IRE: Irreversible Electroporation

EndPC

Evidence N' Decisions:  Pancreatic Cancer

 

 

 

 

How To Use This Site

 

Pancreatic Cancer Warnings

 

Mission:

EndPC, managed by PhilipJax, provides links to all the best and latest pancreatic cancer therapy information.  This is the Evidence needed to make Decisions.

Pancreatic Adenocarcinoma is the principal subject matter, although Pancreatic NET’s and Acinar Cell Carcinoma are sometimes addressed.

Time is an enemy; so patients need information they can use immediately.  Consequently, EndPC omits therapies that are years away from clinical use.  Most don’t materialize anyway.

This is the information source I needed 20 years ago when my brother Mark was dying from pancreatic cancer.

The Warning Signs are:

1.   Low mood or depression

2.   Indigestion

3.   Diabetes

4.   Pale & smelly stools

5.   Jaundice

6.   Mid-back pain

7.   Upper abdominal pain

8.   Pain on eating

9.   Fatigue

10.  Unexplained weight loss

11.  Diabetes onset after 50 in Blacks & Latinos

Download this poster here.

How to Use EndPC:

Use Ctrl-F to search for topics on this page.  Topics are listed alphabetically; but a given topic may appear in several groups.

For example, the role of bacteria may be listed under “bacteria” and “antibiotic.”

Most (but not all) topics link to PhilipJax essays at other sites.  Those without links are under development.  All PhilipJax posts might be found here.

>>> Start Here <<<

This download brings it all together, guiding you through the decision process

Decision Guide

Have Questions?

Send emails to [email protected].  But, do not write until you have studied the materials here related to your question.  Then, reference the materials in your question.

Click the image to download the Guide which covers all treatment issues.  It is updated often, so check back weekly.  Each revision contains an issue date.

 

 

Topics List

Every topic is vital & revealing reading

 

 

 

Minor Breakthrough Potential

 

     Metastatic Stage 4: Some patients now eligible for surgery

     Third-Line Therapy: Some Possibilities

     Chemo or Surgery First?  New Thinking

     Add Cisplatiun to Nab-Paclitaxel+Gemcitabine?

     BRCA Treated By PARP Inhibitors

     PAXG (with Cisplatin) Performs Well

     How To Pick The Best Treatment Facilities

     Find The Best Clinical Trials

     New NCCN Guidelines & How To Use Them

     mFOLFIRINOX Superior After Resection

     Right To Try Act: Experimental Drugs

     US Healthcare For Non-Citizens

 

 

 

 

Acinar Cell Carcinoma (ACC) here & here

 

 

 

Anaplastic, Pleomorphic Carcinoma of the Pancreas here

 

 

 

Adjuvant Chemotherapy (After Resection)

 

 

mFOLFIRINOX – Labeled a “Breakthrough” at the 2018 ASCO Annual Meeting, here1, here2 & here3

 

 

 

Anorexia & Cachexia (Prevent Wasting) here

 

 

 

Ascites here1, here2, here3, here4, here5 & here6

 

 

 

ASCO Meetings & Symposia

 

 

2018 Gastrointestinal, January here & abstracts

 

 

2018 Annual Meeting, June here & abstracts

 

 

ASCO Clinical Practice Guidelines

 

 

 

ASCO 2017 Stages 1 & 2 guide

 

 

 

ASCO 2016 Stage 3 guide

 

 

 

ASCO 2018 Stage 4 guide

 

 

 

Bacteria Aid Cancer, Thwart Chemo Agent; Antibiotics Helpful here1, here2 , here3 & here4

 

 

 

Beta Blockers Help here

 

 

 

Blood Transfusion (harmful, avoid it), see this

 

 

 

Care Management

 

 

2018, available in the column to the right

 

 

 

C. diff Infection here

 

 

 

Chemotherapy Regimens

 

 

Best Adjuvant Therapy (Post Resection) here

 

 

Best Maintenance Therapy (Post-Resection & Post Adjuvant) here

 

 

Third Line Therapy here

 

 

Emerging Agents here

 

Other Chemo Regimens follow:

 

 

New & Emerging Regimens here

 

 

Which is the better first therapy Nab-Paclitaxel + Gemcitabine or FOLFIRINOX? here

 

 

Which sequence is better, NabP/Gem + NabP/Gem or NabP/Gem + FOLFIRINOX? here

 

 

FOLFIRI better than FOLFIRINOX & FOLFOX? here

 

 

mFOLFIRINOX better than FOLFIRINOX? here

 

 

 

Predict FOLFIRINOX Response here

 

 

 

BRCA Role for FOLFIRINOX & Cisplatin here

 

 

2018 ASCO Gastrointestinal Symposium, Jan here

 

 

2018 ASCO Annual Meeting, Jun here & abstracts

 

 

Critical!: Third-Line Therapy Regimens here

 

 

Add Cisplatin to Nab-Paclitaxel/Gemcitabine here

 

 

 

Cisplatin: How to manage harsh cytotoxics here

 

 

 

PAXG: Good performance was reported in 2018 for Metastatic Stage 4 & Locally Advanced Stage 3

 

 

 

Cisplatin requires hydration.  Review the topic: Wrong IV Bag here

 

 

BRCA Role for FOLFIRINOX & Cisplatin here

 

 

Nab-Paclitaxel/Gemcitabine Upgrades here

 

 

GABRINOX: Merged Gem/NabP + FOLFIRINOX, Abstract 4109 here

 

 

Chemo Regimens where Nab-Paclitaxel is not available (as in some European nations) here

 

 

 

PEXG, PEFD & PDFG Regimens here & here

 

 

OXIRI & AGAP Regimens here

 

 

Metronomic Chemotherapy Schedule here

 

 

 

Chemo Agents, Emerging.  NOT a priority list

 

 

AM0010 here, bottom of page

 

 

CPI-613 here

 

 

Napabucasin (BBI-608) here & Phase 3 Trial here

 

 

EGFR BATs Immunotherapy, Abstract 4108 here & 2015 report here

 

 

TTFields (Tumor Treating Fields) here

 

 

PEGPH20 details below

 

 

For Liver Metastases see Pressure Delivered CAR-T therapy here, a new clinical trial may be available in 2019

 

 

 

Clinical Trials

 

 

How to Select the Best, column at right

 

 

IRE + Chemo Trial at the University of Louisville (limited to 20 patients), details here & here

 

 

Jan 2018 ASCO Gastrointestinal Symposium details good ongoing trials starting here, bottom of page

 

 

Jun 2018 ASCO Annual Meeting describes good ongoing trials starting here

 

 

Jun 2018 ESMO Meeting cites a few good trials here

 

 

 

ESMO European Society For Medical Oncology

 

 

Jun 2018 Meeting here

 

 

 

Financial Help

 

 

Travel & Support: Angel Flight and CancerNet

 

 

Charity Grants: CancerCare

 

 

Drug Discounts: Contact the manufacturer’s customer assistance team

 

 

 

Genetic Testing here & the discussion to the right

 

 

BRCA Mutation

 

 

 

Role of FOLFIRINOX & Cisplatin here

 

 

 

Early evidence of PARP benefit is presented here in 2014, here & here in 2016, here in 2017 & here in 2018

 

 

 

PARP-inhibitor Rucaparib may help BRCA-defect patients, but appears to work better as 2nd Line monotherapy

 

 

DDR Defects & PARP Inhibitors, Abstract 4128 here

 

 

MSI, dMMR & Lynch Syndrome, Abstract e16254 here

 

 

 

High Volume Facilities Are Life & Death here

 

 

 

Hospital Threats

 

 

Wrong IV Solution here

 

 

Medical Devices Likely To Hurt Patients here

 

 

Prevent Hospital-Acquired Infections here

 

 

Prevent & Treat C. diff Infection here

 

 

Immuno-Nutrition, taken before IRE or surgery here & here

 

 

Prevent wasting (Anorexia & Cachexia) here

 

 

 

Immunotherapy (see also Targeted Therapy)

 

 

MSKCC’s Eileen O’Reilly on Immunotherapy here

 

 

AM0010 here, bottom of page

 

 

EGFR BATs Immunotherapy, Abstract 4108 here & 2015 report here

 

 

Pamrevlumab (FG-3019), Abstract 4016 here

 

 

Pembrolizumab (Keytruda) (PD-1 blocker): MSI, dMMR, Lynch Syndrome, Abstract e16254 here

 

 

 

Beware: In rare cases PD-1/PD-L1 blockers have caused rapid disease progression, called hyperprogression, more here

 

 

 

Irreversible Electroporation (NanoKnife®)

 

 

IRE + Chemo Trial at the University of Louisville (limited to 20 patients), details here & here

 

 

How IRE Works here and see discussion below

 

 

Pancreatic Cancer & Training Materials here

 

 

3D IRE Needle Guidance System here

 

 

IRE vs Microwave Ablation here & here

 

 

Facilities Offering IRE

 

 

 

Pancreatic Specialists 2016 here1

 

 

 

Manufacturer List here2, here3 & here4

Disease & Specialty (Surgeon Vs Radiologist) are revealed in List-1, but not in Lists 2-4.

 

 

 

Some IRE Practitioners in Europe here

 

 

Nanoknife Surgery Warriors support group & below

 

 

 

Liver Metastases

 

 

Infusion Chemotherapy here

 

 

IRE Irreversible Electroporation here, here & here (near bottom of page)

 

 

 

Lung Metastases Removed here & here

 

 

Manageable if limited to lung here, here & here

 

 

Ablation Methods here, here & here

 

 

 

Lymph Node Metastases Removed here, here

 

 

 

Metastases Removal If Few Sites here & here

 

 

 

Microsatellite Instability (MSI), Mismatch Repair Deficiency (dMMR) & Lynch Syndrome

 

 

Pembrolizumab (Keytruda): Anti-PD1/PDL1 Checkpoint Inhibitor, Abstract e16254 here & at right

 

 

 

Read about disease hyperprogression above

 

 

 

NCCN Clinical Practice Guidelines, Use Them

 

 

1.2018 here, 2.2018 here

 

 

3.2017 here

 

 

ASCO Clinical Practice Guidelines

 

 

 

ASCO 2017 Stages 1 & 2 guide

 

 

ASCO 2016 Stage 3 guide

 

 

ASCO 2018 Stage 4 guide

 

 

Pain Management: An international group offers a comprehensive guide

 

 

 

PanCAN’s Know Your Tumor Program here

 

 

PanCAN’s Know Your Tumor program fails to improve the chief measure of success: Overall Survival.  Read the Conclusions in this latest trial report.  And, read more about Targeted Therapy here.

 

 

 

Pancreatic NET’s (NeuroEndocrine Tumors) here

 

 

 

Peritoneal Metastases are Treatable

 

 

Study Abstract P-137 here

 

 

 

PEGPH20 (Trials of Metastatic Patients)

 

 

Fails when used with FOLFIRINOX here

 

 

Succeeds when used with Nab-Paclitaxel + Gemcitabine, but only in HA-High patients here

 

 

 

Precision Medicine (Targeted Therapy) here

 

 

 

Proton Therapy (Particle Radiation) here

 

 

Advantages here

 

 

Proton Therapy Centers, list here

 

 

Lung treatment here

 

 

Lymph Node treatment here

 

 

Temporarily, UK’s NHS funds some Proton Therapy in the USA plus travel, see this, this & this

 

 

 

Radiation (This is X-Ray Photon, not Proton)

 

 

Case For here

 

 

Radiation does NOT benefit metastatic patients, see Abstract e16257 here.  And it does NOT benefit R1 resection patients, the report is here & review here

 

 

Case Against here

 

 

ChemoRadiation here

 

 

2018 Gastrointestinal Symposium here

 

 

Warning: Fiducial insertion could seed malignant cells unless a peripheral path is used, see this

 

 

 

Resection / Surgery

 

 

Surgery Scope & Details

 

 

 

Surgical Resection options

 

 

 

Prevent Complications

 

 

 

Minimally-Invasive Techniques

 

 

Surgery-First vs Neoadjuvant-First here & here

 

 

New Maintenance Therapy After-Surgery here

 

 

Pasireotide halves resection-related risk here

 

 

ImmunoNutrition before surgery here & here

 

 

 

Right To Try Act here

 

 

 

Sleep Method

 

 

Bright Light Sleep Therapy here

 

 

PhilipJax Sleep Method here

 

 

 

Stents to Manage Biliary & Duct Obstruction

 

 

Ensure that stents are removable, to allow IRE later

 

 

 

Surgery-First vs Neoadjuvant-First here & here

 

 

 

Symptom Management here

 

 

Control Venous ThromboEmbolis (VTE) here

 

 

 

Targeted Therapy (Precision Medicine)

 

 

Current status of Targeted Therapy detailed here.

 

 

 

This 2018 NY Times story describes the uncertainty of Targeted Therapy.

 

 

 

PanCAN’s Know Your Tumor program fails to improve the chief measure of success: Overall Survival.  Read the Conclusions in this latest trial report.  More on the PanCAN project here.

 

 

Some active Targeted Therapies

 

 

 

MSI, dMMR & Lynch Syndrome Immunotherapy, Abstract e16254 here

 

 

 

EGFR BATs Immunotherapy, Abstract 4108 here & 2015 report here

 

 

 

Third-Line Therapy

 

 

LV5FU2 + Nab-Paclitaxel & Others here & here

 

 

Erlotinib + Gemcitabine here1, here2, here3 & the sequence algorithm here4

 

 

A possibility for some patients: Nanoliposomal Irinotecan (MM-398) + 5FU (or Capecitabine) here

 

 

PARP-inhibitor Rucaparib may help BRCA-defect patients, but works better as 2nd Line monotherapy

 

 

NabP+G is a possible 3rd line therapy even after 1st line NabP+G, see Abstract P-147 here

 

 

3rd Line regimens may be gleaned from this 2014 article.  The 3rd Line search vexes oncology leaders

 

 

 

Transfusion (harmful, to be avoided), see this

 

 

 

Vitamin D (Paricalcitol, aka Zemplar®) here

 

 

 

 

 

Right To Try Act

 

One Hundred Fifteenth Congress

 

Click the following to view

 

 

The Right To Try Act

 

 

Excellent Legal Background Paper

 

 

CSPAN Interviews Chief RTT Advocate

 

On May 22, 2018 Congress passed (and on May 30 the President signed) legislation which allows an “eligible patient” (one suffering from a life-threatening disease or condition”) to access “unapproved medical products” (also called an “eligible investigational drug”) without FDA approval.

The Right To Try Act (RTT Act) makes it easier for people to access experimental treatments outside of a clinical trial.  Not all the details are yet known.  However, the following is certain:

1.    The patient must have “exhausted approved treatment options” “as certified by a physician” and must be “unable to participate in a clinical trial involving the eligible investigational drug.”

2.    The “eligible investigational drug” must be the focus of a completed Phase 1 (or later) clinical trial.

3.    It is not certain what TYPE of medical intervention constitutes an ELIGIBLE investigational “drug.”

It is not known for example whether Stem Cell infusion, Irreversible Electroporation, Proton Therapy or TT Fields might be considered a “drug.”  The answer will be found in existing Congressional acts, since the drug must be “the subject of an active investigational new drug application under section 505(i) of this Act or section 351(a)(3) of the Public Health Service Act.”

However, some of the promising Emerging Agents, listed above, will likely be available outside clinical trials.

Updates are given below.

 

 

 

RTT update.  The Right To Try Act does NOT mandate manufacturer cooperation.  The Act states: “It is the sense of the Senate that . . . [the Act] does not establish any new mandates, directives, or additional regulations.”

Neither FDA’s current “Expanded Access” (Compassionate Use) program nor the new Right To Try Act compels participation by drug companies.  However, the new Act does offer some slight advantages:

    Right To Try bypasses FDA’s approval process for Compassionate Use of experimental drugs.  Patients now need only the approval of their physician and the drug manufacturer.  Time and red tape are saved.

    The new law protects doctors and companies from the legal risks of allowing unapproved treatments, unless they intentionally harm a patient.

Critics are correct that, in many respects, the Act is dangerous:

    Many Phase 1 drugs (the likely choice by patients under this Act) do not succeed in later clinical trial phases – some are later found to be harmful.

    In addition, when a patient selects a treatment under this Act, he could easily forsake a better therapy, one which has benefits proven by more thorough research.  So time and opportunity are lost – meanwhile the disease progresses.

    Further, the patient will likely have to pay for the new drug, which may not be covered by insurance, often impoverishing the patient and achieving nothing.

    And, of course, some therapies cannot be mass-produced, so may be unavailable at any price.

The above assessment is early.  Time may reveal better features of this law.  But, it is certain that drug manufacturers are NOT required to participate.

A better law would allow patients to use drugs which are FDA-approved for other applications.  For example, some drugs, approved for lung cancer or ovarian cancer, are not FDA-approved for pancreatic cancer.  Yet some emerging pancreatic chemo regimes might employ those lung/ovarian drugs.  However, their costs are not covered by insurance because they lack FDA approval for the pancreatic application.

 

 

 

 

 

Keywords: best-pancreatic, new-pancreatic, pancreatic-cancer-cure, pancreatic-cancer-development, best-drugs-for-pancreatic, targeted-therapy, precision-medicine, best-clinical-trials, care-management, irreversible-electroporation, lung-metastases, nccn-guidelines, third-line-therapy, chemotherapy-regimens, cachexia, anorexia, philipjax, folfirinox, nab-paclitaxel, hospital-acquired-infection, ascites, symposium, chemo-agents, proton, pembrolizumab, egfr, microsatellite-instability, dmmr, hyperprogression, right-to-try.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Rules for Patients & Care Managers

 

“A Lack Of Wisdom Is Fatal”

Care Management.  Below are practices that should be adopted when dealing with a life-taking disease.

1.    Family Researcher.  The family must identify at least one bright, skilled person, with excellent computer savvy, to devote 100% of his time to care management – and the family must support that person by taking over the normal work and home responsibilities which he now must abandon.  The lack of such good organization costs lives.

2.    Care Manager.  The family Care Manager must maintain updates on all reports at all times: Overall condition, surgery, biopsy, PET/MRI/CT, bloodwork, etc.  And, be prepared to convert them immediately into one clean, logically-sequenced pdf file.  Software can help the manager – Fax, pdf and definition software.

Fax.  For a hospitalized patient, often the surest way to reach a physician is via Fax.  A physician will always read a fax.  All medical offices and nursing stations are Fax-equipped.  There are online services, like eFax, and PC-based software like FaxTalk and (for WinXP) WinFaxPro.  Win8 and Win10 have built-in software, but you will need a $10 USB modem (buy on eBay) and a landline.

PDF conversion.  PDFCreator will convert most documents (graphic or text) to pdf, available free here.

Definitions.  Many medical (and other) terms are defined for you via free WordWeb, just Ctrl Right-Click over a difficult word and get the definition.  Free here.

3.    Planning Is Critical.  The Care Manager and patient must chart a COMPLETE course from the very beginning.

For example, make sure that all metal stents are removable so that they can be extracted before an IRE procedure.  Metal will distort IRE’s electrical field.

Further, there must always be multiple irons in the fire, so the patient can jump immediately to another best therapy when one BEGINS to fail.  Too often managers make the fatal mistake of waiting until one therapy fails before starting the search for another.

An “iron” is in the fire ONLY if the therapy is suitable; the patient is eligible, and the related physician is in agreement.  “Thinking about it” doesn’t count as an iron.  See Item 7, below, for therapy sequencing.

4.    Discard Managed Health Plans.  If the patient has a managed plan, be certain that the major out-of-state cancer centers (those highest ranked by US News) are available (which is not likely).  If an unlimited-access plan can be had, get it.

If Medicare can be changed BEFORE diagnosis, do so.  Avoid Medicare Advantage, since it often prohibits access to the highest-ranked cancer centers.  Get Original Medicare plus 100% Medigap plan F or G.  The Medigap puzzle is addressed here.

      From Link-1 it appears that you can switch from Advantage to Original Medicare during the period January 01 through February 14 each year or PERHAPS October 15 through December 07.  But Medigap complicates the issue.  Keep reading.

      And, according to Link-2, you can be granted a Special Enrollment Period (SEP), if you enrolled in the Medicare Advantage plan based upon 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.

      It is possible that you don’t actually have to PROVE that you were misled.  Your reasonable, unwavering instance may be enough.  Press hard; you have nothing to lose.

Further, Medicare patients need a Medigap plan that pays the 20% which Medicare does not cover.  Medigap Plans F & G do that.  Plan G does not cover the $183 Part B deductable, but its price savings nearly always exceeds the $183 deductible, so offers a savings opportunity.

Finally, switching to Medigap AFTER diagnosis is complicated.  Many of the issues are addressed here.

It is possible to purchase Medigap BEFORE leaving managed Medicare, giving the buyer a chance to learn whether he will be issued Medigap.

If you can achieve it, Original Medicare plus Medigap will assure that you are welcomed financially at the best care facilities.

5.    US Healthcare For Non-Citizens.  See the section below: US Healthcare For Non-Citizens.

6.    Financial Help.  Travel and Financial Aid may be available through Angel Flight and CancerNet.  Charity grants can be found through CancerCare.  And drug discounts and donations often can be had by contacting the manufacturer’s customer assistance team.

7.    Best Facilities.  The general public tends to believe that all physicians have equal competence and equal skills, and thus they select a local surgeon to manage life-threatening illnesses.  A mistake: Community hospitals should be used for broken bones and stitches, not for the treatment of life-threatening diseases.  For deadly cancers, treatment should be sought at major cancer centers, those highest ranked by US News – the only exception being IRE facilities.  Not every institution that calls itself a “cancer center” is indeed one.

Resectability (the only chance for cure) is often determined by the skill of the surgeon.  MD Anderson Cancer Center explains here.  Read about the advantages of “high volume” hospitals here.

Certainly, travel is inconvenient, but death is far more inconvenient.  We must seek help from those who write the books, not from those who won’t find the time to read them.

For example, only the most skilled and experienced IRE practitioners should be used.  IRE has a significant learning curve.  If the placement of probe-pairs is incorrect or the pair spacing is 5mm outside specifications, IRE ablation will be imperfect, as noted in this report.

8.    NCCN Guidelines.  Study (not read) the NCCN Guidelines in the sequence recommended here.  In one day’s hard work the family Care Manager will be well-acquainted with therapy, and via the Authors and References will learn the names of oncology leaders to consult.  Reprehensibly, more than half of all oncologists fail to follow the guidelines.

9.    Therapy Sequence.  Sequence and timing are critical.  It is vital that the patient or Care Manager (not the treating physician) selects the best therapy path right from the beginning (with adjustments along the journey).  See Many Irons in the Fire, below.

This is a swiftly moving parade – one misstep and you cannot go back and take a path previously forsaken.  For example:

9.1.  Most (but not all) clinical trials require patients to be therapy naïve (that is, no prior therapy).  So, at the moment of diagnosis, the Care Manager (skilled friend or relative) must begin an intensive self-education and search effort.

That effort requires a solid week of hard work.  But, that’s how this website helps.  See the section below on prudent Clinical Trials.  There is no time for hand-ringing.

And, the physician will NOT do this work for you.  In most community settings his path is predicable: Start with First Line Therapy; when that fails employ a Second Line Therapy, and when he runs out of ideas send the patient to his radiation colleague to share the wealth.

9.2.  Further, for initially-resectable patients recent research (presented at the 2018 ASCO meeting) argues that mFOLFIRINOX is the best adjuvant (post surgery) therapy.  That means that Nab-Paclitaxel + Gemcitabine should be considered for initial neoadjuvant (pre-surgery) chemotherapy.  Neoadjuvant therapy is now recommended, rather than immediate surgery for those patients who are resectable at diagnosis.  Unfortunately, most patients are metastatic (not resectable) when first diagnosed.

9.3.  If possible, Irreversible Electroporation (IRE) should be undertaken as part of open surgery and before any radiotherapy.  Leading IRE surgeon Robert CG Martin, MD, PhD cautions in this 2016 journal article: “IRE . . . will not be successful as a salvage therapy . . . patients who have already gone through extensive surgical dissection are not suitable candidates [and] IRE should be used with caution after high dose radiation therapy because of the significant damage that the radiation therapy induces . . . ”

IRE might also be used for lymph nodes and for liver metastases if there are 3 or fewer lesions in one organ.  Lung metastases can be managed, but not by IRE.

10.  Many Irons In The Fire.  Most families tend to seek care in SERIES, meaning that they seek treatment at one location, and, when it fails, BEGIN the search for the next path – with an enormous loss of life-taking time.

This is a great mistake.  One must have multiple irons in the fire (called “contingency planning”), by which the family has prepared MULTIPLE institutions to undertake the next chapter of treatment.

      Getting input from distant physicians, without traveling, is possible, if you are organized and have computer skills (and have been wise enough to collect the key diagnostic and treatment reports).

Gather the latest key reports.  Convert them into pdf format.  Make them easy to read, large and oriented properly – and remove all static and blemishes from the pages.  Send them by email to IRE practitioners in ONE multi-page file, in logical order: Overall condition report first, then surgery, then MRI/PET/CT, then biopsy, bloodwork, etc.  Use a cover letter which gets to the point in about 6 sentences and avoids sentimentality.  Don’t waste the physician’s time.  For example:

Dear Dr X, Will you consider accepting X under your care?  He suffers from X and has been treated with X.  He is physically strong and well-insured.  Attached are the current reports.  I am indebted to you for your help.

      When scanning documents, set the TWAIN preferences to “line art” or “line drawing”, not “color”, to produce a cleaner B/W product; then save it as .pdf, .png, .bmp, .tif or .gif file, but not .jpg, since a .jpg will smear the pixels.

11.  Research.  There are four principles to practice:

      The patient and family must be so well educated about therapy that they know in advance of the next physician meeting what the physician will recommend.

      You must fight hard to get any new therapy.  If you don’t seek it, you won’t get it.

      Many family “Care Managers” think that they will find a physician who will do all the searching and future arrangements for them – those managers are often lazy and looking for an excuse to avoid hard work.  There is no such magic physician.  And, if you find one, you wouldn’t know whether he is correct unless you yourself do the research.  A life is at stake; trust no one else.

      If the physician disagrees with the medical literature (NCCN and journal articles), the physician is wrong.  In medicine Truth and Falsity are determined by carefully-designed clinical trials.  No amount of physician anecdotal experience can override the findings of clinical trials.

12.  Genetic Testing.  At the time of diagnosis genetic testing should be undertaken.  So urges Cedars-Sinai Medical Center (Abstract 4128) and Stanford University Medical Center (Abstract e16254) via 2018 ASCO Meeting reports.

Some genetic defects are now somewhat druggable, including BRCA, DDR and especially Microsatellite Instability (MSI), Mismatch Repair Deficiency (dMMR) and perhaps Lynch Syndrome.  Find details in Abstracts 4128 and e16254 explained in the commentary here.  The tests are identified in these documents: MSI and BRCA.

13.  IRE Facilities.  This 2016 list identifies practitioners targeting pancreatic tumors.

And, the following lists from manufacturer AngioDynamics identify IRE facilities.  But, they do NOT necessarily name those facilities which target pancreatic tumors, nor do they specify whether the practitioner is a surgeon or an interventional radiologist.  AngioDynamics: 2016 document, its 2016 spreadsheet and its online facility search.

14.  Hospital Admission.  Accept financial responsibility for an incapacitated patient ONLY if he is a bona fide legal dependant.

Never, under any circumstances, sign for a non-dependent (including parents) during hospital admission.  This is how the facility hopes to bind you to patient costs.  If the patient is incapable of signing, just write “Mr XXX is unable to sign” in the signature space, and don’t draw attention to it.  Every US hospital is obliged to treat the patient without your legal commitment.

15.  Hospital-Acquired Infections.  Infection can cause life-taking delays in cancer therapy.  Read about IV solutions, C. diff and hospital acquired infections here.

The family must make sure that prevention measures are followed.  And, if an infection occurs, the family must understand the remedy thoroughly to assure that the treatment is correct.  Medical mistakes are too common.

 

 

US Healthcare For Non-Citizens

Obamacare MIGHT be a vehicle for non-citizen access to US healthcare.  And, it might be acquired in a few months.

The US ACA Affordable Care Act (ObamaCare) claims to ignore preexisting conditions, so existing pancreatic cancer should be covered.

Further, ACA is available to aliens who possess “nonimmigrant visas” and who are “lawfully present” in the US.

Recent federal rules may have reduced the number of geographic areas where ACA is reasonably-priced or active.  Nevertheless, this is a strategy that should be considered earnestly.

Details on how to qualify are available here.

Applications for nonimmigrant visas can be made online at this site and this site.  And, frequently asked questions are answered here.

In addition, this non-government site offers some insights which may be true, but which should be verified at the government sites.

ObamaCare’s open enrollment period begins in November.  However, there may be exceptions, allowing Special Enrollment at other times.  Learn more about enrollment periods at these three sites: At this site, at this site and this site

With some online work a non-citizen might be treated in the US before long.

It would be prudent to pursue the visa and Obamacare plan, even if you are uncertain whether you will use them.  This is part of the “contingency planning” and the “irons in the fire” which every pancreatic patient must practice at all times.

Before selecting a specific insurance plan, make sure your preferred US medical institutions will accept it.

 

 

How to Find the Best Clinical Trials.  We are always urged to seek clinical trials.  However, there must be great caution with this particular disease.  As noted oncologist Philip A. Philip remarked recently: “Clinical trials in pancreatic cancer have been famous for being negative.  [After] many clinical . . . trials, with thousands of patients and millions of dollars in costs . . . I would count maybe five clinical trials [in 20 years] . . . that led to . . . adoption in our daily practices.”

During those 20 years nearly all trials led to nothing.  And, every failed human trial began as successful non-human research.

So, how should we evaluate clinical trials?

First, look for agents which ADD TO therapies already known to be effective.  Then, participate in the trail ONLY if the new agent has shown value in earlier trial phases.  There are usually 3 trial phases.  Dosage and efficacy are usually determined in Phases 1 and 2.  So, at the end of Phase 1 or 2, some effectiveness will be known.

Thus, we want to find the agents and practices which will LIKELY produce the greatest impact.

Download the excellent journal article, titled: Pancreatic cancer: Optimizing treatment options, new, and emerging targeted therapies, 2015 Chiorean & Coveler.

Its tables give comparative data on current and promising agents.  The data provide only a rough comparison.  And, of course, a seemingly good regimen may not be suitable, if the patient’s disease has progressed on the regimen’s principal component (like Gemcitabine or Irinotecan).

Then, search the Clinical Trials website here.

1.    Select “Open Studies”

2.    Then, enter key search terms.  Place “pancreatic” on the Conditions line, without quotations marks.

3.    Enter standard therapies (one at a time) on the Interventions line.  You could enter Gemcitabine, Irinotecan, FOLFIRINOX (FOLFIRINOX will also find FOLFIRINOX alternatives), etc.  This way you are more likely to find new therapies combined with acceptable mainstay therapies (also called backbone therapies).

4.    If you have undergone resection or IRE, you might also put “resected” on the Search Terms line.  This approach does not guarantee a perfect search of trials, but it is a good start.

5.    The search will produce a column of results.  If you see a trial of interest, right-click and open a new tab.  That way, when you close a tab, you preserve the original search response page.  If you don’t use a mouse, get one.  It will reduce errors and save time.

6.    When reviewing the various trials look for trials that have a known, reliable backbone regimen (FOLFIRINOX or Nab-Paclitaxel+Gemcitabine) with and without the experimental agent.  That way the patient gets some good therapy, even if the new agent does nothing;

7.    If data on the experimental agent is missing from the Chiorean-Coveler article, look for trials in Phase-2 or later, that way there may be results in Phase-1 to review.  This is usually the best approach, although there can be exceptions.  Also, Phase-3 trials are usually randomized, meaning that about half the patients do NOT get the experimental therapy (at least not initially).

8.    Look for large multi-institutional trials, which often identify a “breakthrough” drug (or, on the negative side, they may simply identify a wealthy manufacturer).

9.    Read the Inclusion and Exclusion criteria carefully; when in doubt contact the researcher (an email address is usually given), using the most concise email possible – get to the point in two sentences or less; for example: “For this trial will you accept a locally-advanced patient who has recently undergone resection and who has good performance status?”

10.When you find an experimental therapy of interest to you, search Google (or PubMed), placing the name of the new therapy and the word “pancreatic” on the Google word line.

Then, in the column of search results, if you see a response of interest, right-click and open a new tab.  That way you preserve the original search response page, and you can open new tabs while the other tabs are loading.  A mouse is essential for this search.

Any other approach is unwise.  There are no cures at present.  Therapy agents should be chosen BY THE NUMBERS.  If the performance numbers: Response Rate (RR), Progression Free Survival (PFS), and Overall Survival OS) are not known, you take great risk, forsake an opportunity to use a better therapy, and lose time which can never be recovered.  Meanwhile, the disease progresses.

To be prudent do not rely on preclinical (non-human) studies.  Every failed human pancreatic trial began with a successful preclinical study.  In the past 20 years hundreds of human trials have failed, the vast majority of them.  And the very few successful trials produced only four chemo regimens now used in clinical practice – four regimens in 20 years.

Occasionally you will discover a trial which tests a new agent on nearly all cancers: Breast, colon, lung, kidney, pancreas, head and neck.  Beware.  The manufacturer doesn’t know what organ will benefit if any.  So, he wants to find out cheaply by callously squandering the lives of you and other human guinea pigs.  Exceptions to this warning are (1) experimental agents applied to a specific genetic defect like BRCA or (2) agents applied to a class of organs, such as the gastrointestinal system (pancreas, liver, intestine, colon).

Do not choose a trial just because it is offered or is local.  Find the BEST one available on earth, and travel to it, if necessary.  Far more inconvenient than travel is death.

If you seek a trial recommendation from your medical oncologist, ask him to identify the BEST one available regardless of geographic location.  If he names a trial that he administers, consider: What a monumental coincidence that the BEST of all clinical trials on earth is being conducted by your oncologist (one among the multitude of oncologists), who is also being paid to find trial subjects.  That physician may not be your friend, no matter what he pretends to be.

Often, oncologists make a “God’s judgment”: Shall I make every effort to treat this patient responsible and cleverly, which might help her somewhat but postpone the inevitable, or should I use her life in an uncertain trial which may help all mankind?

Frequently, they push the patient into the trial without telling her the grave uncertainties.  And, sometimes these oncologists prod patients into trials which they administer (trials which are not the BEST available) – that conflict-of-interest is unethical and frequent.

 

 

Other Guidance.

1.    If the NUMBERS for a specific therapy don’t exist, you are squandering an opportunity offered by a different, NUMBERS-rich therapy.  Wise financial investors review the past performance of stocks and funds before investing.  But, when it comes to a life and death decisions, they cast away that wisdom.  The numbers are Response Rate (RR), Progression Free Survival (PFS) and Overall Survival (OS).

2.    Do NOT base your therapy decision on preclinical (non-human) trials.  Every failed human trial, of which there have been hundreds in the past 20 years, began with a successful non-human study.  And the very few successful clinical trials produced only four chemo regimens now used in clinical practice – four regimens in 20 years.  The failed human trials cost many millions and enrolled thousands of patients – most of whom sacrificed themselves and gained nothing.  Select the therapy wisely, based on the NUMBERS.

3.    Do not be seduced by a researcher’s use of the term “significant”, as in “significant increase” or “significant improvement.”  He is often referring to statistical significance, a technical term in probability theory.  For example, an experimental agent might add 1 week to Overall Survival, the 1-week being “statistically significant”, but not a significantly long time in our quest.

4.    Urge PET scans, early and frequently.  In February 2018 NICE, the guidance agency for the UK socialized health care system, began recommending early PET scans.  NICE is the misnamed National Institute for Clinical Excellence.

 

 

Nanoknife Surgery Warriors.  The Warriors Facebook forum was started several years ago by David Shell who recognized the need for an IRE information exchange – to educate and to bolster past and future Irreversible Electroporation (IRE) patients.

It is an excellent support group; but, unlike this site, it is not a reliable source of medical information.

With the help of IRE Mr Shell survived four years against this terrible disease.  He passed away Feb 20, 2018.

In 2016 he told his story here, of ineptitude and confusion at major cancer centers.  Incidentally, it is a false claim by others in the story that IRE performs better following radiation.

 

 

Irreversible Electroporation (IRE), a type of knifeless surgery, is the most significant therapy advance in 20 years, allowing many Stage 3 Locally-Advanced patients to become resectable, and improving surgical margins.  IRE became commercially available for research purposes in 2009.  Robert C.G. Martin, MD, PhD, FACS, Director of Surgical Oncology, University of Louisville Medical School, is the principal developer of IRE techniques for pancreatic cancer.

IRE, in the form of Nanoknife®, is a soft tissue ablation method using ultra short but strong electrical fields to create permanent, lethal nanopores in the cell membrane.  The advantage of IRE lies in its ability to ablate unwanted tissue without harming vital protein-sheathed structures such as blood vessels, ducts and nerves.  This tissue-selectivity, as well as real-time monitoring capability and sharp ablation margins are its superior features.

In the region beyond its ablation zone the cell poration is reversible, allowing chemo agents to enter more easily before the pores eventually close.

IRE is performed by an interventional radiologist percutaneously (through the skin) or by a surgeon laparoscopically or intraoperatively (as part of open surgery).

The surgical approach allows greater precision, which is paramount – the ablation needles must be positioned within 5mm of required spacing, or the ablation will be imperfect.  To achieve that precision proficient IRE practitioners employ the new 3D needle guidance system.

An excellent introductory paper on IRE is available for download here, and other IRE information is here.  Pancreatic IRE may be covered by Medicare and private insurance under CPT Code 49203.

Metal stents must be extracted, so that IRE’s electrical current is not misdirected by the metal.  So, use removable stents; their manufacturers are identified here.

IRE is being evaluated for the treatment of bone and brain tumors, as well as other soft tissue tumors.