nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Mar 03, 2018 02:32 PM

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Radiation May Not Be Helpful
Radiation Fails in R1 Resection

Everyone.
          American researchers, to determine the efficacy of post-resection radiation, reviewed the records of 1,392 patients detailed in the National Cancer Data Base.  Of these patients, 67.4% received adjuvant radiation and chemotherapy, and 32.6% received chemotherapy only.
          All patients had experienced “margin positive” resections, often called R1 resections – the type of imperfect resection thought to benefit from post-resection radiation.
         The strict definition of R0 requires a 1mm tumor-free margin. R1 means microscopic residual tumor in the margins, and R2 means macroscopic (visible to the eye) residual tumor.

Findings.  The researchers recount the following findings in their September 2017 report:
1. The benefit of radiation was found to be statistically significant only in “node-positive” patients – those with metastases to the lymph nodes.
2. For these node-positive patients radiation produced a median Overall Survival of 17.5 months, compared to 15.2 months for chemotherapy-only patients.
3. For healthier node-negative patients, “there was no survival benefit associated with adding XRT [radiation therapy] to adjuvant chemotherapy.”
          The researchers also referenced two trials (EORTC and ESPAC-1) which showed either no benefit to chemoradiation or a “deleterious effect [due] to . . . chemoradiation.”  The authors noted some defects with these studies (which may or may not be true), and referred to other research which revealed a “survival benefit [to] adjuvant chemoradiation over chemotherapy or resection alone.”
          Nevertheless, the authors consider its current research more reliable than the earlier efforts, since theirs is “the largest, multi-institutional analysis with the most contemporary dataset.”

Bottom line.  The researchers conclude: “There seems to be national trends in the utilization of XRT toward patients with node-NEGATIVE disease.  This is counterintuitive, as this group seems less likely to benefit from adjuvant radiation treatment” – a finding from their current research.
          So, the authors suggest even for node-POSITIVE patients: Given the limited observed survival benefit (~2.5 months), it may be more prudent to withhold radiation and consider adding it later.”

Severe Adverse Events.  The researchers warn that radiation is not risk-free, stating: “Radiation therapy to the abdominal region has been associated with substantial short- and long-term risks . . . These include pancreatitis, pancreatic insufficiency, steatorrhea, diabetes mellitus, peptic ulceration, delayed gastric emptying, enteritis, and small bowel obstruction, and the potential for radiation-related toxicity.”
          I will add that many of these adverse events do not occur until months later and could cause life-taking delays to other vital therapies.  The report can be downloaded here:
http://jaxelection.altervista.org/pancreatic/RadiationFailsR
          PROTON therapy, unlike the photon (X-Ray) therapy described above, causes fewer adverse events, but the therapy outcomes are likely to be the same.  There are about 15 Proton Therapy centers in the US, each costing approximately $150M each.  The facilities at Massachusetts General and the University of Florida, Jacksonville, have pancreatic experience.
          The NCCN Guidelines state: “Negative margin status (ie, R0 resection), tumor DNA content, tumor size, and absence of lymph node metastases are the strongest prognostic indicators for long-term patient survival.”
          The desired R0 resection can often be assisted by Irreversible Electroporation (IRE) performed intra-operatively (as part of open surgery).  And, some IRE practitioners are using IRE to treat lymph node metastases with some success.  See
http://jaxelection.altervista.org/pancreatic/IRE_LymphNodesG
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Mon Mar 05, 2018 08:52 PM

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Hospital & Surgery, Reduce the Risk
Avoid a Stupid Death

Everyone:
          No one wants to die for a stupid reason.
          Vanderbilt researchers estimate that each year 50,000 to 70,000 patients suffer death and 100,000 suffer kidney damage, because they are administered common, yet dangerous, IV fluids in critical care settings.
         Most often patients receive risky saline fluid which has been the mainstay in the US for 100 years. But “Balanced Crystalloid” fluids in a similar IV bag reduce the risk and cost about the same. And individual suppliers manufacture both IV products.

Wrong IV Bag. The typical saline IV contains high concentrations of sodium chloride, which is similar to table salt.  Vanderbilt researchers found, however, that patients do better if they were given balanced crystalloid fluids that closely resemble plasma, the liquid part of blood.
          The researchers found that for every 100 patients on “balanced” fluids there was one fewer death or severe kidney problem.  The use of such balanced fluids is widespread in Europe and Australia.  The hospitals at Vanderbilt and University of Pittsburg have largely switched to them.  Get more details in these articles:
http://jaxelection.altervista.org/pancreatic/BalancedCrystal
http://jaxelection.altervista.org/pancreatic/BalancedCrystal

Hospital-Acquired Infections.  Hospital-Acquired Infections are an enormous problem.
          About 770,000 patients contract hospital-acquired infections each year, and 75,000 die from the unexpected infection.  In 2017 congressman Steve Scalise, after being shot by an assassin, endured surgery to control a hospital-acquired infection.  See
http://jaxelection.altervista.org/pancreatic/SuperbugStalksN
http://www.cdc.gov/HAI/pdfs/hai/infections_deaths.pdf
http://www.cdc.gov/HAI/surveillance/index.html
http://health.usnews.com/health-news/news/articles/2013/09/0
          There are ways to prevent such infections, described in the articles below.
          In addition, you personally should undertake disinfection on a daily and hourly basis.  Use sanitizing bleach wipes on every surface which patients, family or employees MIGHT touch.
          That includes the obvious and the less obvious: Bed rails, TV remote, light switches, faucets, toilet controls, walls patients might use to steady themselves, chair arms, table tops, bed adjustment switches, everything one MIGHT touch.  And, if an employee or physician leaves some inexpensive invasive apparatus behind, to be used the next day, consider throwing it away when no one is looking.
          The disinfectant wipes might be obtained at home health product suppliers – hospital-grade germicidal wipes using a 1:10 dilution of sodium hypochlorite (5.25–6.15%).  CaviWipes is a brand made by Metrex.  If not available, use residential disinfectant wipes plus a Clorox bleach solution in a spray bottle.
https://www.metrex.com/en-us/products/surface-disinfectants/
https://www.metrex.com/sites/default/files/content/education
          And, bring a box of rubber gloves (it there’s not one in the room) and ask all visitors to use them.  After installing the gloves wash the glove-covered hands with soap and water and dry them with disposable towels.
          If the patient gets an infection, it may or may not kill him, but it will certainly cause a delay in vital cancer therapy, perhaps a fatal delay.
          A 2017 news report addresses sepsis.  Research shows that for every additional hour it takes to begin sepsis treatment, the probability of death increases by 4 percent.
          Some prevention measures are described in the following papers:
http://jaxelection.altervista.org/pancreatic/16_ProtectYours
http://jaxelection.altervista.org/pancreatic/Top10HealthTech

Clostridium Difficile (C-diff).  Each year in the US there are approximately 453,000 cases of C. difficile infection, and 29,000 deaths.  And, for pancreatic cancer patients, Cdiff recovery postpones vital cancer therapy, often a fatal postponement.  And the Cdiff recurrence rate approaches 20-30%, creating time for cancer to spread and metastasize.
          The following professional articles explain how to PREVENT and to TREAT a Cdiff infection.  You should study the prevention guide now.  And, if an infection occurs, below is linked the professional treatment guide; so, you know whether the proper measures are being implemented.
http://jaxelection.altervista.org/pancreatic/PreventCdiff201
http://jaxelection.altervista.org/pancreatic/TreatCdiffTrial
http://jaxelection.altervista.org/pancreatic/CdiffTreatmentG
http://jaxelection.altervista.org/pancreatic/CdifficileTreat

Immuno-Nutrition
          Several studies have found that a certain type of “over the counter” nutrition supplement improves surgery outcomes.
          In careful studies the pre-operative immuno-nutrition was found clinically significant in decreasing post-operative complications, length of stay, and improving post-surgery nutritional status.  The following reports give the details.
http://jaxelection.altervista.org/pancreatic/ImmunoNutrition
http://jaxelection.altervista.org/pancreatic/ImmunoNutrition
          The nutritional supplement is IMPACT ADVANCED RECOVERY from Nestle-HealthScience, described here:
https://www.nestlehealthscience.us/brands/impact/impact-adva
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by CASDAD on Mon Mar 12, 2018 06:17 PM

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Hello PhilipJax,

I have found this site and all of the information you share immensely helpful and I am continuing to comb through it. Thank you! I was wondering if there is an NCCN Guidelines document for Billiary cancers (specifically looking for extrahepatic cholangiocarcinoma). On a related note, do you know if IRE has been useful for recurrent bile duct tumors (with vascular involvement)?

Thank you, in advance, for your response.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Tue Mar 13, 2018 03:30 PM

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Dear CASDAD,
          Go to the NCCN website and complete the free user registration.  Then search among the “professionals” guidelines, and download the appropriate guide, probably “Hepatobiliary Cancers”.  Don’t waste your time on the patient downloads.
          Read the guidelines in the same sequence I suggest for pancreatic victims.
          IRE can manage any soft tissue tumor and, almost miraculously, leaves blood vessels and ducts without damage.  Previous posts, perhaps 6-12 months ago, offer many downloads of IRE training articles, most authored by Robert CG Martin.
          Dr Martin is certainly the world leader in the application of IRE to pancreatic cancer.  No matter whose care you seek, make sure the professional utilizes the new 3D needle guidance system.  The needle positioning must be within 5mm of standard, or the ablation will be imperfect.  You need an IRE practitioner who knows what he is doing.  If that means travel, do it.  Death is far more inconvenient than travel.  This disease doesn’t allow second chances.
          IRE may eventually be used for bone and brain tumors.  And a new generation of IRE machines will be needed for lung tumors due to the lung’s gossamer-like air sacs.
          I omitted links because the forum system delays posts containing hyperlinks.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Mar 23, 2018 01:55 AM

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Antibiotics May Help
Bacteria Influence Pancreatic Cancer Growth

Everyone:
          I rarely draw attention to pre-clinical findings.  However, a new report published 22Mar2018, based on animal studies, reveals that specific bacteria promote pancreatic cancer growth.  See
http://jaxelection.altervista.org/pancreatic/CertainBacteria
          An early study six months ago speculated that bacteria in the pancreas itself hampered the clinical effectiveness of Gemcitabine.  More on Gemcitabine later.  Back to the latest research.
          The new animal research, led by NYU’s schools of medicine and dentistry, found that, in pancreatic cancer patients, “pathogenic gut bacteria migrate to the pancreas through the pancreatic duct” where they “change the immune environment around cancer cells to let them grow faster.”
          These bacteria, specifically “proteobacteria, actinobacteria, and fusobacteria” “shut down the immune reaction to cancer cells.”  In the test animals “eliminating the bacteria using antibiotics restored the ability of immune cells . . . into immune-suppression.”
          And, the addition of oral antibiotics increased threefold the efficacy of checkpoint inhibitors, a form of immunotherapy.
          Soon researchers will recruit pancreatic patients into a clinical trial at Perlmutter Cancer Center, to test whether a combination of antibiotics (ciprofloxacin and metronidazole) can improve the effectiveness of a checkpoint inhibitor, an anti-programmed death receptor 1 (PD-1) antibody.
         But, if you are not responding dramatically to chemotherapy (especially Gemcitabine), do not wait for the trial. Consider asking that this antibiotic combination be applied immediately in your case. You have little to lose.

          Six months earlier in the other study researchers discovered that bacteria MAY explain why some pancreatic patients respond poorly to Gemcitabine.
          The 15Sep2017 research report, prepared by Israeli and MIT scientists, suggests that bacteria within pancreatic tumors can thwart Gemcitabine, a key therapy agent.  The culprit is bacteria equipped with the long form of the CDD gene.
          Tests, conducted in lab animals, demonstrated that antibiotics could suppress the unwanted bacteria and make Gemcitabine active again.  The report is at
http://jaxelection.altervista.org/pancreatic/BacteriaThwartC
          In addition, it has been widely suspected for years that bacteria from periodontal disease of the gums is a contributing factor to pancreatic cancer.
         Again, if you are not responding dramatically to chemotherapy (especially Gemcitabine), do not wait for the trial. Consider asking that the above antibiotic combination be applied in your case.

         PhilipJax

 

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Mar 30, 2018 03:15 AM

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Third-Line Therapy
More on Erlotinib + Gemcitabine

Everyone:
          New research, published February 2018, gives credulity to Erlotinib + Gemcitabine as a useful Third-Line Therapy, if the patient develops a rash.  The research, conducted at 20 German institutions, actually looked at the Erlotinib combination as a first-line therapy, not third-line.
          Nevertheless, the Erlotinib combo performed nearly as well as FOLFIRINOX, with comparable Overall Survivals of 10.1 vs 10.9 months, respectively.  Erlotinib is an EGFR tyrosine kinase inhibitor.  However, the compassionate switching of patients from Erlotinib and FOLFIRINOX to other chemo regimens (when the first therapies failed) clouds the comparison somewhat.  The report is downloadable at
http://jaxelection.altervista.org/pancreatic/Erlotinib+Gem_RashFOLFIRINOX2018Europe1771HiLite.pdf
          This new Erlotinib research follows a 2016 German article (from a different institution) which offers Erlotinib + Gemcitabine as a reasonable option for Third-Line therapy.  The article’s Therapeutic Algorithm (Figure 6), linked below in a cleaner format, offers many alternatives for each of the three treatment lines.
http://jaxelection.altervista.org/pancreatic/3rdThirdLine201
http://jaxelection.altervista.org/pancreatic/TherapeuticAlgo
          The Figure 6 algorithm repeats Gemcitabine in two different lines with some success.  And, the authors rely frequently on Erlotinib for part of a Third Line therapy, although other targeted therapies, for example Refametinib, might be used in the pair.
          In one Figure 6 path (G/P, then G+E, then C+E) Oxaliplatin might be added to G+E for more impact.  And, Cisplatin might be added to G/P in at least two treatment paths (path G/P, then G+E, then C+E and path G+E, then G/P, then C+E).
          The advantages of adding Cisplatin to Gemcitabine + Nab-Paclitaxel are described in this document.
http://jaxelection.altervista.org/pancreatic/AddCisplatinToGem+NabPaclitaxel2017.doc
          Abstracts 358 and 449 of the 2018 Gastrointestinal Cancers Symposium report very good performance due to the additions of Cisplatin, Nivolumab, Paricalcitol and Anakinra to Gemcitabine + Nab-Paclitaxel.  However, the test groups were small, creating less reliability.
          The two abstracts can be found in the following document.  Each abstract gives a link to its clinical trial website, so you can determine the agent dosages.
http://jaxelection.altervista.org/pancreatic/2018ASCOGICance
Also, be certain to study a recent post, titled: NEW Third Line Therapy.  It offers data supporting LV5FU2 + Nab-Paclitaxel as a well-performing third-line regimen.  LV5FU2 is a “simplified” 5FU/Leucovorin formulation called the “de Gramont simplification.”
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Mar 31, 2018 11:38 AM

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IRE + Chemotherapy Trial
Robert CG Martin, U of Louisville

Everyone,
          Yesterday, the University of Louisville announced a clinical trial to evaluate “the efficacy and tolerability of IRE in combination with either FOLFIRINOX or gemcitabine in patients with locally advanced pancreatic cancer.”  Robert CG Martin, MD, PhD, is the principal investigator.
          In the Phase-1 (or Phase-2) trial (the text contains a typographic error), “all subjects undergoing IRE will receive treatment with either FOLFIRINOX or gemcitabine (based on which regimen was received prior to IRE).”
          Enrollment is limited to 20 Stage-3, locally-advanced patients, and the trial is not yet recruiting.
          This is an opportunity for IRE treatment by the most experienced and skilled IRE staff in the world.  More details at
https://clinicaltrials.gov/show/NCT03484299
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by Barbara19 on Sun Apr 01, 2018 06:13 PM

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Terrific news @PhilipJAX Do you have any feedback on the use of the synthetic VITAMIN D: ZEMPLAR in combination with GEMZAR ABRAXANE. Trying this before any IRE. Love to hear your input

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Mon Apr 02, 2018 01:44 AM

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Vitamin D Supplementation
Does it Decrease or Increase Risk?

Barbara19 & Everyone,
          You’ve elected to take the Vitamin D derivative Paricalcitol (Zemplar).  What is your scientific basis for taking it?
          Paricalcitol’s role alone is not known.  However, Abstract 358 of the 2018 Gastrointestinal Symposium reports very good results for a new Gemcitabine and Nab-Paclitaxel regimen which adds Nivolumab, Paricalcitol and Cisplatin.
          Of 10 previously-untreated patients suffering from metastatic disease, 8 experienced Partial Response, and 2 had Stable Disease, for an 80% Response Rate.  And, Progression Free Survival was 8.2 months.  Median Overall Survival has not been reached.  See the posting here:
https://www.cancercompass.com/message-board/message/all,6312
          The exceptionally good response COULD be due to Cisplatin primarily, and Paricalcitol may contribute little.  No one knows.  Cisplatin’s performance is documented in this report:
http://jaxelection.altervista.org/pancreatic/AddCisplatinToGem+NabPaclitaxel2017.doc
          If you are currently utilizing Nab-Paclitaxel + Gemcitabine, please consider adding Cisplatin.
          The focus on Vitamin D started many years ago, and was heightened by a favorable 2014 report from the Salk Institute.
          However, last month a far-reaching European study (1) reported little prevention benefit to higher Vitamin D blood concentrations, and (2) hinted at INCREASED cancer risk, stating: “We cannot state that higher vitamin D concentrations are related to a higher PC risk, but it seems reasonable to conclude that higher vitamin D concentrations are not related to a lower PC risk in this population.”  The full report is here:
http://jaxelection.altervista.org/pancreatic/VitaminD2018Eur
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813219/
          The European research examined supplementation by the general population, not by diagnosed pancreatic cancer patients.
          Conclusion: Vitamin D supplementation MAY help and MAY not be harmful, but help is far from certain.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by Barbara19 on Tue Apr 03, 2018 11:05 PM

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Thank you @PHILIPJAX My brother is on GEMZAR/ABRAXANE & doing well.CA 19-9 down CRM 7900 in Dec to 195 now. Tumor is shrinking by 30-40% as seen by CT SCAN @ JOHNS HOPKINS. FOLFIRINOX didn’t work for him. Last April we went to see Dr Allyson Ocean @WEILL CORNELL. She recommended adding the PARACALCITROL to his regimen. She is finding it aids in breaking down the stroma to allow chemo to penetrate better to this tumor She felt he didn’t need CISPLATIN at this time. I am taking him to DR BARANZCI end of this week to get his input. Hearing many having awful side effects with the CISPLATIN. We are holding off on IRE at this time.
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