MR-Guided Adaptive Radiotherapy for Head and Neck Cancer: Prospective Evaluation of Migration and Anatomical Changes of the Major Salivary Glands.

The aim of this study was to quantify anatomical changes of parotids and submandibular glands and evaluate potential dosimetric advantages during weekly adaptive MR-guided radiotherapy (MRgRT) for the definitive treatment of head and neck cancer (HNC). The data and plans of 12 patients treated with bilateral intensity-modulated radiotherapy for HNC using MR-linac, with weekly offline adaptations, were prospectively evaluated. The positional and volumetric changes of the salivary glands were analyzed by manual segmentation in weekly MRI images and the dosimetric impact of these anatomical changes on the adapted treatment plans was assessed. The mean volume change in parotid and submandibular gland volume was -31.9% (p < 0.0001) and -29.7% (p < 0.0001) after five weeks, respectively. The volume change was significantly correlated with the cumulative dose for the respective gland at the time of volume measurement. Inter-parotid distance changed by -5.4% (6.5 mm) on average after five weeks (p = 0.0005). The distance became significantly smaller only in the left-right direction. The inter-submandibular gland distance changed by 0.7 mm (p = 0.38). This study demonstrated significant changes in salivary gland volumes and position following daily MR guidance and weekly plan adaptation. Ongoing clinical trials will provide data on the clinical impact of these changes and novel MR-based adaptation strategies.

Distance to isocenter is not associated with an increased risk for local failure in LINAC-based single-isocenter SRS or SRT for multiple brain metastases.

PURPOSE: To evaluate the impact of the distance between treatment isocenter and brain metastases on local failure in patients treated with a frameless linear-accelerator-based single-isocenter volumetric modulated arc (VMAT) SRS/SRT for multiple brain metastases. METHODS AND MATERIALS: Patients treated with SRT for brain metastases (BM) between April 2014 and May 2019 were included in this retrospective study. BM treated with a single-isocenter multiple-target (SIMT) SRT were evaluated for local recurrence-free intervals in dependency to their distance to the treatment isocenter. A Cox-regression model was used to investigate different predictor variables for local failure. Results were compared to patients treated with a single-isocenter-single-target (SIST) approach. RESULTS: In total 315 patients with a cumulative number of 1087 BM were analyzed in this study of which 140 patients and 708 BM were treated with SIMT SRS/SRT. Median follow-up after treatment was 13.9 months for SIMT approach and 11.9 months for SIST approach. One-year freedom from local recurrence was 87% and 94% in the SIST and SIMT group, respectively. Median distance to isocenter (DTI) was 4.7 cm (range 0.2-10.5) in the SIMT group. Local recurrence-free interval was not associated with the distance to the isocenter in univariable or multivariable Cox-regression analysis. Multivariable analysis revealed only volume as an independent significant predictor for local failure (p-value <0.05). CONCLUSION: SRS/SRT using single-isocenter VMAT for multiple targets achieved high local metastases control rates irrespective of distance to the isocenter, supporting efficacy of single-isocenter stereotactic radiation therapy for multiple brain metastases.

Comparison of beam segment versus full plan re-optimization in daily magnetic resonance imaging-guided online-adaptive radiotherapy.

The optimal approach for magnetic resonance imaging-guided online adaptive radiotherapy is currently unknown and needs to consider patient on-couch time constraints. The aim of this study was to compare two different plan optimization approaches. The comparison was performed in 238 clinically applied online-adapted treatment plans from 55 patients, in which the approach of re-optimization was selected based on the physician's choice. For 33 patients where both optimization approaches were used at least once, the median treatment planning dose metrics of both target and organ at risk differed less than 1%. Therefore, we concluded that beam segment weight optimization was chosen adequately for most patients without compromising plan quality.

Head and neck radiotherapy on the MR linac: a multicenter planning challenge amongst MRIdian platform users.

PURPOSE: Purpose of this study is to evaluate plan quality on the MRIdian (Viewray Inc., Oakwood Village, OH, USA) system for head and neck cancer (HNC) through comparison of planning approaches of several centers. METHODS: A total of 14 planners using the MRIdian planning system participated in this treatment challenge, centrally organized by ViewRay, for one contoured case of oropharyngeal carcinoma with standard constraints for organs at risk (OAR). Homogeneity, conformity, sparing of OARs, and other parameters were evaluated according to The International Commission on Radiation Units and Measurements (ICRU) recommendations anonymously, and then compared between centers. Differences amongst centers were assessed by means of Wilcoxon test. Each plan had to fulfil hard constraints based on dose-volume histogram (DVH) parameters and delivery time. A plan quality metric (PQM) was evaluated. The PQM was defined as the sum of 16 submetrics characterizing different DVH goals. RESULTS: For most dose parameters the median score of all centers was higher than the threshold that results in an ideal score. Six participants achieved the maximum number of points for the OAR dose parameters, and none had an unacceptable performance on any of the metrics. Each planner was able to achieve all the requirements except for one which exceeded delivery time. The number of segments correlated to improved PQM and inversely correlated to brainstem D0.1cc and to Planning Target Volume1 (PTV) D0.1cc. Total planning experience inversely correlated to spinal canal dose. CONCLUSION: Magnetic Resonance Image (MRI) linac-based planning for HNC is already feasible with good quality. Generally, an increased number of segments and increasing planning experience are able to provide better results regarding planning quality without significantly prolonging overall treatment time.

Probing spatiotemporal fractionation on the preclinical level.

In contrast to conventional radiotherapy, spatiotemporal fractionation (STF) delivers a distinct dose distribution in each fraction. The aim is to increase the therapeutic window by simultaneously achieving partial hypofractionation in the tumour along with near uniform fractionation in normal tissues. STF has been studied in silico under the assumption that different parts of the tumour can be treated in different fractions. Here, we develop an experimental setup for testing this key assumption on the preclinical level using high-precision partial tumour irradiation in an experimental animal model. We further report on an initial proof-of-concept experiment. We consider a reductionist model of STF in which the tumour is divided in half and treated with two complementary partial irradiations separated by 24 h. Precise irradiation of both tumour halves is facilitated by the image-guided small animal radiation research platform X-RAD SmART. To assess the response of tumours to partial irradiations, tumour growth experiments are conducted using mice carrying syngeneic subcutaneous tumours derived from MC38 colorectal adenocarcinoma cells. Tumour volumes were determined daily by calliper measurements and validated by CT-volumetry. We compared the growth of conventionally treated tumours, where the whole tumour was treated in one fraction, to the reductionist model of STF. We observed no difference in growth between the two groups. Instead, a reduction in the irradiated volume (where only one half of the tumour was irradiated) resulted in an intermediate response between full irradiation and unirradiated control. The results obtained by CT-volumetry supported the findings of the calliper-derived measurements. An experimental setup for precise partial tumour irradiation in small animals was developed, which is suited to test the assumption of STF that complementary parts of the tumour can be treated in different fractions on the preclinical level. An initial experiment supports this assumption, however, further experiments with longer follow-up and varying fractionation schemes are needed to provide additional support for STF.

Treatment plan quality during online adaptive re-planning.

BACKGROUND: Online adaptive radiotherapy is intended to prevent plan degradation caused by inter-fractional tumor volume and shape changes, but time limitations make online re-planning challenging. The aim of this study was to compare the quality of online-adapted plans to their respective reference treatment plans. METHODS: Fifty-two patients treated on a ViewRay MRIdian Linac were included in this retrospective study. In total 238 online-adapted plans were analyzed, which were optimized with either changing of the segment weights (n = 85) or full re-optimization (n = 153). Five different treatment sites were evaluated: prostate, abdomen, liver, lung and pelvis. Dosimetric parameters of gross tumor volume (GTV), planning target volume (PTV), 2 cm ring around the PTV and organs at risk (OARs) were considered. The Wilcoxon signed-rank test was used to assess differences between online-adapted and reference treatment plans, p < 0.05 was considered significant. RESULTS: The average duration of the online adaptation, consisting of contour editing, plan optimization and quality assurance (QA), was 24 ± 6 min. The GTV was slightly larger (average ± SD: 1.9% ± 9.0%) in the adapted plans than in the reference plans (p < 0.001). GTV-D95% exhibited no significant changes when considering all plans, but GTV-D2% increased by 0.40% ± 1.5% on average (p < 0.001). There was a very small yet significant decrease in GTV-coverage for the abdomen plans. The ring Dmean increased on average by 1.0% ± 3.6% considering all plans (p < 0.001). There was a significant reduction of the dose to the rectum of 4.7% ± 16% on average (p < 0.001) for prostate plans. CONCLUSIONS: Dosimetric quality of online-adapted plans was comparable to reference treatment plans and OAR dose was either comparable or decreased, depending on treatment site. However, dose spillage was slightly increased.

Leukoencephalopathy after prophylactic whole-brain irradiation with or without hippocampal sparing: a longitudinal magnetic resonance imaging analysis.

PURPOSE: Neurocognitive changes are well described after prophylactic or therapeutic whole-brain radiotherapy (WBRT) and have been reported as early as 3 months after radiotherapy (RT). Therefore, WBRT with protection of the hippocampal region (hippocampal avoidance, HA) has been proposed to preserve neurocognition. Our aim was to compare the risk of leukoencephalopathy after prophylactic cranial irradiation (PCI) with or without HA. METHODS: Patients with small-cell lung cancer who received either lateral-opposed field PCI (non-HA-PCI; n = 9) or hippocampus avoidance PCI (HA-PCI; n = 9) with available magnetic resonance imaging (MRI) follow-up were identified and age matched. Pre-therapeutic and follow-up MRI after RT was analysed for leukoencephalopathy based on the Fazekas score. Bilateral cortical and subcortical brain structures were segmented and analysed for alterations in dosimetric parameters and volumes. RESULTS: There was no significant difference of Fazekas scores between groups at baseline. Fazekas score differed in post-treatment with a median of 1 in the HA-PCI group and 2 in the non-HA-PCI group (p = 0.007). Significant increase of Fazekas score over time after RT was observed for HA-PCI patients (p = 0.001) but not for non-HA-PCI patients. Dmax (highest radiation dose) and brain volume receiving doses >25Gy were higher in HA-PCI patients. There were no significant volumetric differences for segmented brain structures between groups. CONCLUSION: Radiological changes are more prominent after HA-PCI than after non-HA-PCI. Although no standardised neurocognitive testing was performed, the significantly increased Fazekas scores after HA-PCI are expected to interfere with neurocognitive function. Prospective long-term neurocognitive studies are warranted before HA-PCI is implemented in routine clinical practice.

Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial.

Postoperative radiotherapy after extrapleural pneumonectomy of malignant pleural mesothelioma was investigated in the randomized phase II trial SAKK17/04. The relapse rate within the high and/or low-dose PTV without previous distant failure was 24%, the isolated in-field-relapse rate within the PTVs was 5% and the distant relapse rate outside of the PTVs was 81%. Clinical outcome was mainly determined by distant disease progression outside of the radiation field.

Optimizing radiosurgery with photons for ocular melanoma.

BACKGROUND AND PURPOSE: Photon radiotherapy has been established for the treatment of ocular melanoma (OM). Here we investigate the planning qualities of two different planning approaches, a combination of dynamic conformal arcs (DCA) complemented with multiple non-coplanar static intensity-modulated (IMRT) fields (DCA-IMRT), and volumetric modulated arc therapy (VMAT) in combination with automated planning (AP). MATERIALS AND METHODS: Thirteen consecutive patients treated for ocular melanoma with curative intent on a Linac-based radiosurgery system were analyzed. Fractionated stereotactic radiosurgery (fSRS) was applied using 50 Gy in 5 fractions using the combination of DCA-IMRT. Plans were reviewed and the thirteen cases were compared to plans obtained with optimized automated VMAT based on a set of 28 distinct patients treated with DCA-IMRT who were selected to generate the AP model for the prediction of dose volume constraints. RESULTS: Overall, plan quality of DCA-IMRT was superior to AP with VMAT. PTV coverage did not exceed 107% in any case treated with DCA-IMRT, compared to seven patients with VMAT. The median PTV covered by >95% was 98.3% (91.9%-99.7%) with DCA-IMRT, compared to 95.1% (91.5%-97.9%) (p < 0.01) with VMAT. The median mean dose delivered to the treated eye was 22.4 Gy (12.3 Gy-33.3 Gy) with DCA-IMRT compared to 27.2 Gy (15.5 Gy-33.7 Gy) (p < 0.01). Dose to the ipsilateral lacrimal gland and the ipsilateral optic nerve were comparable for DCA-IMRT and VMAT, however, the dose to the lens was lower with DCA-IMRT compared to VMAT. CONCLUSIONS: The combination of multiple arcs complemented with multiple IMRT fields sets the gold standard for fSRS of ocular melanoma for photon therapy.

Evaluation of an automated knowledge based treatment planning system for head and neck.

BACKGROUND: This study evaluated an automated inverse treatment planning algorithm, Pinnacle Auto-Planning (AP), and compared automatically generated plans with historical plans in a large cohort of head and neck cancer patients. METHODS: Fifty consecutive patients treated with volumetric modulated arc therapy (Eclipse, Varian Medical System, Palo Alto, CA) for head and neck were re-planned with AP version 9.10. Only one single cycle of plan optimization using one single template was allowed for AP. The dose to the planning target volumes (PTV's; 3-4 dose levels), the organs at risk (OAR's) and the effective working time for planning was evaluated. Additionally, two experienced radiation oncologists blind-reviewed and ranked 10 plans. RESULTS: Dose coverage and dose homogeneity of the PTV were significantly improved with AP, however manually optimized plans showed significantly improved dose conformity. The mean dose to the parotid glands, oral mucosa, swallowing muscles, dorsal neck tissue and maximal dose to the spinal cord were significantly reduced with AP. In 64 % of the plans, the mean dose to any OAR (spinal cord excluded) was reduced by >20 % with AP in comparison to the manually optimized plans. In 12 % of the plans, the manually optimized plans showed reduced doses by >20 % in at least one OAR. The experienced radiation oncologists preferred the AP plan and the clinical plan in 80 and 20 % of the cases, respectively. The average effective working time was 3.8 min ± 1.1 min in comparison to 48.5 min ± 6.0 min using AP compared to the manually optimized plans, respectively. CONCLUSION: The evaluated automated planning algorithm achieved highly consistent and significantly improved treatment plans with potentially clinically relevant OAR sparing by >20 % in 64 % of the cases. The effective working time was substantially reduced with Auto-Planning.

Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.

BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Implementation and validation of a new fixation system for stereotactic radiation therapy: An analysis of patient immobilization.

PURPOSE: Stereotactic radiation therapy is an established treatment technique for intracranial malignancies. We evaluated a new intracranial immobilization system with an emphasis on determining the intrafraction motion and the correlation of this motion with treatment time. METHODS AND MATERIALS: Patients were immobilized using the trUpoint ARCH fixation system (CIVCO Medical Solutions). We collected data from 85 lesions in 73 patients treated between November 2011 and December 2013. Sixty-nine of 73 patients (95%) used the complete mask system; for the remaining 4 patients, the system had to be adapted. Patients were treated using volumetric modulated arc therapy stereotactic radiation therapy on a TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA). Fraction doses of 2-8 Gy were applied in 4-30 fractions. Daily cone beam computed tomography imaging was performed before the treatment and was matched to the reference computed tomography using a 6-degrees-of-freedom automatching procedure. Additionally, posttreatment cone beam computed tomography scans were performed to assess intrafraction motion for 67 patients (375 fractions). RESULTS: The average 3-dimensional setup error was 2.1 ± 2.9 mm. The mean pitch and roll was -0.1 ± 0.7° and 0.2 ± 0.7°. A total of 98.0% of the pitch values and 98.9% of the roll values were <1.5°. Mean intrafractional motion was 0.51 mm (±0.27) and mean treatment time was 10.1 minutes (±1.4). The maximum intrafractional motion was 2.0 mm in the longitudinal direction; 95% of the total shifts were <1.4 mm. The linear regression showed a weak but significant influence (R(2) = 0.26, P = .01) of the treatment time on the total intrafractional shift. CONCLUSIONS: The new intracranial immobilization system appears to be robust in terms of setup accuracy, intrafraction motion, and repositioning of the mask system.

Clinical outcome of postoperative highly conformal versus 3D conformal radiotherapy in patients with malignant pleural mesothelioma.

BACKGROUND: Radiotherapy (RT) is currently under investigation as part of a trimodality treatment of malignant pleural mesothelioma (MPM). The introduction of highly conformal radiotherapy (HCRT) technique improved dose delivery and target coverage in comparison to 3-dimensional conformal radiotherapy (3DCRT). The following study was undertaken to investigate the clinical outcome of both radiation techniques. METHODS: Thirty-nine MPM patients were treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant RT. Twenty-five patients were treated with 3DCRT, and 14 with HCRT (Intensity modulated radiotherapy or volumetric modulated arc therapy). Overall survival, disease free survival, locoregional recurrence and pattern of recurrence were assessed. A matched pair analysis was performed including 11 patients of each group. RESULTS: After matching for gender, age, histology, tumor stage and resection status, HCRT seemed superior to 3DCRT with a local relapse rate of 27.3% compared to 72.7% after 3DCRT (p = 0.06). The median time to local relapse was increased by 49% with HCRT in comparison to 3DCRT from 10.9 ± 5.4 months to 16.2 ± 3.1 months (p = 0.06). The median overall survival was 22.3 ± 15.3 months for HCRT and 21.2 ± 9.2 months for 3DCRT (p = 0.57). Recurrence analysis showed that in-field local relapses occurred in previously underdosed regions of the tumor bed in 16% of patients treated with 3DCRT and in 0% of HCRT patients. CONCLUSIONS: The use of HCRT increases the probability of local control as compared to 3DCRT by improving target volume coverage. HCRT did not improve overall survival in this patient series due to the high rate of distant recurrences.

Hierarchical enhanced non-rigid registration for target volume correction and propagation for adaptive external beam radiotherapy of carcinoma of the prostate.

Volumes change during fractionated radiotherapy (RT). We investigate a tool based on the Hierarchical Enhanced Registration Algorithm (HERA) to project a 3D segmentation set of the prostate into the subsequent imaging sets at any time point during RT by using intensity-based image registration techniques. Sequential CT sets during RT at 15, 30, 45, and 60 Gy of two patients were used. Five expert clinicians outlined the prostate in a blinded fashion, defining intraobserver and interobserver variability on a set of 35 and 25 scans, respectively. The observer variability and positioning for manual correction was compared to both affine and elastic image registration-based contour propagation. The overall mean error of the registration-based correction of the planning target volume was comparable to the interobserver variability of manual target volume definition. The correction by affine image fusion was inferior to the results of elastic registration. The maximal deviation for the interobserver segmentation was 15.4 mm, 10.5 mm for the affine and 8.0 mm for the elastic registration. The mean interobserver variability was 1.5 (± 1.4) mm, 2.8 (± 2.3) mm for the affine, and 2.2 (± 1.9) mm for the elastic registration. Intensity-based elastic registration of deformable anatomical structures with HERA is suitable for the assessment of changes of prostate volumes for the purpose of target propagation and adaptive radiotherapy.

Intensity-modulated radiotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy.

Radiotherapy reduces the local relapse rate after pleuropneumonectomy of malignant pleural mesothelioma (MPM). The optimal treatment technique with photons remains undefined. Comparative planning for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) was performed. Six MPM patients with significant postoperative intrathoracic air cavities were planned with IMRT and VMAT. A dose comparison for the targets and organ at risks (OAR) was performed. Robustness was assessed in respect to the variation of target dose with change in volume of air cavities. VMAT reduced the dose to the contralateral lung by reducing the volume covered by 13 Gy and 20 Gy by a factor 1.8 and 2.8, in respect to IMRT (p = 0.02). Dose distribution with VMAT was the most stable technique in regard to postsurgical air cavity variation. For IMRT, V90, V95, and the minimal target dose decreased by 40%, 64%, and 12% compared to 29%, 47%, and 7% with VMAT when air cavity decreased. Two arcs compared to one arc decreased the dose to all the organs at risk (OAR) while leaving PTV dose coverage unchanged. Increasing the number of arcs from two to three did not reduce the dose to the OAR further, but increased the beam-on time by 50%. Using partial arcs decreased the beam-on time by 43%. VMAT allows a lower lung dose and is less affected by the air cavity variation than IMRT. The best VMAT plans were obtained with two partial arcs. VMAT seems currently the most suitable technique for the treatment of MPM patients when air cavities are remaining and no adaptive radiotherapy is performed.

Proton therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy.

PURPOSE: To perform comparative planning for intensity-modulated radiotherapy (IMRT) and proton therapy (PT) for malignant pleural mesothelioma after radical surgery. METHODS AND MATERIALS: Eight patients treated with IMRT after extrapleural pleuropneumonectomy (EPP) were replanned for PT, comparing dose homogeneity, target volume coverage, and mean and maximal dose to organs at risk. Feasibility of PT was evaluated regarding the dose distribution with respect to air cavities after EPP. RESULTS: Dose coverage and dose homogeneity of the planning target volume (PTV) were significantly better for PT than for IMRT regarding the volume covered by >95% (V95) for the high-dose PTV. The mean dose to the contralateral kidney, ipsilateral kidney, contralateral lung, liver, and heart and spinal cord dose were significantly reduced with PT compared with IMRT. After EPP, air cavities were common (range, 0-850 cm(3)), decreasing from 0 to 18.5 cm(3)/day. In 2 patients, air cavity changes during RT decreased the generalized equivalent uniform dose (gEUD) in the case of using an a value of < - 10 to the PTV2 to <2 Gy in the presence of changing cavities for PT, and to 40 Gy for IMRT. Small changes were observed for gEUD of PTV1 because PTV1 was reached by the beams before air. CONCLUSION: Both PT and IMRT achieved good target coverage and dose homogeneity. Proton therapy accomplished additional dose sparing of most organs at risk compared with IMRT. Proton therapy dose distributions were more susceptible to changing air cavities, emphasizing the need for adaptive RT and replanning.

Combined photon and electron three-dimensional conformal versus intensity-modulated radiotherapy with integrated boost for adjuvant treatment of malignant pleural mesothelioma after pleuropneumonectomy.

PURPOSE: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. METHODS AND MATERIALS: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coverage were analyzed. RESULTS: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring >or=95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. CONCLUSION: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected.

Dynamic intensity-modulated non-coplanar arc radiotherapy (INCA) for head and neck cancer.

BACKGROUND AND PURPOSE: To define the potential advantages of intensity-modulated radiotherapy (IMRT) applied using a non-coplanar dynamic arc technique for the treatment of head and neck cancer. MATERIALS AND METHODS: External beam radiotherapy (EBRT) was planned in ten patients with head and neck cancer using coplanar IMRT and non-coplanar arc techniques, termed intensity modulated non-coplanar arc EBRT (INCA). Planning target volumes (PTV1) of first order covered the gross tumor volume and surrounding clinical target volume treated with 68-70 Gy, whereas PTV2 covered the elective lymph nodes with 54-55 Gy using a simultaneous internal boost. Treatment plan comparison between IMRT and INCA was carried out using dose-volume histogram and "equivalent uniform dose" (EUD). RESULTS: INCA resulted in better dose coverage and homogeneity of the PTV1, PTV2, and reduced dose delivered to most of the organs at risk (OAR). For the parotid glands, a reduction of the mean dose of 2.9 (+/- 2.0) Gy was observed (p = 0.002), the mean dose to the larynx was reduced by 6.9 (+/- 2.9) Gy (p = 0.003), the oral mucosa by 2.4 (+/- 1.1) Gy (p < 0.001), and the maximal dose to the spinal cord by 3.2 (+/- 1.7) Gy (p = 0.004). The mean dose to the brain was increased by 3.0 (+/- 1.4) Gy (p = 0.002) and the mean lung dose increased by 0.2 (+/- 0.4) Gy (p = 0.87). The EUD suggested better avoidance of the OAR, except for the lung, and better coverage and dose uniformity were achieved with INCA compared to IMRT. CONCLUSION: Dose delivery accuracy with IMRT using a non-coplanar dynamic arc beam geometry potentially improves treatment of head and neck cancer.