巨块型NSCLC质子部分立体定向消融推量放疗的剂量学优势

目的 探索肿瘤长径>8 cm的巨块非小细胞肺癌（NSCLC）放疗中质子部分立体定向消融推量放疗（P‐SABR）的剂量学优势。方法 收集既往应用光子P‐SABR治疗的9例巨块NSCLC的定位影像。在光子肿瘤推量靶区（光子GTVb）基础上逐步外扩,直到重要危及器官受量达3.0 Gy/次时停止,形成质子肿瘤推量靶区（质子GTVb）,质子GTV、CTV范围同光子,分别制订光子固定野调强放疗（光子FF‐IMRT）、光子容积调强弧形治疗（光子VMAT）、质子调强放疗（IMPT）计划。对比不同治疗技术的剂量学参数。结果 光子GTVb和质子GTVb占GTV体积比分别为25.4%±13.4%和69.7%±30.0%（P<0.001）。光子IMRT、光子VMAT、IMPT的CTV平均剂量分别为（76.1±4.9）Gy、（78.2±3.6）Gy、（84.7±4.9）Gy,生物有效剂量（BED）≥90 Gy所包含肿瘤占GTV体积的百分比分别为70.7%±21.7%、76.8%±22.1%、97.9%±4.0%,质子较光子P‐SABR计划显著提高了靶区剂量及BED（P<0.05）。质子较光子计划还降低了危及器官受量,其中光子FF‐IMRT、光子VMAT和IMPT的双肺V_{5 Gy}分别为49.2%±22.0%、56.8%±19.0%和16.1%±6.3%（P<0.001）。结论 质子P‐SABR较光子可在降低危及器官受量情况下,扩大肿瘤推量靶区范围并提高肿瘤内BED,有望进一步提高巨块NSCLC的局部控制率。     

巨块型NSCLC质子部分立体定向消融推量放疗的剂量学优势

目的 探索肿瘤长径>8 cm的巨块非小细胞肺癌（NSCLC）放疗中质子部分立体定向消融推量放疗（P‐SABR）的剂量学优势。方法 收集既往应用光子P‐SABR治疗的9例巨块NSCLC的定位影像。在光子肿瘤推量靶区（光子GTVb）基础上逐步外扩,直到重要危及器官受量达3.0 Gy/次时停止,形成质子肿瘤推量靶区（质子GTVb）,质子GTV、CTV范围同光子,分别制订光子固定野调强放疗（光子FF‐IMRT）、光子容积调强弧形治疗（光子VMAT）、质子调强放疗（IMPT）计划。对比不同治疗技术的剂量学参数。结果 光子GTVb和质子GTVb占GTV体积比分别为25.4%±13.4%和69.7%±30.0%（P<0.001）。光子IMRT、光子VMAT、IMPT的CTV平均剂量分别为（76.1±4.9）Gy、（78.2±3.6）Gy、（84.7±4.9）Gy,生物有效剂量（BED）≥90 Gy所包含肿瘤占GTV体积的百分比分别为70.7%±21.7%、76.8%±22.1%、97.9%±4.0%,质子较光子P‐SABR计划显著提高了靶区剂量及BED（P<0.05）。质子较光子计划还降低了危及器官受量,其中光子FF‐IMRT、光子VMAT和IMPT的双肺V_{5 Gy}分别为49.2%±22.0%、56.8%±19.0%和16.1%±6.3%（P<0.001）。结论 质子P‐SABR较光子可在降低危及器官受量情况下,扩大肿瘤推量靶区范围并提高肿瘤内BED,有望进一步提高巨块NSCLC的局部控制率。     

Target Volume Coverage and Organ at Risk Doses for Left-sided Whole-breast Irradiation With or Without Internal Mammary Chain Irradiation: A Comparison Between Three Techniques Representing the Past and the Present

AimsThe 15-year results of the EORTC 229922-10925 phase III trial showed a significant reduction in breast cancer mortality and breast cancer recurrences after internal mammary chain (IMC) and medio-supraclavicular irradiation. Unexpectedly, cardiac death was not increased, and the incidence of cardiac events did not differ between left- and right-sided cases, although target volume coverages and organ at risk doses were unknown. Therefore, a planning study was carried out comparing the past and the present, to eventually enable, thereafter, an increased therapeutic ratio of IMC irradiation.Materials and methodsA planning study was carried out on target volume coverage and organ at risk doses for whole-breast irradiation (WBI) ± IMC comparing the results between two-dimensional radiotherapy (free-breathing), hybrid intensity-modulated radiotherapy (IMRT; breath-hold) and robust intensity-modulated proton therapy (IMPT; free-breathing) for 10 left-sided breast cancer cases. Two-dimensional radiotherapy consisted of two tangential wedged photon breast fields and mixed electron/photon beams for the IMC. Hybrid IMRT included two tangential photon breast fields (70%) complemented with IMRT (30%). IMPT plans were created using multi-field robust optimisation (5 mm set-up and 3% range uncertainties) with two (WBI) or three (WBI + IMC) beams.ResultsTarget volume dose objectives were met for hybrid IMRT and IMPT. For two-dimensional radiotherapy, target coverage was 97% and 83% for breast and IMC, respectively. The mean heart dose for WBI only was <2 Gy for all techniques. For WBI + IMC, heart doses (mean heart dose, mean left anterior descending region, volume of the heart receiving 5 Gy (V5) were significantly higher for two-dimensional radiotherapy when compared with contemporary techniques. The V5 left anterior descending region reduced from 100% (two-dimensional radiotherapy) to 70% and 20% for hybrid IMRT and IMPT, respectively. Conclusion: Contemporary radiotherapy techniques result in improved target volume coverage and significantly decreased heart doses for WBI + IMC radiotherapy. Hence, nowadays an increased therapeutic ratio of elective IMC irradiation may be anticipated.     

Treatment planning for conformal proton radiation therapy

Clinical results from various trials have demonstrated the viability of protons in radiation therapy and radiosurgery. This has motivated a few large medical centers to design and build expensive hospital based proton facilities based proton facilities (current cost estimates for a proton facility is around 100 million US dollars). Until this development proton therapy was done using retrofitted equipment originally designed for nuclear experiments. There are presently only three active proton therapy centers in the United States, 22 worldwide. However, more centers are under construction and being proposed in the US and abroad. The important difference between proton and x-ray therapy is in the dose distribution. X-rays deposit most of their dose at shallow depths of a few centimeters with a gradual decay with depth in the patient. Protons deliver most of their dose in the Bragg peak, which can be delivered at most clinically required depths followed by a sharp fall-off. This sharp falloff makes protons sensitive to variations in treatment depths within patients. Treatment planning incorporates all the knowledge of protons into a process, which allows patients to be treated accurately and reliably. This process includes patient immobilization, imaging, targeting, and modeling of planned dose distributions. Although the principles are similar to x-ray therapy some significant differences exist in the planning process, which described in this paper. Target dose conformality has recently taken on much momentum with the advent of intensity modulated radiation therapy (IMRT) with photon beams. Proton treatments provide a viable alternative to IMRT because they are inherently conformal avoiding normal tissue while irradiating the intended targets. Proton therapy will soon bring conformality to a new high with the development of intensity modulated proton therapy (IMPT). Future challenges include keeping the cost down, increasing access to conventional proton therapy as well as the clinical implementation of IMPT. Computing advances are making Monte Carlo techniques more accessible to treatment planning for all modalities including proton therapy. This technique will allow complex delivery configurations to be properly modeled in a clinical setting.     

A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas

PURPOSE: A comparative treatment planning study has been undertaken between intensity modulated (IM) photon therapy and IM proton therapy (IMPT) in paraspinal sarcomas, so as to assess the potential benefits and limitations of these treatment modalities. In the case of IM proton therapy, plans were compared also for two different sizes of the pencil beam. Finally, a 10% and 20% dose escalation with IM protons was planned, and the consequential organ at risk (OAR) irradiation was evaluated. METHODS AND MATERIALS: Plans for 5 patients were computed for IM photons (7 coplanar fields) and protons (3 coplanar beams), using the KonRad inverse treatment planning system (developed at the German Cancer Research Center). IMPT planning was performed assuming 2 different sizes of the pencil beam: IMPT with a beam of full width at half-maximum of 20 mm, and IMPT with a "mini-beam" (IMPT(M), full width at half-maximum = 12 mm). Prescribed dose was 77.4 Gy or cobalt Gray equivalent (CGE) for protons to the gross tumor volume (GTV). Surface and center spinal cord dose constraint for all techniques was 64 and 53 Gy/CGE, respectively. Tumor and OAR dose-volume histograms were calculated. Results were analyzed using dose-volume histogram parameters, inhomogeneity coefficient, and conformity index. RESULTS: Gross tumor volume coverage was optimal and equally homogeneous with both IM photon and IM proton plans. Compared to the IM photon plans, the use of IM proton beam therapy leads to a substantial reduction of the OAR total integral dose in the low-level to mid-dose level. Median heart, lung, kidney, stomach, and liver mean dose and dose at the 50% volume level were consistently reduced by a factor of 1.3 to 25. Tumor dose homogeneity in IMPT(M) plans was always better than with IMPT planning (median inhomogeneity coefficient, 0.19 vs. 0.25). IMPT dose escalation (to 92.9 CGE to the GTV) was possible in all patients without exceeding the normal-tissue dose limits. CONCLUSIONS: These results suggest that the use of IM photon therapy, when compared to IM protons, can result in similar levels of tumor conformation. IM proton therapy, however, reduces the OAR integral dose substantially, compared to IM photon radiation therapy. As a result, tumor dose escalation was always possible with IM proton planning, within the maximal OAR dose constraints. In IM proton planning, reducing the size of the proton pencil beam (using the "mini-beam") improved the dose homogeneity, but it did not have a significant effect on the dose conformity.     

Proton radiation therapy for head and neck cancer

Due to the close spatial relationship of head and neck and skull base tumors to numerous normal anatomical structures, conventional photon radiation therapy can be associated with significant acute and long-term treatment-related toxicities. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissues to be irradiated than is feasible with any photon technique. Intensity-modulated proton therapy (IMPT) is a powerful delivery technique which results in improved dose distribution as compared to that of intensity-modulated radiation therapy (IMRT). Initial clinical experience with proton radiation therapy in treatment of head and neck and skull base tumors is promising. Prospective multi-institutional trials are underway to define the role of proton radiation therapy, particularly IMPT, in the treatment of head and neck and skull base tumors.     

Radiation therapy with charged particles

Charged particle beams can offer an improved dose conformation to the target volume as compared with photon radiotherapy, with better sparing of normal tissue structures close to the target. In addition, beams of ions heavier than (4)He exhibit a strong increase of the linear energy transfer in the Bragg peak as compared with the entrance region. These physical and biological properties are much more favorable than in photon radiotherapy. As a consequence, particle therapy with protons and heavy ions has gained increasing interest worldwide, and many clinical centers are considering introducing radiation therapy with charged particles. This contribution summarizes the physical and technical principles of charged particle therapy with protons and heavy ions. It briefly reviews the clinical experience gathered so far with proton therapy and gives a more detailed summary of the recent results in carbon ion therapy of skull base tumors, head and neck tumors, non-small-cell lung cancer, hepatocellular carcinomas, bone and soft-tissue sarcomas, and prostate cancer.     

Place de la protonthérapie en cancérologie ORL

The absence of exit dose and the sharp lateral penumbra are key assets for proton therapy, which are responsible for its dosimetric superiority over advanced photon radiotherapy. Dosimetric comparisons have consistently shown a reduction of the integral dose and the dose to organs at risk favouring intensity-modulated proton therapy (IMPT) over intensity-modulated radiotherapy (IMRT). The structures that benefit the most of these dosimetric improvements in head and neck cancers are the anterior oral cavity, the posterior fossa, the visual apparatus and swallowing structures. A number of publications have concluded that these dosimetric differences actually translate into reduced toxicities with IMPT, for example with regards to reduced weight loss or need for feeding tube. Patient survival is usually similar to IMRT series, except in base of skull or sinonasal malignancies, where a survival advantage of IMPT could exist. The goals of the present review is to describe the major characteristics of proton therapy, to analyse the clinical data with regards to head and neck cancer patients, and to highlight the issue of patient selection and physical and biological uncertainties.     

Current status of radiotherapy with proton and light ion beams

Several model studies have shown potential clinical advantages with charged particles (protons and light ions) compared with 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in many disease sites. The newly developed intensity-modulated proton therapy (IMPT) often yields superior dose distributions to photon IMRT, with the added advantage of a significant reduction in the volume of healthy normal tissues exposed to low-to-medium doses. Initially, the major emphasis in clinical research for proton and light ion therapy was dose escalation for inherently radioresistant tumors, or for lesions adjacent to critical normal structures that constrained the dose that could be safely delivered with conventional x-ray therapy. Since the advent of IMRT the interest in particle therapy has gradually shifted toward protocols aimed at morbidity reduction. Lately the emphasis has mostly been placed on the potential for reduced risk of radiation-induced carcinogenesis with protons. Compared with 3D-CRT, a 2-fold increase has been theoretically estimated with the use of IMRT due to the larger integral volumes. In the pediatric setting, due to a higher inherent susceptibility of tissues, the risk could be significant, and the benefits of protons have been strongly emphasized in the literature. There is a significant expansion of particle therapy facilities around the world. Increasing public awareness of the potential benefits of particle therapy and wider accessibility for patients require that treating physicians stay abreast of the clinical indications of this radiotherapy modality. The article reviews the available literature for various disease sites in which particle therapy has traditionally been considered to offer clinical advantages and to highlight current lines of clinical research. The issue of radiation-induced second malignancies is examined in the light of the controversial epidemiological evidence available. The cost-effectiveness of particle therapy is also discussed.     

The clinical potential of intensity modulated proton therapy

Intensity Modulated Proton Therapy (IMPT) differs from conventional proton therapy in its ability to deliver depth-shifted, arbitrarily complex proton fluence maps from each incident field direction. As the individual Bragg peaks delivered from any field can be distributed in three-dimensions throughout the target volume, IMPT provides many more degrees of freedom for designing dose distributions than IMRT or conventional proton therapy techniques. So how can the flexibility of IMPT best be exploited? Here we argue that IMPT has two main advantages over photon IMRT and conventional proton therapy: the ability to better 'sculpt' the dose to the target and around neighbouring critical structures, and the ability to find clinically acceptable solutions whilst simultaneously reducing the sensitivity of the treatments to potential delivery errors. The concept of IMPT as a tool for generating 'safer' plans opens an interesting new avenue of research from the point of view of plan optimisation, the potential of which is only just beginning to be explored.     

Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study

The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).

CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH).

Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively.

This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.     

Critical appraisal of treatment techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast.

PURPOSE: To analyse different treatment techniques with conventional photon beams, intensity modulated photon beams, and proton beams for intact breast irradiation for patients in whom conventional irradiation would cause potentially dangerous lung irradiation. MATERIALS AND METHODS: Five breast cancer patients with highly concave breast tissue volume around the lung were considered at planning level in order to assess the suitability of different irradiation techniques. Three-dimensional dose distributions for conventional two-field tangential photon treatment, two-field intensity modulated radiotherapy (IMRT), three-field non-IMRT, three-field IMRT, and single-field proton treatment were investigated, aiming at assessing the possibility to reduce lung irradiation below risk levels. Analysis of dose-volume histograms and related physical and biological parameters (significant minimum, maximum and mean doses, conformity indexes and equivalent uniform dose (EUD)) for planned target volume (PTV) and lung was carried out. Dose plans were compared with the conventional two-field tangential photon technique. RESULTS: PTV coverage was comparable for non-IMRT and IMRT techniques (EUD from 47.1 to 49.4 Gy), and improved with single-field proton treatment (EUD=49.8 Gy). Lung irradiation was reduced, in terms of mean dose, with three-field (9.5 Gy) and proton technique (3.5 Gy), with respect to the conventional two-field treatment (12.9 Gy); also a reduction of the lung volume irradiated at high doses was observed. Better results could be achieved with protons. In addition, cardiac irradiation was also reduced with those techniques. CONCLUSIONS: Geometrically difficult breast cancer patients could be irradiated with a three-field non-IMRT technique thus reducing the dose to the lung which is proposed as standard for this category of patients. Intensity modulated techniques were only marginally more successful than the corresponding non-IMRT treatments, while protons offer excellent results.     

Dose conformation of intensity-modulated stereotactic photon beams, proton beams, and intensity-modulated proton beams for intracranial lesions

PURPOSE: This study evaluates photon beam intensity-modulated stereotactic radiotherapy (IMSRT) based on dynamic leaf motion of a micromultileaf collimator (mMLC), proton beams, and intensity-modulated proton therapy (IMPT) with respect to target coverage and organs at risk. METHODS AND MATERIALS: Dose plans of 6 stereotactically treated patients were recalculated for IMSRT by use of the same field setup and an inverse planning algorithm. Proton and IMPT plans were calculated anew. Three different tumor shapes, multifocal, ovoid, and irregular, were analyzed, as well as dose to organs-at-risk (OAR) in the vicinity of the planning target volume (PTV). Dose distributions were calculated from beam-setup data for a manual mMLC for stereotactically guided conformal radiotherapy (SCRT), a dynamic mMLC for IMSRT, the spot-scanning technique for protons, and a modified spot-scanning technique for IMPT. SCRT was included for a part of the comparison. Criteria for assessment were PTV coverage, dose-volume histograms (DVH), volumes of specific isodoses, and the dose to OAR. RESULTS: Dose conformation to the PTV is equally good for all three techniques and tumor shapes considered. The volumes of the 90% and 80% isodose were comparable for all techniques. For the 50% isodose volume, a divergence between the two modes was seen. In 3 cases, this volume is smaller for IMSRT, and in the 3 other cases, it is smaller for IMPT. This difference was even more pronounced for the volumes of the 30% isodose; IMPT shows further improvement over conventional protons. OAR in concavities (e.g., the brainstem) were similarly well spared by protons and IMSRT. IMPT spares critical organs best. Fewer proton beams are required to achieve similar results. CONCLUSIONS: The addition of intensity modulation improves the conformality of mMLC-based SCRT. Conformation of dose to the PTV is comparable for IMSRT, protons, and IMPT. Concerning the sparing of OAR, IMSRT is equivalent to IMPT, and IMPT is superior to conventional protons. The advantage of protons lies in the lower integral dose.     

Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons

PURPOSE: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. METHODS AND MATERIALS: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial and supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. RESULTS: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. CONCLUSIONS: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.     

Number and orientation of beams in inversely planned intensity-modulated radiotherapy of the female breast and the parasternal lymph nodes

Intensity-modulated radiotherapy (IMRT) provides better sparing of normal tissue. We evaluated the optimum beam configuration for IMRT based on inverse treatment planning in adjuvant radiotherapy for breast cancer in a case of left-sided tumor. In addition to radiotherapy planning with the conventional technique of tangential wedged 6-MV photon beams and an oblique 15-MeV electron beam, we performed inversely planned IMRT with the step-and-shoot-technique. Dose calculation was carried out using the treatment planning system Virtuos with the inverse optimization module KonRad adapted to it. IMRT plans were generated for 2 to 16 beams. The results were compared with conventional techniques. For a maximum treatment time of 20 minutes, it is shown that IMRT with 12 modulated photon beams and 7 intensity steps is best suited for treatment in the presented case. Compared with a conventional technique with photons combined with electrons, dose conformality and homogeneity of the planning target volume was increased. The mean heart dose was reduced from 9.1 Gy to 6.1 Gy. The volume of heart irradiated with a dose higher than 30 Gy was reduced from 7.6% to 1.9%, and the volume of the left lung from 13.6% to 11.5% as well. Inverse optimization for IMRT with multiple beams is feasible in the adjuvant treatment of breast cancer. Because of the reduction of the high-dose area of a substantial cardiac volume, it is superior to conventional techniques in cases where the parasternal lymph nodes should be integrated into the target volume. Here, a clinical advantage might be detectable.     

Basics of particle therapy: introduction to hadrons

With the arrival of 3-dimensional conformal radiation therapy and intensity modulated radiation therapy, radiation dose distributions in radiation oncology have improved dramatically over the past couple of decades. As part of a natural progression there recently has been a resurgence of interest in hadron therapy, specifically charged particle therapy, because of the even better dose distributions potentially achievable. In principle, using charged particle beams, radiation dose distributions can be achieved that surpass those possible with even the most sophisticated photon radiation delivery techniques. Certain charged particle beams might possess some biologic advantages in terms of tumor kill potential as well as this dosimetric advantage. The particles under consideration for such clinical applications all belong to the category of particles known as hadrons. This review introduces some of the elementary physics of the various hadron species previously used, currently used or being considered for future use in radiation oncology.     

Current status and future prospects of 3D treatment planning in radiation therapy, focusing on IMRT]

The ultimate goal of radiation therapy is to confine a high dose to the target area while sparing the surrounding normal structures in order to increase the delivered dose and decrease the likelihood of organ injuries. In Japan, the rotational conformal technique, which is a combination of gantry rotation and dynamic movement of multi-leaf collimators (MLC), has been widely used as a standard method for high-precision radiation therapy. The non-coplanar technique in which radiation beams are given in three dimensions has the advantage of dose concentration as well as organ sparing. In intensity modulated radiotherapy (IMRT), an uneven intensity map within a beam is generated with various methods such as "sliding window technique" and "stop and shoot technique". Several intensity modulated beams are combined to create arbitrary dose distribution including concave distribution. Although a substantial number of proton therapy facilities are planned in this country, IMRT should be considered as a competitive rival from the viewpoint of cost-benefit analysis as well as clinical effectiveness.     

Inverse planning of intensity modulated proton therapy

A common requirement of radiation therapy is that treatment planning for different radiation modalities is devised on the basis of the same treatment planning system (TPS). The present study presents a novel multi-modal TPS with separate modules for the dose calculation, the optimization engine and the graphical user interface, which allows to integrate different treatment modalities. For heavy-charged particles, both most promising techniques, the distal edge tracking (DET) and the 3-dimensional scanning (3D) technique can be optimized. As a first application, the quality of optimized intensity-modulated treatment plans for photons (IMXT) and protons (IMPT) was analyzed in one clinical case on the basis of the achieved physical dose distributions. A comparison of the proton plans with the photon plans showed no significant improvement in terms of target volume dose, however there was an improvement in terms of organs at risk as well as a clear reduction of the total integral dose. For the DET technique, it is possible to create a treatment plan with almost the same quality of the 3D technique, however with a clearly reduced number (factor of 5) of beam spots as well as a reduced optimization time. Due to its modular design, the system can be easily expanded to more sophisticated dose-calculation algorithms or to modeling of biological effects.     

Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma

We sought to assess the feasibility and estimate the benefit of sparing the neurogenic niches when irradiating the brain of pediatric patients with medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors experience a high risk of neurocognitive adverse effects, often attributed to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26.6%-51.2%) with IMAT, IMRT, and IMPT, respectively, while maintaining at least 95% of the prescribed dose in 95% of the whole-brain target volume. Estimated risks for developing memory impairment after a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%-69%), 44% (95% CI, 21%-65%), 41% (95% CI, 22%-60%), and 33% (95% CI, 23%-44%) with opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing during cranial irradiation of pediatric patients with MB is feasible and is estimated to lower the risks of long-term neurocognitive sequelae. Greatest sparing is achieved with intensity-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial.