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nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Fri Feb 28, 2020 06:50 PM

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On Feb 25, 2020 7:14 PM PhilipJax wrote:

Mkk2018,
          Have you studied the Decision Guide and my last 2 years of posts as yet?  That means studying every line and every reference.  It takes a lot of work.  But, there are rewards: If there is an answer, that is where it will be found.
          I prepared the Guide and created the CancerCompass posts (taking scores of hours of work) to answer such questions as yours.  The best answer is within those two sources.
          For example, using those sources (1) a patient recently pursued a peritoneal metastases therapy; (2) another added Cisplatin to a common combination; (3) others have taken advantage of the new willingness to treat metastases when they are few; (4) another has enrolled in the hard-to-enter BATs trial, and (5) another is investigating hepatic arterial 5FU infusion combined with systemic chemotherapy. 
          You do not have to limit yourself to BRCA targeting.
         PhilipJax

Yes - and we are treating metastases as there are few, but 2 significant spots we need to stop/kill and or stablize - similar to your option 3, of this new willingness. That is our plan right now. The pancreas (original tumor) is atrophic. 

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Feb 28, 2020 07:31 PM

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Mkk2018,
          Thanks.  Please give links to the trial reports that you cite, the Phase 1 & 2 trial reports showing good performance for “SBRT in combination with immuno+parp” in metastatic cases (or BRCA cases, if you wish).
          Also, I do not understand your following two statements.  I hope you will take a moment to clarify:
1. but not everyone follows under those guidelines:” The Decision Guide addresses all disease stages and multiple lines of therapy, and the posts on past ASCO symposia address literally scores of research abstracts.  Virtually every case is addressed.
2. If you have information to support this:” Please tell me what you mean by “information to support this”?  Support what?
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Feb 29, 2020 04:15 AM

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Mkk2018,
          You may have misunderstood my 5 examples of non-standard therapies.  They were not meant as suggestions for you.  They are example of therapies found by recent users of the Guide and ASCO abstracts, as alternatives to standard of care.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Mar 02, 2020 06:29 PM

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On Feb 28, 2020 7:31 PM PhilipJax wrote:

Mkk2018,
          Thanks.  Please give links to the trial reports that you cite, the Phase 1 & 2 trial reports showing good performance for “SBRT in combination with immuno+parp” in metastatic cases (or BRCA cases, if you wish).
          Also, I do not understand your following two statements.  I hope you will take a moment to clarify:
1. but not everyone follows under those guidelines:” The Decision Guide addresses all disease stages and multiple lines of therapy, and the posts on past ASCO symposia address literally scores of research abstracts.  Virtually every case is addressed.
2. If you have information to support this:” Please tell me what you mean by “information to support this”?  Support what?
         PhilipJax

For sure. I just know that although your steps are extensive sometimes the route they suggest as far as finding treatment just is not working for everyone. Hence, us and it is. Rey hard to hear from other “don’t go that route”. It does address multiple lines of therapy but there are other lines out there. Immuno+Parp and SBRT just to name one. And yes the posts on ASCO symposia is fantastic also of which some do support what we are doing. Thank you for your posts and information! I will provide our sources we have looked at when we are ready. Anyone is able to search the combinations or contact other oncologists as ours do for some information ! Thanks so much for your extensive research in pan.can I read your information and search further some things you suggest! Thank you!

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Mon Mar 02, 2020 08:35 PM

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Mkk2018,
          It would be helpful, if you would answer the questions I pose, because others read these posts.  We must not mislead them.  
          Perhaps we could begin with the first question: Please be so kind as to give links to the trial reports that you cite, the Phase 1 & 2 trial reports showing good performance for “SBRT in combination with immuno+parp” in metastatic cases. Thanks.

         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Wed Mar 04, 2020 01:18 PM

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2020 Gastrointestinal Cancers Symposium
Installments, Part 4

Everyone,
          This is likely the final installment of abstract reviews from the 2020 GI Cancers Symposium, held January 23-25, 2020 in San Francisco.  There are at least 50 relevant abstracts; so, over a period of several days or weeks, I will cover the “best”.  If you can’t wait, the abstracts are found here:
http://pancreatic.altervista.org/downloads/GI20PancreaticCan
          The order in which I present the abstracts does NOT signify their importance.  I am merely beginning with the first abstract meeting my search criteria.
          Be sure to study my Decision Guide, downloadable at
PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg
or use Google to find the file: PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">PJaxDecisionAlgorithm.pdf
         PhilipJax

Abstract 716: A phase I/II study combining a TMZ-CD40L/4-1BBL-armed oncolytic adenovirus and nabpaclitaxel/ gemcitabine chemotherapy in advanced pancreatic cancer: An interim report
          American and Swedish researchers provide an interim report on the use of LOAd703, an immunotherapy, as a supplement to Gemcitabine / Nab-Paclitaxel.  In Phase 1/2b trial NCT02705196 the adenovirus LOAd703 was injected into the primary pancreatic tumor or metastasis of 13 advanced patients using image guidance.  Three subjects received low-dose LOAd703, and the remaining 10 received higher doses.
          The research is incomplete.  However, the results thus far are the following:
1. Of the 10 higher-dose patients 6 (60%) experienced Partial Responses, a very good outcome.  “Only 1 patient has had progressive disease.”  The median Overall Survival is not yet known, but the Response Rate portends a good outcome.
2. “Circulating MDSCs decreased in 8 of 13 subjects, while effector memory T-cells increased in 10 of 13” patients.  MDSCs are Myeloid-Derived Suppressor Cells.
          NCT02705196 is ongoing at Baylor University facilities in Houston, and is limited to a total of 43 patients who have not undergone prior immunotherapy.  The eligibility criterion (not eligible for a complete surgical resection”) IMPLIES that patients must be Stage 3 or 4.  So, if you are borderline resectable or locally-advanced, you might inquire.  ECOG performance status can be 0, 1 or 2, so somewhat feeble patients are eligible.  Check the trial description for more eligibility details.
          The clinical trial description is found here:
https://clinicaltrials.gov/ct2/show/NCT02705196

Abstract 702: Multicenter phase I/II study of intravenous gemcitabine + nab-paclitaxel combined with intraperitoneal paclitaxel for pancreatic ductal adenocarcinoma patients with peritoneal metastasis
          For the past two years leading research and treatment centers have been moving toward direct treatment of metastases, at least when there are few of them.  In this Phase 1-2 research 7 Japanese centers evaluated the treatment of peritoneal metastases which present “an extremely poor prognosis.”
          A total of 46 chemotherapy-naïve patients (no prior chemotherapy) received a combination of intravenous Gemcitabine and Nab-Paclitaxel, plus intraperitoneal Paclitaxel during a median treatment period of 6 months.
          The researchers reported the following outcomes:
1.The response rate and disease control rate were 45.7% and 95.7%, respectively (implying 50.0% Stable Disease – all are very good performance values).
2. “The median survival time was 12.8 months, and the 1-year survival rate was 52.2%.
3. “Ascites disappeared in 40.0%, and cytology turned negative in 67.4%.  Median CA19-9 decrease ratio was 84.4%
(“negative cytology” means that no cancer cells were identified).
4. “Finally, conversion surgery was performed in 8 (17.4%) patients, and those who received conversion surgery survived significantly longer than those who did not (not reached vs. 11.7 months
.”  “Not reached” means that more time must pass before researchers know; however, the value will exceed 11.7 months.
          Although this pancreatic research is incomplete, these researchers have published reports on intraperitoneal therapy for other primary tumors, such as gastric cancer.  See this report:
http://pancreatic.altervista.org/downloads/IntraperitonealPa
         In the USA theUniversity of Pennsylvania’s Abramson Cancer Center (and others) may be receptive to undertaking this intraperitoneal therapy.

691: The surgical outcomes of borderline resectable or locally advanced pancreatic cancer
          In this abstract Japanese surgeons reveal how they achieved “curative resection” in 67 (83%) of 81 borderline and locally-advanced patients, and how the 7-hour procedure achieved R0 resection in 96% of the 67 cases.  Their tactics achieve a 3-year after-surgery survival rate of 70.3%, with the same success in borderline resectable (contact with the main artery) and locally advanced cases.
          The surgeons describe their successful decision guide as the following:
1. “If a tumor is in contact with the superior mesenteric artery (SMA), we select the mesenteric approach.
2. “If a tumor is in contact with the common hepatic artery (CHA) and/or celiac artery (CA), we open the lesser omentum and then dissect from the cranial side of pancreas to the diaphragm leg to judge the resectability before dividing the stomach.
3. “When arterial plexus infiltration is observed during surgery, we abandoned curative surgery or we performed combined resection of CHA and reconstruction if possible.”
          The procedures are explained in the following 425-page surgery manual.  You should download it, rather then load it into your browser:
Pancreatic Cancer With Special Focus on Topical Issues and Surgical Techniques (2018)
http://pancreatic.altervista.org/downloads/PancreaticCancerS

693: Phase Ib study of gemcitabine, nab-paclitaxel, and ficlatuzumab in patients with advanced pancreatic cancer
            At two major US institutions researchers added Ficlatuzumab to standard care Gemcitabine plus Nab-Paclitaxel, as part of Phase 1b clinical trial NCT03316599.  The test subjects were 24 previously-untreated metastatic patients.  The results were the following:
1. Of the 24 patients 7 (29%) patients had partial response, 15 (63%) had stable disease, and 2 (8%) could not be evaluated.
2. “Median progression-free survival was 8 months (range, 3-16 months), 4 patients are still on study treatment.”
          These are all good results.  However, the sample size was too small to assure reliable application to the larger metastatic population.  A much larger scale trial will be needed. 
          Trial NCT03316599 is no longer recruiting.  But, it is reasonable to expect a Phase 2 trial, although none has been announced as yet.
         Ficlatuzumab, the experimental agent, was rather harsh, causingnine (38%) of the 24 patients to discontinue treatment prior to disease progression. Theprimary toxicities were hypoalbuminemia and edema.

685: The role of neoadjuvant chemotherapy in elderly patients with borderline or locally advanced pancreatic cancer: Is it safe and feasible?
          Sometimes Borderline (BL) and Locally-Advanced (LA) patients may be rendered resectable by means of Neoadjuvant Therapy (NAT), often employing either FOLFIRINOX (FFX) or Gemcitabine plus Nab-Paclitaxel (GnP).
          To determine whether elderly BL and LA patients might benefit from NAT, University of Colorado researchers reviewed the records of 230 consecutive BL and LA patients who underwent NAT at its cancer center.  214 cases were eligible for analysis and divided into three groups: <70, 70-74, >75 years of age.
          The researchers found the following:
1. “Resection rates were not statistically different between three groups (<70: 62%; 70-74: 70%; >75 years: 56%) . . . Neoadjuvant therapy . . . is a good option for fit and elderly patients >75 years.
2. “There was a slight trend towards worse survival in the two older groups.
3. “FOLFIRINOX group was superior to GnP group in all three age groups (Median Survival Time: <70: 25.6 vs 18.2 months; 70-74: 33.2 vs 16.1months; >75 years: not reached vs 16.1 months)”

690: Tumor downsizing following neoadjuvant therapy for borderline-resectable pancreatic adenocarcinoma
          Researchers associated with the Florida Hospital Cancer Institute sought to determine the effect of Neoadjuvant Therapy (NAT) on tumor downsizing.  To do so they reviewed the cases of 97 consecutive nonmetastatic unresectable patients, 40 of which undertook NAT.
          The Orlando researchers found the following:
1. Among the 40 NAT patients 90% experienced an average tumor downsizing of 8%.
2. There were no differences in rates of tumor downsizing between FOLFIRINOX or Gemcitabine/Nab-Paclitaxel-treated patients.
3. “Both regimens achieving a similar rate of R0 resections, a mean 61%.
4. “The type of chemotherapy regimen used did not affect the ratio of positive lymph nodes harvested.”
          This concludes my review of the ASCO 2020 GI conference, unless other news develops.  Some of the GI 2020 abstracts are worth greater attention, principally:
Abstract 716 LOAd703 Tumor Injection (clinical trial currently available)
Abstract 702 Intraperitoneal Chemotherapy (clinical trial not required)
Abstracts 664 & 672 Neoadjuvant vs Surgery First (clinical trial not required)
Abstract 681 Upper Abdominal Perfusion (clinical trial not required)
Abstract 754 Ipilimumab/Nivolumab For BRCA (clinical trial not required)
Abstract 682 Node Resection (clinical trial not required)
          The ASCO annual meeting takes place in mid-2020.  I expect to review the related abstracts at that time.
          It is important that you study my downloadable Decision Guide.  Within a few days of hard work you will understand how to approach this terrible disease, based on your disease stage – and learn what therapies work and which ones don’t.  The Guide is downloadable at
PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg
          If the link doesn’t work, do a Google search for the file: PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">PJaxDecisionAlgorithm.pdf
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by Tad187 on Sat Apr 04, 2020 05:07 PM

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Hi PhillipJax,

What worked for me to access the Decision Guide was Googling the file name.

Many thanks for your research work and insights.  

It's been a week since a CT scan identified a large mass in my pancreas, later confirmed to be an adenosarcoma. No showing of cancer elsewhere. A surgeon recommended chemo next because of celiac artery involvement and to reduce the size.  The surgeon also raised nanoknife/IRE.  I got to your posts at CancerCompass when trying to find out more about nanoknife. I'm in the SF Bay Area.  I've contacted PanCan network for their resources on expertise in the area.  

Tad187

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Apr 04, 2020 08:09 PM

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Tad187 & Everyone,
          When you STUDY the Decision Guide, you will find that Robert CG Martin of the University of Louisville is the world leader in IRE clinical practice research.  You will find his instruction guides linked at my website.
          Knowledge and skill make a difference.  The IRE probes must be positioned within 5mm of requisite distance for proper effect.  And, few practitioners have the desired 3D positioning radiology.  You are fortunate that you are in the US healthcare system.
          Be sure to study everything the Decision Guide has to offer, which includes two years of past CancerCompass postings.  Several days of hard work will save months of wasted wheel-spinning and lost opportunities.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by Tad187 on Sun Apr 05, 2020 05:22 PM

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Thanks you PhilipJax for the additional suggestions.

RE: nanoknife IRE for pancreatic cancer

by readerxxx on Tue Apr 07, 2020 03:43 PM

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WOW, this sounds wonderful.

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