Whole body irradiation with intensity-modulated helical tomotherapy prior to haematopoietic stem cell transplantation: analysis of organs at risk by dose and its effect on blood kinetics.

BACKGROUND: Intensity-modulated helical tomotherapy (HT) is a promising technique in preparation for bone marrow transplantation. Nevertheless, radiation-sensitive organs can be substantially compromised due to suboptimal delivery techniques of total body irradiation (TBI). To reduce the potential burden of radiation toxicity to organs at risk (OAR), high-quality coverage and homogeneity are essential. We investigated dosimetric data from kidney, lung and thorax, liver, and spleen in relation to peripheral blood kinetics. To further advance intensity-modulated total body irradiation (TBI), the potential for dose reduction to lung and kidney was considered in the analysis. PATIENTS AND METHODS: 46 patients undergoing TBI were included in this analysis, partially divided into dose groups (2, 4, 8, and 12 Gy). HT was performed using a rotating gantry to ensuring optimal reduction of radiation to the lungs and kidneys and to provide optimal coverage of other OAR. Common dosimetric parameters, such as D05, D95, and D50, were calculated and analysed. Leukocytes, neutrophils, platelets, creatinine, GFR, haemoglobin, overall survival, and graft-versus-host disease were related to the dosimetric evaluation using statistical tests. RESULTS: The mean D95 of the lung is 48.23%, less than half the prescribed and unreduced dose. The D95 of the chest is almost twice as high at 84.95%. Overall liver coverage values ranged from 96.79% for D95 to 107% for D05. The average dose sparing of all patients analysed resulted in an average D95 of 68.64% in the right kidney and 69.31% in the left kidney. Average D95 in the spleen was 94.28% and D05 was 107.05%. Homogeneity indexes ranged from 1.12 for liver to 2.28 for lung. The additional significance analyses conducted on these blood kinetics showed a significant difference between the 2 Gray group and the other three groups for leukocyte counts. Further statistical comparisons of the dose groups showed no significant differences. However, there were significant changes in the dose of OAR prescribed with dose sparing (e.g., lung vs. rib and kidney). CONCLUSION: Using intensity-modulated helical tomotherapy to deliver TBI is a feasible method in preparation for haematopoietic stem cell transplantation. Significant dose sparing in radiosensitive organs such as the lungs and kidneys is achievable with good overall quality of coverage. Peripheral blood kinetics support the positive impact of HT and its advantages strongly encourage its implementation within clinical routine.

Total marrow irradiation versus total body irradiation using intensity-modulated helical tomotherapy.

BACKGROUND: Total body irradiation (TBI) is often a component of the conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematological malignancies. However, total marrow irradiation (TMI) could be an alternative method for reducing radiation therapy-associated toxicity, as it specifically targets the skeleton and thus could better protect organs at risk. Here, we compared dosimetric changes in irradiation received by the target volume and organs at risk between TBI and TMI plans. MATERIALS AND METHODS: Theoretical TMI plans were calculated for 35 patients with various hematological malignancies who had already received TBI in our clinic. We then statistically compared irradiation doses between the new TMI plans and existing TBI plans. We examined whether TMI provides greater protection of organs at risk while maintaining the prescribed dose in the targeted skeletal area. We also compared beam-on times between TBI and TMI. RESULTS: TMI planning achieved significant reductions in the mean, minimum, and maximum irradiation doses in the lungs, kidneys, liver, spleen, and body (i.e., remaining tissue except organs and skeleton). In particular, the mean dose was reduced by 49% in the liver and spleen and by 55-59% in the kidneys. Moreover, TMI planning reduced the corpus beam-on time by an average of 217 s. CONCLUSION: TMI planning achieved significant dose reduction in organs at risk while still achieving the prescribed dose in the target volume. Additionally, TMI planning reduced the beam-on time for corpus plans despite a high modulation factor.

Lung sparing and ribcage coverage in total body irradiation delivered by helical tomotherapy.

PURPOSE: Helical tomotherapy (HT) is a viable method for delivering total body irradiation (TBI) when preparing patients for allogenic stem cell or bone-marrow transplantation. TBI can be planned to reduce the amount of radiation delivered to organs at risk, such as the lungs, with the aim of decreasing toxicity. However, it is important for the ribcage to receive the prescribed radiation dose in preparation for bone-marrow transplantation. In this retrospective study, we analyzed radiation dose coverage of the lungs and ribcage in patients who underwent TBI delivered by HT to achieve lung dose sparing. METHODS: Thirty-five patients were included in the analysis and divided into three groups based on their prescribed radiation dose (4, 8, or 12 Gy). HT was performed using a rotating gantry to reduce radiation to the lungs. Dosimetric parameters for the lungs and ribcage as well as dose-volume histograms were calculated. RESULTS: The mean lung D95 was 60.97%, 54.77%, and 37.44% of the prescribed dose for patients receiving 4 Gy, 8 Gy, and 12 Gy, respectively. Ribcage coverage was most optimal for patients receiving 4 Gy, with a D95 of 91.27% and mean homogeneity index of 1.17, whereas patients receiving 12 Gy had a mean D95 of 78.65% and homogeneity index of 1.37, which is still within the range recommended by treatment guidelines. CONCLUSIONS: Using HT to achieve lung tissue sparing is a viable approach to minimizing pulmonic complications in patients undergoing TBI. As this planning adjustment does not compromise the dose and quality of coverage received by the ribcage, it is a feasible tool within conditioning regimens for allogeneic bone-marrow transplantation.

Helical versus static approaches to delivering tomotherapy to the junctional target for patients taller than 135 cm undergoing total body irradiation.

BACKGROUND: Helical TomoTherapy® is widely used for total body irradiation as a component of conditioning regimens before allogeneic bone-marrow transplantation. However, this technique limits the maximum length of a planning target volume to 135 cm. Therefore, patients taller than 135 cm require two planning computed tomography scans and treatment plans. The junctional target between these two treatment plans is thus a critical region for treatment planning and delivery. Here, we compare radiation coverage of the junctional target between helical and static approaches to treatment planning and delivery to determine which approach allows high quality irradiation planning and provides more robustness against patient movement. METHODS: We retrospectively analyzed 10 patients who underwent total body irradiation using a static four-field box planning approach and nine patients who underwent total body irradiation using a helical planning approach. All patients were taller than 135 cm. The junctional target volume was divided into 10 slices of 1 cm thickness (JT1-JT10) for analysis. Dosimetric parameters and dose-volume histograms were compared to assess the quality of coverage of the junctional target between the helical and static planning approaches. RESULTS: The D50 for the total junctional target was slightly higher than the prescribed dose for both helical and static approaches, with a mean of 108.12% for the helical group and 107.81% for the static group. The mean D95 was 98.44% ± 4.19% for the helical group and 96.20% ± 4.59% for the static group. The mean homogeneity index covering the entire junctional target volume was 1.20 ± 0.04 for the helical group and 1.21 ± 0.05 for the static group. The mean homogeneity index ranged from 1.08 ± 0.01 in JT1 to 1.22 ± 0.06 in JT6 for the helical group and from 1.06 ± 0.02 in JT1 to 1.19 ± 0.05 in JT6 for the static group. There were no significant differences in parameters between helical and static groups. However, the static approach provided robustness against up to 30 mm of lateral movement of the patient. CONCLUSIONS: As long as TBI using helical TomoTherapy® is limited to a maximum length of 135 cm, the junctional target must be addressed during treatment planning. Our analysis shows that the static four-field box approach is viable and offers higher robustness against lateral movement of the patient than the helical approach.

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.

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.