ADT/Chemo ASAP vs Later w/short doubl... - Advanced Prostate...

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ADT/Chemo ASAP vs Later w/short doubling time

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At 12 years post-RRP and age 73, my PSA is 35-45 (WHO vs Hybritech protocol) and my doubling time (DT) is a very consistent 4 months but I have no symptoms … yet. My fourth c-11 choline PET/CT scan finally found many scattered lymph node mets producing the PSA; no other scans can see them … yet. A long list of oncologists want me on ADT (hormone therapy) + chemo yesterday, but of course they care only about longevity and their NCCN-approved Standards of Care, and like most oncologists they expressly delegate side effect/SE management to our primary care physicians/PCPs. (e.g., “They” can just remove any breasts we grow, give us painkillers for the mastalgia/breast pain”, and implant a sling to fix incontinence; we can just dang well ignore our night sweats; and so what if we’re tethered to a toilet for life?”) However, even the most dismissive discussions of SEs admit that ADT mitigation efforts leave athletes like me fresh outta solutions.

I keep telling them there’s more to life than heartbeat, but they don’t want to hear it. Thus these questions, under the statistical assumption that my median prognosis with all-out drug warfare is two years until castrate resistance (CR) then another 18 months until death:

1. Is it sane to even consider delaying ADT until I feel symptoms, as many med oncs advise with less threatening risk profiles? With my previous DT of 30 months, that was a no-brainer; at 4 mo it’s not.

2. How about delaying until ADT becomes palliative … i.e., feels better than the symptoms … as a significant minority of med oncs such as Scholz of the PCRI advise? Or is the scattered herd of lesser but growing alligators too threatening to even consider that?

3. Let’s complicate #1 and #2 with this: two med oncs strongly advise a biopsy/bx of my most blatant node first because I had a carcinoid cancer removed from my bowel 12 years ago, post-op pathology gave it a >.50 chance of recurring, and its primary chemical marker (chromogranin A) now suggests it could be returning in conjunction with my PC. If so, my prognosis and my treatment options are dramatically reduced. The most accurate and quickest way to determine whether there’s a neuroendocrine (NE, aka “carcinoid”) component to my PC is a bx of my most prominent node, which is crammed in between my carotid artery and my trachea. Even the Mayo Clinic’s “Mr. Whac-a-Mole” himself, c-11 choline scan guru Eugene Kwon, threw in the towel on whac-a-mole at that definitive scan last November and pronounced it “time for ADT + chemo”.) Its location allows only laparoscopic biopsy. That, in turn, raises this question: If they’re going to access the node anyway for a bx, why not just excise it while they’re in there, if that’s feasible, before it matures into a new primary tumor? Shouldn’t that buy me some time on the PSA curve and reduce the threat to those nearby vital components both now and then again when ADT fails?

OK, your followup question is clearly and justifiably, “Why not just try ADT first?”. “If your T and your PSA drop significantly, yor PC is not NE” (NEPC is castrate resistant from the start, leading to a very short life expectancy). My response, and my next question of this group, is …

4. “But mightn’t a laparoscopic bx and possibly an excision:

a) answer the NE question AND

b) maybe remove a serious near- and long-term vital organ threat while it’s still discrete AND

c) do it all sooner and more definitively than an ADT trial AND

d) perhaps provide some useful insight into the nature of my returning PC?

(This would be done by a full-time cardiothoraxic surgeon at a major hospital, I sleep through anesthesia, and surgeries simply give me a bit of time to catch up on some neglected reading and TV.)

5. If such a bx proves negative for NEPC, we’re done with this line of questioning. But if it’s positive, and my median survival prognosis is thus cut from 3.5 years to < one year, why screw that year up with a bunch of awful intended and unintended blows to my QOL?

Discussion?

I.P. Freely (but slings are considered successful if they bring leakage down to my normal level)

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gusgold profile image
gusgold

My guess is excision is to dangerous or Kwon would have rec'd it. Did you look into Proton Beam as a possible option.

in reply to gusgold

I pondered several implications of Kwon's non-mention of the NE factor, among at least four options: too many mets, DT too fast to mess around, excision difficulty, or dismissal of the odds it's NE. I asked, and he said there were just too many moles lined up, and probably more hiding just beyond detection ... for now.

My main objective is evaluating the NE threat, and any beam ... Proton, laser, Tricorder ... would destroy the evidence. Unless this cardiac surgeon considers it risky beyond the standard anesthesia and invasion concerns, I'm tending towards bx and will at least raise the question of same-time excision. Then I'll bounce his answers off my medical oncologist. It's nice to have a backup means of evaluating the NE factor (if the node doesn't shrink w/castrate T levels, it's NE and my time shrinks from years to months) if the surgeon balks.

BigRich profile image
BigRich

" found many scattered lymph node mets"; How many and where are they located?

Rich

in reply to BigRich

They haven't even counted them. They cite "many", with locations from "supraclavicular to mediastinum" (the main one) to "iliac crest" to "diffused towards the pelvis. Heck, my first c-11 scan suggested diffused meserentic recurrence ... an event he's encountered only once. They didn't show at a PSA 0f 17, but at 34, they all popped to varying degrees.

But that's GOOD, IMO. At least now the threat is assessable and we can make informed decisions. It also makes me VERY glad I very informedly rejected my long-time, highly regarded uro onc's insistence on salvage radiation upon recurrence three years ago. We know now (and I had explicit reasons to believe then) that the final score in that game would have been SEs 100, Benefits 0.

1. Correct. But if positive for NE involvement, it changes my prognosis and tx options so much that two med oncs feel it's very important IN MY CASE (always an important caveat lest the next guy think it's important to HIM.)

2. I'm normally biased more towards QOL than the generally safe path. But with a DT of 4 months, the two paths seem to be merging towards one option ... immediate ADT followed shortly by chemo ... unless this bx is NE-positive.

3. I fully support citations, but haven't time right now to cite this one yet again (I've cited it many times in alt.support.cancer.prostate.) The rest of my life depends on decisions made in the next few days, so I'm 100% immersed in research at the moment. Scholz also advises choosing our second tx based on SEs rather than outcome statistics, because the SEs will dominate our limited time remaining.

in reply to

ADT with possible later chemo maybe.

3. Understood. I was questioning the accuracy of Scholz being as skeptical on ADT as he is on RP. You are seeing him!? ADT wont worsen NET.

As you know, Martin, ADT is becoming a no-brainer, and adjuvant chemo adds a dramatic boost to its median effectiveness. But while some varieties of NET respond to ADT, others render it useless, leaving only the ADT SEs ... a losing battle. In addition, NET cuts my remaining MTTF ... Median Time To Funeral :) ... by something like 75%. That would tempt me to just go windsurfing until even chemotherapy made me feel BETTER, then reevaluate. I'm just beginning to look into the implications and tx options for NET. I'd like to believe at that time that I made the best decisions I could at the previous times along the way.

I'm not seeing Scholz, but his name and comments surface often. As my cancers' faces have changed in just the past three years, I've consulted with many oncologists at several local, regional and national level cancer centers. Advice and sometimes medical priorities have been all over the map, so it's up to me to choose among the many institutions, individuals, and treatment options/variations. Thus my research (and a powerful hint for every man here), and thus my focus on a medical oncologist 10 minutes from where I sit. If I'm going to buy a can of Standard of Care brand ADT and a can of Standard of Care Chemo off the shelf, I don't need to drive or fly hundreds or thousands of miles for it. I've not yet ruled out Leibowitz in Los Angeles now or down the road; they were the ones who raised the biopsy concern echoed days later by my local med onc.

If this crap weren't so darned personal, it might be fun. It's at the very least interesting. But ... and here's another heartfelt tip ... WE ARE NOT GOING TO LIVE FOREVER. Think long and hard about that every time the slightest opportunity for an early retirement appears.

I.P.

in reply to

I should add that I recognize Scholz's well-documented bias against the Prostate Snatchers, but he's not alone in that or his dislike for onerous drug regimens, either. I'm seeing a trend ... heck, a tidal wave ... in PubMed of oncologists criticizing the casual attitude of their peers towards prescribing ADT and chemo with little regard for their downsides. Many studies don't even log SEs unless they cripple a patient (or require multiple followup open abdominal surgeries, in the case of surgery or radiation). One renowned oncologist stunned a symposium of his peers years ago by announcing that he was stopping his ADT because he preferred death to his side effects.

On the other side of that bell curve is my brother, who never even noticed his seven weeks of salvage radiation or 6 months of adjuvant ADT (and whose PSA dropped to undetectable).

JoelT profile image
JoelT

The few very small mets found on the last choline scan are not, by themselves, the answer to your higher PSA.

Therefore, going after them would not provide enough positive effect to balance out the risks of side effects from any procedure.

There is some other thing or things generating your PSA that have not been detected. Could be many micro-mets or one or two other mets somewhere else in your body.

Joel

in reply to JoelT

Joel wrote: There is some other thing or things generating your PSA that have not been detected. Could be many micro-mets or one or two other mets somewhere else in your body.

That's probably Kwon's conclusion. He can see enough such nodes to render individual intervention impractical, but figures that PSA=40 and doubling every 4 months is too threatening to ignore any longer. That, from a man who has "brought back" PSAs from 25,000 to 2.5, is a pretty powerful statement. (That patient's scans showed many pounds of tumors in every bone and organ throughout his entire torso. )

But I'm not giving up on excision until and unless this cardiothoraxic surgeon throws in the towel. As long as ... and IF ... he's in there anyway, what the heck?

BigRich profile image
BigRich in reply to JoelT

: very small mets" What size in centimetets is small and medium and large tumors?

Rich

in reply to BigRich

In cm ... or furlongs or cubits or hands ... I don't know what qualifies as a "big" PC tumor (or node). But relatively speaking, if it's big enough to appear on a scan, it's time to consider killing or removing it, depending on what else is going on. My biggest one wasn't visible at PSA = 17, but was visible at 35. How much PSA it contributes vs the other 10 (40? a hundred?) lesser ones is anybody's guess.

Another measure might be whether we can feel its effects (e.g., bone mets) or what threat it imposes (e.g., an organ? A carotid? A trachea?)

With purely carcinoid/NE tumors, the cutoff point for declaring a 50/50 chance of recurrence is 2 cm. Three involved lymph nodes is another such threshold. I had both.

BigRich profile image
BigRich in reply to

The question on size, I addressed to Joel. However, I appreciate your input, for knowledge is empowerment.

Thank you.

Rich

in reply to BigRich

Big ... Rich ( :) ) ... wrote "The question on size, I addressed to Joel. "

Oops! I missed that. I'm having enough trouble finding the new posts among the 30 or so that pop up.

BigRich profile image
BigRich in reply to JoelT

Joel,

:very small mets" What size in centimetets is small and medium and large tumors?

Rich

Hi

First a caution in attempting to handicap a timeline to treatment failure "2 years to castrate ...18 months to death". IMO these are not statistics on which to base treatment decisions. Patients respond differently and you could well do very well on ADT. Also the clinical trials that showed increased benefit for adding chemotherapy to ADT was for patients initially diagnosed with metastatic disease where ADT + Chemotherapy was used as the first line therapy. The results were less clear for patients such as you who had surgery as first line treatment and BCR. So ADT + chemotherapy might not be best for you. However, I am not an expert only a patient so that is just my personal opinion. You can view my cancer and treatment history in my profile on this site. In 2008 I did combine chemotherapy with my initial ADT. I am not sure it helped me or not.

I am not sure why you are so focused on neuroendocrine cancer. My understanding is that this type of cancer normally makes little to no psa and is usually a type of cancer that develops in patients who have been heavily pre-treated. I would expect if you had a large amount of NE you would have a more mets and less psa. Again I no expert.

From your description I believe you have not tried any ADT as of yet, so why not try some ADT and see how you respond? If you don't like the side effects you can always stop and all the side effects would reverse. On the other hand you may not have bad side effects and you may have a good response. In my experience in dealing with my disease I have learned to avoid making predictions about treatment outcome. You just don't know what may happen. Try to take one step at a time.

As I said above I am not an expert and what I have written is only my opinion based on my personal experience. Medical advice should only come from qualified medical experts in context of your particular situation. If you don't like the medical advice you have gotten so far please continue to search for experts who can provide you with a treatment plan and follow your progress.

I hope this helps

Bill Manning

in reply to

You're right, $Bill, about that study being based on first-time treatment, and that matters. That's why I'm still reading and inquiring. However, I tend to base my decisions on median expectations rather than less common deviations and CERTAINLY not on anecdotes; it's less likely to bite me in whichever nevermind(s) you choose. My overriding ADT decision factor right now is that inescapably ominous 4 month DT. As far as I can tell, it must be stopped in its tracks if I want to enjoy -- not merely acknowledge -- another Christmas. If ADT is necessary by this summer anyway (EVERY oncologist so far says waiting that long would be a HUGE mistake), it makes a lot of sense to pull that trigger before symptoms appear. OTOH, eking out one more unimpaired summer would mean more to me than you can imagine ... just not EVERYTHING.

Several oncologists have commented that my prostate cancer has already saved my life twice because met searches have found and let us eliminate two other more threatening primary cancers before they did any harm. One of those was a carcinoid (NE) tumor whose size and number of involved nodes imply it will return (that darned bell curve again). The foremost readily observed marker of that recurrence is my high and rising chromogranin A, and Leibowitz's partner, Eshaghian, is also concerned that my PSA is so high without any bone mets. This whole scenario led him to postpone discussing treatment until we biopsy the most obnoxious node. My local med onc volunteered similar concerns, at least until we found out that a bx will not be a simple image-guided needle bx. At that point he expressed his opinion and tossed the ball back into my court. I'm running with it because even a small NE component to my PC changes everything very significantly. It is much more quickly lethal, some forms of NEPC render ADT useless, and going down wrong treatment paths can delay (or even impede?) whatever might best fight NEPC. On top of that was the look on my local med onc's face when he brought up the NE possibility; it was brief and well-hidden, but alarming. I even heard it in Eshaghian's voice over the phone, and medical literature discussions of NEPC are no more encouraging.

It's thus the impact, rather than the likelihood, of NE involvement that has caught my attention. That, and cancer symposium comments paraphrased as "lymph nodes can trap PC cells and mutate into primary tumors with tentacles of their own" and "PC mets can mutate into NEPC and quickly kill". I'm just stubborn and opinionated, not stupid. :)

I'm leaning ever more to trying ADT before, rather than with, chemo, unless I see significant peer-reviewed proof that that's just plain stupid. ADT WILL ruin my summer (my foremost passion for the last 35 years has been an extremely demanding water sport), and even the most optimistic ADT SE discussions have said that athletes need not apply. But that DT=4 rules, AFAIK. The one concession I may make is beginning a statin when I start ADT; I'm very much anti-statins for cholesterol control, but since they appear to boost ADT benefits, I may acquiesce.

OTOH, the older we are, the less likely is our T to return upon stopping ADT. I guess that's where T replacement therapy may come in handy if I find that ADT is intolerable, as some men do. My greatest ADT concern besides the unavoidable fatigue is its impact on sleep. I've fought serious, life-affecting insomnia for decades. One mild hot flush can mean the end of my night's sleep, and without sleep we die. And, no, drugs don't fix chronic primary insomnia.

in reply to

Ok well you sounds like you already know it all so just ignore my comment.

Good luck and best wishes in your treatment decision.

Bill Manning

in reply to

And here I thought I was largely agreeing with your concerns and ideas, plus my clarifications and elaborations where appropriate. This whole NEPC thing is new to me, and I haven't even considered chemo until whac-a-mole was shot down and there MAY be a significant advantage to adjuvant chemo in recurrence. I have no idea what I said that offended you.

in reply to

I am not offended at all. I have been through all the available treatments and I have had doubling times shorter than yours. I have learned not to rely on the median anything. I only participate on this site to try to give folks the benefit of my experience. I am not trying to convince you of anything. I do sincerely wish you best of luck in your journey.

My hospital's tumor board was privately sure 12 years ago that I'd be in dire straights within 5 years. At about 6 my surgeon whispered that I may be cured. Three rad oncs told me my odds of cure and severe SEs w/SRT were .75 and 0.03, respectively. In fact, by the very references they cited when pressed, they were about 0.08 and .95, respectively, and by "cured" their source merely meant "still alive four years later" -- the same result one would expect if he played hooky from his radiation appts and went fishing instead. So I don't rely on medians, either, but they're all that "the next guy" can meaningfully and scientifically apply to his case. OTOH, your very short DTs and your present ability to type DO prove that those two are not incompatible, as the literature often implies.

Your comments about the chemo pts who had received no prior treatments made me look. Thank you. I quickly found several other studies with no such restrictions that found huge benefits -- 12-18 months -- to any and all cohorts which started chemo with their ADT. I gotta keep reading, as I like your approach -- ADT first, then sneak up on chemo -- better. Equally common, although shorter, benefits appear with statins + ADT.

IP, Enjoy your wind surfing.

GD

in reply to

I'm afraid it's gone, unless my prognosis is so short (I doubt that) that tx makes little sense.

The comment that NET does not create PSA seems to remove the basis of your raising NET - except insofar as you may argue that anything you do will be futile, and you will get only the side effects of ADT. It seems incorrect to argue futility at this point. You dont need to get a multi month ADT depot. You can go month by month and see how it affects you. That seems like a reasonable path.

i have to go back and see if the other systemic treatments have been talked about - the anti PD1 and CTLA4 combo, plus the fringe drugs.

I heard about something U of Iowa is doing for NET. Will go look for it. Just as a backup.

here it is:

youtube.com/watch?v=Lwx0lum...

binds to the somatostatin receptor in the NET cell, and delivvers beta radiaton. Alpha radiation would be better.

Joseph Dillon, MD Associate Professor of Internal Medicine Endocrinology and Metabolism, University of Iowa NCI Center of Designated Excellence in NET Care

in reply to

celebrex - ncbi.nlm.nih.gov/pubmed/213...

I heard a talk that said "showed that addition of celecoxib resulted in survival benefit similar to addition of docetaxel, possibly because drug down regulates expression of androgen receptors (AR)". Fairly unexpected I would say.

pdf summary here: audio-digest.org/adfwebcast...

in reply to

Wow, what a resource! I've seen some of the papers discussed in that link, but many of these are new to me and this puts them into perspective and will lead to many more such papers. You've just given me this morning's homework. This is the kind of stuff we should be basing our decisions on, and is the root source of the Standards of Care our oncologists ultimately employ. The double-edged sword is that those standards lag new findings by years to decades, but then many of the new findings turn out to be wrong upon closer examination.

Leibowitz has been using Celebrex for many years, plus other precautions to reduce its reported propensity to cause heart attacks. Of course, now we know that that propensity was vastly overblown ... unless, of course, the next big study reverses that reversal.

I feel like my HEAD's reversed. :)

It's not NET that my oncologists are concerned about; I've been there, done that, 12 years ago. Their concern now is NECP. See am.asco.org/daily-news/trea... , which begins with

"Neuroendocrine prostate cancer (NEPC) is a lethal disease subset with median overall survival of less than 1 year from time of detection."

My thinking since learning in November that I need systemic tx has been just what you suggest: 28 days of ADT at a time, then evaluation of benefits and SEs, then chemo if the ADT is going well, etc. It made sense until every med onc I've consulted and most studies I've found so far suggest or even SHOUT that with a high tumor burden and too many mets to attack individually, we'd be nuts not to start ADT, chemo, and a statin ASAP. Even the delay incurred in seeking this biopsy concerns them.

But are they right, or am I justified in seeking the knowledge (and possible benefit) a bx (and possible excision) may provide? That decision is too personal for your guys or a doctor to make for me. Where you guys and the doctors can best contribute is in helping me find peer-reviewed evidence as decision fodder. The lead you suggested above is a good example except for its confinement to strictly NE tumors.

This brings up a powerful point applicable, maybe vital, to every person on the planet: Too many physicians are like carpenters in that every nail must be hit by the specific hammer hanging on HIS/HER belt. The corollary to that trend is that almost none of our physicians have as much time to devote to OUR case as WE do ... neither in thinking about it nor in researching it. I could list at least 20 occasions (some worthy of losing their licenses) from just my own personal history on which I've caught providers making significant to even grave errors in their advice and/or actions. I hope to die or be crippled of or by something I can NOT prevent rather than something I CAN prevent. What's OUR best hammer to help prevent such errors?

Knowledge.

Our best sources of knowledge include reading credible literature and asking almost ANY questions of almost ANY body. Even the most casual response can sometimes lead to a flash of insight or a golden nugget of solid information. More important to others around us are the discussions that ensue and the investigatory process that is revealed. (Whether my healthy and well-deserved skepticism of providers is useful to the next person is more arguable; there are whole books on that topic.)

in reply to

Are you concerned that any treatment you start may confound the biopsy?

in reply to

Leibowitz's partner, Eshaghian, emphasized, and my local med onc agreed, that NE assessment must precede my initial ADT injection if the bx is to be of any use. The remaining question is whether the NE possibility warrants the invasive bx rather than the needle bx they expected. I hope to find that out tomorrow after my initial surgery consult and maybe a discussion between that surgeon and my med onc.

One lesson worth considering by anyone is that all this logistical complication has reinforced my decision to pursue this locally rather than running off to the "Big Boys" in Los Angeles or Seattle. Sure, I had to go to the Mayo Clinic four times to even find the source of my PSA, but

a) JEEZ, that's an easy trip.

b) No one else has the technology that found my source.

c) Now that we understand my threat(s) much better, I feel more comfortable having local providers* deal with it ... as long as no big surprises such as NEPC show up.

* My "town" has ~300,000 people, three big hospital systems, a great deal of absolutely state-of-the-art medical equipment, and a long list of specialists with whom I can get appointments within days. I hope that I and these providers can recognize the need, if it arises, to go to the big city (as they advised me to do when my first two major cancers struck at once). Otherwise I, and most others in our life raft, can do very well in most big towns or small cities, especially if we educate ourselves sufficiently to (we hope) recognize substandard care.

I did not know thar NET is dfferent from late stage prostate cancer, "small cell".

in reply to

I'm still trying to sort that out, but it's a low priority for me until some oncologist determines otherwise.

in reply to

Every time I as much as consider delaying ADT, the list of likely PC symptoms flashes before my eyes and brings me right back to earth. Starting ASAP at least gives me the option, for a month or a few years, of choosing which effects I prefer ... those of low T or those of PC. Even chemo, let alone whether statins or Celebrex or chest pre- irradiation, become lesser dilemmas.

Charlesd profile image
Charlesd in reply to

I am writing this is as a wife( of 49 years in April) my husband being with me the past 3 years vs proficient in athletics - is really a no brainer. I thank GOD he is still here with a remarkable quality of life. He will be 82 feb. Check out his fight.

That's great that your husband's presence is a no-brainer blessing; I and my wife of 47 years are envious of his "remarkable QOL". However, I just now asked her which she'd prefer ... 6 years of me on horrible drugs, feeling like roadkill, behaving like a raging hemorrhoid when not crying, and thinking like a fencepost ... vs 3-4 years of me high on glorious endorphins from my sports, feeling like a kid on sugar, being my usual quick-tempered self, and thinking like a student. Her hesitancy answered my question exactly as I suspected.

I have said to her and to many audiences that she means far too much to me to voluntarily impose years of my behavior on ADT/chemo's normal SEs on her. SO much depends on each individual's starting point and where cancer drugs take him. I am very curious to find out where these drugs try to take me and how much I can do about it. Will like be the oncologist whose ADT SEs were so severe he chose death instead, like the man who chose the drugs but had to live in bed because he lacked the energy to stand up, or somewhere in between ... and how much choice will I have about it?

I've seen her sacrificing her sleep and thus her health just taking care of our household; she's a workaholic, will not let me help, and NEEDS me for nothing she can't Call The Guy for (e.g., cleaning out the gutters). Taking care of sick and injured dogs pushes her over the edge; a year of taking care of and putting up with me with bad SEs would take years off her life. The LAST thing I will foist upon her is taking care of me once I'm bedridden. I love her too much to do that to her. Will my, and thus her, QOL be manageable or nightmarish? We'll know by this time next year.

This is sad. I had hoped to find rational discourse and knowledge in this forum to help guide me through what will be the worst year of my life to date. It did start out that way, but Darryl has destroyed it for me and some others. It's bad enough when unmoderated forums become overwhelmed with political lies, but when it's the ADMINISTRATOR who's doing it and he CENSORS DISSENT and allows obscene, personal, false vitriol from his side, I'm moving on. I can get that crap in alt.FU. You guys just go on with your little drastically misinformed far left enclave here; I'm moving on in the hope of finding a prostate cancer forum worthy of the name.

Alan, I'm disappointed in the company you're keeping here.

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