Tripping through Uncertainty - seeking closure
I was very touched by Alessandro Liberati’s ‘An Unfinished Trip
through Uncertainties’ (BMJ 2004;328:531 28 February 2004). I do not
have a medical or scientific background. I am a journalist and part of my
training is to seek the truth which lies behind the data, in much the same
way that an academic will do, but with a different outcome in mind. I will
be looking for a story. I find it fascinating therefore that my own story
brings me to similar conclusions to those of Alessandro Liberati.
I was diagnosed with a leiomyosarcoma on my left leg in early 1999.
It was interfered with prior to diagnosis and that almost certainly helped
it disseminate in my lymph system despite the tumour bed being
satisfactorily excised. The lymph metastasis which resulted is unusual in
this disease and again, although excised, resulted in a further tumour in
the groin which was unresectable. I entered a Phase 3 RCT comparing two
experimental schedules of ifosfamide against ‘standard dose’ doxorubicin.
I was randomised to one of the experimental schedules and had the full six
cycles in the protocol. My tumour showed regression after two cycles and
although it could be seen (and can still be seen) on CT scans after the
course was finished I was told I was in remission.
At this stage the trial had been running for three years. Soft tissue
sarcomas are rare and accruing the number of patients necessary to
satisfactorily demonstrate that one schedule was better than another was
expected to take 6 to 7 years. In 2002 I found out that the trial had been
halted in 2001 by the Data Monitoring Committee after 322 patients had
been accrued. Preliminary results were given at ASCO and you can imagine
my shock when I saw that just 4 patients were recorded as CR (Complete
Remission) and could presume that one of these was me. The trial had been
halted because it was clear at the halfway point that the null hypothesis
I can recognise that this trial added something to the knowledge of
the treatment of soft tissue sarcoma, although it is unclear whether this
is really significant. I can also recognise that the unusual pathway my
own disease had taken was almost certainly a contributory factor in my
survival. But I want to know the whole story, even though that will have
no impact on my continuing follow-up.
It is now nearly three years since the trial finished. The interim
conclusions confirmed much that was already known about the response to
chemotherapy for advanced and metastatic soft tissue sarcomas. A lot of
data was gathered and I understand that various sub-group analyses have
now been undertaken. If there was a significant conclusion from this
further work it has not yet been published.
So what do I feel at this stage? Humbled by my own survival when so
many other contributors to the trial have died – true. And questioning of
the original purpose of the trial – was it scientific curiosity or a
potentially valuable clinical investigation? I suspect the former and
that the underlying story is uncomfortable and unchanging. It may well
state that metastatic soft tissue sarcoma (usually in the lungs) is only
survivable long-term when treated surgically (in the absence of new
compounds) but that unresectable tumours elsewhere, treated with current
standard treatments, do have a small chance of responding well. However,
honesty to tomorrow’s patients demands that we know what conclusions the
researchers have reached and we will not find that out until the results
have been published.
Perhaps the only real lesson will be that it should be clearly
explained to patients what stage their disease has reached, what
chemotherapy entails and what the most probable outcome is in their unique
circumstance, but explaining that should be good practice anyway. It is an
uncomfortable story on which I seek ‘closure’.
Competing interests: No competing interests