{"title":"Outstanding Outcome of Pancreatic Cancer: What Lessons Do We Learn","authors":"M. Saif","doi":"10.17140/POJ-4-E012","DOIUrl":"https://doi.org/10.17140/POJ-4-E012","url":null,"abstract":"The American Cancer Society’s estimates that 57,600 people (30,400 men and 27,200 women) will be diagnosed with pancreatic cancer in the United States for 2020 and approximately 47,050 people (24,640 men and 22,410 women) will die of pancreatic cancer in 2020.1 Despite advances in first-line therapy such as gemcitabine/nab-paclitaxel and fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) in advanced pancreatic cancer (aPC), median overall survival remains less than 12-months.2","PeriodicalId":20001,"journal":{"name":"Pancreas (Fairfax, Va.)","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89092421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Outstanding Outcome of Pancreatic Cancer: What Lessons Do We Learn.","authors":"Muhammad W Saif","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":20001,"journal":{"name":"Pancreas (Fairfax, Va.)","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38169868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nausheen Hakim, Rajvi Patel, Craig Devoe, Muhammad W Saif
{"title":"Why HALO 301 Failed and Implications for Treatment of Pancreatic Cancer.","authors":"Nausheen Hakim, Rajvi Patel, Craig Devoe, Muhammad W Saif","doi":"10.17140/POJ-3-e010","DOIUrl":"https://doi.org/10.17140/POJ-3-e010","url":null,"abstract":"<p><p>Survival rates for pancreatic cancer (PC) remain dismal. Current standard of care treatment regimens provide transient clinical benefit but eventually chemoresistance develops leading to poor outcomes. PC is a relatively chemoresistant tumor and one of the explanations for this is attributed to desmoplasia that impedes drug delivery. Based on this, stromal modifying agent such as Pegvorhyaluronidase alfa (PEGPH20) was developed and investigated in phase I-III studies. Although phase I-II studies showed promising results in patients with high hyaluronic acid (HA) expressing tumors, the phase III HALO 301 study failed to miss it's primary endpoint and further development of PEHPH20 is halted. This failure implies that targeting desmoplasia alone is not sufficient and other intrinsic factors such as lack of significant neoantigens, low tumor mutational burden, and epithelial to mesenchymal transition may be at play. It is also important to consider that although the tumor stroma may be a physical barrier hampering drug delivery, it may also have protective effects in restraining tumor growth and progression. Further studies in molecular biology to better characterize the complex interaction between the microenvironment and cancer cells are warranted.</p>","PeriodicalId":20001,"journal":{"name":"Pancreas (Fairfax, Va.)","volume":"3 1","pages":"e1-e4"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37618991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Evolving Field of Stereotactic Body Radiation Therapy in Pancreatic Cancer.","authors":"Maged Ghaly, Emile Gogineni, Muhammad W Saif","doi":"10.17140/POJ-3-110","DOIUrl":"https://doi.org/10.17140/POJ-3-110","url":null,"abstract":"<p><p>Pancreatic cancer remains a devastating disease with dismal outcomes despite the development of novel chemotherapeutic regimens and radiation techniques. Stereotactic body radiation therapy (SBRT) offers an advantage both in image guidance and radiation dose delivery to direct ablative doses to tumors with acceptable toxicity compared to conventional techniques. Recent literature is clustered with data pertaining to SBRT in patients with resectable, borderline resectable and locally advanced pancreatic tumors. We here present a summary of the current data and highlight the limitations and potential for future growth. Further clinical study in the form of multi-institutional trials is warranted to establish the role of SBRT in combination with new chemo- therapeutic agents as well as a non-invasive alternative to surgery.</p>","PeriodicalId":20001,"journal":{"name":"Pancreas (Fairfax, Va.)","volume":"3 1","pages":"9-14"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37536188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rajvi Patel, Daniel Fein, Carolina B Ramirez, Kevin Do, Muhammad W Saif
{"title":"PARP Inhibitors in Pancreatic Cancer: From Phase I to Plenary Session.","authors":"Rajvi Patel, Daniel Fein, Carolina B Ramirez, Kevin Do, Muhammad W Saif","doi":"10.17140/POJ-3-e011","DOIUrl":"https://doi.org/10.17140/POJ-3-e011","url":null,"abstract":"<p><p>Survival rates for pancreatic cancer remain dismal. Current standard of care treatment regimens provide transient clinical benefit but eventually chemoresistance develops. Tumors deficient in deoxyribonucleic acid (DNA) damage repair mechanisms such as <i>BRCA</i> mutants show better responses to platinum based agents, however, such tumors can utilize the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) pathway as a salvage mechanism. Therefore, inhibition of PARP pathway could lead to tumor destruction and synthetic lethality in presence of <i>BRCA</i> mutation. Various PARP inhibitors have been approved for treatment of patients with germline or somatic <i>BRCA</i> mutant breast and ovarian cancer. This provides basis of using PARP inhibitors in patients with pancreatic cancer that harbor <i>BRCA</i> mutation. A recent phase III Pancreas Cancer Olaparib Ongoing (POLO) study showed impressive results with near doubling of progression free survival compared to placebo (7.4 <i>vs</i> 3.8 months). These results highlight the importance of germline testing for all patients with pancreatic cancer and inclusion of additional deficiencies in homologous recombination repair (<i>ATM</i> and <i>PALB2</i>) including <i>BRCA</i> variants of uncertain significance should be further explored.</p>","PeriodicalId":20001,"journal":{"name":"Pancreas (Fairfax, Va.)","volume":"3 1","pages":"e5-e8"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37620188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}