Updates in pancreatic cancer: Modest gains and hopeful targets

2018 ◽  
Vol 25 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Amber Draper
Keyword(s):  
Pancreatic Cancer ◽  
Drug Targets ◽  
Systemic Disease ◽  
Tumor Biology ◽  
Standard Of Care ◽  
The United States ◽  
Incidence Rates ◽  
Delayed Presentation ◽  
Early Presentation ◽  
Cytotoxic Therapies

Pancreatic cancer is the twelfth most common cancer in the United States, representing 3.2% of all new cancer cases. While composing a small percentage of cancer diagnoses, pancreatic cancer is amongst the most lethal carcinomas, with an overall 5-year survival of 8.2% and incidence rates almost equivocal to death rates. By the time of diagnosis, a majority of patients will present with advanced stage disease. For patients with resectable disease, the estimated overall survival (OS) remains low at 20% as most will develop metastatic disease within 5 years. The lethality of this cancer is attributed to several factors including delayed presentation, lack of effective screening, and complex tumor biology and genetics. Data also suggest that even upon early presentation, pancreatic cancer is a systemic disease with micrometastasis present in the early stages. Traditional cytotoxic therapies have not been clinically impactful in pancreatic cancer, especially in advanced stages, and very little headway has been made in the development of new targeted therapies. As such, this review will discuss current advances in standard of care treatments and novel drug targets being researched.

scholarly journals Making Sense of Current and Emerging Therapies in Pancreatic Cancer: Balancing Benefit and Value

2015 ◽  
pp. e222-e227 ◽  
Author(s):  
Daniel H. Ahn ◽  
Andrew H. Ko ◽  
Neal J. Meropol ◽  
Tanios S. Bekaii-Saab
Keyword(s):  
Pancreatic Cancer ◽  
Standard Of Care ◽  
The United States ◽  
Economic Effects ◽  
Making Sense ◽  
Dismal Prognosis ◽  
Emerging Therapies ◽  
Metastatic Setting ◽  
Localized Disease ◽  
New Treatments

Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.1In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.2Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.

Updated use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6607-6607
Author(s):  
Thomas H. Cartwright ◽  
Aimee Ginsburg Arlen ◽  
Lalan S. Wilfong ◽  
Robyn K. Harrell ◽  
J. Russell Hoverman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Community Setting ◽  
Standard Of Care ◽  
The United States ◽  
Age At Diagnosis ◽  
Phase Iii ◽  
Combination Regimen ◽  
First Line ◽  
Asco 2012

6607 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 45,220 patients will be diagnosed in 2013 and 38,460 will die (Siegel, CA Cancer J Clin 2013). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment created a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) for patients with good Karnofsky performance status (PS) (Conroy, NEJM 2011). This retrospective analysis was conducted as an update to results reported at ASCO 2012 (Ginsburg Arlen, JCO 2012) to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. This is the largest study describing FOLFIRINOX patients to date. Methods: Patients with advanced PC treated within The US Oncology Network entered into the iKnowMed (iKM) database between June 2010 and November 2012 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Compared to ASCO 2012 results, 1,000 additional patients were identified in iKM. Of the 1,714 total patients, 24% received FOLFIRINOX (up from 13% in 2012) and 76% gemcitabine-based therapy (87% in 2012). Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (55% male), the median age at diagnosis was 67 years and the majority (85%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (9.6 mos) versus gemcitabine (6.3 mos) (p<0.0001). This held true for PS of 70% or greater patient given FOLFIRINOX (9.6 mos) versus gemcitabine (7 mos) (p<0.0001). Conclusions: Utilization of FOLFIRINOX has continued to expand after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community, we agree that FOLFIRINOX should become a standard of care for good PS patients.

Treatment of Metastatic Pancreatic Cancer

2005 ◽  
Vol 3 (5) ◽  
pp. 627-636 ◽  
Author(s):  
Andrew H. Ko ◽  
Margaret A. Tempero
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Standard Of Care ◽  
The United States ◽  
Cytotoxic Agents ◽  
Metastatic Pancreatic Cancer ◽  
Fixed Dose ◽  
Fixed Dose Rate ◽  
Advanced Stages ◽  
Fixed Dose Rate Infusion

Pancreatic adenocarcinoma represents the fourth-leading cause of cancer-related mortality in the United States. The vast majority of patients are diagnosed at advanced stages of the disease when surgery is no longer an option. For these patients, systemic therapy remains the mainstay of care. Although single-agent gemcitabine has remained the standard of care since its approval in 1997, improvements in patient outcomes may potentially be realized by (1) applying pharmacokinetic principles to optimize drug delivery, such as the administration of gemcitabine at a “fixed-dose rate” infusion; (2) combining gemcitabine with other cytotoxic agents for which evidence of synergy exists, such as platinum compounds; and (3) integrating novel targeted agents such as bevacizumab, erlotinib, and cetuximab into treatment paradigms, based on an increasing understanding of the molecular pathways that govern pancreatic tumor growth and maintenance. This article provides the evidence to support each of these approaches and highlights future directions in the management of metastatic pancreatic cancer.

Use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16536-e16536 ◽  
Author(s):  
Aimee Ginsburg Arlen ◽  
Thomas H. Cartwright ◽  
Lalan S. Wilfong ◽  
J. Russell Hoverman ◽  
Greg C Nelson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Community Setting ◽  
Standard Of Care ◽  
The United States ◽  
Age At Diagnosis ◽  
Phase Iii ◽  
Combination Regimen ◽  
First Line

e16536 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 43,920 patients will be diagnosed in 2012 and 37,390 will die (Siegel, CA Cancer J Clin, 2012). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment options have led to the utilization of a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) in patients with good Karnofsky performance status (PS). This regimen was compared to single-agent gemcitabine, presented at ASCO 2010 and recently published (Conroy, NEJM, 2011). This retrospective analysis was conducted to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. Methods: Patients with advanced PC treated within The US Oncology Network and entered into the iKnowMed (iKM) database between June 2010 and November 2011 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Of the 717 patients identified within the iKM database, 13% received FOLFIRINOX and 87% gemcitabine-based therapy. Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (54% male), the median age at diagnosis was 67 years and the majority of patients (89%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (8.4 months) versus gemcitabine (6.4 months) (p=0.036). OS was also significantly longer for PS of 70% or greater given FOLFIRINOX (9.0 months) versus gemcitabine (6.7 months) (p=0.022). After controlling for PS, the use of gemcitabine led to a shorter OS (HR 1.4; 95% CI: 1.02-2.01). Conclusions: Utilization of FOLFIRINOX has rapidly been adopted in patients with good PS after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community setting, we agree that should FOLFIRINOX become a standard of care for good PS patients.

Pancreatic Cancer

2018 ◽  
Author(s):  
Vassiliki Benetou ◽  
Anders Ekbom ◽  
Lorelei Mucci
Keyword(s):  
United States ◽  
Pancreatic Cancer ◽  
Smoking Cessation ◽  
Risk Factor ◽  
Cancer Risk ◽  
Positive Association ◽  
The United States ◽  
Incidence Rates ◽  
Coffee Intake ◽  
Pancreatic Cancer Risk

In 2012, more than 337,000 pancreatic cancer cases were diagnosed globally, ranking twelfth in cancer incidence. Pancreatic cancer has one of the highest fatality rates of any cancer, and as such ranks higher in cancer mortality, including in the United States, where it is the third most common cause of cancer death. There are concerning increases in incidence rates in the United States, although the reason for this is not known. Smoking is the strongest established risk factor for pancreatic cancer. Risk decreases after smoking cessation, and is similar to that of nonsmokers within 15 years of smoking cessation. Early epidemiological studies had suggested a positive association between coffee intake and pancreatic cancer risk, but subsequently the association was found to be due to bias. Obesity has emerged as a consistent risk factor for pancreatic cancer risk. Finally, conditions such as hereditary pancreatitis are strongly associated with cancer risk.

scholarly journals Evaluation of Empiric β-Lactam Susceptibility Prediction among Enterobacteriaceae by Molecular β-Lactamase Gene Testing

2019 ◽  
Vol 57 (10) ◽  
Author(s):  
Kyle Spafford ◽  
Shawn MacVane ◽  
Romney Humphries
Keyword(s):  
Standard Of Care ◽  
The United States ◽  
Resistance Mechanisms ◽  
Incidence Rates ◽  
Beta Lactam ◽  
Content Type ◽  
Gene Testing ◽  
Resistance Rates ◽  
Lactamase Gene ◽  
Third Generation Cephalosporins

ABSTRACT The use of rapid diagnostic tests (RDTs) for blood cultures has become standard of care in the United States to inform early antimicrobial optimization. The relative ability of genotypic and phenotypic approaches to identify beta-lactam susceptibility in Escherichia coli, Klebsiella spp., and Proteus mirabilis was evaluated, using incidence rates of resistance mechanisms to third-generation cephalosporins, aztreonam, and piperacillin-tazobactam seen across U.S. census regions. Overall, the presence of CTX-M, KPC, and/or NDM genes was 81% (range, 57 to 87%) sensitive for the prediction of ceftriaxone, ceftazidime, and aztreonam resistance and 73% (range, 25 to 90%) sensitive for the detection of piperacillin-tazobactam resistance. The sensitivity of KPC or NDM to predict imipenem or meropenem resistance was 94.3% overall, and for meropenem ranged from 70 to 100% across U.S. census regions. Institutions that use genotypic RDTs to inform therapeutic de-escalation decisions should be aware of the incidence-base performance across U.S. geographies and in different patient populations, where resistance rates may vary.

Opiophobia in Cancer Biology- Justified? - The Role of Perioperative Use of Opioids in Cancer Recurrence

2019 ◽  
Vol 25 (28) ◽  
pp. 3020-3027 ◽  
Author(s):  
Mir W. Sekandarzad ◽  
Chris Doornebal ◽  
Markus W. Hollmann
Keyword(s):  
Pain Management ◽  
Cancer Biology ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Standard Of Care ◽  
Cancer Surgery ◽  
Perioperative Pain Management ◽  
Tumor Growth And Metastasis

: Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. : The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis. : This narrative review highlights earlier and more recent in vitro, in vivo and human retrospective studies that yield conflicting results as to the immune-modulatory effects of morphine on tumor biology. The article examines and explains the discrepancies with regards to the seemingly opposite results of morphine in the tumor milieu. The results of both, earlier studies that demonstrated procarcinogenic effects versus the data of more recent refined rodent studies that yielded neutral or even anti-carcinogenic effects are presented here. : Until the results of prospective randomized controlled trials are available to clarify this important question, it is currently not warranted to support opiophobia and opioids continue to constitute a pivotal role in the pain management of cancer patients.

scholarly journals Testing telediagnostic thyroid ultrasound in Peru: a new horizon in expanding access to imaging in rural and underserved areas

2021 ◽  
Author(s):  
T. J. Marini ◽  
S. L. Weiss ◽  
A. Gupta ◽  
Y. T. Zhao ◽  
T. M. Baran ◽  
...  
Keyword(s):  
Thyroid Nodule ◽  
Standard Of Care ◽  
The United States ◽  
Epidemiological Studies ◽  
Thyroid Ultrasound ◽  
Target Region ◽  
Experienced Radiologist ◽  
Significant Difference ◽  
Size Evaluation

Abstract Purpose Thyroid ultrasound is a key tool in the evaluation of the thyroid, but billions of people around the world lack access to ultrasound imaging. In this study, we tested an asynchronous telediagnostic ultrasound system operated by individuals without prior ultrasound training which may be used to effectively evaluate the thyroid and improve access to imaging worldwide. Methods The telediagnostic system in this study utilizes volume sweep imaging (VSI), an imaging technique in which the operator scans the target region with simple sweeps of the ultrasound probe based on external body landmarks. Sweeps are recorded and saved as video clips for later interpretation by an expert. Two operators without prior ultrasound experience underwent 8 h of training on the thyroid VSI protocol and the operation of the telemedicine platform. After training, the operators scanned patients at a health center in Lima. Telediagnostic examinations were sent to the United States for remote interpretation. Standard of care thyroid ultrasound was performed by an experienced radiologist at the time of VSI examination to serve as a reference standard. Results Novice operators scanned 121 subjects with the thyroid VSI protocol. Of these exams, 88% were rated of excellent image quality showing complete or near complete thyroid visualization. There was 98.3% agreement on thyroid nodule presence between VSI teleultrasound and standard of care ultrasound (Cohen’s kappa 0.91, P < 0.0001). VSI measured the thyroid size, on average, within 5 mm compared to standard of care. Readers of VSI were also able to effectively characterize thyroid nodules, and there was no significant difference in measurement of thyroid nodule size (P = 0.74) between VSI and standard of care. Conclusion Thyroid VSI telediagnostic ultrasound demonstrated both excellent visualization of the thyroid gland and agreement with standard of care thyroid ultrasound for nodules and thyroid size evaluation. This system could be deployed for evaluation of palpable thyroid abnormalities, nodule follow-up, and epidemiological studies to promote global health and improve the availability of diagnostic imaging in underserved communities.

scholarly journals Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Colorectal Cancer

2020 ◽  
Vol 33 (06) ◽  
pp. 372-376
Author(s):  
Hideaki Yano
Keyword(s):  
Colorectal Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Peritoneal Cancer Index ◽  
Systemic Disease ◽  
Good Reason ◽  
Standard Of Care ◽  
Peritoneal Cancer

AbstractPeritoneal metastasis from colorectal cancer (PM-CRC) is used to be considered a systemic and fatal condition; however, it has been growingly accepted that PM-CRC can still be local disease rather than systemic disease as analogous to liver or lung metastasis.Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now considered an optimal treatment for PM-CRC with accumulating evidence. There is a good reason that CRS + HIPEC, widely accepted as a standard of care for pseudomyxoma peritonei (PMP), could be a viable option for PM-CRC given a similarity between PM-CRC and PMP.Recent years have also seen that modern systemic chemotherapy with or without molecular targeted agents can be effective for PM-CRC. It is possible that neoadjuvant or adjuvant chemotherapy combined with CRS + HIPEC could further improve outcomes.Patient selection, utilizing modern images and increasingly laparoscopy, is crucial. Particularly, diagnostic laparoscopy is likely to play a significant role in predicting the likelihood of achieving complete cytoreduction and assessing the peritoneal cancer index score.

scholarly journals The Potential of OMICs Technologies for the Treatment of Immune-Mediated Inflammatory Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7506
Author(s):  
Charles Gwellem Anchang ◽  
Cong Xu ◽  
Maria Gabriella Raimondo ◽  
Raja Atreya ◽  
Andreas Maier ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Standard Of Care ◽  
Incidence Rates ◽  
Irreversible Damage ◽  
Omics Technologies ◽  
Progressive Development ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Affected Tissue ◽  
Systemic Nature

Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular insults and colitis-associated neoplasia. Only 40–60% of patients respond to currently used standard-of-care immunotherapies. In addition to this limited long-term effectiveness, all current therapies have to be given on a lifelong basis as they are unable to specifically reprogram the inflammatory process and thus achieve a true cure of the disease. On the other hand, the development of various OMICs technologies is considered as “the great hope” for improving the treatment of IMIDs. This review sheds light on the progressive development and the numerous approaches from basic science that gradually lead to the transfer from “bench to bedside” and the implementation into general patient care procedures.

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