Pleomorphic Carcinoma Research Articles

EGFR mutation genotyping and ALK status determination in liquid-based cytology samples of non-small cell lung cancer.

Personalised medicine for primary lung cancers (PLCs) requires molecular analysis of cancer tissue or cells. The primary objective of the present prospective study was to assess the concordance between epidermal growth factor receptor (EGFR) gene mutation detection and echinoderm microtubule-associated protein-like (EML) 4-anaplastic lymphoma kinase protein (ALK) expression using liquid-based cytology (LBC) samples and matched histology samples of PLC patients. A total of 117 patients who underwent surgical resection of non-small cell PLC were enrolled. Cytological specimens scratched from the resected PLC lesion were fixed in CytoRich Red. DNA extracted from LBC samples was examined for EGFR gene mutations. Anaplastic lymphoma kinase arrangement was analysed by immunostaining and fluorescence in situ hybridisation. Our patient cohort comprised 93 cases of adenocarcinoma, 16 squamous cell carcinoma, three adenosquamous carcinoma, two large cell neuroendocrine carcinoma, one pleomorphic carcinoma and two other cases. Sixty-six (58.4%) LBC samples harboured EGFR gene mutations. The overall concordance rate in EGFR gene mutation status, including minor mutations, between histologic and paired LBC specimens (N = 105) was 100%. The overall concordance rate of EGFR gene mutation status, including minor mutations and ALK status according to immunostains between histologic and paired LBC specimens, was 100% (105/105) and 100% (48/48), respectively. Genotyping and protein expression studies can be reliably performed using LBC samples prepared with CytoRich Red. Analysis of such samples may guide individual therapy in PLC patients.

Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies. According to the most recent 2015 World Health Organization (WHO) classification, PSC includes several different variants of malignant epithelial tumors (carcinomas) histologically mimicking sarcomas showing or entirely lacking a conventional component of non-small cell lung cancer (NSCLC). Thus, this rare subheading of lung neoplasms includes pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma. A diagnosis of PSC may be suspected on small biopsy or cytology, but commonly requires a surgical resection to reach a conclusive definition. The majority of patients with PSC consists of elderly, smoking men with a large, peripheral mass characterized by well-defined margins. However, presentation with a central, polypoid endobronchial lesion is well-documented, particularly in pleomorphic carcinoma and carcinosarcoma showing a squamous cell carcinoma component. As expected, PSC may pose diagnostic problems and immunohistochemistry is largely used when pathologists deal these tumors in routine practice. Indeed, PSC tends to overexpress molecules associated with the epithelial-to-mesenchymal transition, such as vimentin, but the panel of immunostains also includes epithelial markers (cytokeratins, EMA), TTF-1, p40 and negative markers (e.g., melanocytic, mesothelial and sarcoma-related primary antibodies). Although rare, PSC has increased their interest among oncologist community for different reasons: a. identification of the epithelial-to-mesenchymal phenomenon as a major mechanism of secondary resistance to tyrosine kinase inhibitors; b. over-expression of PD-L1 and effective treatment with immunotherapy; c. identification of c-MET exon 14 skipping mutation representing an effective target to crizotinib and other specific inhibitors. In this review, the feasibility of the diagnosis of PSC, its differential diagnosis and novel molecular findings characterizing this group of lung tumor are discussed.

Pleomorphic Ductal Carcinoma of Breast: Two Cases and Review Literature

Abstract- We report two cases of pleomorphic breast carcinoma, a rare variant of high-grade invasive ductal breast carcinoma of no special type, which is a combination of pleomorphic and bizarre giant cells in an adenocarcinoma background. For gaining better insights, available literature is also reviewed. © 2019 Tehran University of Medical Sciences. All rights reserved.

Trousseau's syndrome associated with pulmonary pleomorphic carcinoma exhibiting aggressive features: A case report.

Trousseau's syndrome is characterized as an unexpected, cancer-related thrombotic event, such as a cerebral infarction or a deep vein thrombosis/pulmonary embolism. We describe the first reported case of Trousseau's syndrome with pulmonary pleomorphic carcinoma and aggressive features. A 74 year-old man presenting with a pulmonary mass, which was identified as pleomorphic carcinoma with extensive lymph node involvement, in the left lower lobe, underwent a left lower lobectomy. Immunohistochemical analysis revealed that neoplastic cells exhibited an extensive expression of tissue factors with a mucin-producing adenocarcinoma component. Three months postoperatively, diffuse infiltration rapidly appeared in the left lung, which was identified as lymphangitic carcinomatosis via bronchoscopy. Prior to treatment for cancer recurrence, the patient presented with a left hemiplegia due to a cerebral infarction via multiple thromboses, with no evidence of atherosclerotic or cardiogenic thrombi. Elevated D-dimer and carbohydrate antigen 125 levels and the presence of a fibrin thrombus retrieved from the occluded vessel suggested Trousseau's syndrome as the etiology of the brain infarction. A hypercoagulable state associated with the aggressive recurrence of pulmonary pleomorphic carcinoma, accompanied by cancer cell production of mucin and tissue factors may be a potential mechanism for cancer-related thrombosis.

Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma.

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin β3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

Impact of Histopathologic Changes Induced by Polyethylene Glycol Hydrogel Pleural Sealants Used During Transthoracic Biopsy on Lung Cancer Resection Specimen Staging.

Patients undergoing transthoracic needle core lung biopsy (TTNB) are at risk for biopsy-related pneumothorax. Instilling pleural sealant at the pleural puncture site reduces this risk. The impact of histologic changes associated with pleural sealant on assessing the histologic type and pathologic stage in lung cancer resection specimens has not been previously evaluated. All lung cancer resection specimens from 2015 to 2018 in which polyethylene glycol hydrogel pleural sealant was instilled during TTNB were reviewed. Thirty-three cases were identified. TTNB preceded lobectomy by an average of 35 days. Amphophilic, weakly polarizable, crinkled pleural sealant material was associated with tumor in 11 cases (33%), including 8 adenocarcinomas, 2 squamous cell carcinomas, and 1 pleomorphic carcinoma that averaged 1.7 cm in greatest dimension. Surrounding the sealant material was a 0.25 to 1.0 cm in greatest dimension pseudocystic space with a thin granulomatous rim of macrophages and multinucleated giant cells that occupied on average 17% of the tumoral area. Pleural sealant could have impaired assessment of pathologic stage in 1 case by obscuring the visceral pleural elastic layer, but definitive visceral pleural invasion was present nearby. Although hydrogel pleural sealant instilled during TTNB has the potential to obscure important histologic features, in practice, it appears to have little or no adverse impact on the assessment of histologic type and pathologic stage in subsequent lung cancer resection specimens. Recognition of the histologic appearance of hydrogel pleural sealant and its associated tissue response is important for avoiding diagnostic misinterpretation.

P2.17-41 Treatment Outcomes of Pulmonary Resection in NSCLC Patients with Autoimmune Diseases

Surgical resection for early stage non-small cell lung cancer (NSCLC) patient with autoimmune disease(s) is a relatively rare occasion. Most of such patients have received steroid therapy with/without immunosuppressant agent for a long period before the surgery. However, short-term or long-term treatment outcomes of NSCLC patients with autoimmune disease are unclear. Between January 2007 to December 2018, thirty-nine NSCLC patients with autoimmune disease(s) received pulmonary resection with curative intent in our department. Patients with interstitial lung disease were excluded from this study. Patient clinical and pathological characteristics and treatment outcomes were evaluated. There were 17 males and 22 females in out cohort. The median age was 68 years old (39 – 84), and thirty patients were smokers. Twenty-three patients had rheumatoid arthritis, and among them, three patients had additional autoimmune disease (autoimmune hepatitis, Sjogren syndrome, or polyneuropathy). Other autoimmune diseases included Hashimoto disease (n = 4), systemic lupus erythematosus (n = 3), Behcet’s disease (n = 2), primary biliary cirrhosis (n = 2), and others. Only three patients received limited resections (2 partial resections and one segmentectomy), and 36 patients received lobectomy or bi-lobectomy. At the post-operative pathological diagnosis, there were 13 patients with squamous cell carcinomas, 21 patients with adenocarcinomas, four patients with pleomorphic carcinomas, and one patient with adenosquamous cell carcinoma. Post-surgical complications included pneumonia (n = 1, 3%), prolonged air leakage (n = 1, 3%), and no patient experienced bronchopleural fistula or empyema. The median post-surgical hospital stay was eight days (4 – 28 days). Pulmonary resection for NSCLC patients with autoimmune disease(s) were safely performed. We will also report the long-term outcome for this cohort at the conference.

Cancer Progress and Priorities: Lung Cancer.

In the United States, lung cancer is the second most common diagnosed cancer and the leading cause of cancer-related death. Although tobacco smoking is the major risk factor accounting for 80% to 90% of all lung cancer diagnoses, there are numerous other risk factors that have been identified as

P1.04-63 Correlation of Mutations in TP53, CDKN2A and PIK3CA with VISTA Expression in Pleomorphic Lung Carcinoma

P1.04-63 Correlation of Mutations in TP53, CDKN2A and PIK3CA with VISTA Expression in Pleomorphic Lung Carcinoma

EP1.09-09 Surgical Cases of Pulmonary Pleomorphic Carcinoma at Our Institution

EP1.09-09 Surgical Cases of Pulmonary Pleomorphic Carcinoma at Our Institution

EP1.18-27 Study of Five Cases Resected Pulmonary Pleomorphic Carcinoma - Immune Checkpoint Inhibitors Are Improved the Prognosis?

EP1.18-27 Study of Five Cases Resected Pulmonary Pleomorphic Carcinoma - Immune Checkpoint Inhibitors Are Improved the Prognosis?

EP1.01-73 Trousseau’s Syndrome Associated with Pulmonary Pleomorphic Carcinoma Showing Aggressive Features: A Case Report

EP1.01-73 Trousseau’s Syndrome Associated with Pulmonary Pleomorphic Carcinoma Showing Aggressive Features: A Case Report

EP1.08-06 Postoperative Oligo-Recurrence of Non-Small Cell Lung Cancer

Postoperative recurrences of non-small cell lung cancer (NSCLC) are usually disseminated and systemic. The concept of oligo-recurrence, defined as a small number of new lesions at a distant site theoretically curable by local therapy, has recently been proposed for several cancers. The aim of this study was to clarify clinical features and outcomes of patients with postoperative oligo-recurrence of NSCLC. From 364 patients who underwent resection for NSCLC between January 2008 and December 2017 at our hospital. A total of 43 patients who developed recurrence were included in this study. Oligo-recurrence was defined as 1-2 loco-regional or distant recurrence lesions restricted to a single organ. Other recurrences were classified as poly-recurrence. Local therapy included surgery, stereotactic radiotherapy and radiotherapy. Oligo-recurrence was identified in 12 (27.9%) patients, mainly as a solitary recurrence (n=11, 91.7%) in regional lymph nodes (n=1), surgical stump (n=2), brain (n=5), lung (n=1), bone (n=2) and liver (n=1). Primary tumor histopathological types included 9 cases of adenocarcinoma, one case of squamous cell carcinoma, one case of pulmonary pleomorphic carcinoma and one case of large cell neuroendocrine carcinoma.The patients with oligo-recurrence had a longer time to recurrence than those with poly-recurrence (median: 23.5 months, 11.0 months). A case of mediastinal lymph node recurrence was performed radiation therapy. A case of surgical stump recurrence underwent lobectomy and other case was performed concurrent chemo-radiotherapy. 4 case of brain metastasis were underwent tumor resection and were performed stereotactic radiotherapy, one case of brain metastasis was performed stereotactic radiotherapy only. A case of lung metastasis underwent wedge resection and was used EGFR-TKI. A case of bone recurrence was performed radiation therapy and was used EGFR-TKI, other case was performed concurrent chemo-radiotherapy. A case of liver metastasis underwent tumor resection. 7 of 12 cases confirmed re-recurrence after local therapy. But 9 patients were alive between 30.4 and 110.0 months after local therapy, whereas three of 5 brain metastatic patients died between 24.9 and 71.8 months. The 5 year overall survival rates after local therapy were 81.5%. The presence of oligo-recurrence can predict a favorable prognosis in patients with NSCLC treated with aggressive local therapy.

Clinicopathological Features, Surgical Outcomes, Oncogenic Status and PD-L1 Expression of Pulmonary Pleomorphic Carcinoma.

Pulmonary pleomorphic carcinoma (PPC) is rare, and few studies have reported its features. We assessed the clinicopathological features, surgical outcomes, oncogenic status and programmed death-ligand 1 (PD-L1) expression of PPC. We retrospectively reviewed data from 22 consecutive patients who underwent resection of PPC between 2007 and 2017. The predominant tissue type of the epithelial component was adenocarcinoma in 15 patients (68%) and the others in 7 patients (32%), and the 3-year disease-free survival rate tended to be better in patients with an adenocarcinoma component compared to patients with another component (40.0% vs. 17.1%, p=0.059). PD-L1 expression was observed in all eight tumors whose PD-L1 status could be examined and high PD-L1 expression (≥50%) was frequent (5/8, 63%). A predominant adenocarcinoma epithelial component in PPC might be associated with better survival outcomes and high PD-L1 expression might be frequent in PPC.

Expression of CD44v6 and COX-2 in pleomorphic adenomas and carcinomas of parotid gland

To investigate the correlation between CD44v6 and cyclooxygenase-2(COX-2) expression and recurrence and deterioration of pleomorphic adenoma of parotid gland. Immunohistochemistry was used to detect the expression of CD44v6 and COX-2 in 19 normal parotid tissues, 25 primary pleomorphic adenomas, 15 first recurrent pleomorphic adenoma, 15 second recurrent pleomorphic adenoma and 13 cancer in pleomorphic adenomas. The correlation between CD44v6 and COX-2 and the recurrence and deterioration of pleomorphic adenomas was evaluated using SPSS 15.0 software package. The positive expression rate of CD44v6 in normal parotid gland, primary pleomorphic adenoma, first recurrent pleomorphic adenoma, second recurrent pleomorphic adenoma and cancer was 5.26%, 44.00%, 60.00%, 93.37% and 100.00%, respectively;and the positive expression rate of COX-2 was 10.53%, 40.00%, 63.33%, 93.37% and 100.00%, respectively. There was significant difference in the positive expression intensity of CD44v6 and COX-2 among the groups (P<0.05). The positive expression rate and intensity of CD44v6 and COX-2 in normal parotid gland tissue were significantly lower than those in other groups (P<0.05). There was no significant difference in the positive expression rate and intensity of CD44v6 between primary pleomorphic adenoma and first recurrent pleomorphic adenoma (P>0.05). There was no significant difference in the expression intensity of COX-2 between the two groups (P>0.05), but the positive expression rate of COX-2 between the two groups was not significant(P>0.05). The positive expression rate and intensity of CD44v6 and COX-2 in the second recurrent pleomorphic adenoma were significantly higher than those in the first recurrent pleomorphic adenoma(P<0.05), but there was no significant difference between the two groups(P>0.05). CD44v6 in the second recurrent pleomorphic adenoma and cancer was significantly higher than that in the first recurrent pleomorphic adenoma(P<0.05). There was no significant difference in the expression rate and intensity of COX-2 (P>0.05). CD44v6 and COX-2 may play an important role in promoting occurrence, invasion, recurrence and deterioration of pleomorphic adenoma through synergistic action.

Analysis of Amplified Genes in Samples of Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma by CGH-Array Technique

Abstract Introduction Pleomorphic adenoma (PA) is a benign lesion of the salivary glands that can suffer malignant transformation to carcinoma ex adenoma pleomorphic (CXPA). The pathogenesis of CXPA has been attributed to the accumulation of genetic disorders in preexisting PAs. However, there is no confirmation whether there is a common target gene involved in all histopathological subtypes or the decisive factors for malignant transformation in a histopathological subtype are specific. Objectives To further analyze genes found in PA and CXPA using the CGH-array technique. The genes found were analyzed using the InteractiVenn virtual tool (http://www.interactivenn.net/) and grouped into a Microsoft Excel worksheet. Results: Of the 460 genes amplified in the studied samples, 287 (62.4%) were related only to CXPA, whereas 144 (31.3%) were related to residual PA. Twenty-nine (6.3%) of these genes were common between residual PA and CXPA. Regarding the degree of invasion of CXPA, there was an increase in the number of genes amplified as the degree of invasion and aggression increased: 8 genes related to intracapsular CXPA, 65 to minimally invasive CXPA, and 373 to weakly invasive. Moreover, when comparing residual AP and intracapsular CXPA, two genes were common to these groups: ERRB2 and GRB7. As for the histological subtype, the high-grade samples had more amplifications (320 amplified genes) than the low-grade ones (129 genes). Three of these genes were common among residual PAs and CXPA: HMGA2, RPSAP52, and LOC100129940. As for the replicates, MYNC, ERBB2, BRIP1, and HMGA2 were the most repeated amplified genes in the residual PAs. HMGA2, ERRBB2, CDK12, RPSAP52, LOC100129940, and LOC100507250 were the genes with the most replicates in CXPA. Conclusion HMGA2, ERRB2, and RPSAP52 may play a key role in PA carcinogenesis, whereas GRB7, CDK12, MYNC, and BRIP1 appear to act as coadjutants.

Analysis of the Expression of Genes Related to Lipidic and Glycogenic Metabolism in Pleomorphic Adenomas and Carcinomas Ex Pleomorphic Adenomas

Abstract Introduction The carcinoma ex pleomorphic adenoma (CXPA) arises from a pleomorphic adenoma (PA) and is supposed to gain lipogenesis and glycogenesis during its malignant transformation. Increased lipogenesis is a characteristic of cancer cells, consisting of increased fatty acid synthesis by the enzyme fatty acid synthase (FASN) and by the accumulation of cytoplasmic lipid droplets, which express adipophilin. The increase in glycolytic metabolism has been associated with the activity of glycolytic enzymes and glucose transporters (GLUTs), whose expression is induced by HIF-1 (inducing factor of hypoxia 1). Objectives To analyze the gene expression of FASN, adipophilin, HIF-1α, and GLUT-1 in PA and CXPA samples. Methodology Gene expression analysis of the FASN, adipophilin, HIF1-α, and GLUT-1 genes was performed by the real-time PCR (qPCR) method. Fourteen cases of PA and 14 cases of CXAP were evaluated. Results FASN, adipophilin, HIF-1α, and GLUT-1 were more expressed in CXAP than in AP, although there was no significant difference between levels of adipophilin expression in CXPA and PA. Conclusion Increased expression of FASN, HIF1-α, and GLUT-1 in CXAP may be associated with malignant transformation of PA, while additional studies are needed to understand the role of adipophilin in PA carcinogenesis. Moreover, this is the first study to investigate the role of these genes in the malignant transformation of PA.

A case of rapid progress of pulmonary pleomorphic carcinoma with ground glass nodules following solid metastasis in the right lung

A case of rapid progress of pulmonary pleomorphic carcinoma with ground glass nodules following solid metastasis in the right lung

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature

BackgroundPleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated. AimTo collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature. MethodsA multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed. ResultsA total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274). ConclusionsThe data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.

Abstract 3229: Radiation and chemotherapies result in increasing neoantigen intratumor heterogeneity and resistance to nivolumab in a patient with pleomorphic lung cancer

Abstract BACKGROUND:Immune checkpoint inhibitors (ICIs) have significantly changed the landscape of cancer treatment, but the response rate of non-small-cell lung carcinoma (NSCLC) to ICIs is less than 30%. Tumor mutational burden (TMB) is the most promising predictive biomarker for NSCLC immunotherapies. However, some NSCLC patients with high-TMB have little response to ICIs. The neoantigen intratumor heterogeneity (ITH), which determined by the ratio of subclonal neoantigen in the tumor, has been verified to be a potential therapeutic biomarker for immunotherapies in some cancer types. Pulmonary pleomorphic carcinoma, a rare subtype of pulmonary sarcomatoid carcinoma, has been shown to respond remarkably to ICIs, but the biomarkers for ICIs in pulmonary pleomorphic carcinoma have not been fully proven. CASE PRESENTATION:A 57 years old female pulmonary pleomorphic carcinoma patient, who underwent surgery, chemotherapy, anti-angiogenic therapy, radiotherapy, and anti-PD1 therapy, with disease relapse at the last, was included in this study. Primary and relapse tumor samples were collected for gene sequencing by a target sequencing panel which covered 811 cancer genes, during ICIs treatment. Peripheral bloods were collected for ctDNA and T cell receptor sequencing every two months. The results showed that the TMB (&amp;gt;10 muts/Mb) was high, but the clonal neoantigen load (1.33 neos/Mb) was low. The neoantigen ITH was increased after chemotherapy and radiotherapy with a score at nearly 0% in the primary tumor but increased to 85.72% in relapse tissues. The clonal neoantigen ratio detected by ctDNA was increased ~0.8 fold, while the high-frequency clonotypes of TCR to neoantigens dropped during ICIs treatment. CONCLUSIONS:Our results indicated that cytotoxic chemotherapy and radiotherapy can induce the subclonal neoantigens production and increase the neoantigen ITH, thus might negatively regulating patients’ response to ICIs therapy. These results highlight that the neoantigen ITH might be an important auxiliary to TMB in predicting patient response to immune therapies. More studies and clinical trials are needed to further validate these results. Citation Format: Xiaohua Hong, Yuting Liu, Yiying Liu, Yue Hu, Qifan Yang, Di Wu, Kai Zhang, Yongchao Li, Jinsong Yang, Jiaqian Wang, Jun Liu, Li Liu. Radiation and chemotherapies result in increasing neoantigen intratumor heterogeneity and resistance to nivolumab in a patient with pleomorphic lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3229.