return to: Cancer Care Principles

see also: Case Example Sequence of Response to External Beam Irradiation for T1 Glottic SCC

Note: Reviewed March 2024

(irradiation, radiotherapy, radiation malignancy, radioactive)  

protocol by Hoffman H, Buatti J, Pagedar N, Anderson C, Funk G

Ionizing radiation can induce cancers in humans (Mole 1975). The increased incidence of cancer arising in atomic bomb survivors, in workers handing radioactive substances, and among those treated with irradiation is well established (Amemiya et al 2005). Additional interest in the carcinogenic effect of diagnostic X-rays has received additional emphasis over the past decade (Gonzalez et al 2004). Despite these concerns, as recently as 1990 the following assertion has been published: "the potential of radiation-induced cancers should not be a factor in the selection of treatment for patients with cancer." (Parker R 1990).

It may be difficult to distinguish between radiation-induced cancers, late recurrences after radiation and second primary tumors that develop despite radiation. The definition of a radiation -induced cancer was established by Cahan in 1948  and specifies that a radiation induced cancer must occur within the treatment field, have a significant latency and be a different kind of cancer than the original type (Cahan et al 1948). The high frequency of second primary cancers appearing in patients with squamous cell carcinoma of the head and neck confounds analysis in this region largely due to field cancerization, often of a similar type. Although higher rates have been reported in the past, a study from 1999 identified second malignancies to develop at a rate of 2.3% per year in the respiratory and upper tracts of 1609 patients with early stage squamous cell carcinoma of the head and neck (Leon et al 1999).

Analysis by Parker and Enstrom (1988) suggested the risk of developing a second cancer for head and neck cancer patients treated surgically was 2.2/1000 person years compared to 2.9/1000 person years among those treated with radiation. The risk of a second cancer has been shown to increase with time and radiation dose – with the latency before appearance of a second cancer differing between organs. The risk of cancer of the rectum and bladder starts to increase 10 years after exposure, whereas leukaemia develops within 2-3 years after exposure with a peak at 5 to 6 years (Amemiya et al 2005).

Amemiya et al (2005) identified through a comparative review of patients treated with radiation for lymphoma and squamous cell carcinoma of the H+N that all second primary tumors developing in the lymphoma group (all occurring with a latency of greater than 8 years) were squamous cell carcinoma. This finding refutes the previously held concept that radiation-induced cancers are dominated by sarcomas. These investigators identified the 10-year probability of developing a radiation-induced cancer to be 0.8% in the lymphoma group and 1.6% in the early stage squamous cell carcinoma group. Amemiya et al conclude that the advantage of radiation therapy appears great enough to compensate for the risk of radiation--induced cancer. They identify that "the probability of radiation-induced cancers should not be a factor in the selection of treatment for patients with early stage head and neck cancers at this time." Amemiya et al, in determining this conclusion, contend that most radiation induced cancers can be detected when small and can be cured with surgical excision if close follow-up permits early identification.

Amemiya et al. do not focus on young age in their discussion of the risk of radiation carcinogenesis other than to identify that close follow-up of this younger group will permit early detection with higher chance of cure of radiation-induced cancers. They do identify that most cancer patients are over 60 years - with an average life expectancy following successful treatment in the 17- year range. They conclude that in this older patient group the latency period before developing a radiation induced cancer is nearly the same as their life expectancy.

We (co-authors listed above at the U of Iowa) feel the decisions made regarding use of radiation are difficult and require a multi-disciplinary approach focused on the desires of an informed patient. In general, younger patients (<40 years of age) are steered toward a treatment approach avoiding irradiation. This counseling addresses not only the small (but real) risk of radiation-induced malignancy, but also progressive fibrosis and long term changes that continue to develop across decades in the face of radiation-induced compromise of the microcirculation. Targeting treatment principles toward patients groups determined by age may not be as relevant as a classification that includes their co-morbidities – in addressing ‘physiologic age’. All decisions about the relative merits of radiation versus surgery warrant attention to survival analysis, quality of life, and the long term effects of treatment. The impact of contemporary radiation treatment on the development of second malignancies after more than a decade remains uncertain.

References

Mole RH. Ionizing radiationas a carcinomagen: practical questions and academic pursuits. Br J Radiol 1975;48:157-169

Amemiya K, Shibuay H, Yoshimura R and Okada N: The risk of radiation --induced cancer in patients with squamous cell carcinoma of the head and neck and its results of treatment. The British Journal of Rdiology, 78 (2005), 1028-1033

Gonzalez AB, Darby S. Risk of cancer from diagnostic X-rays: estimates for UK and 14 other countries. Lancet 2004;363:345-51

Leon X, Quer M, Diez S et al Second neoplasmin patients with head and neck cancer. Head Neck 1999;21:204-10

Parker RG and Enstrom JE. Second primary cancer of the head and neck following treatment of initial primary head and neck cancers. Int J Radiat Oncol Biol Phys 1988;14:561-4

Parker RG: Radiation-induced cancer as a factor in clinical decision making (the 1989 ASTRO Gold Medal address). Int J Radiat Oncol Biol Phys.#124;20Phys.International journal of radiation oncology, biology, physics.124 1990 May;18(5):993-1000

Cahan WG, Woodard HQ,Higinbotham ND, et al Sarcoma arising in irradiated bone: report of eleven cases. Cancer 1948;1:3-29