› Forums › General Melanoma Community › Zelboraf & Blood-Brain barrier
- This topic has 51 replies, 10 voices, and was last updated 9 years, 8 months ago by
kalisama.
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- October 29, 2013 at 2:51 am
As some of you know, I've been on Zelboraf for a year, NED for at least nine months. Well, unfortunately I found out last Friday that I have multiple brain mets in all four brain quadrants after waking up that morning with severe neurological double vision problems and nystagmus. Both the oncologist and the radiologist think there are just too many (and too much edema, currently) for SRS or other targeted prodedures, and fearing I might have a stroke, put me on dexamethazone right away, along with WBR. I've been doing the treatments and responding well, in that my vision has cleared up for now. But we know this is only a temporary thing.
But here's the kicker: The Zelboraf apparently is still working on the tumors within my body, as the PET-CT I did last weekend shows NED anywhere outside my skull. Since there is no decisive data on whether Zelboraf does or does not cross the blood-brain barrier, the Onc wants to try dose escalation, thinking that higher concentrations might help get more of the drug into my brain. He said that in his searches, he has found two documented cases worldwide where it has been tried. One was for a person who had stopped responding entirely to Z, and the dose escalation had no effect. But the other case was a person like me, who had brain mets while the body remained clear, and they were able to elicit a partial response.
Anybody else here tried any does escalation of Z? Thoughts?
- Replies
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- October 29, 2013 at 7:39 am
Hi bj63,
Sorry to read about your dilemma. This situation is one I have wondered about myself before – I am on the GSK braf drug for the past year and have often thought about what would happen if brain mets returned but body remained stable.
The GSK BRAF/MEK drug (dabrafenib/trametinib also known as Tafinlar/Mekinist) has some limited clinical data that suggests it is effective in dealing with brain mets – I dont have a link for that info but if you search this forum you should find it. There is also some anecdotal evidence to suggest the same. In my own case, two brain mets shrunk by 50% in the space of 10 days on Dabrafenib before I received radiation treatment.
Might be worth discussing with your oncologist whether a change to dabrafenib (or the combo if possible) would be worth a shot.
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- October 29, 2013 at 10:18 am
I am sorry that you are having to struggle with brain mets. For reasons nobody seems to understand, it is common to develop one or more brain mets while on Zelboraf even though the tumors in the rest of your body are still responding.
I agree with John, the Tafinlar/Mekinist combination might just work better on brain mets than Zelboraf alone. It's certainly worth a try.
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- October 29, 2013 at 10:18 am
I am sorry that you are having to struggle with brain mets. For reasons nobody seems to understand, it is common to develop one or more brain mets while on Zelboraf even though the tumors in the rest of your body are still responding.
I agree with John, the Tafinlar/Mekinist combination might just work better on brain mets than Zelboraf alone. It's certainly worth a try.
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- October 29, 2013 at 10:18 am
I am sorry that you are having to struggle with brain mets. For reasons nobody seems to understand, it is common to develop one or more brain mets while on Zelboraf even though the tumors in the rest of your body are still responding.
I agree with John, the Tafinlar/Mekinist combination might just work better on brain mets than Zelboraf alone. It's certainly worth a try.
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- October 29, 2013 at 3:04 pm
Thanks for your reply. The dabrafenib / tranetinib combo is one of the options we discussed, actually. I'm thinking that might be my first fallback position if I don't respond to the dose escalation. Or maybe teozolomide / MEK, since the teozolomide is known at least to cross the barrier. Decsions decisions …
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- October 29, 2013 at 3:04 pm
Thanks for your reply. The dabrafenib / tranetinib combo is one of the options we discussed, actually. I'm thinking that might be my first fallback position if I don't respond to the dose escalation. Or maybe teozolomide / MEK, since the teozolomide is known at least to cross the barrier. Decsions decisions …
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- October 29, 2013 at 3:04 pm
Thanks for your reply. The dabrafenib / tranetinib combo is one of the options we discussed, actually. I'm thinking that might be my first fallback position if I don't respond to the dose escalation. Or maybe teozolomide / MEK, since the teozolomide is known at least to cross the barrier. Decsions decisions …
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- October 29, 2013 at 7:39 am
Hi bj63,
Sorry to read about your dilemma. This situation is one I have wondered about myself before – I am on the GSK braf drug for the past year and have often thought about what would happen if brain mets returned but body remained stable.
The GSK BRAF/MEK drug (dabrafenib/trametinib also known as Tafinlar/Mekinist) has some limited clinical data that suggests it is effective in dealing with brain mets – I dont have a link for that info but if you search this forum you should find it. There is also some anecdotal evidence to suggest the same. In my own case, two brain mets shrunk by 50% in the space of 10 days on Dabrafenib before I received radiation treatment.
Might be worth discussing with your oncologist whether a change to dabrafenib (or the combo if possible) would be worth a shot.
-
- October 29, 2013 at 7:39 am
Hi bj63,
Sorry to read about your dilemma. This situation is one I have wondered about myself before – I am on the GSK braf drug for the past year and have often thought about what would happen if brain mets returned but body remained stable.
The GSK BRAF/MEK drug (dabrafenib/trametinib also known as Tafinlar/Mekinist) has some limited clinical data that suggests it is effective in dealing with brain mets – I dont have a link for that info but if you search this forum you should find it. There is also some anecdotal evidence to suggest the same. In my own case, two brain mets shrunk by 50% in the space of 10 days on Dabrafenib before I received radiation treatment.
Might be worth discussing with your oncologist whether a change to dabrafenib (or the combo if possible) would be worth a shot.
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- October 31, 2013 at 9:49 am
Hello, I am very sorry that you are facing this difficult situation. My husband was a total responder on Zelboraf but switched to the Dabrafenib/Mekinist combo while still responding because the combo offered more benefits, one of which is that there is clinical evidence that it does cross the BB barrier. My husband is doing great on the combo and is having less side effects than he had while on Zel. I would worry about the possible side effects of dose escalation if that was an option that we were offered only because my husband suffered many severe side effects on Zel and actually had a dose reduction. It seems that your odds are better with trying the combo if there is only one case of a partial response with dose escalation of Zel. That is just my opinion.
Wishing you strength, comfort and guidance from above in your decisions for treatment in your battle against melanoma.
God bless you,
Gina
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- October 31, 2013 at 9:49 am
Hello, I am very sorry that you are facing this difficult situation. My husband was a total responder on Zelboraf but switched to the Dabrafenib/Mekinist combo while still responding because the combo offered more benefits, one of which is that there is clinical evidence that it does cross the BB barrier. My husband is doing great on the combo and is having less side effects than he had while on Zel. I would worry about the possible side effects of dose escalation if that was an option that we were offered only because my husband suffered many severe side effects on Zel and actually had a dose reduction. It seems that your odds are better with trying the combo if there is only one case of a partial response with dose escalation of Zel. That is just my opinion.
Wishing you strength, comfort and guidance from above in your decisions for treatment in your battle against melanoma.
God bless you,
Gina
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- October 31, 2013 at 9:49 am
Hello, I am very sorry that you are facing this difficult situation. My husband was a total responder on Zelboraf but switched to the Dabrafenib/Mekinist combo while still responding because the combo offered more benefits, one of which is that there is clinical evidence that it does cross the BB barrier. My husband is doing great on the combo and is having less side effects than he had while on Zel. I would worry about the possible side effects of dose escalation if that was an option that we were offered only because my husband suffered many severe side effects on Zel and actually had a dose reduction. It seems that your odds are better with trying the combo if there is only one case of a partial response with dose escalation of Zel. That is just my opinion.
Wishing you strength, comfort and guidance from above in your decisions for treatment in your battle against melanoma.
God bless you,
Gina
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- December 8, 2013 at 12:46 am
I was all set to start the dose escalation but the insurance company is balking and doesn't want to pay for the dose increase. If I can't get them to agree, what next? Switch to Tafinlar / Mekinist?
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- December 8, 2013 at 9:26 pm
I'm on Tafinlar only (9 wks) and it seems to be keeping my 2 brain mets stable.
Amy
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- December 8, 2013 at 9:26 pm
I'm on Tafinlar only (9 wks) and it seems to be keeping my 2 brain mets stable.
Amy
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- December 8, 2013 at 9:26 pm
I'm on Tafinlar only (9 wks) and it seems to be keeping my 2 brain mets stable.
Amy
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- December 20, 2013 at 12:08 am
Well, the dose escalation is a moot point – the insurance won't pay for it. So I've switched to the Tafinlar for now (no Mekinist, again, insurance). My Oncologist also has scheduled me to see Dr. John Kirkwood at UPCI to explore other options.
Anybody else have problems with really bad headaches after starting Tafinlar – like migraine level headaches? Tylenol barely touches them.
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- December 20, 2013 at 12:08 am
Well, the dose escalation is a moot point – the insurance won't pay for it. So I've switched to the Tafinlar for now (no Mekinist, again, insurance). My Oncologist also has scheduled me to see Dr. John Kirkwood at UPCI to explore other options.
Anybody else have problems with really bad headaches after starting Tafinlar – like migraine level headaches? Tylenol barely touches them.
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- December 20, 2013 at 12:08 am
Well, the dose escalation is a moot point – the insurance won't pay for it. So I've switched to the Tafinlar for now (no Mekinist, again, insurance). My Oncologist also has scheduled me to see Dr. John Kirkwood at UPCI to explore other options.
Anybody else have problems with really bad headaches after starting Tafinlar – like migraine level headaches? Tylenol barely touches them.
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- January 18, 2014 at 1:10 am
Had and MRI last Thursday that showed stable brain mets plus about a 25% shrinkage in the two largest tumors – obvious good news. Plus I met with Dr. Kirkwood at UPCI this week. Now that the combo is FDA approved, he wants me to start the trametinib right away in addition to the dabrafenib. Plus we mapped out a tentative future course of action should it become necessary. I also found it interesting that he mentioned PD1 as being on fast-track for FDA approval.
I'm feeling good and having no obvious symptoms, so overall a very positive result over the last six weeks. Now if my hair would only grow back from the WBR!
bj63
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- January 18, 2014 at 12:49 pm
That is wonderful news! Good for you! I hope and expect that the addition of Mekinist will work even better than the Tafinlar alone– there is considerable evidence that the combo is your best bet. WBR and Zelboraf both cause hair loss; apparently the combo does not. So hopefully, your hair will soon grow back now, too.
Keep us posted on your progress!
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- January 18, 2014 at 12:49 pm
That is wonderful news! Good for you! I hope and expect that the addition of Mekinist will work even better than the Tafinlar alone– there is considerable evidence that the combo is your best bet. WBR and Zelboraf both cause hair loss; apparently the combo does not. So hopefully, your hair will soon grow back now, too.
Keep us posted on your progress!
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- January 18, 2014 at 12:49 pm
That is wonderful news! Good for you! I hope and expect that the addition of Mekinist will work even better than the Tafinlar alone– there is considerable evidence that the combo is your best bet. WBR and Zelboraf both cause hair loss; apparently the combo does not. So hopefully, your hair will soon grow back now, too.
Keep us posted on your progress!
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- February 3, 2014 at 2:33 am
HI – so glad to hear your MRI results were good. I've been reading through this post trying to gather info for my sister who is in a similar situation. She has been on Zelboraf since the fall for mets in lung and breast and is having continued great response in those areas but now has multiple small brain mets (>10). She is currently doing WBRT and her doctors are talking about restarting Zelboraf or starting the Dabrafenib/tramatinib combo. Just wondering if your doctors also gave you the option of Ipilimumab? Or any other options (any clinical trials accepting patients with brain mets?). It is certianly good to hear that you and others are having good responses to dabrafenib after already being on Zelboraf. She is not having repeat scans for another 6 weeks (not sure if this is typical after WBRT) but I think the plan is to start back on some type of systemic therapy as soon as the radiation is done next week. Any further info would be appreciated!
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- February 3, 2014 at 4:41 am
We discussed several options, including the dose escalation with vemurafenib, temozolomide, ipi, dabrafenib/tramatinib, etc. Originally my oncologist wanted to do dose escalation with the vemurafenib. His thinking was that, because we know my melanoma is still sensitive to the BRAF drugs outside the brain, we might be able to get the blood concentration high enough to get it into the brain in sufficient quantities to make a difference. I actually started this dose escalation therapy but had to abandon it after two weeks because we could not get my insurance company to pay for this course of treatment.
So we decided the next best course of action was to switch to the dabrafenib / tramatinib combo. Again, the thinking was that the melanoma in my body for now continues to respond to the BRAF drugs, and the dabrafenib has shown evidence of producing a clinical response in the brain for at least some patients. It seems to be helping because, at my last MRI in mid-January, two of my larger tumors did show a signficant amount of shrinkage (around 20 – 25%). So I am hopeful that the dabrafenib / tramatinib combo will hold it at bay.
As for the timing of the scans, that schedule sounds about right. I did 3 weeks of WBR and then I had a scan after about another 3 weeks. I had a second scan after another 6 weeks (I think!) to see how I was responding to the medication.
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- April 2, 2014 at 4:49 pm
Can I ask how many brain mets did you have? My brother has multiple brain mets (which they said Zelboraf isn't working anymore). They said since Zelboraf and WBR didn't work there wasn't anything else they could. They literally sent us home on 3/20 with no other option. This combo wasn't even brought up to us. He had been on Zelboraf for 7 months with regression and little to no new growth and then BAM this. Any insight you have would be extremely helpful!
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- April 2, 2014 at 4:49 pm
Can I ask how many brain mets did you have? My brother has multiple brain mets (which they said Zelboraf isn't working anymore). They said since Zelboraf and WBR didn't work there wasn't anything else they could. They literally sent us home on 3/20 with no other option. This combo wasn't even brought up to us. He had been on Zelboraf for 7 months with regression and little to no new growth and then BAM this. Any insight you have would be extremely helpful!
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- April 2, 2014 at 4:49 pm
Can I ask how many brain mets did you have? My brother has multiple brain mets (which they said Zelboraf isn't working anymore). They said since Zelboraf and WBR didn't work there wasn't anything else they could. They literally sent us home on 3/20 with no other option. This combo wasn't even brought up to us. He had been on Zelboraf for 7 months with regression and little to no new growth and then BAM this. Any insight you have would be extremely helpful!
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- February 3, 2014 at 4:41 am
We discussed several options, including the dose escalation with vemurafenib, temozolomide, ipi, dabrafenib/tramatinib, etc. Originally my oncologist wanted to do dose escalation with the vemurafenib. His thinking was that, because we know my melanoma is still sensitive to the BRAF drugs outside the brain, we might be able to get the blood concentration high enough to get it into the brain in sufficient quantities to make a difference. I actually started this dose escalation therapy but had to abandon it after two weeks because we could not get my insurance company to pay for this course of treatment.
So we decided the next best course of action was to switch to the dabrafenib / tramatinib combo. Again, the thinking was that the melanoma in my body for now continues to respond to the BRAF drugs, and the dabrafenib has shown evidence of producing a clinical response in the brain for at least some patients. It seems to be helping because, at my last MRI in mid-January, two of my larger tumors did show a signficant amount of shrinkage (around 20 – 25%). So I am hopeful that the dabrafenib / tramatinib combo will hold it at bay.
As for the timing of the scans, that schedule sounds about right. I did 3 weeks of WBR and then I had a scan after about another 3 weeks. I had a second scan after another 6 weeks (I think!) to see how I was responding to the medication.
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- February 3, 2014 at 4:41 am
We discussed several options, including the dose escalation with vemurafenib, temozolomide, ipi, dabrafenib/tramatinib, etc. Originally my oncologist wanted to do dose escalation with the vemurafenib. His thinking was that, because we know my melanoma is still sensitive to the BRAF drugs outside the brain, we might be able to get the blood concentration high enough to get it into the brain in sufficient quantities to make a difference. I actually started this dose escalation therapy but had to abandon it after two weeks because we could not get my insurance company to pay for this course of treatment.
So we decided the next best course of action was to switch to the dabrafenib / tramatinib combo. Again, the thinking was that the melanoma in my body for now continues to respond to the BRAF drugs, and the dabrafenib has shown evidence of producing a clinical response in the brain for at least some patients. It seems to be helping because, at my last MRI in mid-January, two of my larger tumors did show a signficant amount of shrinkage (around 20 – 25%). So I am hopeful that the dabrafenib / tramatinib combo will hold it at bay.
As for the timing of the scans, that schedule sounds about right. I did 3 weeks of WBR and then I had a scan after about another 3 weeks. I had a second scan after another 6 weeks (I think!) to see how I was responding to the medication.
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- February 3, 2014 at 2:33 am
HI – so glad to hear your MRI results were good. I've been reading through this post trying to gather info for my sister who is in a similar situation. She has been on Zelboraf since the fall for mets in lung and breast and is having continued great response in those areas but now has multiple small brain mets (>10). She is currently doing WBRT and her doctors are talking about restarting Zelboraf or starting the Dabrafenib/tramatinib combo. Just wondering if your doctors also gave you the option of Ipilimumab? Or any other options (any clinical trials accepting patients with brain mets?). It is certianly good to hear that you and others are having good responses to dabrafenib after already being on Zelboraf. She is not having repeat scans for another 6 weeks (not sure if this is typical after WBRT) but I think the plan is to start back on some type of systemic therapy as soon as the radiation is done next week. Any further info would be appreciated!
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- February 3, 2014 at 2:33 am
HI – so glad to hear your MRI results were good. I've been reading through this post trying to gather info for my sister who is in a similar situation. She has been on Zelboraf since the fall for mets in lung and breast and is having continued great response in those areas but now has multiple small brain mets (>10). She is currently doing WBRT and her doctors are talking about restarting Zelboraf or starting the Dabrafenib/tramatinib combo. Just wondering if your doctors also gave you the option of Ipilimumab? Or any other options (any clinical trials accepting patients with brain mets?). It is certianly good to hear that you and others are having good responses to dabrafenib after already being on Zelboraf. She is not having repeat scans for another 6 weeks (not sure if this is typical after WBRT) but I think the plan is to start back on some type of systemic therapy as soon as the radiation is done next week. Any further info would be appreciated!
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- January 18, 2014 at 1:10 am
Had and MRI last Thursday that showed stable brain mets plus about a 25% shrinkage in the two largest tumors – obvious good news. Plus I met with Dr. Kirkwood at UPCI this week. Now that the combo is FDA approved, he wants me to start the trametinib right away in addition to the dabrafenib. Plus we mapped out a tentative future course of action should it become necessary. I also found it interesting that he mentioned PD1 as being on fast-track for FDA approval.
I'm feeling good and having no obvious symptoms, so overall a very positive result over the last six weeks. Now if my hair would only grow back from the WBR!
bj63
-
- January 18, 2014 at 1:10 am
Had and MRI last Thursday that showed stable brain mets plus about a 25% shrinkage in the two largest tumors – obvious good news. Plus I met with Dr. Kirkwood at UPCI this week. Now that the combo is FDA approved, he wants me to start the trametinib right away in addition to the dabrafenib. Plus we mapped out a tentative future course of action should it become necessary. I also found it interesting that he mentioned PD1 as being on fast-track for FDA approval.
I'm feeling good and having no obvious symptoms, so overall a very positive result over the last six weeks. Now if my hair would only grow back from the WBR!
bj63
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- August 9, 2014 at 12:07 am
So happy I found this forum after the year + battle I have been dealing with. I was started on Zelbarof over a year ago and suffered from every possible side effect. Eventually I developed a met in my left shoulder. The Tafinlar/Mekinist was just FDA approved the week of my Cyberknife surgery for that tumor and my Oncologist switched me to this new combo treatment.
I am now many months in to this treatment enjoying the lack of side effects compared to Z, however I too have developed multiple brain mets. I just received Cyberknife treatments on the 2 largest lesions, with a wait and see approach by both my oncologist and radiologist on the others. Both said the same thing to me, that these meds simply do not cross the brain/blood barrier very well. The rest of my body is clean.
I am extremely interested in this topic. These meds clearly do their job. How do we get them up in to our brains?!
Glad I stepped out and found you folks doing the best we can on this journey so that I feel less alone.
Blessings and grace to you all.
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- August 9, 2014 at 12:07 am
So happy I found this forum after the year + battle I have been dealing with. I was started on Zelbarof over a year ago and suffered from every possible side effect. Eventually I developed a met in my left shoulder. The Tafinlar/Mekinist was just FDA approved the week of my Cyberknife surgery for that tumor and my Oncologist switched me to this new combo treatment.
I am now many months in to this treatment enjoying the lack of side effects compared to Z, however I too have developed multiple brain mets. I just received Cyberknife treatments on the 2 largest lesions, with a wait and see approach by both my oncologist and radiologist on the others. Both said the same thing to me, that these meds simply do not cross the brain/blood barrier very well. The rest of my body is clean.
I am extremely interested in this topic. These meds clearly do their job. How do we get them up in to our brains?!
Glad I stepped out and found you folks doing the best we can on this journey so that I feel less alone.
Blessings and grace to you all.
-
- August 9, 2014 at 12:07 am
So happy I found this forum after the year + battle I have been dealing with. I was started on Zelbarof over a year ago and suffered from every possible side effect. Eventually I developed a met in my left shoulder. The Tafinlar/Mekinist was just FDA approved the week of my Cyberknife surgery for that tumor and my Oncologist switched me to this new combo treatment.
I am now many months in to this treatment enjoying the lack of side effects compared to Z, however I too have developed multiple brain mets. I just received Cyberknife treatments on the 2 largest lesions, with a wait and see approach by both my oncologist and radiologist on the others. Both said the same thing to me, that these meds simply do not cross the brain/blood barrier very well. The rest of my body is clean.
I am extremely interested in this topic. These meds clearly do their job. How do we get them up in to our brains?!
Glad I stepped out and found you folks doing the best we can on this journey so that I feel less alone.
Blessings and grace to you all.
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