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Scan shows progression, need advice.

Forums General Melanoma Community Scan shows progression, need advice.

  • Post
    Nadia
    Participant
      My husband, Dave, is Stage IV, dx in August 2013, and, of course, was told he has 8 months to live.  He was accepted in the Phase III, three arm double blinded Nivo+ipi, nivo, ipi, and he had the first IV on November 1st 2013.   The CT scan (Jan. 28) didn't bring us the good news we were hoping for.  Just to keep it short, some tumours decreased, some tumours increased.  No new tumours were seen.  The preliminary report shows close to 20% progression in the tumour load.  The biggest increase was noted on the liver tumour, and on the lungs nodules. Despite this, Dave feels great, energy levels are high, just like before the treatment started.  All his blood tests are normal, including the liver enzymes.  The LDH is 138 and it's been around this value since the beginning.
       
      We are still part of the Trial, as Dr. strongly feels there is still a chance Dave can benefit from the trial. He is receiving an IV every two weeks, for the next six weeks, at what point he is getting scanned again.
       
      My hopes are:
      1. There were almost three weeks in between the base line scan and the start of the trial.  There is a very good chance the tumours grew fast in this time frame and actually, although the numbers don't reflect it, his tumours are stable in size or even a little smaller.
      2. He is a slow responder to medication, and maybe the treatment will kick in soon.
       
      I kept track of all the side effects he had, and he had a lot.  None of the side effects sent him to the hospital.  The only drug he took  was Reactine, 2/day, to deal with his skin rashes and itchiness. 
       
      At some point I was sure he is on the combo arm (nivo plus ipi).  And then I thought he’s on nivo, and then on ipi only.  To tell you the truth…I have no idea.  I would almost prefer he was on nivo only, because that means ipi is still an option.  But if he was on the combo arm or on ipi only, well, pd1 is not available for him as a follow up.  He is BRaf positive (V600E).
       
      We are very positive people, we are going to fight this with all it takes.  We are not giving up, we have an amazing life and we have all the reasons in the world to fight our fight.
      I don't know how other people deal with the reality of this disease, but I am not listening to motivational tapes, or read positive and uplifting messages from the internet.  All I do in all my spare time is research, reading articles, links, blogs, fb, forums, all melanoma related.
       
       I hope from the bottom of my heart the scan in 6 weeks will show either stable or a decrease in the tumour load.  
      But if there is progression, and he was on ipi, what Plan B, Plan C, and Plan D look like?
      It seems the options would be:
      •  Tafinlar and MEK.  That, of course if this gets approved as standard care for Braf positive patients.
      –  TIL, either at NIH, Moffit, or MD Anderson
      –  Vemurafenib (Zelboraf)) 
       
      Now I need help from everybody involved in any of the above, or they know somebody that knows somebody:  please, let me know 
      – Is there any other treatment option that in your opinion would work as well and I missed?
      – what worked for you from the options listed above?
      – based on what you know from your experience, or somebody else's, in what order would you do the treatments above?
       
      Thank you very much for your patience and for your input.   As I said, I hope everything is going to be ok, but I need to know the answers and the options to the what ifs, it's my way of dealing, it's what keeps me going.  I have no prior experience with any kind of illness, I'm just doing what I can to take care of my man.
       
      Also, english my second language, please be kind with my grammar and choice of words.
       
    Viewing 2 reply threads
    • Replies
        arthurjedi007
        Participant

          I am struggling with the same decisions. I assume your Dr is a melanoma specialist since you are in that trial. I have my first PET scan after ipi this coming Monday. I am also hoping for the best but wondering what to do. I had a few mild side affects from ipi. The Dr told me having side affects from ipi meant it was working. We shall see. I plan to listen carefully to my Dr for what is next and what my Dr believes is the best treatment being developed. If you read lots of peoples posts you will see lots more treatments possible. Just the other day I learned about wdvax and mage3. However like my Dr says everyone is different so what works for one person may not work for another. Being in the ipi/nivo trial was good for your husband. Everything I read is it is the best available although it is closed to new patients now. Also the Dr said ipi takes awhile to work and they don't put much weight on the first scan I'm having Monday.

            BrianP
            Participant

              Hey Arthur,

              Good luck on the scan.  I hope you get good results.  Although I know you can't help but feel deflated if the results aren't what you are hoping for you definitely should not lose hope about Ipi.  I don't know the stats but I wouldn't be surprised if more people than not show either stable or progression on their first scan.  I'm going to go back and look at some webinars and studies on ipi and see if I can come up with that percentage.

              I was curious what you were told about mage3.  I had started the process of enrolling in a Mage vaccine trial for NED Stage IVs but unfortunately I recurred before I couild start the trial.  Do you have any specifics on where or what the mage3 treatment is?

              Good luck on Monday. 

              Brian

              P.S. are you a star wars and a james bond fan by chance?

              arthurjedi007
              Participant

                Hey Brian,

                The only mage3 thing I saw was from this member (frankMill) where if I understand correctly he went NED on it.

                http://www.melanoma.org/find-support/patient-community/mpip-melanoma-patients-information-page/tribute-all-mel-fighters#comment-72364

                ArtieV

                P.S. Yeah Star Wars is awesome 🙂 I remember watching the first one in the theater in 78. Yeah they sometimes stayed in the theater a long time back then. It was my parent's 20th wedding anniversary and mom had to see it.

                arthurjedi007
                Participant

                  Hey Brian,

                  The only mage3 thing I saw was from this member (frankMill) where if I understand correctly he went NED on it.

                  http://www.melanoma.org/find-support/patient-community/mpip-melanoma-patients-information-page/tribute-all-mel-fighters#comment-72364

                  ArtieV

                  P.S. Yeah Star Wars is awesome 🙂 I remember watching the first one in the theater in 78. Yeah they sometimes stayed in the theater a long time back then. It was my parent's 20th wedding anniversary and mom had to see it.

                  BrianP
                  Participant

                    Thanks Artie,

                    The trial Frank is on is actually the one I was in the process of enrolling in when I had a recurrence.  I actually talked to Frank a couple times on the phone during that time frame.  The trial was for Stage IV NED.  At that time (about 8 months ago) it had pretty impressive numbers for the percentage of patients it was keeping NED.  Surprising though around 5 months ago another Mage trial did not meet its endpoint goals and was terminated.  I'm not sure if that trial was for patients with unresectable melanoma or not.  I think it was.  One thing about those mage trials is your melanoma has to have the MAGE A3 gene expression.  It's present in about 50% of melanomas.

                    may the force be with you,

                    Brian

                    BrianP
                    Participant

                      Thanks Artie,

                      The trial Frank is on is actually the one I was in the process of enrolling in when I had a recurrence.  I actually talked to Frank a couple times on the phone during that time frame.  The trial was for Stage IV NED.  At that time (about 8 months ago) it had pretty impressive numbers for the percentage of patients it was keeping NED.  Surprising though around 5 months ago another Mage trial did not meet its endpoint goals and was terminated.  I'm not sure if that trial was for patients with unresectable melanoma or not.  I think it was.  One thing about those mage trials is your melanoma has to have the MAGE A3 gene expression.  It's present in about 50% of melanomas.

                      may the force be with you,

                      Brian

                      BrianP
                      Participant

                        Thanks Artie,

                        The trial Frank is on is actually the one I was in the process of enrolling in when I had a recurrence.  I actually talked to Frank a couple times on the phone during that time frame.  The trial was for Stage IV NED.  At that time (about 8 months ago) it had pretty impressive numbers for the percentage of patients it was keeping NED.  Surprising though around 5 months ago another Mage trial did not meet its endpoint goals and was terminated.  I'm not sure if that trial was for patients with unresectable melanoma or not.  I think it was.  One thing about those mage trials is your melanoma has to have the MAGE A3 gene expression.  It's present in about 50% of melanomas.

                        may the force be with you,

                        Brian

                        arthurjedi007
                        Participant

                          Hey Brian,

                          The only mage3 thing I saw was from this member (frankMill) where if I understand correctly he went NED on it.

                          http://www.melanoma.org/find-support/patient-community/mpip-melanoma-patients-information-page/tribute-all-mel-fighters#comment-72364

                          ArtieV

                          P.S. Yeah Star Wars is awesome 🙂 I remember watching the first one in the theater in 78. Yeah they sometimes stayed in the theater a long time back then. It was my parent's 20th wedding anniversary and mom had to see it.

                          BrianP
                          Participant

                            Hey Arthur,

                            Good luck on the scan.  I hope you get good results.  Although I know you can't help but feel deflated if the results aren't what you are hoping for you definitely should not lose hope about Ipi.  I don't know the stats but I wouldn't be surprised if more people than not show either stable or progression on their first scan.  I'm going to go back and look at some webinars and studies on ipi and see if I can come up with that percentage.

                            I was curious what you were told about mage3.  I had started the process of enrolling in a Mage vaccine trial for NED Stage IVs but unfortunately I recurred before I couild start the trial.  Do you have any specifics on where or what the mage3 treatment is?

                            Good luck on Monday. 

                            Brian

                            P.S. are you a star wars and a james bond fan by chance?

                            BrianP
                            Participant

                              Hey Arthur,

                              Good luck on the scan.  I hope you get good results.  Although I know you can't help but feel deflated if the results aren't what you are hoping for you definitely should not lose hope about Ipi.  I don't know the stats but I wouldn't be surprised if more people than not show either stable or progression on their first scan.  I'm going to go back and look at some webinars and studies on ipi and see if I can come up with that percentage.

                              I was curious what you were told about mage3.  I had started the process of enrolling in a Mage vaccine trial for NED Stage IVs but unfortunately I recurred before I couild start the trial.  Do you have any specifics on where or what the mage3 treatment is?

                              Good luck on Monday. 

                              Brian

                              P.S. are you a star wars and a james bond fan by chance?

                              Nadia
                              Participant

                                Thank you for your reply, I accidentally double posted this (big fingers, small screen combo)!  Please read the replies on that post as well.

                                Be patient, this is the advice I'm getting from lots of people, too early to tell, when it comes to ipi, patients scans showed in some cases a slight increase up to week 20.  There is still hope the next scan it's going to be better. 

                                 

                                JerryfromFauq
                                Participant

                                  Maria, here is a rougj lisst of istems I have an interest in for current treatments for people to look at.  I don't think that Canado has agreed to pay for IL-2 treatments nor has the hospital beds allocated to it utilization.   If this has changed, I would like to learn about the change.

                                  TRIALS -DRUGS OF INTEREST
                                  ************************************
                                  PD-1—38%
                                  LAG-3 ________
                                  MEK162-NRAS & BRAF_________
                                  IL-2 – NRAS  47%
                                  *******************************
                                  ?? BRAF, TVE-c, MEK, PD-1/PD-L1, IDO, ADC,  IPI
                                  ++++++++++++++++++++++++++++
                                  http://www.fool.com/investing/general/2014/01/11/how-researchers-are-waging-war-on-the-most-lethal.aspx
                                  ADC's – Antibody-drug
                                            conjugates: ADCs,
                                  is Immunomedics' (NASDAQ: IMMU  ) IMMU-132, which demonstrated impressive disease control rate in a phase 1 study of solid tumors.
                                  _________________________-
                                  Immunotherapy agents –
                                  ================
                                  AMD3100 was effective in breaking down the protective barrier that protects pancreatic cancer cells, allowing the toxin to eliminate nearly all pancreatic cancer cells in models. The drug works with an antibody to ensure that T-cells designed to destroy pancreatic cancer cells don't interact with the CXCL12 protein that protects these cancerous cells, clearing a pathway for the T-cells to directly target pancreatic cancer cells.
                                  ————-
                                  Anti-cancer stem cell therapeutics: Instead of fighting cancer cells the traditional way, researchers are instead targeting cancer stem cells, or CSCs, which are believed to have similar characteristics as normal stem cells. Specifically, CSCs are believed to be extremely resistant to chemotherapy and are considered the primary cause of secondary tumors, relapses, and global metastases.
                                  ———–
                                  One company targeting the CSCs is OncoMed Pharmaceuticals (NASDAQ: OMED  ) , —-
                                  ——
                                  Tumor hypoxia: I only know of one company smart enough to attempt to treat various types of cancer with hypoxia-targeted drugs, and that's Threshold Pharmaceuticals (NASDAQ: THLD  ) . Because cancerous tumors grow in unregulated patterns, there are often cells within tumors that get starved of oxygen-rich blood. While that does slow their ability to divide and form new cells, they often go undetected by most chemotherapy treatments. A tumor-hypoxia drug will seek out this low-level oxygen grouping of cells that's common in cancerous tumors but rare in normal tissue and attack it.

                                  Threshold's lead product is TH-302, which is a DNA alkylator being targeted at a number of therapies, including pancreatic cancer. Currently, Threshold and its collaborative partner Merck KGaA are running a global phase 3 trial, known as Maestro, to assess the effect and safety of TH-302 in combination with Gemzar on advanced-stage ———–
                                  —–
                                  http://www.marketwatch.com/story/target-enrollment-achieved-in-cavataktm-usa-phase-2-melanoma-trial-with-excellent-interim-results-2014-01-08————

                                  http://clinicaltrials.gov/show/NCT01543698
                                  A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent…
                                  clinicaltrials.gov
                                  **************************************8888
                                  http://www.cancercommons.org/news/new-immune-based-drug-shows-signs-of-effectiveness-in-several-cancers-2/
                                  ASCO Post | May 17, 2013
                                  The new cancer drug MPDL3280A has produced promising results in an early clinical trial that investigated patients with various advanced cancers including lung cancer; melanoma; and cancer of the kidney, intestines, or stomach. All participants had previously seen their cancer worsen despite treatment. Yet, during treatment with MPDL3280A, tumors shrank significantly in more than one-fifth of the patients. Response rates were especially high in lung cancer and melanoma patients. Of the patients who responded to MPDL3280A, almost all continue to see effects now, 3 to 15+ months into the study. MPDL3280A targets a protein, PD-L1, that is often expressed on cancer cells and ‘hides’ the cells from the body’s immune response; by blocking PD-L1, MPDL3280A allows the immune system to attack the tumors. Further studies will be needed to confirm these findings.
                                  . Response rates were even higher in subsets of patients with lung cancer (22%) or melanoma.

                                  **********************************************

                                  JerryfromFauq
                                  Participant

                                    Maria, here is a rougj lisst of istems I have an interest in for current treatments for people to look at.  I don't think that Canado has agreed to pay for IL-2 treatments nor has the hospital beds allocated to it utilization.   If this has changed, I would like to learn about the change.

                                    TRIALS -DRUGS OF INTEREST
                                    ************************************
                                    PD-1—38%
                                    LAG-3 ________
                                    MEK162-NRAS & BRAF_________
                                    IL-2 – NRAS  47%
                                    *******************************
                                    ?? BRAF, TVE-c, MEK, PD-1/PD-L1, IDO, ADC,  IPI
                                    ++++++++++++++++++++++++++++
                                    http://www.fool.com/investing/general/2014/01/11/how-researchers-are-waging-war-on-the-most-lethal.aspx
                                    ADC's – Antibody-drug
                                              conjugates: ADCs,
                                    is Immunomedics' (NASDAQ: IMMU  ) IMMU-132, which demonstrated impressive disease control rate in a phase 1 study of solid tumors.
                                    _________________________-
                                    Immunotherapy agents –
                                    ================
                                    AMD3100 was effective in breaking down the protective barrier that protects pancreatic cancer cells, allowing the toxin to eliminate nearly all pancreatic cancer cells in models. The drug works with an antibody to ensure that T-cells designed to destroy pancreatic cancer cells don't interact with the CXCL12 protein that protects these cancerous cells, clearing a pathway for the T-cells to directly target pancreatic cancer cells.
                                    ————-
                                    Anti-cancer stem cell therapeutics: Instead of fighting cancer cells the traditional way, researchers are instead targeting cancer stem cells, or CSCs, which are believed to have similar characteristics as normal stem cells. Specifically, CSCs are believed to be extremely resistant to chemotherapy and are considered the primary cause of secondary tumors, relapses, and global metastases.
                                    ———–
                                    One company targeting the CSCs is OncoMed Pharmaceuticals (NASDAQ: OMED  ) , —-
                                    ——
                                    Tumor hypoxia: I only know of one company smart enough to attempt to treat various types of cancer with hypoxia-targeted drugs, and that's Threshold Pharmaceuticals (NASDAQ: THLD  ) . Because cancerous tumors grow in unregulated patterns, there are often cells within tumors that get starved of oxygen-rich blood. While that does slow their ability to divide and form new cells, they often go undetected by most chemotherapy treatments. A tumor-hypoxia drug will seek out this low-level oxygen grouping of cells that's common in cancerous tumors but rare in normal tissue and attack it.

                                    Threshold's lead product is TH-302, which is a DNA alkylator being targeted at a number of therapies, including pancreatic cancer. Currently, Threshold and its collaborative partner Merck KGaA are running a global phase 3 trial, known as Maestro, to assess the effect and safety of TH-302 in combination with Gemzar on advanced-stage ———–
                                    —–
                                    http://www.marketwatch.com/story/target-enrollment-achieved-in-cavataktm-usa-phase-2-melanoma-trial-with-excellent-interim-results-2014-01-08————

                                    http://clinicaltrials.gov/show/NCT01543698
                                    A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent…
                                    clinicaltrials.gov
                                    **************************************8888
                                    http://www.cancercommons.org/news/new-immune-based-drug-shows-signs-of-effectiveness-in-several-cancers-2/
                                    ASCO Post | May 17, 2013
                                    The new cancer drug MPDL3280A has produced promising results in an early clinical trial that investigated patients with various advanced cancers including lung cancer; melanoma; and cancer of the kidney, intestines, or stomach. All participants had previously seen their cancer worsen despite treatment. Yet, during treatment with MPDL3280A, tumors shrank significantly in more than one-fifth of the patients. Response rates were especially high in lung cancer and melanoma patients. Of the patients who responded to MPDL3280A, almost all continue to see effects now, 3 to 15+ months into the study. MPDL3280A targets a protein, PD-L1, that is often expressed on cancer cells and ‘hides’ the cells from the body’s immune response; by blocking PD-L1, MPDL3280A allows the immune system to attack the tumors. Further studies will be needed to confirm these findings.
                                    . Response rates were even higher in subsets of patients with lung cancer (22%) or melanoma.

                                    **********************************************

                                    JerryfromFauq
                                    Participant

                                      Maria, here is a rougj lisst of istems I have an interest in for current treatments for people to look at.  I don't think that Canado has agreed to pay for IL-2 treatments nor has the hospital beds allocated to it utilization.   If this has changed, I would like to learn about the change.

                                      TRIALS -DRUGS OF INTEREST
                                      ************************************
                                      PD-1—38%
                                      LAG-3 ________
                                      MEK162-NRAS & BRAF_________
                                      IL-2 – NRAS  47%
                                      *******************************
                                      ?? BRAF, TVE-c, MEK, PD-1/PD-L1, IDO, ADC,  IPI
                                      ++++++++++++++++++++++++++++
                                      http://www.fool.com/investing/general/2014/01/11/how-researchers-are-waging-war-on-the-most-lethal.aspx
                                      ADC's – Antibody-drug
                                                conjugates: ADCs,
                                      is Immunomedics' (NASDAQ: IMMU  ) IMMU-132, which demonstrated impressive disease control rate in a phase 1 study of solid tumors.
                                      _________________________-
                                      Immunotherapy agents –
                                      ================
                                      AMD3100 was effective in breaking down the protective barrier that protects pancreatic cancer cells, allowing the toxin to eliminate nearly all pancreatic cancer cells in models. The drug works with an antibody to ensure that T-cells designed to destroy pancreatic cancer cells don't interact with the CXCL12 protein that protects these cancerous cells, clearing a pathway for the T-cells to directly target pancreatic cancer cells.
                                      ————-
                                      Anti-cancer stem cell therapeutics: Instead of fighting cancer cells the traditional way, researchers are instead targeting cancer stem cells, or CSCs, which are believed to have similar characteristics as normal stem cells. Specifically, CSCs are believed to be extremely resistant to chemotherapy and are considered the primary cause of secondary tumors, relapses, and global metastases.
                                      ———–
                                      One company targeting the CSCs is OncoMed Pharmaceuticals (NASDAQ: OMED  ) , —-
                                      ——
                                      Tumor hypoxia: I only know of one company smart enough to attempt to treat various types of cancer with hypoxia-targeted drugs, and that's Threshold Pharmaceuticals (NASDAQ: THLD  ) . Because cancerous tumors grow in unregulated patterns, there are often cells within tumors that get starved of oxygen-rich blood. While that does slow their ability to divide and form new cells, they often go undetected by most chemotherapy treatments. A tumor-hypoxia drug will seek out this low-level oxygen grouping of cells that's common in cancerous tumors but rare in normal tissue and attack it.

                                      Threshold's lead product is TH-302, which is a DNA alkylator being targeted at a number of therapies, including pancreatic cancer. Currently, Threshold and its collaborative partner Merck KGaA are running a global phase 3 trial, known as Maestro, to assess the effect and safety of TH-302 in combination with Gemzar on advanced-stage ———–
                                      —–
                                      http://www.marketwatch.com/story/target-enrollment-achieved-in-cavataktm-usa-phase-2-melanoma-trial-with-excellent-interim-results-2014-01-08————

                                      http://clinicaltrials.gov/show/NCT01543698
                                      A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent…
                                      clinicaltrials.gov
                                      **************************************8888
                                      http://www.cancercommons.org/news/new-immune-based-drug-shows-signs-of-effectiveness-in-several-cancers-2/
                                      ASCO Post | May 17, 2013
                                      The new cancer drug MPDL3280A has produced promising results in an early clinical trial that investigated patients with various advanced cancers including lung cancer; melanoma; and cancer of the kidney, intestines, or stomach. All participants had previously seen their cancer worsen despite treatment. Yet, during treatment with MPDL3280A, tumors shrank significantly in more than one-fifth of the patients. Response rates were especially high in lung cancer and melanoma patients. Of the patients who responded to MPDL3280A, almost all continue to see effects now, 3 to 15+ months into the study. MPDL3280A targets a protein, PD-L1, that is often expressed on cancer cells and ‘hides’ the cells from the body’s immune response; by blocking PD-L1, MPDL3280A allows the immune system to attack the tumors. Further studies will be needed to confirm these findings.
                                      . Response rates were even higher in subsets of patients with lung cancer (22%) or melanoma.

                                      **********************************************

                                      Nadia
                                      Participant

                                        Thank you for your reply, I accidentally double posted this (big fingers, small screen combo)!  Please read the replies on that post as well.

                                        Be patient, this is the advice I'm getting from lots of people, too early to tell, when it comes to ipi, patients scans showed in some cases a slight increase up to week 20.  There is still hope the next scan it's going to be better. 

                                         

                                        Nadia
                                        Participant

                                          Thank you for your reply, I accidentally double posted this (big fingers, small screen combo)!  Please read the replies on that post as well.

                                          Be patient, this is the advice I'm getting from lots of people, too early to tell, when it comes to ipi, patients scans showed in some cases a slight increase up to week 20.  There is still hope the next scan it's going to be better. 

                                           

                                        arthurjedi007
                                        Participant

                                          I am struggling with the same decisions. I assume your Dr is a melanoma specialist since you are in that trial. I have my first PET scan after ipi this coming Monday. I am also hoping for the best but wondering what to do. I had a few mild side affects from ipi. The Dr told me having side affects from ipi meant it was working. We shall see. I plan to listen carefully to my Dr for what is next and what my Dr believes is the best treatment being developed. If you read lots of peoples posts you will see lots more treatments possible. Just the other day I learned about wdvax and mage3. However like my Dr says everyone is different so what works for one person may not work for another. Being in the ipi/nivo trial was good for your husband. Everything I read is it is the best available although it is closed to new patients now. Also the Dr said ipi takes awhile to work and they don't put much weight on the first scan I'm having Monday.

                                          arthurjedi007
                                          Participant

                                            I am struggling with the same decisions. I assume your Dr is a melanoma specialist since you are in that trial. I have my first PET scan after ipi this coming Monday. I am also hoping for the best but wondering what to do. I had a few mild side affects from ipi. The Dr told me having side affects from ipi meant it was working. We shall see. I plan to listen carefully to my Dr for what is next and what my Dr believes is the best treatment being developed. If you read lots of peoples posts you will see lots more treatments possible. Just the other day I learned about wdvax and mage3. However like my Dr says everyone is different so what works for one person may not work for another. Being in the ipi/nivo trial was good for your husband. Everything I read is it is the best available although it is closed to new patients now. Also the Dr said ipi takes awhile to work and they don't put much weight on the first scan I'm having Monday.

                                        Viewing 2 reply threads
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