Tuesday, June 17, 2008

2-month prognosis in hospitalized cancer patients; Much more

Several notable pieces from a recent JCO:

First is a study about predicting 2 month survival in hospitalized cancer patients. This was a French study from 2 hospitals (n=~170) which used prospectively gathered data (laboratory, performance status, and disease characteristics such as number of metastatic sites, etc.) to predict mortality in hospitalized advanced cancer patients who weren't 'actively dying.' All patients admitted to the hospital who met the criteria were enrolled in the study (if they agreed) - these were not patients identified by a palliative care referral or anything like that. Mean age was 62 years; the patients had a diverse mix of solid tumors (no hematologic); and median survival in the cohort was 58 days (i.e. despite not being actively dying these were very sick patients).

All the typical prognostic indicators were apparent in univariate analysis (Karnofsky performance score, dyspnea at rest, low albumin, high LDH, leukocytosis, number of metastatic sites, etc.), and 4 of these 'survived' multivariate analysis: KPS, albumin, LDH, and number of mets. These 4 were aggregated into a point-based predictive model which divided the cohort into good, medium, and poor prognostic groups (really poor, worse, & dismal) for 2 month survival. Each prognostic group was well-represented in the cohort, which is welcomed since in many of these models patients with the worst prognoses often have very small representation in the initial model development (e.g. an N of 12 - here it was 63). Patients in the dismal group had a 2 month survival of less than 10%. The prognostic scoring system is quite simple and could be done at the bedside (although it's too long to describe here).

Some thoughts about this: Clearly this needs to be validated in further trials, more patients, different institutions, etc. Beyond this, I have mixed reactions to seeing these indices, of which there are numerous (although this one has some advantages - simple data, and quite a powerfully strong prediction of 2 month mortality...assuming its validity is borne out with further investigation). What do these add to clinical care? Or to a clinician's prediction of survival (which was not tested in this study)? This index could, for instance, be used to identify patients acutely in need of palliative care. However what I'm getting at is how much more help/data do we need to predict which of our advanced cancer patients are going to do poorly? That the issue in patient care is not a lack of a solid scientific basis to prognosticate but a lack of will to actually formulate a prognosis and communicate it to a patient (see previous post). Most of us in medicine are positivists (in the scientific sense) whether we'd like it or not; I'm convinced positivism underlies the EBM movement, and underlies our assumption that more data/better indices/etc. improves patient care - cases like this I'm a little less convinced. I'd welcome any comments here....

ResearchBlogging.orgBarbot, A., Mussault, P., Ingrand, P., Tourani, J. (2008). Assessing 2-Month Clinical Prognosis in Hospitalized Patients With Advanced Solid Tumors. Journal of Clinical Oncology, 26(15), 2538-2543. DOI: 10.1200/JCO.2007.14.9518

Next is one evaluating pain as a poor prognostic factor in prostate cancer. When I went through training I was taught that pain really wasn't a significant prognostic factor in cancer (although from time to time you see in crop up in univariate analyses in papers similar to #1 above). The current study in a post-hoc analysis of data prospectively gathered for a couple prostate cancer treatment trials in the 1990s (~600 men, all with castration refractory prostate cancer and who had ECOGs of 0-2). They used pain interference (from the Brief Pain Inventory) and patients with worse pain interference had a markedly worse survival (~10 months) than those with low pain scores (~17 months). My own, likely arbitrary and wrong, take on this is that it has something specifically to do with prostate cancer - more aggressive disease causing more bone pain, etc.

Finally, there's one looking at sleep disturbances in advanced cancer patients, in which a couple nights' worth of polysomnography was performed on over a hundred cancer patients. There was no control group. Nevertheless the sleep quantify and quality of the subjects was quite disturbed: less nocturnal sleep than normals, more periods of day-time sleep than normal, very low amounts of slow wave sleep (believed to be the essential, restorative element of sleep), etc. Per the authors this was the first large study using PSG on advanced cancer patients and may mark the next phase of cancer-sleep research.

JAMA recently had a 'clinicians' corner' piece about family requests for complementary medicine therapy after a declaration of brain death (based on a case in which just that event occurred). It's really a discussion about futility and a physician's role in providing (or not) 'futile' therapies. Given the patient in question was brain dead, and therefore legally not really a patient but a corpse (the fact that brain dead patients routinely aren't treated like corpses however highlights just how viscerally inadequate the concept of brain death is for many clinicians/families), makes the futility point in this case all the more compelling. On the other hand the traditional medicine that was to be given was in no way going to harm the patient (unless one rejects the concept of brain death), and the piece discusses in length just what physicians can and should do in such situations.

For me, the real question is not whether or not families should be allowed to administer 'futile' alternative or traditional treatments to brain dead patients (or dying ones), but in this case it's one of justice: should scarce and costly medical resources be used on dead people (to maintain brain dead people's cardiopulmonary function) at all (when there is no plan for organ donation)? A quote (I'll note however that the conclusion of the article isn't as strident as these stirring paragraphs):

Physicians generally should not agree to requests for clearly futile treatments, even when cost is not an issue, because doing so undermines medical professionalism and the supportable claims to expert authority of medical science. The physician is not an all-purpose technical extension of the patient's will and interests, but a professional committed to the good of health and the relief of suffering by the application of the medical sciences using sound clinical judgment. The terms of a physician's service are properly regulated by the ideals of medicine, reflectively endorsed and broadly conceived. Although the proper practice of medicine will be subject to lively and creative contestation along various frontiers, a physician with professional integrity is permitted, and sometimes required, to refuse to provide requested service that falls far short of medicine's regulative ideals as currently understood. Respect for the autonomy of the patient requires that a competent patient or her surrogate be allowed to refuse almost all treatments (with some exceptions for refusals that harm others), but such respect does not require the physician to administer all possible treatments. This distinction is underappreciated. ...[P]atients are not entitled to treatment that the treating physician judges to be bad medicine.

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