nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by cdaley2 on Tue Sep 05, 2017 07:32 PM

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Just to follow-up on Nano for lung mets situation:

I just heard back from Dr. Martin's office - his assistant Melanie called. First to complain about the order of papering. After explaining the situation, she said that 1) Dr. Martin does not do lungs and 2) Dr. Martin does not do mets. He only does Nano "once the mets is resolved", which assumes that the primary is still there I guess. I asked her if he had looked at my stuff, and she said this was just what she was instructed to say. I had a very similar conversation with Dr. Narayaram's nurse at U. of Miami. No. Mets. Period.

Small rant: I can't tell you how much time I have wasted faxing, filling out papers, etc. because upon reflection I was asking for too specific a treatment. Not only am I not getting through to a doctor, I am getting through to an assistant of maybe the right doctor or maybe the wrong one.

My new tactic is just to say I am looking for any local treatment - surgery, SBRT, Nano, rain dances, etc. I also believe that going to a pancreatic oncologist was a waste of time, after all I have a very good one. I also am asking whether or not I should see a lung specialist v. a PDAC guy, or a surgeor or an interventional radiologist or what, as now I almost feel that I am cut off from an insitution because I can't have nano, but there may be other things that could be offered.

So.......I have now reached out a little more broadly: a doctor that with his co-workers wrote an article about intervention with lung mets in PDAC for examply, other countries.

Finally i have an appoint this month at JH with a lung specialist. But....she seems to have trained under Dr. Martin, so I'm going to call and make sure I'm not barking up the wrong tree again.

PhilipJax, I've used your email format 2x today. Very helpful, thank you.

Any thoughts/idea/related rants welcome. Chris

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Tue Sep 05, 2017 08:30 PM

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Lung Metastases

cdaley2
          If you have studied my posts, you know that I have never suggested faxing or filling out papers as initial steps.  Be sure to read all my previous posts on Care Management.
          How do you know you have a “very good oncologist”?  What are your criteria, and how well does he match them.
          A lung specialist (pulmonologist) is not preferred for now.  STUDY my post to “Chris & Everyone,” titled: Second & Third-Line Chemo Regimens & Lung Metastases.  It may appear on page 76 of this thread, at
https://cancercompass.com/message-board/message/all,63127,75
          Study the paper by Moffitt, on lung metastases, and consider contacting the authors.
          Therapies other than ablating lung metastases may be more pressing.  We do not know the patient’s condition: All locations and sizes of tumors, pervious surgeries, chemo regimens failed and working, CA19-9 history, etc.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by cdaley2 on Tue Sep 05, 2017 10:42 PM

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Hi PhilipJax, thanks for getting back.

My oncologist is Dr. Eileen O'Reilly. She's very good, without question, and neither condescends nor ignores my temperment, which is a bit aggressive after way too many years as the only woman on a wall st trading floor, ha! She's not saying "no" to local treatment, she just wants to see if the lung mets stabilize. That's not crazy advice, IMO, I just want to be ready for when they don't stabilize. Funny enough, I often do a ton of research around her recommendations and ultimately come to the conclusion that she is right.

In this case, though, and especially after reading the Moffitt article as well as a German one, I think there is evidence to show that intervention prolongs life without incurring too much additional risk, at least that's my opinion.

Filling out papers was not the first/only steps I took, and I really do try to follow your older posts, but this forum is not the most user friendly, to be honest. (Either that, or I a too ADD) Seriously though, I think my mistake was to not use your email format first, recently posted to Dessmo - short and  sweet - and using it more broadly. As well, I think I focused too much on Nanoknife, even while knowing their general attitude toward mets. (What surprised me was that Narayaham at Miami wouldn't consider it, as he is a radiologist as opposed to a surgeon.)

Funny you mention Moffit - I did contact one of the authors today, using the Dessmo email formula of couse, and focused on the one that was known by someone I knew (Malafa). Since I had a 1 in 7 chance of picking the right one to contact  I also asked him to redirect me in the event I should have contacted on of the other 7 authors. That was the most on-point article (for me) I have read so far.

Additionally, I have been e-introduced by a friend to a Dr. in Tokyo, and after re-reading one of your posts on p. 76, I think I might email another set of doctors in Japan.

More: As I write, on of my best GFs just got me set up with MDA, where I think I can finally meet with Dr. Joe Herman. Getting through to MDA when you are a patient of MSK is not easy!

Anyway, PhilipJax, I just want to thank you for your posts once again. I think it was a re-read last night past midnight - of the direct email strategy that you set forth they other day. To anyone reading this: IT IS THE WAY TO GO! SEND THE EMAIL, DON'T GIVEN THEM A PRE-CONCEIVED NOTION OF WHAT YOU THINK YOU WANT!

I'll revert when I have more info. Best to all, Chris

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Wed Sep 06, 2017 02:12 PM

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cdaley2
          Several items:
1. I wouldn’t wait for the Lung metastases to “stabilize”.  A patient with metastases ONLY to the lung is somewhat rare, in a good sense, as you will have read in the Moffitt and Japanese articles.
2. Is the primary tumor(s) otherwise resectable and the CA19-9 low?
3. When selecting an author to contact, it is prudent to do research.  It is best to identify the institution’s most skilled practitioner for the subject practice.  If you begin communicating with the wrong physician, it will be very difficult to change physicians later.
4. In the initial communication, it is OK to name the art of interest, if it is a principal focus of the physician being contacted.  For example, it is OK to ask, “whether I might be a candidate for xxx”.  However, one aught not insist to an IRE surgeon “I wish to undergo percutaneous IRE but not intraoperative IRE” – that will be his professional decision, based on achieving the best outcome.  The insistence merely suggests a troublesome patient.
5. Regarding Joseph Herman, I was disappointed by misleading statements in his recent Let’s Win article.  The article and my assessment are available here:
http://jaxelection.altervista.org/pancreatic/StereotacticBod
         Finally, it is important to express ourselves carefully in this forum (that’s why my posts are long and detailed). We must assume that our statements may play a role in someone’s decisions.

         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Sep 08, 2017 11:35 PM

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Napabucasin (BBI-608)
Cancer Stemness Inhibitor

Everyone
          For metastatic patients there is a helpful development.  The cancer stemness inhibitor Napabucasin (BBI-608) performed favorably in a Phase 1b/2 clinical trial when combined with gemcitabine (gem) and nab-paclitaxel (nabPTX)
          Among 66 (Intent To Treat) patients, the Disease Control Rate was 77% (51 patients), with 2 Complete Responses (3%) and 28 Partial Responses (42%).
          Maturing median progression free survival and overall survival (OS) in ITT pts was >7.1 and >10.7 months, respectively.  A Complete Response (absence of disease) is a very usual and welcome event.  The following documents give details:
http://jaxelection.altervista.org/pancreatic/NapabucasinBBI-
http://jaxelection.altervista.org/pancreatic/NapabucasinBBI-
          The study included both therapy naïve patient and those having 1-2 prior therapies.  We don’t know which of the two fared better.
          To be eligible for the Phase 1b trial (link below), the patient may have had two prior systemic therapies.  For the Phase 3 trial, the patient “must not have previously received chemotherapy or any investigational agent.”  There are more limitations, so study the eligibility criteria carefully.
          The Phase 1b/2 trial is still open at 12 sites.  It is non-randomized, so everyone receives the therapy.  Enrollment was initially 250, but currently available berths are probably less than 100.  See
https://clinicaltrials.gov/show/NCT02231723
          Also starting is a Phase 3 trial at 24 sites including Australia, with enrollment of 1,132.  It is randomized, so only about half of patients receive the experimental agent.  See
https://clinicaltrials.gov/show/NCT02993731
          Both trials meet the definition of “prudent” choices, since, at minimum, everyone receives standard therapy, either Nab-Paclitaxel + Gemcitabine or FOLFIRI or a MM-398 (a form of Irinotecan) combination.
          Of course, there is no cure with the exception of resection (surgery), and surgery does not guarantee cure.  The objective is to get the patient resectable, or, if not that, buy time until the next helpful therapy comes along.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Sep 08, 2017 11:38 PM

Quote | Reply

Napabucasin (BBI-608)
Cancer Stemness Inhibitor

Everyone
          For metastatic patients there is a helpful development.  The cancer stemness inhibitor Napabucasin (BBI-608) performed favorably in a Phase 1b/2 clinical trial when combined with gemcitabine (gem) and nab-paclitaxel (nabPTX)
          Among 66 (Intent To Treat) patients, the Disease Control Rate was 77% (51 patients), with 2 Complete Responses (3%) and 28 Partial Responses (42%).
          Maturing median progression free survival and overall survival (OS) in ITT pts was >7.1 and >10.7 months, respectively.  A Complete Response (absence of disease) is a very usual and welcome event.  The following documents give details:
http://jaxelection.altervista.org/pancreatic/NapabucasinBBI-
http://jaxelection.altervista.org/pancreatic/NapabucasinBBI-
          The study included both therapy naïve patient and those having 1-2 prior therapies.  We don’t know which of the two fared better.
          To be eligible for the Phase 1b trial (link below), the patient may have had two prior systemic therapies.  For the Phase 3 trial, the patient “must not have previously received chemotherapy or any investigational agent.”  There are more limitations, so study the eligibility criteria carefully.
          The Phase 1b/2 trial is still open at 12 sites.  It is non-randomized, so everyone receives the therapy.  Enrollment was initially 250, but currently available berths are probably less than 100.  See
https://clinicaltrials.gov/show/NCT02231723
          Also starting is a Phase 3 trial at 24 sites including Australia, with enrollment of 1,132.  It is randomized, so only about half of patients receive the experimental agent.  See
https://clinicaltrials.gov/show/NCT02993731
          Both trials meet the definition of “prudent” choices, since, at minimum, everyone receives standard therapy, either Nab-Paclitaxel + Gemcitabine or FOLFIRI or a MM-398 (a form of Irinotecan) combination.
          Of course, there is no cure with the exception of resection (surgery), and surgery does not guarantee cure.  The objective is to get the patient resectable, or, if not that, buy time until the next helpful therapy comes along.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sun Sep 10, 2017 09:22 AM

Quote | Reply

Napabucasin (BBI-608)
Cancer Stemness Inhibitor

Everyone
          For metastatic patients there is a helpful development.  The cancer stemness inhibitor Napabucasin (BBI-608) performed favorably in a Phase 1b/2 clinical trial when combined with gemcitabine (gem) and nab-paclitaxel (nabPTX)
          Among 66 (Intent To Treat) patients, the Disease Control Rate was 77% (51 patients), with 2 Complete Responses (3%) and 28 Partial Responses (42%).
          Maturing median progression free survival and overall survival (OS) in ITT pts was >7.1 and >10.7 months, respectively.  A Complete Response (absence of disease) is a very usual and welcome event.  The following documents give details:
http://jaxelection.altervista.org/pancreatic/NapabucasinBBI-
http://jaxelection.altervista.org/pancreatic/NapabucasinBBI-
          The study included both therapy naïve patient and those having 1-2 prior therapies.  We don’t know which of the two fared better.
          To be eligible for the Phase 1b trial (link below), the patient may have had two prior systemic therapies.  For the Phase 3 trial, the patient “must not have previously received chemotherapy or any investigational agent.”  There are more limitations, so study the eligibility criteria carefully.
          The Phase 1b/2 trial is still open at 12 sites.  It is non-randomized, so everyone receives the therapy.  Enrollment was initially 250, but currently available berths are probably less than 100.  See
https://clinicaltrials.gov/show/NCT02231723
          Also starting is a Phase 3 trial at 24 sites including Australia, with enrollment of 1,132.  It is randomized, so only about half of patients receive the experimental agent.  See
https://clinicaltrials.gov/show/NCT02993731
          Both trials meet the definition of “prudent” choices, since, at minimum, everyone receives standard therapy, either Nab-Paclitaxel + Gemcitabine or FOLFIRI or a MM-398 (a form of Irinotecan) combination.
          Of course, there is no cure with the exception of resection (surgery), and surgery does not guarantee cure.  The objective is to get the patient resectable, or, if not that, to buy time until the next helpful therapy comes along.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Tue Sep 19, 2017 06:40 AM

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Gemcitabine Thwarted By Tumor Bacteria

Everyone:
          I rarely draw attention to pre-clinical findings.  However, this discovery MAY explain why some pancreatic victims respond poorly to Gemcitabine.  And, people are desperate for reasonable explanations.
          A 15Sep2017 study report suggests that bacteria within pancreatic tumors can thwart Gemcitabine, a key therapy agent.  Specifically, bacteria with the long form of the CDD gene could inactivate Gemcitabine.
          Tests, conducted in lab animals, demonstrated that antibiotics could suppress the bacteria and make Gemcitabine active again.  The report is at
https://medicalxpress.com/news/2017-09-scientists-bacteria-p
https://wis-wander.weizmann.ac.il/life-sciences/how-bacteria
and http://dx.doi.org/10.1126/science.aah5043
         PhilipJax

Role of Intratumor Bacteria in Resistance to Gemcitabine

          To the reasons that chemotherapy sometimes does not work, we can now add one more: Bacteria.  In a study published today in Science, researchers describe findings that certain bacteria can be found inside human pancreatic tumors.  The findings further showed that some of these bacteria contain an enzyme that inactivates a common drug used to treat various cancers, including pancreatic cancer.  Working with mouse models of cancer, they demonstrated how treatment with antibiotics on top of chemotherapy may be significantly superior to treatment with chemotherapy alone. 
          The research was conducted in the lab of Dr. Ravid Straussman of the Weizmann Institute of Science's Molecular Cell Biology Department, led by his graduate student Leore Geller and conducted in collaboration with Dr. Todd Golub and Dr. Michal Barzily-Rokini of the Broad Institute of the Massachusetts Institute of Technology.  Many other collaborators supported different aspects of the study.
          The bacteria the group found, explains Straussman, live within the tumors, and even within the tumor cells.  "Because the topic is so new, we first used different methods to prove that there really were bacteria inside the tumors.  Then we decided to look at the effect that these bacteria might have on chemotherapy."
          The researchers isolated bacteria from the tumors of pancreatic cancer patients and tested how they affect the sensitivity of pancreatic cancer cells to gemcitabine, a chemotherapy drug.  Indeed, some of those bacteria kept the drug from working.  Further investigation showed that these bacteria metabolize the drug, making it ineffective.  The researchers were able to find the bacterial gene responsible for this, a gene called cytidine deaminase (CDD).  They demonstrated that CDD comes in two forms – a long and a short form.  Only bacteria with the long form of the CDD gene could inactivate gemcitabine.  The drug had no apparent effect on the bacteria.
          The group examined over 100 human pancreatic tumors to show that these particular bacteria with long CDD do live in the patient's pancreatic tumors.  They also used multiple methods to visualize the bacteria inside human pancreatic tumors.  This is crucial, since bacterial contamination is a real issue for lab studies.
          Oddly enough, it was an earlier incidence of bacterial contamination that led Straussman and his team to this present study.  He and his group had been looking for evidence that normal cells in the cancer's environment contribute to chemotherapy resistance.  While testing the effect of many normal, non-cancerous, human cells on the sensitivity of cancer cells to chemotherapy, they found a specific sample of normal human skin cells that rendered pancreatic cancer cells resistant to gemcitabine.
          Tracking down the cause led the team to bacteria that had accidently contaminated these skin cells.  "We nearly threw it away," says Straussman, "but then we decided to follow it up, instead." After revealing how these bacteria degraded the drug, he began to wonder if other bacteria might have a similar mechanism for inactivating the drug, and whether such bacteria might be found inside human tumors.
          In the present study, further experiments in mouse models of cancer were done with two groups of bacteria: those containing the long form of the CDD gene and those in which the gene had been knocked out.  Only the group with the CDD gene intact exhibited resistance when the drug was given to the mice.  After treatment with antibiotics, this group also responded to the chemotherapy drug.
          Many questions remain, and Straussman and his group are now asking whether bacteria may be found in other cancer types and, if so, what effects they might have on the cancer and its sensitivity to other anti-cancer drugs including a novel family of immune-mediated anti-cancer drugs.
          More information: Leore T. Geller et al.  Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine, Science (2017). DOI: 10.1126/science.aah5043 .

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sun Oct 01, 2017 07:27 PM

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The Right Insurance Saves Lives
The Crucial Oct 15 – Dec 7 Medicare Enrollment Period

Everyone,
          The right insurance can make the difference between life and death.
          For Medicare recipients it is vital to enroll in ORIGINAL Medicare.  The enrollment period (also called the “election period”) is October 15 - December 7.
          The shortcoming of a Medicare ADVANTAGE plan is that it will not be accepted by many major cancer facilities.  And, of course, Advantage (and other managed care plans) will not be accepted by institutions outside the managed plan (Advantage) network.  Read the report at
http://www.medicarerights.org/pdf/Why-Consumers-Disenroll-fr
          Also, in addition to Original Medicare, get a Medigap (supplemental) plan to cover the 20% of costs which Original Medicare won’t cover.  Many states in the US present Medigap price data online.  For Michigan, for example, search: “medicare supplement” rates Michigan.    If Original Medicare pays a given medical cost, then the Medigap insurer must pay the 20%.
          And, Medigap information is available here:
https://www.medicare.gov/find-a-plan/questions/medigap-home.
          For newcomers: There are two types of Medicare: Original Medicare and Medicare Advantage (which is the general term for all managed plans).
         Nearly all major medical facilities want you to have Original Medicare. Advantage plans often limit you to medical providers who are the least capable and cheapest.

          What if you miss the October 15 to December 07 enrollment period?
          From Link-1 (below) it appears that you can switch during the period January 01 thru February 14 each year or PERHAPS October 15 – December 07.
          And, according to Link-2, you can be granted a Special Enrollment Period (SEP), if you enrolled in a Medicare Advantage plan based on misleading or incorrect information provided by plan materials, employees or insurance agents.  Link-2 covers Ohio, but the conditions are the same in all 50 states.
1. http://jaxelection.altervista.org/pancreatic/1_SEP-Chart_1a.
2. http://jaxelection.altervista.org/pancreatic/2_MedicareAdvan
          If you wish to pursue the SEP, here is how you may wish to proceed.  Make two phone calls (the phone number is within Link-2).  The first call will allow you to get your bearings and to get a feel for how to make a convincing “I was misled” argument:
1. In your first call say you are calling for a friend (which is true).  Don’t give any actual names.  Say your friend was misled into believing that US medical facilities would be included in your plan (or another explanation).  And, find out how quickly an SEP could be issued and its likely effective date.  It may be better not to name the desired medical facility or the medical condition.
2. In the second call, give all the enrollee details and your very well-considered argument.  It is possible that you don’t actually have to PROVE that you were misled.  Your reasonable, unwavering instance may be enough.  Now, whether the granted SEP date will be earlier than the POSSIBLE October 15 date, is another matter.  Press hard; you have nothing to lose.
          Finally, you will need a Medigap insurance plan to cover the unpaid 20% of Medicare Part A.  AARP is often the lowest cost Medigap plan, and the necessary AARP membership can sometimes be found on-sale, if you search online for it.
          And, if an SEP is granted, all Medigap providers must match the enrollment dates granted by Medicare.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Tue Oct 17, 2017 01:33 AM

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Pancreatic Neuroendocrine Tumors
Pancreatic NETs

Everyone:
          We don’t often address Pancreatic NETs, which is not the same as the more common Pancreatic Adenocarcinoma.
          A new, recent NET publication offers an opportunity to update NET therapy information.  The new publication is titled: Pancreatic Neuroendocrine Tumors: State-of-the-Art Diagnosis and Management.  It is available here:
http://jaxelection.altervista.org/pancreatic/PancreaticNETs_
          You may recall that there are two other, slightly older, publications, including the NCCN guideline, a mainstay for treatment.  The documents are available here:
http://jaxelection.altervista.org/pancreatic/NCCN3.2017Neuro
http://jaxelection.altervista.org/pancreatic/Chap65Pancreati
          Best Regards,
         PhilipJax

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