精确放射治疗的发展

精确放射治疗是采用精确的固定、定位、立体定向和三维计算及显示方法。采用常规或非常规剂量分割方式在三维水平上进行的立体适形或调强放疗，可使高剂量区的剂量分布形状在三维水平上与靶区的实际形状一致。靶区内剂量强度可调。目的是在减少或不增加正常组织损伤的前提下增加肿瘤的照射剂量．从而提高肿瘤的局部控制率和患者的生活质量。     

Intensity-modulated radiation therapy (IMRT) for meningioma

To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma.

Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method.

Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy.

IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT.     

乳腺癌五种照射技术比较研究

目的 评价乳腺癌放疗时，适形、调强技术对保护正常组织和改善靶区剂量均匀度的作用。方法 比较五种乳腺癌照射技术，包括常规切线照射技术、三维适形（3DCRT）切线照射技术、野中野照射技术、调强切线照射技术和调强五野照射技术。随机选择5位乳腺癌患者，为每位患者设计上述五种照射技术的治疗计划。处方剂量为46Gy／2Gy／23f。所有计划都使95％靶区体积达到处方剂量要求。分别比较他们的剂量分布、剂量体积直方图（DVH）、靶区剂量均匀度以及正常组织如肺、心脏所受剂量。结果 五种技术靶区剂量均匀度的优劣：3D和凋强技术比常规技术有改善趋势。但所有计划的靶区剂量分布方差分析无显著性差异（P=0．951）。3D技术和野中野技术各项指标值都基本相同。5野调强靶区剂量均匀度最佳。五种技术保护正常组织的效果：3D技术在正常组织的保护方面都优于常规技术。调强技术使患侧肺、心脏高剂量区体积降低，低剂量区增加。但使对侧肺和对侧乳腺的受照剂量略有增加。5野调强使正常组织受低剂量照射的范围显著增加。结论 对于早期乳腺癌保乳术后放疗，在常规技术已达到较好疗效情况下，仍需要为提高患者生存质量、减少晚期并发症而努力。3DCRT技术在改善靶区剂量均匀度的同时，肺和心脏受照体积和受照剂量均低于常规技术；其计划时间和治疗时间与常规技术相近，因而可认为3DCRT是目前取代常规切线照射技术的较好选择。     

A separated primary and scatter model for independent dose calculation of intensity modulated radiotherapy

BACKGROUND AND PURPOSE: Independent checking of beam monitor units is an essential step in the preparation of any radiotherapy plan. The present work describes a simple model for calculating a point dose from an arbitrary number of irregular, asymmetric fields, typical of beam segments used for IMRT. MATERIALS AND METHODS: Primary and scatter dose contributions were separated using a two-parameter exponential fit to measured beam data, from which differential scatter is determined. A total of 60 IMRT patient plans for a five-field prostate class solution were investigated to validate the model. RESULTS: The average difference between the model's prediction and direct measurement of reference dose was found to be -0.6% (ranging from -2.9% to +1.6%), with a standard deviation of 1.0%. This compares well with the observed average difference between treatment planning system prediction and direct measurement of +0.8% (SD 0.6%). CONCLUSIONS: The model is shown to provide a reliable and accurate independent check of planning system monitor units for the prostate IMRT plans studied. Implementation of the model could significantly reduce the time needed for point dose verification of IMRT plans currently performed by direct measurement.     

早期鼻咽癌的治疗及进展

早期鼻咽癌的治疗不仅要考虑生存率，还要考虑患者的生存质量。采用外照射与腔内近距离放射治疗可以降低外照射剂量，减轻部分放射并发症。而调强放射治疗的应用，有更好的适形度和靶区剂量分布，不仅能提高肿瘤的局部控制率，从而进一步提高生存率，还能降低腮腺的剂量，从而降低口干的发生率，同时脑干、脊髓的剂量进一步降低。生物靶向治疗与放射的联合，对晚期鼻咽癌有一定的疗效提高，在早期鼻咽癌还需进一步研究。     

Incorporating prior knowledge into beam orientaton optimization in IMRT

: Selection of beam configuration in currently available intensity-modulated radiotherapy (IMRT) treatment planning systems is still based on trial-and-error search. Computer beam orientation optimization has the potential to improve the situation, but its practical implementation is hindered by the excessive computing time associated with the calculation. The purpose of this work is to provide an effective means to speed up the beam orientation optimization by incorporating a priori geometric and dosimetric knowledge of the system and to demonstrate the utility of the new algorithm for beam placement in IMRT.

: Beam orientation optimization was performed in two steps. First, the quality of each possible beam orientation was evaluated using beam’s-eye-view dosimetrics (BEVD) developed in our previous study. A simulated annealing algorithm was then employed to search for the optimal set of beam orientations, taking into account the BEVD scores of different incident beam directions. During the calculation, sampling of gantry angles was weighted according to the BEVD score computed before the optimization. A beam direction with a higher BEVD score had a higher probability of being included in the trial configuration, and vice versa. The inclusion of the BEVD weighting in the stochastic beam angle sampling process made it possible to avoid spending valuable computing time unnecessarily at “bad” beam angles. An iterative inverse treatment planning algorithm was used for beam intensity profile optimization during the optimization process. The BEVD-guided beam orientation optimization was applied to an IMRT treatment of paraspinal tumor. The advantage of the new optimization algorithm was demonstrated by comparing the calculation with the conventional scheme without the BEVD weighting in the beam sampling.

: The BEVD tool provided useful guidance for the selection of the potentially good directions for the beams to incident and was used to guide the search for the optimal beam configuration. The BEVD-guided sampling improved both optimization speed and convergence of the calculation. A comparison of several five-field IMRT treatment plans obtained with and without BEVD guidance indicated that the computational efficiency was increased by a factor of 10.

: Incorporation of BEVD information allows for development of a more robust tool for beam orientation optimization in IMRT planning. It enables us to more effectively use the angular degree of freedom in IMRT without paying the excessive computing overhead and brings us one step closer to the goal of automated selection of beam orientations in a clinical environment.     

Differential dosing of prostate and seminal vesicles using dynamic multileaf collimation

Purpose: We have investigated the potential of applying different doses to the prostate (PTV2) and prostate/seminal vesicles (PTV1) using multileaf collimation (MLC) for intensity modulated radiation therapy (IMRT). Current dose-escalation studies call for treatment of the PTV1 to 54 Gy in 27 fractions followed by 20 Gy minimum to the PTV2. A daily minimum PTV dose of 2 Gy using a 7-field technique (4 obliques, opposed laterals, and an ant-post field) is delivered. This requires monitor unit calculations, paper and electronic chart entry, and quality assurance for a total of 14 fields. The goal of MLC IMRT is to improve efficiency and deliver superior dose distributions. Acceptance testing and commissioning of the dynamic MLC (DMLC) option on a dual-energy accelerator was accomplished. Most of the testing was performed using segmental MLC (SMLC) IMRT with stop-and-shoot sequences built within the dynamic mode of the DMLC.

Methods and Materials: The MLC IMRT fields were forward planned using a three-dimensional treatment planning system. The 14 fields were condensed to 7 SMLC IMRT fields with two segments each. In this process, steps were created by moving the leaves to the reduced field positions. No dose (<0.01%) was delivered during this motion. The monitor units were proportioned according to the planned treatment weights. Film and ionization chamber dosimetry were used to analyze leaf positional accuracy and speed, output, and depth-dose characteristics. A geometric phantom was used for absolute and relative measurements. We obtained a volumetric computerized tomography (CT) scan of the phantom, performed 3D planning, and then delivered a single treatment fraction.

Results: The acceptance testing and commissioning demonstrated that the leaves move to programmed positions accurately and in a timely manner. We did find an 1 mm offset of the set leaf position and radiation edge (50%) due to the curved-end nature and calibration limitations. The 7-field SMLC IMRT treatment duplicated the 14-field static plan dose distribution with variations no greater than 1.5%.

Conclusions: The MLC IMRT approach will improve efficiency because the number of electronic and chart entries has decreased by a factor of 2. Portal images are able to capture the initial and final MLC segments. The question of differential daily dose to the prostate and seminal vesicles remains.     

Optimierter Einsatz der Strahlentherapie durch IMRT und Präzisionslokalisationsverfahren bei der Behandlung des fortgeschrittenen Prostatakarzinoms

Zusammenfassung Mit der intensitätsmodulierten Strahlentherapie (IMRT) zusammen mit modernen, nichtinvasiven Lokalisationsverfahren steht eine Methodik zur Verfügung, mit der die konformale Bestrahlung des Prostatakarzinoms unter optimaler Schonung des Rektums potentiell verbessert werden kann.Diese Übersicht fasst einerseits die klinischen Erfordernisse an die Strahlentherapie beim fortgeschrittenen Prostatakarzinom und andererseits die neuen nichtinvasiven technischen Möglichkeiten zusammen, die helfen, diese Erfordernisse besser zu erfüllen. Zusammen mit der Diskussion der neuen biologischen Daten, die evtl. die Verkürzung der Radiotherapie ermöglichen, wurde versucht, diese Entwicklungen mit ihren theoretischen Vorteilen und eventuellen Problemen zu schildern, um diese Vorgänge über die Strahlentherapie hinaus transparent zu machen.     

Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?

PURPOSE: To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT. METHODS AND MATERIALS: A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer. RESULTS: The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose. CONCLUSIONS: The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.