nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 08:52 PM

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I am going to look that up right now. Just quickly - is it a parp?

Also, did Dave's tumors stop progression which is why they chose Lynparza? Just curious the state that you began them at?

RE: nanoknife IRE for pancreatic cancer

by DavesGirl70 on Mon Feb 10, 2020 08:57 PM

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On Feb 10, 2020 8:52 PM Mkk2018 wrote:

I am going to look that up right now. Just quickly - is it a parp?

Also, did Dave's tumors stop progression which is why they chose Lynparza? Just curious the state that you began them at?

It is still a PARP inhibitor, yes

He started out with a 3cm mass on the tail of the pancreas and "numerous" liver mets - you truly couldn't count them because there were so many. Within 1 month while we waited to see oncologist etc the biggest one in the liver grew from 6cm to 15cm long. Started FFX on Nov 8 and he responded dramatically. As of July 2019, the pancreatic mass is almost undiscernable on the CT scan and there are 2 liver masses remaining each less than 2cm big. Started Lynparza as "maintenance" (no progression on FFX, we will likely go back to that if ECOG score is still good/if things progress but keeping fingers crossed so so tight that he can stay on the lynparza as long as possible) and it has kept things stable - no further shrinkage, no further growth. His CA19-9 has also stayed more or less stable/falls a point here and there. He started out at a CA19-9 of 360,000! I haven't seen anyone report one that high - I thought maybe the units of measurement were different, but nope it was really just that high. Cut in half with each FFX treatment. 

Always happy to answer any questions <3 no trouble at all, it's very interesting to talk to someone who is on such a similar path. I hope that the GYX works for a while? Or that something comes through <3 

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 09:02 PM

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We are incredibly similar to your measurements and even the pancreas tumor becoming unremarkable. We were and are well over 10,000. The trysts here don’t read over 10,000 so that’s all we know. Everything for us cut right in half also though! Same with liver mets situation. I am going to look into going back to FFX though and just see how this gtx plays out. He hates hates being on it. FFX was way better to be honest Let’s keep in touch. This has turned my day around a bit Thank you so much <3

RE: nanoknife IRE for pancreatic cancer

by DavesGirl70 on Mon Feb 10, 2020 09:05 PM

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On Feb 10, 2020 9:02 PM Mkk2018 wrote:

We are incredibly similar to your measurements and even the pancreas tumor becoming unremarkable. We were and are well over 10,000. The trysts here don’t read over 10,000 so that’s all we know. Everything for us cut right in half also though! Same with liver mets situation. I am going to look into going back to FFX though and just see how this gtx plays out. He hates hates being on it. FFX was way better to be honest Let’s keep in touch. This has turned my day around a bit Thank you so much <3

Feel free to send me an email eve@evecourtney.net . I also wrote more about our experiences on my website evecourtney.net <3 

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 09:11 PM

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Fabulous - I just sent an email now! Thank you <3

RE: nanoknife IRE for pancreatic cancer

by DavesGirl70 on Tue Feb 11, 2020 04:28 PM

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Hey! I replied this morning but just got a bounce back notification now that my email wouldn't go through to the hotmail domain. I promise I'm not ignoring you :) 

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Thu Feb 13, 2020 05:42 PM

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I was just wondering about this - I was thinking it was me sending it to the wrong address. I’ll resend it from another address - Gmail account. Should that work ?

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Fri Feb 14, 2020 02:03 PM

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Hi! I thought it was my fault sending it to a wrong email! Could I resend from a gmail account? Would that be better?

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Feb 15, 2020 08:04 PM

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2020 Gastrointestinal Cancers Symposium
Olaparib (Lynparza), Installments Part 2

Everyone,
          This installment focuses on Olaparib (trade name Lynparza).  FDA-approved Olaparib is a PARP inhibitor which hinders poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.  It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations.  It is more active in some cancers than others.
          This installment is part of a review of abstracts from the 2020 GI Cancers Symposium, held January 23-25, 2020 in San Francisco.  There are at least 50 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:
http://pancreatic.altervista.org/downloads/GI20PancreaticCan  
          Be sure to study my Decision Guide, downloadable at
http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg  
         PhilipJax

          Olaparib may provide some benefit for metastatic patients harboring a germline BRCA mutation (about 4% to 7% of patients).  Olaparib is frequently called a “maintenance therapy” for BRCA patients, which is a generously term, given that nothing to date has “maintained” (kept at bay) this disease.  Usually the “maintenance” label is applied to therapies which follow adjuvant therapy and surgical resection.
          Below are the Olaparib references in the 2020 GI abstracts.  But first, a review of the definitive 2019 Olaparib trial report (linked below) titled: Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer.
http://pancreatic.altervista.org/downloads/Olaparib_BRCA2019
          This report describes a randomized double-blind trial in which 92 patients received Olaparib and 62 received placebo.  The researchers, from 14 institutions worldwide, present the following findings:
1. The median progression-free survival was significantly longer in the Olaparib group than in the placebo group (7.4 months vs. 3.8 months);
2. “An interim analysis of overall survival . . . showed no difference between the Olaparib and placebo groups (median, 18.9 months vs. 18.1 months);
3. “There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline;
4. “The incidence of grade 3 or higher adverse events was 40% in the Olaparib group and 23% in the placebo group.”
          A 2019 report describing the potential of PARP Inhibitors and the status of developing agents is downloadable here:
http://pancreatic.altervista.org/downloads/PARPInhibitors_BR
         The following 2020 ASCO abstracts refine some of the findings of the 2019 Olaparib trial report.

Abstract 653: Pancreatic cancer (PaC)-specific health-related quality of life (HRQoL) with maintenance olaparib (O) in patients (pts) with metastatic (m) PaC and a germline BRCAmutation (g BRCAm): Phase III POLO trial
          In this report we learn that Olaparib is somewhat effective for a metastatic BRCA patient only if the prior first-line FFX therapy produced at least 16 weeks of “disease control” (called DC16), usually meaning a Partial Response or Stable Disease for 16 weeks.  If FFX disease control was <16 weeks, the BRCA patient may not be a good candidate for Olaparib.
          Researchers noted that “the PFS [Progression Free Survival] of patients with DC16 was significantly higher than those with DC<16 weeks (9.3 vs 2.5 months).”

Abstract 648: Pancreatic cancer (PaC)-specific health-related quality of life (HRQoL) with maintenance olaparib (O) in patients (pts) with metastatic (m) PaC and a germline BRCAmutation (g BRCAm): Phase III POLO trial
          This abstract used data from the POLO (NCT02184195) trial to describe the symptom-reduction due to Olaparib in metastatic patients.  Although the table data suggest a slightly better Change From Base Line (CFBL) for Olaparib compared to Placebo (center column grouping), and an uncertain Time to Sustained Clinically Meaningful Deterioration (TSCMD), the researchers presented a contradictory judgment, stating:
1. “There were no clinically meaningful between-group differences in adjusted mean CFBL (Change From Base Line) symptom scores,” according to researchers.  And,
2. “TSCMD (Time to Sustained Clinically Meaningful Deterioration) in symptoms were not significantly different with Olaparib vs P.”  Much is concealed by the missing NR (Not Reached) values whose HR’s are >1.
3. And, “HRQoL (Health Related Quality of Life) was preserved with maintenance Olaparib . . . with no difference vs Placebo.”
          It is critical to note that only quality of life (HRQoL) indicators are presented.  Adverse Event data are presented in Abstract 686. The key life-prolonging indicators (median Progression Free Survival and median Overall Survival) were published in the 2019 trial report linked above.

Abstract 709: A phase I study of olaparib in combination with capecitabine-based chemoradiation (CRT) in patients (pts) with locally advanced pancreatic cancer (LAPC)
          This report describes clinical trial ISRCTN10361292 which exposed a group of 18 Locally Advanced patients (not metastatic) to a combination of Olaparib, Capecitabine (an oral form of 5FU) and radiation as a form of “maintenance therapy.”  Group members must have received a prior 12-week induction (initial treatment) chemotherapy that resulting in Partial Response or Stable Disease.  Most patients (12) had received induction Gemcitabine + Capecitabine, not a very potent combination.
         The UK researchers reported that the Olaparib + chemoradiation combination produced only 2 Partial Responses (a Response Rate of 11%), which is not good. It is hard to imagine that researchers thought that this therapy would be more successful.

Abstract 750: Early progression (progr) in patients (pts) with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation (gBRCAm): Phase III POLO trial of olaparib (O) versus placebo (P)
         In this followup of clinical trialISRCTN10361292 researchers report thatmetastatic BRCA patients having Physical Functioning scores (PhysF <86.7) were more likely to experience early disease progression.

Abstract 754: Exceptional responses to ipilimumab/nivolumab (ipi/nivo) in patients (pts) with refractory pancreatic ductal adenocarcinoma (PDAC) and germline BRCA or RAD51 mutations
          University of Miami investigators reviewed their institutional records and found 3 patients which were treated with a combination of two Immune Checkpoint Inhibitors (ICI’s): Ipilimumab and Nivolumab.  Separately the patients possessed BRAC1, RAD51C and BRCA2 mutations.
          These are the research findings:
1. The BRCA1 patient underwent resection and adjuvant Gemcitabine + Capecitabine (the new adjuvant standard).  Then, upon recurrence he received Ipilimumab/Nivolumab which resulted in a Complete Response (a complete absence of disease).
2. The RAD51C patient, diagnosed with metastatic disease, received induction FFX for 6 months followed by Olaparib for 12 months (perhaps on Olaparib trial ISRCTN10361292).  The disease progressed on this and subsequent 5FU/Liposomal Irinotecan, Gemcitabine/NabPaclitaxel/Cisplatin and FFX.  “He then started Ipilimumab/Nivolumab with immediate improvement in pain and tumor markers.  A radiological Partial Response was seen after 2 doses and is ongoing for 3 months with continued clinical and tumor marker improvement.”
3. The BRCA2 patient did not do well on Ipilimumab/Nivolumab, suffering “Progressive Disease with an exponential rise in tumor markers accompanied by clinical deterioration.”
          It appears that this subgroup of BRCA1 & RAD51C patients MAY respond to Ipilimumab/Nivolumab.  But, 2 robins don’t make a Spring.  Testing via clinical trial is needed.  This concludes the Olaparib references in the 2020 ASCO GI abstracts.
          In a week or so the next 2020 GI Symposium installment will be posted.
          Olaparib will not likely halt the disease.  You will need second-line and third-line therapies, which are detailed in my downloadable Decision Guide.  Within a few days of hard work you will understand how to approach this terrible disease, based on your disease stage – and learn what therapies work and which ones don’t.  The Guide is downloadable at
http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg  
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Mon Feb 17, 2020 04:00 AM

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Everyone
          The link to the Pancreatic Cancer Decision Guide has not copied well in the previous postings.  If the link immediately below does not work, there may be two other means:
http://jaxelection.altervista.org/pancreatic/ PJaxDecisionAlgorithm.pdf " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/ PJaxDecisionAlg
          If the above link fails, add PJaxDecisionAlgorithm.pdf to the end of the following link:
http://jaxelection.altervista.org/pancreatic/
          And, if that approach fails, Google the term “PJaxDecisionAlgorithm.pdf ” which may get you the downloadable file, hopefully.
         PhilipJax

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