Pulsed Therapy (Modified Watch and Wait) a Clinical Update

[PulsedTherapy]

Hello HealthUnlocked Community,

I've written about the idea of pulsed therapy -- aka, adaptive therapy, although I find more acceptance (though not by much) if I refer to it as "modified watch and wait" -- here before, and wanted to give an update.

First a disclosure. as I've been warned by this site, I'm not an oncologist, this is a completely novel idea, at least as it applies to CLL, and may in fact be very dangerous, and certainly no one should take this as any more as something to discuss with their oncologists. All opinions here are solely my own.

The overview from 30,000 feet.

1) I don't like the idea of watch and wait, where treatment is delayed until you have symptoms.

2) I don't like that CLL therapies have very serious adverse events and potentially seriously diminish quality of life. Neutropenia is extremely common, it diminishes the ability of the immune system, and increases the chances of secondary issues including secondary cancers.

3) I don't like that extended treatment can often lead to resistance to drugs and diminished overall survival

4) I think the idea of trying to achieve uMRD sets up exactly the environment that will bring resistance, as the only cells left are necessarily those that are resistant, and as they are then operating in an environment without competition, they have the opportunity to rebound unchecked, in a process termed "competitive release," which has been applied in the field of pesticide use since the 1970s.

5) Because early stage CLL is rather indolent and it's eradication is virtually impossible, I speculated that rather than watch and wait, then going to a full blown attempt at uMRD, why not treat early, and only enough to keep the disease in the indolent phase. Effectively, just control the disease enough so you're asymptomatic and live with it as a chronic disease.

6) I can't say this is my idea. Gatenby has been doing pioneering work on this methodology for almost 2 decades and has been having stunning results with solid tumors, but not CLL. I spoke to him, and he believes the strategy is reasonable in CLL because the highest replication happens in the protected niches of the lymph nodes and BM.

7) Aside from Gatenby, who doesn't work in CLL, I found the community (4 oncoologists so far) are absolutely against this strategy, and I understand why. "We are having great results with current therapies" and "we have no idea what are the consequences of this novel approach." But with uIGHV and mTP53, the results don't look that great to me.

8) Fortunately I was able to find an oncologist, after considerable cajoling, to go along with the approach. I post the results below. I found it amazing that with 4 days of very low dose venetoclax, my ALC was reset back a year. At this point we don't know what the new doubling rate will be, what the other consequences will be, but the resistance window is so short and dose so small, it is very unlikely, though not impossible, that resistance could have been selected for. But biology is complicated and you just never know.

8a) By the way if you watch and wait until your ALC is very high, the chance of TLS increases significantly. I was worried about that even at an ALC of 17 and hydrated like a fiend.

9) if you look at the results so far you might find them stunning, I did. Just a 10mg dose brought a kill of 3000. A second 10mg does brought a minimal kill. A third 20mg dose brought a minimal kill, but a fourth 40mg does brought a kill bigger than the first, 3600. And even more stunning, 3 weeks post venetoclax, the kill is still happening. Which may not be too surprising because as we can see from just these results, there are threshold kills as evidenced by the 40mg kill, and we know venetoclax binds covalently. So there may be more CLL cells that have been compromised by the drug, but are slower to die.

10) Of course, all of this, and everything I am writing is open to interpretation and criticism. But no one is trying the idea of treating CLL as a chronic disease and instead are only in two camps, watch and wait, if you're lucky enough, and treat to uMRD. If miraculously, somehow Gatenby has come up with an idea that translates to CLL, it could potentially be a watershed approach to CLL that cuts costs to next to nothing and dramatically reduces adverse events.

11) So I'm a clinical trial n=1. I will share my results as they continue, and welcome your thoughts, even if highly critical, it's OK, I know I am out on a limb here.

All my best and thanks to everyone in this great community.

[Vlaminck]

Wow, fascinating! Your analysis make sense. Please keep us posted such as when you get your next small dose. Have the killing affects yet ceased or at they still in gear?

[PulsedTherapy in reply to Vlaminck]

Thanks for your post Vlaminck. Making sense is not always enough in the ridiculously complicated world of human biology, but what else do we have to go by? The results I gave you were from last week, so not sure if the delayed kill has stopped yet. I’m not even sure it’s truly a delayed kill or unrelated fluctuation. Hard to know anything for certain. But will keep you and the community updated. Thanks.

[cajunjeff]

Hello Pulsed Therapy. Watch and wait can be a very hard strategy for all of us. It is just so counter intuitive to do nothing as our cancer presses on. I totally understand why you have decided to challenge this treatment paradigm. And you seem to be doing it in a thoughtful and measured way. Our doctors can advise us, but to treat or not treat is ultimately our choice.

That said, your path is not one I would take. I am fortunate enough to have a highly skilled and trained Cll specialist who I am sure knows 10000 times more about how and when to treat cll. While your theory seems reasonable, and indeed the watch and wait paradigm is being reconsidered from cll in light of the new meds, substituting some treatment theory I might have against the advice of my doctor seems really unwise to me.

I am always very skeptical of posts on here promoting alternative therapies. Indeed I think some posters on here that have done that are impostors who have joined the site to prey on a vulnerable population with snake oil remedies.

I appreciate that you, on the other hand, make it very clear that you have no medical background and acknowledge that the path you have chosen might just not work, it could also be dangerous. I think that sort of disclosure is very impt for anyone posting about alternative therapies on here.

Add to that, you are not really on some controversial alternative therapy anyway, you are taking veneoclax, a drug proven to be a very powerful cll med. Its the timing of when you are taking venetoclax that makes your approach experimental.

While I do not think trials of one prove much, I sure hope your plan works for you. Your theory certainly seems a reasonable one. But there is also the risk that using cll drugs before we need them can lead to early resistance.

Good luck to you. I would not be surprised to see the watch and wait paradigm for cll change in the future. I think you used the right word though in saying that choosing a treatment our doctors do not approve can be dangerous. I did not even know what Cll was when I was diagnosed and I have no medical background. Substituting my plan for my doctors plan for me is like saying I know more than my doctor, and clearly I do not.

[PulsedTherapy in reply to cajunjeff]

Thanks CajunJeff, there is a lot of wisdom in what you wrote. I cannot argue with you, trusting your oncologist must be the default. I am just offering arguments that you can use to discuss with your oncologist if they make sense to you. Ultimately, shouldn't everything make sense?

But I will add, I was exactly like you, CLL? What the hell is that? But nothing like the diagnosis to focus the mind. Since then, I have read a mountain of papers. It's absolutely fascinating when you step back. If you want to read more on adaptive therapy, google gatenby and scientific american. He wrote a great article a few years back that spells it all out in a very convincing case.

[cajunjeff in reply to PulsedTherapy]

I did google Gatenby. He appears to be a legitimate doctor who has some interesting theories about cancer therapies. He is not one of these YouTube pseudo-science doctors that hype unproven alternative therapies for financial gain.

For every theory or medicine that pans out, there are typically dozens more that do not. It does not appear that Gatenby has any experience with cll. Even if his theory is correct as to one cancer, it might not as to another.

With most all cancers, early detection and treatment is critical to survival. Clinical trials and experience have led cll doctors to conclude that our survival is longer by watching and waiting.

I am lucky to be close enough to Houston to treat at MD Anderson. I have at one time or another seen Dr Keating and Dr Weirda, two of the most recognized cll specialists in the world. Dr Keating was my doctor through my watch and wait stage.

So I were to consider a plan like you have undertaken, I would ask myself this:

Should I follow the advice of Dr Keating on when to treat and what medicine dose to take or should I craft my own treatment plan based on some articles I read about a doctor who does not treat cll and has never tested his theories on cancer with cll?

It’s just not remotely a close call for me. I wish you the best with your plan. It appears you have thought thus out well and you sound like a bright guy. But to be honest with you, it seems very ill advised to me for anyone with cll to think they know better than Cll specialist and craft their own one of one trial.

I would be more concerned if you were using an unproven supplement. I have little doubt ventoclax used at almost any dose and frequency will not treat your cll and kill cll cells. But I think any lay person using a complicated cancer drug different than as approved to craft their own treatment plan based on some theory they read about is, in general, a terrible idea. I mean no disrespect, we are all in it together. I do hope it works for you.

[PulsedTherapy in reply to cajunjeff]

Absolutely CajunJeff. You get no argument from me. Follow your oncologist.

[Vlaminck in reply to cajunjeff]

I have posted articles I find about supplements, not as alternative therapies but possibly additional help or of at least possible interest. I hope I'm not one you are speaking about. I like people feeling free to bring up whatever they find that might be of interest. By the way, snake oil became know as a scam cause traveling salesmen of old sold fake snake oil, but real snake oil had some healthful benefits, being a type oil (Omega 3) that many of us don't get that much of (and pretty certain they didn't in the ole West).

[cajunjeff in reply to Vlaminck]

No, I was not referring to you. It was a generalization about posts we get from time to time advocating the use of supplements over proven therapies which contradicts medical advice of cll specialists. I think that’s dangerous.

Snake oil originated in China. There are some proven benefits from the oil of chinese water snakes.

Snake oil sold in the Wild West usually had no snake oil in it at all. That’s a problem with lots of supplements. No one knows for sure what’s in them. That’s how snake oil became part of our lexicon. It’s a catch all term for unproven miracle cures

I am not anti supplement, I took iron supplements when I had hemolytic anemia prescribed for me by my cll doctor. Likewise I think supplements can help people with vitamin deficiency.

So I am sorry if I offended you. But we do have people on here at times suggesting supplements to treat cancer where there is no medical proof that can cause harm.

[Vlaminck in reply to cajunjeff]

Thank you, cajunjeff. No, you didn't offend me confirming you weren't referring to me or those that merely mention supplements. Sure, if anyone says to ignore all medical info and take instead this or that, they could harming people who believe it. I didn't know about the China water snake or its connection to snake oil. But it's my understanding that a large % of folks don't get enough omega 3 which could be supplied by any snake, as I understand it. Fortunately, we now have Omega 3 supplements if not also eating fish.

[cajunjeff in reply to Vlaminck]

Hey, no worries at all. I could have worded my first reply a lot better. In no way was it my intent to suggest supplements can not be beneficial in some cases, nor that supplements are not an appropriate topic on here. But there a lot of charlatans promoting supplements and unproven remedies who target cancer forums like this.

Here is a link about snake oil consistent with your remarks about the benefits of omega oils. I was using snake oil in the context of how it has become a catch all phrase for anyone selling bogus remedies.

en.m.wikipedia.org/wiki/Sna...

[Vlaminck in reply to cajunjeff]

Oh, I fully understood what you meant by referencing snake oil, as it has that horrible reputation because of all the fake sellers who instead sold mineral oil and other stuff as snake oil. It is always used as a scam thing. I just remember learning about its original health benefits (I think in a book called something like "Good fats/Bad fats") so thought I'd just mention that.

[may04cll]

Interesting ! More then interesting !!

[PulsedTherapy in reply to may04cll]

Yes, it really is. I tell my doctor all the time, the only way this could be more interesting is if it weren't happening to me!

[may04cll in reply to PulsedTherapy]

Wondering if the any or all of the members of the iwCLL would or could comment on this strategy ?!

[BigfootT]

Certainty a thought provoking idea. I guess if I saw a downside it might be that the low dose may help "teach" the CLL to evade it's Venetoclax "poison". I'm thinking sort of a vaccine effect in reverse. By exposing the cancer to low doses does it help the CLL to eventually overcome the Ven? I'm assuming there is good trial data that drove recommended doseage guidelines. Bigfoot

[PulsedTherapy in reply to BigfootT]

Thanks BigfootT, you are definitely on to something here, and a subject that I have been in endless debate over.

Venetoclax, unlike older chemotherapies, is not mutagenic (damage the dna), so the chance of a drug created new resistant strain from traditional dna mutations is not high, but certainly not zero. There are many studies that do show, fortunately, venetoclax does not usually create resistance -- usually is the operative word here.

Can it however select for CLLs with existing resistance, yes, definitely. BUT, the who point of adapted therapy is to always keep a large population of non-resistant cells around to compete with the resistant cells. When you go to uMRD, you take that competitive environment away, and if you do get a resistant line, there's nothing to keep it in check.

And if you do have a pre-existing population of resistant cells, well, it's too late anyway. If you go the traditional approach, you will face this problem anyway.

But let me just offer the argument to your concern that I have never received a reasonable answer to. If you are worried that a short term low dose therapy taken maybe once or twice a year will create a resistant line, well, then why aren't we worried about creating a resistant line by taking the drug for a year or longer?

The stars have lined up to give us bad alternatives, that's the simple truth. The best we can do is choose the least bad alternative. And of course, as I am the first to admit, I don't know what that least bad alternative is. Does anyone?

[Alex830 in reply to PulsedTherapy]

But would it promote the creation of CLL resistant cells to Venetoclax with the end result that Venetoclax would not work anymore because all cells created are resistant to Venetoclax.

[PulsedTherapy in reply to Alex830]

Hi Alex, definitely a concern, but in my last post I offered some reasoning on exactly this issue. It's a good one! The main argument I repost here:

"But let me just offer the argument to your concern that I have never received a reasonable answer to. If you are worried that a short term low dose therapy taken maybe once or twice a year will create a resistant line, well, then why aren't we worried about creating a resistant line by taking the drug for a year or longer?"

[cajunjeff in reply to PulsedTherapy]

For me, the least bad alternative, considering I have cancer, is not that bad. Under the direction of a Cll specialist I can take medicines, some just oral pills, that in combination or in sequence with other cll meds, give me a decent chance to live a full life.

The worst alternative for me would be to draft my own plan. To adopt my own plan over what Dr Keating at MD Anderson made for me would necessarily mean that I think I know better about cll and resistance than a leading expert in the field.

Resistance to cancer medications is one of the most complicated topics discussed and debated by the biomedical scientists in the world. I read about Cll stuff all the time, but my level of understanding the chemistry of mutations and resistance is below rudimentary.

I am not clear with the options we have, why you would do this experiment. You have designed your own trial, based on an unproven cancer theory, a theory that has nothing to do with cll. Have you come to the conclusion that all the top Cll specialists know less than you on how to dose and sequence our meds? I am just curious how you can think that.

I wish you the best and dont question your right to treat as you want. You seem like a bright guy. It confuses me how an obviously intelligent guy, with no medical experience, would think he knows more than doctors and scientists who deal with this issue for a living.

[Vlaminck in reply to BigfootT]

Yes, important consideration.

[AussieNeil Partner Administrator]

Thank you for providing such detailed reporting of your N of 1 experiment. You've provided an excellent example of the degree of reporting that is necessary to be reasonably convincing from anyone espousing unproven treatments. In 16 years of reading such reports, I've never seen much beyond statements of percentage changes from a commonly unmentioned WBC baseline count. It's rare that quantitative absolute lymphocyte counts are documented by those promoting alternative treatments , let alone changes in platelets and haemoglobin.

Of course this is just a start and it will be impossible to know without a reasonably large trial of randomly assigned people whether your approach has merit, though you will have the satisfaction of knowing that you've reduced your CLL tumour burden earlier than would otherwise be the case. I just wish you'd had the opportunity to ask CLL researchers for their opinion of your central hypothesis, outlined in your point 4.

May I suggest that you add a column for your neutrophil count (ANC) and use common units for your WBC, ALC and ANC - or you could drop your WBC and just report ALC, ANC and other WBCs. You did note that "Neutropenia is extremely common, it diminishes the ability of the immune system, and increases the chances of secondary issues including secondary cancers." However, I'd be very interested where you heard of an association between neutropenia and secondary cancers, as I've never heard of this. It's your cytotoxic T and Natural Killer lymphocytes that perform cancer surveillance by detecting peptide expression on our cell membrane Major Histocompatibility Complexes, for example;

Natural Killer Cells: Tumor Surveillance and Signaling

pmc.ncbi.nlm.nih.gov/articl...

Effects of Peptide on NK Cell-Mediated MHC I Recognition

pmc.ncbi.nlm.nih.gov/articl...

Do keep in mind that you are currently reporting just the tumour load of CLL in the blood, along with proxy reporting of the CLL bone marrow infiltration through changes in your haemoglobin and platelets. I appreciate that it is far harder to report changes in node and spleen side.

Neil

[PulsedTherapy in reply to AussieNeil]

Hi AussieNeil, thanks for you thoughtful comments.

"I've never seen much beyond statements of percentage changes from a commonly unmentioned WBC baseline count."

"May I suggest that you add a column for your neutrophil count (ANC)"

Yes, I've noticed that too. But clearly, the more data the better. Funny, SkyShark said the same thing about ANC. It's a great idea, I will definitely add ANC with my next update. I took a quick look, and ANC edged up after treatment, so hopefully a sign of improvements in the BM>

"I just wish you'd had the opportunity to ask CLL researchers for their opinion of your central hypothesis, outlined in your point 4."

I asked at least 4. I hope I made it clear, no one is onboard with this, except Gatenby, the pioneer in the field but importantly, not a pioneer in CLL, and the oncologist I was finally able to convince that this was worth a shot. We are faced with tradeoffs all the time and have to make decisions on imperfect information.

"You did note that "Neutropenia is extremely common, it diminishes the ability of the immune system, and increases the chances of secondary issues including secondary cancers."

You are right to challenge this assertion. Neutropenia does not directly increase the risk of secondary cancers as far as I can tell, but we do know that secondary cancers is a definite risk in CLL. So I was using neutropenia incorrectly to make the point the general point that these drugs compromise the immune system generally, and by disturbing the complex signaling that is used to signal, warn, and orchestrate defenses against cancer, you thereby increase the risk. T-cells and NK cells seem to be somewhat compromised too, though not nearly as much as neutrophils.

"Do keep in mind that you are currently reporting just the tumour load of CLL in the blood," along with proxy reporting of the CLL bone marrow infiltration through changes in your haemoglobin and platelets. I appreciate that it is far harder to report changes in node and spleen side. :("

Yes, you are spot on. I worry about this too. I am going to speak to my oncologist about a BM MRI to get a baseline on BM cellularity. This will very accurately show what's going on there.

On a related note. Did you notice in the details I posted, that 3 weeks post treatment, I showed an ALC decrease from 9160 to 8700? I fully expected an increase as I resume some type of doubling time. I was rather stunned to see a decrease. Any thoughts on that?

Thanks again AussieNeil.

[bennevisplace]

PT, thanks for posting this. I appreciate that you are doing so to inform people about your n=1 clinical trial, rather than to promote Pulsed Therapy (Modified W&W) as the way to go for all.

As you are doing this in the care of an oncologist, I assume you discussed with him or her various treatment options. I'm wondering why venetoclax mono? Did you have at baseline: a physical exam, comprehensive blood analyses, cytogenetics, scans? Did your onc make you sign a disclaimer before agreeing to administer pulsed therapy?

In any case, I hope you'll continue to keep us updated with your progress. I think the approach is attractive in principle, and I admire the courage of your conviction.

[PulsedTherapy in reply to bennevisplace]

Thanks for your post bennevisplace. Yes, I have numerous conversations with numerous oncologists. All are inclined to watch and wait, except as I wrote, one I was able to convince. And yes, I've had all the works, at least those that I'm aware of. No, no disclaimer, venetoclax is a standard treatment.

So why venetoclax? What are the choices? BTK inhibitors, antibodies, and BCL. BTK works slowly and migrates CLL out of the BM and lymph. I am thinking very conservative here. I didn't want to start with BTK because it would disrupt the microenvironment. But you also can't get a quick response with low does short term BTK. Keeping the resistance window small was very important. Obinutuzumab is a powerful drug, and is clears CLL cells with phagocytosis, which reduces TLS, so it is definitely an option, but complicated being an IV. So I am left with BCL2.

Venetoclax is not mutagenic, and provides an excellent bang for the buck. They start in regular treatment ramp up at 20mg. I started at 10mg, and had a 3000 kill. So seemed like a good choice, and in retrospect, still does.

As you can see I am in a completely new experiment, I don't know what the future treatments will look like. I couldn't have even told you in advance my first course would be 10, 10, 20, 40. All game time decisions.

Using a combination though seems very reasonable in that you can keep resistance down by ensuring the new mutation has to overcome two drugs instead of one. But with treatment windows so small, I don't know if it's worth the extra risk yet. Every drug, every dose has risks.

Will keep you posted.

[bennevisplace in reply to PulsedTherapy]

Thanks for your detailed reply. My questions stem from the thought that peripheral blood counts don't necessarily represent tumour burden very well. A CT scan, which I believe is capable of detecting asymptomatic CLL in secondary lymph organs, could help. Venetoclax monotherapy while good at clearing the peripheral blood of CLL cells is less able to clear lymph nodes, spleen etc. So, despite your reservations about BTKi, it might be prudent to combine one with Ven, is my thinking. Did you discuss that possibility with your oncologist? I take your point regarding the extra risk of the extra drug, but that's versus the extra risk of resistance to the single drug, right?

I guess it's really hard to design a clinical trial from scratch!

[PulsedTherapy in reply to bennevisplace]

Yes, you raise a great point that I have labored over, "ALC only measure blood."

Fortunately, I've seen several studies showing venetoclax is effective in the niches of lymph and BM to a significant degree, so I'm running on the assumption it's a fair proxy. But you are right, it's only an assumption.

I don't like CTs, who needs the extra radiation. How did we get into this situation in the first place?

However, a bone marrow MRI can measure cellularity. very accurately. And this seems to be an ideal way to measure CLL trends in the BM. I am planning on speaking to my oncologist about have this done to get a baseline.

Your point about BTK is a good one. I have been and will be considering it.

[Skyshark]

Well wow!

Good to see your platelets that seemed marginal are recovering.

Rule of thumb Neut = WBC - ALC - 1 indicates that Neuts have increased.

Together this would indicate you have affected marrow and not just peripheral blood.

None of the treat early trials have looked at very short duration treatments like this for the very early diagnosed with low counts like yours.

So this was just 80mg of Venetoclax in total?

Maybe worth testing for the clonal count, you could have set it back to MBL, clone count >5,000. If it's not MBL that may be a better target for next round, looks achievable.

Most certainly hope your gamble pays off.

But for idiots like me that arrive at the doctors with an ALC > 80(k) and swollen lymph nodes conventional treatments are needed. But this raises the question what should come after? There is one trial of Ven+Obin that aims to reduce first treatment to 9 cycles if uMRD4 is reached at cycle 7. STATIC trial is looking at MRD directed continuing maintenance treatment using (slow acting) cBTKi after cBTKi + Ven but that only tests MRD at 3 monthly intervals, which sets the on/off periods. There isn't a trial for maintenance using pulsed Ven.

[PulsedTherapy in reply to Skyshark]

Hi Skyshark, and thanks for your comments, insightful as always.

"Rule of thumb Neut = WBC - ALC - 1 indicates that Neuts have increased. Together this would indicate you have affected marrow and not just peripheral blood."

Seems so obvious, but I never thought of doing this. What a great idea. In my next update I will include neutrophils. Just a quick look, seems like they bumped up, so perhaps space has been freed up in the BM.

"So this was just 80mg of Venetoclax in total?"

Yes, 10 10 20 40. Amazing the results from 80mg, when the daily dose in traditional therapy is 400mg per day. My thanks to the absolute brilliance of the researchers who developed this drug.

"Maybe worth testing for the clonal count, you could have set it back to MBL, clone count >5,000. If it's not MBL that may be a better target for next round, looks achievable."

Yes, that seems about right. B cells typical range 2-3000, so with a total of 8700, the MBL is probably around 5000-6000. Of course, when you are going for uMRD, you need to test for the MBL, but here, the rough arithmetic seems fine.

I am not sure what the next round will look like yet or when. My inclination right now is to, not surprisingly, just watch and weight. And when my ALC returns to where it was before this last treatment (16700), treat again the same way. Do it exactly the same creates great data points.

"But for idiots like me that arrive at the doctors with an ALC > 80(k) and swollen lymph nodes conventional treatments are needed."

Ha, I don't know if it would have mattered. The conventional approach is to just wait until you finally walk in with those symptoms anyway.

"There isn't a trial for maintenance using pulsed Ven."

This has me scratching my head. But the truth is, while I have the utmost respect for the brilliant researchers and clinicians in the field, there just isn't enough time to try so many reasonable approaches. It's not that the approaches are defective, it is that trials take an enormous amount of time, effort, and money.

Thanks again for your thoughts.

[LeoPa]

This is exactly the thing I'm interested in. I wish you a world of luck with this experiment because if you pull it off, I might do this one day. Calculated risk taking is sometimes all we are left with. Pity there are no clinical trials verifying this approach, but as long as it's all about money, there's no incentive to do so. I don't even need to be some conspiracy theorist (which I'm not, anyways) to be sure that this is so. Keep posting your results please.

[PulsedTherapy in reply to LeoPa]

You're right LeoPa. Who's going to finance a trial that turns a $250k/year drug treatment regimen into $265? That was my venetoclax cost.. But it's way too early to know if I'm on the right path. Just hope I don't get hit by a bus because I'd be disappointed if I didn't get to find out how this turns out.

[PaulaS Volunteer in reply to PulsedTherapy]

I also hope you won't get hit by a bus, Pulsed Therapy! 😮🙏🏻