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BLOG: May 2009
Late health effects of toxicity
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POST-TREATMENT
CANCER INCIDENCE IN PEDIATRIC HODGKIN'S PATIENTS |
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MALIGNANCY |
INCIDENCE |
RISK INCREASE |
20-YEAR |
30-YEAR |
All cancers |
143 (10.4) |
18.5 |
10.6 |
26.3 |
Leukemia |
27 (2) |
174.8 |
2.1 |
2.1 |
Non-Hodgkin's |
7 (0.5) |
11.7 |
1.5 |
1.5 |
Solid tumors |
109 (7.9) |
18.5 |
7.3 |
23.5 |
Breast (female) |
39 (2.8) |
55.5 |
5.6 |
16.9 |
Thyroid |
19 (1.4) |
36.4 |
1.9 |
4.4 |
Bone |
8 (0.6) |
37.1 |
0.5 |
0.8 |
Colorectal |
8 (0.6) |
36.4 |
0.4 |
2.4 |
Gastric |
3 (0.2) |
63.9 |
0.3 |
0.6 |
Lung |
4 (0.3) |
27.3 |
0.1 |
2.1 |
Risk ratio to expected (general population based) incidence was 79 times higher for any leukemia, and 321 for AML (acute myeloid leukemia) and MDS (myelodysplastic syndrome, blood disorder that can escalate to leukemia) combined. Cumulative 20- and 30-year incidence indicate that some form of post-treatment cancer, like leukemia and lymphomas, are mainly limited to the first 15-20 years following the treatment. Most other cancer forms
keep plaguing patient
population at an increasing rate as far as
30 years after treatment, and beyond.
Premature deaths from cardiac diseases resulting from cardiac toxicity of the therapy are the next most frequent "other cause" of premature death in pediatric Hodgkin's patients. Cardiac diseases include pericarditis, valvular defects and coronary artery disease. Conventional Hodgkin's treatment's cardiotoxicity has been associated with chemotherapy agents vinca alkaloids, alkylating agents and anthracyclines (especially doxorubiein), as well as radiotherapy - mantle field radiation, and high-dose mediastinal (mid-chest) radiation.
So, what does the big picture look like, with these major risks combined? You are not likely to get straight answer to that question, if you ask those who should know it and fully inform you. Government sources, like the National Cancer Institute, do mention side effects, but rarely specify the risks. Instead, they use general terms like "increased risk of" or, occasionally, "significantly increased risk".
How much of a risk that implies? My guess is as good as yours.
What you can hear from a doctor are also generalized phrases, like "it depends", "the success - some even use word 'cure' - rate is 80-90%", "it is highly curable malignancy" (with conventional treatment), "serious side effects are rare, and significantly reduced with newer therapies", or alike.
The reality of it - as you already suspect - is not nearly as rosy. After all, these treatments soak the body with toxins and/or radiation strong enough to kill cancer cells. And we all know how tough cookies they are. While Daniel may have had 85-90% chance of being alive in 5 years, the chances that he'll be also doing well after treatment are considerably lower. And the more we go beyond 10-year period,
the more side effects of poisoning the body start surfacing.
They can be very serious and, not seldom, they do cause premature death.
But if you want to know more specifically to what extent,
you have to do your own homework.
Part of the problem in obtaining straight, complete information on post-treatment mortality and morbidity in children conventionally treated for Hodgkin's is that results vary from one Hodgkin's study to another, sometimes significantly. Due to different patient populations (i.e. proportion of favorable vs. unfavorable cases), criteria, procedures and designs, studies most often are not directly comparable.
A quick digression to explain terms "favorable" and "unfavorable": Favorable prognosis in Hodgkin lymphoma is limited to IA, IIA stages, where A stands for "asymptomatic". Unfavorable is for any stage III and IV (metastatic), and for stages I and II with B, E or X annotation, where B stands for the defined set of symptoms (i.e. symptomatic disease), E for extension to a single adjacent extralymphatic organ, and X for bulky disease.
Also, unfavorable prognostic factors are erythrocyte sedimentation rate ESR≥40mm, hemoglobin level Hb<11g/dL, total leukocyte count TLC>13,500, male sex and less than 70% response to the first two chemo cycles (criteria for hemoglobin level and ESR vary somewhat).
Also, the overall efficacy and safety of conventional Hodgkin's therapy has improved, particularly with respect to the period preceding 1960s, and somewhat less from the 1980s on, so that older or mixed data is not representative of the current efficacy/safety level. But plenty of data is available, and it can certainly can be used to create a big picture of the overall efficacy and safety of the conventional - should we say, "law enforced" - Hodgkin's treatment. So let's do it.
In order to keep it simple, only the two most important outcomes are addressed: (1) overall survival rate, and (2) quality of life.
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