nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Tue Jan 22, 2019 03:59 AM

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2019 Gastrointestinal Cancers Symposium
Installments, Part 1

          Today, I begin reviewing abstracts from the 2019 GI Cancers Symposium which was held in San Francisco on January 17-18, 2019.  There are at least 45 relevant abstracts; so, over a period of several days or weeks, I will cover the “best”.  If you can’t wait, the abstracts are found here:
          The order in which I present the abstracts does NOT signify their importance.  I am merely beginning with the first abstract meeting my search criteria.

Abstract 168344: Single-shot celiac plexus radiosurgery in pancreatic cancer: Palliative and functional outcomes—Final results of a prospective clinical trial
          As a means to reduce epigastric/lower back pain Canadian and American researchers irradiated the celiac plexus of 17 patients using a single-fraction 25 Gy.  The median patient ECOG was 1, and about half suffered liver metastases.  The results:
1. Median baseline pain was reduced from 6.0 IQR to 2.3.  And, at 6 weeks “BPI pain interference” dropped from a 7.1 baseline to 0.
2. Opioid consumption decreased from 52.9 MME to 37.5 MME at 6 weeks.
          Trial information is here, although a patient does not have to participate in this trial to adopt practice.  A follow-up international trial is accruing.

Abstract 168385: Impact of neoadjuvant radiation on survival in patients with pancreatic cancer undergoing neoadjuvant chemotherapy followed by pancreatectomy
          Using the National Cancer Database, University of Miami researchers sought to learn whether Neoadjuvant ChemoRadiation (NACR) was superior to Neoadjuvant Chemotherapy (NAC, without radiation) for resected patients.
          The records of stage I-III patients who underwent surgical resection from 2004 to 2014 were examined, yielding 3,133 patient cases.  A total of 2,351 (75%) patients underwent NACR, and 782 (25%) underwent NAC alone, and 74% underwent pancreaticoduodenectomy.  The result:
1. The rates of margin positivity were similar: 15% for NACR and 17% for NAC.
2. Median Overall Survival and 5-year Overall Survival were similar: 25.7 months for NACR vs. 25.1 months for NAC, and 20% vs. 22%, respectively
          Researchers found that NACR is associated with lower rates of lymph node positivity.  However, they concluded: (1) that “NACR did NOT translate into a survival or margin positivity benefit compared to NAC alone”, and (2) that “no convincing data is currently available to advocate the widespread use of radiotherapy in the neoadjuvant setting.”
         Keep in mind that these were cases of resected patients who should be expected to do well.

Abstract 168476: Effect of neoadjuvant chemoradiotherapy on prognosis in resectable and borderline resectable pancreatic cancer with venous involvement
          In a somewhat contradictory study Japanese researchers sought to learn the value of NACR by analyzing the records of 181 patients, from 2006 through 2017, who preoperatively received full-dose gemcitabine (1000mg/m2) plus concurrent radiation of 54 Gy.  The NACR patients were compared to 149 patients who were candidates for upfront surgery and who served as the control group.
          It is important to note that it is uncertain whether the no-NACR group received any neoadjuvant chemotherapy whatsoever.  The research outcome:
1. Among the 181 NACR patients, 23 (13%) couldn’t undergo pancreatic resection following NACR due to distant metastasis in 10, tumor progression in 7 and poor physical status in 6. Among the 149 upfront-surgery patients (the control group), 10 (7%) couldn’t undergo pancreatic resection at laparotomy because of distant metastasis in 8 and tumor progression in 2.
2. NACR patients in general had a better prognosis than those without, acquiring a Median Overall Survival of 37.0 vs. 27.1 months.
3. Median Overall Survival differed by resectability status.  For R (Resectable) patients Overall Survival was 45.7 months with NACR therapy versus 33.8 months without.  For BR-P (Borderline Resectable Venous Involvement) patients the Overall Survival was 61.7 vs. 14.6 months.
4. For BP-A (Borderline Resectable Arterial Involvement) patients the researchers found that “NACR had no significant impact on prognosis.”
The research designs for Abstracts 168385 and 168476 may explain their contradictory outcomes.  In Abstract 168385 researchers considered a far greater number of cases, which tends to enhance accuracy.  And in 168476 it is possible that non-NACR patients received NO neoadjuvant therapy at all – no neoadjuvant chemotherapy – although we might assume that both groups received some post-resection therapy.
          Radiotherapy has always been controversial, although most radiation oncologists will not admit that.  More information can be found here:,6312
          The next 2109 GI Symposium installment will begin addressing new chemotherapy regimens.  And, be sure to study my website thoroughly including the downloadable Decision Guide, found at

RE: nanoknife IRE for pancreatic cancer

by Baloo on Tue Jan 22, 2019 03:33 PM

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Thanks PhilipJax for posting these.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sun Jan 27, 2019 03:15 AM

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2019 Gastrointestinal Cancers Symposium
3rd Line Therapy & New Adjuvant HAI Therapy, Installment Part 2

          In this second installment I address two chemotherapy regimens, including SM-88 which may offer a third line therapy following FOLFIRINOX and Gemcitabine + Nab-Paclitaxel. 
          There are at least 45 relevant abstracts; so, there will be other installments.  If you can’t wait, the abstracts are found here:
          The order in which I present the abstracts does NOT signify their importance.  I am merely beginning with the first abstract meeting my search criteria.

Abstract 168775: Phase II trial of SM-88 in patients with metastatic pancreatic cancer: Preliminary results of the first stage
          As a potential Third Line therapy American researchers are testing SM-88 in a Phase 2 trial which is not yet complete.  So, data is incomplete.  SM-88 is a tyrosine derivative [Td], mTOR inhibitor, CYP3a4 inducer and oxidative stress catalyst which is relatively non-toxic/
          The trial is not far enough along to have developed definitive performance numbers such as Response Rate, Overall Survival and Progression Free Survival.  However, for the desperate Stage 4 patient, the Abstract and the Poster presentation offer hints of what is to come:
1. At baseline Circulating Tumor Cells (CTC’s) were detected in 97% of patients (mean 93.1 cells/4 ml) and fell in 69% (11/16) of evaluable subjects from 141.4 to 30.7/4 ml, a median reduction of 77% (3% - 97%).  74% of subjects (16/23) experienced CTC reductions of 30% or greater.
2. Two of 9 subjects (22.2%) experienced CA19.9 declines, both of which also showed CTC declines.
3. Lesion SUVs decreased an average of 24.1% (8.3 - 35.7%).  SUV (Standard Uptake Value) is a measure of metabolic activity (growth) in tumors revealed by PET imaging.
4. The survival period has been doubled compared to the historical survival of third-line pancreatic patients.  As 06Jan2019, 67.8% (19 of 28) evaluable subjects remain alive at a median follow up of 4.3 months (range 1.3 to 8.3 months).  Of 14 third-line patients 79% remain alive after a median follow-up of 4.7 months.
          The ASCO presentation poster is here:
          The trial seeks subjects who have failed at least one chemotherapy line.  But, ECOG performance status must be ≤2.  Thusfar 86% of patients have undergone 2 or more prior lines of therapy.  The overall enrollment is 115 patients at 30 locations, and 60 to 70 patients are still being sought.  The trial description is here.
          See also the interview here:

Abstract 168523: Impact of adjuvant hepatic arterial chemoinfusion using high-dose 5-fluorouracil with systemic gemcitabine for pancreatic cancer: A propensity score–matched analysis
          In this trial Japanese researchers hoped to improve the survival of resected patients by infusing high-dose 5FU into the hepatic artery, in addition to the typical systemic Gemcitabine therapy.
          Hepatic Arterial Infusion (HAI) plus systemic Gemcitabine were administered to 151 resected patients, and another 73 resected patients received only systemic Gemcitabine, the standard adjuvant therapy (post-resection therapy) of the time.  The results:
1. The estimate Overall Survival (OS) for patients treated with HAI was 54 months, and the OS for non-HAI patients was 24 months.  All received Gemcitabine as an adjuvant therapy.
2. The liver was only tumor recurrence site; however, a “significant [recurrence] decrease was observed in the HAI group compared to the control group,” the non-HAI group.
          If I obtain the 2019 ASCO poster, I will make it available here:
          A previous posting describes the advantages of modified FOLFIRINOX (mFFX) as an adjuvant therapy following resection, whose dramatic performance was revealed at the 2018 ASCO Annual Meeting.  Adjuvant mFFX was subsequently adopted by many oncology leaders.  See the posting here.  Search for the word “breakthrough”:,63127,90
         However, mFFX may be exceedingly harsh for some relatively frail resected patients. So, high-dose 5FU via HAI may be a more tolerable alternative, achieving an OS outcome similar to that of adjuvant mFFX.


RE: nanoknife IRE for pancreatic cancer

by caseyzson on Mon Jan 28, 2019 06:57 PM

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Thank you PhillipJax for these write-ups.  I was speaking to a researcher who was excited about a cohort from this study:

This was SBRT + PD1 + CTLA4, in both stage 3 and stage 4 patients.  In a subset of patients, 2 had >12 months response.  The researcher said they will likely push for a larger trial based on this dosage (SBRT before, followed by combo PD1 + CTLA4).  The reason I thought this was exciting is that this type of therapy could be given off-label currently.  We actually met with a NIH hospital and based on the small results, the radiologist said that he would be willing to try this as an option down the line for my mother.  He has done it in lung cancer before and is ok with the safety profile.  However, he would also like to see the data validated in a larger study.

The idea of priming the immune system with SBRT has been studied before, but this is the first time I've seen responses in unresectable pancreatic cancer.  Hopefully biomarkers can be used in the future to find populations of patients this would help the most, but would love your opinion on this new study.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Wed Jan 30, 2019 07:27 PM

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2019 Gastrointestinal Cancers Symposium
New 1st Line GTX & S-1 Better Than Surgery, Installment Part 3

          In this third installment I address a new first line therapy and the efficacy of S-1 which has performed better then upfront surgery. 
          There are at least 45 relevant abstracts; so, there will be other installments.  If you can’t wait, the abstracts are found here:
          The order in which I present the abstracts does NOT signify their importance.  I am merely beginning with the first abstract meeting my search criteria.

Abstract 192: Immune checkpoint inhibition (ICI) in combination with SBRT in patients with advanced pancreatic adenocarcinoma (aPDAC)
          This Phase 1/2 trial of Immune Checkpoint Inhibitors (ICI) and Radiation (SBRT) for “advanced patients”, suggested by Caseyzson, is not a good performer.  The Response Rate, at 9.6%, is no better than that of Gemcitabine alone and is certainly worse than standard therapies FOLFIRINOX and Gemcitabine + Nab-Paclitaxel.  Locally-Advanced and Metastatic disease are usually considered “Advanced”.
          There were some beneficial outcomes, but it is not certain whether they were due to the speculated ICI-SBRT synergy or to radiation alone, or to the small cohorts.
         This trial is a good example of why patients must select trials very carefully, a process which requires assessment of the NUMBERS, a process detailed on my website.

Abstract 385: Gemcitabine, Docetaxel, and Capecitabine (GTX) as a first-line regimen in metastatic pancreatic adenocarcinomas (mPAC): A single institution experience
          GTX may be emerging as a new first line therapy for metastatic patients.  A review of 50 cases at its facilities by the University of Louisville found that GTX yielded an Overall Survival of 9.45 months compared to 6.08 months for FOLFIRINOX.  And, GTX was “associated with fewer severe GI and hematologic toxicities,” making it a worthwhile, less harsh alternative to FOLFIRINOX.
         All GTX components are readily available, so interested patients could undertake the regimen immediately without a clinical trial.

          Abstract 189: Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05)
          This Phase 2/3 trial represents a remarkable advance for Asians.  In this study of 364 resectable and borderline resectable patients at 57 Japanese centers were randomly assigned either (a) to neoadjuvant Gemcitabine + S-1 or (b) to upfront surgery – 182 patients to each group.  All patients who fully recovered within 10 weeks of curative resection received adjuvant S-1 for 6 months.
          S-1 consists of Tegafur (a prodrug of 5-fluorouracil) and two biomodulators (Gimeracil and Oteracil) which maintain high serum 5-fluorouracil concentrations while reducing gastrointestinal toxicity.
          The chemotherapy patients did not undergo resection.  The researchers report the following:
1. The Overall Survival was 36.72 months for the neoadjuvant Gemcitabine/S-1 group versus 26.65 months with upfront surgery group.
2. The incidence of liver metastasis was significantly lower with neoadjuvant Gemcitabine/S-1 compared with upfront surgery, 30.0% vs. 47.5%.
3. Lymph node metastasis was significantly decreased in the neoadjuvant group vs upfront surgery group, 59.6% vs. 81.5%.
4. The 2-year overall survival rates were 63.7% for the neoadjuvant group, compared to 52.5% for the upfront surgery group.
          S-1 is used to treat advanced gastric cancer.  In Europe it is labeled for use in combination with cisplatin to treat head and neck cancer, colorectal cancer, non–small-cell lung, breast, pancreatic.  In Asian countries it is used to treat biliary tract cancers.  S-1 has not been approved by the FDA.
          it is known that, compared with Asians, Caucasians receiving S-1 develop more severe gastrointestinal toxicities due to metabolic differences between the populations.  For this reason, lower doses of S-1 might be required in Caucasian patients, which could affect the drug’s efficacy.
          It should be noted that this neoadjuvant combination (Gemcitabine + S-1) was not compared to surgery plus adjuvant mFOLFIRINOX – that surgery/adjuvant combination has produced a “breakthrough” Overall Survival of 54.4 months.  See bottom of page here:,6312

          See also the video presentation of Dr Andrew X XZhu at
          Be sure to study my website thoroughly including the downloadable Decision Guide, found at



RE: nanoknife IRE for pancreatic cancer

by susanmarie on Thu Jan 31, 2019 04:42 PM

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What stage was she?  

RE: nanoknife IRE for pancreatic cancer

by susanmarie on Thu Jan 31, 2019 04:49 PM

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MD Anderson will not treat stage 4 Pancreatic cancer patients, they are not interested.  fYI

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Feb 02, 2019 05:24 AM

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2019 Gastrointestinal Cancers Symposium
PEG-G-CSF Enhances FFX, Neoadjuvant Benefit, DNA & Platinum and Radiation
Installment Part 4

          MD Anderson will indeed treat Stage 4 patients and with great fervor.
          Now, in this fourth (and perhaps final) installment I address a way to boost FOLFIRINOX performance by adding one currently-available agent.
          There are at least 45 relevant abstracts; so, there will be other installments.  If you can’t wait, the abstracts are found here:
          The order in which I present the abstracts does NOT signify their importance.  I am merely beginning with the first abstract meeting my search criteria.

Abstract 411: Effect of FOLFIRINOX with PEG-G-CSF for unresectable/recurrent pancreatic cancer
          Japanese researchers sought to determine whether the addition of PEG-G-CSF improved the performance of FOLFIRINOX (FFX) for unresectable/recurrent patients.  Patients were divided into two groups.  The G Group consisted of 23 patients who received PEG-G-CSF in addition to FFX (or modified FFX).  Of these 74% had metastatic disease (the remainder were locally-advanced).
          The second group, the NoG Group, consisted of 17 patients who received FFX or mFFX only.  In the NoG Group 29% had metastatic disease.  So, the G Group had twice the percentage of metastatic patients and might expect a worse outcome.  But, that is not what happened.  The findings:
1. The Response Rates (RRs) were 30% and 6% for groups G and NoG respectively.
2. Progression Free Survival were 7.3 vs 4.5 months for G and NoG, respectively.
3. Median Overall Survivals were 16.9 and 14.2 months for G and NoG, respectively.
          The researcher conclusion: “A high tumor shrinking effect of FFX with PEG-G-CSF indicated that it might be useful as a neoadjuvant chemotherapy.”
          Human pegylated granulocyte colony-stimulating factor (PEG-G-CSF) is a readily-available product which can be added without the need for a clinical trial.
         How is it useful? Chemotherapy can cause unacceptably low levels of white blood cells (neutropenia), making patients susceptible to infections and sepsis. G-CSF stimulates the production of granulocytes, a type of white blood cell. G-CSF also allows higher-intensity treatment regimens. It is administered via subcutaneous or intravenous routes.

Abstract 312: Neoadjuvant chemotherapy followed by surgery versus upfront surgery in patients with borderline resectable and locally advanced unresectable pancreatic adenocarcinoma
          For resectable patients this South Korean research reminds us of the advantages of Neoadjuvant Chemotherapy (NACT) compared to upfront surgery.  Researchers analyzed the records of 135 patients who underwent NACT and 359 patients who received upfront surgery.  The findings:
1. The NACT followed-by-surgery group showed significantly less advanced tumor stage (93% vs 99%) and lymph node stage (49% vs 71%) than the upfront surgery group.
2. NACT followed-by-surgery was significantly associated with better OS (25.4 vs 17.1 months) and Disease Free Survival (9.0 vs 7.1 months) than upfront surgery.
3. There was no difference in length of hospital stay, and the NACT followed-by-surgery group showed a significantly lower incidence of postoperative complication.
         The NACT consisted of Gemcitabine-based regimens and FOLFIRINOX, equally divided among the NACT group.

Abstract 191: Outcomes in pancreatic adenocarcinoma (PDA) patients (pts) with genetic alterations in DNA damage repair (DDR) pathways: Results from the Know Your Tumor (KYT) program.
          A limited number of patients harbor mutations in a broad range of DDR genes, particularly in BRCA1/2, PALB2, or ATM, ATR, ATRX, or BAP1, BARD1, BRIP1, CHEK1/2, RAD50/51/51B, or FANCA/C/D2/E/F/G/L.  Such patients are categorized as DDR mutated (DDRmut).
          Researchers analyzed Know Your Tumor data to determine whether platinum-based therapy aided DDRmut patients.  The findings:
1. For resected DDRmut patients Overall Survival (OS) was similar, irrespective of exposure to platinum therapy.
2. However, advanced DDRmut patients (metastatic and locally-advanced) have an improved OS when treated with platinums, compared to non-DDRmut patients.
3. “But, in the absence of platinum-based therapy, there is no OS difference observed in DDRmut vs non-DDRmut patients, suggesting that DDR status has no pure prognostic value.”
          The researchers recommend: “These findings support the need to test all patients with advanced PDA, to ensure that DDRmut pts are treated with platinum-based therapy.”

Abstract 409: Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer
          Using the National Cancer Database American researchers again sought to identify the best therapy for resectable patients: Either UpFront Surgery (UFS) or one of several Neoadjuvant Therapies (NT) consisting of Single Agent Chemotherapy (SAC), Multi-Agent Chemotherapy (MAC) or radiation (RT) with or without MAC.
          The researchers identified 26,563 patients of which, 23,877 (89.9%) received UFS; 1,482 (5.6%) received NT+RT (SAC+RT 768, MAC+RT 560), and 1,204 (4.5%) received chemotherapy only (SAC 262, MAC 864).  The findings:
1. The rate of R0 resections were the following: For NT+RT 82.4%, for NT-RT 80.5% and for UFS 76%.  Neoadjuvant chemotherapy offered a slight benefit over upfront surgery, but the benefit of radiation was less certain.
2. But, the bottom line is given by medial Overall Survival, which was 22.2 months for UFS, 23.1 months for SAC, 26 months for SAC+RT, 27.9 months for MAC+RT, and 29.8 months for MAC.  So, MAC proved superior, and radiation offered an uncertain benefit.
          The researchers concluded: “Multi-agent chemotherapy with or without radiation improves overall survival.” So, the radiation benefit is so uncertain that it does not matter whether or not it is added to multi-agent chemotherapy (such as FOLFIRINOX and Gemcitabine plus Nab-Paclitaxel).

          The lessons of this 2019 ASCO Gastrointestinal Symposium:
>> The benefits of radiation are uncertain and controversial;
>> SM-88 may prove to be an effective third line therapy, and the trial is still open to patients;
>> Hepatic Arterial Infusion may be a worthwhile consideration for resected patients, perhaps with benefits similar to those of adjuvant mFFX;
>> For metastatic patients GTX appears to be an effective, less-harsh alternative to First Line FFX:
>> For Asians S-1 + Gemcitabine may be as effective as surgery; however, a comparison to surgery plus adjuvant mFFX has not been undertaken;
>> When possible PEG-G-CSF should be added to FFX for metastatic patients;
>> Unresectable DDR mutation patients should be treated with platinum agents.
          The next major ASCO conference takes place in mid-year, and I expect to report on it.
          Be sure to study my website thoroughly, including the downloadable Decision Guide, found at


RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Feb 02, 2019 01:20 PM

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NCCN 1.2019 Guidelines
How to Study the Guidelines

          The new 1.2019 NCCN guidelines are now available, released in December 2018.  The new guidelines can be downloaded here:

How to Use the NCCN Guidelines
          NCCN guidelines are used by medical oncologists to make treatment decisions.  However, more than half of all treating physicians ignore these guidelines.  Read about the detrimental consequences to patients here:
          These guidelines (link above) will allow you to determine whether your physician is applying the best available therapy.  It takes a few days of real work to study them, but they reduce suffering in the long run.
          Every care manager MUST study the document carefully (and study the last two years of posts on this website).
          The following is a list of NCCN features by page number.  You should study the guide in the following order:
>>> Pg-4: The new Evidence Block system.
>>> Pg-39: The ranking of chemo regimens using Evidence Blocks.  Focus on the far-left column of each block: Efficacy.
>>> Pg-50: Staging code.  Coding to this detail should appear in the patient’s overall-condition and biopsy reports.
>>> Pg-51: Discussion of the disease and therapies.  And, note well the Categories of Evidence and Consensus, upper left.  Using this code the authors rank the reliability of therapies with Category-1 the most reliable.
>>> Pg 105: Genetic Syndromes and Risk.
>>> Pg-106: Indications for Various Therapies.
>>> Pg 108 Graphics of surgical sections.
>>> Pg-113: References.  Here you will find research leaders AND physicians you may wish to seek for treatment.
>>> Pg-2: Oncology leaders who authored this guideline.  They are physicians you may wish to consult for treatment.
>>> Pg-6: Physician decision tree.  With the exception of IRE, your physicians should be following this decision tool.
          Be sure to study my new website EndPC, which offers guidance on all pancreatic cancer topics, including the latest therapy, care management and clinical trials. 
There is also a new Decision Guide, which will help guide you to the proper therapy.  Both are located here:

Footnote.  The NCCN panel irrationally recommends against IRE for locally advanced disease “due to concerns about complications and technical expertise.”
          NCCN bases its absurd recommendation on the 2016 musings of several non-IRE practitioners – statements selectively chosen by freelance writer Susan Jenks.  Those physicians never address IRE’s unique application: The removal of tumors which encase blood vessels and ducts, thus making surgical resection (and cure) possible.
          NCCN’s unfounded concern about “complications” is based on the first 10 IRE patients at the inexperienced Roswell Park Cancer Institute.  In 2016 Roswell’s Steven Hochwald pondered “What’s unclear is whether IRE really makes a difference in patient outcomes.” 
          Now, two years and only 15 patients later, a still-inexperienced Roswell Park thinks differently, insisting: “We have had some success in extending survival using IRE.”  Yet, NCCN ignores the Roswell correction and keeps its irresponsible recommendation.  See the 2018 Roswell statement here:
          NCCN has allowed its politics to overthrow good medicine.
          And the poorly-researched 2-page 2016 interview, which nixed a favorable IRE recommendation, is downloadable here:



RE: nanoknife IRE for pancreatic cancer

by denver88 on Thu Feb 07, 2019 04:00 PM

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your comments on cyberknife caught my eye.  i have read many good results with this process from patients and medical journals.  you made  statement about "lasting results"?  would you mind providing clarification as this implies the cancer is initially killed off but due to weaknesses/flaws in the procedure it comes back?  thanks

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