Biopsy Of Liver Metastases Research Articles

Transcriptomic analysis of the tumor immune microenvironment (TIME) in patients with breast cancer with liver metastasis (BCLM).

e13045 Background: Breast cancer with liver metastasis (BCLM) is a significant predictor of worse prognosis and poor overall survival. Liver specific homing of breast cancer is not well understood, and the tumor immune microenvironment (TIME) likely plays a critical role in the process of forming BCLM. This retrospective study was conducted to determine the clinical risk factors and transcriptomic biomarkers associated with BCLM. Methods: A retrospective single institute chart review was conducted. Patient, disease characteristics and treatment variables were reviewed. Liver metastasis specific survival (defined by overall survival time from the diagnosis of liver metastasis) were compared across three breast subtypes (i.e., ER+/HER2-, HER2+, and triple-negative (TN) breast cancer) using Kaplan-Meier curves. Next generation sequencing (NGS) via commercial platforms were then used to obtain transcriptomic data. Transcriptomic analysis including differential gene expression analysis, gene set enrichment analysis (GSEA), as well as gene deconvolution analysis with TIMER2.0 were conducted for comparison of transcriptomic profiles and immune compositions across the three breast cancer subtypes. Results: 176 patients with BCLM and available liver metastasis biopsy were identified through retrospective chart review. Liver metastasis specific survival was compared, HER2+ BCLM patients (n = 17) had the best outcome and TN BCLM patients (n = 46) had the worst outcome with ER+ BCLM patients (n = 112) in the middle (p < 0.0001, ER+ vs TNBC p < 0.0001, ER+ vs HER2+ p = 0.038, HER2+ vs TNBC p = 0.00011). Principle component analysis on the transcriptomic data of 30 liver metastatic samples revealed different expression profiles between ER+ (n = 20) and TN (n = 7) BCLM, while HER2+ (n = 3) BCLM did not shown statistical differences with either group. B cell mediated immunity was upregulated in TN BCLM compared to ER+HER2- BCLM by GSEA (normalized enrichment score = 2.35, adjusted P-value = 0.19). Consistently, plasma cells were relatively enriched in TN BCLM compared to ER+ and HER2+ BCLM (p = 0.037) based on CIBERSORT estimation. In contrast, monocytes and neutrophils were enriched in ER+ BCLM (p = 0.0093 & 0.018) based on TIMER2.0 estimation. Additional NGS analysis is currently underway for increased sample size. Conclusions: BCLM in TNBC was associated with significantly worse overall survival. TIME in TN BCLM enriched for genes associated with B cell mediated immunity while ER+ BCLM had more monocyte/neutrophil mediated immunity.

Pancreatic cancer with multiple liver metastasis complicating multi organ infarcts from Marantic endocarditis and Trousseau’s syndrome

Background: Marantic endocarditis and Trousseau’s syndrome are historically linked with pancreatic cancer. The patient had catastrophic embolic events which caused multi organ infarct due to underlying advanced pancreatic cancer. Doctors should be aware of early signs and symptoms of pancreatic cancer and conduct necessary clinical assessments and investigations that can prevent any severe complications. Case Presentation: A middle-aged healthy gentleman who presented with left-sided weakness, slurred speech, left-sided sensory neglect, mild headache, and fever. CT head showed acute right-sided temporal ischemic changes with subsequent magnetic resonance imaging (MRI) head showed multiple infarcts in the brain. A transesophageal echocardiogram reported possible MV vegetation. MRI of the liver was done due to deranged LFTs which showed multiple liver metastasis with a primary mass in the tail of the pancreas. Left leg ultrasound Doppler showed a large left leg deep vein thrombosis involving the femoral vein as he complained of left leg pain for 2 months and went to GP with right leg pain 3 months ago which was treated as a right ankle sprain. The clinical events explained that most likely he developed Trousseau’s syndrome 3 months ago and the embolic phenomena were due to rare Marantic endocarditis (Non-bacterial thrombotic endocarditis) secondary to pancreatic cancer. Ultrasound-guided biopsy of liver metastasis was planned, but sadly the patient passed away the next day. Conclusion: The diagnosis of early pancreatic cancer with imaging poses a challenge sometimes, therefore the pancreatic protocol of CT or MRI is the first line of investigation. Moreover, the cause of unprovoked thrombo-embolism should be investigated to rule out any underlying malignancy.

Pancreatic cancer with multiple liver metastasis complicating multi organ infarcts from Marantic endocarditis and Trousseau’s syndrome.

Background Marantic endocarditis and Trousseau’s syndrome are historically linked with pancreatic cancer. The patient had catastrophic embolic events which caused multi organ infarct due to underlying advanced pancreatic cancer. Doctors should be aware of early signs and symptoms of pancreatic cancer and conduct necessary clinical assessment and investigations which can prevent any severe complications. Case presentation A middle-aged healthy gentleman who presented with left sided weakness, slurred speech, left sided sensory neglect, mild headache and fever. CT head showed acute right sided temporal ischaemic changes with subsequent MRI head showed multiple infarcts in the brain. Transoesophageal echocardiogram reported possible MV vegetation. MRI of the liver was done due to deranged LFTs which showed multiple liver metastasis with primary mass in the tail of pancreas. Left leg ultrasound doppler showed a large left leg deep vein thrombosis involving femoral vein as he complained of left leg pain for 2 months and went to GP with right leg pain 3 months ago which was treated as right ankle sprain. The clinical events explained that most likely he developed Trousseau's syndrome 3 months ago and the embolic phenomena was due to rare Marantic endocarditis (Non-bacterial thrombotic endocarditis) secondary to pancreatic cancer. Ultrasound guided biopsy of liver metastasis was planned, but sadly the patient passed away the next day. Conclusion The diagnosis of early pancreatic cancer with imaging poses a challenge sometimes, therefore the pancreatic protocol of CT or MRI is the first line investigation. Moreover, the cause of unprovoked thrombo-embolism should be investigated to rule out any underlying malignancy.

Fibroblast inhibition by tocilizumab enabled gemcitabine/nab-paclitaxel rechallenge for pancreatic cancer.

Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC). We sought to determine the safety and recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with gemcitabine (GEM)/nanoparticle albumin-bound paclitaxel (nab-PTX)-refractory MPC. This phase 1 study enrolled 10 patients with MPC who had progressed after GEM/nab-PTX. Patients initially received TCZ 8 mg/kg on Day 1 and nab-PTX 100 mg/m2 + GEM 750 mg/m2 on Days 2, 9, and 16. Before and at the end of Cycle 1, biopsy of liver metastases was performed 3-5 h after levofloxacin (LVFX) administration to measure LVFX infiltration into tumor tissue. No dose-limited toxicities occurred, and the recommended dosage of TCZ was determined to be 8 mg/kg. Treatment-emergent adverse events occurred in 80% of patients, of which decreased neutrophil count was the most common. Tumor reduction during Cycle 1 was observed in four patients, who were defined as responders. In paired-biopsy samples, responder-related biological activities were an increase of cleaved PARP expression of tumor nuclei (p = 0.01), a decrease of proliferative cancer-associated fibroblasts (CAFs) (p = 0.08), and an increase of LVFX infiltration in the tumor (p = 0.04). A decrease of phosphorylated STAT3 expression (p = 0.02) favored an increase in LVFX infiltration. In conclusion, TCZ + GEM/nab-PTX-rechallenge had a manageable safety profile and showed preliminary activity via inhibition of CAF and improved intratumoral drug infiltration in MPC.

Abstract CT565: Clinical and translational results of a phase I study, tocilizumab plus gemcitabine/nab-paclitaxel in patient with gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer

Abstract Background: Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC) refractory to gemcitabine + nab-paclitaxel (GN) due to suppression of cancer associated fibroblast (CAF) and increase of drug infiltration in tumor. We sought to determine the safety, recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with GN-refractory MPC. Methods: This phase 1, dose finding trial was conducted following preclinical study of IL-6 signaling blockade in genetically engineered mouse model of pancreatic cancer (pGEMM) and patients-derived CAF, enrolled 10 patients with MPC that had progressed after GN. During the dose-finding part to determine dose-limiting toxicity (DLT), patients initially received TCZ 8 mg/kg on Day 1 and nab-paclitaxel 100 mg/m2 + gemcitabine 750 mg/m2 on Days 2, 9, and 16. The subsequent dose-expansion part used the TCZ dose identified in the dose-finding study. Before Cycle 1 and at the end of Cycle 1, biopsy of liver metastasis was performed 3 to 5 hours after levofloxacin (LVXF) administration to measure LVFX infiltration in tumor using matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). Results: In pGEMM tumor, mouse IL-6 receptor antibody plus GN led pathological response. The growth of CAFs from patients with pancreatic cancer was inhibited by TCZ. In this phase I study, no DLTs occurred and the recommended dosage of TCZ was determined to be 8 mg/kg. Treatment-emergent adverse events (TEAEs) occurred in 80% of patients (Grade ≥3 in 60%) with decreased neutrophil count (n=5, 7 events) being the most common TEAE. Disease control rate was 80·0% (95%CI: 44·4-97·5) and tumor reduction during cycle 1 was observed in 4 patients who were defined as responder. In paired-biopsied samples, decrease of phosphorylated (p) STAT3 expression in tumor was observed in 7 of 8 patients (88%). Responder-related biological activities were increase of cleaved PARP expression of tumor nuclei (P = 0.01), decrease of proliferative CAF (P = 0.08), and increase of LVFX infiltration in tumor (P = 0.04). Decrease of pSTAT3 expression (P = 0.02) was favor to increase of LVFX infiltration against increase of gamma-H2AX, an index of gemcitabine exposure (P = 0.20). Conclusion: TCZ+GN-rechallenge had a manageable safety profile and showed preliminary activity via inhibition of CAF and gain of intratumoral drug infiltration in MPC. Citation Format: Shuichi Mitsunaga, Masafumi Ikeda, Kazunori Aoki, Kyoko Yamaguchi, Noriaki Sawada, Etsuko Fujii, Masanobu Nishidate, Takashi Fujitomo, Hideaki Mizuno, Yoko Kayukawa, Atsuhiko Kato, Mayu Makikawa, Hiroshi Imaoka, Mitsuhito Sasaki, Kazuo Watanabe, Hiroyuki Tsunoda, Kimio Terao, Atsushi Ochiai. Clinical and translational results of a phase I study, tocilizumab plus gemcitabine/nab-paclitaxel in patient with gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT565.

Abstract 6145: Increased PD-L1 expression levels were observed on both tumor cells and macrophages by tocilizumab plus gemcitabine/nab-paclitaxel treatment in gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer patients

Abstract Background: Blockade of interlukine-6 (IL-6) and programmed death-1-ligand 1 (PD-L1) limits tumour progression in murine models of pancreatic cancer. When PD-L1 expression of metastatic pancreatic cancer (MPC) is increased under the influence of gemcitabine exposure plus IL-6 inhibition, the spectrum of benefit from immune checkpoint blockade may expand to MPC patients with combined blockade of IL-6 and PD-L1 plus gemcitabine-based chemotherapy. We sought to determine PD-L1 expression of liver metastasis during cycle 1 of a phase I study, tocilizumab (TCZ) plus gemcitabine/nab-paclitaxel (GN) in patient with GN-refractory MPC. Methods: This phase 1 study enrolled 10 patients with MPC that had progressed after GN. All patients experienced cycle 1 of TCZ plus GN, TCZ 8 mg/kg on Day 1 and nab-paclitaxel 100 mg/m2 + gemcitabine 750 mg/m2 on Days 2, 9, and 16. Biopsy of liver metastasis was performed before Cycle 1 and at the end of Cycle 1. Tumour microenvironment including PD-L1 expression were evaluated in paired-biopsied specimen from 7 patients by multicolour immunofluorescence staining. Tumour cell and PD-L1 expression were labelled by anti-cytokeratin 19 antibody and anti-PD-L1 antibody clone SP263, respectively. Cell numbers per millimetre squared (cell density) and the percentage of PD-L1 positive cell in tumor area were calculated according to cell types including tumour cell as cytokeratin 19 positive cell and macrophage as CD68 positive cell. Results: Cell density and the percentage of PD-L1 positive tumor cell were 29/mm2 and 1.1% in mean at baseline and tended to be increased up to 142/mm2 (P = 0.11) and 5.2% (P = 0.06) at the end of cycle 1. Means of PD-L1 positive macrophages were 28/mm2 and 6.9% at baseline and were increased to 69/mm2 (P = 0.01) and 14% (P = 0.08). When region of interest was selected from tumor stroma, differences of PD-L1 positive macrophage during cycle 1 was also maintained in cell density (P = 0.02) and the percentage of PD-L1 positive cell (P = 0.06). Conclusion: TCZ+GN induced an increase of PD-L1 expression levels on tumor cell and macrophages. Citation Format: Kyoko Yamaguchi, Etsuko Fujii, Shuichi Mitsunaga, Noriaki Sawada, Masafumi Ikeda, Takashi Fujitomo, Hideaki Mizuno, Yoko Kayukawa, Mayu Makikawa, Kazunori Aoki, Hiroshi Imaoka, Mitsuhito Sasaki, Kazuo Watanabe, Atsukiko Kato, Hiroyuki Tsunoda, Kimio Terao, Atsushi Ochiai. Increased PD-L1 expression levels were observed on both tumor cells and macrophages by tocilizumab plus gemcitabine/nab-paclitaxel treatment in gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6145.

Analyzing the Estrogen Receptor Status of Liver Metastases with [18F]-FES-PET in Patients with Breast Cancer.

Background: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. Methods: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER− metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. Conclusion: In the majority of liver metastases, ER status can be determined with [18F]-FES-PET if background correction and separate thresholds are applied.

DNA methylation profiling demonstrates superior diagnostic classification to RNA-sequencing in a case of metastatic meningioma

Meningiomas are the most common primary intracranial tumors, but meningioma metastases are rare. Accordingly, the clinical workup, diagnostic testing, and molecular classification of metastatic meningioma is incompletely understood. Here, we present a case report of multiply recurrent meningioma complicated by liver metastasis. We discuss the patient presentation, imaging findings, and conventional histopathologic characterization of both the intracranial lesion and the metastatic focus. Further, we perform multiplatform molecular profiling, comprised of DNA methylation arrays and RNA-sequencing, of six stereotactically-guided samples from the intracranial meningioma and a single ultrasound-guided liver metastasis biopsy. Our results show that DNA methylation clusters distinguish the liver metastasis from the intracranial meningioma samples, and identify a small focus of hepatocyte contamination with the liver biopsy. Nonetheless, DNA methylation-based classification accurately identifies the liver metastasis as a meningioma with high confidence. We also find that clustering of RNA-sequencing results distinguishes the liver metastasis from the intracranial meningiomas samples, but that differential gene expression classification is confounded by hepatocyte-specific gene expression programs in the liver metastasis. In sum, this case report sheds light on the comparative biology of intracranial and metastatic meningioma. Furthermore, our results support methylation-based classification as a robust method of diagnosing metastatic lesions, underscore the broad utility of DNA methylation array profiling in diagnostic pathology, and caution against the routine use of bulk RNA-sequencing for identifying tumor signatures in heterogeneous metastatic lesions.

Clinical Significance and Problems of Percutaneous Biopsy of Liver Metastasis in Patients with Breast Cancer

Clinical Significance and Problems of Percutaneous Biopsy of Liver Metastasis in Patients with Breast Cancer

Indolent evolution of a distal pancreatic adenocarcinoma with central osseous metaplasia managed by multivisceral resection, excisional biopsy of liver metastasis and adjuvant chemotherapy

Indolent evolution of a distal pancreatic adenocarcinoma with central osseous metaplasia managed by multivisceral resection, excisional biopsy of liver metastasis and adjuvant chemotherapy

Usefulness of contrast-enhanced endoscopic ultrasonography for diagnosis of pancreatic tumors

Background and Objectives:Contrast-enhanced endoscopic ultrasonography (CE-EUS) is noninvasive and can evaluate pancreatic tumors in detail. We investigated the usefulness of CE-EUS for diagnosis of pancreatic tumors.Methods:CE-EUS was performed for consecutive patients having a pancreatic solid lesion, and tumors were classified into three vascular patterns (hypervascular, isovascular, and hypovascular) at two time phases (early phase and late phase). Correlation between vascular patterns and histopathology of pancreatic tumors was ascertained.Results:The final diagnoses of 235 tumors histopathologically examined by surgery, EUS-guided fine needle aspiration (EUS-FNA), or biopsy of liver metastases were pancreatic cancer (PC) (n = 179), inflammatory mass (n = 12), autoimmune pancreatitis (n = 11), neuroendocrine tumor (n = 15), and others (n = 18). In late-phase images, 162 of 179 PCs had hypovascular pattern, for a diagnostic sensitivity, specificity, and accuracy of 91%, 68%, and 85%, respectively. In PCs, cases in which the contrast effect changed from early phase to late phase were seen in 80.7%, and this rate was significantly higher than others (P = 0.007). Hypervascular pattern was seen in five cases, and all of them were neuroendocrine tumor.Conclusion:CE-EUS could be useful for distinguishing PCs from other solid pancreatic lesions.

Complete remission through icotinib treatment in Non-small cell lung cancer epidermal growth factor receptor mutation patient with brain metastasis: A case report.

Brain metastasis (BM) has been universally recognized as a poor prognostic factor in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown efficacy in treating BM with an EGFR mutation. This paper reports a case of BM patient with EGFR-mutated NSCLC. According to the findings, a complete remission (CR) of the BM was achieved by icotinib treatment without conducting a radiotherapy, which was followed by a resection of the primary lung cancer lesion and lymph nodes. After one-year follow-up, the disease progressed to liver metastasis and liver lesion biopsy showed a T790M mutation. The patient responded well to the combination treatment of AZD9291 and icotinib after the failure of transcatheter arterial chemoembolization (TACE). This case report suggests that icotinib has a sustainable anticancer response to BM and the combination with icotinib and AZD9291 is effective for liver metastasis with T790M.

Seeding after ultrasound-guided percutaneous biopsy of liver metastases in patients with colorectal or breast cancer

Background: Neoplasm seeding is a serious complication after liver metastases biopsy. Reported incidences vary between 10% and 19% for colorectal cancer (CRC) and are unknown for breast cancer (BC). The aim of this retrospective study was to determine the frequency of tumor seeding after ultrasound-guided percutaneous biopsy of CRC and BC liver metastases.Material and methods: Unselected liver biopsies performed in the period of 2005–2012 at our institution were extracted from the National Pathology Registry. Medical records including imaging from patients with biopsy-verified BC and CRC liver metastases were retrospectively reviewed. The endpoint was the development of abdominal wall recurrence following liver biopsy.Results: Of total 2981 biopsies we identified 278 patients with CRC and 155 patients with BC biopsy-verified liver metastases. During the median follow-up of 25 months after biopsy (range 3–253 months), no seeding was recorded in patients with BC. Within the median follow-up of 34 months (3–111 months), seeding was registered in 17/278 (6%) of patients with CRC; three patients of 278 (1%) had undoubtedly biopsy-related seeding, which became apparent six, nine, and 26 months after biopsy, respectively; and in nine patients (3%) seeding occurred due to either biopsy or other interventions; and five patients had seeding, which were assessed as a consequence of other invasive procedures than biopsies. The median overall survival of the 17 patients with seeding was 70 months compared to 39 months of patients without seeding.Conclusions: The results showed no seeding in BC patients. Seeding rate after biopsy in CRC patients is not negligible, however, without affecting outcome.

Abstract 5233: Prediction and response evaluation of EGFR blockade for colorectal cancer by using circulating cell-free DNA

Abstract Aim: In 10% of metastatic colorectal cancer patients, discordance of KRAS mutational status between primary tumor and metastatic tumor is observed. However biopsy of liver or lung metastasis is invasive and risky. Liquid biopsy (LB) is a new method of molecular diagnosis using circulating tumor DNA in peripheral blood. Here, we evaluated KRAS mutations using LB as a biomarker to predict the efficacy of EGFR blockade and observed concentration variability of ccfDNA by chemotherapy. Methods: We enrolled 44 colorectal cancer patients (14 KRAS mutant and 30 KRAS wild in primary tumors) with distant metastases. Circulating cell-free DNA (ccfDNA) was purified from 1 mL serum using the QIAamp Circulating Nucleic Acid Kit. We quantitated the concentration of ccfDNA and detected nine KRAS (G12A, G12R, G12D, G12C, G12S, G12V, G13D, Q61H, and Q61R) mutations. We administered EGFR blockade to 13 patients with KRAS wild in their primary tumor as the first line chemotherapy, and used computed tomography 3 months after starting EGFR blockade therapy to evaluate its effect. The study protocol was approved by the Ethics Review Committee of our institution. Written informed consent was obtained from each patient. Results: KRAS mutations in ccfDNA were detected in 85% (12/14) of patients with KRAS mutation in their primary tumor but in 10% (3/30) of patients without KRAS mutations in their primary tumors. In one of the 3 patients, primary tumor had wild KRAS but metastatic liver tumor and ccfDNA was mutated KRAS. We administered EGFR blockade to 13 patients. Twelve patients with KRAS wild in ccfDNA had a good clinical response (1CR and 12PR). One patient with KRAS mutation (G13D) in ccfDNA had no response. In majority of metastatic colorectal cancer patients, concentration of ccfDNA is more than 1000ng/ml. After curative resection, concentration of ccfDNA is less than 100ng/ml in non-metastatic colorectal cancer patients. In chemotherapy effective cases, the concentration of ccfDNA decreased immediately after administration, but the concentration of ccfDNA did not decrease in non-effective case. In our CR case, ccfDNA did not disappear (minimum 180ng/ml) while CR was continuing and new metastatic liver tumor appeared 28 weeks after detection of ccfDNA marked increasing. Conclusions: LB detection of KRAS mutations is less-invasive and repeatable compared with current techniques and may be useful for prediction of EGFR blockade. The concentration of ccfDNA decreased immediately in objective response case that is administered EGFR blockade. Conversely, the concentration of ccfDNA increased before imaging detection of disease progression. Citation Format: Takuma Iwai, Takeshi Yamada, Hatato Kan, Michihiro Koizumi, Seiichi Shinji, Goro Takahashi, Atushi Watanabe, Satoshi Matumoto, Akihisa Matuda, Aya Yamagishi, Yasuyuki Yokoyama, Eiji Uchida. Prediction and response evaluation of EGFR blockade for colorectal cancer by using circulating cell-free DNA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5233. doi:10.1158/1538-7445.AM2015-5233

Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics?

BackgroundAssessment of the pathological characteristics of pancreatic neuroendocrine tumours is crucial for appropriate management. We compared preoperative pathological data with surgical specimens for accuracy. MethodsSurgical patients with pancreatic neuroendocrine tumours who underwent preoperative endoscopic ultrasound-guided fine needle aspiration of the primary tumour or biopsy of liver metastasis were retrospectively included. Tumour differentiation and the Ki67 proliferation index on biopsies were compared with pancreatic specimens. ResultsFifty-seven patients were included. A preoperative biopsy of the primary tumour or of a liver metastasis was obtained in 48 and 9 patients respectively. Tumour differentiation was high in 98%, and poor in 2% on biopsy and high in 100% of surgical specimens. Ki67 index values were 0 (0–19) and 2 (0–15) on biopsy and surgical specimens (p=0.01). Correlation between preoperative and surgical findings was stronger for liver (r=0.62, p=0.001) than for pancreas (r=0.23, p=0.11). Correlation for pancreas varied according to the tumour pattern: solid (r=0.24, p=0.16), mixed (r=0.91, p=0.0036) or cystic (r=0.04, p=0.89). Tumour grade was different between pancreatic biopsies and surgical specimens, for grade 1 (63% vs 37%) and grade 2 (28% vs 72%), p=0.0007. ConclusionsTumour grade assessment is accurate in biopsies of liver metastases of pancreatic neuroendocrine tumours, while pancreatic fine-needle aspiration biopsies are less accurate.

Primeri bilinmeyen karaciğer metastazlarında ince iğne aspirasyon biyopsi sonuçlarının değerlendirilmesi

Background and Aims: Five percent of all cancers in patients are unknown primary carcinoma, and 33% of the patients with unknown primary carcinoma have liver metastasis. Thus, the histopathological diagnosis is important. The aim of this study was to evaluate the histopathological data with liver metastasis retrospectively. Materials and Methods: Fifty-eight patients (40 males, 18 females) with unknown liver mass who were hospitalized in Celal Bayar University Faculty of Medicine, Gastroenterology Department between January 2000 and August 2009 were reviewed retrospectively. The biopsy was taken by Tru-cut technique with 18G X 200mm-22mm needle guided by ultrasonography. The mean age of the 58 patients was 63.05 (32-86) years. Age, sex, histopathological/cytological diagnoses, and primary focus of the malignancy, if found, were evaluated. Results: The histopathological spectrum of liver metastasis included: 43 (72%) adenocarcinomas, 4 (6.8%) small cell carcinomas, 4 (6.8%) indifferent tumors, and 3 (5.2%) neuroendocrine tumors. Primary focus of malignancy was found in 43.1% of patients as: 60% colon, 16% pancreas and 12% stomach and gallbladder. Conclusions: Fine-needle aspiration biopsy of liver metastasis is a method used in determining histopathology.

Seeding after biopsy of liver metastases in patients with primary colorectal and breast cancer.

e14545 Background: Seeding is a potential complication after liver metastases biopsy. Incidences reported in the sparse literature vary between 10-19% for colorectal cancer (CRC) and are unknown fo...

A phase I study of EpCAM/CD3-bispecific antibody (MT110) in patients with advanced solid tumors.

2504 Background: MT110 is a bispecific T cell engaging antibody construct (BiTE) that directs CD3 expressing T cells to kill target cells that express EpCAM, which is widely found on solid tumors. Methods: Safety, tolerability, pharmacokinetics and anti-tumor activity of MT110 in patients (pts) with advanced solid tumors were studied using a 3+3 design. Continuous IV infusions for at least 28 days of doses ranging from 1 to 48 µg/d have been tested. Stepwise intra-patient dose escalations within cycle 1 or at start of cycle 2 have been explored. Results: 51 pts (6 gastric cancers, 32 CRC, 2 SCLC, 5 NSCLC, 3 HRPC, 1 ovarian cancer) have been treated in 12 dose cohorts. The maximally administered dose includes day 1 dose of 3 µg/d escalated up to 48 µg/d. The maximum tolerable dose (MTD) has not yet been established. Diarrhea and elevations in liver function tests have been reported as dose limiting toxicity (DLT) for individual patients. Transaminase elevations were fully reversible and mitigated by dexamethasone at initiation or escalation of dose. Other adverse events of grade 3 or higher included transient lymphopenia, increase in lipase or amylase, nausea, vomiting, and hypoalbuminaemia. No CNS safety signal was observed. The mean serum half-life of MT110 was 4.5 hours. Mean steady state serum concentrations of MT110 were linear with dose across treatment cycles. At 48 µg/d, the mean Css was 3.2 ng/mL. This compares to preclinical EC90 of 1.35 – 3.85 ng/ml in CRC cell lines. Sixteen pts who received a dose of ≥ 24 µg/d were evaluable for anti-tumor response. Best response of SD was reported in 38%; median duration was 155 days (95% CI 92; 161). Anti-tumor activity was demonstrated on biopsy of liver metastases in one patient. Following at least 1 week of MT110 treatment at 48 µg/d, a decrease in circulating tumor cells was observed with a median nadir 74% below baseline. Conclusions: The use of stepwise dose escalation and concomitant dexamethasone resulted in improved tolerability. A dose of 48 µg/d appears tolerable. Tumor biopsy evaluation on treatment and pharmacodynamic evidence of anti-tumor activity are encouraging. Additional dose cohorts will seek to identify the recommended phase II dose and further evidence of anti-tumor activity.

A fatal event in a patient receiving Ipilimumab for metastasic melanoma: causality analyses

BackgroundIpilimumab has been approved to treat patients with late-stage melanoma and it has been associated with potentially fatal immunological adverse effects due to T cell activation and proliferation.PurposeTo analyse the...

Biopsy of liver metastasis for women with breast cancer: Impact on survival

BackgroundBiopsy of metastatic site of disease can influence treatment decisions, but its impact on survival remains uncertain. Patients and methodsOne-hundred patients with first metachronous liver metastases (LM) from breast cancer (BC) who underwent liver biopsy between 1999 and 2009 were identified. One-hundred matched control patients with LM from BC and no biopsy were selected. ResultsLiver biopsy had no statistically significant impact on survival when comparing biopsied patients to controls [HR 0.82 (95% CI 0.58–1.16)]. Patients with early metastasis (within 3 years) undergoing liver biopsy had a better survival [HR 0.60 (95% CI 0.38–0.97)] compared to those who did not. Liver biopsy had no statistically significant impact on survival in patients with late LM (after 3 years) [HR 1.09 (95% CI 0.69–1.74)]. We observed that 18 out of 100 biopsied patients (18.0%) had a conversion of predictive factors which allowed adjusting for therapy, specifically new expression of ER (n=5), overexpression of HER2 (n=12) or both (n=1). Fourteen out of 18 (77.8%) received anti-HER2 treatment for the first time at the time of metastasis and 3 others (16.7%) received hormone therapy. Those 18 patients showed a better survival compared to the other 82 biopsied patients [HR 0.55 (95% CI 0.28–1.10)] and compared to the 13 biopsied patients with disappearance of features which predicted responsiveness to a given treatment [HR 0.19 (95% CI 0.06–0.62)]. ConclusionsLiver biopsy can impact survival of patients with early metastases from BC. Discordance between primary and distant lesions can offer the patients new treatment options.