Correlation between DNA damage responses of skin to a test dose of radiation and late adverse effects of earlier breast radiotherapy.

AIM: To correlate residual double strand breaks (DSB) 24h after 4Gy test doses to skin in vivo and to lymphocytes in vitro with adverse effects of earlier breast radiotherapy (RT). PATIENTS AND METHODS: Patients given whole breast RT ⩾5years earlier were identified on the basis of moderate/marked or minimal/no adverse effects despite the absence ('RT-Sensitive', RT-S) or presence ('RT-Resistant', RT-R) of variables predisposing to late adverse effects. Residual DSB were quantified in skin 24h after a 4Gy test dose in 20 RT-S and 15 RT-R patients. Residual DSB were quantified in lymphocytes irradiated with 4Gy in vitro in 30/35 patients. RESULTS: Mean foci per dermal fibroblast were 3.29 (RT-S) vs 2.80 (RT-R) (p=0.137); 3.28 (RT-S) vs 2.60 (RT-R) in endothelium (p=0.158); 2.50 (RT-S) vs 2.41 (RT-R) in suprabasal keratinocytes (p=0.633); 2.70 (RT-S) vs 2.35 (RT-R) in basal epidermis (p=0.419); 12.1 (RT-S) vs 10.3 (RT-R) in lymphocytes (p=0.0052). CONCLUSIONS: Residual DSB in skin following a 4Gy dose were not significantly associated with risk of late adverse effects of breast radiotherapy, although exploratory analyses suggested an association in severely affected individuals. By contrast, a significant association was detected based on the in vitro response of lymphocytes.

Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin.

PURPOSE: The aim of this study was to compare inter-individual and inter-cell type variation in DNA double-strand break (DSB) repair following in vivo irradiation of human skin. MATERIALS AND METHODS: Duplicate 4mm core biopsies of irradiated and unirradiated skin were collected from 35 patients 24h after 4Gy exposure using 6MeV electrons. Residual DSB were quantified by scoring 53BP1 foci in dermal fibroblasts, endothelial cells, superficial keratinocytes and basal epidermal cells. RESULTS: Coefficients of inter-individual variation for levels of residual foci 24h after in vivo irradiation of skin were 39.9% in dermal fibroblasts, 44.3% in endothelial cells, 32.9% in superficial keratinocytes and 46.4% in basal epidermal cells (p<0.001, ANOVA). In contrast, the coefficient of inter-cell type variation for residual foci levels was only 11.3% in human skin between the different epidermal and dermal cells (p=0.034, ANOVA). Foci levels between the different skin cell types were correlated (Pearson's R=0.855-0.955, p<0.001). CONCLUSIONS: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin.

Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: acute toxicity results of a phase I study.

BACKGROUND AND PURPOSE: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. METHODS: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. RESULTS: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G< or =1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. CONCLUSIONS: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects.

Fractionated stereotactic conformal radiotherapy following conservative surgery in the control of craniopharyngiomas.

PURPOSE: To describe the technique and results of stereotactically guided conformal radiotherapy (SCRT) in patients with craniopharyngioma after conservative surgery. METHODS AND MATERIALS: Thirty-nine patients with craniopharyngioma aged 3-68 years (median age 18 years) were treated with SCRT between June 1994 and January 2003. All patients were referred for radiotherapy after undergoing one or more surgical procedures. Treatment was delivered in 30-33 daily fractions over 6-6.5 weeks to a total dose of 50 Gy using 6 MV photons. Outcome was assessed prospectively. RESULTS: At a median follow-up of 40 months (range 3-88 months) the 3- and 5-year progression-free survival (PFS) was 97% and 92%, and 3- and 5-year survival 100%. Two patients required further debulking surgery for progressive disease 8 and 41 months after radiotherapy. Twelve patients (30%) had acute clinical deterioration due to cystic enlargement of craniopharyngioma following SCRT and required cyst aspiration. One patient with severe visual impairment prior to radiotherapy had visual deterioration following SCRT. Seven out of 10 patients with a normal pituitary function before SCRT had no endocrine deficits following treatment. CONCLUSION: SCRT as a high-precision technique of localized RT is suitable for the treatment of incompletely excised craniopharyngioma. The local control, toxicity and survival outcomes are comparable to results reported following conventional external beam RT. Longer follow-up is required to assess long-term efficacy and toxicity, particularly in terms of potential reduction in treatment related late toxicity.