Respectful Insolence

Blogging on Peer-Reviewed ResearchI’ve always wondered, as I’m sure many of my readers have, whether human beings have it in them to delay their own death, even briefly. Very early in the history of this blog, a mere 11 days after I started it, I discussed a study that strongly suggested that we cannot. In brief, it looked at the common belief that people dying from cancer can somehow, through sheer force of will, hold death at bay for brief periods of time, usually until some milestone that they wanted to see one more time is reached, be it a birthday, anniversary, holiday, or whatever. After they reach that milestone, the belief goes, they then die. Alas for this popular myth, investigators who examined 300,000 cancer deaths over 12 years and were completely unable to find any evidence of spikes in death rates around the times of birthdays, Christmas, or Thanksgiving. Sadly, it appears that, as always, death wins, and there’s nothing we can do about it.

A corollary of this popular belief is that people with a positive attitude do better when they have cancer, even to the point of living longer than people who lack a positive attitude. Among residents, there’s actually what’s probably a myth that says the opposite: Namely, that the nastiest, most cantankerous people tend to do the best, presumably because they’re fighters and just too ornery to die, and that “nice” people tend to do worst and die like dogs. No doubt this latter belief is a case of confirmation bias. Be that as it may, for quite a while the prevailing dogma has been that support groups and/or psychotherapy can prolong survival in cancer patients, although this dogma has little bsis in firm evidence to support it. More than likely, it, too, is a case of confirmation bias.

Earlier this week, this question came to the fore again, because a study was published that strongly questions the dogma that a positive mental attitude can prolong survival. The abstract follows:

Emotional well-being does not predict survival in head and neck cancer patients

A radiation therapy oncology group study

James C. Coyne, PhD 1 *, Thomas F. Pajak, PhD 2, Jonathan Harris, MS 2, Andre Konski, MD 3, Benjamin Movsas, MD 3, Kian Ang, MD 4, Deborah Watkins Bruner, PhD 5
1Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
2Radiation Oncology Group, Statistics Department, American College of Radiology, Philadelphia, Pennsylvania
3Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
4Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
5School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania
email: James C. Coyne (jcoyne@mail.med.upenn.edu)
*Correspondence to James C. Coyne, Department of Psychiatry, University of Pennsylvania Health System, 3535 Market Street, Room 676, Philadelphia, PA 19104

ABSTRACT

BACKGROUND.
The objective of the current study was to examine whether emotional well-being predicted survival in a large sample of patients with head and neck cancer who were participating in multicenter clinical trials.

METHODS.
Participants were enrolled in 2 Radiation Oncology Group (RTOG) clinical trials (RTOG 9003 and RTOG 9111) and completed a baseline measure of quality of life (the Functional Assessment of Cancer Therapy-General [FACT-G]), which included an Emotional Well-Being subscale. The outcome measure was overall survival. Main statistical analyses included overall survival rates, which were estimated by using the Kaplan-Meier method with univariate comparisons analyzed using the log-rank test. A multivariate Cox proportional hazards model was used to determine whether emotional well-being had prognostic impact on survival after accounting for tumor-related and sociodemographic variables. Additional exploratory analyses examined possible subgroup effects.

RESULTS.
No statistically significant univariate or multivariate effects were observed for emotional well-being, and there were no effects limited to subgroups. These results stand in sharp contrast to the prognostic value of a variety of demographic and clinical variables.

CONCLUSIONS.
The current results add to the weight of the evidence that emotional functioning is not an independent predictor of survival in cancer patients. The study had the advantage of a large number of deaths to be explained in a sample with the uniformity of treatment and quality of care that is required in clinical trials.

(News report summarizing the trial here.)

This study, the largest yet to study this question, combined two randomized, phase III radiation therapy studies, with a total of 1,093 patients with head and neck cancer from two different radiation therapy studies, of which 646 patients died during the course of the studies. One of the studies was a comparison of different radiation dose fractionation schedules, and the other was designed to study concurrent radiation and chemotherapy. As a part of these studies, quality-of-life estimates were examined, and patients were assessed upon entry to the protocol with five questions on the FACT-G quality of life questionnaire evaluating whether patients felt sad, were losing hope, feeling nervous, worrying about dying, worrying that their condition would worsen, and whether they were proud of how they were dealing with their condition. In neither univariate (the more sensitive but less specific way of looking for correlations) or multivariate (the more statistically appropriate method), did the investigators find any correlation between feelings of well-being and survival. This held true in the face of multiple calculations to take into account stage of disease, demographics, smoking, and performance status. Even doing subgroup analyses, often the last resort when looking for some result or correlation in a trial that is yielding none, failed to find subgroups for whom well being correlated with survival. Because the number of deaths observed was larger than the combined sample sizes of most previous studies, this represents the most resoundingly negative study to date looking at this question.

Head and neck cancers are particularly vicious cancers. This is not so much because they kill as rapidly as some of the more deadly cancers out there, such as pancreatic or esophageal cancer, but more because of the treatment needed to eliminate them. Often the surgery necessary is disfiguring, depending upon the location. In the case of laryngeal cancer, for example, it is sometimes necessary to take the vocal cords, leading to the loss of the ability to speak normally, necessitating learning esophageal speech or the use of an electromechanical device that produces a robotic-sounding voice. Sometimes it’s necessary literally to remove a big chunk of the face, even the mandible, to cure some cancers, leaving a deformity not easily reconstructed even by the best plastic surgeon. Moreover, there’s the chemotherapy, and the radiation therapy has a distressing tendency to fry the salivary glands, leading to a condition of xerostomia, or inadequate saliva production. It may not sound like much, but it can have a horrible impact on a patient’s quality of life. As The Cheerful Oncologist puts it, it would be the rare head and neck cancer patient indeed who would not be depressed.

The population chosen naturally has led critics of the study to argue that, while perhaps a positive attititude doesn’t prolong survival in head and neck cancer, perhaps it does in other cancers for which the treatment is not so harsh. In the case of breast cancer, however, there are multiple retrospective studies that also failed to find a correlation between health-related quality of life scores and survival (1, 2, 3) and one randomized trial testing whether supportive group therapy had any impact on survival that failed to find any benefit in terms of survival.

Although there are still mixed results among studies looking at this question, I think that the pendulum is starting to swing towards where the main driver of survival in cancer is biology:

University of Pennsylvania researchers say that among head and neck cancer patients, emotional health — good or bad — is not an independent factor affecting prognosis.

“We anticipated finding that emotional well-being would predict the outcome of cancer. We exhaustively looked for it, and we concluded there is no effect for emotional well-being on cancer outcome,” said study author and University of Pennsylvania psychologist James Coyne. “I think [cancer survival] is basically biological. Cancer patients shouldn’t blame themselves — too often we think if cancer were beatable, you should beat it. You can’t control your cancer. For some, this news may lead to some level of acceptance.”

[...]

Another expert said he wasn’t surprised by the Pennsylvania findings.

“People are more likely to find this news a relief than a disappointment,” said Dr. Michael Fisch, an associate professor of gastrointestinal medical oncology at the University of Texas M.D. Anderson Cancer Center, in Houston.

Survival depends on the location of the cancer, the risk factors for the cancer, and how advanced the cancer is when it’s diagnosed, said Fisch.

In fact, Dr. Fisch has a term for trying to persuade a patient who doesn’t speak optimistically about his cancer to be more more positive as the “tyranny of guilt systems,” where others seem to imply that the patient has some sort of “mind over matter” control over their cancer. I tend to agree. One pernicious consequence of this emphasis on “bucking up” and being cheerful in the face of adversity is that patients can tend to blame themselves if they are not doing well or if their tumor is growing in spite of therapy. It could indeed bring more piece of mind if patients could simply accept that their state of mind will not determine how fast their cancer grows.

For course, none of these new results should be construed to say that depression in cancer patients doesn’t have a potentially devastating effect on the quality of their remaining life, nor should any of these results be taken as meaning that it’s pointless to try to treat depression and foster a more optimistic, positive attitude. There is little doubt that such positive attitudes can do wonders for improving quality of life, and it’s very important to make cancer patients’ lives, particularly when there is not much life left, as filled with joy as their disease will permit. What these results do say is that we should not oversell what a positive attitude can do. It may make cancer patients happier, something that is in and of itself of great value, but it won’t prolong their lives.

ADDENDUM: Dr. Steve Novella has also commented on this study.

Comments

  1. #1 darius
    October 24, 2007

    I think that the only effect you’d really see from a more pessimistic outlook would be a directly causal one; i.e. if a patient doesn’t think they’re going to live, they might skip some chemo sessions. Other than that, your outlook is really just going to affect your quality of life, not the length of it.

  2. #2 AnnR
    October 24, 2007

    I find this to be a relief.

    The notion that a cheerful attitude has some influence on survival smacks of “blame the victim” to me.

    I got a chuckle out of your residents myth that nasty patients live longer than nice ones. I guess it just seems like they live longer.

  3. #3 Sid Schwab
    October 24, 2007

    I’ve always made an effort to establish confidence and a positive attitude going into surgery of any kind. The reason, however, is not that I think it affects the ultimate outcome, but the immediate recovery period. Being less afraid has such immediate effects as not having a racing pulse on induction of anesthesia. Being less fearful about the process means being more willing to get out of bed after. Trusting the surgeon to do — and to have done — the right thing means having a collaborative attitude in doing the things necessary to recover from the operation. So I think it’s very important. (And no, I haven’t done a study…) But I’ve NEVER believed attitude would impact cure, nor implied it to my patients. It’s like prayer (as I wrote in my most commented on post ever); implying attitude affects outcome puts a guilt trip on those whose conditon doesn’t respond to treatment. And on everyone around them, for that matter.

  4. #4 outre
    October 24, 2007

    Speaking of positive attitude, have seen Crazy Sexy Cancer? It’s a documentary by Kris Carr (an actress of some sort) with stage IV epithelioid hemangioendothelioma. It was a 2-hr documenary that seemed to promote CAM, green goo and positive thinking to her survival(totally ignoring the fact her cancer is typically slow growing). The documentary got me really concerned that people will think CAM/green goo in lieu of proven conventional treatments will keep them alive. I don’t know how the thing ended, I couldn’t watch after an hour…ugh. Hopefully people will realize her disease course and HER story isn’t typical of most cancer patients.

  5. #5 Uncle Dave
    October 24, 2007

    The positive attitude is clearly an indangible data point, however as Orac stated;
    “it’s very important to make cancer patients’ lives, particularly when there is not much life left, as filled with joy as their disease will permit.”

    Not many of us out here in the blogisphere can speak from personal experience in this matter (patient perspective) thank god. Hopefully our experiences will primarily encompass witnessing those whom have set an example of what a positive attitude means, both personally and to those around them.

    I would imagine that oncology requires a certain amount of resiliance on the part of practitioner as well….

  6. #6 woodchopper
    October 24, 2007

    I suspect that one reason why people are encouraged to buck up and put a brave face on it is that a patient with a positive attitude is a lot easier on all the other people around them than one that keeps breaking down and weeping.

  7. #7 obscurifer
    October 24, 2007

    So, “cheer up, and you’ll recover” is functionally equivalent to “behave, or Santa won’t bring you presents.” The speaker is trying to influence the behavior of the listener in order to make the interaction easier.

  8. #8 jen_m
    October 24, 2007

    I’ve always viewed the positive-attitude hypothesis through the same jaundiced eye I use for faith healing – it seems a pretty quick jump to blaming the patient. That said, I lost my father to anaplastic thyroid cancer this summer. It was such a fast and gruesome disease progression, and it so drastically affected his cognition (pathway unclear – maybe sepsis, maybe cerebral bloodflow problems, maybe electrolyte issues), that by the time he was diagnosed there was no way he could adjust to his prognosis, even had he understood it. From a study design perspective, it’s pretty challenging to understand how to work around that potential source of bias – it takes some time to absorb a diagnosis, and during that time, attitudes are probably pretty negative. Some patients have more time than others to get that positive attitude back in balance. If it takes the same average amount of time for everyone to get over the shock and grief of a diagnosis of metastatic cancer, and if that time exceeds the survival time of some patients, you might see a false association between positive attitude and survival time. Admittedly, if the measurement is of a more stable personality trait, and the instrument doesn’t respond to that instability, there’s less possibility of bias.

    This RTOG study design seems to me to be problematic in a way I would have expected to bias in favor of finding an association between positive attitude and survival time. Patients were tested at the time of enrolment in the clinical trial, so if having a worse prognosis was associated with increased tumor pain or intermittent delirium from tumor necrosis or more intensive radiation treatment, all of which would reasonably be expected to be associated with more negative attitude, then negative attitude would be associated with lower survival time. (Pain is subjective and is really hard to adjust for statistically; cognitive status wasn’t part of the inclusion/exclusion criteria, although presumably patients had to be able to consent.)

    Very interesting stuff, indeed.

  9. #9 Woodwose
    October 25, 2007

    Personal and family observations indicate that the only positive attitude that helps in serious health related issues is a commitment to question, understand and then to meticulously follow the drug, treatment and other regimes established by the certified, competent team of medical practitioners working with you.

    When you consider the effort folks are willing to put into knowing the sports stats for their favourite team or the standing of the players in the latest Survivor or Idol program, the involvement with the treatment to prolong their own lives should be at a much higher level.

  10. #10 MikeB
    October 25, 2007

    Its true that the crabby patients do tend to survive (Sod’s Law perhaps?). And its clear that patients who believe in their doctors don’t tend to indulge in useless alternative therapies, give up their chemo, etc.

    However, there is a strange effect that I observed when responsible for processing deaths in a cancer hospital for some years. Looking through the records, it was apparent that relatively few patients died over the Christmas period, or certainly markedly less than the statistical norm. The senior ward nurses thought this was due to the desire of patients not to ‘spoil Christmas’ for relatives, and so would hang on until after Christmas.
    Now it could be due to several factors, such as the moving of some terminal patients to hospices nearer their home, or possibly the relatively few surgical ops undertaken at that time of the year, or simple chance. Whatever the reason, it was clear that there would be a spike in deaths when I came back to work after Boxing Day.

    Perhaps there is a study waiting to be done, although thankfully not by me…

  11. #11 Courter
    October 28, 2007

    Kate is Courty long time no hear,went over the hiv project the one you were also involved with from time to time,in which 20 million were saved-world clean form hiv under Generals orders.I also wen tover that one particular project when I saved 400 thousand African children with my image from hiv really really high-tech stuff we did witht he Generals and Vladimir Putin.Writ eme back ove to talk with you again.