The Effect of Nonmalignant Systemic Disease on Tolerance to Radiation Therapy

Abstract

Purpose. Some patients with nonmalignant systemic diseases, like collagen vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each of these disease processes are different, they share a common microvessel pathology that is potentially exacerbated by radiotherapy. This article reviews and evaluates available data examining the effects of these benign disease processes on radiation tolerance.Methods. We conducted a thorough review of the Anglo-American medical literature from 1960 to 2001 on the effects of radiotherapy on CVD, hypertension, diabetes mellitus, and IBD.Results. Fifteen studies were identified that examined the effects of radiation therapy for cancer in patients with CVDs. Thirteen of 15 studies documented greater occurrences of acute and late toxicities (range 7%-100%). Higher rates of complications were noted especially for nonrheumatoid arthritis CVDs. Nine studies evaluated the effects of hypertension and diabetes on radiation tolerance. All nine studies documented higher rates of late toxicities than in a "control" group (range 34%-100%). When patients had both diabetes and hypertension, the risk of late toxicities was even higher. Six studies examined radiation tolerance of patients with IBD irradiated to the abdomen and pelvis. Five of these six studies showed greater occurrences of acute and late toxicities for patients with IBD, even with precautionary measures like reduced fraction size and volume and patient immobilization (13%-29%).Conclusion. The majority of published studies documented lower radiation tolerance for patients who have CVD, diabetes mellitus, hypertension, and IBD. This may reflect a publication bias, as the majority of these studies are retrospective with small numbers of patients and use different scoring scales for complications. These factors may contribute to an overestimation of true radiationinduced morbidity. Although the paucity of data makes precise estimates difficult, a subset of patients, in particular, those with active CVD, IBD, or a combination of uncontrolled hypertension with type I diabetes, is likely to be at higher risk. Future prospective trials need to document these disease entities when reporting treatmentrelated complications and also must monitor toxicities associated with quiescent versus active IBD and CVD, type I versus type II diabetes, and levels of hypertension (controlled versus uncontrolled) matched for radiationspecific treatment sites, field size, fractionation, and total dose.

Prospective evaluation of weekly concomitant tumor bed boost with three-week hypofractionated whole breast irradiation in early breast cancer

“…Diabetes mellitus was the only variable in this current study identified as a statistically significant predictor of acute skin toxicity on univariable (p<0.001) and multivariable (p=0.003, OR 95%CI = 5.00-30.82) analyses, similar to what has been observed in some other trials [38,39]. In contrast, other groups have reported no significant correlation between diabetes mellitus and acute skin toxicity [29].…”

Toxicity of radiotherapy in patients with collagen vascular disease

“…Morris and Powell 11 reported that severe late effects were associated with CVD other than RA, a finding that was also supported by a meta-analysis by Chon and Loeffler. 12 Other studies suggest that a diagnosis of scleroderma 13,14 or lupus 15 may increase the risk of RTassociated toxicity. However, 2 separate matched control studies failed to observe any increased risk of acute or late complications in patients with CVD versus patients without CVD.…”

“…[1][2][3][4][5][6][7][8] However, 2 separate matched control studies failed to observe any increased risk of acute or late complications in patients with CVD versus patients without CVD. 9,10 Other publications suggested that patients with nonrheumatoid arthritis CVD, 11,12 or patients with specific subtypes of CVD, may be at increased toxicity risk. [13][14][15] Further complicating the issue is the finding that some commonly prescribed medications, many of which are used in patients with CVD, may alter the radiation toxicity profile.…”

Role of radiation therapy in patients with a diagnosis of both systemic lupus erythematosus and cancer

“…Even within a group of identically treated patients, large variability exists in both the incidence and severity of radiation toxicity, partly the result of the random nature of radiation-induced cell mortality and the variability in intrinsic cellular radiosensitivity among individuals. It is also due to certain cofactors, such as age; hemoglobin level; smoking habits; and the presence of diabetes mellitus, hypertension, or inflammatory bowel disease (25,26). Therefore, particularly in women with both a diagnosis of SLE and breast cancer, RT with curative intent could be prescribed more often to those who wish to avoid a complete mastectomy.…”

“…Prospective, randomized controlled trials have shown that in patients with operable breast cancer, the outcome after BCS followed by radiation was equivalent to that of mastectomy with respect to local and distant recurrence, as well as overall survival (28). Currently, the recommended radiotherapy technique includes treatment of the entire breast with tangential opposed fields using Cobalt 60 beam or X-rays (26). Acute skin reactions during RT of the breast occur in ϳ50% of the cases, and may include brisk erythema to confluent moist desquamation (29).…”