at the excision zone of the tumor.Indications for MRI were the exclusion of continued tumor growth in the surgical intervention area and clinical manifestations of suture failure in the tumor excision area.Results. All patients were divided into two groups: 11 patients with a normal course of the postoperative period where visualized a zone of scar changes in the area of surgical intervention with a low intensity signal in the T2‑WI mode, without signs of true diffusion restriction, hyper‑ and the average intensity of the signal and 14 patients with identified deviations from the normal picture: of these 10 patients with a relapse after surgical treatment, who had additional formations with signs of pathological MR signal, true diffusion restriction, which were regarded as recurrent formations in the tumor excision zone, as well as 4 patients in the tumor excision zone, a defect in the rectal wall was visualized against the background of a low intensity signal from the zone of fibrous changes, with the formation of liquid leaks, indicating the insolvency of the seams.Conclusion. The method of MRI can be recommended as the method of choice for assessing the pelvic region after transanal endoscopic microsurgery (TEM), which allows for high accuracy to exclude continued tumor growth; to assess the pelvic region for the presence of distant metastases; to determine the defect of the walls in the excision zone of tumors. MRI provides safe dynamic control.

Tetraspanin CD9 Expression Predicts Sentinel Node Status in Patients with Cutaneous Melanoma.

The tetraspanin CD9 is considered a metastasis suppressor in many cancers, however its role is highly debated. Currently, little is known about CD9 prognostic value in cutaneous melanoma. Our aim was to analyse CD9 expression in melanocytic nevi and primary cutaneous melanomas through immunohistochemistry and immunofluorescence approaches to determine its correlation with invasiveness and metastatic potential. CD9 displayed homogeneous staining in all melanocytic nevi. In contrast, it showed a complete loss of reactivity in all thin melanomas. Interestingly, CD9 was re-expressed in 46% of intermediate and thick melanomas in small tumor clusters predominantly located at sites of invasion near or inside the blood or lymphatic vessels. The most notable finding is that all CD9 stained melanomas presented sentinel node positivity. Additionally, a direct association between CD9 expression and presence of distant metastasis was reported. Finally, we confirm that CD9 expression is consistent with an early protective role against tumorigenesis, however, our data endorse in melanoma a specific function of CD9 in vascular dissemination during late tumor progression. The presence of CD9 hotspots could be essential for melanoma cell invasion in lymphatic and endothelial vessels. CD9 could be a valid prognostic factor for lymph node metastasis risk.

KRAS Mutations in Colorectal Cancer: Relationship With Clinicopathological Characteristics and Impact on Clinical Outcomes in Saudi Arabia.

BackgroundFew studies have addressed the prevalence and prognostic impacts of KRAS mutations in Saudi patients with colorectal cancer (CRC). The present study aimed to address the prevalence of KRAS mutations and evaluate their impact on clinical outcomes (if any) among Saudi patients.MethodsThis retrospective cohort study was conducted at King Saud University Medical Centre (KSUMC), Saudi Arabia. All medical records of biopsy-proven CRC patients between 2015 and 2021 were reviewed. Statistical analysis was carried out to address the associations between KRAS mutations and the clinicopathological patients’ variables and survival.ResultsKRAS mutations were found in 97/194 (50%) CRC patients. In comparison to wild type KRAS tumors, KRAS- mutated ones had shown a trend toward right-sided tumors (30% and 4.3% vs 16% and 1.1%, p-value = 0.032, respectively) and peritoneal metastases (34% vs 19%, p-value = 0.014). Older age at diagnosis, gender, tumor grade, microsatellite instability (MSI), tumor stage (T), and the presence of distant metastasis were independent prognostic factors for poor overall survival (OS). There was no significant association between KRAS mutations and the hazard of mortality (HR: 0.653, 95% CI 0.873-1.134, p = 0.131). For progression-free survival (PFS), older age at presentation, MSI, tumor nodal stage (N), the presence of liver and lung metastasis, and recurrence were poor prognostic factors for PFS. There was no significant relation between KRAS mutations and PFS (HR ratio: 0.756, 95% CI 0.229-2.497, p = 0.646).ConclusionsThe prevalence of KRAS mutations in CRC patients was similar to that observed in previous studies of Saudi patients. KRAS mutations showed a trend toward right-sided tumors and peritoneal metastases. Survival was significantly related to different clinicopathologic variables of the study cohort but was not affected by the KRAS mutational status.

Canine Transmissible Venereal Tumor in the Larynx with Pulmonary Metastasis

Background: Canine transmissible venereal tumor (TVT) is one of the most common canine neoplasms in Brazil. Lesions develop mainly in the genital tissue and less frequently in other areas, in the extragenital form. Metastasis is rare, and the disease progression depends on the patient's immune status. The treatment of choice is chemotherapy with vincristine sulfate, considered an effective and safe modality. The present work describes the first case of extragenital TVT in the larynx with pulmonary metastasis at the time of diagnosis. Case: An approximately 4-month-old mixed-breed bitch was attended manifesting acute clinical respiratory signs. The patient had been rescued from the street 2 months beforehand. Physical examination revealed pale mucous membranes and crackling pulmonary auscultation. Thoracic radiography was performed in 3 projections, showing multiple nodules in the lung parenchyma, followed by cytopathological examination using fine needle puncture guided by thoracic ultrasound, confirming the diagnosis of TVT. Considering the cytological finding and the absence of primary tumor lesions in the genital, oral, cutaneous or nasal regions, endoscopy was performed in order to locate a possible primary focus. The exam revealed a small erythematous tumor with smooth and regular surface, measuring approximately 2.5 cm, located in the larynx, between the arytenoid cartilages. Chemotherapy was performed with vincristine sulfate with radiographic follow-up throughout the treatment. Full remission of the pulmonary and laryngeal nodules was achieved at the end of the protocol. The animal remained in complete remission for a period of 2 years. Discussion: TVT is more frequently observed in animals of active reproductive age, and rarely in animals under 1 year of age, as in the case described here. When considering extragenital lesions, the manifestation can be single or multiple, occurring more frequently in the cutaneous, oral and nasal forms. This case describes a laryngeal lesion with pulmonary involvement, without lesion in the genitalia or any other site. Cases of TVT in young and prepubescent animals, associated with extragenital involvement and aggressive behavior, similar to this case, have been described in literature, but never in this location. Literature suggests there is a relationship with the immune status of such patients, which do not have a well-developed immune system, facilitating disease progression. In these animals, transmission can be maternal, since in some cases the patient develops the disease without having contact with other animals except the mother. This form of transmission would facilitate the extragenital form in the oral cavity, airways and ocular region, related to licking, lactation and direct contact. Vincristine sulfate chemotherapy, considered the treatment of choice, was effectively used in this case, despite the atypical form. The TVT prognosis tends to be favorable, with the exception of the aggressive presentations with the presence of distant metastases. However, in the case described here, even though metastatic pulmonary nodules were present, complete remission was achieved, with survival exceeding 2 years. The development of TVT in the larynx is a rare form of the disease, and this report is possibly the first description of this tumor location. Thus, we highlight the importance of a complete investigation of the patient and of TVT as a differential diagnosis in this location. Keywords: dog, bitch, coitus, neoplasm, round cells, extragenital. Título: Tumor venéreo transmissível canino em laringe com metástase pulmonar Descritores: cão, cadela, coito, neoplasia, células redondas, extragenital.

Survival of Non-Small Cell Lung Cancer Patients with Unexpected N2 after Complete Resection: Role of Aggressive Invasive Mediastinal Staging should be Considered

Objective: Mediastinal lymph node (N2) metastasis is one of the poor prognostic factors in non-small cell lung cancer patients (NSCLC). However, the accuracy of mediastinal lymph node staging in real practice is uncertain and inadequate. Consequently, the aim of this study was to determine the survival of NSCLC patients with clinically non-suspicious mediastinal lymph node metastases who underwent complete resection but were pathologically confirmed as having N2 metastases (unexpected N2).Materials and Methods: A retrospective review was performed of all pathology-proven N2 metastases NSCLC patients who underwent curative surgical resection from January 2007 to December 2016. A total of 158 patients were initially included in the study. After the exclusions (known N2, small cell carcinomas, neuroendocrine tumor), 125 unexpected N2 patients who underwent complete resection were analyzed. Survival analysis was determined using the Kaplan–Meier method and multivariate analysis was determined using the Cox regression method.Results: The overall 2-year, 3-year, and 5-year survival rates were 40%, 24%, and 20% respectively. Complete resection was achieved in all patients. Invasive mediastinal staging (IMS) was performed in 47 patients (37.6%), by endobronchial ultrasonography (EBUS) in 46 (36.8%) patients (82.6% negative and 17.4% inadequate tissue) while only 1 patient underwent mediastinoscopy. The factors affecting the survival rate upon comparison were the histology type (p=0.019), differentiate characteristics (p=0.004), adjuvant therapy (p=0.011), and presence of distant metastasis by postoperative re-staging (p=0.003). The independent predictive factors for survival werechemo-radiation therapy (odds ratio 0.367, 95% confidence interval 0.176–0.766) and distant metastasis (odds ratio 2.280, 95% confidence interval 1.334–3.897). However, a small size, periphery lesion, T staging, and number of N2 lesions were not significant factors.Conclusion: The survival rate of unexpected N2 patients was low despite complete resection being achieved in these patients. Adjuvant therapy seemed to improve survival for those with unexpected N2 metastasis as it is a systemic disease. However, not all patients received IMS, which was mostly done by EBUS and which had a high false negative, leading to underestimating the staging. Other modalities, such as cervical mediastinoscopy, videoassisted mediastinoscopic lymphadenectomy (VAMLA) or open biopsy should be considered for the adequate evaluation of N2 metastasis, nonetheless further study is still needed.

Metachronous metastasis of renal cell carcinoma, 21 years after surgery

On the 2018, the prevalence of kidney cancer is 3.9% of all cases of cancer in the Russian Federation. The 5-year survival rate patients with RP is approximately 60%, while in the presence of distant metastases, the 5-year survival rate is from 5 to 9%. The case presented of operational treatment of a patient with metachronous metastasis clear-cell renal cell cancer of the right kidney into the paranephric cellulose of the contralateral the only left kidney. In 1999, the patient underwent a radical nephrectomy on the right side regarding kidney carcinoma. No data for distant metastases were received, chemotherapy was not carried out for the patient, after surgery was observed on an outpatient basis by an oncologist. Removed from the register by an oncologist after 5 years. Since 2019, the patient began to notice relapses of renal colic, in March 2020 he was hospitalized in the urology department of the North-Western Medical University named after I.I. Mechnikov, according to emergency indications with a clinical picture of renal colic on the left. The patient underwent MSCT of the abdominal organs with intravenous contrast. The formation of retroperitoneal space on the left was revealed, measuring 11.0×10.1×9.2 cm, accumulating contrast and adjacent to the left kidney. There are no data for other focal formations in the abdominal cavity. The left kidney is located typically, increased in size. The patient underwent surgery in the amount of resection of retroperitoneal education. According to the results of histological examination: the picture more corresponds to with metastasis of clear cell renal-cell carcinoma of the kidney Grade 1. ICD-0 8310/3. The presented clinical case is valuable in that kidney carcinoma metachronic metastasis was detected only after 21 years, at the same time, it had an extraorgan arrangement in the retroperitoneal space, lying tightly on the kidney, but did not grow into the renal capsule. Based on this, we consider it important to continue monitoring patients after radical nephrectomy about a kidney tumor, even beyond the pale of 5 year survival.

A Predictive Nomogram for Early Death in Pheochromocytoma and Paraganglioma

BackgroundPheochromocytoma (PHEO) and paraganglioma (PGL) are relatively rare neuroendocrine tumors. The factors affecting patients with early death remain poorly defined. We aimed to study the demographic and clinicopathologic pattern and to develop and validate a prediction model for PHEO/PGL patients with early death.MethodsData of 800 participants were collected from the Surveillance Epidemiology and End Results (SEER) database as a construction cohort, while data of 340 participants were selected as a validation cohort. Risk factors considered included the year of diagnosis, age at diagnosis, gender, marital status, race, insurance status, tumor type, primary location, laterality, the presence of distant metastasis. Univariate and multivariate logistic regressions were performed to determine the risk factors. R software was used to generate the nomogram. Calibration ability, discrimination ability, and decision curve analysis were analyzed in both construction and validation cohorts.ResultsPHEO and PGL patients accounted for 54.3% (N=434) and 45.7% (N=366), respectively. More than half of tumors (N=401, 50.1%) occurred in the adrenal gland, while 16.9% (N=135) were in aortic/carotid bodies. For the entire cohort, the median overall survival (OS) was 116.0 (95% CI: 101.5-130.5) months. The multivariate analysis revealed that older age (versus age younger than 31; age between 31 and 60: OR=2.03, 95% CI: 1.03-4.03, P=0.042; age older than 60: OR=5.46, 95% CI: 2.68-11.12, P<0.001), female gender (versus male gender; OR=0.59, 95% CI: 0.41-0.87, P=0.007), tumor located in aortic/carotid bodies (versus tumor located in adrenal gland; OR=0.49, 95% CI: 0.27-0.87, P=0.015) and the presence of distant metastasis (versus without distant metastasis; OR=4.80, 95% CI: 3.18-7.23, P<0.001) were independent risk factors of early death. The predictive nomogram included variables: age at diagnosis, gender, primary tumor location, and distant metastasis. The model had satisfactory discrimination and calibration performance: Harrell’s C statistics of the prediction model were 0.733 in the construction cohort and 0.716 in the validation cohort. The calibration analysis showed acceptable coherence between predicted probabilities and observed probabilities.ConclusionsWe developed and validated a predictive nomogram utilizing data from the SEER database with satisfactory discrimination and calibration capability which can be used for early death prediction for PHEO/PGL patients.

Abstract P5-01-05: Transcriptional signature of metastatic triple negative breast cancer in humanized mice

Abstract Triple-negative breast cancer (TNBC) is a particularly aggressive form of breast cancer with high risk of recurrence and approximately 22% rate of five-year survival when the disease becomes metastatic. Thus, understanding of mechanisms supporting metastatic colonization of distant organs is of critical importance for the development of new therapies and possibly improved outcomes. Syngeneic mouse models suggest the role of innate immune cells, particularly neutrophils, in support of metastatic dissemination of TNBC. However, it is not possible to study human cancer in immunocompetent mice. Furthermore, organoids or other 3D tissue models do not allow investigations of distant organs colonization with metastatic TNBC tumors. Here, we used humanized mice and patient-derived xenograft (PDX) from treatment naïve primary TNBC tumors to investigate the mechanisms that promote metastasis. NSG mice with transgenic expression of human hematopoietic cytokines SCF/GM-CSF/IL-3 were engrafted with human CD34+ hematopoietic progenitor cells (HPCs) to generate humanized (h)NSG-SGM3 mice. All PDX tumors grew after orthotopic implantation at week 8-12. The presence of distant metastasis was determined by macroscopic evaluation of distant organs and further confirmed by E-cadherin and cytokeratin 19 expression using polychromatic immunofluorescence on frozen tissue section. Among ten PDX tumors tested, four did not develop metastasis, four developed only lung metastasis and two developed multi-organ metastases (lung and liver). We find that different TNBC PDX tumors have different metastatic potential. Their metastatic potential is linked with differences in cellular composition and transcriptional signatures at the level of the primary tumor. Interferon Response signature is enriched in primary TNBC PDXs with metastatic potential, while non-metastatic primary tumors display a TNF signature as well as allograft rejection signature. Furthermore, liver metastases were enriched in myeloid transcripts. Thus, our model enables mechanistic and pre-clinical studies of human TNBC metastasis. Citation Format: Chun I Yu, Te-Chia Wu, Francesca Menghi, Joshy George, Kyung In Kim, Florentina Marches, Edison T Liu, Jacques Banchereau, Karolina Palucka. Transcriptional signature of metastatic triple negative breast cancer in humanized mice [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-01-05.

Abstract P5-05-08: CXCL16 as a potential therapeutic target of triple-negative breast cancer

Abstract CXCL16, as a chemotactic cytokine, promotes cancer proliferation, migration, and immune cell infiltration in tumor microenvironment. However, CXCL16 has been shown to play a conflicting role in breast cancer. The aim of this study was to investigate the therapeutic potential of CXCL16 in breast cancer. Breast cancer patients (n=1097) from the TCGA dataset were divided into two group according to the CXCL16 expressions, the CXCL16low (n=548) and the CXCLhigh (n=549) groups. Mean diagnostic ages were similar between groups (59 ± 13.5 vs 58 ± 12.9 years, P=0.233). The ratio of triple-negative breast cancer (TNBC) was significantly higher in the CXCLhigh than that of the CXCL16low groups (24.8 vs 6.8%, P&amp;lt;0.001), while the presence of distant metastasis or overall survivals were not different between groups. Interestingly, gene scoring analysis showed that oncogenic molecules including M2-macrophage- (r=0.36, P&amp;lt;0.001), efferocytosis- (r=0.42, P&amp;lt;0.001), and chemokine- (r=0.46, P&amp;lt;0.001) related gene sets showed significantly strong positive relations with the CXCL16 expressions in all patients including both TNBC (n=924) and non-TNBC (n=173). Additionally, the gene set score from PI3K/Akt pathway showed positive relation with the CXCL16 expressions in the non-TNBC (r=022, P&amp;lt;0.001) but not in the TNBC group. Next, a xenograft mouse model of TNBC was established with MDA-MB-231 cells, and anti-mouse CXCL16 antibody (designated as aCXCL16 group) or control IgG (designated as control group) were intravenously injected (25µg/100µl), twice per week. During 3 weeks, tumor growth was significantly delayed in the aCXCL16 than the control group by 37%. In conclusion, CXCL16 is highly expressed in TNBC and positively correlates with M2-macrophage related genes. Neutralizing CXCL16 by anti-CXCL16 shows therapeutic effects on the xenograft model of TNBC, suggesting that CXCL16 can be a potential therapeutic target for breast cancer. Citation Format: Sun Wook Cho, Mi Gyeong Jang, Hyun Jin Sun, Han Sai Lee, Young Shin Song, Seong Keun Kim. CXCL16 as a potential therapeutic target of triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-05-08.

Abstract P1-23-01: Male breast cancer- a 20 year multi-center experience

Abstract Background-. Male breast cancer (MaBC) is a rare disease and accounts for approximately 1% of breast cancer. Treatment is largely extrapolated from female breast cancer (FeBC) due to lack of data in MaBC. However, there are distinct features of MaBC that warrant different treatment approach. We aim to better characterize the risk factors, clinicopathologic features, treatment and outcome of MaBC patients from 6 hospitals across Steward Healthcare Network. Methods-. 107 men with breast cancer were identified from the respective cancer registry at Steward and 64 patients were included with complete medical records. Their clinical, histopathological and treatment records were retrospectively reviewed. Results-. Of these 64 patients, median age at diagnosis was 68 years, 58 patients were white (90.6%), 13 patients had family history of breast or ovarian cancer (20.3%), 4 patients tested positive for BRCA2 (6.25%), 1 patient had liver cirrhosis, and no patient had Klinefelter syndrome or testicular dysfunction. 57 patients (89%) presented with a breast mass with 4 of these patients having nipple changes (6.25%). 59 patients (92.2%) had invasive ductal carcinoma, 42 patients (65.6%) had grade 2 tumors, 31 patients (48.4%) had tumor size between 2-5 cm, and 31 patients (48.4%) had lymph node involvement at time of diagnosis. 62 patients (96.8%) had M0 disease at time of diagnosis. 97% of patients had ER positive cancer, 87.5% of patients had PR positive cancer, and 7.8% of patients had HER2 positive cancer. Most patients underwent mastectomy (87.5%). Only 16% of patients with T1 tumors (5/31) underwent breast conserving surgery. 10 patients (15.6%) received neoadjuvant chemotherapy, 35 patients (54.6%) received adjuvant radiation therapy, 19 patients (30%) received adjuvant chemotherapy, and 98.4% of patients received adjuvant hormonal therapy. The median follow up was 71.5 months (range 6-250 months), 5-year survival rate was 86.9% (95% CI, 74.5% to 93.6%), 5-year relapse free survival rate was 89.9% (95% CI, 77.4% to 95.7%) and 10-year survival rate was 58.1% (95% CI, 41.0% to 71.8%). The presence of distant metastasis at the time of initial diagnosis was the only factor associated with shorter overall survival (hazard ratio 22.54, p &amp;lt;0.0001). Conclusion-. Majority of MaBC patients present with palpable breast mass and the tumors are almost exclusively hormone receptor positive. Majority of patients present without distant metastasis and received surgical therapy however only a small subset of patients received breast conserving surgery for T1 tumor. Almost all patients received adjuvant hormonal therapy. Overall survival and relapse free survival in our cohort is similar to historic reports in female breast cancer. Citation Format: Guoliang Zheng, Haoyang Wang, Fang-Yu Liu, Jose Pablo Leone. Male breast cancer- a 20 year multi-center experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-23-01.

Historical aspects and modern concepts in the treatment of patients with differentiated thyroid cancer, refractory to radioactive iodine therapy

Radioiodine therapy for differentiated thyroid cancer has been used for a long time, mainly in patients of intermediate and high risk, as well as in the presence of distant metastases. However, about 30–40 % of patients are refractory to radioiodine therapy, which significantly worsens the prognosis. In patients with radioiodine-refractory differentiated thyroid cancer, therapy with targeted agents, primarily tyrosine kinase inhibitors, is indicated.This review addresses the criteria for refractoriness and criteria for prescription of targeted therapy, and presents the results of clinical studies of the targeted agents used. As of today, lenvatinib is the most well-known targeted agent. In particular. In SELECT trial lenvatinib demonstrated efficacy in terms of progression-free survival and overall survival in patients with radioiodine-refractory differentiated thyroid cancer. As a result, lenvatinib was included in the international and Russian clinical guidelines for the management of this group of patients as a drug of the 1st line of targeted therapy.