Acute radiation-induced skin toxicity in hypofractionated vs. conventional whole-breast irradiation: An objective, randomized multicenter assessment using spectrophotometry.

PURPOSE: Radiation dermatitis represents one of the most frequent side effects in breast cancer patients undergoing adjuvant whole-breast irradiation (WBI). Whether hypofractionated WBI induces comparable or less acute radiation-induced skin reactions than conventional WBI is still not fully clarified, as randomized evidence and objective assessments are limited. The aim of this study was to objectively determine frequency and severity of acute radiation-induced skin reactions during hypofractionated vs. conventionally fractionated adjuvant WBI. METHODS: In this randomized multicenter study, a total of 140 breast cancer patients underwent either hypofractionated or conventional WBI following breast-preserving surgery. Maximum radiation dermatitis severity was assessed at completion and during follow-up by physician-assessed CTCAE v4.03 and the patient-reported RISRAS scale. Additionally, photospectrometric skin readings were performed to objectify skin color differences between both treatment arms. RESULTS: Radiation dermatitis severity was significantly lower in patients receiving hypofractionation compared with conventional fractionation (mean 1.05 vs. 1.43, p = .024). Grade 0 radiation dermatitis occurred in 21.43% vs. 4.28%, grade ≥2 in 27.14% vs. 42.91% and grade ≥3 in 0% vs. 4.34% of patients following hypofractionated and conventional WBI, respectively. Objective photospectrometric measurements (n = 4200) showed both decreased erythema severity (p = .008) and hyperpigmentation (p = .002) in the hypofractionation arm. Patients allocated to hypofractionated WBI also reported less pain (p = .006), less hyperpigmentation (p = <0.001) and less limitations of day-to-day activities (p = <0.001). CONCLUSION: Physician and patient-assessed toxicity scorings as well as objective photospectrometric skin measurements revealed that hypofractionated WBI yielded lower rates and severity of acute radiation-induced skin toxicity.

Hydrofilm Polyurethane Films Reduce Radiation Dermatitis Severity in Hypofractionated Whole-Breast Irradiation: An Objective, Intra-Patient Randomized Dual-Center Assessment.

Radiation-induced skin injury represents the most frequent side effect in breast cancer patients undergoing whole-breast irradiation (WBI). Numerous clinical studies on systemic and topical treatments for radiation dermatitis have failed to provide sustainable treatment strategies. While protective skin products such as dressings are undoubtedly the standard of care in wound care management, their utilization as preventive treatment in radiotherapy has been somewhat neglected in recent years. In this prospective, intra-patient randomized observational study, Hydrofilm polyurethane films were prophylactically applied to either the medial or lateral breast-half of 74 patients with breast cancer undergoing hypofractionated whole-breast irradiation following breast-preserving surgery. Maximum radiation dermatitis severity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 toxicity scores, photospectrometric erythema and pigmentation measurements and patient-assessed modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) scale. Phantom studies revealed a clinically negligible dose build-up of less than 0.1% with Hydrofilm. Compared to the control compartments physician-assessed radiation dermatitis severity was reduced in the hydrofilm compartments (mean 0.54 vs. 1.34; p = < 0.001). Objective photospectrometric skin measurements showed decreased erythema (p = 0.0001) and hyperpigmentation (p = 0.002) underneath Hydrofilm. Hydrofilm also completely prevented moist desquamation, and significantly reduced patients' treatment-related symptoms of itching, burning, pain, and limitations of day-to-day-activities. Significant beneficial effects were observed in terms of radiation dermatitis severity, erythema, hyperpigmentation as well as subjective treatment-related symptom experiences, while adverse reactions were rare and minor. Therefore, a prophylactic application of Hydrofilm polyurethane films can be suggested in hypofractionated WBI.

Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients.

BACKGROUND AND PURPOSE: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment. PATIENTS AND METHODS: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m(2) (n = 21) and 340 mg/m(2) (n = 18), were compared for protection against radiation induced toxicity. Total radiation dose was 60-70Gy (2Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions. RESULTS: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1-3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P = 0.007) but not by amifostine dose (P = 0.156). CONCLUSION: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.

Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?

PURPOSE: Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. PATIENTS AND METHODS: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. RESULTS: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. CONCLUSIONS: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.