CHART for head and neck cancers

Summary:

Is CHART going to make comeback or is it going to be another altered fractionation scheme that bit the dust

CHART for head and neck cancers

Santam Chakraborty 24 Apr 2010 17:36

This is with reference to the recently published 15 year mature results of the CHART vs Conventional RT trial. See here :
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7X-4YV7M3M-4&_user=2622728&_coverDate=05%2F01%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000057891&_version=1&_urlVersion=0&_userid=2622728&md5=f331320cd4ea673e1b6d5b223fc4fd79
What are your thoughts on the issue ? Do you think an altered fractionation schedule like CHART has a place in modern radiotherapy?

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Re: CHART for head and neck cancers

Rohit Malde 24 Apr 2010 21:51

Santam, i find it difficult to comprehend how such a conclusion is made by them.
They initially ran this trial, thinking CHART would prove to have a 15% improvement in locoregional tumour control compared with conventional RT before 1990.
In fact if you look at any of these primary endpoints, all seem to be inferior compared with conventional RT (though statistically non-significant).

I wonder how a superiority trial can be concluded as a equivalent trial, saying its as good as conventional RT.
when the reality may be that if you run a non-inferiority trial or equivalent trial, which may require over 1500 pts, it may be that CHART is detrimental.

Survival estimates, HRs, and 95% CIs for treatment outcome 10 years after randomization

Endpoint
CHART (±1 SE) Conventional RT (±1 SE) Log-rank p value HR 95% CI

Locoregional relapse-free survival 43% ± 2% 50% ± 3% 0.2 1.06 0.97–1.17
Local relapse-free survival 52% ± 2% 54% ± 3% 0.9 1.00 0.91–1.11
Disease-free survival 41% ± 2% 46% ± 3% 0.3 1.04 0.95–1.14
Disease-specific survival 56% ± 3% 58% ± 3% 0.5 1.04 0.93–1.17
Overall survival 26% ± 2% 29% ± 3% 0.4 1.04 0.96–1.12

Anyways the reality is that in the UK there are 5-6 centres who practice CHART, but for only Lung.
I have not seen any Head and neck cancer pt in the last 5 years ever treated with CHART.

Moreso, the answer for pts who cannot tolerate CTRT or who cannot be given platinum compounds , the answer is use CETUXIMAB as per the Bonner study which shows survival advantage compared to conventional RT.

So, to conclude CHART in head and neck cancers is DEAD.
Would be interested if you or someone else are aware of any centres in the world offering this routinely or are using it in a trial setting.

Re: CHART for head and neck cancers

Santam Chakraborty 25 Apr 2010 04:52

You are right indeed Rohit, the initial expected gain of 15% was not seen which is why this study has been presented as a non-inferiority study. I was intrigued by this fact and have emailed the authors for this reason.
I personally don't know any institution using CHART on a regular basis but the hypothesis behind CHART always seemed radiobiologically sound to me. I fail to understand how the authors had initially made the assertion of a 15% improvement when the dose is being reduced so drastically in a moderately radiosensitive tumour.
What I am intrigued about is the fact the high epidermal growth factor expression is associated with a greater benefit when using altered fractionation in the form of CHART as reported by Bentzen et al http://jco.ascopubs.org/cgi/content/full/23/24/5560 . Will this finding allow us to design a hyperfractionated accelerated radiotherapy regimen without a dose reduction and use it for the patient population unable to afford cituximab which is a common phenomenon i the 3rd world.

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Re: CHART for head and neck cancers

b3n 15 May 2010 08:20

Following the positive results of DAHANCA 6&7, the IAEA addressed your question with their IAEA-ACC study, published last month in Lancet Oncology. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70072-3/abstract
Their report was quite encouraging indeed, with locoregional control benefit of 12% (more or less similar to what you'd expect from concurrent chemotherapy?)
The real problem in applying their methods, however, is that we will have to convince the hospital administration AND the staffs that the increase in working hours is really worth it.
What do you think?

Re: CHART for head and neck cancers

RAJESH R NAIR 15 May 2010 08:57

12% 5year acturial locoregional control in head and neck .Defenitely my opinion it has to be implemented.At same time if we reduce fraction in other site like breast 40gy /15fr or 42/16 fr the work load can be even out.

Re: CHART for head and neck cancers

Nikhilesh Patil 17 May 2010 05:28

How many of you who practice Head Neck radiation oncology are willing to start 6 treatments per week with all the evidence you have ?
Also it will be interesting to see if the centres who did IAEA-ACC trial change there practice.

Re: CHART for head and neck cancers

Rohit Malde 17 May 2010 08:01

Whats the cuurent practice of TMH ?
Are they treating pts 6 days / week

There would always be this dillema..
that US, UK, Canada — will continue to use concurrent chemoRT as their Std of care.
Those pts who cannot tolerate CTRT, will be offered Concurrent Rx with Cetuximab as per the Bonner study.
There is not much role of RADIOTHERAPY ALONE in head and neck and even in Cervical cancers.

Whereas in centres from Asia, Europe, the Middle East, Africa, and South America who participated in the trial , the so called IAEA centres.. where developing countries, where there are fewer therapeutic resources
there is no doubt that ACCELERATED RT seems to be logical and the way forward.
However, there will be more manpower required in terms of making the radiation oncologist as well as the radiation technologist work 6 days a week.

Of course this will certainly benefit our poor pts at the end.

Re: CHART for head and neck cancers

radtuxabhishek 07 Sep 2010 12:22

I am all for the benefit of CHART. For one simple reason. It is radiobiologically sound because it aims to counter the proliferation. I am not too happy for using Cetuximab (or rather not convinced) for the following reasons:

1) There is an upregulation of EGFR receptors (including it's various subtypes) during conventional radiation. It tends to promote survival signals as well as angiogenesis. This means that it probably worsens the outcomes in terms of increasing radioresistance. At the same time, it is NOT the ONLY pathway by which cells tend to escape the EGFR blockade.

2) I again believe that targetting the clonogenic cells (aka Stem Cells) would give us the real control. Unfortunately, there are no means to detect them invivo unless they are known to exist in certain niches like for example around in ventricular area in brain. Although they can be detected by means of IHC, but then need biopsies. This apart, EGFR targets the bulk of the cells ( I would say the scum over the roots i.e. stem cells) which although gives a "local control" but then it is not durable. It is a common known fact that ANY surviving clonogen would again lead to recurrence.

3) Using EGFR based on a flawed trial (it did not compare with standard of care i.e. chemoradiation) is one of the most important point against it's use because if you see the Bonner trial carefully, much of radiation was given based on physician's preference i.e. concomitant boost based on the practise prevalent in US. (This was a multi-centre trial). I feel that the results need to taken with extreme caution.

I prefer CHART and /or altered fractionation because it is proven and radiobiologically sound. Although there were intense reactions, they tended to wear off by 6-8 weeks. Further, there has been no "long term sequelae" as mentioned in the update. It is doable and worthwhile. As for the acute reactions, even in the conventional fractionation, I get to see Grade III reactions on a routine basis. Don't we all manage them? Why should we restrict ourselves to the criticism of gain of 15%

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