Thrombin generation as a predictor of radiotherapy induced skin erythema.

BACKGROUND AND PURPOSE: Biological mechanisms underlying radiation induced erythema remain largely unknown, with no simple way to accurately predict or prevent extreme cases. Based on the recent findings in patients suffering from chronic urticaria, we sought to determine if similar mechanisms of hypercoagulation contributed to comparable skin reactions during radiotherapy. MATERIALS AND METHODS: Plasma levels of prothrombin factor 1+2 (F1+2), D-dimers and plasminogen activator inhibitor-1 (Pai-1) were tested in 32 women undergoing irradiation following breast conserving surgery for early breast cancer. Reflectance spectrophotometry was used to objectively assess erythema throughout the treatment by measuring the amount of light reflected from the skin surface as a function of wavelength. Correlations between peak levels of erythema and plasma biomarkers were then assessed. RESULTS: Individual peak reflectance readings generally occurred between day 29 of treatment and 2 weeks post radiotherapy, and represented a median increase of 66% (range: 11-146%; p<0.001) from baseline. Peak reflectance correlated with F1+2 and Pai-1 levels measured both at baseline and day 29 of treatment, and multivariate analysis indicated that these two baseline measurements were the best predictors of peak reflectance, accounting for 59% of the variability in erythema (p=0.000004). CONCLUSIONS: Patients with signs of intravascular thrombin generation are at higher risk of radiotherapy-induced skin reactions, providing a new therapeutic avenue for possibly predicting and preventing this side effect of cancer treatment.

Breast edema in patients undergoing breast-conserving treatment for breast cancer: assessment via high frequency ultrasound.

To identify factors that can influence breast edema in women undergoing breast-conserving therapy. Breast edema was assessed clinically and via high frequency ultrasound (HFUS) prior to, during and following radiotherapy. Fifty-four women were assessed. Breast edema was present prior to radiotherapy in patients who had undergone level 2 node dissection or had wound infection after sentinel node dissection. Edema increased during and after radiotherapy and peaked at 4-6 months. The time course of breast edema was related to the extent of nodal dissection, postoperative wound infection and regional radiotherapy. HFUS prior to irradiation was found to be no better than clinical assessment in predicting prolonged parenchymal breast edema but was significantly better at the end of irradiation. Breast edema levels are minimal in patients who do not undergo axillary node dissection or have an uncomplicated sentinel node dissection. Most edema is due to compromise of the draining lymphatics, which relates largely to the extent of axillary node dissection. HFUS appears to be a useful in the research setting in quantifying the effect of techniques that aim to reduce complications such as edema.

'When measurements mean action' decision models for portal image review to eliminate systematic set-up errors.

The aim of the present paper is to evaluate how the use of decision models in the review of portal images can eliminate systematic set-up errors during conformal therapy. Sixteen patients undergoing four-field irradiation of prostate cancer have had daily portal images obtained during the first two treatment weeks and weekly thereafter. The magnitude of random and systematic variations has been calculated by comparison of the portal image with the reference simulator images using the two-dimensional decision model embodied in the Hotelling's evaluation process (HEP). Random day-to-day set-up variation was small in this group of patients. Systematic errors were, however, common. In 15 of 16 patients, one or more errors of >2 mm were diagnosed at some stage during treatment. Sixteen of the 23 errors were between 2 and 4 mm. Although there were examples of oversensitivity of the HEP in three cases, and one instance of undersensitivity, the HEP proved highly sensitive to the small (2-4 mm) systematic errors that must be eliminated during high precision radiotherapy. The HEP has proven valuable in diagnosing very small (<4 mm) errors. When combined with the potential for rapid diagnosis of larger (>4 mm) systematic errors using one-dimensional decision models, HEP can eliminate the majority of systematic errors during the first 2 treatment weeks.

Effect of surgery on normal tissue toxicity in patients treated with accelerated radiotherapy.

The aim of this study was to assess the effect of surgery on normal tissue toxicity in head and neck cancer patients treated with accelerated radiotherapy. Toxicity data from two trials of accelerated radiotherapy were compared. The first group was taken from a phase III trial of definitive radiotherapy and the second group from a phase II trial of postoperative radiotherapy. The general eligibility criteria (apart from surgery), data collection and radiotherapy details for both trials were similar. The definitive group included 172 eligible patients and the postoperative group 52 eligible patients. At 3 weeks into treatment, by which time the dose and rate of dose accumulation were identical, there was no difference in acute toxicity. Analysis of late toxicity showed greater subcutaneous fibrosis in the postoperative group.