Risk of Secondary Cancers

Risk of Secondary Cancers

radtuxabhishek 23 Aug 2010 05:14

I am interested to know:
1) What is the risk of secondary cancers, if any by delivery of IMRT. I am concerned about the "low dose cloud" including the leakages from the treatment head. Is there any robust data and/or estimates for the same?

2) It has been seen that majority of secondary cancers for patients treated for Carcinoma Cervix have been in bladder. Does that mean that when we perform brachytherapy and inadvertently the dose is "high" to any specific point on bladder, it would add on to risk of secondary cancer? This is more important because chronic atrophic changes in bladder mucosa is associated with a higher risk of turning into cancer.

3) What is the importance of dose delivered during daily imaging for IGRT. How much "extra dose" over and above prescribed dose is delivered to patient? Is there any defined protocol to limit the dose? Does delivering higher MU to the patient give a better image quality (for MVCT machines).

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Reality is merely a persistent illusion

Re: Risk of Secondary Cancers

Harsha Dod 23 Aug 2010 12:00

good questions but I think there are no clear cut answers.
Radiation Oncology was built on total Empirical concepts initially. Slowly gradually as we understood late effects and radiobiology, we became evidence based.
In Perez and Bradys , first chapter ,they remark that, if by reasoning alone we had to proceed, the field of RO would not have taken off.

What we have today is a set of mathematical formulas and dose calclation engines eg. Monte Carlo etc, but only time will tell what are the bebefits and damages. We can try to limit damage using certain models but we should humbly accept that we have limitations with our knowledge. WE have to acknowledge that we do not always work with complete understanding , but there is light coming after we have worked in darkeness.

the best we can do and should do is to document everything as it is. This with pragmatism can limit damage but also allow progress.
The problem of induction is a constant one !!!

Re: Risk of Secondary Cancers

Santam Chakraborty 23 Aug 2010 13:24

Hi Abhishek,
Nice questions. The first one probably stems from the famous editorial by Hall. In fact Dr Vijay from our institute (presently TMH) has had a thesis on this aspect and the results are being published. Actual documented increases in incidence will take decades if it ever happens that way. You can look at articles by Schneider et al for a "balanced" mathematical estimate (taking into account the increased cell kill in the high dose region) for a look at the other end of the spectrum and there was lively "war of words" between hall and Schneider on this issue.
As far as brachytherapy induced second cancers is concerned the question is not going to be reliably answered for the simple reason that we cant design a good study on this aspect - I will elaborate here:
In order to quantify an "increased" risk of cancers secondary to brachytherapy the control group will be one which doesn't receive brachytherapy. That control arm should have the same control rate as the brachytherapy arm - radiobiologically impossible to achieve with any other modality (other than surgery - and no one will do a surgery after EBRT - as it can be done before also then!). It is important here that you have the "same" control rates in both arms else the inferior arm will show a spurious reduction in the risk of a second cancer as patients will die off earlier.
Having said this I am yet to see a patient of Carcinoma Cervix developing a second cancer in bladder though I have seen on developing it in rectum.
The answer to your third question will be best given by a person who has equipment for this :-)
P.S. : From one Linux user to another - Google talk now allows video chat in Linux for buntus

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Last edited on 23 Aug 2010 13:26 by Santam Chakraborty Show more

Re: Risk of Secondary Cancers

radtuxabhishek 23 Aug 2010 14:52

I too have been giving a thought to this and it's my personal perspective. Though I am not sure how "right" or "wrong" I am in my thinking and look up to you all for guidance.

1) I would prefer to avoid IMRT in a pediatric patient and would prefer to give 3DCRT with proper dose coverage unless a critical OAR necessitates it to be given IMRT.

2) Is it entirely justified in Indian scenario to worry about the risk of secondary cancers at all? I mean much of the blame goes to Radiation. Is it true that ipso facto patients with primary cancers are "more prone" for secondary cancers? Does radiation cause the "unmasking effect"? I don't have any answers to it but just food for thought.

3) I get the point about Brachytherapy and yes theoretically it sounds improbable. But then it would not be ethically correct to have "case control study". However, it could be a retrospective review as done in SEER reviews although they have not specifically mentioned about the patients undergoing brachy.

4) Any insight in the IGRT question? I haven't been able to get that reliably.

@ Santam Sir. The link to the "war of words". Sounds interesting to see tow giants fight it out with arguments and counter arguments! Unfortunately, video ports in Ubuntu doesn't work in Opera :-( But works great in FF. If Ubuntu is your favoured distro check out OMG Ubuntu website (http://www.omgubuntu.co.uk/) for inside scoops. Check out the new ad videos on upcoming version and you'd love the new Unity interface.

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Reality is merely a persistent illusion

Re: Risk of Secondary Cancers

Santam Chakraborty 23 Aug 2010 19:35

Abhishek good points about the dilemmas and yes the questions are worth pondering. My personal two cents - if u need concave doses/ dose escalation IMRT is way to go. Worrying about radiation induced cancers is moot if patient fails to survive. In pediatric population caution is justified but then again the cost in terms of late toxicity may be much more relevant to the patient. What is the need of the hour ? In absence of trials as Andrew says collection of data in a systematic way across the patient population and publication (with a semantics based database esp. for pediatric malignancies. Since we have large consortiums dedicated to treating pediatric tumors we shud have no problems in this respect. I am sure most savy pediatric radiation oncologists are maintaining such databases actively.
Now coming to question of a case control or retrospective study - for the former what will be ur control arm as I asked ? Retrospective studies suffer from too many biases and it will be impossible to dissect out the exact impact of brachy.
That said two things abhishek :
Even if brachy had increased the risk of second cancers in cervix 3 times more over EBRT alone I will still be using it for the simple reason u cant cure cervix with RT without brachy.
The area of high dose with brachy will be probably a less area of concern for the simple reason that cells in the area which undergo a potential mutation are likely to die out too - more likely its those areas of bladder which are receiving a lower dose comparatively that are comparatively likely to develop a RIM. And its these areas that would be treated by EBRT too - so u are stuck.
Another thing here is the fact that pinpointing an area where RIM develops and correlating that with dose distributions delivered a decade ago with the post RT changes superimposed is likely to be an exercise in futility.

My personal opinion on this whole rigmarole of 2nd cancers is In a country like India where we cant even cure 20% of our patients we should not talk of 2nd cancers before increasing that proportion to 50 -60%. If you see carefully the entire concern about 2nd cancers come to fore once the patient survives in the first place - first let us achieve that and if IMRT and CBCT can allow that I see no reason why we should not use them.

See this on how we should approach this problem for the future : http://jnci.oxfordjournals.org/cgi/content/full/98/1/15#TBL1

A small study on a closely related topic http://www.oncozone.net/uploads/pdf/000225.pdf
Infact abhishek if a study has to be done on this issue that weather the increased dose with BRT is responsible for increased cancers due to the local high dose it has to be with prostate where we have a cohort of patients who post treatment with EBRT/BRT/Surgery/Followup will have long term survival and good bladder surveillance. This is one patient group where the study u want can be done.

P.P.S What is the exact magnitude of this increased risk ? 35 more patients 10000 patients treated and followed more than 5 years .. :-). And I am a KDE guy more than the gnome of buntu.

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Last edited on 23 Aug 2010 19:39 by Santam Chakraborty Show more

Re: Risk of Secondary Cancers

radtuxabhishek 24 Aug 2010 08:29

@ Santam Sir.

This is the "reality" that we have to face here. Cancer survivors (or even those who get adequate access to a proper health care) are minuscule to achieve "significant proportions". But the write up in JNCI you linked, is very much relevant to the present question here. We simply don't have enough data because of heterogeneity; any "controlled trial" would be impossible ethically.

Yet, cancer is multi-factorial which means that any one "cause of secondary cancers" would be ruled out. Unfortunately, that seems to be recurring theme of most of Pediatric Oncologists where they crow about "secondary cancers" and "harmful effects of radiation" that it is difficult to counter them on basis of solid evidence.

In the best case scenario, this could be well of "theoretical interest" and reliance on "estimated datasets" by ICRP and UNSCEAR.

I haven't been able to access the guidelines brought out by AERB (including it's recommendations for India) anywhere. Any link?

As for Prostate, yes. But perhaps the magnitude of cases may not be justified to say that "radiation causes secondary cancers"! For that I would need to know the "bare minimum threshold" for cancer induction! Don't want a burnt bladder or an old man with a fistula just because the dose was exceeded.

On the sidelines, KDE is awesome with it's newer release 4.5 and where plasma widgets have matured to a different level of experience now. I use Compiz Fusion to jazz up my desktop so I don't notice it's absence really!

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Reality is merely a persistent illusion

Re: Risk of Secondary Cancers

radtuxabhishek 31 Aug 2010 02:45

Just to refresh this thread; although not related to "secondary cancers" but the best estimates of doses to critical organs reviewed from retrospective studies are prone for errors and biases.

Here is the link to the write up on JCO and subsequent letter to the editor which lays out clearly the issues discussed above.
http://jco.ascopubs.org/content/28/8/1308.abstract?ijkey=615c291bd3ecc627efc55bcff5627ca969eeb102&keytype2=tf_ipsecsha

Letter to editor:
http://jco.ascopubs.org/content/28/25/e436.short?rss=1#ref-1

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Reality is merely a persistent illusion