Intrathoracic Metastases Research Articles

Feasibility of chest spiral 3D ultrashort echo time magnetic resonance imaging for intrathoracic metastasis work-up in breast cancer.

Chest computed tomography (CT) is routinely performed to evaluate intrathoracic metastasis in patients with breast cancer, but radiation exposure and its potential carcinogenic risks are major drawbacks. Furthermore, pulmonary imaging by magnetic resonance imaging (MRI) is limited by low proton density, rapid signal decay, and sensitivity to respiratory and cardiac motions in lung tissue. Recently, a respiratory gating spiral three-dimensional (3D) ultrashort echo time (UTE) volume interpolated breath-hold examination (VIBE) sequence for lung MRI provides high spatial-resolution images with reasonable scan times. Our objective was to investigate the feasibility of chest spiral 3D UTE VIBE MRI to detect intrathoracic metastasis in breast cancer patients. This retrospective study of a prospectively collected database was conducted between February and July 2019 after institutional review board approval. All participants provided informed consent for MRI scans. Ninety-three female patients with breast cancer were retrospectively enrolled and underwent preoperative breast MRI, including a chest spiral 3D UTE VIBE sequence. Two chest radiologists evaluated image qualities of intrapulmonary vessels and bronchial wall visibilities, the presence of pulmonary nodules, significant lymph nodes (LNs), and other lung abnormalities on spiral 3D UTE magnetic resonance (MR) images and compared them using chest CT as a reference standard. Intrapulmonary vessels and bronchial walls were visible up to sub-subsegmental and sub-subsegmental levels, respectively, on spiral 3D UTE MR images, and better than fair quality was obtained for artifact/noise and overall image quality for 95.7% and 98.9% of the patients, respectively. The overall detection rate for pulmonary nodules was 62.8% (59/94). Furthermore, 59 of the 81 solid nodules detected by CT were detected by spiral 3D UTE MRI (72.8%), and 31 of the 33 solid nodules (≥5 mm in diameter) detected by CT were identified by spiral 3D UTE MRI (93.9%). Significant LNs in the axillary area were similarly detected by spiral 3D UTE MRI and chest CT. Preoperative breast MRI with a chest spiral 3D UTE sequence could be used to evaluate breast cancer and axillary LNs and intrathoracic metastasis simultaneously and offers a potential alternative to chest CT for breast cancer patients without additional radiation exposure.

Life-threatening hemoptysis in patients with metastatic kidney cancer.

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n=4, 67%), concurrent anticoagulant therapy (n=1, 17%) and concurrent systemic therapy (n=4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n=130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH.

The Diagnostic and Prognostic Value of EBUS-TBNA for Intrathoracic Metastasis in Previously Treated Patients With Head and Neck Cancer.

The present study assessed the diagnostic and prognostic significance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for suspected intrathoracic metastasis after HNC treatment. A retrospective analysis was conducted on 75 patients with a prior history of head and neck cancer treatment who underwent EBUS-TBNA for suspected intrathoracic metastases between March 2012 and December 2021. A total of 126 targeted lesions, including 107 mediastinal/hilar lymph nodes and 19 intrapulmonary/mediastinal masses, were sampled. The metastatic head and neck cancer (HNC) cases detected by EBUS-TBNA consisted of nasopharyngeal carcinoma (n = 24), oropharyngeal carcinoma (n = 3), hypopharynx carcinoma (n = 6), laryngeal carcinoma (n = 6), and oral cavity carcinoma (n = 6). Cases with negative EBUS-TBNA results consisted of tuberculosis (n = 9), sarcoidosis (n = 3), anthracosis (n = 9), and reactive lymphadenitis (n = 9). Six false-negative cases were found among the 75 patients with suspected intrathoracic metastases. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the EBUS-TBNA procedure for metastatic HNC were 88.2, 100.0, 100.0, 80, and 92.0%, respectively. The diagnosis of HNC intrathoracic metastasis by EBUS-TBNA correlated with an adverse prognosis in terms of overall survival (OS) (P = .008). The log-rank univariate analysis and Cox regression multivariate analysis results indicated that the detection of metastatic HNC through EBUS-TBNA was a significant independent prognostic factor for patients with HNC who had received prior treatment. Endobronchial ultrasound-guided transbronchial needle aspiration is a safe, effective, and minimally invasive procedure for assessing suspected intrathoracic metastasis in HNC patients after treatment. The intrathoracic metastasis detected by EBUS-TBNA has crucial prognostic significance in previously treated HNC patients.

A novel NGS‐based diagnostic algorithm for classifying multifocal lung adenocarcinomas in pN0M0 patients

The classification of multifocal lung adenocarcinomas (MLAs), including multiple primary lung adenocarcinomas (MPLAs) and intrapulmonary metastases (IPMs), has great clinical significance in staging and treatment determination. However, the application of molecular approaches in pN0M0 MLA diagnosis has not been well investigated. Here, we performed next-generation sequencing (NGS) analysis in 45 pN0M0 MLA patients (101 lesion pairs) who were initially diagnosed as having MPLA by comprehensive histologic assessment (CHA). Five additional patients with intrathoracic metastases were used as positive controls, while 197 patients with unifocal lung adenocarcinomas (425 random lesion pairs) were used as negative controls. By utilizing a predefined NGS criterion, all IPMs in the positive control group could be accurately classified, whereas 13 lesion pairs (3.1%) in the negative control cohort were misdiagnosed as IPMs. Additionally, 14 IPM lesion pairs were diagnosed in the study group, with at least 7 misdiagnoses. We thus developed a refined algorithm, incorporating both NGS and histologic results, that could correctly diagnose all the known MPLAs and IPMs. In particular, all IPMs identified by the refined algorithm were diagnosed to be IPMs or suspected IPMs by CHA reassessment. The refined algorithm-diagnosed MPLAs patients also had significantly better progression-free survival than the refined algorithm-diagnosed IPMs (p < 0.0001), which is superior to conventional NGS or CHA diagnoses. Overall, we developed an NGS-based algorithm that could accurately distinguish IPMs from MPLAs in MLA patients. Our results demonstrate a promising clinical utility of NGS to complement traditional CHA-based MLA diagnosis and help determine patient staging and treatment.

Diagnosis and Pattern Identification of Intrathoracic Malignant Melanoma Metastasis: A Retrospective Single Center Analysis.

The lung is a frequent site of secondary malignancies. Melanoma is a malignant tumor originating from melanocytes, that accounts for the majority of death related to skin cancers. In advanced stages, it can also present with intrathoracic metastasis, particularly in the lungs, but infrequent intrathoracic manifestations are possible. A retrospective analysis of the cases referred to the pulmonary endoscopy unit of the hospital of Reggio Emilia in the last 10 years (since December 2012) was carried out, discovering 17 cases of melanoma metastasis with thoracic localizations, either with or without a diagnosis of primary melanoma. Four repetitive patterns of clinical-radiological presentation have been identified and described through the same number of paradigmatic clinical cases: nodal involvement (35%), lung mass(es) (41%), diffuse pulmonary involvement (12%), and pleural involvement (12%). These different presentations imply the use of different diagnostic techniques, with an overall high diagnostic yield (87.5%). Finally, a brief analysis of survival based on the pattern of presentation has been performed, finding no statistically significant differences between the four groups at metastasis diagnosis (p-value = 0.06, median survival of respectively 54, 8, 9, and 26 months from metastasis diagnosis), while there is a significant difference considering patients with lung involvement versus nodal/pleural involvement (p = 0.01).

Prognosis of different extrathoracic metastasis patterns in patients with M1c lung adenocarcinoma receiving immunotherapy.

Lung cancer with extrathoracic metastases is classified as M1c. However, extrathoracic metastases can be further classified into different patterns. The purpose of this study was to analyze the survival differences between different patterns of extrathoracic metastases in patients with stage M1c lung adenocarcinoma after receiving immunotherapy. This study included 160 stage M1c lung adenocarcinoma patients and treated with immunotherapy. The enrolled patients were divided into two groups: those with multiple extrathoracic metastases alone (EM group) and those with simultaneous multiple extrathoracic and intrathoracic metastases (EIM group). Progression-free survival (PFS) and overall survival (OS) were evaluated. The median PFS and OS in the whole group were 7.7months and 25.4months, respectively. The patients in the EM group show better PFS (13.0months vs. 5.0months; hazard ratio [HR] = 0.462, 95% confidence interval [CI] 0.317-0.673, P < 0.0001) and OS (35.0months vs. 18.9months; HR 0.592, 95% CI 0.380-0.922, P = 0.019) compared with the EIM group. Furthermore, in patients with lung adenocarcinoma with simultaneous extrathoracic and intrathoracic metastases who received immunotherapy, immunotherapy combined with chemotherapy has better PFS and OS than immunotherapy alone. There was no difference between immunotherapy alone or combined with chemotherapy in patients with lung adenocarcinoma with extrathoracic metastasis alone. The different patterns of extrathoracic metastasis were related to the efficacy and prognosis of immunotherapy in M1c cohort. In addition, patients with simultaneous extrathoracic and intrathoracic metastases were more recommended to choose immunotherapy in combination with chemotherapy rather than immunotherapy alone.

Outcome and Prognostic Factors in Cats Undergoing Resection of Intestinal Adenocarcinomas: 58 Cases (2008-2020).

The purpose of this multi-institutional retrospective study was to expand the available data pertaining to pre-operative clinical findings, progression-free and overall survival times, and potential prognostic factors for cats undergoing surgery for intestinal adenocarcinomas. Fifty-eight cats treated over a 12-year period were included in the study. Progression-free and overall survival times were estimated using Kaplan-Meier analyses. Potential prognostic variables were evaluated for associations with progression-free and overall survival using univariate Cox proportional hazards regression analyses. Prior to surgery, the intestinal mass was identified using ultrasonography in 89% of cats in which it was applied; however, imaging findings suggestive of intrathoracic metastases were observed in only 9% of cats. Among 22 cats undergoing ultrasound-guided fine needle aspiration cytology, the results agreed with the results of histopathology in only 10 cats. Discordant results were most commonly related to the presence of marked inflammation in cytology samples, which may have obscured the presence of neoplastic cells. Diffuse intestinal small cell lymphoma was identified as a comorbidity in 5 cats. Resection of the tumor with the objective of obtaining wide surgical margins was performed in each cat. On histopathology, 20 tumors were classified as mucinous adenocarcinoma and 28 were adenocarcinoma not otherwise specified. Intestinal transection site margins were complete in 94% of cats; however, complete mural margins were present in only 15% of cats. Local lymph node metastases were identified in 52% of cats and carcinomatosis was diagnosed in 81% of cats. Disease progression was documented in 32 of the 58 cats (55%). Of these 32 cats, 14 (43%) had local recurrence of the primary intestinal tumor. Median progression-free survival was 203 days (95% CI 130–299 days), and median overall survival time was 284 days (95% CI 200–363 days). Mitotic count was inversely associated with progression-free survival (HR 1.04; 95% CI 1.01–1.07, P = 0.005); however, none of the remaining potential prognostic factors, including administration of adjuvant chemotherapy, were significantly associated with progression-free or overall survival. Feline intestinal adenocarcinoma remains an aggressive and highly fatal disease. Large, randomized controlled clinical trials will be needed to improve the survival prospects for affected cats.

59P Clinical utility of plasma cell-free DNA EGFR mutation analysis in treatment-naïve stage IV non-small cell lung cancer patients

Plasma cell-free DNA epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC. In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction. The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. The diagnostic sensitivity of the plasma EGFR mutation assay (80.5%) was similar to that of the tissue EGFR mutation assay (79.3%, p = 0.787). In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days, p < 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group. Smoking status and the factors reflecting tumor burden were associated with detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.

Clinical Utility of Plasma Cell-Free DNA EGFR Mutation Analysis in Treatment-Naïve Stage IV Non-Small Cell Lung Cancer Patients.

Background: Plasma cell-free Deoxyribo nucleic acid epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC. Methods: In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction. Results: The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days, p < 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group. Conclusion: Smoking status and the factors reflecting tumor burden were associated with the detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.

The airway microbiota of non-small cell lung cancer patients and its relationship to tumor stage and EGFR gene mutation.

BackgroundAccumulating studies have suggested the airway microbiota in lung cancer patients is significantly different from that of healthy controls. However, little is known about the relationship between airway microbiota and important clinical parameters of lung cancer. In this study, we aimed to explore the association between sputum microbiota and lung cancer stage, lymph node metastasis, intrathoracic metastasis, and epidermal growth factor receptor (EGFR) gene mutation.MethodsThe microbiota of sputum samples from 85 newly‐diagnosed NSCLC patients were sequenced via 16S rRNA sequencing of the V3–V4 region. Sequencing reads were filtered using QIIME2 and clustered against UPARSE.ResultsAlpha‐ and β‐diversity was significantly different between patients in stages I to II (early stage, ES) and patients in stages III to IV (advanced stage, AS). Linear discriminant analysis Effect Size (LEfSe) identified that genera Granulicatella and Actinobacillus were significantly enriched in ES, and the genus Actinomyces was significantly enriched in AS. PICRUSt2 identified that the NAD salvage pathway was significantly enriched in AS, which was positively associated with Granulicatella. Patients with intrathoracic metastasis were associated with increased genus Peptostreptococcus and incomplete reductive TCA cycle, which was associated with increased Peptostreptococcus. Genera Parvimonas, Pseudomona and L‐valine biosynthesis were positively associated with lymph node metastasis. L‐valine biosynthesis was related with increased Pseudomona. Finally, the genus Parvimonas was significantly enriched in adenocarcinoma patients with EGFR mutation.ConclusionThe taxonomy structure differed between different lung cancer stages. The tumor stage, intrathoracic metastasis, lymph node metastasis, and EGFR mutation were associated with alteration of specific airway genera and metabolic function of sputum microbiota.

Incidence and Prognosis Nomogram of Small Solitary Lung Cancer (≤2cm) With Extra-Thoracic Metastasis at Initial Diagnosis:A Population-Based Study.

Small solitary lung cancer (≤2cm) with extra-thoracic metastasis and no nodal metastasis or intra-thoracic metastasis is a rare situation in clinic. Lung cancer patients with stage T1aN0M0 and T1aN0M1b from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results database. The identified significant parameters were utilized to develop 2 nomogram to predict the extra-thoracic metastasis rates and the overall survival for the group of patients with stage T1aN0M1b. Small solitary lung cancers which occur in the males, younger patients, or locate in the main bronchus or left lung, or with histologic type as small cell lung cancer, or with undifferentiated type, tend to have extra-thoracic metastasis. Application of the nomogram in the intra-group still gave good discrimination and good calibration. Univariable and multivariable analysis identified several clinical data as the prognostic factors for lung cancer patients with stage T1aN0M1b, all the factors above were incorporated into the nomogram. ROC curve analysis showed that the nomogram had good discrimination, with AUC of .779, .786 and .77 for 1-, 3- and 5-year survival in the development group and validation group, respectively. Moreover, decision curve analysis has been implemented to evaluate and compare prediction and prognostic nomogram. Younger male patients whose lung cancer locates in main bronchus or left lung, or with undifferentiated type, or with histologic type as small cell lung cancer are more likely to have extra-thoracic metastasis. The proposed nomogram reliably predicted OS for lung cancer patients with stage T1aN0M1b, though further validation is needed, it may be a useful tool in clinical practice. These models can be wildly used for easy facilitate the lung cancer individualized prediction of extra-thoracic metastasis and OS.

Role of delayed phase contrast-enhanced CT in the intra-thoracic staging of non-small cell lung cancer (NSCLC): What does it add?

PurposeThe aim of the study was to investigate differences in non-small cell lung cancer (NSCLC) intra-thoracic staging by using contrast-enhanced computed tomography (ce-CT) at the arterial phase (AP), at the arterial plus delayed phases (AP + DEP), and at the delayed phase (DEP), and to evaluate their potential impact on disease staging. Materials and methodsTwo chest radiologists with different level of expertise and a general radiologist independently reviewed the chest CT exams of 150 patients with NSCLC; CT scans were performed 40 s (AP) and 60 s (DEP) after contrast material injection. Image assessment included three reading sessions: session A (AP), session B (AP + DEP) and session C (DEP). CT descriptors for the primary tumour (T), regional nodal involvement (N), and intra-thoracic metastases (M) were evaluated in each reading session. Readers had to assign a confidence level (CL) for the assessment of each descriptor and define the TNM stage. Friedman and Cochran Q test was used to compare the assessments of the 3 reading sessions; inter-reader agreement was determined (Intraclass Correlation Coefficient – ICC). ResultsThe CL was significantly higher in sessions B and C than in session A for all descriptors, with the exception of pulmonary arterial invasion. Primary tumour inner necrosis and regional nodal involvement were detected in a significantly higher number of cases in sessions B and C as compared to session A (p ≤ 0.001). DEP significantly changed N stage determination (p < 0.001), particularly N3, and excluded chest wall invasion (p = 0.05) and venous invasion (p = 0.001). The agreement was good among the 3 readers (ICC = 0.761) and excellent between the 2 chest radiologists (ICC ≥ 0.940), regardless of the contrast phase. ConclusionsThe 60-second DEP ce-CT for staging NSCLC significantly increased the readers’ CL, changed the N stage determination, and helped excluding chest wall invasion and venous invasion.

Proton Beam Therapy for Hepatocellular Carcinoma after the Fontan Procedure

Background: Hepatocellular carcinoma (HCC) is more likely to occur in patients with a history of Fontan surgery, possibly due to long-term liver congestion. Proton beam therapy (PBT) may be effective for HCC that develops after Fontan surgery. Methods: Six lesions in 5 patients (3 females, 2 males) received PBT. The median age of the patients was 33 (range 21 - 42) years, and the median age at the time of the Fontan procedure was 6 (5 - 13) years. Four patients had multiple HCC at the time of PBT. The median tumor size was 57 (22 - 80) mm and 4 patients were classified as Child-Pugh B. Two patients received transcatheter arterial chemoembolization before PBT. The schedule of PBT was 66 Gy (RBE) in 10 fractions for 2 lesions, 72.6 Gy (RBE) in 22 fractions for 2 lesions, and 74 GyE (RBE) in 37 fractions for 2 lesions. Results: The median follow-up period was 31 (10 - 46) months, and the numbers of survivors, deaths from primary diseases, and deaths from other diseases were 3, 1, and 1, respectively. There were no local recurrences, one intrahepatic metastasis, one lung metastasis, and one intrathoracic metastasis. Conclusion: Although experiences on a small number of patients cannot conclude things, we believe that PBT can be a reasonable choice of radical treatment for HCC occurring after the Fontan procedure.

S3550 A Very Rare Primary Adenocarcinoma of the Duodenum

INTRODUCTION: Primary duodenal cancers are a rare occurrence among gastrointestinal malignancies. Cancers that occur within the duodenum include adenocarcinoma, neuroendocrine, lymphomas and leiomyosarcomas. Diagnosis is often delayed leading to worsening disease burden and poorer outcomes. We present an unusual case of a female with a history of triple negative invasive ductal carcinoma who was unfortunately found to have a primary adenocarcinoma of the duodenum. CASE DESCRIPTION/METHODS: The patient is a 61 year old female with a history of triple negative invasive ductal carcinoma status post mastectomy, radiation and chemotherapy who presented to her outpatient oncologist. Six years following her completed treatment, the patient developed symptoms of dyspepsia and iron deficiency anemia. She underwent CT imaging of the abdomen demonstrating duodenal obstruction and evidence of intrathoracic metastasis. The patient subsequently underwent push enteroscopy which revealed a duodenal mass. Duodenal stents were subsequently placed and biopsies taken intraoperatively. A PET scan was then performed and demonstrated hypermetabolic activity at the third and fourth portion of the duodenum with additional lung nodules consistent with metastasis. The biopsies resulted as a primary adenocarcinoma of the duodenum. The patient was started on oxaliplatin chemotherapy. Three months later a follow up PET scan was performed revealing interval improvement of the primary duodenal tumor and lung nodules. The patient continues to undergo palliative chemotherapy and has been consistently following up for her office visits. DISCUSSION: Primary duodenal cancer is a rare disease which reflects approximately 0.3–0.5% of all gastrointestinal malignancies. Adenocarcinoma commonly arises in the third and fourth portions of the duodenum. Most common presenting signs and symptoms include epigastric pain, anemia and weight loss. Since presenting symptoms are vague in nature, early diagnosis is often missed. One study found that at time of diagnosis, less than 40% could pursue curative resection. Tumor resectability and presence of metastasis have been regarded as the strongest factors influencing patient outcomes. One retrospective study demonstrated that patients who underwent tumor resection had a significantly longer survival rate compared to those who had no surgery. At the time of diagnosis, our patient demonstrated metastatic disease and therefore underwent palliative duodenal stenting and chemotherapy with oxaliplatin.

S2469 A Rare Case of Hepatocellular Carcinoma With Isolated Recurrence to the Stomach

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth-most common cancer worldwide and fourth leading cause of cancer-related mortality according to the WHO. It primarily metastasizes to the lungs, lymph nodes, and bones. Metastases of HCC to the gastrointestinal (GI) tract and specifically to the stomach are very infrequent. In this report, we present a unique case of HCC metastatic to the stomach. CASE DESCRIPTION/METHODS: A 61-year-old African-American (AA) female with hepatitis C-related cirrhosis complicated by HCC, originally diagnosed in 2015 and managed by partial hepatic resection. In April 2020, she underwent routine HCC surveillance imaging. MRI abdomen and pelvis (Figure 1) demonstrated no new liver lesions but was significant for an isolated 3.4 × 2.7 cm mass that was identified at the greater curvature of the stomach. She underwent upper endoscopy with endoscopic ultrasound revealing a 3.1 × 2.9 cm hypoechoic mass (Figure 2). Fine needle aspiration biopsy was performed, and pathology demonstrated an epithelioid mass compatible with HCC. Immunohistochemistry staining was positive for Cam5.2, glypican-3, and hepatocyte (partial) positive, confirming metastatic HCC. CT chest was negative for intrathoracic metastasis. The patient underwent partial gastrectomy in May 2020 given the isolated metastatic gastric lesion. Surgical pathology confirmed the diagnosis of moderately-differentiated metastatic HCC. DISCUSSION: We report a very rare case of metastatic HCC in an asymptomatic AA female, diagnosed on routine surveillance imaging for HCC. To our knowledge, this is the first reported case of HCC metastatic to the stomach in an African-American. Cases of HCC metastatic to the GI tract are exceedingly rare. The majority of cases of HCC with metastatic lesions in the stomach occur by direct extension rather than by hematologic dissemination. In documented cases, patients have presented most frequently with either iron deficiency anemia or abdominal pain. Almost all the reported cases have occurred in non-white individuals, and most have occurred in patients of East Asian ethnicities.Figure 1.: Greater curvature gastric mass.Figure 2.: EUS image of gastric mass.

High-Grade Cutaneous Mast Cell Tumour with Widespread Intrathoracic Metastasis and Neoplastic Pericardial Effusion in a Dog

An 8-year-old neutered male French Bulldog was presented with a 2-day history of intermittent vomiting, reduced appetite and recent rapid development of multiple cutaneous masses over the head and neck regions. On presentation, the patient had a moderate volume of pericardial and bilateral pleural effusion. Echocardiography demonstrated irregular, heterogeneous thickening of the walls of the right ventricle and right atrium, consistent with infiltrative intramyocardial disease. Cytological examination of fine needle aspirates from one of the cutaneous masses confirmed a mast cell tumour. Pericardial fluid analysis revealed a haemorrhagic neoplastic effusion due to mast cell neoplasia. Histopathological and immunohistochemical examination of tissues obtained post mortem confirmed a high-grade cutaneous mast cell tumour with metastasis to the heart, pericardium, mediastinum and spleen. No metastatic disease was present in the submandibular lymph nodes or liver. Immunohistochemistry demonstrated KIT staining pattern 2. There was strong nuclear Ki67 labelling in an average of 65.0cells per grid and an average of three positive AgNORs per nucleus in neoplastic cells. Polymerase chain reaction for the activating duplication mutation in exons 8 and 11 of c-Kit were negative. To the authors' knowledge, this is the first report of a canine cutaneous mast cell tumour associated with neoplastic pericardial effusion and widespread intrathoracic metastasis.

Clinicopathologic and Imaging Features of Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations.

MET exon 14 (METex14) skipping mutations are an emerging potentially targetable oncogenic driver mutation in non-small-cell lung cancer (NSCLC). The imaging features and patterns of metastasis of NSCLC with primary METex14 skipping mutations (METex14-mutated NSCLC) are not well described. Our goal was to determine the clinicopathologic and imaging features that may suggest the presence of METex14 skipping mutations in NSCLC. This IRB-approved retrospective study included NSCLC patients with primary METex14 skipping mutations and pre-treatment imaging data between January 2013 and December 2018. The clinicopathologic characteristics were extracted from electronic medical records. The imaging features of the primary tumor and metastases were analyzed by two thoracic radiologists. In total, 84 patients with METex14-mutated NSCLC (mean age = 71.4 ± 10 years; F = 52, 61.9%, M = 32, 38.1%; smokers = 47, 56.0%, nonsmokers = 37, 44.0%) were included in the study. Most tumors were adenocarcinoma (72; 85.7%) and presented as masses (53/84; 63.1%) that were peripheral in location (62/84; 73.8%). More than one in five cancers were multifocal (19/84; 22.6%). Most patients with metastatic disease had only extrathoracic metastases (23/34; 67.6%). Fewer patients had both extrathoracic and intrathoracic metastases (10/34; 29.4%), and one patient had only intrathoracic metastases (1/34, 2.9%). The most common metastatic sites were the bones (14/34; 41.2%), the brain (7/34; 20.6%), and the adrenal glands (7/34; 20.6%). Four of the 34 patients (11.8%) had metastases only at a single site. METex14-mutated NSCLC has distinct clinicopathologic and radiologic features.

91P - Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns

Introduction: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations. Materials and Methods: Patients who were diagnosed only with intrathoracic metastasis between March 2011 and October 2016 and had EGFR-mutations were selected for this study. Prognosis was determined based on metastatic patterns by univariate and multivariate analysis. Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and 33 patients who had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were selected for this in the study. The median OS (overall survival) time was 38.1 (95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p=0.037). Multivariate analysis demonstrated that Group A and Group B had higher OS compared to Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p=0.018; HR=0.473, 95%CI: 0.241-0.931, p=0.030, respectively) among lung adenocarcinoma patients with EGFR mutations. With regard to patients with pleural or contralateral metastasis only, OS benefit (p=0.579) was not significant between the two groups. Subgroup analysis demonstrated that OS benefit in Group A was significant in patients with N0-1 disease and 21L858R mutations but not in EGFR exon 19 deletions, N2-3 stage or T3-4 stage patients. Conclusion: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis was different, indicating that M1a staging should be refined.

Predictive factors for long-term responders of pemetrexed maintenance treatment in non-small cell lung cancer.

BackgroundWe determined the clinical characteristics and predictive factors of long‐term response to pemetrexed maintenance therapy as first‐line treatment for non‐small cell lung cancer (NSCLC).MethodsA total of 950 advanced NSCLC patients received pemetrexed (500 mg/m2) plus cisplatin (60 mg/m2) (Pem‐Cis) induction chemotherapy every three weeks as first‐line treatment between January 2010 and August 2018. Patients who did not show progression after four cycles of Pem‐Cis and received at least one cycle of pemetrexed maintenance were recruited (n = 199).ResultsPatients were divided into subgroups according to total cycles of pemetrexed: ≤ 10 (F10, n = 134) and > 10 (M10, n = 65). The M10 group had a higher proportion of patients with stage M1a (intrathoracic metastasis alone) and exhibited lower levels of thymidylate synthase (TS) than the F10 group (median H‐score 10.0% vs. 60.0%; P = 0.031). Further subgrouping identified extreme responders: ≤ 7 (F7, n = 101) and ≥ 20 (M20, n = 26) cycles. The M20 group showed lower mean serum CEA levels before (17.5 vs. 147.0; P = 0.099) and after (6.9 vs. 53.2; P = 0.001) Pem‐Cis treatment, and a higher incidence of normalization after Pem‐Cis (abnormal 41.7% vs. 68.5%; P = 0.015). M1a stage, normalization of CEA levels after Pem‐Cis, and lower TS H‐score were predictors of progression‐free survival in patients administered pemetrexed maintenance.ConclusionM1a stage and lower TS expression were predictors of long‐term response to pemetrexed maintenance. CEA normalization after Pem‐Cis could be an additional surrogate marker of positive response to long‐term treatment.

Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns.

Introduction: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations.Materials and Methods: Patients who were diagnosed only with intrathoracic metastasis between March 2011 and October 2016 and had EGFR-mutations were selected for this study. Prognosis was determined based on metastatic patterns by univariate and multivariate analysis.Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and 33 patients who had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were selected for this in the study. The median OS (overall survival) time was 38.1 (95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p=0.037). Multivariate analysis demonstrated that Group A and Group B had higher OS compared to Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p=0.018; HR=0.473, 95%CI: 0.241-0.931, p=0.030, respectively) among lung adenocarcinoma patients with EGFR mutations. With regard to patients with pleural or contralateral metastasis only, OS benefit (p=0.579) was not significant between the two groups. Subgroup analysis demonstrated that OS benefit in Group A was significant in patients with N0-1 disease and 21L858R mutations but not in EGFR exon 19 deletions, N2-3 stage or T3-4 stage patients.Conclusion: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis was different, indicating that M1a staging should be refined.