Maree O'Brien

Underprediction of human skin erythema at low doses per fraction by the linear quadratic model

BACKGROUND AND PURPOSE The erythematous response of human skin to radiotherapy has proven useful for testing the predictions of the linear quadratic (LQ) model in terms of fractionation sensitivity and repair half time. No formal investigation of the response of human skin to doses less than 2 Gy per fraction has occurred. This study aims to test the validity of the LQ model for human skin at doses ranging from 0.4 to 5.2 Gy per fraction. MATERIALS AND METHODS Complete erythema reaction profiles were obtained using reflectance spectrophotometry in two patient populations: 65 patients treated palliatively with 5, 10, 12 and 20 daily treatment fractions (varying thicknesses of bolus, various body sites) and 52 patients undergoing prostatic irradiation for localised carcinoma of the prostate (no bolus, 30-32 fractions). RESULTS AND CONCLUSIONS Gender, age, site and prior sun exposure influence pre- and post-treatment erythema values independently of dose administered. Out-of-field effects were also noted. The linear quadratic model significantly underpredicted peak erythema values at doses less than 1.5 Gy per fraction. This suggests that either the conventional linear quadratic model does not apply for low doses per fraction in human skin or that erythema is not exclusively initiated by radiation damage to the basal layer. The data are potentially explained by an induced repair model.

A comparison of methods of cosmetic assessment in breast conservation treatment

Abstract The aim of this study was to compare live and photographic methods of assessing variables which can influence cosmetic outcome following breast conserving treatment. This study was undertaken in 47 patients who had previously received breast conserving surgery, radiotherapy and simultaneous chemotherapy for stage I and II breast cancer and a matched group of patients who had received surgery and radiotherapy alone. The assessment consisted of patient and spouse self-assessment, a live assessment by two trained observers and a photographic assessment by five observers, two trained and three untrained. Patients rated their outcome more favourably than their spouses, and both rated the outcomes above those of the other observers. Quantitative variables such as measurement of nipple retraction were assessed by different observers more consistently than qualitative variables such as overall perception of assessed cosmetic outcome. Upward retraction of the nipple emerged as the most powerful determinant of cosmetic outcome in the eyes of both the patient and the trained observers and was reproducibly measured by both live and photographic techniques. The distinction between post-surgical effects and post-radiation effects was more readily made by live assessment. Photographic assessment is as effective as live assessment in post-surgical cosmetic assessment. It provides reliable information about all of the factors which were important to both the patient and observers in formulating an overall cosmetic outcome score. The effects of surgery, which include nipple retraction, need to be taken into account in future trials of adjuvant therapy in which cosmesis is an important outcome measure. Stratification using upward retraction of the nipple is a possibility.

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

Normal variation in cutaneous blood content and red blood cell velocity in humans

This study was designed to determine normal variations in cutaneous blood content, red blood cell content and skin thickness in healthy human volunteers. The blood content (BC) of human skin and the velocity of red blood cells (RBV) has been comprehensively mapped over 30 anatomical sites in 28 volunteers between the age of 7 and 77 years using reflectance spectrophotometry (RFS) and laser Doppler (LD) techniques respectively. Total skin thickness, which may have a relationship with blood content, has been mapped at the same anatomical sites in six of the volunteers using two-dimensional array, 12 MHz ultrasound equipment. The major determinant of BC and RBV was found to be anatomical site. Regardless of age, gender or prior sun exposure, anatomical sites above the waist produced higher readings than below. BC and RBV were found to be dependent on age and gender at most sites with higher readings being observed in males and younger volunteers. The largest difference was seen in males under 55 years whose RFS readings above the waist were significantly higher than in older males or females of any age. Heavy prior sun exposure and skin thickness could not be demonstrated to impact on either RFS or LD readings independently of the effects of anatomical site, gender or age. In general, RFS and LD readings paralleled one another and correlated linearly at most anatomical sites. While RFS readings tended to decrease in the cranio-caudal direction, LD readings were relatively uniform across the body except for the head and groin where they were higher, and the abdomen where they were lower. The site-to-site variations in RFS readings observed in this study correspond well to capillary density variations noted in previous studies.

Acute reaction parameters for human oropharyngeal mucosa

The purpose of this study was to determine the influence of changes in dose rate over the range 0.8-240 Gy/h on acute oropharyngeal mucosal reactions in human subjects, and to estimate the values of the important parameters that influence these reactions. Sixty-one patients requiring radiotherapy to palliate incurable head and neck cancer were treated on a telecaesium unit, using opposing lateral portals to total midline doses, varying between 30 and 42 Gy in 10 daily fractions over 2 weeks, at dose rates of 0.8, 1.8, 3.0 and 240 Gy/h according to a central composite study design. The severity and time course of reactions were charted at least twice weekly for each patient, using the EORTC/RTOG acute mucosal reaction grading system. Duration of reaction at each grade was observed to provide a more sensitive reflection of effect than the proportion of patients reaching any particular reaction grade. Analysis of duration by direct and indirect methods suggest alpha/beta ratios in the range 7-10 Gy and half-time (t1/2) values in the range 0.27-0.5 h, if mono-exponential repair kinetics are assumed. The t1/2 values are short and raise the question as to whether the repair kinetics of this tissue are well described by a mono-exponential function. Further prospective studies involving multiple daily fraction treatment regimes delivered at high dose rate, in which interfraction interval is deliberately varied, are needed to find out whether the parameters derived from this project are applicable to fractionated treatment courses at high dose rate.