Optimization of combined electron and photon beams for breast cancer

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.     

全乳腺放射治疗3种照射技术对比

目的评价不同全乳腺放射治疗技术的剂量学优缺点。方法选取乳腺癌保乳术后患者10例,均为女性,年龄25～58岁,中位年龄42岁。用常规切线野、野中野调强、多野调强3种技术设计全乳腺放射治疗计划并进行剂量学对比。结果与常规切线野计划比较,野中野调强计划99%靶区体积含盖剂量从（4640±72）cGy增加到（4753±25）cGy;剂量不均匀指数从1.104±0.017下降到1.060±0.008。常规切线野计划与野中野调强计划在危及器官受量上的差异无统计学意义。野中野调强计划与多野调强计划在靶区剂量分布上的差异无统计学意义;与野中野调强计划比较,多野调强计划中心脏接受高于10Gy剂量的体积（V10）从（13.0±8.5）%增加到（53.3±22.7）%;同侧肺的V10从（25.2±3.4）%增加到（42.7±3.7）%;对侧乳腺、对侧肺、非特异正常组织的V5分别从（1.9±3.1）%增加到（32.6±2.3）%、从0到（18.5±8.3）%、从（9.9±1.0）%到（32.1±3.6）%。结论野中野调强技术较常规切线野技术明显改善靶区剂量分布;在此基础上多野调强技术未能明显进一步改善靶区剂量,但增加正常组织照射。     

颈段及胸上段食管癌调强放射治疗计划的比较

目的：射野数目的多少在调强放射计划中直接影响着靶区的适形性（conformity）,均匀度（uniformity）以及对周围危及器官（organs at risk,OAR）的保护。本文就颈段及胸上段食管癌,对不同射野数目进行调强放射治疗计划的比较。方法：回顾继往颈段及胸上段食管癌病例,从中挑选5位患者,运用5,7,9个射野的调强放射治疗计划,同时对IMRT的靶区运用200 cGy/fx,30fx总共60 Gy剂量,比较在这个给定相同的剂量的条件下,通过剂量体积直方图（dose volumehistograms,DVH）,等剂量曲线分布（iso-dose distributions）以及靶区的适形指数（conformity index,CI）等来比较各个计划中计划靶区（planning target volume,PTV）,以及危及器官（OARs）的剂量学差异。结果：随着射野数目的增加靶区适形度以及等剂量线分布越来越好。7、9个射野对肺的损伤也不像想象中那么大。甚至7、9野的IMRT在肺的V20更低。结论：相比5个射野的IMRT计划,7个射野能提供更好的适形度和均匀性,以及对肺组织的保护;而相比9野计划,7个射野能运用更短的治疗时间和更少的加速器跳数（monitor unite,MU）,减少器官运动对靶区剂量的影响。     

Combined modulated electron and photon beams planned by a Monte-Carlo-based optimization procedure for accelerated partial breast irradiation

The purpose of this study was to present a Monte-Carlo (MC)-based optimization procedure to improve conventional treatment plans for accelerated partial breast irradiation (APBI) using modulated electron beams alone or combined with modulated photon beams, to be delivered by a single collimation device, i.e. a photon multi-leaf collimator (xMLC) already installed in a standard hospital. Five left-sided breast cases were retrospectively planned using modulated photon and/or electron beams with an in-house treatment planning system (TPS), called CARMEN, and based on MC simulations. For comparison, the same cases were also planned by a PINNACLE TPS using conventional inverse intensity modulated radiation therapy (IMRT). Normal tissue complication probability for pericarditis, pneumonitis and breast fibrosis was calculated. CARMEN plans showed similar acceptable planning target volume (PTV) coverage as conventional IMRT plans with 90% of PTV volume covered by the prescribed dose (D(p)). Heart and ipsilateral lung receiving 5% D(p) and 15% D(p), respectively, was 3.2-3.6 times lower for CARMEN plans. Ipsilateral breast receiving 50% D(p) and 100% D(p) was an average of 1.4-1.7 times lower for CARMEN plans. Skin and whole body low-dose volume was also reduced. Modulated photon and/or electron beams planned by the CARMEN TPS improve APBI treatments by increasing normal tissue sparing maintaining the same PTV coverage achieved by other techniques. The use of the xMLC, already installed in the linac, to collimate photon and electron beams favors the clinical implementation of APBI with the highest efficiency.     

Calculation of effective dose from measurements of secondary neutron spectra and scattered photon dose from dynamic MLC IMRT for 6 MV, 15 MV, and 18 MV beam energies

Effective doses were calculated from the delivery of 6 MV, 15 MV, and 18 MV conventional and intensity-modulated radiation therapy (IMRT) prostate treatment plans. ICRP-60 tissue weighting factors were used for the calculations. Photon doses were measured in phantom for all beam energies. Neutron spectra were measured for 15 MV and 18 MV and ICRP-74 quality conversion factors used to calculate ambient dose equivalents. The ambient dose equivalents were corrected for each tissue using neutron depth dose data from the literature. The depth corrected neutron doses were then used as a measure of the neutron component of the ICRP protection quantity, organ equivalent dose. IMRT resulted in an increased photon dose to many organs. However, the IMRT treatments resulted in an overall decrease in effective dose compared to conventional radiotherapy. This decrease correlates to the ability of an intensity-modulated field to minimize dose to critical normal structures in close proximity to the treatment volume. In a comparison of the three beam energies used for the IMRT treatments, 6 MV resulted in the lowest effective dose, while 18 MV resulted in the highest effective dose. This is attributed to the large neutron contribution for 18 MV compared to no neutron contribution for 6 MV.     

Comparative analysis of 60Co intensity-modulated radiation therapy

In this study, we perform a scientific comparative analysis of using (60)Co beams in intensity-modulated radiation therapy (IMRT). In particular, we evaluate the treatment plan quality obtained with (i) 6 MV, 18 MV and (60)Co IMRT; (ii) different numbers of static multileaf collimator (MLC) delivered (60)Co beams and (iii) a helical tomotherapy (60)Co beam geometry. We employ a convex fluence map optimization (FMO) model, which allows for the comparison of plan quality between different beam energies and configurations for a given case. A total of 25 clinical patient cases that each contain volumetric CT studies, primary and secondary delineated targets, and contoured structures were studied: 5 head-and-neck (H&N), 5 prostate, 5 central nervous system (CNS), 5 breast and 5 lung cases. The DICOM plan data were anonymized and exported to the University of Florida optimized radiation therapy (UFORT) treatment planning system. The FMO problem was solved for each case for 5-71 equidistant beams as well as a helical geometry for H&N, prostate, CNS and lung cases, and for 3-7 equidistant beams in the upper hemisphere for breast cases, all with 6 MV, 18 MV and (60)Co dose models. In all cases, 95% of the target volumes received at least the prescribed dose with clinical sparing criteria for critical organs being met for all structures that were not wholly or partially contained within the target volume. Improvements in critical organ sparing were found with an increasing number of equidistant (60)Co beams, yet were marginal above 9 beams for H&N, prostate, CNS and lung. Breast cases produced similar plans for 3-7 beams. A helical (60)Co beam geometry achieved similar plan quality as static plans with 11 equidistant (60)Co beams. Furthermore, 18 MV plans were initially found not to provide the same target coverage as 6 MV and (60)Co plans; however, adjusting the trade-offs in the optimization model allowed equivalent target coverage for 18 MV. For plans with comparable target coverage, critical structure sparing was best achieved with 6 MV beams followed closely by (60)Co beams, with 18 MV beams requiring significantly increased dose to critical structures. In this paper, we report in detail on a representative set of results from these experiments. The results of the investigation demonstrate the potential for IMRT radiotherapy employing commercially available (60)Co sources and a double-focused MLC. Increasing the number of equidistant beams beyond 9 was not observed to significantly improve target coverage or critical organ sparing and static plans were found to produce comparable plans to those obtained using a helical tomotherapy treatment delivery when optimized using the same well-tuned convex FMO model. While previous studies have shown that 18 MV plans are equivalent to 6 MV for prostate IMRT, we found that the 18 MV beams actually required more fluence to provide similar quality target coverage.     

A 4 MV flattening filter-free beam: commissioning and application to conformal therapy and volumetric modulated arc therapy

Recent studies have indicated that radiotherapy treatments undertaken on a flattening filter-free (FFF) linear accelerator have a number of advantages over treatments undertaken on a conventional linear accelerator. In addition, 4 MV photon beams may give improved isodose coverage for some treatment volumes at air/tissue interfaces, compared to when utilizing the clinical standard of 6 MV photons. In order to investigate these benefits, FFF beams were established on an Elekta Beam Modulator linear accelerator for 4 MV photons. Commissioning beam data were obtained for open and wedged fields. The measured data were then imported into a treatment planning system and a beam model was commissioned. The beam model was optimized to improve dose calculations at shallow, clinically relevant depths. Following verification, the beam model was utilized in a treatment planning study, including volumetric modulated arc therapy, for a selection of lung, breast/chest wall and larynx patients. Increased dose rates of around 800 MU min(-1) were recorded for open fields (relative to 320 MU min(-1) for filtered open fields) and reduced head scatter was inferred from output factor measurements. Good agreement between planned and delivered dose was observed in verification of treatment plans. The planning study indicated that with a FFF beam, equivalent (and in some cases improved) isodose profiles could be achieved for small lung and larynx treatment volumes relative to 4 MV filtered treatments. Furthermore, FFF treatments with wedges could be replicated using open fields together with an 'effective wedge' technique and isocentre shift. Clinical feasibility of a FFF beam was therefore demonstrated, with beam modelling, treatment planning and verification being successfully accomplished.     

乳腺癌螺旋断层放射治疗与调强放射治疗的剂量学研究与临床剂量实测比较

目的:利用螺旋断层放射治疗技术与传统医用直线加速器对乳腺癌放疗中重要正常组织与靶区剂量-体积参数进行剂量学比较。同时,在剂量学研究基础上进行临床实际吸收剂量测量验证各种技术间临床应用的优势与劣势。 方法:选取10例T1N0M0期乳腺癌保乳术后行乳腺靶区放射治疗病人（无锁骨上照射区域）,处方剂量为50 Gy/25次,利用螺旋断层放射治疗定角调强技术、螺旋断层放疗技术与医用直线加速器调强技术,比较乳腺癌靶区剂量和正常组织剂量的优劣。评估靶区剂量与适形度指数（CI）、均匀性指数（HI）和正常组织剂量-体积参数,进行剂量学比较。同时,利用热释光剂量仪在乳腺癌病人表皮进行实测剂量,比较3种技术处理由于病人呼吸运动对表面剂量的影响,及评估时间因素对治疗效率的影响。 结果:10例乳腺癌病人采用定角调强技术、螺旋断层放疗技术与医用直线加速器调强技术PTV HI分别为0.15±0.01、0.06±0.01和0.20±0.15（P<0.001）;CI分别为0.76±0.00、0.81±0.03和0.74±0.04（P>0.05）;心脏平均剂量分别为4.12±0.87、3.82±0.53、6.33±2.49 Gy（P<0.001）,左前降支最大剂量分别为20.38±5.66、13.34±3.78、34.56±4.12 Gy（P<0.001）,患侧肺组织平均剂量分别为6.78±1.33、7.22±2.34、12.76±2.10 Gy（P<0.001）。患者6个实测剂量点的吸收剂量3种技术比较有统计学意义（P<0.001）。 结论:从综合靶区覆盖、正常组织剂量-体积参数、剂量实测与治疗效率等方面比较,螺旋断层放射治疗的定角调强技术相对于其他两种技术而言有低剂量范围小、靶区覆盖佳、解决治疗中呼吸运动影响等优势,推荐使用该技术用于乳腺癌病人放射治疗。     

不同能量X线胸段食管癌调强放疗计划的剂量学研究

目的:研究不同能量X射线治疗胸段食管癌调强放疗(IMRT)计划的剂量学差异。方法:选择l2例胸段食管癌患者,在ADAC Pinnacle3三维治疗计划系统(TPS)中分别采用6 MV、10 MV和15 MV X线给每位患者设计三个调强放疗计划,在规定计划靶区(PTV)至少达到95%处方剂量的前提下,根据剂量体积直方图(DVH)比较三种计划的靶区剂量分布及脊髓、肺、心脏等正常组织受照射剂量的差异。结果:三种计划中靶区的最大剂量、最小剂量、平均剂量及靶区适形度指数、均匀性指数均无明显差异,但15 MV计划高剂量覆盖程度大于6 MV和10 MV计划,脊髓、双肺及心脏受照剂量都在可耐受的范围内,差异也无统计学意义(P>0.05)。结论:6 MV、10 MV、15 MV X射线都能满足胸段食管癌临床调强放疗需求。     

Planning evaluation of radiotherapy for complex lung cancer cases using helical tomotherapy

Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate primary planning target volume (PTV2) and 1 cm margin around elective nodes for secondary planning target volume (PTV1) resulting in PTV1 volumes larger than 1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an inverse treatment planning system (TomoTherapy Inc.) based on superposition/convolution dose calculation for a fan beam thickness of 25 mm and a pitch factor between 0.3 and 0.8. For comparison, plans were created using an intensity-modulated radiation therapy (IMRT) approach planned on a commercial treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times for the large target volumes were estimated to be between 4 and 19 min. Using a prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8+/-4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with patient specific parameters. A good correlation was found between the quality of the HT plans and the IMRT plans with HT being slightly better in most cases. The overlap between lung and PTV was found to be a good indicator of plan quality for HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent overlap volume. Helical tomotherapy planning resulted in highly conformal dose distributions. It allowed easy achievement of two different dose levels in the target simultaneously. As the overlap between PTV and lung volume is a major predictor of mean lung dose, future work will be directed to control of margins. Work is underway to investigate the possibility of breath-hold techniques for tomotherapy delivery to facilitate this aim.     

Three-dimensional IMRT verification with a flat-panel EPID

A three-dimensional (3D) intensity-modulated radiotherapy (IMRT) pretreatment verification procedure has been developed based on the measurement of two-dimensional (2D) primary fluence profiles using an amorphous silicon flat-panel electronic portal imaging device (EPID). As described in our previous work, fluence profiles are extracted from EPID images by deconvolution with kernels that represent signal spread in the EPID due to radiation and optical scattering. The deconvolution kernels are derived using Monte Carlo simulations of dose deposition in the EPID and empirical fitting methods, for both 6 and 15 MV photon energies. In our new 3D verification technique, 2D fluence modulation profiles for each IMRT field in a treatment are used as input to a treatment planning system (TPS), which then generates 3D doses. Verification is accomplished by comparing this new EPID-based 3D dose distribution to the planned dose distribution calculated by the TPS. Thermoluminescent dosimeter (TLD) point dose measurements for an IMRT treatment of an anthropomorphic phantom were in good agreement with the EPID-based 3D doses; in contrast, the planned dose under-predicts the TLD measurement in a high-gradient region by approximately 16%. Similarly, large discrepancies between EPID-based and TPS doses were also evident in dose profiles of small fields incident on a water phantom. These results suggest that our 3D EPID-based method is effective in quantifying relevant uncertainties in the dose calculations of our TPS for IMRT treatments. For three clinical head and neck cancer IMRT treatment plans, our TPS was found to underestimate the mean EPID-based doses in the critical structures of the spinal cord and the parotids by approximately 4 Gy (11%-14%). According to radiobiological modeling calculations that were performed, such underestimates can potentially lead to clinically significant underpredictions of normal tissue complication rates.     

Comparison of IMRT optimization based on a pencil beam and a superposition algorithm

To investigate the role of sophisticated dose calculation methods for treatment planning, we compared conventional pencil beam optimized 6 and 15 MV intensity-modulated treatment plans with optimizations based on the superposition technique. Five lung and five head and neck IMRT cases with spatial resolutions of bixels and dose voxels usually employed in clinical practice were considered for tumor volumes between 15 and 500 cm3. We investigated the systematic error of the pencil beam algorithm and the pencil beam induced error to the optimal solution of bixel weights. For the lung cases, the pencil beam overestimated the mean dose deposited inside the planning target volume (PTV) by about 8%, for small lung tumors even up to 20.6%. In the head and neck cases only a slight overestimation in mean PTV dose of 1.5% was observed. The optimization with the superposition method substantially improved the dose coverage of the considered radiation targets. Additionally, for the head and neck cases, the brainstem was significantly spared by about 4% mean PTV dose through the use of the superposition technique. Our studies showed that, in target regions with intricate tissue inhomogeneities, superposition or Monte Carlo techniques have to be used for the optimization and the final dose calculation of intensity-modulated treatment plans.     

Energy- and intensity-modulated electron beams for radiotherapy

This work investigates the feasibility of optimizing energy- and intensity-modulated electron beams for radiation therapy. A multileaf collimator (MLC) specially designed for modulated electron radiotherapy (MERT) was investigated both experimentally and by Monte Carlo simulations. An inverse-planning system based on Monte Carlo dose calculations was developed to optimize electron beam energy and intensity to achieve dose conformity for target volumes near the surface. The results showed that an MLC with 5 mm leaf widths could produce complex field shapes for MERT. Electron intra- and inter-leaf leakage had negligible effects on the dose distributions delivered with the MLC, even at shallow depths. Focused leaf ends reduced the electron scattering contributions to the dose compared with straight leaf ends. As anticipated, moving the MLC position toward the patient surface reduced the penumbra significantly. There were significant differences in the beamlet distributions calculated by an analytic 3-D pencil beam algorithm and the Monte Carlo method. The Monte Carlo calculated beamlet distributions were essential to the accuracy of the MERT dose distribution in cases involving large air gaps, oblique incidence and heterogeneous treatment targets (at the tissue-bone and bone-lung interfaces). To demonstrate the potential of MERT for target dose coverage and normal tissue sparing for treatment of superficial targets, treatment plans for a hypothetical treatment were compared using photon beams and MERT.     

A quality assurance phantom for IMRT dose verification

This paper investigates a quality assurance (QA) phantom specially designed to verify the accuracy of dose distributions and monitor units (MU) calculated by clinical treatment planning optimization systems and by the Monte Carlo method for intensity-modulated radiotherapy (IMRT). The QA phantom is a PMMA cylinder of 30 cm diameter and 40 cm length with various bone and lung inserts. A procedure (and formalism) has been developed to measure the absolute dose to water in the PMMA phantom. Another cylindrical phantom of the same dimensions, but made of water, was used to confirm the results obtained with the PMMA phantom. The PMMA phantom was irradiated by 4, 6 and 15 MV photon beams and the dose was measured using an ionization chamber and compared to the results calculated by a commercial inverse planning system (CORVUS, NOMOS, Sewickley, PA) and by the Monte Carlo method. The results show that the dose distributions calculated by both CORVUS and Monte Carlo agreed to within 2% of dose maximum with measured results in the uniform PMMA phantom for both open and intensity-modulated fields. Similar agreement was obtained between Monte Carlo calculations and measured results with the bone and lung heterogeneity inside the PMMA phantom while the CORVUS results were 4% different. The QA phantom has been integrated as a routine QA procedure for the patient's IMRT dose verification at Stanford since 1999.     

Dosimetric evaluation of breast radiotherapy in a dynamic phantom

This phantom study quantifies changes in delivered dose due to respiratory motion for four breast radiotherapy planning techniques: three intensity-modulated techniques (forward-planned, surface-compensated and hybrid intensity-modulated radiation therapy (IMRT)); using a combination of open fields and inverse planned IMRT) and a 2D conventional technique. The plans were created on CT images of a wax breast phantom with a cork lung insert, and dose distributions were measured using films inserted through slits in the axial and sagittal planes. Films were irradiated according to each plan under a static (modeling breathhold) and three dynamic conditions--isocenter set at mid-respiratory cycle with motion amplitudes of 1 and 2 cm and at end-cycle with 2 cm motion amplitude (modeling end-exhale). Differences between static and moving deliveries were most pronounced for the more complex planning techniques with hot spots of up to 107% appearing in the anterior portion of all three IMRT plans at the largest motion at the end-exhale set-up. The delivered dose to the moving phantom was within 5% of that to the static phantom for all cases, while measurement accuracy was ±3%. The homogeneity index was significantly decreased only for the 2 cm motion end-exhale set-up; however, this same motion increased the equivalent uniform dose because of improved posterior breast coverage. Overall, the study demonstrates that the effect of respiratory motion is negligible for all planning techniques except in occasional instances of large motion.