Author
Mokenge P. Malafa
Other affiliations: Northwestern University, Moffitt Cancer Center, City of Hope National Medical Center
Bio: Mokenge P. Malafa is an academic researcher from University of South Florida. The author has contributed to research in topics: Pancreatic cancer & Medicine. The author has an hindex of 22, co-authored 42 publications receiving 4942 citations. Previous affiliations of Mokenge P. Malafa include Northwestern University & Moffitt Cancer Center.
Topics: Pancreatic cancer, Medicine, Cancer, Adenocarcinoma, Neoadjuvant therapy
Papers published on a yearly basis
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2,314 citations
University of California, San Francisco1, Moffitt Cancer Center2, University of Michigan3, Mayo Clinic4, Roswell Park Cancer Institute5, University of Tennessee Health Science Center6, Northwestern University7, Washington University in St. Louis8, Vanderbilt University9, Yale Cancer Center10, Seattle Cancer Care Alliance11, City of Hope National Medical Center12, Duke University13, Ohio State University14, Fox Chase Cancer Center15, Harvard University16, Case Western Reserve University17, University of Texas MD Anderson Cancer Center18, Stanford University19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Memorial Sloan Kettering Cancer Center23, University of Alabama at Birmingham24, University of Utah25, University of Colorado Boulder26, Dana Corporation27
TL;DR: The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection, as well as on management of locally advanced unresectable and metastatic disease.
Abstract: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.
762 citations
University of California, San Francisco1, University of South Florida2, University of Michigan3, University of Tennessee Health Science Center4, Northwestern University5, Vanderbilt University6, Seattle Cancer Care Alliance7, City of Hope National Medical Center8, Duke University9, University of Colorado Boulder10, Ohio State University11, University of California, Los Angeles12, Fox Chase Cancer Center13, Harvard University14, Roswell Park Cancer Institute15, Case Western Reserve University16, Washington University in St. Louis17, University of Nebraska Medical Center18, Yale Cancer Center19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Johns Hopkins University23, University of Texas Southwestern Medical Center24, University of Alabama at Birmingham25, Memorial Sloan Kettering Cancer Center26, University of Utah27, Stanford University28, University of Pennsylvania29, University of Texas MD Anderson Cancer Center30, Brigham and Women's Hospital31, National Comprehensive Cancer Network32
Abstract: Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.
402 citations
University of California, San Francisco1, University of South Florida2, University of Tennessee Health Science Center3, Northwestern University4, Memorial Sloan Kettering Cancer Center5, Seattle Cancer Care Alliance6, City of Hope National Medical Center7, Fox Chase Cancer Center8, Duke University9, Pancreatic Cancer Action Network10, University of Michigan11, Washington University in St. Louis12, Johns Hopkins University13, Stanford University14, University of California, San Diego15, Roswell Park Cancer Institute16, Vanderbilt University17, University of Utah18, Ohio State University19, Harvard University20, University of Alabama at Birmingham21, University of Nebraska Medical Center22, University of Colorado Boulder23, University of Texas MD Anderson Cancer Center24, Brigham and Women's Hospital25, National Comprehensive Cancer Network26
TL;DR: These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCn Pancreatic Adenocarcinoma Panel meeting, which focused mainly on the management of borderline resectable and locally advanced disease.
Abstract: The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.
341 citations
University of California, San Francisco1, University of Alabama at Birmingham2, University Of Tennessee System3, University of Michigan4, Northwestern University5, Memorial Sloan Kettering Cancer Center6, Fox Chase Cancer Center7, Duke University8, City of Hope National Medical Center9, Washington University in St. Louis10, Johns Hopkins University11, Stanford University12, Roswell Park Cancer Institute13, University of South Florida14, Vanderbilt University15, University of Utah16, Ohio State University17, Harvard University18, University of Nebraska Medical Center19, Pancreatic Cancer Action Network20, Fred Hutchinson Cancer Research Center21, University of Texas MD Anderson Cancer Center22, Brigham and Women's Hospital23, National Comprehensive Cancer Network24
TL;DR: The panel made 3 significant updates to the guidelines: more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.
301 citations
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TL;DR: The results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas by significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone.
Abstract: ContextThe role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists.ObjectiveTo test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more.Design, Setting, and PatientsOpen, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups.InterventionPatients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175).Main Outcome MeasuresPrimary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat).ResultsMore than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank).ConclusionsPostoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas.Trial Registrationisrctn.org Identifier: ISRCTN34802808
2,242 citations
TL;DR: A model is proposed in which this species is a degenerate tetraploid resulting from a whole-genome duplication that occurred after the divergence of Saccharomyces from Kluyveromyces, and protein pairs derived from this duplication event make up 13% of all yeast proteins.
Abstract: Gene duplication is an important source of evolutionary novelty Most duplications are of just a single gene, but Ohno proposed that whole-genome duplication (polyploidy) is an important evolutionary mechanism Many duplicate genes have been found in Saccharomyces cerevisiae, and these often seem to be phenotypically redundant Here we show that the arrangement of duplicated genes in the S cerevisiae genome is consistent with Ohno's hypothesis We propose a model in which this species is a degenerate tetraploid resulting from a whole-genome duplication that occurred after the divergence of Saccharomyces from Kluyveromyces Only a small fraction of the genes were subsequently retained in duplicate (most were deleted), and gene order was rearranged by many reciprocal translocations between chromosomes Protein pairs derived from this duplication event make up 13% of all yeast proteins, and include pairs of transcription factors, protein kinases, myosins, cyclins and pheromones Tetraploidy may have facilitated the evolution of anaerobic fermentation in Saccharomyces
1,760 citations
Memorial Sloan Kettering Cancer Center1, University College London2, National Taiwan University3, University of Southern California4, University of Ulsan5, Trakya University6, University of Bordeaux7, University of Bologna8, University of Amsterdam9, The Chinese University of Hong Kong10, University of California, San Francisco11
TL;DR: Treatment with cabozantinib resulted in longer overall survival and progression‐free survival than placebo among patients with previously treated advanced hepatocellular carcinoma, and the rate of high‐grade adverse events in the cabozaninib group was approximately twice that observed in the placebo group.
Abstract: Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...
1,471 citations
TL;DR: Jörg Kleef and colleagues systematically reviewed studies on neoadjuvant therapy and tumor response, toxicity, resection, and survival percentages in pancreatic cancer and suggest that patients with locally nonresectable tumors should be included in neoad juvant protocols.
Abstract: Background
Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non-metastatic but locally advanced disease and microscopic incomplete resections are common. The objective of the present analysis was to systematically review studies concerning the effects of neoadjuvant therapy on tumor response, toxicity, resection, and survival percentages in pancreatic cancer.
Methods and Findings
Trials were identified by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1966 to December 2009 as well as through reference lists of articles and proceedings of major meetings. Retrospective and prospective studies analyzing neoadjuvant radiochemotherapy, radiotherapy, or chemotherapy of pancreatic cancer patients, followed by re-staging, and surgical exploration/resection were included. Two reviewers independently extracted data and assessed study quality. Pooled relative risks and 95% confidence intervals were calculated using random-effects models. Primary outcome measures were proportions of tumor response categories and percentages of exploration and resection. A total of 111 studies (n = 4,394) including 56 phase I–II trials were analyzed. A median of 31 (interquartile range [IQR] 19–46) patients per study were included. Studies were subdivided into surveys considering initially resectable tumors (group 1) and initially non-resectable (borderline resectable/unresectable) tumors (group 2). Neoadjuvant chemotherapy was given in 96.4% of the studies with the main agents gemcitabine, 5-FU (and oral analogues), mitomycin C, and platinum compounds. Neoadjuvant radiotherapy was applied in 93.7% of the studies with doses ranging from 24 to 63 Gy. Averaged complete/partial response probabilities were 3.6% (95% CI 2%–5.5%)/30.6% (95% CI 20.7%–41.4%) and 4.8% (95% CI 3.5%–6.4%)/30.2% (95% CI 24.5%–36.3%) for groups 1 and 2, respectively; whereas progressive disease fraction was estimated to 20.9% (95% CI 16.9%–25.3%) and 20.8% (95% CI 14.5%–27.8%). In group 1, resectability was estimated to 73.6% (95% CI 65.9%–80.6%) compared to 33.2% (95% CI 25.8%–41.1%) in group 2. Higher resection-associated morbidity and mortality rates were observed in group 2 versus group 1 (26.7%, 95% CI 20.7%–33.3% versus 39.1%, 95% CI 29.5%–49.1%; and 3.9%, 95% CI 2.2%–6% versus 7.1%, 95% CI 5.1%–9.5%). Combination chemotherapies resulted in higher estimated response and resection probabilities for patients with initially non-resectable tumors (“non-resectable tumor patients”) compared to monotherapy. Estimated median survival following resection was 23.3 (range 12–54) mo for group 1 and 20.5 (range 9–62) mo for group 2 patients.
Conclusions
In patients with initially resectable tumors (“resectable tumor patients”), resection frequencies and survival after neoadjuvant therapy are similar to those of patients with primarily resected tumors and adjuvant therapy. Approximately one-third of initially staged non-resectable tumor patients would be expected to have resectable tumors following neoadjuvant therapy, with comparable survival as initially resectable tumor patients. Thus, patients with locally non-resectable tumors should be included in neoadjuvant protocols and subsequently re-evaluated for resection.
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1,315 citations
TL;DR: Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.
Abstract: Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.
1,278 citations