Full Text Journal Articles by
Author Anthony F Shields

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Molecular profile of BRCA-mutated biliary tract cancers.

Gilbert Spizzo, Alberto Puccini, Joanne Xiu, Richard M Goldberg, Axel Grothey, Anthony F Shields, Sukeshi Patel Arora, Moh'd Khushmann, Mohamed E Salem, Francesca Battaglin, Yasmine Baca, Wafik S El-Deiry, Philip A Philip, Madiha Nassem, Michael Hall, John L Marshall, Florian Kocher, Arno Amann, Dominik Wolf, W Michael Korn, Heinz Lenz, Andreas Seeber,

INTRODUCTION:Prognosis of biliary tract cancers (BTC) remains dismal and novel treatment strategies are needed to improve survival. BRCA mutations are known to occur in BTC but their frequency and the molecular landscape in which they are observed in distinct sites of BTC remain unknown. MATERIAL AND METHODS:Tumour samples from 1292 ... Read more >>

ESMO Open (ESMO open)
[2020, 5(3):]

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Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors.

Mohamed E Salem, J Nicholas Bodor, Alberto Puccini, Joanne Xiu, Richard M Goldberg, Axel Grothey, W Michael Korn, Anthony F Shields, William M Worrilow, Edward S Kim, Heinz-Josef Lenz, John L Marshall, Michael J Hall,

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in ... Read more >>

Int. J. Cancer (International journal of cancer)
[2020, :]

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WRN-Mutated Colorectal Cancer Is Characterized by a Distinct Genetic Phenotype.

Kai Zimmer, Alberto Puccini, Joanne Xiu, Yasmine Baca, Gilbert Spizzo, Heinz-Josef Lenz, Francesca Battaglin, Richard M Goldberg, Axel Grothey, Anthony F Shields, Mohamed E Salem, John L Marshall, W Michael Korn, Dominik Wolf, Florian Kocher, Andreas Seeber,

Werner syndrome gene (WRN) contributes to DNA repair. In cancer, WRN mutations (WRN-mut) lead to genomic instability. Thus, WRN is a promising target in cancers with microsatellite instability (MSI). We assessed this study to investigate the molecular profile of WRN-mut in colorectal cancer (CRC). Tumor samples were analyzed using next-generation ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(5):]

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Contribution of Immunoscore and Molecular Features to Survival Prediction in Stage III Colon Cancer.

Frank A Sinicrope, Qian Shi, Fabienne Hermitte, Tyler J Zemla, Bernhard Mlecnik, Al B Benson, Sharlene Gill, Richard M Goldberg, Morton S Kahlenberg, Suresh G Nair, Anthony F Shields, Thomas C Smyrk, Jerome Galon, Steven R Alberts,

Background:The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. Methods:Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 ... Read more >>

JNCI Cancer Spectr (JNCI cancer spectrum)
[2020, 4(3):pkaa023]

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Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.

Matthew K Stein, Forrest W Williard, Joanne Xiu, Miriam W Tsao, Michael G Martin, Benjamin W Deschner, Paxton V Dickson, Evan S Glazer, Danny Yakoub, David Shibata, Axel F Grothey, Philip A Philip, Jimmy J Hwang, Anthony F Shields, John L Marshall, W Michael Korn, Heinz-Josef Lenz, Jeremiah L Deneve,

BACKGROUND AND OBJECTIVES:Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined. METHODS:We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational ... Read more >>

J Surg Oncol (Journal of surgical oncology)
[2020, 121(8):1320-1328]

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Patterns and genomic correlates of PD-L1 expression in patients with biliary tract cancers.

Kabir Mody, Jason Starr, Michelle Saul, Kelsey Poorman, Benjamin A Weinberg, Mohamed E Salem, Ari VanderWalde, Anthony F Shields,

Background:Patients with biliary tract cancer (BTC) have a dismal prognosis and limited treatment options. Given the potential for immunotherapy in patients with BTC, we studied the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) and evaluated for associated genetic alterations in patients with BTC. Methods:By immunohistochemistry (IHC), PD-L1 (SP142 antibody; ... Read more >>

J Gastrointest Oncol (Journal of gastrointestinal oncology)
[2019, 10(6):1099-1109]

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Molecular Analyses of Left- and Right-Sided Tumors in Adolescents and Young Adults with Colorectal Cancer.

Mohamed E Salem, Francesca Battaglin, Richard M Goldberg, Alberto Puccini, Anthony F Shields, David Arguello, W Michael Korn, John L Marshall, Axel Grothey, Heinz-Josef Lenz,

BACKGROUND:The incidence of colorectal cancer (CRC), particularly left-sided tumors (LT), in adolescents and young adults (AYA) is rising. Epigenetic events appear to play an important role in tumorigenesis and cancer progression, especially in younger patients. We compared molecular features of LT to right-sided tumors (RT) in AYA. MATERIALS AND METHODS:A ... Read more >>

Oncologist (The oncologist)
[2020, 25(5):404-413]

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Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets.

Benjamin A Weinberg, Joanne Xiu, Michael R Lindberg, Anthony F Shields, Jimmy J Hwang, Kelsey Poorman, Mohamed E Salem, Michael J Pishvaian, Randall F Holcombe, John L Marshall, Michael A Morse,

Background:Biliary tract cancers (BTCs) are a heterogeneous group of aggressive, rare malignancies with limited standard chemotherapeutic options for advanced disease. Recent studies have demonstrated potential novel biliary cancer targets and a possible role for immunotherapy in the treatment of patients with this disease. Intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and ... Read more >>

J Gastrointest Oncol (Journal of gastrointestinal oncology)
[2019, 10(4):652-662]

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The current state of molecular testing in the treatment of patients with solid tumors, 2019.

Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall,

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor ... Read more >>

CA Cancer J Clin (CA: a cancer journal for clinicians)
[2019, 69(4):305-343]

Cited: 2 times

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Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma With the Introduction of New Chemotherapeutic Drugs: 10-Year Experience of a Single NCI-designated Comprehensive Cancer Center.

Kevin J Zhang, Greg Dyson, Joshua L Gatz, Michael E Silverman, Anteneh A Tesfaye, Anthony F Shields, Philip A Philip,

OBJECTIVES:Adenocarcinoma of the pancreas represents the third leading cause of cancer-related death in the United States. Drug combinations, FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel, showed a clinically meaningful benefit when compared with single-agent gemcitabine in phase III trials. The goal of this study was to investigate whether there ... Read more >>

Am. J. Clin. Oncol. (American journal of clinical oncology)
[2019, 42(3):243-246]

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The use of 3'-deoxy-3'-18F-fluorothymidine (FLT) PET in the assessment of long-term survival in breast cancer patients treated with neoadjuvant chemotherapy.

Benjamin E Ueberroth, Jawana M Lawhorn-Crews, Lance K Heilbrun, Daryn W Smith, Janice Akoury, Rouba Ali-Fehmi, Nicole T Eiseler, Anthony F Shields,

OBJECTIVE:To assess the role of serial FLT-PET scans during early neoadjuvant treatment as a prognostic marker of response to treatment and survival. METHODS:This study is a prospective cohort study which draws from a larger original study which examined the utility of FLT-PET imaging across multiple cancers. Our cohort consisted of ... Read more >>

Ann Nucl Med (Annals of nuclear medicine)
[2019, 33(6):383-393]

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Phase IB/II Randomized Study of FOLFIRINOX Plus Pegylated Recombinant Human Hyaluronidase Versus FOLFIRINOX Alone in Patients With Metastatic Pancreatic Adenocarcinoma: SWOG S1313.

Ramesh K Ramanathan, Shannon L McDonough, Philip A Philip, Sunil R Hingorani, Jill Lacy, Jeremy S Kortmansky, Jaykumar Thumar, E Gabriela Chiorean, Anthony F Shields, Deepti Behl, Paul T Mehan, Rakesh Gaur, Tara Seery, Katherine A Guthrie, Howard S Hochster,

PURPOSE:Pegylated recombinant human hyaluronidase (PEGPH20) degrades hyaluronan (HA) and, in combination with chemotherapy, prolongs survival in preclinical models. The activity of PEGPH20 with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) was evaluated in patients with metastatic pancreatic cancer (mPC). MATERIALS AND METHODS:Patients had untreated mPC, a performance status of 0 ... Read more >>

J. Clin. Oncol. (Journal of clinical oncology : official journal of the American Society of Clinical Oncology)
[2019, 37(13):1062-1069]

Cited: 5 times

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Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer.

Ryuma Tokunaga, Joanne Xiu, Curtis Johnston, Richard M Goldberg, Philip A Philip, Andreas Seeber, Madiha Naseem, Jae Ho Lo, Hiroyuki Arai, Francesca Battaglin, Alberto Puccini, Martin D Berger, Shivani Soni, Wu Zhang, Jimmy J Hwang, Anthony F Shields, John L Marshall, Hideo Baba, W Michael Korn, Heinz-Josef Lenz,

PURPOSE:The natural history and prognosis of appendiceal adenocarcinomas differ from those of adenocarcinomas arising in other large bowel sites. We aimed to compare the molecular profiles exhibited by appendiceal adenocarcinomas and colorectal cancers, or between the histopathologic subtypes of appendiceal adenocarcinoma. EXPERIMENTAL DESIGN:A total of 183 samples from appendiceal adenocarcinoma ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2019, 25(10):3096-3103]

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Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer.

Ulka N Vaishampayan, Izabela Podgorski, Lance K Heilbrun, Jawana M Lawhorn-Crews, Kimberlee C Dobson, Julie Boerner, Karri Stark, Daryn W Smith, Elisabeth I Heath, Joseph A Fontana, Anthony F Shields,

PURPOSE:Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2019, 25(2):652-662]

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Safety and pharmacokinetics of MM-302, a HER2-targeted antibody-liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study.

Pamela Munster, Ian E Krop, Patricia LoRusso, Cynthia Ma, Barry A Siegel, Anthony F Shields, István Molnár, Thomas J Wickham, Joseph Reynolds, Karen Campbell, Bart S Hendriks, Bambang S Adiwijaya, Elena Geretti, Victor Moyo, Kathy D Miller,

BACKGROUND:This phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer. METHODS:Patients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus ... Read more >>

Br. J. Cancer (British Journal of Cancer)
[2018, 119(9):1086-1093]

Cited: 2 times

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Impact of Patient Age on Molecular Alterations of Left-Sided Colorectal Tumors.

Alberto Puccini, Heinz-Josef Lenz, John L Marshall, David Arguello, Derek Raghavan, W Michael Korn, Benjamin A Weinberg, Kelsey Poorman, Arielle L Heeke, Philip A Philip, Anthony F Shields, Richard M Goldberg, Mohamed E Salem,

BACKGROUND:The incidence of colorectal cancer (CRC) in younger patients is rising, mostly due to tumors in the descending colon and rectum. Therefore, we aimed to explore the molecular differences of left-sided CRC between younger (≤45 years) and older patients (≥65). SUBJECTS, MATERIALS, AND METHODS:In total, 1,126 CRC tumor samples from ... Read more >>

Oncologist (The oncologist)
[2019, 24(3):319-326]

Cited: 3 times

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Comparative Molecular Analyses of Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, and Gastric Adenocarcinoma.

Mohamed E Salem, Alberto Puccini, Joanne Xiu, Derek Raghavan, Heinz-Josef Lenz, W Michael Korn, Anthony F Shields, Philip A Philip, John L Marshall, Richard M Goldberg,

BACKGROUND:Gastroesophageal cancers are often grouped together even though cancers that originate in the esophagus often exhibit different histological features, geographical distribution, risk factors, and clinical characteristics than those originating in the stomach. Herein, we aimed to compare the molecular characteristics of three different gastroesophageal cancer types: esophageal squamous cell carcinoma ... Read more >>

Oncologist (The oncologist)
[2018, 23(11):1319-1327]

Cited: 6 times

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Immuno-Oncology Biomarkers for Gastric and Gastroesophageal Junction Adenocarcinoma: Why PD-L1 Testing May Not Be Enough.

Benjamin A Weinberg, Joanne Xiu, Jimmy J Hwang, Anthony F Shields, Mohamed E Salem, John L Marshall,

PURPOSE:The treatment of patients with advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas has been transformed by the U.S. Food and Drug Administration approval of pembrolizumab. Tumor and adjacent tissue must stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. However, some patients with PD-L1-negative ... Read more >>

Oncologist (The oncologist)
[2018, 23(10):1171-1177]

Cited: 2 times

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Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers.

Mohamed E Salem, Alberto Puccini, Axel Grothey, Derek Raghavan, Richard M Goldberg, Joanne Xiu, W Michael Korn, Benjamin A Weinberg, Jimmy J Hwang, Anthony F Shields, John L Marshall, Philip A Philip, Heinz-Josef Lenz,

The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal ... Read more >>

Mol. Cancer Res. (Molecular cancer research : MCR)
[2018, 16(5):805-812]

Cited: 11 times

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Using Radiolabeled 3'-Deoxy-3'-18F-Fluorothymidine with PET to Monitor the Effect of Dexamethasone on Non-Small Cell Lung Cancer.

Christopher I McHugh, Monica R Thipparthi, Jawana M Lawhorn-Crews, Lisa Polin, Shirish Gadgeel, Janice Akoury, Thomas J Mangner, Kirk A Douglas, Jing Li, Manohar Ratnam, Anthony F Shields,

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality in the United States, and pemetrexed-based therapies are regularly used to treat nonsquamous NSCLC. Despite widespread use, pemetrexed has a modest effect on progression-free survival, with varying efficacy between individuals. Recent work has indicated that dexamethasone, given to ... Read more >>

J. Nucl. Med. (Journal of nuclear medicine : official publication, Society of Nuclear Medicine)
[2018, 59(10):1544-1550]

Cited: 1 time

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Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.

Axel Grothey, Alberto F Sobrero, Anthony F Shields, Takayuki Yoshino, James Paul, Julien Taieb, John Souglakos, Qian Shi, Rachel Kerr, Roberto Labianca, Jeffrey A Meyerhardt, Dewi Vernerey, Takeharu Yamanaka, Ioannis Boukovinas, Jeffrey P Meyers, Lindsay A Renfro, Donna Niedzwiecki, Toshiaki Watanabe, Valter Torri, Mark Saunders, Daniel J Sargent, Thierry Andre, Timothy Iveson,

BACKGROUND:Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS:We performed a prospective, ... Read more >>

N. Engl. J. Med. (The New England journal of medicine)
[2018, 378(13):1177-1188]

Cited: 48 times

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Imaging bone-marrow activity with 18F-fluorothymidine PET.

Anthony F Shields,

Lancet Haematol (The Lancet. Haematology)
[2018, 5(1):e8-e9]

Cited: 0 times

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A Pilot Trial Evaluating Zoledronic Acid Induced Changes in [18F]FMAU-Positron Emission Tomography Imaging of Bone Metastases in Prostate Cancer.

Ulka N Vaishampayan, Omid S Tehrani, Jawana M Lawhorn-Crews, Lance K Heilbrun, Kimberlee Dobson, Daryn Smith, Brenda Dickow, Anthony F Shields,

PURPOSE:We conducted a pilot trial utilizing [18F]FMAU [1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl thymine] as a tumor tracer in positron emission tomography (PET) and evaluated its reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM). PROCEDURES:Eligible ... Read more >>

Mol Imaging Biol (Molecular imaging and biology)
[2017, 19(6):810-816]

Cited: 1 time

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Hospice Admission and Survival After 18F-Fluoride PET Performed for Evaluation of Osseous Metastatic Disease in the National Oncologic PET Registry.

Ilana F Gareen, Bruce E Hillner, Lucy Hanna, Rajesh Makineni, Fenghai Duan, Anthony F Shields, Rathan M Subramaniam, Barry A Siegel,

We have previously reported that PET using 18F-fluoride (NaF PET) for assessment of osseous metastatic disease was associated with substantial changes in intended management in Medicare beneficiaries participating in the National Oncologic PET Registry (NOPR). Here, we use Medicare administrative data to examine the association between NaF PET results and ... Read more >>

J. Nucl. Med. (Journal of nuclear medicine : official publication, Society of Nuclear Medicine)
[2018, 59(3):427-433]

Cited: 3 times

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Intended Versus Inferred Treatment After 18F-Fluoride PET Performed for Evaluation of Osseous Metastatic Disease in the National Oncologic PET Registry.

Bruce E Hillner, Lucy Hanna, Rajesh Makineni, Fenghai Duan, Anthony F Shields, Rathan M Subramaniam, Ilana Gareen, Barry A Siegel,

We have previously reported that PET with 18F-fluoride (NaF PET) for assessment of osseous metastatic disease led to changes in intended management in a substantial fraction of patients with prostate or other types of cancer participating in the National Oncologic PET Registry. This study was performed to assess the concordance ... Read more >>

J. Nucl. Med. (Journal of nuclear medicine : official publication, Society of Nuclear Medicine)
[2018, 59(3):421-426]

Cited: 1 time

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