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

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.

Extraretinal induced visual sensations during IMRT of the brain.

BACKGROUND: We observed visual sensations (VSs) in patients undergoing intensity modulated radiotherapy (IMRT) of the brain without the beam passing through ocular structures. We analyzed this phenomenon especially with regards to reproducibility, and origin. METHODS AND FINDINGS: Analyzed were ten consecutive patients (aged 41-71 years) with glioblastoma multiforme who received pulsed IMRT (total dose 60Gy) with helical tomotherapy (TT). A megavolt-CT (MVCT) was performed daily before treatment. VSs were reported and recorded using a triggered event recorder. The frequency of VSs was calculated and VSs were correlated with beam direction and couch position. Subjective patient perception was plotted on an 8x8 visual field (VF) matrix. Distance to the orbital roof (OR) from the first beam causing a VS was calculated from the Dicom radiation therapy data and MVCT data. During 175 treatment sessions (average 17.5 per patient) 5959 VSs were recorded and analyzed. VSs occurred only during the treatment session not during the MVCTs. Plotting events over time revealed patient-specific patterns. The average cranio-caudad extension of VS-inducing area was 63.4mm (range 43.24-92.1mm). The maximum distance between the first VS and the OR was 56.1mm so that direct interaction with the retina is unlikely. Data on subjective visual perception showed that VSs occurred mainly in the upper right and left quadrants of the VF. Within the visual pathways the highest probability for origin of VSs was seen in the optic chiasm and the optic tract (22%). CONCLUSIONS: There is clear evidence that interaction of photon irradiation with neuronal structures distant from the eye can lead to VSs.

Intensity-modulated radiotherapy of the prostate: dynamic ADC monitoring by DWI at 3.0 T.

BACKGROUND AND PURPOSE: Diffusion weighted imaging (DWI) as a functional MR technique allows for both qualitative and quantitative assessment of tumour cellularity and changes during therapy. The objective of this study was to evaluate changes of apparent diffusion coefficient (ADC) in biopsy proven prostate cancer (PCa) under intensity modulated radiotherapy (IMRT) at 3T. MATERIAL & METHODS: Thirteen patients with biopsy proven PCa treated with intensity modulated external beam radiotherapy (IMRT) underwent four standardized MR examinations after approval of the local institutional review board. These included DWI at 3T on a strict time table: before, in between, directly after (between 1 and 4 days after the last radiation), as well as 3 months after IMRT. Quantitative analysis of two different ADCs, - the ADC(0,800) and the ADC(50,800), was performed dynamically over 4 time points in PCa, gluteal muscle and healthy prostate tissue. RESULTS: In PCa, a significant increase of ADC(0,800)/ADC(50,800) values was measured under IMRT by about 16%/15% (P=0.00008/0.00017), 21%/21% (P=0.00006/0.00030), and 33%/34% (P=0.00004/0.00002) at the three time points compared to initial value. Healthy prostate tissue did not show any significant increase. CONCLUSION: DWI is suitable as a biomarker for radiation therapy response of PCa by allowing the dynamic monitoring of treatment effectiveness.

State-of-the-art classification and multimodality treatment of malignant thymoma.

Thymomas are the most common tumors of the anterior mediastinum. Classification, treatment options and understanding of the pathophysiology of thymoma have changed over the past years. It is hoped that novel therapeutic strategies will lead to a survival benefit in these patients. It has turned out that patients with thymoma are best treated with multimodality therapy. In this review, a pathologist, an immunologist, a surgeon, a radiotherapist, a pneumologist and oncologists discuss the current status of classification and strategies for the treatment of thymoma patients.

Survival after accidental extrahepatic distribution of Y90 microspheres to the mesentery during a radioembolization procedure.

We present the acute management and outcome of a patient after an accidental mesenteric distribution of Y90 microspheres during radioembolization (RE). This report describes and highlights: (1) the incidence of a significant reflux during a RE session while injecting into a replaced right hepatic artery from the superior mesenteric artery, (2) the appearance of diffuse mesenteric Y90 distribution in bremsstrahlung-imaging, (3) the management protocol with the radiation protection agent amifostine, (4) the development of typical adverse effects in the expected time window, and (5) survival of the patient without long-term sequelae. This report should sensitize physicians to this particular problem and may help to avoid as well as manage similar radioembolization incidences.

[Prediction of clinical course of glioblastomas by MRI during radiotherapy]. / Prognoseeinschätzung durch MR-verlaufskontrollen während der strahlentherapie bei glioblastom-patienten.

PURPOSE: determine the value of MR studies in patients undergoing radiotherapy for glioblastomas pre and during radiotherapy to predict the clinical course. PATIENTS AND METHODS: MR follow-up studies were performed in 33 patients with glioblastomas before radiotherapy, after 30 Gy, after 60 Gy, and in the treatment follow-up. Findings on MR were categorized into: definite progress, questionable progress, status idem. Patients were followed clinically (median for 11 months). RESULTS: after 30 Gy 23/33 (70%) of the MR examination showed status idem. 10/33 (30%) demonstrated definite (n = 6) or questionable (n = 4) progress. Further tumor progress was faster in these patients and patients succumb to their disease earlier (9 vs. 22 months). The 60 Gy study showed definite (n = 8) and questionable (n = 6) progress in 14/33 (42%) cases. All these tumors were progressing faster and were associated with a comparatively reduced life expectancy. CONCLUSION: MR follow-up studies after 30 Gy in patients undergoing radiotherapy for glioblastomas allow for prognostic appraisal, and potentially early modification of treatment.

A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors.

PURPOSE: Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen. METHODS AND MATERIALS: From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m(2)/day for 5 days over 4 weeks within 2 h to radiation therapy. RESULTS: Because of the higher toxic rates seen in patients receiving 0.5 mg/m(2)/day, the recommended dosage for phase II was 0.4 mg/m(2)/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders. CONCLUSIONS: Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.

Disclosing the cancer diagnosis: what contributes to patient satisfaction?

BACKGROUND: Despite the growing attention to the how, when and where of disclosing a cancer diagnosis, not all patients are satisfied with how the news is broken to them. As in German-speaking countries there is a lack of empirical studies on this subject, this analysis was conducted to determine how the cancer diagnosis was given in a German sample, and how satisfied the patients are with the disclosure experience. PATIENTS AND METHODS: 162 outpatients received a self-report questionnaire focusing on their experiences with physician-patient communication when the diagnosis was disclosed. RESULTS: Guidelines had been respected in most cases. 17% of patients were dissatisfied with the diagnosis disclosure. They reported a significantly shorter duration of the interaction, lack of privacy, deficits in understanding the information, and less emotional support by the physician. CONCLUSION: Adherence to guidelines of diagnosis disclosure in the German sample was fairly high. Respecting both informational and emotional needs is essential for patient satisfaction and can be taught in communication training.

[Volumetric changes of the breast during radiotherapy. Is a replanning necessary for the electron boost?]. / Volumetrische Veränderungen der Mamma während der Radiotherapie. Ist vor Boostbestrahlung mit Elektronen eine Nachplanung erforderlich?

BACKGROUND AND PURPOSE: Radiotherapy can induce tissue reactions with an edema leading to increased breast volume. The aim of the present study was to quantify this increase and analyze its effect on the electron boost technique. PATIENTS AND METHODS: 140 patients with breast cancer treated with breast-conserving surgery underwent CT planning before, during and/or after radiotherapy in order to evaluate breast volume changes due to radiotherapy. CT data were analyzed using the HELAX planning system and dose distribution was assessed. Determination of the breast volume was achieved using an interpolation algorithm. Three subgroups were analyzed: group 1 (n = 47): < or = 670 cm(3), group 2 (n = 46): 671-999 cm(3), and group 3 (n = 47): > or = 1000 cm(3) breast volume. RESULTS: The mean initial breast volume was 907 cm(3) (100-3073 cm(3)). After radiotherapy, mean breast volume increased by 81 cm(3) to 988 cm(3) (109-3185 cm(3)). Significant changes in volume were observed after a dose of 40 Gy. According to the subgroups mean volume increase was as follows: group 1: 53 cm(3) (3-120 cm(3)), group 2: 85 cm(3) (20-200 cm(3)), and group 3: 105 cm(3) (5-340 cm(3)). This difference was statistically significant for all subgroups (p < 0.001). Corresponding to the volume increase, depth of the boost target volume changed up to 1.0 cm. CONCLUSION: As radiotherapy may lead to a significant increase in breast volume, it seems appropriate to perform a second planning CT after about 40 Gy in order to optimize dose distribution for boost irradiation.

[Craniospinal irradiation -- patient positioning and verification with portal films]. / Kraniospinale Bestrahlung -- Patientenlagerung und Verifikation.

BACKGROUND: Implementation of an important step for quality assurance in irradiation of the craniospinal axis was made through changes in the irradiation technique. Crucial improvements in patient positioning and the possibility of taking portal films of the field junctions are described. MATERIAL AND METHODS: A box for the positioning of the head of the patient in has been developed. In combination with vacuum cushions, it is a cheap method for the individual and secure positioning of the patient in prone position. Furthermore, a method for taking portal films of the field junctions between the lateral cranial and the upper dorsal spinal field as well as between the two dorsal spinal fields is described. DISCUSSION: The use of the "Bonner Box" improves the patient positioning with respect to reproducibility, setup time and comfort. The documentation of the field junctions in craniospinal irradiation, which is described for the first time, is an important tool for quality assurance.