nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sun Jul 09, 2017 04:14 AM

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          You haven’t actually asked a question.  You’ve given much of your history.  So, you don’t have to repeat it.  But, please do the following:
1. Please reveal your age and physical condition.  How far can you walk in 15 minutes:  A mile, a half mile a quarter mile?
2. Find out the names of the trial agents currently offered you, and send a link to the one trial you consider the best in the nation.
3. Please formulate several questions you hope to answer. 
          Apparently, you want to know how to manage the pulmonary metastases and what therapy to undergo next.  But, I am not sure, and there may be more questions.

RE: nanoknife IRE for pancreatic cancer

by cdaley2 on Sun Jul 09, 2017 12:06 PM

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PhilipJax, here are the answers to your questions, followed by my questions.

1) I am 59 and in excellent physical condition, work out with weights 3 x a week and I can walk a mile in 15 minutes or maybe less. I also spin/cycle when I have time.

2) The name of the agent is KO-947, and here is the link:

Unfortunately, I would have move to Pheonix for a 2 years so it kind of ruins the point of spending time with my 16 year old daughter as she finishes her last 2 years of HS and is starting the college process.

3) If I could take one trial, it would be this:

My questions:

1) If I had only one question for O'Reilly next appointment, what should it be? I was thinking "what do you mean by slow?" but too vague.

2) Is there any room for balance and measured-ness in treatment or has it been shown that I'm supposed to throw the kitchen sink at it right now.

3) Dr. Martin and the Dr at Stonybrook's websites say they dont do IRE on mets. Are you aware of anyone that does?

4) given that I have such a small amount of cancer in my body - but obviously hope it stays in the lungs for now - and that they grew slightly while on gem/xeloda, does that mean gemcitibine is "out" as a therapy for me?

5) what/who is considered the best SBRT practice/practioner in the country, as I know MSKCC is probably a no-go. (I live in Brooklyn NY). I can travel but cannot move away, see above. 

Thanks PhilipJax, I have appointments with the Emerging Drug guy, Dr. Harding, on Wednesday and O'Reilly the following Tuesday, so this is very helpful in preparing for that. I'm sure I annoy them by going in with typed questions, but I don't care, ha!

Best, Chris

RE: nanoknife IRE for pancreatic cancer

by stepuha on Tue Jul 11, 2017 06:24 AM

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Dear PhilipJax, I have just seen an article about the experimental agent CPI-613 which has previously appeared on your thread. The pharmaceutical company Rafael Pharmaceutical can provide the drug free of charge for compassionate use. To qualify a patient needs to complete the form in the link below and send it to the company: Given the positive results of the early trial this seems to be a viable option for those who are running out of options. I just thought this may be of interest. Kind regards. Stepuha

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Wed Jul 12, 2017 01:48 AM

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To Stepuha & Chris:

Dear Stepuha,
          Your contributions have been very helpful.  And, the CPI-613 update is very useful.  It appears from the form that the patient (together with the medical records he should have at all times) does not require a physician referral to apply for compassionate use.  Forum visitors will be indebted to you.
         Unfortunately, a storm 2 days ago knocked out my Internet service and my landline. I am operating from a library computer, so I cannot refer to my past documents on this agent.

Dear Chris,
          As soon as my Internet service is restored (I don’t have a date) I can send information on the pulmonary metastases.  I have two excellent 2016 papers which encourage removal of the lung metastases.
          Regarding the ERK inhibitor KO-947, this is the first human trial.  The enrollment is 72, and the experimental subjects can have any non-blood cancer.  Even when the trial is finished there will be too few pancreatic patients to derive useful projections of future effectiveness.
          The trial appears to be a manufacture shotgun to find out which cancers to pursue in the future, the price being paid by the bodies of desperate patients.
          I could be wrong.  However, the PC patient doesn’t get many “do overs”, and this is not a prudent choice.  A prudent trial contains a new agent in addition to known highly-regarded chemo regimens, and the preferred new agent trial has results from prior Phase-1 or Phase-2 studies.
         An agent’s success in a pre-clinical (non-human) trial has little assurance of human success. Every failed human trial (of which there have been many hundreds) began as a successful pre-clinical trial.


RE: nanoknife IRE for pancreatic cancer

by cdaley2 on Wed Jul 12, 2017 11:23 AM

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Dear Philip, 

I have the same vibe about this test. I am on my way there to grill him about it anyway, figuring I might learn something. Will post if there is anything interesting. I wish I were a mouse!

Good luck getting your internet back - I would be crazy without it...

Best, Chris

RE: nanoknife IRE for pancreatic cancer

by HelenT on Wed Jul 12, 2017 11:15 PM

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On Jul 05, 2017 2:12 PM PhilipJax wrote:

Here are the two messages I sent, but you did not receive.

          I note that AM0010 and PEGPH20 have trials in Australia.  Study the very important Inclusion/Exclusion criteria.
>> AM0010 is randomized, meaning that about half the patients do NOT receive the experimental drug.  Also, a prior, failed Gemcitabine regimen is required. And, prior radiation appears to exclude a patient.  But, contact the facility, because details on required prior therapies are confusing.  See "" target="_blank" rel="nofollow"> " target="_blank" rel="nofollow">  
>> PEGPH20 is also randomized.  Prior treatment of any kind apparently excludes the patient.  Check with the facility to confirm this.  See  "" target="_blank" rel="nofollow">  " target="_blank" rel="nofollow"> 
          Your initial oncologist is remiss by failing to refer you to these trials.
>> Cisplatin + Nab-Paclitaxel + Gemcitabine.  This combination does not require any trial participation.  It can be administered by any medical oncologist who will research the protocol.
          Please assure me that you got this letter, and please confirm my assumptions in this and the previous message.  By “assumption” I mean whenever I use the expression “I assume”.

Dear Helen,
          As you likely know by now, even with the best therapy and the best care management, this disease most often wins.
          I assume that the IRE was performed percutaneously (thru the skin), which is not as accurate as intraoperative IRE (part of open surgery) or laparoscopic surgery.
          The IRE should have been followed by potent systemic combination therapy (not just Gemcitabine monotherapy), but apparently was not.  There are microscopic metastases which must be managed, and radiation won’t do it, because it targets a specific site.
          In fact, radiation may not be helpful, and creates a risk: Possible gut perforations and spinal cord damage, which may delay or prevent future therapy.  Proton Therapy (not the same as Photon X-ray therapy) has far less damage risk.  See the following: tNotRadiation2016.doc "" target="_blank" rel="nofollow"> target="_blank" rel="nofollow"> eficial2016.doc "" target="_blank" rel="nofollow"> target="_blank" rel="nofollow"> ic2015UFProton_WJGO-7-141.pdf "" target="_blank" rel="nofollow"> target="_blank" rel="nofollow"> nTherapy2015.pdf "" target="_blank" rel="nofollow"> target="_blank" rel="nofollow"> eaticC100612.pdf "" target="_blank" rel="nofollow"> target="_blank" rel="nofollow">
          You should consider one of the recently posted therapies if she is strong enough to endure them:
1. CPI-613 combined with FOLFIRINOX (if she is strong).  Check the clinical trials website to learn when the next trial begins.
2. One of the 4 PEGPH20 trials which are now open and geographically plentiful.  She will be tested (perhaps by your current facility) to learn whether she has high levels of Hyaluronic Acid (HA) – a requirement for treatment and for therapy benefit.  This is one of the least toxic.
3. AM0010.  See the recent post.
4. Add Cisplatin to Nab-Paclitaxel + Gemcitabine – somewhat toxic.  Consider, if Gemcitabine has not failed.  But, it seems that she has not failed any therapies yet.
5. IRE can be performed on lung sites, if the practitioner is highly skilled on lung applications.  However, there must still be systemic therapy (systemic chemotherapy) to address the micrometastases.
          Immunotherapy (although it sounds intellectually appealing) is generally not consistent with pancreatic adenocarcinoma, although some exceptions MAY appear soon.  Some benefit might be had, if not now, some time in the future.  Read the linked articles (in pervious posts) on immunotherapy cautions to find out more.
          Additional radiation probably will not yield a cure.  However, it might be beneficial to relieve pain only after all other therapies have failed and the end is approaching.
          Be sure to study the last 2 years of posts.  And, get WordWeb to help understand technical terms.  See "" target="_blank" rel="nofollow"> " target="_blank" rel="nofollow">

Hi Philip, 

my mother has become quite weak, and her cough is worsening, with lots of fluid/phlegm being coughed up. She's seeing her oncologist today, but I can't see her doing any chemotherapy - I don't think she can tolerate it at this stage, and we're running out of time. Am devastated.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Thu Jul 13, 2017 01:20 AM

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Second & Third-Line Chemo Regimens & Lung Metastases

Chris & Everyone,
          You can always find someone who will do photon (X-ray) radiation.  And, clinical trials have an incentive to recruit experimental subjects.
          We should not make trial decisions based on pre-clinical (non-human) studies.  Every one of the failed human trials (of which there have been many hundreds) began as a successful pre-clinical (animal) trial.
          Regarding immunotherapy, before making any decision you must read the immunotherapy articles whose links are posted above.
         Also, time is wasted waiting for upcoming physician meetings. Great volumes of information are available online. Before each meeting you should already have figured out what agent will be offered, what therapies work and which don’t. It just takes a little work and some cautious reasoning.

1. Chemotherapy performance numbers.  Performance numbers are all that matter; there is no other way to compare different therapy regimens.  Anecdotal stories by physicians or forum contributors do not count.
          To learn about the relative-performance of different regimens (and what regimens might be available for the future) study the performance numbers in the tables of the articles linked below.  Look for Response Rate, Progression Free Survival (PFS) and Median Overall Survival (OS).  For the NCCN document search for the Block rankings of chemo regimens, around page-42, and pay attention to the far-left column.
          Keep in mind that the performance numbers usually (but not always) result from experimental therapies received by previously untreated patients.  And, some agents, like Gemcitabine, will be less useful in future regimens if they have failed previously.  See
          And review new therapies in the 2016 ASCO forum linked below
          The two forum “instructors” are creative oncology leaders who could be consulted in your own case.
          In addition, MM-398 (Nanoliposomal Irinotecan, nal-IRI) might be a component of a future third-line therapy.  MM-398 accesses the tumor more easily, often allowing lower doses than the original Irinotecan.  See

2. Response Rate & Hitting hard.  When you review the above reports you will see that even the best regimens under the best circumstances rarely have Response Rates exceeding 50%.  That means that about half of patients receive no benefit at all.  And, those who benefit often receive minimal benefit, and they are rarely if ever cured.
          So, the better strategy may be to attack the disease with the most potent available therapy while the patient is strong and while the tumor burden is relatively small.  Wait, or select mild therapies, and one day the patient, in a weaker condition, may find himself with multiple metastases in multiple organs and with a tumor burden that no strong regimen can restrain.
           “Tumor Burden” refers to the amount of cancer in the body.  If the “burden” is slight, the chemo agents may be more successful, because there are fewer cells which must be eradicated.
         The documents cited in Item 1 will help identify a third-line regimen. I cannot suggest a best therapy for you, because you must study the research and apply it to your specific conditions.

3. Pulmonary metastases.  IRE may not be best suited to this application due to the saclike structure of the lung, resulting in great differences in electrical conductivity between the lung and the tumor tissues.  The following article describes several lung ablation technologies:
          Perhaps a preferable, less-invasive approach would be PROTON therapy, not the same as photon (X-ray) therapy.  Both Massachusetts General and the University of Florida Proton Therapy Institute at Jacksonville have programs for lung cancer (some of the other 15 proton facilities may have such programs as well).    Perhaps they will treat lung metastases, especially if you acquaint them with the journal articles in Item 4.  Regarding proton facilities:
         These are enormously expensive, $170M facilities. So, they may have an incentive to help you gain insurance coverage.

4. Treat lung mets?  A physician claim, that pancreatic patients live “for years” with pulmonary metastases, is misleading.  Even a Median Overall Survival (OS) of 2 years means that, at 2 years, half the patients have already died.
          Two recent journal articles (below) address pulmonary metastases due to pancreatic cancer.  Median Overall Survival (OS) is given.  But, readers should not compare their performance numbers, because the sample sizes are small, and patient selection criteria and therapy histories are different.
          The first article reports on a very informative 2016 German study, which found that metastatic patients lived months longer (a) if the metastases developed solely in the lung (22 patients studied) following prior resection of the primary site (that is, if the lung metastases were not present at initial PC diagnosis), (b) if the metastases were 10 or fewer, and (c) if the metastases were confined to one lung.
          The researchers conclude that “patients with solitary lung recurrence after resection of PC might also benefit from surgical intervention or stereotactic radiosurgery.”  “Solitary” means in the lung only, not the liver or elsewhere.  See
          The second, thoughtful 2016 Moffitt report on 16 patients offers a similar recommendation: “Pancreaticobiliary cancer . . . may derive therapeutic benefit from pulmonary metastasectomy [surgical removal of metastases] when they meet the standard criteria, especially if they have a low preoperative serum CA 19-9 level.  “Pancreaticobiliary” means cancer of the pancreas or biliary system.
          The researchers noted: “Not all new lung masses in pancreatic cancer patients are metastases, and resection should be considered, for a potentially curable, second primary lung cancer is often found.”
          They added: “Most oncologists think that any pancreatic cancer patient who has or develops a lung mass is most likely to have stage IV pancreatic cancer, and only palliative chemotherapy is recommended.  Even if the lung lesion is known to be a [primary] lung cancer, surgery is generally not recommended, based on the reasoning that the pancreatic cancer will kill the patient long before the stage I lung cancer will harm the patient.  Fortunately, this reasoning seems to be flawed . . . ”  The Moffitt article is here:
          Finally, the authors conclude that pulmonary metastasis, as the first site of PC dissemination, is a rare event and might define a biologically distinct subgroup in metastatic PC (Liver metastasis represents the first site of dissemination in over 80% of metastatic pancreatic cancer patients).  “Dissemination” means metastasis.
          A third article, from Japan, describes the results of pulmonary metastasectomy in 4 cases, describing them as “favorable outcomes”:


RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Thu Jul 13, 2017 01:23 AM

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I cannot express how sorry I am to hear this.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Thu Jul 13, 2017 01:39 AM

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Dead Links In PhilipJax Posts

          In my lengthy post immediately above many links appear dead.  However, the forum system has added trash after the pdf file name, irrelevant trash like %c2%a0.
          To make the link work, merely right-click the link and select “copy the shortcut.”  Then, paste the link in a new tab.
          If AFTER pasting, the trash is still present at the end of the file name, remove the trash and press Enter.  That action should either load the file in a pdf reader or allow the file’s download.

RE: nanoknife IRE for pancreatic cancer

by HelenT on Thu Jul 13, 2017 09:44 AM

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Philip, you are very kind - your thoughts are appreciated. 

Mum saw her oncologist today. He told us she is being evaluated for a trial at Sydney's St Vincent hospital, but that could take 6-8 weeks. He didn't give much away, but I think he called it a 'motion' trial? I wasn't there and was told by my father.

So, in the meantime, he wants to start her on Folfirinox for the lung metastases, possibly as early as next week. It's once every two weeks in hospital for 5 hours and she'll have the tube (can't remember its name) implanted to protect her veins. He said this won't affect her eligibility for the trial. 

What do you make of this? 

Many thanks, Helen

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