nanoknife IRE for pancreatic cancer

The Phase II clinical trial included 214 patients from June 2010 to June 2011 at 45 centers

Monday, April 02, 2012 http://www.mayoclinic.org/news2012-sct/6792.html

SCOTTSDALE, Ariz. — The combination of the novel drug TH-302 with the standard drug gemcitabine has shown early signs of delaying the worsening of cancer in patients with advanced pancreatic cancer, a Mayo Clinic-led study has found. This was evaluated using a measure termed progression-free survival (PFS). According to the results of a multi-center Phase II clinical trial, patients receiving the combination of gemcitabine and TH-302 demonstrated a progression-free survival of 5.6 months compared to 3.6 months in those patients who received gemcitabine alone.

Video alert: Click hereto watch Dr. Borad share the results of the study. http://www.youtube.com/watch?v=qv9Jb-aN_aM

The two-month delay in worsening of the cancer is considered significant given that the average survival of patients withadvanced pancreatic canceris only six to seven months.

Lead researcherMitesh Borad, M.D., of Mayo Clinic in Arizona, will present the results of the Phase II study on Monday, April 2, at the American Association for Cancer Research (AACR) Annual Meeting.

The scientific basis of using TH-302 is to target low-oxygen (hypoxic) areas in cancers that are a common source of drug resistance to conventional chemotherapy drugs. Promising results of the combination of TH-302 and gemcitabine in pancreatic cancer animal models preceded this clinical trial in patients.

The Phase II clinical trial included 214 patients from June 2010 to June 2011 at 45 centers. Patients were randomized to receive standard therapy with gemcitabine or gemcitabine in combination with one of two doses of TH-302.

"The results of the trial support ongoing study of TH-302 in pancreatic cancer," Dr. Borad says.

The study was funded by Threshold Pharmaceuticals, the manufacturer of TH-302.

Diabetes Drug Could Prove Effective For Pancreatic Cancer

RTTNews.com 04/Apr2012 http://www.nasdaq.com/article/diabetes-drug-could-prove-effe

A new study from researchers at the University of Texas MD Anderson Cancer Center has found that pancreatic cancer patients with diabetes may benefit from use of the diabetes drug metformin. The study lead researcher Donghui Li and a team of researchers observed 302 pancreatic cancer patients with diabetes, 117 of which were also taking metformin. They found that over the course of two years those taking metformin enjoyed a 32 percent decreased chance of death as compared with those who were not on the drug. "This study suggests that metformin use in patients with diabetes was associated with improved pancreatic cancer survival, so we should certainly begin study of its supplemental use in pancreatic cancer treatment," Li says in a news release. The decreased chance of death appeared to be equally likely at all stages of the study, which collected data at one and two year marks.

Vaccine Associated with Stable Disease in Treatment of Pancreatic Cancer

Source: http://www.cinj.org/PressReleases/PANVAC_AACR.htm

The ongoing trail is still accepting patients; see http://www.cinj.org/PressReleases/PANVAC.html

Research from The Cancer Institute of New Jersey Presented at Annual AACR Meeting

New Brunswick, N.J. – Research from The Cancer Institute of New Jersey (CINJ) shows that a series of vaccine injections given directly into a pancreatic cancer tumor is shown to be associated with stable disease in patients who are not candidates for surgery. Early results of a clinical trial being conducted at CINJ are being presented as part of a "highly-rated poster" at the Annual Meeting of the American Association for Cancer Research (AACR) being held in Chicago this week. CINJ is a Center of Excellence of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

Previous laboratory research by CINJ investigators has shown that injecting a vaccine and other immunity-producing drugs directly into a cancer tumor -- as opposed to the normal injection site of the skin -- can result in a reversal of the traditional immune blockade and the development of specific immunity to the tumor throughout the body. This tumor-specific immunity has the potential of blocking the growth of the original tumor as well as eliminating small tumor deposits that can cause the cancer to spread. Stemming from this research is a clinical trial that is the focus of this abstract. The study by CINJ investigators further tests this vaccine strategy, designed to heighten the role of the body’s own immune system in fighting cancer.

The investigational vaccine known as PANVAC contains gene additives that might stimulate a person's immune system to recognize and develop an immune response to the disease. Two types of PANVAC have been utilized in this trial. PANVAC-V, which uses the same virus as the smallpox vaccine, is a live but weakened vaccinia vaccine (meaning the virus can still multiply) that is given in the arm. PANVAC-F (a live Fowlpox virus that cannot multiply) is injected into the tumor itself and subsequently into the arm as a boost. Direct tumor injection takes place during a procedure known as endoscopic ultrasound, in which a scope is inserted through the mouth and into the stomach so that the tumor in the pancreas can be seen.

During the first phase of the study, which looked at six participants whose cancer could not be removed through surgery, patients were evaluated for toxicity, tumor progression and the presence of tumor markers for pancreatic cancer. One patient was treated with gemcitabine, followed by capecitabine and radiation, prior to the vaccination regimen and received no other treatment after.

Two patients were removed from the study after two weeks due to rapid disease progression; one died six months after first being placed on the trial and the other after one month. Of the remaining four patients, three received gemcitabine – a standard treatment for pancreatic cancer – after receiving vaccination treatment.

Of these four patients, all were shown to have clinically stable disease after 24 months, 22 months, 21 months and 18 months respectively. The second part of the trial is still accruing additional participants, who are being given a higher dosage of PANVAC-F during direct injection of the tumor.

CINJ Deputy Director Edmund Lattime, PhD, is the senior researcher on the study, which is sponsored by the National Cancer Institute (NCI). "We're seeing results of clinically stable disease for a year and a half now in some cases with this treatment regimen. Considering pancreatic cancer only carries a five-year, five percent survival rate, these findings are very encouraging and will hopefully lead to more effective ways of managing and treating this disease," noted Dr. Lattime who is also a professor of surgery and a professor of molecular genetics, microbiology and immunology at UMDNJ-Robert Wood Johnson Medical School.

Along with Lattime, authors include Elizabeth Poplin, David August, Tamir Ben-Menachem, Hazar Michael and Renee Artymyshyn of CINJ and UMDNJ-Robert Wood Johnson Medical School; James L. Gulley and Jeffrey Schlom of the NCI; and Robert S. DiPaola of CINJ and UMDNJ-Robert Wood Johnson Medical School.

The work was supported by the NCI Cancer Therapeutics Evaluation Program and by NCI U01-CA07031 and P30-CA72720. This research also was presented at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics meeting held in San Francisco this past November.

Image Guided Irreversible Electroporation in Locally Advanced Pancreatic Cancer: Improved Overall Survival

R.C. Martin,1* D. Hayes,3 W. Goodwin,3 K. McFarlin,2 M. Prasad,2 V. Velanovich.2

1. Surgery, Division of Surgical Oncology, Univ Louisville, Louisville, KY; 2. Henry Ford Hospital, Detroit, MI; 3. Baptist Health, Little Rock, AR.

Abstract 18 http://www.surgonc.org/uploads/SSO_Annual_Cancer_Symposium_2

Background: Locally advanced unresectable pancreatic adenocarcinoma (LAC) is characterized by poor survival despite chemotherapy and conventional radiation therapy. We have recently reported on the safety of the use of irreversible electroporation (IRE) in the management of LAC. The aim of this study was to evaluate the overall survival in patients with LAC treated with IRE.

Methods: A prospective multi-institutional evaluation of 44 patients undergoing IRE for unresectable pancreatic cancer 12/2009 to 10/2010were evaluated for overall survival and compared to 85 matched stage III patients treated with standard therapy defined as chemotherapy and radiation therapy alone.

Results: A total of 44 LAC pts have successfully undergone IRE, with 21women, 21 men, median age of 61( 45 – 80 years). Twenty-nine patients had pancreatic head primary and 15 with body tumors, with 12 pts undergoing margin accentuation with IRE and 32 undergoing in-situ IRE. 40(90%) had pre-IRE chemotherapy alone or chemo-radiation therapy for a median duration 5 months. 32(73%) pts underwent post-IRE chemotherapy or chemo-radiation. The 90 day mortality in the IRE patients was 1(2%). In a comparison of IRE patients to standard therapy we have seen a significant improvement in Local progression free survival (14 vs 6 months, P=0.01), Distant progression free survival (15 vs 9 months, p=0.02), and overall survival (20 vs 13 months, p=0.03).

Conclusion: IRE ablation of locally advanced pancreatic tumors remains safe and in the appropriate patient who has undergone standard neo-adjuvant therapy for a minimum of 4 months can achieve greater local palliation and improved overall survival when compared to standard chemo-radiation - chemotherapy treatments. Validation of these early results will need to be validated in the current multi-institutional Phase 2 IDE study (G110102).

On Mar 26, 2012 7:02 PM PhilipJax wrote:

The following news release was issued today, 26Mar2012

Keep in mind that the IRE specialists at the U of Miami (Sylvester Cancer Center) are Interventional Radiologists; they are not surgeons.

There are advantages to selecting oncological SURGEONS for IRE, since surgeons can combine IRE with open surgery to access otherwise inaccessible areas.

Electrical Pulse Treatment [IRE] Gives Pancreatic Cancer Patients New Hope

PR Newswire

SAN FRANCISCO, March 26, 2012 http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel eases/California/2012/03/26/DC70477"" target="_blank" rel="nofollow">http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel target="_blank" rel="nofollow">http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel

Innovative Interventional Radiology Procedure Zaps Around Complicated Pancreatic Tumors, Improving Prognosis and Pancreatic Cancer Treatment Paradigm

SAN FRANCISCO,March 26, 2012/PRNewswire-USNewswire/ -- Results of a study presented at the Society of Interventional Radiology's 37th Annual Scientific Meeting inSan Francisco, Calif., signal a light at the end of the tunnel for individuals with inoperable locally advanced pancreatic cancer. A new procedure called irreversible electroporation or IRE uses microsecond electrical pulses to force open and destroy tumor cells around a vast and delicate network of blood vessels of the pancreas. The technique has been successful in treating primary and metastatic liver cancer, and IRE is now in the first stages of implementation as a treatment for pancreatic cancer.

"We think in another 15 to 24 months we will have a lot more evidence to support the use of irreversible electroporation for inoperable pancreatic cancer patients," saidGovindarajan Narayanan, M.D., chief of vascular and interventional radiology, associate professor of clinical radiology and program director for the vascular interventional radiology fellowship at theUniversity of Miami's Miller School of Medicine inMiami, Fla."If we continue to get good results, this procedure could provide a huge benefit for people who honestly don't have a lot of choices. It could potentially change the rules of how these cases are managed," he added.

Pancreatic tumors are notoriously difficult to treat because any method that uses heat or cold to remove the cancer comes with too much risk of collateral damage to important blood vessels in and around the organ. IRE involves guiding electrode needles into the tumor, which damages cancer cells with a series of jolts of localized high-voltage electricity that break open the cell membranes—effectively killing the cancerous tissues around these blood vessels.

"People with locally advanced pancreatic cancer don't have a lot of treatment choices available. Irreversible electroporation gives these individuals a new treatment option and a potentially greater chance of survival," said Narayanan. "Without IRE, these individuals are essentially left with chemotherapy and radiation therapy. At this point, the prognosis for this group is pretty dismal and they have an estimated survival of less than one year. With this procedure, there is the potential to change the inoperable status in some of these patients and make them surgical candidates, he added.

An estimated 44,000 people will be diagnosed with pancreatic cancer and approximately 37,390 people will die of the disease this year, according to the American Cancer Society. About one in 71 people are expected to develop pancreatic cancer in their lifetime.

For this study, researchers gathered records for eight patients with locally advanced pancreatic cancer referred for percutaneous irreversible electroporation. All subjects had the procedure performed between December 2010and September 2011. Pancreatic tumors were found to be between 2.5 and 6.8 centimeters in size, and each participant had formerly received a median of two other methods of treatment. A median span of time of about 9 months took place between diagnosis and treatment with IRE. Participants underwent post-procedure CT imaging to gauge the effectiveness of treatment. Out of the original eight inoperable individuals, two went on to have surgery. Both had successful resections and remain cancer-free after months following treatment.  [PhilipJax: IRE should NOT be considered the sole therapy; it is part of a multi-therapy approach, which includes open surgery.]

IRE is performed with a technology dubbed NanoKnife, which has received clearance from the U.S. Food and Drug Administration for the surgical ablation of soft tissue.

"As we move forward there will be a lot of new technology and techniques like this that will help shape cancer care," said Narayanan.

More information about the Society of Interventional Radiology, interventional radiologists and minimally invasive treatments can be found online at www.SIRweb.org "" target="_blank" rel="nofollow">http://www.SIRweb.org " target="_blank" rel="nofollow">www.SIRweb.org .

Abstract 8: "Downstaging Locally Advanced Pancreatic Adenocarcinoma (LAPC) With Vascular Encasement Using Percutaneous Irreversible Electroporation (IRE)," G. Narayanan, G. Arora , K.J. Barbery, T. Froud, J. Yrizarry, radiology, division of vascular/interventional radiology, University of Miami, Miami, Fla.; A. Livingstone, D. Franceschi, surgery, division of surgical oncology, University of Miami, Miami, Fla.; P. Hosein, C.M. Rocha Lima, medicine, division of hematology/oncology, University of Miami, Miami, Fla., SIR 37th Annual Scientific Meeting, March 24–29, 2012. This abstract can be found at www.JVIR.org "" target="_blank" rel="nofollow">http://www.JVIR.org " target="_blank" rel="nofollow">www.JVIR.org .

Hello, We are researching this new procedure for my mother. We are wondering if they have to do surgery for this or is it done a more non invasive way. We contacted Martin in Ky and he says surgery???? Thanks,waiting in Wisconsin

The links listed;  SAN FRANCISCO, March 26, http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel eases/California/2012/03/26/DC70477""" target="_blank" rel="nofollow">2012http://www.bizjournals.com/sanfrancisco/prnewswire/press target="_blank" rel="nofollow">http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel target="_blank"" target="_blank" rel="nofollow">http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel rel="nofollow">http://www.bizjournals.com/sanfrancisco/prnewswire/press_rel

can't be reached.  Is there another link I can read the original article?

thanks for your reply. All the sites are closed. Do you have any other info?

When I give links to journal articles, their purpose is solely to verify that the articles are not fabrications.  You will find no additional IRE information at the sites.

For an excellent background paper on IRE read the following: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989557/pdf/gnl-

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989557/?tool=pu

The IRE procedure is performed thru the skin, with no surgical opening.  Most IRE practitioners are Interventional Radiologists.  They are not surgical oncologists (surgeons).

There is an advantage to seeking a surgical oncologist who is also an IRE practitioner, since a surgeon can use an incision to gain better IRE access to the tumor sites, or will combine IRE with surgical oncology.

Get yourself educated.  Read the physician version of the NCCN guidelines for Pancreatic Cancer, free at http://www.nccn.org/professionals/physician_gls/f_guidelines

Start with the background and therapy near the center of the document.  Then, read the decision trees at the beginning.  Read them over and over, until you understand them.  Medical management takes real work.

Finally, IRE is just one component in the treatment mix.  Read my postings throughout this thread, including the new developments announced this past month, posted near pages 8-11.

Philip

shirley22

Try Drs' Watkins-Stony Brook U or Dr. Martin at Uof Kentucky on Google. These doctors are surgeons not Interventional Radiologists. Also there's another surgeon  in Florida. Try Googling I.R.E. or NanoKnife surgeons for more info.

Pat

Hi Shirley

Everything depends on your situation. Interventional Radiologist do not do open surgery. Ask Dr. Martin why. We had surgery because there are other things that go with I.R.E. ei; bypasses if possible. Dr. Moeslein in Maryland just did one for kelilizabeth on this blog, she may have more info as he is a Interventional Radiologist. Sometimes just an e-mail will do or a phone call. There are many places that do the Interventional one but just a few surgeons. Dr. Martin should be able to tell you why.  Good luck!!!!

Pat