Target coverage and local recurrences after radiotherapy for sinonasal cancer in Denmark 2008-2015. A DAHANCA study.

PURPOSE: The study aimed to investigate the pattern of failure and describe compromises in the definition and coverage of the target for patients treated with curatively intended radiotherapy (RT) for sinonasal cancer (SNC). METHODS AND MATERIAL: Patients treated with curatively intended RT in 2008-2015 in Denmark for SNC were eligible for the retrospective cohort study. Information regarding diagnosis and treatment was retrieved from the national database of the Danish Head and Neck Cancer Group (DAHANCA). Imaging from the diagnosis of recurrences was collected, and the point of origin (PO) of the recurrent tumour was estimated. All treatment plans were collected and reviewed with the focus on target coverage, manual modifications of target volumes, and dose to organs at risk (OARs) above defined constraints. RESULTS: A total of 184 patients were included in the analysis, and 76 (41%) relapsed. The majority of recurrences involved T-site (76%). Recurrence imaging of 39 patients was evaluated, and PO was established. Twenty-nine POs (74%) were located within the CTV, and the minimum dose to the PO was median 64.1 Gy (3.1-70.7). The criteria for target coverage (V95%) was not met in 89/184 (48%) of the CTV and 131/184 (71%) of the PTV. A total of 24% of CTVs had been manually modified to spare OARs of high-dose irradiation. No difference in target volume modifications was observed between patients who suffered recurrence and patients with lasting remission. CONCLUSION: The majority of relapses after radical treatment of SNC were located in the T-site (the primary tumour site). Multiple compromises with regards to target coverage and tolerance levels for OARs in the sinonasal region, as defined from RT guidelines, were taken. No common practice in this respect could be derived from the study.

The role of computational methods for automating and improving clinical target volume definition.

Treatment planning in radiotherapy distinguishes three target volume concepts: the gross tumor volume (GTV), the clinical target volume (CTV), and the planning target volume (PTV). Over time, GTV definition and PTV margins have improved through the development of novel imaging techniques and better image guidance, respectively. CTV definition is sometimes considered the weakest element in the planning process. CTV definition is particularly complex since the extension of microscopic disease cannot be seen using currently available in-vivo imaging techniques. Instead, CTV definition has to incorporate knowledge of the patterns of tumor progression. While CTV delineation has largely been considered the domain of radiation oncologists, this paper, arising from a 2019 ESTRO Physics research workshop, discusses the contributions that medical physics and computer science can make by developing computational methods to support CTV definition. First, we overview the role of image segmentation algorithms, which may in part automate CTV delineation through segmentation of lymph node stations or normal tissues representing anatomical boundaries of microscopic tumor progression. The recent success of deep convolutional neural networks has also enabled learning entire CTV delineations from examples. Second, we discuss the use of mathematical models of tumor progression for CTV definition, using as example the application of glioma growth models to facilitate GTV-to-CTV expansion for glioblastoma that is consistent with neuroanatomy. We further consider statistical machine learning models to quantify lymphatic metastatic progression of tumors, which may eventually improve elective CTV definition. Lastly, we discuss approaches to incorporate uncertainty in CTV definition into treatment plan optimization as well as general limitations of the CTV concept in the case of infiltrating tumors without natural boundaries.

Recurrences after intensity modulated radiotherapy for head and neck squamous cell carcinoma more likely to originate from regions with high baseline [18F]-FDG uptake.

BACKGROUND AND PURPOSE: To analyze the recurrence pattern in relation to target volumes and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemoradiation. MATERIAL AND METHODS: 520 patients received radiotherapy for HNSCC from 2005 to 2009. Among 100 patients achieving complete clinical response and a later recurrence, 39 patients with 48 loco-regional failures had a recurrence CT scan before any salvage therapy. The estimated point of origin of each recurrence was transferred to the planning CT by deformable image co-registration. The recurrence position was then related to the delineated target volumes and iso-SUV-contours relative to the maximum standard uptake value (SUV). We defined the recurrence density as the total number of recurrences in a sub-volume divided by the sum of that volume for all patients. RESULTS: 54% (95% CI 37-69%) of recurrences originated inside the FDG-positive volume and 96% (95% CI 86-99%) in the high dose region. Recurrence density was significantly higher in the central target volumes (P<0.0001) and increased with increasing FDG avidity (P=0.036). CONCLUSIONS: The detailed pattern-of-failure data analysis suggests that most recurrences occur in the FDG PET positive areas or the solid tumor.

Irregular breathing during 4DCT scanning of lung cancer patients: is the midventilation approach robust?

BACKGROUND: With 4DCT the risk of introducing positional systematic errors in lung cancer radiotherapy can be minimised. A common approach is to plan on the phase bin of the 4DCT best representing the tumour's time-weighted mean position also called the midventilation scan. However breathing irregularities can introduce uncertainties and potentially misrepresent both the tumour trajectory and the determination of the midventilation phase. In this study we evaluated the robustness of the midventilation approach in the presence of irregular breathing patterns. METHODS: A LEGO Mindstorms(®) phantom with compact balls simulating lung tumours was constructed. The breathing curves loaded in the phantom were either acquired from a human volunteer or constructed with various magnitudes (ranging from 12 to 29 mm) as well as various irregularities of motion pattern. Repeated 4DCT scans were performed while tumour trajectories were recorded with two motion tracking systems. RESULTS: The time-weighted mean tumour position is accurately represented in 4DCT scans, even for irregular breathing patterns: the position presentation in the midventilation scan was always within in one standard deviation of the global position presentation (3 mm and 2 mm for regular and irregular breathing patterns, respectively). The displacement representation tended to be underestimated in 4DCT scans. CONCLUSION: The midventilation approach is robust even in the presence of breathing irregularity. The representation of the tumour trajectory in 4DCT scans is affected by breathing irregularity and the extent of tumour motion can be underestimated, which will affect the calculation of patient-individualised margins based on the 4DCT scan.

Motion in radiotherapy: photon therapy.

This review considers the management of motion in photon radiation therapy. An overview is given of magnitudes and variability of motion of various structures and organs, and how the motion affects images by producing artifacts and blurring. Imaging of motion is described, including 4DCT and 4DPET. Techniques for monitoring motion in real time by use of surrogates are reviewed. Treatment planning for various motion-management treatment delivery strategies is discussed, including choice of planning image, treatment field margins and dose calculation. Imaging techniques displaying motion in the treatment room for pre-treatment as well as real-time imaging for localization and verification are covered, and their use for various motion-management treatment delivery techniques is discussed. Use of motion management for different treatment sites­breast, lung and other sites­is elaborated, and gating, breath-hold and beam tracking strategies are described. Suggestions are given for breast and lung for practicable protocols for routine clinical use of motion management, including decision strategies. Finally, a perspective of the future of motion management in photon radiation therapy is given.

Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer.

BACKGROUND: Traditionally, radiation therapy plans are optimized without consideration of chemotherapy. Here, we model the risk of radiation pneumonitis (RP) in the presence of a possible interaction between chemotherapy and radiation dose distribution. MATERIAL AND METHODS: Three alternative treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration of the chemotherapy effect. The effect of chemotherapy is modeled as an independent cell killing process using a uniform chemotherapy equivalent radiation dose (CERD) added to the entire organ at risk. We estimate the risk of grade 3 or higher RP (G3RP) using the critical volume model. RESULTS: The mean risk of clinical G3RP at zero CERD is 5% for tomotherapy (range: 1-18 %) and 14% for 3D-CRT (range 2-49%). When the CERD exceeds 9 Gy, however, the risk of RP with the tomotherapy plans become higher than the 3D-CRT plans. The IMPT plans are less toxic both at zero CERD (mean 2%, range 1-5%) and at CERD = 10 Gy (mean 7%, range 1-28%). Tomotherapy yields a lower risk of RP than 3D-CRT for 17/18 patients at zero CERD, but only for 7/18 patients at CERD = 10 Gy. IMPT gives the lowest risk of all plans for 17/18 patients at zero CERD and for all patients with CERD = 10 Gy. CONCLUSIONS: The low dose bath from highly conformal photon techniques may become relevant for lung toxicity when radiation is combined with cytotoxic chemotherapy as shown here. Proton therapy allows highly conformal delivery while minimizing the low dose bath potentially interacting with chemotherapy. Thus, intensive drug-radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting.

Rotational radiotherapy for prostate cancer in clinical practice.

BACKGROUND AND PURPOSE: Radiotherapy is the standard treatment in locally advanced prostate cancer. The latest technological improvement is modulated rotational radiotherapy, where one single rotation of the treatment machine is used to conform the dose delivery to the target and spare organs at risk, requiring less than 2 min of beam-on time per treatment fraction. MATERIALS AND METHODS: We report herein our experience from the first 46 patients treated for prostate cancer, clinical stage T1-3 with rotational therapy ("RapidArc®", Varian Medical systems) (RA). This patient group is compared to a group of 50 patients treated with a 5-field Intensity Modulated Radiation Therapy (IMRT) technique over the same period. The comparison parameters include target coverage, dose to OAR, treatment time and number of monitor units. Daily-IGRT using implanted gold markers is used before and after treatment to investigate intra-fractional prostate displacement. RESULTS: RA results in improved sparing of the rectum and achieves desired dose distributions with fewer monitor units and a shorter treatment time (<1.5 min versus up to 8.9 min with IMRT). This shorter treatment time also translates in a decreased risk of patient motion during treatment: daily-IGRT demonstrates reduced prostate motion (<3mm 3D vector) from 16.7% to 4.7% in RA patients. Only slight side-effects were seen in the two groups of patients. CONCLUSIONS: RA results in improved sparing of the rectum, however, at the expense of an increase in dose to the femoral heads in prostate patients. The treatment time is significantly reduced from 4.9 min on average with 5-field IMRT to 1.1 min with RA, which allows for a reduction of infractional prostate motion.

Feasibility of dose painting using volumetric modulated arc optimization and delivery.

PURPOSE: Dose painting strategies are limited by optimization algorithms in treatment planning systems and physical constraints of the beam delivery. We investigate dose conformity using the RapidArc optimizer and beam delivery technique. Furthermore, robustness of the plans with respect to positioning uncertainties are evaluated. METHODS: A head & neck cancer patient underwent a [(61)Cu]Cu-ATSM PET/CT-scan. PET-SUVs were converted to prescribed dose with a base dose of 60 Gy, and target mean dose 90 Gy. The voxel-based prescription was converted into 3, 5, 7, 9, and 11 discrete prescription levels. Optimization was performed in Eclipse, varying the following parameters: MLC leaf width (5 mm and 2.5 mm), number of arcs (1 and 2) and collimator rotation (0, 15, 30 and 45 degrees). Dose conformity was evaluated using quality volume histograms (QVHs), and relative volumes receiving within ±5% of prescribed dose (Q(0.95-1.05)). Deliverability was tested using a Delta4(®) phantom. Robustness was tested by shifting the isocenter 1 mm and 2 mm in all directions, and recalculating the dose. RESULTS: Good conformity was obtained using MLC leaf width 2.5 mm, two arcs, and collimators 45/315 degrees, with Q(0.95-1.05)=92.8%, 91.6%, 89.7% and 84.6%. Using only one arc or increasing the MLC leaf width had a small deteriorating effect of 2-5%. Small changes in collimator angle gave small changes, but large changes in collimator angle gave a larger decrease in plan conformity; for angles of 15 and 0 degrees (two arcs, 2.5 mm leaf width), Q(0.95-1.05) decreased by up to 15%. Consistency between planned and delivered dose was good, with ∼90% of gamma values <1. For 1 mm shift, Q(0.95-1.05) was decreased by 5-15%, while for 2 mm shift, Q(0.95-1.05) was decreased to 55-60%. CONCLUSIONS: Results demonstrate feasibility of planning of prescription doses with multiple levels for dose painting using RapidArc, and plans were deliverable. Robustness to positional error was low.

A treatment planning study of the potential of geometrical tracking for intensity modulated proton therapy of lung cancer.

BACKGROUND: Proton therapy of lung cancer holds the potential for a reduction of the volume of irradiated normal lung tissue. In this work we investigate the robustness of intensity modulated proton therapy (IMPT) plans to motion, and evaluate a geometrical tumour tracking method to compensate for tumour motion. MATERIAL AND METHODS: Seven patients with a nine targets with 4DCT scans were selected. IMPT plans were made on the midventilation phase using a 3-field technique. The plans were transferred and calculated on the remaining nine phases of the 4DCT, and the combined dose distribution was summed using deformable image registration (DIR). An additional set of plans were made in which the proton beam was simply geometrically shifted to the centre of the gross tumour volume (GTV), i.e. simulating tracking of the tumour motion but without on-line adjustment of the proton energies. A possible interplay effect between the dynamics of the spot scanning delivery and the tumour motion has not been considered in this work. RESULTS: Around 97-100% of the GTV was covered by 95% of the prescribed dose (V95) for a tumour displacement of less than about 1 cm with a static beam. For the remaining three of nine targets with a larger motion the tracking method studied provided a marked improvement over static beam; raising the GTV V95 from 95 to 100%, 82 to 98% and 51 to 97%, respectively. CONCLUSION: The possibility of performing DIR and summing the dose on the 4DCT data set was shown to be feasible. The fairly simplistic tracking method suggested here resulted in a marked improvement in GTV coverage for tumours with large intra-fractional motion (>1 cm displacement), indicating that on-line adjustment of the proton energies may be redundant.

RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo simulation.

The aim of this study was to verify the advanced inhomogeneous dose distribution produced by a volumetric arc therapy technique (RapidArc) using 3D gel measurements and Monte Carlo (MC) simulations. The TPS (treatment planning system)-calculated dose distribution was compared with gel measurements and MC simulations, thus investigating any discrepancy between the planned dose delivery and the actual delivery. Additionally, the reproducibility of the delivery was investigated using repeated gel measurements. A prostate treatment plan was delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC-Arc code. The relative absorbed dose differences were calculated voxel-by-voxel, within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS versus gel and TPS versus MC. The differences between the verification methods, MC versus gel, and between two repeated gel measurements were investigated in the same way. For all volume comparisons, the mean value was within 1% and the standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5 mm (% dose difference and mm distance to agreement) within the volume enclosed by the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)), respectively. All comparisons resulted in very high pass rates. More than 95% of the TPS points were within 3%/3 mm of both the gel measurement and MC simulation, both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements showed excellent consistency, indicating reproducible delivery. Using MC simulations and gel measurements, this verification study successfully demonstrated that the RapidArc plan was both accurately calculated and delivered as planned.

The effect of different lung densities on the accuracy of various radiotherapy dose calculation methods: implications for tumour coverage.

PURPOSE: To evaluate against Monte-Carlo the performance of various dose calculations algorithms regarding lung tumour coverage in stereotactic body radiotherapy (SBRT) conditions. MATERIALS AND METHODS: Dose distributions in virtual lung phantoms have been calculated using four commercial Treatment Planning System (TPS) algorithms and one Monte Carlo (MC) system (EGSnrc). We compared the performance of the algorithms in calculating the target dose for different degrees of lung inflation. The phantoms had a cubic 'body' and 'lung' and a central 2-cm diameter spherical 'tumour' (the body and tumour have unit density). The lung tissue was assigned five densities (rho(lung)): 0.01, 0.1, 0.2, 0.4 and 1g/cm(3). Four-field treatment plans were calculated with 6- and 18 MV narrow beams for each value of rho(lung). We considered the Pencil Beam Convolution (PBC(Ecl)) and the Analytical Anisotropic Algorithm (AAA(Ecl)) from Varian Eclipse and the Pencil Beam Convolution (PBC(OMP)) and the Collapsed Cone Convolution (CCC(OMP)) algorithms from Oncentra MasterPlan. RESULTS: When changing rho(lung) from 0.4 to 0.1g/cm(3), the MC median target dose decreased from 89.2% to 74.9% for 6 MV and from 83.3% to 61.6% for 18 MV (of dose maximum in the homogenous case at both energies), while for both PB algorithms the median target dose was virtually independent of lung density. CONCLUSIONS: Both PB algorithms overestimated the target dose, the overestimation increasing as rho(lung) decreased. Concerning target dose, the AAA(Ecl) and CCC(OMP) algorithms appear to be adequate alternatives to MC.

Interfractional changes in tumour volume and position during entire radiotherapy courses for lung cancer with respiratory gating and image guidance.

INTRODUCTION: With the purpose of implementing gated radiotherapy for lung cancer patients, this study investigated the interfraction variations in tumour size and internal displacement over entire treatment courses. To explore the potential of image guided radiotherapy (IGRT) the variations were measured using a set-up strategy based on imaging of bony landmarks and compared to a strategy using in room lasers, skin tattoos and cupper landmarks. MATERIALS AND METHODS: During their six week treatment course of 60Gy in 2Gy fractions, ten patients underwent 3 respiratory gated CT scans. The tumours were contoured on each CT scan to evaluate the variations in volumes and position. The lung tumours and the mediastinal tumours were contoured separately. The positional variations were measured as 3D mobility vectors and correlated to matching of the scans using the two different strategies. RESULTS: The tumour size was significantly reduced from the first to the last CT scan. For the lung tumours the reduction was 19%, p=0.03, and for the mediastinal tumours the reduction was 34%, p=0.0007. The mean 3D mobility vector and the SD for the lung tumours was 0.51 cm (+/-0.21) for matching using bony landmarks and 0.85 cm (+/-0.54) for matching using skin tattoos. For the mediastinal tumours the corresponding vectors and SD's were 0.55 cm (+/-0.19) and 0.72 cm (+/-0.43). The differences between the vectors were significant for the lung tumours p=0.004. The interfractional overlap of lung tumours was 80-87% when matched using bony landmarks and 70-76% when matched using skin tattoos. The overlap of the mediastinal tumours were 60-65% and 41-47%, respectively. CONCLUSIONS: Despite the use of gating the tumours varied considerably, regarding both position and volume. The variations in position were dependent on the set-up strategy. Set-up using IGRT was superior to set-up using skin tattoos.

Can audio coached 4D CT emulate free breathing during the treatment course?

BACKGROUND: The image quality of 4DCT depends on breathing regularity. Respiratory audio coaching may improve regularity and reduce motion artefacts. We question the safety of coached planning 4DCT without coaching during treatment. We investigated the possibility of coaching to a more stable breathing without changing the breathing amplitude. The interfraction variation of the breathing cycle amplitude in free and coached breathing was studied as well as the possible impact of fatigue on longer coaching sessions. METHODS: Thirteen volunteers completed respiratory audio coaching on 3 days within a 2 week period. An external marker system monitoring the motion of the thoraco-abdominal wall was used to track the respiration. On all days, free breathing and two coached breathing curves were recorded. We assumed that free versus coached breathing from day 1 (reference session) simulated breathing during an uncoached versus coached planning 4DCT, respectively, and compared the mean breathing cycle amplitude to the free versus coached breathing from day 2 and 3 simulating free versus coached breathing during treatment. RESULTS: For most volunteers it was impossible to apply coaching without changes in breathing cycle amplitude. No significant decrease in standard deviation of breathing cycle amplitude distribution was seen. Generally it was not possible to predict the breathing cycle amplitude and its variation the following days based on the breathing in the reference session irrespective of coaching or free breathing. We found a significant tendency towards an increased breathing cycle amplitude variation with the duration of the coaching session. CONCLUSION: These results suggest that large interfraction variation is present in breathing amplitude irrespective of coaching, leading to the suggestion of daily image guidance for verification of respiratory pattern and tumour related motion. Until further investigated it is not recommendable to use coached 4DCT for planning of a free breathing treatment course.

The role of image guidance in respiratory gated radiotherapy.

Respiratory gating for radiotherapy beam delivery is a widely available technique, manufactured and sold by most of the major radiotherapy machine vendors. Respiratory gated beam delivery is intended to limit the irradiation of tumours moving with respiration to selected parts of the respiratory cycle, and thereby enable dose escalation and/or reduction of dose to organs at risk. Without adequate use of respiratory correlated image guidance on a regular basis, respiratory beam gating may however have a detrimental effect on target coverage. Image guidance of tumour respiratory motion is therefore of utmost importance for the safe introduction of respiratory gating. In this short overview, suitable image guidance strategies for respiratory gated radiotherapy are reviewed for two cancer sites; breast cancer and lung tumours.

Respiratory gated beam delivery cannot facilitate margin reduction, unless combined with respiratory correlated image guidance.

PURPOSE/OBJECTIVE: In radiotherapy of targets moving with respiration, beam gating is offered as a means of reducing the target motion. The purpose of this study is to evaluate the safe magnitude of margin reduction for respiratory gated beam delivery. MATERIALS/METHODS: The study is based on data for 17 lung cancer patients in separate protocols at Rigshospitalet and Stanford Cancer Center. Respiratory curves for external optical markers and implanted fiducials were collected using equipment based on the RPM system (Varian Medical Systems). A total of 861 respiratory curves represented external measurements over 30 fraction treatment courses for 10 patients, and synchronous external/internal measurements in single sessions for seven patients. Variations in respiratory amplitude (simulated coaching) and external/internal phase shifts were simulated by perturbation with realistic values. Variations were described by medians and standard deviations (SDs) of position distributions of the markers. Gating windows (35% duty cycle) were retrospectively applied to the respiratory data for each session, mimicking the use of commercially available gating systems. Medians and SDs of gated data were compared to those of ungated data, to assess potential margin reductions. RESULTS: External respiratory data collected over entire treatment courses showed SDs from 1.6 to 8.1mm, the major part arising from baseline variations. The gated data had SDs from 1.5 to 7.7mm, with a mean reduction of 0.3mm (6%). Gated distributions were more skewed than ungated, and in a few cases a marginal miss of gated respiration would be found even if no margin reduction was applied. Regularization of breathing amplitude to simulate coaching did not alter these results significantly. Simulation of varying phase shifts between internal and external respiratory signals showed that the SDs of gated distributions were the same as for the ungated or smaller, but the median values were markedly shifted. The gated distributions could generally not be covered by margins derived from ungated data, if the phase shift was not accounted for. CONCLUSIONS: Margins can only be reduced for respiratory gated radiotherapy, if respiratory baseline shifts and variations in external/internal motion correlation are accounted for. Gated beam delivery alone cannot facilitate margin reduction. In the worst case, margins must be increased to accommodate inter-fraction variations in respiration.

Cardiac and pulmonary complication probabilities for breast cancer patients after routine end-inspiration gated radiotherapy.

PURPOSE: Substantial reductions of radiation doses to heart and lung can be achieved using breathing adaptation of adjuvant radiotherapy following conservative surgery for breast cancer. The purpose of this study was to estimate the radiobiological implications after routine use of an end-inspiration gated treatment, and to compare the results with predictions based on pre-clinical CT-studies. PATIENTS AND METHODS: Nineteen consecutive patients with axillary lymph node-positive left-sided breast cancer were referred for adjuvant radiotherapy after breast conserving surgery. Treatment was performed with gating in the end-inspiration phase of audio-coached enhanced free breathing. The target intended to encompass the remaining breast, ipsilateral internal mammary and periclavicular nodes, and the prescription dose was 48Gy in 24 fractions. A three-field mono-isocentric conformal technique using deep tangentials and a supraclavicular field was employed. NTCPs were calculated using the relative seriality model for the heart, and the model proposed by Burman et al. for the lung. The observed values were compared to those predicted from two previous CT-studies for a deep inspiration breath-hold technique and an uncoached end-inspiration gating technique. RESULTS: The ipsilateral lung V(50) (relative volume receiving more than 50% of the prescription dose) had a median value of 23.7% (range 10.8-35.1%) over the patient population. The corresponding median lung pneumonitis probability was 1.1% (range 0-14%). The median heart V(50) was 0.8% (range 0-19.1%) with a corresponding median cardiac mortality NTCP of 0.1% (range 0-5.7%). These results compare well with the predictions of our previous CT-studies. There is a significant reduction in dose to the left anterior descending coronary artery for the enhanced end-inspiration gating technique compared to the uncoached end-inspiration technique employed in the CT-studies. CONCLUSIONS: In a routine clinical practice involving adjuvant breast radiotherapy gated in an enhanced end-inspiration phase, remarkably low doses to organs at risk are observed. The corresponding cardiac and pulmonary complication risks are of the order of 1% and smaller.

Reduction of cardiac and pulmonary complication probabilities after breathing adapted radiotherapy for breast cancer.

PURPOSE: Substantial reductions of cardio-pulmonary radiation doses can be achieved using voluntary deep inspiration breath-hold (DIBH) or free breathing inspiration gating (IG) in radiotherapy after conserving surgery for breast cancer. The purpose of this study is to evaluate the radiobiological implications of such dosimetric benefits. METHODS AND MATERIALS: Patients from previously reported studies were pooled for a total of 33 patients. All patients underwent DIBH and free breathing (FB) scans, and 17 patients underwent an additional IG scan. Tangential conformal treatment plans covering the remaining breast, internal mammary, and periclavicular nodes were optimized for each scan, prescription dose 48 Gy. Normal tissue complication probabilities were calculated using the relative seriality model for the heart, and the model proposed by Burman et al. for the lung. RESULTS: Previous computed tomography studies showed that both voluntary DIBH and IG provided reduction of the lung V50 (relative volume receiving more than 50% of prescription dose) on the order of 30-40%, and a 80-90% reduction of the heart V50 for left-sided cancers. Corresponding pneumonitis probability of 28.1% (range, 0.7-95.6%) for FB could be reduced to 2.6% (range, 0.1-40.1%) for IG, and 4.3% (range, 0.1-59%) for DIBH. The cardiac mortality probability could be reduced from 4.8% (range, 0.1-23.4%) in FB to 0.5% (range, 0.1-2.6%) for IG and 0.1% (range, 0-3.0%) for DIBH. CONCLUSIONS: Remarkable potential is shown for simple voluntary DIBH and free breathing IG to reduce the risk of both cardiac mortality and pneumonitis for the common technique of adjuvant tangential breast irradiation.

Breathing adapted radiotherapy for breast cancer: comparison of free breathing gating with the breath-hold technique.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy after breast-conserving surgery for breast cancer implies a risk of late cardiac and pulmonary toxicity. This is the first study to evaluate cardiopulmonary dose sparing of breathing adapted radiotherapy (BART) using free breathing gating, and to compare this respiratory technique with voluntary breath-hold. PATIENTS AND METHODS: 17 patients were CT-scanned during non-coached breathing manoeuvre including free breathing (FB), end-inspiration gating (IG), end-expiration gating (EG), deep inspiration breath-hold (DIBH) and end-expiration breath-hold (EBH). The Varian Real-time Position Management system (RPM) was used to monitor respiratory movement and to gate the scanner. For each breathing phase, a population based internal margin (IM) was estimated based on average chest wall excursion, and incorporated into an individually optimised three-field mono-isocentric wide tangential photon field treatment plan for each scan. The target included the remaining breast, internal mammary nodes and periclavicular nodes. RESULTS: The mean anteroposterior chest wall excursion during FB was 2.5mm. For IG and EG, the mean excursions within gating windows were 1.1 and 0.7 mm, respectively, whereas for DIBH and EBH the excursions were 4.1 and 2.6mm, respectively. For patients with left-sided cancer, the median heart volume receiving more than 50% of the prescription dose was reduced from 19.2% for FB to 2.8% for IG and 1.9% for DIBH, and the median left anterior descending (LAD) coronary artery volume was reduced from 88.9% to 22.4% for IG and 3.6% for DIBH. Simultaneously, the median ipsilateral relative lung volume irradiated to >50% of the prescribed target dose for both right- and left-sided cancers was reduced from 45.6% for FB to 29.5% for IG and 27.7% for DIBH. For EBH and EG, both the irradiated heart, LAD and lung volumes increased compared to FB. CONCLUSIONS: This is the first study to demonstrate the dosimetric benefits of free breathing gated breast cancer radiotherapy. IG compared favourably with DIBH, substantially reducing cardiac doses simultaneous with significant pulmonary tissue sparing.