By Michael J. Katin, MD
The past is never dead; in fact, it's not even past.
William Faulkner, 1950
Lately it seems we have been experiencing a metaphorical version of trench warfare, where we get modest gains which are then just as rapidly taken away in terms of establishing the value of radiation therapy in the treatment of cancer. In last month's column we briefly celebrated the recognition that symptoms from radiation therapy for prostate cancer were in some cases less severe than for radical prostatectomy. Within only a few weeks, the media gleefully covered an article in The New England Journal of Medicine addressing the huge public health hazard of bird flu? Drug-resistant tuberculosis /? No....the huge public health hazard of....breast irradiation. ??????????
It seems that it required no fewer than16 authors (Darby,SC., Ewertz, M, McGale, P,
Bennet AM, Blom-Goldman, U, Bronnum, D, Correa, C, Cutter, D, Gagliardil, G, Gigante B, Jensen, M-B, Nisbet, A, Peto, R, Rahimi, K, Taylor, C, and Hall, P) to analyze the long-term status of 2,168 women in Sweden and Denmark who were or were not treated with radiation therapy for breast cancer between 1958 (!!!!) and 2001 (1977 and 2000 for Danish women). The news articles were immediately disseminated throughout the known world, landing into the hands of patients coming in to our offices with appropriate anguish upon being informed that "exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease."
This monthly column goes through a rigorous peer-review process, but one would expect even more intense scrutiny of a publication accepted by The New England Journal of Medicine, but perhaps this is not the case. Maybe it's too difficult when an issue has to be produced every week. Then, on top of that, they have an editorial by Javid Moslehi from the Survivorship Program at Dana-Farber Cancer Institute. The CPC this week involves a woman with carcinoma-in-situ of the breast who receives radiation therapy!!!! Is this a vendetta?
I have a soft spot in my heart (maybe not a good cliche to use under the circumstances) for reports that analyze cardiac effects of archaic radiation therapy techniques ever since publication of the landmark article
by Gottdiener, Katin, et al. in 1983 in....The New England Journal of Medicine. How about that! We reported late cardiac effects in patients treated for Hodgkin's disease using primitive (such as AP only) treatment techniques which no longer in use even by 1983. I was distressed that the Nobel Prize Committee has totally ignored this work and somewhat less so that the current article did not use it as a reference. Despite having been disrespected to the max, I still want to be fair to the authors.
The American Society of Radiation Oncology had a rapid response to the article by Darby et al., providing four talking points for members to use to answer questions from patients and media. These "four" talking points were essentially the same point restated four times, i.e., that, yes, we probably did give too much dosage to the heart years ago, but we don't do that anymore, and even if we did, the benefits would outweigh the risk...without mentioning that the New England Journal article didn't deal with the relative benefit/risk question at all.
It might have to fall to the private sector, again, to modestly raise a few questions about some of the shortcomings of this article. Maybe about seven to start with.
Although these women were treated between 1958 and 2001, it was not described how many were treated in each time period, let along what techniques were used (allegedly doses were able to be calculated, which would have been a remarkable accomplishment from reviewing records from the 1950's and 60's). Second, the true denominator was not established—they reported on 963 women with major coronary events and then selected out 1,205 controls from an unknown number of women who had been diagnosed with breast cancer in that time period but who did not receive radiation therapy (a mystery that there were 337 out of 1205 who had breast-conserving surgery without radiation therapy!). Third, a minority of the women had their smoking history established, but on top of that there were more non-smokers in the control group. Fourth, there was no comment on the types of adjuvant chemotherapy and its possible role in survival and complications. Fifth, there was no distinction described as to late cardiac effects in patients who received chest wall rather than intact breast irradiation.. Sixth, a much smaller number of controls had a pre-existing history of ischemic heart disease! Seventh, there was no recognition that women who had longer follow-up histories also were more likely to have been treated with less sophisticated techniques, also making accurate dose calculations less probable and making comparisons less appropriate. Eighth, there was no recognition of how many patients who did or did not receive radiation therapy had died and were not able to be assessed for their cardiac status at 5, 10 or 20 years. Did the treated patients live longer, allowing them to develop complications of aging, or did untreated patients die sooner? Ninth.....actually, I've already overshot. You get the idea.
An interesting associate topic is whether patients who have been treated for cancer are followed regularly for non-cancer related problems. A report in the March 20, 2013, issue of the Journal of Clinical Oncology used Surveillance, Epidemiology, and End Results (SEER) Medicare-linked data to follow the course of 8,661 cancer survivors and 17,322 controls, selected from patients who lived in 12 different SEER regions. Despite this large number of patients, it required 8 rather than 16 authors. Patients had been diagnosed in 2004 and had survived at least three years.
It was encouraging to know that patients treated for loco-regional breast cancer were followed as closely as those who had not been treated for cancer, in terms of evaluating nine chronic and nineteen acute condition quality indicators. Interestingly, patients with prostate cancer were less likely than controls to have quality acute care, and patient with colorectal cancer less likely to achieve both chronic and acute quality standards. As with many such reports, however, it was not possible to show a survival advantage due to achieving quality measures. It would be interesting to see if there were more cardiac events in treated breast cancer patients, but this was not reported in this study.
What did we learn from all this? We learned that irradiation of normal tissue may had the potential for causing side effects and that it is logically better to use techniques that restrict the dose, as much as possible, to the area that needs to be treated. Well, we sort of already knew that for the past 100 years, but the next time Aetna or United Health tries to disallow more sophisticated planning and treatment techniques, at least we can refer to this report on Swedish/Danish antiquated therapy methods (or, preferentially, to the USA Today summary ).
We also learned that one's CV can be enhanced by writing papers on complications of medical treatments no longer in use. I am already working on several of these, for submission to
- Incidence of Infection in Leech Application for Relief of Dropsy.
- Comparison of Techniques to Reduce Morbidity from Subarachnoid Hemorrhage and Meningoencephalitis in Trepanning.
- Iron Metabolism and Lung Cancer Risk
in Patients Utilizing Iron Lungs
- Anemia: An Unexpected Complication of Humoural Balancing
- And, undoubtedly to be presented in the plenary session of the ASTRO 44th Annual Meeting:
Digital Necrosis from Radiation Exposure: Early Recognition and Intervention
EPILOGUE: After its effort to assure the public that breast irradiation is safe and wholesome, ASTRO, through its official journal, has presented to us that subclinical cardiotoxicity, detected by strain rate imaging, can be seen up to 14 months after breast irradiation. Apparently the PR clout of the International Journal of Radiation Oncology, Biology, and Physics is not equal to that of The New England Journal of Medicine, since there has not been another flurry of reports in the popular press about this. Note that it is not known that these measurements are correlated at all with any clinical sequelae. The patients in this study were, again, from Europe (Belgium, this time). . There are two conclusions to be reached from this paper. The first, as stated under "Conclusions" on the summary page, is to "encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients" The second is that when it turns out that "ALL PATIENTS IN OUR STUDY WERE TREATED WITH ANTHRACYCLINE-BASED CHEMOTHERAPY BEFORE RT," it might be reasonable for the editors to make sure that minor detail is included ANYWHERE in the abstract or summary page. Just a thought.