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Hot on the heels of the article about the "need" of radiotherapy in clinical stage I testicular seminoma, I am delighted to present to you another article epub in the Red Journal.
The article is
Koshy M, Rich SE, Mahmood U, Kwok Y. Declining Use of Radiotherapy in Stage I and II Hodgkinʼs Disease and Its Effect on Survival and Secondary Malignancies. International Journal of Radiation Oncology*Biology*Physics [Internet]. [cited 21:04:37];In Press, Corrected Proof. Available from: http://www.sciencedirect.com/science/article/B6T7X-52226TX-7/2/a692bea19235946e885d2f5ffe928227
The abstract is here
Purpose : Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin’s disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies.
Methods and Materials :The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged ≥20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends.
Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72–2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089).
Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.
What is interesting about this article is that it is dealing with a really large cohort (though only 21% had actually had a 10 year followup by the time of analysis). And what is conclusively shows is that those who did not receive RT did fare poorly in terms of both OS and CSS. There are the usual fallacies with this being a retrospective study, inadequate information about prognositic factors. However the shape of the survival curves tells us a very interesting story - the survival benefit provided by upfront radiation therapy even in these early HD patients is substaintial and sustained. This is important as it shows that its not like that in the late term patients are dying off because of radiotherapy related side effects in which case we would have seen the curves coming together as follow up progressed. Adjusting for known poor prognostic factors not giving RT in these early stage patients is associated with a 1.5 times higher risk of dying.
Why is it that the most of the randomized trials never showed this interesting result?
As an aside what may come out as a surprise to some is that the number of 2nd cancers was similar in the irradiated and non irradiated cohort - which is partly secondary to the less follow up. However we really need to ask ourselves this question - are we justified in not offering the patients a therapy that can potentially offer them a better survival just for the fear of inducing cancer in the long term?
What is the opinion of the house in this matter.
For those interested full text is available - just email us at contact dot isocentre at gmail dot com as before
Definitely a relieving paper!! The authors r well aware of the limitations of their study, but one thing which they shd hav added is the treatment n survival of the patients who developed second malignancies i.e. salvageable vs non salvalgeable!!
Even the meta-analysis (Franklin et al) quotes the same, i could not get the full paper though. They too hav reported better OAS n DFS in ES HD with CT + RT than CT alone with similar rates of secondary malignancies. However curiously they hav not reported this benefit in advanced stage HD.
But all these papers (including RCTs) hav not found any difference in incidence of secondary malignancies neither with change of chemotherapeutic drugs nor with switch over to IFRT from EFRT…. how do we explain this, is it some inherent genetic susceptibility or something else which we hav not yet focussed upon???
Hi Suruchi if you see the curves of the probability of a second neoplasm in the paper which I am reproducing below its is apparent why this is happening.
As you can see the curves seperate between 5 -10 years. That may be explained by the fact that most 2nd cancers after chemotherapy are hematological cancers typically with a latent period of this many years. RT induced cancers are building up in to 10 -15 year F/U period though and the curves are coming closer. Now one should not read too much into KM curves towards the tail as it gets affected by the smaller fu and smaller sample size under consideration at the longer FU times. Plus there is the small fact that more CCT people had died off than RT .. as also the fact that CCT patients possibly had a smaller FU.
All things said and done, the increased risk of SMN in HD is definitely related to bad genes but therapy does play a part.. of course it has to be kept in perspective that at the time of Thomas Hodgkin no one developed SMN as they died of HD itself.
Please provide your comments on this journal article reviewing the need for RT in early stage HL. Is it something we are throwing out without hard evidence?