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Pancreatic Neoplasms: HELP
Articles by Leonard B. Saltz
Based on 7 articles published since 2009
(Why 7 articles?)

Between 2009 and 2019, Leonard Saltz wrote the following 7 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature. 2012

Karamurzin, Yevgeniy / Zeng, Zhaoshi / Stadler, Zsofia K / Zhang, Liying / Ouansafi, Ihsane / Al-Ahmadie, Hikmat A / Sempoux, Christine / Saltz, Leonard B / Soslow, Robert A / O'Reilly, Eileen M / Paty, Philip B / Coit, Daniel G / Shia, Jinru / Klimstra, David S. ·Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ·Hum Pathol · Pubmed #22516243.

ABSTRACT: Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum. Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome. The fourth tumor was an adrenocortical carcinoma, which has rarely been reported previously in Lynch syndrome. Three of our 4 patients carried a pathogenic germ-line mutation in a mismatch repair gene. The unusual tumor in each of the 3 patients showed loss of the mismatch repair protein corresponding to the mutation. The fourth patient did not have mutation information but had a history of colonic and endometrial carcinomas; both lacked MSH2 and MSH6 proteins. Interestingly, none of the 4 unusual tumors revealed microsatellite instability on polymerase chain reaction testing, whereas an appendiceal carcinoma from 1 of the study patients who was tested simultaneously did. The recognition of such tumors expands the repertoire of usable test samples for the workup of high-risk families. As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome.

2 Clinical Trial A phase 2 study of the insulin-like growth factor-1 receptor inhibitor MK-0646 in patients with metastatic, well-differentiated neuroendocrine tumors. 2012

Reidy-Lagunes, Diane L / Vakiani, Efsevia / Segal, Michal F / Hollywood, Ellen M / Tang, Laura H / Solit, David B / Pietanza, M Catherine / Capanu, Marinela / Saltz, Leonard B. ·Department of Medicine, Division of Solid Tumors, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. reidy@mskcc.org ·Cancer · Pubmed #22437754.

ABSTRACT: BACKGROUND: Neuroendocrine tumor (NET) cell lines frequently express both insulin-like growth factor (IGF) ligand and the cognate IGF-1 receptor (IGF-1R) and, as such, potentially depend on the activation of IGF-1R and its downstream effectors for growth and survival. Preclinical studies suggest that somatostatin analogs and mammalian target of rapamycin (mTOR) inhibitors exhibit antitumor activity against NETs through inhibition of IGF-1-dependent signaling, suggesting that IGF-1R inhibition may be a promising therapeutic approach to NETs. Therefore, the authors of this report evaluated the safety and efficacy of MK-0646, a fully human monoclonal antibody (MoAb) that binds to the IGF-1R, as monotherapy in patients with metastatic, well-differentiated NETs. METHODS: A phase 2 study was performed in which patients received intravenous MK-0646 10 mg/kg once weekly over 1 hour. Archived pretreatment tumor tissue was obtained and genotyped for v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-3-kinase, catalytic, alpha polypeptide (PIK3CA); and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations, and immunohistochemistry was performed to measure the expression IGF-1R. RESULTS: Twenty-five patients received treatment (40% women; median age, 61 years; age range, 37-83 years), including 15 patients with carcinoid tumors and 10 patients with pancreatic NETs. No partial or complete responses were observed. The median progression-free survival was 4.2 months in the pancreatic NET cohort (range, 0.7-6.7 months) and 2.7 months in the carcinoid cohort (range, 2-3 months). Serious adverse events that were potentially related to MK-0646 included grade 3/4 hyperglycemia in 8 of 25 patients (32%), grade 2 hypersensitivity reaction in 1 of 24 patients (4%), and grade 3 lipase elevation in 1 of 25 patients (4%). CONCLUSIONS: Despite a compelling preclinical rationale, MK-0646 was inactive as a single agent in well-differentiated NETs. Further studies of MK-0646 as a monotherapy in unselected NETs are unwarranted.

3 Clinical Trial Phase I study of weekly cisplatin, bolus fluorouracil and escalating doses of irinotecan in advanced solid tumors. 2009

Ku, Geoffrey Y / O'Reilly, Eileen M / Saltz, Leonard B / Schrag, Deborah / Maki, Robert G / Kelsen, David P / Ilson, David H. ·Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ·Cancer Invest · Pubmed #19219674.

ABSTRACT: PURPOSE: We performed a phase I study of 5-fluorouracil (5-FU), cisplatin and irinotecan. METHODS: Twenty-nine patients received cisplatin 25 mg/m(2) and bolus 5-FU 425 mg/m(2), along with irinotecan at 40, 50, and 65 mg/m(2) weekly for 4 out of 6 weeks. RESULTS: The maximum tolerated dose (MTD) for untreated patients was irinotecan 65 mg/m(2) while the MTD for previously treated patients was irinotecan 40 mg/m(2). Neutropenia and diarrhea were the major dose-limiting toxicities. Antitumor activity was noted in gastric, esophageal and pancreatic cancers. CONCLUSION: Because of the toxicity profile, combinations with continuous infusion 5-FU or capecitabine should be explored.

4 Article Real-Time Genomic Profiling of Pancreatic Ductal Adenocarcinoma: Potential Actionability and Correlation with Clinical Phenotype. 2017

Lowery, Maeve A / Jordan, Emmet J / Basturk, Olca / Ptashkin, Ryan N / Zehir, Ahmet / Berger, Michael F / Leach, Tanisha / Herbst, Brian / Askan, Gokce / Maynard, Hannah / Glassman, Danielle / Covington, Christina / Schultz, Nikolaus / Abou-Alfa, Ghassan K / Harding, James J / Klimstra, David S / Hechtman, Jaclyn F / Hyman, David M / Allen, Peter J / Jarnagin, William R / Balachandran, Vinod P / Varghese, Anna M / Schattner, Mark A / Yu, Kenneth H / Saltz, Leonard B / Solit, David B / Iacobuzio-Donahue, Christine A / Leach, Steven D / O'Reilly, Eileen M. ·Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. maevelowery@gmail.com oreillye@mskcc.org. · David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, Weill Cornell Medical College, New York, New York. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. · Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. ·Clin Cancer Res · Pubmed #28754816.


5 Article Identification of germline genetic mutations in patients with pancreatic cancer. 2015

Salo-Mullen, Erin E / O'Reilly, Eileen M / Kelsen, David P / Ashraf, Asad M / Lowery, Maeve A / Yu, Kenneth H / Reidy, Diane L / Epstein, Andrew S / Lincoln, Anne / Saldia, Amethyst / Jacobs, Lauren M / Rau-Murthy, Rohini / Zhang, Liying / Kurtz, Robert C / Saltz, Leonard / Offit, Kenneth / Robson, Mark E / Stadler, Zsofia K. ·Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer · Pubmed #26440929.

ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling/testing are not well-defined. In the current study, the authors sought to determine mutation prevalence and characteristics that are predictive of an inherited predisposition for PAC. METHODS: A total of 175 consecutive patients with PAC who underwent clinical genetics assessment at Memorial Sloan Kettering Cancer Center between 2011 and 2014 were identified. Clinical data, family history, and germline results were evaluated. RESULTS: Among 159 patients with PAC who pursued genetic testing, 24 pathogenic mutations were identified (15.1%; 95% confidence interval, 9.5%-20.7%), including BRCA2 (13 mutations), BRCA1 (4 mutations), p16 (2 mutations), PALB2 (1 mutation), and Lynch syndrome (4 mutations). BRCA1/BRCA2 prevalence was 13.7% in Ashkenazi Jewish (AJ) patients (95 patients) and 7.1% in non-AJ patients (56 patients). In AJ patients with a strong, weak, or absent family history of BRCA-associated cancers, the mutation prevalence was 16.7%, 15.8%, and 7.4%, respectively. The mean age at the time of diagnosis in all mutation carriers was 58.5 years (range, 45-75 years) compared with 64 years (range, 27-87 years) in those not carrying a mutation (P = .02). Although BRCA2 was the most common mutation identified, no patients with early-onset PAC (diagnosed at age ≤ 50 years) harbored a BRCA2 mutation and the mean age at diagnosis in BRCA2 carriers was equivalent to that of individuals who were not mutation carriers (P = .34). Mutation prevalence in patients with early-onset disease (21 patients) was 28.6%, including BRCA1 (2 mutations), p16 (2 mutations), MSH2 (1 mutation), and MLH1 (1 mutation). CONCLUSIONS: Mutations in BRCA2 account for > 50% of patients with PAC with an identified susceptibility syndrome. AJ patients were found to have high BRCA1/BRCA2 prevalence regardless of personal/family history, suggesting that ancestry alone indicates a need for genetic evaluation. With the exception of BRCA2-associated PAC, an inherited predisposition for PAC is associated with an earlier age at PAC diagnosis, suggesting that this subset of patients may also represent a population warranting further evaluation.

6 Article Pharmacogenomic modeling of circulating tumor and invasive cells for prediction of chemotherapy response and resistance in pancreatic cancer. 2014

Yu, Kenneth H / Ricigliano, Mark / Hidalgo, Manuel / Abou-Alfa, Ghassan K / Lowery, Maeve A / Saltz, Leonard B / Crotty, Joseph F / Gary, Kristen / Cooper, Brandon / Lapidus, Rena / Sadowska, Mariola / O'Reilly, Eileen M. ·Memorial Sloan Kettering, Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York. yuk1@mskcc.org. · CellPath Therapeutics, Baltimore, Maryland. · Clinical Research Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain. · Memorial Sloan Kettering, Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York. · University of Maryland Greenebaum Cancer Center, Baltimore, Maryland. ·Clin Cancer Res · Pubmed #25107917.

ABSTRACT: PURPOSE: Despite a challenging prognosis, modern cytotoxic therapy can induce tumor responses and extend life in pancreatic adenocarcinoma (PDAC). Pharmacogenomic (PGx) modeling of tumor tissue can predict the efficacy of chemotherapeutic agents in preclinical cancer models. We hypothesized that PGx profiling of circulating tumor and invasive cells (CTIC) isolated from peripheral blood could predict tumor response, progression, and resistance. EXPERIMENTAL DESIGN: A PGx model was created and validated in preclinical models. A prospective clinical trial was conducted. Fifty patients with advanced PDAC were enrolled. Before treatment, 10 mL of peripherally drawn blood was collected. CTICs isolated from this blood sample were expression profiled and the PGx model was used to predict effective and ineffective chemotherapeutic agents. The treating physicians were blinded to PGx prediction. RESULTS: We found that CTICs could be reliably isolated, total RNA extracted and profiled from 10 mL of peripheral blood from patients with unresectable PDAC before chemotherapy treatment and at disease progression. Using previously created PGx models to predict chemotherapy sensitivity, we found that clinical benefit was seen for study participants treated with chemotherapy regimens predicted to be effective versus chemotherapy regimens predicted to be ineffective with regard to progression-free (10.4 mo vs. 3.6 mo; P < 0.0001; HR, 0.14) and overall survival (17.2 mo vs. 8.3 mo; P < 0.0249; HR, 0.29). CONCLUSIONS: These findings suggest that PGx profiling of CTICs can predict treatment response.

7 Minor Albumin-bound paclitaxel plus gemcitabine in pancreatic cancer. 2014

Saltz, Leonard B / Bach, Peter B. · ·N Engl J Med · Pubmed #24476439.

ABSTRACT: -- No abstract --