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Steve Jobs’ cancer and pushing the limits of science-based medicine

Editor’s note: There is an update to this post.

An Apple fanboy contemplates computers and mortality

I’m a bit of an Apple fanboy and admit it freely. My history with Apple products goes way back to the early 1980s, when one of my housemates at college had an Apple IIe, which I would sometimes use for writing, gaming, and various other applications. Indeed, I remember one of the first “bloody” battle games for the IIe. It was called The Bilestoad and involved either taking on the computer or another opponent with battle axes in combat that basically involved hacking each other’s limbs off, complete with chunky, low-resolution blood and gore. (You youngsters out there will be highly amused at the gameplay here.) Of course, it’s amazing that nothing’s changed when it comes to computer games except the quality of graphics. Be that as it may, this same roommate was one of the first students to get a hold of the new Macintosh when it was released in early 1984. I really liked it right from the start but only got to play with it occasionally for a few months. After using a Macintosh SE to do a research project during my last year of medical school, I have used the Macintosh platform more or less exclusively, and the first computer I purchased with my own money was a Mac LC back in 1990 or 1991. Today, I have multiple Apple products, including my MacBook Air, my iPhone, and my old school iPod Classic, among others. Oddly enough, I do not have an iPad, but that’s probably only a matter of time, awaiting software that lets me do actual work on it.

All of this is my typical long-winded way of explaining why I was immensely saddened when I learned of Steve Jobs’ death last week. Ever since speculation started to swirl about his health back 2004 and then again in 2008, capped off by the revelation that he had undergone a liver transplant for a rare form of pancreatic cancer in 2009, I feared the worst. Last week, the end finally came. However, there is much to learn relevant to the themes of this blog in examining the strange and unusual case of Steve Jobs. Now, after his death five days ago, which coincidentally came a mere day after the launch of iCloud and the iPhone 4S, it occurs to me that it would be worthwhile to try to synthesize what we know about Jobs’ battle with cancer and then to discuss the use (and misuse) of his story. Of course, this is a difficult thing to do because Jobs was notoriously secretive and I can only rely on what has been published in the media, some of which is conflicting and all of which lacks sufficient detail to come to any definite conclusions, but I will try, hoping that the upcoming release of his biography by Walter Isaacson in couple of weeks might answer some of the questions I still have remaining, given that Isaacson followed Jobs through his battle with cancer and was given unprecedented access to Jobs and those close to him.

In the meantime, I speculate. I hope my speculations are sufficiently educated as not to be shown to be completely wrong, but they are speculations nonetheless.

Jobs and pancreatic cancer

Back in 2003, Jobs was flying high. Ousted from Apple in 1985 and then brought back in 1997, over the last six years he had brought the company back from the brink of bankruptcy, first with the launch of the iMac and then a few years later with the wildly successful iPod. It was at this time that he received news that no one wants to hear. Having recently undergone an abdominal CT scan, a mass had been found in his pancreas, apparently at the head of the pancreas.

Now, for all the reports I’ve read of this initial diagnosis, it’s utterly unclear to me exactly what the indication for the scan was, and at the time Jobs’ diagnosis was shrouded in secrecy. It wasn’t until 2008 that an article was published in Fortune entitled The Trouble With Steve Jobs and described his diagnosis thusly:

During a routine abdominal scan, doctors had discovered a tumor growing in his pancreas. While a diagnosis of pancreatic cancer is often tantamount to a swiftly executed death sentence, a biopsy revealed that Jobs had a rare — and treatable — form of the disease. If the tumor were surgically removed, Jobs’ prognosis would be promising: The vast majority of those who underwent the operation survived at least ten years.

So, right from the beginning, SBM bumped up against how Jobs was treated, as even now, the indications for “routine” abdominal CT scanning in an otherwise healthy man in his late 40s are virtually nonexistent, as Sharon Begley points out in an article published last week:

He reportedly had the scan — which is seldom done, much less advised, as a routine part of a physical — because he had a history of gastrointestinal problems, but he also may have been experiencing symptoms, most likely gastrointestinal ones.

Whatever the reason Jobs underwent a CT scan, either “routine” (which is almost never indicated) or for vague symptoms (for which the indication might have been weak but not nonexistent). At the time, Jobs would appear to have been incredibly lucky in two ways. First, he was lucky in that his tumor was discovered by what would in the absence of clear cut symptoms normally be a very low-yield test that exposes patients to both the risk of intravenous contrast and radiation exposure. These risks are quite low, but difficult to justify without clearer indications. However, CT scans are frequently overused in this country, and it is not surprising that Jobs underwent one for “soft” indications; it’s just that this time he was the exception, with disease detected early, rather than the rule, where the scan usually finds nothing helpful. Secondly, a biopsy of the lesion demonstrated that it was not the much more common (and deadly) form of pancreatic cancer, adenocarcinoma, which arises from the ducts of the pancreas, is rarely cured, and generally produces a median survival of less than a year. Rather, he had the much less aggressive form of pancreatic cancer, a neuroendocrine tumor. These tumors are often indolent and slow-growing. Unfortunately, they also tend to secrete hormones, which also tend to be responsible for most of the symptoms they cause. In Jobs’ case, it was insulin and his tumor was an insulinoma. Although, again thanks to Jobs’ secrecy, we have no idea what symptoms he was experiencing at the time, insulinomas typically result in a profound drop in blood sugar, and this hyperinsulinemia can lead to symptoms of insulin shock, such as tremors, cold sweats, nausea and vomiting, blackouts, and neurological symptoms such as confusion, apathy, and irritability.

Whatever Jobs’ talents, it became obvious that one of them was not good judgment about medicine. Whatever his business and design savvy, when it came to medicine, he demonstrated critical thinking skills that, if applied to his business dealings, would bring Apple down from its heights to utter ruin. Neuroendocrine tumors of the pancreas make up less than 2% of all pancreatic tumors, and he was lucky enough to have gotten that form rather than the more common deadly version. Surgery would have a high probability of curing him.

Here’s more of the story:

But Jobs sought instead to treat his tumor with a special diet while launching a lengthy exploration of alternative approaches. “It’s safe to say he was hoping to find a solution that would avoid surgery,” says one person familiar with the situation. “I don’t know if he truly believed that was possible. The odd thing is, for us what seemed like an alternative type of thing, for him is normal. It’s not out of the ordinary for Steve.”

Apple director Levinson, who has a Ph.D. in biochemistry, monitored the situation for the board. He and another director, Bill Campbell, tried to persuade Jobs to have the surgery. “There was genuine concern on the part of several board members that he may not have been doing the best thing for his health,” says one insider. “But Steve is Steve. He can be pretty stubborn.”

If it was fear that motivated Jobs, I can understand it. Although he was fortunate enough to have an islet cell cancer instead of the more common and deadly adenocarcinoma of the pancreas, it was in the head of the pancreas, the part that is closest to the duodenum. Lesions in the tail of the pancreas can often be removed with an operation called a distal pancreatectomy, which involves removing only part of the pancreas. Because of the anatomy of the head of the pancreas, its attachment to the duodenum, and the blood vessels in the area, the only way to remove lesions in the head of the pancreas is to do a much larger operation known as a pancreaticoduodenectomy, or, as it is more commonly known, the Whipple operation. There are a lot of potential complications to a Whipple operation. Sometimes, we weigh those complications and how long they would keep a patient in the hospital, against how long a patient has left. If a pancreatic cancer patient has only a few months left, doing an operation that will have him spending a significant chunk of his brief remaining time left in the hospital is a real consideration. However, that wasn’t a consideration for Steve Jobs. He would very likely be cured by the surgery. Moreover, in competent hands, the complication rate from a Whipple is acceptable, particularly if the patient is otherwise healthy. Even though the article quotes a 5% mortality rate, that is usually in the case of patients with pancreatic adenocarcinoma, most of whom tend to be somewhat debilitated to start with due to the tumor. It would probably have been less in Jobs’ case. True, because the duodenum is removed, another expected sequela of the operation is, depending on whether the pylorus is spared, having to eat a diet like that of patients who have their stomachs (or large portions thereof) removed (more on that later)

This is not a controversial issue in medicine; there is no other effective treatment for these neuroendocrine tumors:

By the standards of medical science, it was an open-and-shut case: There was no serious alternative to surgery. “Surgery is the only treatment modality that can result in cure,” Dr. Jeffrey Norton, chief of surgical oncology at Stanford, wrote in a 2006 medical journal article about this kind of pancreatic cancer. It was Norton, one of the foremost experts in the field, who eventually operated on the Apple CEO, Fortune is told. (He declined to comment.)

Dr. Roderich Schwarz, chairman of surgical oncology at the University of Texas Southwestern Medical Center in Dallas, who has performed the procedure more than 150 times (but who was not involved in Jobs’ case), says that waiting more than a few weeks with this diagnosis “makes no sense because you don’t know what the potential for growth or spread is.” Schwarz says he knows of no evidence that diet can be helpful. “But the patient decides. If they believe an herbal diet can do miracles, they have to make the decision. Every once in a while you have somebody who decides something you wish they wouldn’t.”

I couldn’t resist including this quote because Rod used to be one of my partners back in the day when I worked at The Cancer Institute of New Jersey. In any case, even though insulinomas tend to be indolent, waiting nine months to undergo surgery was probably not the best idea. It might not have hurt him (or it might have), but it certainly didn’t help (more on that later). Nowhere have I been able to find a detailed description of how large the tumor was upon its discovery or by how much it grew during those nine months. Whatever the case was, the surgery was apparently a success, with complete removal of the tumor.

For four years, Jobs appeared to do quite well after that.

Complications of the Whipple operation or something more dire?

In June 2008, Apple introduced the iPhone 3G, its second-generation iPhone. When Jobs took the stage to dazzle the crowd with his usual aplomb, many in the audience were shocked at his gaunt appearance. Soon after, it was revealed that he had undergone a second surgical procedure to reverse some nutritional issues related to his first surgery.

At the time, I thought I knew what might be going on. Jobs underwent a Whipple operation, more correctly referred to these days as a pancreaticoduodenectomy. This is a huge operation, one of the biggest and most radical rearrangements of a patient’s anatomy that is done routinely. What’s done is that the head of the pancreas and duodenum are removed en bloc (mainly because their close proximity to each other and their shared blood supply make it virtually impossible to remove the pancreatic head alone). This tour de force operation then necessitates putting things back together thusly:

There are many potential complications of the Whipple procedure, because it’s a big operation and it’s an operation on the pancreas. There’s a famous saying in surgery that goes, “Eat when you can, sleep when you can, but don’t mess with the pancreas.” (Usually another, far less savory word than “mess” is used.) In any case, there are almost always long term nutritional consequences that derive from rearranging a patient’s anatomy in so radical a fashion. First off, patients almost always lose 5-15% of their body weight right off the bat, although that usually levels off fairly quickly. Jobs, however, was never exactly what you would call robust-looking. He was always on the thin side; so losing that much weight for him could be more problematic. Although it has been speculated that Steve Jobs was a vegan or vegetarian, apparently such was not the case (he was pescetarian, which is basically a vegetarian diet plus seafood). So post-surgical difficulties maintaining nutrition because of a special diet that might not have meshed well with Jobs’ new anatomy could have been the problem. Some other potential serious problems over the long term include glucose intolerance or even diabetes requiring insulin; malabsorption because of diminished production of pancreatic enzymes; delayed gastric emptying; the afferent loop syndrome; or the “dumping syndrome,” which is common after stomach resections and results from undigested food being “dumped” too fast into the proximal small intestine, which draws in fluid.

At the time, I speculated that perhaps it was afferent loop syndrome (ALS) that necessitated another operation. You’ve probably never heard of it unless you’ve been unfortunate enough to have it (or are a surgeon or gastroenterologist), but ALS is a potential complication after a certain type of gastrojejunostomy, which is when the stomach is connected to a loop of small bowel in an anastomosis. This leaves two “loops.” The efferent loop is the small bowel leading away from the anastomosis. The afferent loop is the loop proximal to the anastomosis, whose peristalsis runs towards the anastomosis. Bile and pancreatic juice dump into the afferent loop, as can be seen in the illustration above. If there is a mechanical problem with the afferent loop, it can result in symptoms soon after surgery or as long as many years later. That Jobs seems to be rather quickly looking worse nearly four years after his operation also suggests ALS.

There are two forms of the problem, acute and chronic. Acute ALS involves a high grade obstruction of the afferent limb, in which pancreatic juices and bile back up behind the obstruction under pressure, and is potentially life-threatening. The more common and chronic form is what can produce nutritional deficiencies over time. Usually, approximately 10-20 minutes to an hour after a meal, the patient will experience abdominal fullness and pain as the liver and pancreas pump bile and pancreatic juice into the partially obstructed afferent limb. These symptoms usually last from several minutes to an hour, although they occasionally last as long as several days. Pressure will build up and the obstruction will resolve by then, sometimes with vomiting. Prolonged ALS with stasis of digestive juices in the afferent limb can result in bacterial overgrowth of the digestive juices sitting there, fatty stools, diarrhea, and vitamin B-12 deficiency. The treatment is surgical, and if Jobs had ALS then his undergoing additional surgery made perfect sense.

Unfortunately, my speculation was wrong, as I found out a year later.

Pushing the limits of science-based medicine

The real bombshell regarding Steve Jobs’ health came in 2009. It’s a useful story to discuss because it demonstrates the limits of SBM and how sometimes they can be pushed in the cases of rare diseases for which there is little data. In early January, Jobs reported that he had been experiencing a “hormone imbalance” that needed treatment. In retrospect, even with all the secrecy, it should have been blazingly obvious that his insulinoma had recurred. All the signs were there, even through the veil of Apple secrecy, but somehow it was kept mostly out of the news until June, when the Wall Street Journal reported that Jobs had undergone a liver transplant:

In early January, Mr. Jobs said he had a hormone imbalance that was “relatively simple and straightforward” to treat. But about a week later, he announced that the issue was more complex than he had thought, and in a letter to employees he said he would be taking a leave and Mr. Cook would take over temporarily.

William Hawkins, a doctor specializing in pancreatic and gastrointestinal surgery at Washington University in St. Louis, Mo., said that the type of slow-growing pancreatic tumor Mr. Jobs had will commonly metastasize in another organ during a patient’s lifetime, and that the organ is usually the liver. “All total, 75% of patients are going to have the disease spread over the course of their life,” said Dr. Hawkins, who has not treated Mr. Jobs.

Getting a liver transplant to treat a metastasized neuroendocrine tumor is controversial because livers are scarce and the surgery’s efficacy as a cure hasn’t been proved, Dr. Hawkins added. He said that patients whose tumors have metastasized can live for as many as 10 years without any treatment so it is hard to determine how successful a transplant has been in curing the disease.

At the time, I looked into the issue, given that it had been a long time since I had finished my surgical oncology fellowship and I no longer took care of patients with neuroendocrine tumors, having specialized in breast cancer. In general, for neuroendocrine tumors metastastic to the liver, the first options to be considered are ablative options. These can include surgery, if the tumors are resectable, or ablation by various methods, such as radiofrequency ablation (RFA, or, as we like to say, “cooking the tumors”) or cryoablation (cryo, a.k.a. freezing the tumors). Surgery can be curative if the lesions are confined to a volume of liver that can be completely resected, and RFA is generally reserved when there are lesions in multiple lobes not amenable to surgical resection. For the consideration of a liver transplant, a patient must have multiple lesions in multiple lobes of the liver that are too numerous even to be cooked by RFA or frozen by cryo. Moreover, there can be no evidence of tumor anywhere other than in the liver. In addition, another indication is that symptoms must be such that they can’t be controlled by medical therapy. For an insulinoma, controlling the symptoms due to hypoglycemia can actually be quite difficult; so the type of tumor Jobs produced symptoms that are more difficult to palliate than the average neuroendocrine tumor.

So what are the results of liver transplant for neuroendocrine tumors? Because these tumors are so uncommon, there’s never going to be a randomized clinical trial. All that can be found in the literature consists of small case series or retrospective analyses.The kindest and most generous characterization that can be made is that that the evidence for treating neuroendocrine tumors metastatic to the liver with liver transplantation is mixed at best. A recent retrospective analysis of the UNOS database produced this survival curve (click to embiggen):

A picture’s worth a thousand words, and based on this curve alone Jobs had a little better a 50-50 chance of living as long as he did (almost two and a half years). Unfortunately, he fell out on the wrong side of those odds. Jobs’ case aside, the authors conclude:

Although surgical resection still should be considered the treatment of choice in patients with liver metastases from NETs, transplantation for unresectable disease is indicated in patients with stable disease without disseminated metastases. A national database should be developed to better understand predictors of outcomes in this patient population and to help produce and standardize selection criteria to obtain better outcomes. We believe it is time to carefully revise this indication.

Who could argue with more research? Jobs’ case is, however, an excellent example of the difficulties in deciding on a course of action when the evidence available is sparse. For instance, if he had progressive disease (and in retrospect it sounds as though he probably did), he probably should not have undergone transplantation, given that immunosuppression would probably facilitate the growth of microscopic tumor deposits and also given that it is possible to provide prolonged palliation by other means. Yet, to Jobs and his doctors at the time, the picture was probably anything but clear, other than that things were getting worse.

The war to claim Steve Jobs’ narrative

Since the death of Steve Jobs, there has been a struggle to claim his narrative as “evidence” to support a world view. On the one side, there are quacks using and abusing Jobs’ memory, as they’ve used and abused those of so many other dead celebrities to “prove” that “conventional medicine killed them.” Predictably, first out of the box is the despicable crank known as Mike Adams. Adams has made a not-so-savory name for himself for ghoulishly (and gleefully) taking advantage of the death of celebrities in order to blame “conventional” medicine for having killed them. It’s a depressing and predictable pattern that continued with Steve Jobs. Indeed, Adams produced an article on Steve Jobs’ death so quickly (within hours of the announcement of Jobs’ passing) that I have to wonder if he had already had it written and teed up, just waiting for Jobs to die. Whatever the case, Adams entitled his article, again predictably enough given his past history, Steve Jobs dead at 56, his life ended prematurely by chemotherapy and radiotherapy for cancer, which begins with a typical charge (from Adams) that Jobs’ gaunt appearance was due to chemotherapy, not the progression of his cancer, blaming his death on the “cancer industry” and claiming that it was “toxins” that caused his cancer and that “natural” treatments could have cured him.

Just yesterday, Joe Mercola chimed in, apparently managing to interview Nicholas Gonzalez right after Jobs’ death to produce this video:

Gonzalez, you may recall, is the originator of the “Gonzalez therapy” for pancreatic cancer, a therapy involving various juices, dietary manipulations, coffee enemas, and many, many supplements, as many as 150 pills per day. Also recall that his therapy, besides having no biological plausibility, has been convincingly demonstrated not to work.

The truly ironic thing, of course, is that Jobs lived a lifestyle very similar to the one that Adams touts as an all-purpose cancer preventative. As I mentioned before, Jobs was widely reported to be a vegan but was a was in fact a pescatarian. Jobs did not eat meat and the animal rights group PETA has paid homage to him after his death for being a vegetarian and sympathetic to animal rights causes. The point, of course, is that Steve Jobs ate a diet and lived a lifestyle far more similar to the kind that Adams touts as a cure-all or prevent-all for cancer than the “typical” fat- and meat-laden American diet that Adams lambastes. Upon his initial diagnosis, as we have seen, he eschewed surgery for nine months, trying to treat his cancer with a “special diet.” It’s not clear just what, exactly, this “special diet” was. Oddly enough, Gonzalez hints that he knows something:

He wanted to see an alternative. In fact when he was first diagnosed, he got some dietary program — again, he was very secretive of that — So I don’t exactly know what he did at that point. But through his acupuncturist, there was communication. He was getting acupuncture, and he was doing some alternative things as far as I know. This acupuncturist actually talked to me, discussing the situation. She was really anxious for him to come and see me. But he chose not to do that.

You know, I always respect the patients’ right to choose the therapy they want to choose, so I would never dispute that. The patients have to make the decisions based on what they want to do. But she was very adamant; in fact, she knew about all my works in the alternative world. He had seen alternative-type practitioners. She really wanted for him to come and see me. He chose not to do that. From my perspective, it was unfortunate, because he was such a gift to the world in terms of his inventions and genius in the past 30 years.

Yes, that’s Gonzalez claiming that he could have saved Jobs if only Jobs had listened to an acupuncturist.

For as much as the quacks are trying to claim that they could have cured Jobs if only they had given them the chance, there is, however, the chance of taking the opposite argument, namely that Jobs might have died because of his embrace of non-science-based treatments, too far in the other direction. Unfortunately, there is a skeptic who should really know better who did just that, using Steve Jobs’ death as evidence of the harm that alternative medicine can do. Now, given my reputation as someone who relentlessly applies the cudgel of reason, science, and critical thinking squarely to the back of the head of woo on a regular basis, you just might think that I would heartily approve of this line of argument. You’d be wrong, and not because I have any qualms whatsoever about appropriately blaming alternative medicine when someone pursues alternative medicine and ultimately dies. (I have, after all, done it myself on several occasions.) The key word is “appropriately,” and the reason that I’m not so hot on using Jobs’ death as a “negative anecdote” against “alternative” medicine is because I’m not so sure how appropriate doing so is in Jobs’ case. While Jobs certainly didn’t do himself any favors by waiting nine months to undergo definitive surgical therapy of his tumor, it’s very easy to overstate the potential harm that he did to himself by not immediately letting surgeons resect his tumor shortly after it was diagnosed eight years ago. Unfortunately, Brian Dunning does exactly that in his post A Lesson in Treating Illness (also posted over at Skepticblog):

I’m sad that today I’m adding a slide to one of my live presentations, adding Steve Jobs to the list of famous people who died treating terminal diseases with woo rather than with medicine.

Except that Jobs didn’t; at least, he didn’t for the most part. Aside from the initial nine months, Jobs, as far as we know, relied on exclusively on conventional therapy to treat his disease. In fact, he underwent the most invasive, cancer aggressive operation (the Whipple pancreaticoduodenectomy), which is one of the biggest, if not the biggest operation, that surgical oncologists do. Then, after his tumor recurred in his liver, he underwent the biggest, mot technically complex type transplant operation there is, a liver transplant. When his cancer recurred a second time earlier this year, Jobs was seen going to the Stanford Cancer Center in Palo Alto, California, looking frail and thin.

Moreover, the other “alternative” therapy reportedly pursued by Jobs in Switzerland was a therapy based on radiation therapy, you know, the kind of therapy known to the likes of Adams as “burning” the cancer. In any case, Jobs apparently traveled to the University Hospital of Basel in Switzerland to receive a form of “hormone-delivered radiotherapy.” For some reason this is being portrayed in the press as somehow “alternative.” In reality, from what I can tell, it’s science-based, but experimental. Basically, in this therapy, radioisotopes are linked to a peptide hormone, receptors for which are found on the tumor being treated. The hormone then binds to the receptors, bringing the radioisotope close enough to the tumor cells to deliver a high dose of radiation. This therapy is not “alternative”; although it’s not standard of care, it’s definitely science-based.

All of this leaves the sole remaining question regarding the issue of “alternative” medicine and cancer in the case of Steve Jobs as: Did Jobs significantly decrease his chance of surviving his cancer by waiting nine months to undergo surgery? It seems like a no-brainer, but it turns out that that’s actually a very tough question to answer. Certainly, it’s nowhere near as certain as Dunning tries to make it seem when he writes things like:

Eventually it became clear to all involved that his alternative therapy wasn’t working, and from then on, by all accounts, Steve aggressively threw money at the best that medical science could offer. But it was too late. He had a Whipple procedure. He had a liver transplant. And then he died, all too young.

One has to be very, very careful about making this sort of argument. For one thing, it could not have been apparent that it was “too late” back in 2004, when it became clear that Jobs’ dietary manipulations weren’t working. For another thing, we don’t know how large the tumor was, whether it progressed or simply failed to shrink over those nine months, and by how much it increased in size, if increase in size it did. Again, I hope that information will be revealed in the Jobs’ biography; such data would go a long way in clarifying just how much, if at all, Jobs might have compromised his chance for cure by delaying. Right now, we just don’t know enough to make even a good guesstimate. Based on what we do know now, the thing that has to be remembered is that neuroendocrine tumors of the pancreas tend for the most part to be fairly indolent, slow-growing tumors It’s very much overstating the case to write, as Dunning does:

As he dieted for nine months, the tumor progressed, and took him from the high end to the low end of the survival rate.

We don’t know that this was the case, and we certainly can’t say that for sure — or even with a great deal of certainty. Dunning is massively overstating the case in his eagerness to attack alternative medicine. This is a mistake. Again, I would certainly agree that Jobs did himself no favors by waiting. If I were his physician or the surgeon to whom he was referred, I would have done my best to talk him out of such a course of action, but I would do so more out of the uncertainty of not knowing how fast his tumor would progress. So, is it possible, even likely, that Jobs compromised his chances of survival? Yes. Is it definite that he did? No, it’s not, at least it’s not anywhere as definite as Dunning makes it sound. In fact, based on statistics alone, it’s unlikely that a mere nine months took Jobs “from the high end to the low end of the survival rate,” as Dunning puts it. That’s just not how insulinomas usually behave from a biological standpoint. They’re too indolent, and that’s not even taking into account issues of lead time bias and other confounding factors that would make comparisons of operating early versus operating later not as straightforward as one might think. Remember, Jobs’ tumor was probably what we call an “incidentaloma”; i.e., a finding picked up incidentally on a diagnostic test done for another reason. Consequently, it might not have caused symptoms for a long time. Or it might have already been causing symptoms, just symptoms that normally don’t warrant a CT scan. We don’t know; there isn’t enough information. Be that at it may, I have no doubt that Jobs might well have compromised his chances of survival by delaying, but it’s just not scientifically supportable to leap to the conclusion, as Dunning does, that he compromised his chances so much that “alternative medicine killed him.” What is known about Jobs’s case and insulinomas do not support such a conclusion; at worst they support a conclusion that Jobs might have decreased his chances somewhat.

If there’s one thing we’re learning increasingly about cancer, it’s that biology is king and queen, and that our ability to fight biology is depressingly limited. In retrospect, we can now tell that Jobs clearly had a tumor that was unusually aggressive for an insulinoma. Such tumors are usually pretty indolent and progress only slowly. Indeed, I’ve seen patients and known a friend of a friend who survived many years with metastatic neuroendocrine tumors with reasonable quality of life. Jobs was unfortunate in that he appears to have had an unusually aggressive form of the disease that might well have ultimately killed him no matter what. That’s not to say that we shouldn’t take into account his delay in treatment and wonder if it contributed to his ultimate demise. It very well might have, the key word being “might.” We don’t know that it did, which is one reason why we have to be very, very careful not to overstate the case and attribute his death as being definitely due to the delay in therapy due to his wanting to “go alternative.” Finally, Jobs’ case illustrates the difficulties with applying SBM to rare diseases. When a disease is as uncommon as insulinomas are, it’s very difficult for practitioners to know what the best course of action is, and that uncertainty can make for decisions that are seemingly bizarre or inexplicable but that, if you have all the information, are supportable based on what we currently know.

Posted in: Cancer, Medical Ethics, Nutrition, Science and the Media, Surgical Procedures

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48 thoughts on “Steve Jobs’ cancer and pushing the limits of science-based medicine

  1. Thank you again for emphasizing (here and elsewhere) that we simply do not yet know exactly what Mr. Jobs did or did not do, or how dangerous it was. This post is one of the only sensible things I’ve read on the topic, and it’s particularly helpful that you’ve explained the awful uncertainties that were inherent in the choices he had to make. I briefly protested Dunning’s smug overconfidence about this last week, and have seen alarmingly few signs of other skeptics reserving judgement until we know the facts of the case. If anything, your analysis here makes it clear that we actually do have enough information to feel reasonably confident that there was probably nothing too disastrous about Jobs’ medical choices.

    It is a black eye for the entire skeptical community that, apparently, all that so many of us could see in Dunning’s allegation was a juicy opportunity to confirm our bias. And there’s the real skeptical lesson here: a rather sobering reminder that no one is immune to cognitive distortions.

    Oh, and of course … everything is always more complicated than it seems at first.

  2. BobbyG says:

    My reaction to Mr. Jobs’ passing:

    http://www.bgladd.com/Loss.jpg

    He was a husband and father.

    “Dunning’s allegation was a juicy opportunity to confirm our bias. And there’s the real skeptical lesson here: a rather sobering reminder that no one is immune to cognitive distortions.”

    Yeah, well that goes to the Sperber / Mercier paper “Why do humans reason?” (which I first ran into in a comment here).

    Why (according to the authors)? To WIN arguments, irrespective of the relative objective evidentiary and syllogistic merits of the pros/cons.

  3. ConspicuousCarl says:

    First, I won’t claim to be as reserved and rational as others. When I heard the limited news, my internal response was much the same as Dunning’s.

    Did I want to hijack Jobs’ death to make a case against Macs, oops I mean a case against alternative medicine? Well, yes. It’s the perverted reward of feeling right, even though I know nothing about Jobs’ particular type of cancer and only slightly more about cancer in general. Clearly a leap of logic to be resisted, not published.

    Instead of feeling the need to know the absolute details in a specific case (that’s for the doctors), it should be enough of a rant for us laypersons to just point out how pathetic our current culture must be, that we should even have to wonder exactly what forms of nonsense might have been pursued by an intelligent person, or if it was ultimately harmful. We don’t have to “wait for the data to come in” to find out of Steve Jobs might have hastened his death by sacrificing goats for nine months because we can say with confidence that there is no way that Steve Jobs would have engaged in such useless and insane behavior.

    And to that bastard Gonzalez, I say… have a cup of coffee, and then find something to also plug your mouth.

  4. BobbyG says:

    Interesting how one’s HIPAA PHI privacy rights are to a great degree inversely proportional to the magnitude of one’s celebrity status.

  5. Harriet Hall says:

    There is another issue here. Jobs wanted to maintain privacy, but it has been argued that he had a responsibility to his company and stockholders to inform them of his medical issues. I maintain that it is enough to announce when you are too ill to do your job well, and when death is imminent and it is necessary to plan for continuity, but that details need not be announced. What do the rest of you think?

  6. joroncho says:

    Thank you for this post, sincerely. I was one of those that jumped in early on the anti-alternative band wagon. But not out of some sense of superiority, I was just truly saddened by the loss and the thought that his life could have been extended, even by just a few months. Like you, I have been an Apple user since the late 80s and could be considered a “fanboi”

    I am surrounded by a lot of woo here in Mexico, where I do research (at a medical school!), and I’m always on the look-out for “what’s the harm” anecdotes to share with my colleagues who are mostly shruggies. And on the face of it, this seemed like a clear-cut example. I should have taken the time to look into it more thouroughly, so thanks for your insight.

    As an aside: I really appreciate the tone that you take in this post. It made getting through your post easier.

  7. Harriet, many tech pundits have always displayed exaggerated petulance with regards to Apple, convinced that the company owes them something, and this often carried over into demands for Mr. Jobs to be more forthcoming about his health. However, he didn’t owe that to them, any more than he owed them an iPod with more buttons, or Flash on the iPhone, or any of the countless other foolish things that people thought Apple “should” do.

    If shareholders don’t like the conduct of a CEO, they can sell their stock. “Rights” don’t even come into it, and Steve Jobs had as much right to privacy as anyone else. The financial community can be “infuriated” that Steve Jobs refused to disclose his health problems all they like, but the man’s civil rights were unscathed. Turns out Apple’s stock value was in no danger either.

  8. windriven says:

    “The kindest and most generous characterization that can be made is that that the evidence for treating neuroendocrine tumors metastatic to the liver with liver transplantation is mixed at best.”

    Nonetheless, he got on the list and got a liver. One wonders if he had been Jay Stevens instead of Steve Jobs, would he have gotten on the list?

    Other questions abound and answers are apparently not yet within the bounds of what is known with anything approaching scientific certainty.

    Medical care is a scarce commodity (that is there is more demand, even in medically and economically advanced societies, than services available). Therefore, by definition, medical care is in some way rationed. Organ transplantation is an especially limited subset. It is fair to ask whether scarce lungs should be implanted in chronic smokers or scarce livers in continuing alcoholics. Should patients who deviate significantly from best therapeutic practice have the same access to scarce resources as those who rigorously follow best practices therapies? Do these answers change depending on who is footing the bill?

  9. ConspicuousCarl says:

    CEOs can leave for all kinds of reasons, just as anyone would. Quit, fired, died, got arrested, whatever. It’s not like cancer is the only thing about which investors lack perfect knowledge, so I don’t see why too much detail should be expected.

    Jobs made arrangements to be replaced, and seems to have worked for as long as he thought he ought to. Good enough.

  10. Greg says:

    Thank you for the thoughtful analysis.

  11. Josie says:

    BobbyG,
    No information has been shared that didn’t come directly from or with the permission of Mr. Jobs. The fact that he let certain details be known, like the insulinoma, the transplant etcetera, allows professionals plenty of room for educated speculation on what actually happened.

    No one violated Mr. Jobs’ rights.

  12. BobbyG says:

    Yeah, Josie, I know. I didn’t make my inferential point clear, which goes to this unwarranted expectation that we somehow have a right to know about his PHI because of his lofty station.

    It’s actually noteworthy that no one apparently looked at and leaked things out of his chart. People would have paid big $$$ for that. The keystroke monitoring in the audit logs must have been pretty good.

  13. Quill says:

    I’ve been an SBM reader for a while and decided to de-lurk to comment on this posting. Thank you very much for this article. I appreciate the fair assessment of possibilities based on what little is exactly known about the medical record of Steve Jobs. I also appreciate the thoughtfulness that went into the writing.

    I am also, from an old-fashioned, personal point of view, appalled at both Dunning and Gonzalez’ self absorption in working so hard to put their agendas forward before the funeral had even taken place. An old word to describe such behavior is simple: tacky.

    Harriet Hall wrote: “I maintain that it is enough to announce when you are too ill to do your job well, and when death is imminent and it is necessary to plan for continuity, but that details need not be announced.”

    I agree.

  14. windriven says:

    @Dr. Hall
    Publicly traded companies have a responsibility to disclose information that could negatively affect future earnings. I think that any fair-minded person would have to agree that Apple disclosed Jobs’ illness in a timely fashion. Jobs had reasonable cause to believe his disease would be manageable until fairly recently. Shareholders, in my estimation, had sufficient information.

    But I would question whether, “it is enough to announce when you are too ill to do your job well, and when death is imminent and it is necessary to plan for continuity” in the case of someone like Jobs whose singular vision is a major strategic asset. An announcement that, say, Lloyd Blankfein (CEO Goldman Sachs) had a potentially fatal disease would carry different weight in the investor community than a similar announcement regarding Jobs. Goldman has a deep bench of similarly qualified individuals to take the helm. Jobs was sui generis and therefore timely disclosure (of the fact but not the details) would be material.

  15. Josie says:

    I see you now BobbyG :)

    When Mr. Jobs took his recent medical leave I remember seeing a mini-interview with a pension administrator. She thought she had a right to know health details of Apple’s CEO because she owned stock in the company (it was something smallish too, small fraction of a percent)

    At the time it hadn’t occurred to me that anyone would claim such a right. I also quickly dismissed it –everyone dies, no one knows when and privacy is important. It’s the company you invest in, not an individual person.

    If she was administering my portfolio I would fire her. She clearly didn’t understand that Uncle Steve’s contribution was more than spitting out cool marketable ideas. The company he built is going to grow for a long time to come.

  16. Harriet Hall says:

    @windriven,

    I don’t understand why it wouldn’t be “enough to announce when you are too ill to do your job well, and when death is imminent and it is necessary to plan for continuity” just because someone’s singular vision is a major strategic asset. What do you think the criteria should be in that case, and why? Is there some essential point that I am missing?

  17. BobbyG says:

    @Josie -

    I could see Wall St. taking out the viaticals equivalent of “Credit Default Swaps” on him.

    New, from Michael Lewis: “Shorting Steve Jobs.”

  18. windriven says:

    @Dr. Hall
    I think this is a small point but perhaps important. There is a difference between “too ill to do your job well” and a more nebulous circumstance that could nonetheless have a quite material negative effect in the foreseeable future.

    To use an example, it is not enough for a publicly traded company to announce that it has lost a major patent infringement suit and that quarterly results may be negatively (too ill). They must disclose the very fact that suit has been filed against them even if, as is customary, they simultaneously declare that they feel likely to prevail in court. This gives the investor the opportunity to judge for him or herself whether to make or maintain an investment.

  19. Harriet Hall says:

    @windriven,

    ” a more nebulous circumstance that could nonetheless have a quite material negative effect in the foreseeable future.”

    If he was having marital problems or insomnia or was drinking more than he used to, or had a teenage child who was abusing drugs or was experiencing a crisis of faith in his religion, do you think he would be obliged to report it? Where do you draw the line between need-to-know and invasion of privacy?

  20. windriven says:

    @Dr. Hall
    I certainly understand the slippery slope. As I noted earlier, I believe that Apple walked that line quite well. Jobs’ pancreatic cancer was made public and his liver transplant was made public, both without graphic details. In my book that satisfies the investors’ rights to material information without descending into matters best left to the tabloid press.

    To answer your question directly, and again speaking specifically about an individual having unique skills critical to the future of the company, I would argue that disclosure would hinge on the probability that the circumstance to be disclosed would be likely to have a material effect on the company’s future performance.

    The specifics that you mention do not, possibly with the exception of incipient alcoholism, rise to that level in my opinion. Diagnosis of a disease with a high possibility of lethality would. Diagnosis of high blood pressure? Nah, that is generally manageable. Diagnosis of esophageal cancer? You betcha ;-)

  21. @windriven, that’s all just a bit squishy, isn’t it? :-) It is a matter of highly subjective opinion — and hotly contested, in Jobs case — whether or not a CEO has “unique skills critical to the future of the company.” Quite a lot of people didn’t think highly of Jobs at all, and thought Apple’s success was due to other factors entirely (i.e. fad and fashion). Presumably investors generally thought rather more highly of Jobs talents … but then again, one would hope that an investor in any company would give its CEO credit for unique and critical skills. If not, why would he or she have been hired, exactly?

  22. pmoran says:

    A good account, David. As you say, this cancer looks to be towards the more aggressive end of the neuroendocrine cancer behaviour, so it is quite likely that the nine months delay before surgery made no difference to the final outcome.

  23. David Gorski says:

    Nonetheless, he got on the list and got a liver. One wonders if he had been Jay Stevens instead of Steve Jobs, would he have gotten on the list?

    Probably. Cancer is one of the indications that puts a patient near the top of the transplant list.

    On the other hand, Jobs established residence in Tennessee in order to be in a state where the waiting list for a donor wasn’t as long as it was in his region of California and lived there for a few months before he got his liver. That’s not something that someone of limited means could do.

    http://www.nytimes.com/2009/06/23/business/23liver.html

    http://www.uthsc.edu/news/ne.php?HYPER=/news/june/jobs_liver_transplant.htm

  24. BobbyG says:

    Wow, that’s interesting, David.

    The Shit Sandwich Theory of Life. The More Bread You Got, The Less Shit You Gotta Eat.

    Though, I have to wonder, Juice and shorter waiting list aside, did his green light hinge on viability or likely outcome?

    As I wrote on another blog:

    “My late daughter might have survived with a liver transplant (she had Hep-B, and subsequent hepatoma; a new liver would have been clean of Hep-B). She was considered for it, but denied, ultimately. Insurance coverage had nothing to do with it directly (she was busted, and on Medi-Cal). It was based on survival potential and the likelihood of recurrence. Notwithstanding that it was her best shot, we all understood.”

    http://www.bgladd.com/1in3

  25. windriven says:

    @Paul Ingraham

    “It is a matter of highly subjective opinion — and hotly contested, in Jobs case…”

    A fair point, but I would suggest that you consider Apple from IPO to Jobs’ termination, its downward spiral when he was gone, and its rebirth and subsequent growth since he rejoined the company.

    Competent CEOs, despite their often high pay, aren’t that hard to come by. Executive functions are well understood and executive decisions, while sometimes painful, aren’t arrived at through ‘golden guts’. Management is a discipline like any other.

    Jobs and a few more like him are something else. Jobs held the title of CEO but his role was more like a melange of marketing, design, pitchman and visionary. One can like Jobs or not but it is very hard to argue convincingly that he did not make a singular contribution to Apple and to the world of personal digital devices.

  26. If only that actually stopped anyone from trying to argue it!

    I’ve followed the Mac press closely for many years now. Surreal double standards, straw men, and hyperbole have characterized punditry about Apple since the earliest days. Only since the freakish success of the iPad have some of Apple’s harshest critics started dropping acknowledgements that he was a competent CEO, but (1) it’s generally been begrudging, miserly and backhanded praise of the “well, he there’s no denying he can sell shiny shit” variety, and (2) this is all amazingly recent. At the time that the fuss started over Jobs’ “responsibility” to disclose his health worries, the iPhone was still new and pundits were absolutely tripping over themselves predicting that the infallible Jobs was about to fail. And they did it again with the iPad, even when it was fairly clear that the iPhone couldn’t be stopped or beat. Insanely great success was conspicuously not enough to win over a bunch of his critics.

    So it’s really only extremely recently that it’s been “very hard to argue convincingly” that Jobs skills were “unique and critical” to the company’s fate. Certainly lots of people knew it, probably most, but the value of his contribution was definitely argued, the whole way and still now. There’s an column at MacWorld (“The Macalope”) that catalogs the inanity of anti-Apple punditry; it’s been running forever, and there’s never been a shortage of material, not once.

  27. Mark P says:

    On the other hand, Jobs established residence in Tennessee in order to be in a state where the waiting list for a donor wasn’t as long as it was in his region of California and lived there for a few months before he got his liver. That’s not something that someone of limited means could do.

    Does it matter that he was able to do this because he was wealthy? If rich people aren’t able to do things with their money there doesn’t seem to be much point being rich.

    The issue only arises when someone else misses out because a rich person is able to buy illicit access. Queue jump or get permission to avoid normal requirements. And that’s bad not because he is rich, but because illegal things are inappropriate from anybody.

  28. windriven says:

    @Mark P

    “The issue only arises when someone else misses out because a rich person is able to buy illicit access”

    Organs are a very rare commodity. More often than not someone getting an organ means someone else does not.

  29. windriven says:

    @Paul Ingraham

    “Only since the freakish success of the iPad have some of Apple’s harshest critics started dropping acknowledgements that he was a competent CEO”

    Actually, I would argue that he wasn’t much of a CEO; his management skills where never his forte. But sometimes a visionary – especially a visionary founder – gets the title while the COO or someone else actually makes the trains run on time.

    I’m trying to understand where you come down on this and why. You note that Jobs’ harshest critics have recently started allowing some backhanded compliments. But so what? Unless those critics were shareholders. And if they were, they should be very happy with their investment during the time Jobs was running the show. I haven’t looked this up so don’t hold me to the particulars, but as I recall Apple IPOd at around 20 and right now it is in the mid 300 range. That didn’t happen during Sculley’s reign.

  30. BillyJoe says:

    “Does it matter that he was able to do this because he was wealthy?”

    Would it matter to you if his money cheated you out of the liver you needed to save your life?

  31. @David Gorski, Nice article. I appreciate your fair approach in presenting the unknowns that a patient and doctor face when dealing with a rare disease.

    I guess I either misunderstand or disagree with this comment though.

    “On the other hand, Jobs established residence in Tennessee in order to be in a state where the waiting list for a donor wasn’t as long as it was in his region of California and lived there for a few months before he got his liver. That’s not something that someone of limited means could do.”

    Why couldn’t someone of limited means move from California to Tennessee? True, moving can be difficult, but depending upon your support systems from family and friends I wouldn’t consider it something reserved for millionaires. Also, Tennessee does have a much lower cost of living than California, apartments in Nashville start at $600, while those in San Jose start around $1100.

  32. Windriven “Nonetheless, he got on the list and got a liver. One wonders if he had been Jay Stevens instead of Steve Jobs, would he have gotten on the list?”

    So it’s not like you’re trying to imply that the people who administered the transplant system AND Steve Jobs were corrupt without any sort of actual evidence of corruption…

    you’re ‘just sayin’ wink, wink.

  33. Harriet Hallon 10 Oct 2011 at 12:19 pm
    There is another issue here. Jobs wanted to maintain privacy, but it has been argued that he had a responsibility to his company and stockholders to inform them of his medical issues. I maintain that it is enough to announce when you are too ill to do your job well, and when death is imminent and it is necessary to plan for continuity, but that details need not be announced. What do the rest of you think?

    I agree with you Dr Hall, There’s a certain set of stockholders and investors that are like gambling addicts. They always thinks some extra information is going to help them predict the “winning” companies. If you let them have their way they’d have your driving record, medical records, phone tapped, etc. If they don’t like the amount of info they’re receiving they are free to invest in something else.

  34. Anthro says:

    I appreciate your evenhandedness on this and was waiting for you to weigh in on this before forming any views. I’m happy to report that I did not succumb to my immediate urge to blame the woo. The thing about the nine months waiting, though, is that he even contemplated it. That is where the danger lies. No woo-free doctor would recommend that–especially when the reason was to allow for the trial of a totally unproven (and probably disproven) diet approach.

    Dunning says it was an Ornish diet. I read in the NY Times that Ornish was one of the few allowed to visit in Jobs’ final days. So, no regrets apparently for Jobs.
    ———
    @Michelle

    I agree that moving to Tennessee would be possible for other than the filthy rich, but not for the poor probably. I don’t begrudge Jobs this move, but would like to see some group make it possible for less fortunate people to do the same.

  35. ConspicuousCarl says:

    windriven on 10 Oct 2011 at 11:24 pm

    @Mark P

    “The issue only arises when someone else misses out because a rich person is able to buy illicit access”

    Organs are a very rare commodity. More often than not someone getting an organ means someone else does not.

    Yes, but consider…

    Poor “Person A” lives in Tennessee and needs a liver. They are marked as low priority for whatever medical reasons.

    However, because they happen to live in Tennessee where there are fewer recipients waiting vs. availability, they are close to getting a transplant anyway.

    “Person B” from New York is marked as high priority, and in theory SHOULD receive that liver in Tennessee before Person A does. But they can’t afford to fly to Tennessee to get the liver they need, so Person A is about to get the liver.

    Ideally, anyone needing a new liver would be given instant free transport to wherever the organ and service was available. But this is not the case.

    BUT, there is also Person C from California. He is also marked high priority, and CAN afford to go to Tennessee to get the operation, bumping Person A back down.

    Ignoring the existence of Person B, one could say that Person C used his money to get a transplant, negatively affecting Person A.

    However, that only looks true because Person B was too poor to take their proper place in line. If life were rosy and anyone needing a transplant were given free transport and board in whichever location necessary, Person A wouldn’t have been next on the list anyway because Person B would have been zipped in. Someone else, rich or poor, still would have come before them. In fact, there are probably loads of people similar to Person B, so Person A would probably be even further down the list if money was not an issue.

    Obviously nobody is comfortable with the fact that Steve Jobs got a transplant faster because he happens to be rich. But why should the hypothetical Person A get a transplant faster because they just happen to be born in Tennessee?

    Also to be considered, even though waiting in California may be longer, the fact that Steve Jobs DIDN’T have an operation there still left open a spot he otherwise would have filled. Someone in California moved up a slot because of this.

  36. Anthro
    “I agree that moving to Tennessee would be possible for other than the filthy rich, but not for the poor probably. I don’t begrudge Jobs this move, but would like to see some group make it possible for less fortunate people to do the same.”

    I was considering this, I came to the conclusion that it really depends upon how you are poor. If you are on social security disability, then your benefit should move with you, but if you are on Medicaid, then you would need to apply to the new state, which, I’m assuming could result in a gap of coverage, it’s going to come down to individual state policies.

    The actual cost of the move might be covered by friends, family, church help and or donations. Or not, if you don’t have a helpful support network. It really depends so much on individual circumstances, I hate to see sweeping generalizations.

    To me it’s just funny that folks get riled up that Jobs moved to Tennessee to get on a shorter donor wait list. The fact is that most people who have group insurance coverage have access to better healthcare than those without health insurance or those on medicaid. I don’t see anyone turning away their insurance cause it’s not fair.

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  38. sandygottstein says:

    Thank you for your thoughtful, fair-minded, informative piece on Steve Jobs. You might be surprised to know that I was utterly offended by Mike Adams’ cruel, misinformed (being kind), agenda-driven piece.

  39. Fifi says:

    For what it’s worth, Steve Jobs’ biographer indicates that Jobs told him that he regretted his decision to delay medical treatment and even brings up “magical thinking” and the role it played.

    http://www.cbsnews.com/video/watch/?id=7385390n

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