CLL experts = longer OS

[Guest guest]

Re: Experts At 12:51 AM 8/30/2011, Koffman wrote:

>See my blog: http://tinyurl.com/3l2dcqm

Re: Experts At 11:48 AM 8/30/2011, Dwyer replied:

>Perhaps the considerably higher number of patients enrolled in

>clinical trials rather than the actual 'CLL haematologist' afforded

>patients a survival benefit?

At first glance, it would seem that the researchers could have

performed analyses to quantify the impact of enrollment in clinical

trials on the magnitude of improved overall survival (OS). However,

these were retrospective analyses of past studies, which may have

created technical barriers to such comparative analyses.

Because all the patients were treated at the Mayo Clinic, the paper

indicates they all had identical access to clinical trials (see SNIP

below); yet the ratio of patients participating in clinical trials

was 48% vs. 16%, respectively, for patients seeing CLL specialists

vs. patients seeing non-specialist hematologists. A 3-fold

difference in enrollment seems large in the context of all the

hematologists practicing at the same research clinic. Even a larger

difference would be expected if the non-specialists practiced at

non-research clinics.

It may be that greater enrollment in clinical trials derives from the

greater general wisdom (from experience) of specialists, e.g.

intuition about what characteristics of a patient make a given

clinical trial the best of all options for which patients.

One of the more important decisions for a patient, which is founded

on guidance from the clinicians, is when to first treat a patient and

how to first treat the patient. This importance was reflected in the

Discussion section of this paper, e.g. " Early treatment exposes

patients to the toxic effects of therapy which places them at risk

for a variety of treatment-related complications including infection,

second malignancy, and myelodysplasia, and may also induce clonal

selection that renders the residual leukemia more resistant to future

treatment. " (see SNIP below).

I believe patients who slowly progress to having pathologies that

require their first treatment have a biological state that probably

should not be harshly disrupted, so as to make more likely the

emergence of more resistant dominant clones of CLLcells.

Al Janski

REFERENCE:

" Hematologist/oncologist disease-specific expertise and survival:

Lessons from chronic lymphocytic leukemia (CLL)/small lymphocytic

lymphoma (SLL) " ; Tait D. Shanafelt MD et al.; Article first published

online: 26 AUG 2011; DOI: 10.1002/cncr.26474

ABSTRACT: http://onlinelibrary.wiley.com/doi/10.1002/cncr.26474/abstract

DISCUSSION SNIP.......

" ......all cared for at the same medical center where treating

hematologists/oncologists had identical access to clinical trials,

technology, supportive care, and multidisciplinary consultation.

Several findings of the study are notable.

First, although all treating/supervising physicians were board

certified hematologists/oncologists, significant differences in

clinical management and disease outcome were observed based on

physician's disease-specific expertise. Earlier stage (Rai 0-I)

patients cared for by a disease-specific expert were more likely to

undergo prognostic testing, had a longer TTFT, received different

types of therapy when treatment was initiated, and were markedly more

likely to participate in a clinical trial.

Second, patients cared for by physicians with disease-specific

expertise also had longer OS, a finding that persisted on

multivariate analysis controlling for other prognostic factors. This

finding suggests that the expertise of the physician caring for the

patient with CLL/SLL is an independent prognostic variable.

Third, the clinical outcomes of patients cared for by hematology

fellows at our center differed according to the disease- specific

expertise of the supervising physician; a powerful internal

validation of the importance of disease specific expertise. The

patients cared for by fellows were being cared for by the same

physicians (eg, each fellow can care for multiple CLL patients);

however, patient management and outcome differed based on the

expertise of the physician supervising/advising the fellow.

Although we are unable to definitively identify the reasons for a

difference in OS based on physician's disease-specific expertise in

this observational study, a number of possible explanations are apparent.

First, a longer TTFT was observed for earlier stage patients when

cared for by a CLL physician. Similar observations were reported by

Tsimberidou and colleagues for CLL/SLL patients cared for at the MD

Cancer Center. This finding persisted for both Rai stage 0

or Rai stage 1 patients when analyzed independently and may reflect

different application of the NCI Working Group criteria among CLL

experts and nonexperts, particularly regarding what constitutes

''massive/progressive lymphadenopathy'' and/or whether physicians

treat for a progressive lymphocytosis. Early treatment exposes

patients to the toxic effects of therapy which places them at risk

for a variety of treatment-related complications including infection,

second malignancy, and myelodysplasia, and may also induce clonal

selection that renders the residual leukemia more resistant to future

treatment.

Second, when patients received therapy, the type of treatment they

received differed based on the disease-specific expertise of their

physician with CLL hematologists more likely to use purine nucleoside

analog regimens. Although in early follow-up Phase III trials

suggested no difference in survival based on whether patients

received purine analogs compared with alkylating agent-based

regimens, recently updated results suggest a survival advantage to

patients receiving first-line purine analog based therapy.

Third, CLL experts may be more likely to administer salvage therapy

(including multiple salvage attempts) for patients with progressive disease.

Fourth, CLL experts may recognize disease-specific complications (eg,

cytomegalovirus [CMV] reactivation, ITP, AIHA) earlier and provide

better management of these complications. "