Non-invasive physical plasma for preventing radiation dermatitis in breast cancer: Results from an intrapatient-randomised double-blind placebo-controlled trial.

Background and Purpose: To investigate the effect of topical non-invasive physical plasma (NIPP), a volatile mix generated out of ambient air, on prevention of acute radiation dermatitis (RD) during and after whole-breast irradiation (WBI). Materials and Methods: Lateral and medial breast halves were randomised within each patient to receive either 120 s of NIPP or sham treatment daily during WBI. Standard skin care with urea lotion was applied to the whole breast. Blinded acute skin toxicity was assessed weekly for each breast half separately and included clinician- (CTCAE) and patient-reported (modified RISRAS), and objective (spectrophotometry) assessments. As an additional external control, a comparable standard of care (SoC) patient collective from a previous prospective trial was used. Results: Sixty-four patients were included. There were no significant differences between breast halves. Post-hoc comparison with a similar SoC control collective revealed OR = 0.28 (95% CI 0.11-0.76; p = 0.014) for grade ≥ 2 RD upon WBI completion, along with less hyperpigmentation (p < 0.001), oedema (p = 0.020), dry (p < 0.001) and moist desquamation (p = 0.017), pain, itching, and burning (p < 0.001 for each). Tolerability of NIPP was excellent and side effects were not observed. Conclusion: Even though there were no differences between intrapatient-randomised breast halves, the overall incidence and severity of acute radiation-induced skin toxicity were considerably lower when compared to a prospectively collected SoC cohort. Our data suggest the potential benefit of NIPP in RD prevention. A randomised trial with a physical control group is warranted to confirm these promising results (DRKS00026225).

Barrier films for the prevention of acute radiation dermatitis in breast cancer: A systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Radiation dermatitis (RD) is the most common side effect of adjuvant whole-breast or chest wall irradiation, majorly impacting quality of life in numerous patients. The use of barrier films (polyurethane dressings such as Hydrofilm® and Mepitel® film remaining on the skin for the duration of the radiation treatment) has been investigated as a prophylactic measure in several prospective trials. Here, we critically appraise the available evidence behind preventive barrier film application in the context of breast cancer treatment. METHODS: International literature was reviewed and high-quality randomised controlled trials (RCTs) were included in this meta-analysis. RESULTS: The results of 5 RCTs (663 patients; >90% Caucasian) were analysed. Overall, barrier films lead to improved clinician- and patient-reported outcomes: fewer grade ≥2 RD (11% vs. 42%; OR = 0.16; p < 0.001) and moist desquamation (2% vs. 16%; OR = 0.12; p = 0.006), as well as less patient-reported pain (standardised mean difference [SMD] -0.51; p < 0.001), itching (SMD -0.52; p = 0.001), burning (SMD -0.41; p = 0.011), and limitations in daily activities (SMD -0.20; p = 0.007). Furthermore, barrier films have a high acceptance rate among patients, as well as a favourable cost-benefit ratio. Possible side effects due to its application are mild and mostly self-limiting. Overall, there was a lack of information on the radiation treatment techniques used. CONCLUSION: The evidence presented in this meta-analysis suggests that barrier films are an excellent tool in the prevention of RD among Caucasian patients receiving whole-breast or chest wall irradiation. Its use should therefore be considered routinely in these patients.

Five-Fraction Stereotactic Radiotherapy for Brain Metastases-A Retrospective Analysis.

PURPOSE: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. METHODS: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). RESULTS: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1-56.2) months. The median age was 64.5 (34-92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8-23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1-56.2) months and significantly superior in those patients presenting with RN. CONCLUSIONS: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings.

Objective Evaluation of Risk Factors for Radiation Dermatitis in Whole-Breast Irradiation Using the Spectrophotometric L*a*b Color-Space.

Background: Radiation-induced dermatitis (RID) is frequent in breast cancer patients undergoing radiotherapy (RT). Spectrophotometry (SP) is an objective and reliable tool for assessing RID severity. Despite intensive research efforts during the past decades, no sustainable prophylactic and treatment strategies have been found. Estimation of new and reevaluation of established risk factors leading to severe RID is therefore of major importance. Methods: 142 early breast cancer patients underwent whole-breast irradiation following breast-conserving surgery. RID was evaluated by physician-assessed Common Terminology Criteria of Adverse Events (CTCAE v4.03). Spectrophotometers provided additional semi quantification of RID using the L*a*b color-space. A total of 24 patient- and treatment-related parameters as well as subjective patient-assessed symptoms were analyzed. Results: Values for a*max strongly correlated with the assessment of RID severity by physicians. Breast volume, initial darker skin, boost administration, and treatment technique were identified as risk factors for severe RID. RID severity positively correlated with the patients' perception of pain, burning, and reduction of everyday activities. Conclusions: Physician-assessed RID gradings correlate with objective SP skin measurements. Treatment technique and high breast volumes were identified as objective and significant predictors of RID. Our data provide a solid benchmark for future studies on RID with objective SP.

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.

Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy.

PURPOSE: Total body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®. MATERIAL AND METHODS: Forty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12Gy delivered in six equal fractions (2×2Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan. RESULTS: For all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76Gy=114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI>31 (minimum dose 11.31Gy=dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18Gy (range 6.4-9.5Gy). The left lung showed a median (D50) dose of 7.9Gy (range 6.7-9.3Gy). Central lung dose showed a mean dose (D50) of 5.16Gy (range 4.02-7.29Gy). The D80 of the central lung showed an average dose of 3.87Gy. CONCLUSIONS: Total body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.

Tomotherapy in malignant mesothelioma: a planning study to establish dose constraints.

PURPOSE: A planning study was performed for helical tomotherapy treatment. We evaluated the maximum achievable protection of organs at risk (OARs) in patients with malignant pleural mesothelioma after pleurectomy with simultaneous optimal target coverage. MATERIALS AND METHODS: The datasets of 13 patients were included. The applied dose to the planning target volume (PTV) was 50.4 Gy with single doses of 1.8 Gy per fraction. Presuming optimal target coverage, we evaluated the applied dose to the OARs with special regard to the contralateral lung. RESULTS: For left-(lsRT)/right(rsRT)-sided radiotherapy, target coverage for the PTV showed a D98 (mean) of 49.37/49.71 Gy (98.0%/98.6%) and a D2 (mean) of 54.19/54.61 Gy (107.5%/108.3%). The beam-on time was kept below 15 min. The achieved mean dose (D50) to the contralateral lung was kept below 4 Gy for lsRT and rsRT. With regard to the other organs at risk the applied doses were as follows: mean dose (lsRT): ipsilateral kidney (Dmean) 13.03 (5.32-22.18) Gy, contralateral kidney (Dmean) <2.0 Gy, heart (Dmean) 22.23 (13.57-27.72) Gy, spinal cord D1

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.

Prophylactically applied Hydrofilm polyurethane film dressings reduce radiation dermatitis in adjuvant radiation therapy of breast cancer patients.

PURPOSE: Radiation-induced skin injury represents one of the most common side effects in breast cancer patients receiving adjuvant whole-breast radiotherapy. Numerous systemic and topical treatments have been studied in the prevention and management of radiation-induced skin injury without providing sustainable treatment strategies. While superficial barrier-forming skin products such as dressings are the standard of care in wound care management, their utilization as preventive treatment approach in radiotherapy has barely attracted attention. METHODS: In this prospective, intra-patient randomized study, Hydrofilm polyurethane film dressings were applied prophylactically to either the medial or lateral breast half of 62 patients with breast cancer undergoing adjuvant radiation therapy following breast conserving surgery. The breast half contralateral to the film dressing was concurrently treated with 5% urea lotion as control skin care. Maximum severity of radiation dermatitis was assessed using RTOG/EORTC toxicity scores, photospectrometric erythema measurements and patient-assessed modified RISRAS scale. RESULTS: In the Hydrofilm compartments, mean maximum RTOG/EORTC radiation dermatitis severity grades were significantly reduced from 1.33 to 0.35 and photospectrometric measurements showed significantly reduced erythema severity, as compared to the control compartments, with an overall response rate of 89.3%. Hydrofilm completely prevented moist desquamation and significantly reduced patients' subjective experience of itching and pain. CONCLUSION: The obtained results along with a favorable cost-benefit ratio and an easy and quick application suggest a prophylactic application of Hydrofilm in adjuvant radiotherapy of breast cancer patients to reduce or even prevent radiation dermatitis.

Patient positioning in head and neck cancer : Setup variations and safety margins in helical tomotherapy.

OBJECTIVE: To evaluate the interfractional variations of patient positioning during intensity-modulated radiotherapy (IMRT) with helical tomotherapy in head and neck cancer and to calculate the required safety margins (sm) for bony landmarks resulting from the necessary table adjustments. MATERIALS AND METHODS: In all, 15 patients with head and neck cancer were irradiated using the Hi-Art II tomotherapy system between April and September 2016. Before therapy sessions, patient position was frequently checked by megavolt computed tomography (MV-CT). Necessary table adjustments (ta) in the right-left (rl), superior-inferior (si) and anterior-posterior (ap) directions were recorded for four anatomical points: second, fourth and sixth cervical vertebral body (CVB), anterior nasal spine (ANS). Based upon these data sm were calculated for non-image-guided radiotherapy, image-guided radiotherapy (IGRT) and image guidance limited to a shortened area (CVB 2). RESULTS: Based upon planning CT the actual treatment required ta from -0.05 ± 1.31 mm for CVB 2 (ap) up to 2.63 ± 2.39 mm for ANS (rl). Considering the performed ta resulting from image control (MV-CT) we detected remaining ta from -0.10 ± 1.09 mm for CVB 4 (rl) up to 1.97 ± 1.64 mm for ANS (si). After theoretical adjustment of patients position to CVB 2 the resulting ta ranged from -0.11 ± 2.44 mm for CVB6 (ap) to 2.37 ± 2.17 mm for ANS (si). These data imply safety margins: uncorrected patient position: 3.63-9.95 mm, corrected positioning based upon the whole target volume (IGRT): 1.85-6.63 mm, corrected positioning based upon CVB 2 (IGRT): 3.13-6.66 mm. CONCLUSIONS: The calculated safety margins differ between anatomic regions. Repetitive and frequent image control of patient positioning is necessary that, however, possibly may be focussed on a limited region.

Visualization of data in radiotherapy using web services for optimization of workflow.

BACKGROUND: Every day a large amount of data is produced within a radiotherapy department. Although this data is available in one form or other within the centralised systems, it is often not in the form which is of interest to the departmental staff. This work presents a flexible browser based reporting and visualization system for clinical and scientific use, not currently found in commercially available software such as MOSAIQ(TM) or ARIA(TM). Moreover, the majority of user merely wish to retrieve data and not record and/or modify data. Thus the idea was conceived, to present the user with all relevant information in a simple and effective manner in the form of web-services. Due to the widespread availability of the internet, most people can master the use of a web-browser. Ultimately the aim is to optimize clinical procedures, enhance transparency and improve revenue. METHODS: Our working group (BAS) examined many internal procedures, to find out whether relevant information suitable for our purposes lay therein. After the results were collated, it was necessary to select an effective software platform. After a more detailed analysis of all data, it became clear that the implementation of web-services was appropriate. In our institute several such web-based information services had already been developed over the last few years, with which we gained invaluable experience. Moreover, we strived for high acceptance amongst staff members. RESULTS: By employing web-services, we attained high effectiveness, transparency and efficient information processing for the user. Furthermore, we achieved an almost maintenance-free and low support system. The aim of the project, making web-based information available to the user from the departmental system MOSAIQ, physician letter system MEDATEC(R) and the central finding server MiraPlus (laboratory, pathology and radiology) were implemented without restrictions. CONCLUSION: Due to widespread use of web-based technology the training effort was effectively nil, since practically every member of staff can master the use of a web-browser. Moreover, we have achieved high acceptance amongst staff members and have improved our effectiveness resulting in a considerable time saving. The many MOSAIQ-specific parts of the system can be readily used by departments which use MOSAIQ as the departmental system.

[Automated delivery of codes for charge in radiotherapy]. / Automatisierte Leistungsübermittlung in der Strahlenheilkunde.

BACKGROUND AND PURPOSE: For the medical billing of Radiotherapy every fraction has to be encoded, including date and time of all administered treatments. With fractions averaging 30 per patient and about 2,500 new patients every year the number of Radiotherapy codes reaches an amount of 70,000 and more. Therefore, an automated proceeding for transferring and processing therapy codes has been developed at the Department of Radiotherapy Freiburg, Germany. This is a joint project of the Department of Radiotherapy, the Administration Department, and the Central IT Department of the University Hospital of Freiburg. MATERIAL AND METHODS: The project consists of several modules whose collaboration makes the projected automated transfer of treatment codes possible. The first step is to extract the data from the department's Clinical Information System (MOSAIQ). These data are transmitted to the Central IT Department via an HL7 interface, where a check for corresponding hospitalization data is performed. In the further processing of the data, a matching table plays an important role allowing the transformation of a treatment code into a valid medical billing code. In a last step, the data are transferred to the medical billing system. RESULTS AND CONCLUSION: After assembling and implementing the particular modules successfully, a first beta test was launched. In order to test the modules separately as well as the interaction of the components, extensive tests were performed during March 2006. Soon it became clear that the tested procedure worked efficiently and accurately. In April 2006, a pilot project with a few qualities of treatment (e.g., computed tomography, simulation) was put into practice. Since October 2006, nearly all Radiation Therapy codes (approximately 75,000) are being transferred to the comprehensive Hospital Information System (HIS) automatically in a daily routine.

[Department and patient management in radiotherapy. The Freiburg model]. / Abteilungs- und Patientenmanagement in der Strahlenheilkunde. Das Freiburger Modell.

BACKGROUND AND PURPOSE: The activities in radiotherapy are mainly affected by numerous partly very complex operational procedures which have to be completed while high safety requirements have to be fulfilled. This fact and steadily increasing economic pressure are forcing us to develop new strategies which help us to optimize our operational procedures and assure their reliability. As there are not so many radiotherapeutic institutions and the main focus, up to now, was mainly stressed on the acceleration systems (radiation planning, acceleration control), only few industrial systems are available which could also support the economic, organizational and administrative needs of radiotherapy. METHODS: During the building operations for the "new clinic for radiotherapy" at the University Hospital Freiburg, Germany, the staff of the clinical and administrative information and the medical physicists developed, in close cooperation with the physicians, a comprehensive concept to control and organize a radiotherapeutic institution. This concept was examined during the construction phase of the new clinic and the adjoined HBFG ("Hochschulbauförderungsgesetz") process by the "Deutsche Forschungsgemeinschaft" and financed totally by federal funds. RESULTS AND CONCLUSION: The precondition for the goal to operate a homogeneous and comprehensive management of a clinic for radiotherapy was the direct connection of the acceleration area with the organizational/administrative surrounding. The thus developed common basic dates and consistence created transparency and allowed us for the first time to control all operational procedures by EDV-technical means. After 2 years full-time operation and implementation of numerous particular projects we are now ready for film- and paperless digital work.

[Long term registration of linear accelerator parameters for quality assurance in stereotaxic radiosurgery]. / Langzeitverfolgung von Linearbeschleunigerparametern zur Qualitätssicherung stereotaktischer Strahlenbehandlungen.

Long-term observations of mechanical parameters have been performed in Freiburg for the last 7 years within the quality assurance of stereotactic irradiation at linear accelerators. The deviations between the laser indication and the position of the beam isocentre are recorded, as well as parameters for the stability of the couch rotation and the additional devices for patient adjustment and beam collimation. The deviations are used for the correction of the calculated isocentre coordinates. The long-term observation of the measured values and their standard deviations allow conclusions about the quality of the measuring procedure itself, the laser adjustment, the extension of the isocentre sphere, as well as the mechanical slackness of the treatment couch and the fixation device of the stereotactic ring. The standard deviations of the isocentre position were within 0.3 to 0.8 mm, those of the measurement quality approximately 0.2 mm. The analysis of long-term observation has contributed to improvements of the equipment and of quality assurance procedures.