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One of the oft-cited arguments against IMRT is that it can increase the chance of developing a second malignancy. However one of the articles in the articles in press section of the red journal brings a provocative finding to fore.
The article is Galloway TJ, Indelicato DJ, Amdur RJ, Morris CG, Swanson EL, Marcus RB. Analysis of Dose at the Site of Second Tumor Formation After Radiotherapy to the Central Nervous System. International Journal of Radiation Oncology*Biology*Physics [Internet]. [cited 21:21:10];In Press, Corrected Proof. Available from: http://www.sciencedirect.com/science/article/B6T7X-51Y2SRB-D/2/6a92762a3b61b3b630195ecc07b2342e
P.S. If you need the full text drop in an email to contact.isocentre at gmail dot com with the JC1 in subject line and we will tell you where to get the pdf from. Of course you have to be a member for that to happen.
The salient features of the article:
- 370 consecutive patients with median FU of 20.4 years (median age 8.9 months)
- 16 developed a Second brain tumor
- Only two tumors - one nasal sarcoma and one thyroid occured outside the brain
- Radiation details:
- 8 patients CSI
- 4 patients WBRT
- 4 patients partial brain RT
- SMN location:
- 2 occurred in volumes receiving dose > 45 Gy
- 1 occurred in volume receiving < 20 Gy
- Rest in region receiving moderate dose 20 - 36 Gy
While the study is limited by the number of patients and by the fact that the field descriptions of the patients who did not go on to develop a cancer (26% were treated for CSI / WBRT ALL or AML). So while the population with the cancer is primarily comprised of patients receiving WBRT and CSI it is difficult to make a comparison with the cohort who did not develop a SMN in terms of the brain dose.
However what is important nonetheless is in the whole cohort only one patient developed a tumor distant from the beam at thyroid. Excluding this patient all patients developed cancers at region receiving > 20 Gy. Even accounting for the fact that all these are brain tumor patients, it stands to reason that if we can reduce the volume of brain receiving 20 - 36 Gy we can expect a reduction in the risk of SMN. This coupled with the advantages of IMRT in terms of reduced morbidity and a potentially better control secondary to dose escalation can shift the balance in favour of IMRT. This is more so in limited brain tumor treatments where IMRT can certainly spare a larger volume of the brain from the moderate dose level w.r.t 3DCRT which is the standard treatment planning modality today (even better sparing will be achived if we are considering a parallel opposed configuration as standard).
When patient population includes patients treated over 40 years, 1963 to 2006, we have to accommodate guestimates… the larger proportion of volumes receiving moderate doses can be well attributed to traditional clinically planned 2-3 flds arrangement.
actually i agree that major relevance of this paper is the extrapolation of the hypothesis/ conclusion to other sites viz. abdomen, pelvis etc.
Another interesting or confusing part in this paper was "The median potential follow-up was deļ¬ned according
to the hypothetical situation of 100% survival at analysis with all follow-up data available; it was, effectively, the upper bound of how much follow-up could be achieved at the initiation of the project. The intent of thiswas to give the reader a complete picture of how much follow-up data were not available owing to death and patients lost to follow-up" if anyone can throw some light on this….
Although I am not 100% clear on this .. what they mean by this passage is that they assumed all patients were alive at the time of analysis irrespective of the outcome. How this helps the analysis I am not sure as there is really not much actuarial analysis given in the paper.
Why is it that most meningiomas occurred after WBRT in the frontal lobe ?
When dose to a region is at best a guestimate.. their conclusions should be viewed with a pinch of salt…
And it would be worthwhile assessing the risk-benefit ratio before advocating avoidance of WBRT in all pediatric leukemia cases.
The volume of brain exposed to low dose and high dose is small for the group of patients in this study…and is maximum for the moderate dose range. So is it just probability ?
In patients planned for WBRT, can IMRT offer any reduction in SMN… i guess not
Where as in patients for partial brain irradiation, IMRT is potentially useful, when we can reduce the moderate dose region, while not substantially increasing the low dose region..
Good points Arun,
Actually if you see the study there are some crucial points:
thanks santam for initiating this discussion!
The paper speaks abt treating CNS, which is definitely a peculiar tissue. I agree that they should have discussed other adverse events also viz. drug (chemotherapy) induced complications, but probably that would hav drifted them from the original topic.
The other important thing which has not been addressed/correlated is age at which the patients (who developed SMN)recd RT. The median age of these patients was definitely lesser than that of total population (7.2 vs 8.1). If treating a fully developed mature brain/ CNS has lesser rates of developing SMN, the protocols can be decided accordingly.
Coming to SMN in thyroid, it can sometimes come in junction of CSI portal n this structure being mobile with swallowing, the actual dose recd by this gland might be different from wat is quoted.
I agree with u that IMRT can definitely help in reducing moderate dose areas not only in brain but also in CSI, where doses to heart, bowel, liver etc were matter of concern n fetish t decrease low dose areas left us with limited beam arrangements!!!
Hi Suruchi,
The first thought that came to my mind after reading this article was that the superior dosimetry and better control of the moderate dose region with IMRT coupled with something Jyotirup has published on (i.e. using a lead shield to protect non irradiated regions from stray leakage radiation) can go a long way in reducing the dose from IMRT. In addition leakage radiation can be cut off more by improving the head design. Given these improvements further reductions in SMN incidence can be realised.
Please comment on your thoughts on this topic above.
Santam, in the description it has been mentioned that the SMN's have happened in the area receiving greater than 20 Gy. So how would reducing leakage radiation reduce SMN.
Would like to receive the original article.
Regards.
Hi Harsha,
Enough literature now exists that states even low level radiation exposure can cause SMN. The importance of this article was highlighting how important the moderate dose levels were. While IMRT can reduce the moderate dose region, leakage radiation exposure is more simply as a function of time and increased MUs required. Going by the ALARA principle anything that can reduce unecessary radiation exposure is good.