射波刀治疗31例晚期非小细胞肺癌患者的疗效观察

背景与目的射波刀是近年来新出现的一种立体定向放射治疗技术,具有大剂量、高精度和周围受照射的正常组织或是重要器官的范围小等优点,在治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)方面取得了显著的效果。本研究旨在探讨射波刀(Cyberknife)治疗晚期NSCLC的疗效和安全性。方法在2009年3月-2010年3月间,我们应用射波刀治疗31例(34个肿瘤病灶)临床III期-IV期的周围型NSCLC患者,其中III期5例,IV期26例,腺癌15例,鳞癌12例,大细胞癌1例,腺鳞癌2例,不确定NSCLC1例。28例患者联合了化疗。平均肿瘤体积67.2cm3,处方总剂量36Gy-60Gy,分割2次-5次。等计量线65%-85%。治疗后1-2个月复查胸部CT,观察近期疗效,每3个月随访一次。结果 2例完全缓解,16例部分缓解,7例稳定,6例进展,总体有效率达58%,疾病控制率为81%。所有患者治疗耐受性良好,最主要的不良反应表现为乏力,无4级或是4级以上的不良反应发生。结论射波刀治疗晚期NSCLC安全性好,有较好的近期疗效,不良反应轻,患者易耐受。但是远期疗效有待进一步随访。     

Un accélérateur linéaire peut-il faire aussi bien qu’un appareil de tomothérapie ou un Cyberknife™ ?

Tomotherapy is a new external beam radiation therapy technique using helicoidal intensity modulated radiation principle. It is able to avoid multiple isocenters requested to irradiate large volumes. This machine integrates image acquisition, treatment planning, positioning of the patient and irradiation into a sole engine. Six degrees of freedom robot coupled with a 6 MV linear accelerator, InCA has installed the Cyberknife in France in 3 sites chosen. The last generation of linac is a multifunction machine able to deliver conformal irradiations with or without intensity modulated radiation therapy, cranial or extracranial stereotactic irradiation with or without arctherapy or modulation. Performances of each machine have to be measured and compared in a medical and economical procedure.     

螺旋断层放疗在肿瘤治疗中的应用

螺旋断层放疗是CT和直线加速器结合的放疗设备,具有360度照射、兆伏级螺旋CT(MVCT)影像引导、自适应计划等技术,可进行调强放疗、自适应放疗、立体定向外科等多种功能,适应证广泛.     

射波刀在治疗非小细胞肺癌中的临床应用

早期非小细胞肺癌（NSCLC）的主要治疗手段仍是外科手术切除,如患者有手术禁忌证或者拒绝手术,放疗则成为患者的另一选择.射波刀（cyberkife）是近年来新出现的一种立体定向放射治疗技术,兼具有放射外科和放射治疗两种功能.其采用实时图像引导系统和呼吸追踪系统通过大剂量、高精度照射,在NSCLC的治疗中取得显著效果.     

Low-dose radiosurgery for benign intracranial lesions

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.     

射波刀在早期非小细胞肺癌的应用及影响疗效的因素

早期非小细胞肺癌(NSCLC)主要治疗方法是外科切除,放疗是不能耐受或拒绝手术NSCLC患者的另一选择。射波刀是近年来新出现的一种立体定向放射治疗技术,兼具放射外科和放射治疗两种功能。采用实时图像引导系统以及呼吸追踪系统,以其大剂量、高精度和周围受照射的正常组织或重要器官的范围小等优点,在治疗早期非小细胞肺癌(NSCLC)方面取得了与手术相似的疗效。但是对于早期NSCLC,尽管射波刀实施了有效的生物剂量,实时靶区追踪,但局部失效仍会发生。本文就射波刀在早期NSCLC治疗中的应用进行综述并进一步探讨相关的影响因素。     

Cyberknife radiosurgery for squamous cell carcinoma of vulva after prior pelvic radiation therapy

Limited options exist for patients experiencing a local recurrence of vulvar malignancies after surgery and pelvic radiation. These recurrences often are associated with cancer-related skin desquamation and poor clinical outcomes. A new radiotherapeutic treatment modality for the previously irradiated patient is cyberknife radiosurgery, which uses a linear accelerator mounted on an industrial robotic arm to allow non-coplanar radiation therapy delivery with sub-millimeter precision. This study describes the first reported use of cyberknife radiosurgery for the treatment of recurrent vulvar cancer in three women.     

影像引导放射治疗系统

影像引导放射治疗(IGRT)是近年来放射肿瘤学领域最先进的治疗技术。通过新型IGRT系统,将影像获取、治疗计划设计、CT模拟定位及加速器治疗完美地整合到一套放疗系统之中,以精确实施放射治疗。目前IGRT设备主要有传统直线加速器结合影像系统、断层放射治疗机和影像引导的立体定向治疗机。现就该类新技术及其临床应用作一综述。     

Cone beam CT (CBCT) evaluation of inter- and intra-fraction motion for patients undergoing brain radiotherapy immobilized using a commercial thermoplastic mask on a robotic couch

Patients receiving fractionated intensity-modulated radiation therapy (IMRT) for brain tumors are often immobilized with a thermoplastic mask; however, masks do not perfectly re-orient the patient due to factors including the maximum pressure which can be applied to the face, deformations of the mask assembly, patient compliance, etc. Consequently, ~3-5mm PTV margins (beyond the CTV) are often recommended. We aimed to determine if smaller PTV margins are feasible using mask immobilization coupled with 1) a gantry mounted CBCT image guidance system and 2) position corrections provided by a full six-degree of freedom (6-DOF) robotic couch. A cohort of 34 brain tumor patients was treated with fractionated IMRT. After the mask set-up, an initial CBCT was obtained and registered to the planning CT. The robotic couch corrected the misalignments in all 6-DOF and a pre-treatment verification CBCT was then obtained. The results indicated a repositioning alignment within our threshold of 1.5 mm (3D). Treatment was subsequently delivered. A post-treatment CBCT was obtained to quantify intra-fraction motion. Initial, pre-treatment and post-treatment CBCT image data was analyzed. A total of 505 radiation fractions were delivered to the 34 patients resulting in ~1800 CBCT scans. The initial median 3D (magnitude) set-up positioning error was 2.60 mm. Robotic couch corrections reduced the 3D median error to 0.53 mm prior to treatment. Intra-fraction movement was responsible for increasing the median 3D positioning error to 0.86 mm, with 8% of fractions having a 3D positioning error greater than 2 mm. Clearly CBCT image guidance coupled with a robotic 6-DOF couch dramatically improved the positioning accuracy for patients immobilized in a thermoplastic mask system; however, such intra-fraction motion would be too large for single fraction radiosurgery.     

The Evolving Role of Stereotactic Radiosurgery and Stereotactic Radiation Therapy for Patients with Spine Tumors

Traditional management strategies for patients with spinal tumors have undergone considerable changes during the last 15 years. Significant improvements in digital imaging, computer processing, and treatment planning have provided the basis for the application of stereotactic techniques, now the standard of care for intracranial pathology, to spinal pathology. In addition, certain of these improvements have also allowed us to progress from frame-based to frameless systems which now act to accurately assure the delivery of high doses of radiation to a precisely defined target volume while sparing injury to adjacent normal tissues. In this article we will describe the evolution from yesterday's standards for radiation therapy to the current state of the art for the treatment of patients with spinal tumors. This presentation will include a discussion of radiation dosing and toxicity, the overall process of extracranial radiation delivery, and the current state of the art regarding Cyberknife, Novalis, and tomotherapy. Additional discussion relating current research protocols and future directions for the management of benign tumors of the spine will also be presented.     

Quantitative measurement of CyberKnife robotic arm steering

Respiratory motion is a significant and challenging problem for radiation medicine. Without adequate compensation for respiratory motion, it is impossible to deliver highly conformal doses to tumors in the thorax and abdomen. The CyberKnife frameless stereotactic radiosurgery system with Synchrony provides respiratory motion adaptation by monitoring skin motion and dynamically steering the beam to follow the moving tumor. This study quantitatively evaluated this beam steering technology using optical tracking of both the linear accelerator and a ball-cube target. Respiratory motion of the target was simulated using a robotic motion platform and movement patterns recorded from previous CyberKnife patients. Our results show that Synchrony respiratory tracking can achieve sub-millimeter precision when following a moving object.     

Clinical uses of radiosurgery

Radiosurgery uses stereotactic targeting methods to precisely deliver highly focused, large doses of radiation to small intracranial tumors and arteriovenous malformations (AVMs). This article reviews the most common clinical applications of radiosurgery and the clinical results reported from a number of series using either a cobalt-60 gamma knife or linear accelerator as radiation sources. Radiosurgery is used to treat malignant tumors, such as selected cases of brain metastases and malignant gliomas (for which stereotactic radiosurgical boosts are utilized in conjunction with fractionated radiation therapy), as well as benign tumors, such as meningiomas, acoustic neuromas, and pituitary adenomas. Treatment of small AVMs is also highly effective. Although radiosurgery has the potential to produce complications, the majority of patients experience clinical improvement with less morbidity than occurs with surgical resection.     

An Overview of CyberKnife Radiosurgery

Stereotactic radiosurgery is a non-invasive procedure that utilizes precisely targeted radiation as an ablative surgical tool. Conventional radiosurgery devices, such as the Gamma Knife, rely upon skeletally attached Stereotactic frames to immobilize the patient and precisely determine the 3D spatial position of a tumor. A relatively new instrument, the CyberKnife (Accuray, Inc., Sunnyvale, CA), makes it possible to administer radiosurgery without a frame. The CyberKnife localizes clinical targets using a very accurate image-to-image correlation algorithm, and precisely cross-fires high-energy radiation from a lightweight linear accelerator by means of a highly manipulable robotic arm. CyberKnife radiosurgery is an effective alternative to conventional surgery or radiation therapy for a range of tumors and some non-neoplastic disorders. This report will describe CyberKnife technology and oncologic applications in neurosurgery and throughout the body.     

The Efficacy of Stereotactic Radiosurgery in the Management of Intracranial Ependymoma

OBJECTIVE: A retrospective analysis was performed to determine the outcome of patients with intracranial ependymoma treated with stereotactic radiosurgery (SRS). METHODS: Nine ependymoma patients have been treated with SRS (four with linear accelerator and five with Gamma Knife) since 1990. Two patients had WHO grade III tumors, and the remaining seven had WHO grade II tumors. Eight of nine patients received external beam radiation therapy at some point prior to radiosurgery to a total median dose of 54 Gy. The radiosurgery dose ranged from 14 to 20 Gy. RESULTS: The median follow-up was 28 months. The median age of patients at diagnosis was 35 years. Four patients developed progressive disease following radiosurgery, and two patients have died of progressive disease. The 3-year relapse-free survival was 55.6%. The 3-year overall survival was 71.1%. Patients treated with radiosurgery as a component of initial treatment (generally as a boost following external beam) had an improved relapse-free survival (100%) compared to those treated with radiosurgery to salvage an external beam local failure (20%). CONCLUSION: SRS is an effective treatment for intracranial ependymoma. Further clinical trials are warranted incorporating radiosurgery as a component of initial management in selected ependymoma patients.     

A radiographic and tomographic imaging system integrated into a medical linear accelerator for localization of bone and soft-tissue targets.

PURPOSE: Dose escalation in conformal radiation therapy requires accurate field placement. Electronic portal imaging devices are used to verify field placement but are limited by the low subject contrast of bony anatomy at megavoltage (MV) energies, the large imaging dose, and the small size of the radiation fields. In this article, we describe the in-house modification of a medical linear accelerator to provide radiographic and tomographic localization of bone and soft-tissue targets in the reference frame of the accelerator. This system separates the verification of beam delivery (machine settings, field shaping) from patient and target localization. MATERIALS AND METHODS: A kilovoltage (kV) x-ray source is mounted on the drum assembly of an Elekta SL-20 medical linear accelerator, maintaining the same isocenter as the treatment beam with the central axis at 90 degrees to the treatment beam axis. The x-ray tube is powered by a high-frequency generator and can be retracted to the drum-face. Two CCD-based fluoroscopic imaging systems are mounted on the accelerator to collect MV and kV radiographic images. The system is also capable of cone-beam tomographic imaging at both MV and kV energies. The gain stages of the two imaging systems have been modeled to assess imaging performance. The contrast-resolution of the kV and MV systems was measured using a contrast-detail (C-D) phantom. The dosimetric advantage of using the kV imaging system over the MV system for the detection of bone-like objects is quantified for a specific imaging geometry using a C-D phantom. Accurate guidance of the treatment beam requires registration of the imaging and treatment coordinate systems. The mechanical characteristics of the treatment and imaging gantries are examined to determine a localizing precision assuming an unambiguous object. MV and kV radiographs of patients receiving radiation therapy are acquired to demonstrate the radiographic performance of the system. The tomographic performance is demonstrated on phantoms using both the MV and the kV imaging system, and the visibility of soft-tissue targets is assessed. RESULTS AND DISCUSSION: Characterization of the gains in the two systems demonstrates that the MV system is x-ray quantum noise-limited at very low spatial frequencies; this is not the case for the kV system. The estimates of gain used in the model are validated by measurements of the total gain in each system. Contrast-detail measurements demonstrate that the MV system is capable of detecting subject contrasts of less than 0.1% (at 6 and 18 MV). A comparison of the kV and MV contrast-detail performance indicates that equivalent bony object detection can be achieved with the kV system at significantly lower doses (factors of 40 and 90 lower than for 6 and 18 MV, respectively). The tomographic performance of the system is promising; soft-tissue visibility is demonstrated at relatively low imaging doses (3 cGy) using four laboratory rats. CONCLUSIONS: We have integrated a kV radiographic and tomographic imaging system with a medical linear accelerator to allow localization of bone and soft-tissue structures in the reference frame of the accelerator. Modeling and experiments have demonstrated the feasibility of acquiring high-quality radiographic and tomographic images at acceptable imaging doses. Full integration of the kV and MV imaging systems with the treatment machine will allow on-line radiographic and tomographic guidance of field placement.     

Stereotactic Body Radiotherapy in Prostate Cancer: Is Rapidarc a Better Solution than Cyberknife?

AimsThere is increasing interest in stereotactic body radiotherapy (SBRT) for the management of prostate adenocarcinoma, with encouraging initial biological progression-free survival results. However, the limited literature is dominated by the use of the Cyberknife platform. This led to an international phase III study comparing outcomes for Cyberknife SBRT with both surgery and conventionally fractionated intensity-modulated radiotherapy (the PACE study). We aim to compare Cyberknife delivery with Rapidarc, a more widely available treatment platform.Materials and methodsThe scans of six previous prostate radiotherapy patients with a range of prostate sizes were chosen. The clinical target volume was defined as the prostate gland, with 3 mm added for the Cyberknife planning target volume (PTV) and 5 mm for the Rapidarc PTV. Accuray multiplan v. 4.5 was used for planning with delivery on a Cyberknife VSI system v9.5; Varian Eclipse v10 was used for Rapidarc planning with delivery using a Varian 21EX linear accelerator. Both systems attempted to deliver at least 35 Gy to the PTV in five fractions with PTV heterogeneity <12%.ResultsAll organ at risk (OAR) constraints were achieved by both platforms, whereas the Cyberknife failed to achieve the desired PTV homogeneity constraint in two cases. In other OARs without constraints, Cyberknife delivered higher doses. The volume of the 35 Gy isodose was slightly larger with Rapidarc, but conversely at doses <35 Gy normal tissues received higher doses with Cyberknife. The mean planning and delivery time was in favour of Rapidarc.ConclusionsWe have shown that there is no discernible dosimetric advantage to choosing Cyberknife over Rapidarc for SBRT delivery in prostate cancer. Given the significant benefits of Rapidarc in terms of availability, planning and delivery time, the authors suggest that phase III trials of SBRT should include Rapidarc or equivalent rotational delivery platforms.     

Dosimetry and techniques for simultaneous hyperthermia and external beam radiation therapy.

An increased biological effect is realized when hyperthermia and radiation therapy are combined simultaneously. To take advantage of this effect, techniques have been developed that combine existing hyperthermia devices with a linear accelerator. This allows concomitant delivery of either ultrasound or microwave hyperthermia with photon radiation therapy. Two techniques have been used clinically: the orthogonal technique, in which the microwave or ultrasound beam and the radiation beam are orthogonal to one another, and the en face technique, in which the ultrasound or microwave beam and the radiation beam travel into the tumour through the same treatment window. The en face technique has necessitated the development of special attachments so that the hyperthermia device can be mounted to the linear accelerator and so that non-uniform portions of the hyperthermia device can be removed from the radiation beam. For microwave therapy, applicators are mounted onto the linear accelerator using the compensating filter tray holder. For ultrasound, special reflector devices are mounted to a frame that is mounted onto the compensating filter tray holder of the linear accelerator. Because the linear accelerator is an isocentric device, the height of the radiation source is fixed, and this has necessitated specially designed devices so that the ultrasound support system is compatible with the linear accelerator. The treatment setups for both the en face technique and the orthogonal technique require the interaction of both hyperthermia and radiation therapy personnel and equipment. The dosimetry and day-to-day operations for each technique are unique. The simulation for the en face technique is much different from the simulation of a normal radiation treatment and requires the presence of a hyperthermia physicist. Also, for the en face technique, the attenuation of the microwave applicator and the thickness and attenuation of the ultrasound reflector system are taken into account for radiation dosimetry. This paper presents details of the dosimetry and logistics of the techniques for simultaneous thermoradiotherapy based on 7 years of experience treating more than 50 patients.     

Dosimetry and techniques for simultaneous hyperthermia and external beam radiation therapy

An increased biological effect is realized when hyperthermia and radiation therapy are combined simultaneously. To take advantage of this effect, techniques have been developed that combine existing hyperthermia devices with a linear accelerator. This allows concomitant delivery of either ultrasound or microwave hyperthermia with photon radiation therapy. Two techniques have been used clinically: the orthogonal technique, in which the microwave or ultrasound beam and the radiation beam are orthogonal to one another, and the en face technique, in which the ultrasound or microwave beam and the radiation beam travel into the tumour through the same treatment window. The en face technique has necessitated the development of special attachments so that the hyperthermia device can be mounted to the linear accelerator and so that non-uniform portions of the hyperthermia device can be removed from the radiation beam. For microwave therapy, applicators are mounted onto the linear accelerator using the compensating filter tray holder. For ultrasound, special reflector devices are mounted to a frame that is mounted onto the compensating filter tray holder of the linear accelerator. Because the linear accelerator is an isocentric device, the height of the radiation source is fixed, and this has necessitated specially designed devices so that the ultrasound support system is compatible with the linear accelerator. The treatment setups for both the en face technique and the orthogonal technique require the interaction of both hyperthermia and radiation therapy personnel and equipment. The dosimetry and day-to-day operations for each technique are unique. The simulation for the en face technique is much different from the simulation of a normal radiation treatment and requires the presence of a hyperthermia physicist. Also, for the en face technique, the attenuation of the microwave applicator and the thickness and attenuation of the ultrasound reflector system are taken into account for radiation dosimetry. This paper presents details of the dosimetry and logistics of the techniques for simultaneous thermoradiotherapy based on 7 years of experience treating more than 50 patients.     

Stereotactic radiosurgery for intracranial arteriovenous malformations using a standard linear accelerator

We have previously described the development of a technique which utilizes a standard linear accelerator to provide stereotactic, limited field radiation. The radiation is delivered using a modified and carefully calibrated 6 MV linear accelerator. Precise target localization and patient immobilization is achieved using a Brown-Roberts-Wells (BRW) stereotactic head frame which is in place during angiography, CT scanning, and treatment. Seventeen arteriovenous malformations (AVMs) have been treated in 16 patients from February 1986 to July 1988. Single doses of 1500-2500 cGy were delivered using multiple non-coplanar arcs with small, sharp edged x-ray beams to lesions less than 2.7 cm in greatest diameter. The dose distribution from this technique has a very rapid dropoff of dose beyond the target volume. Doses were prescribed at the periphery of the AVMs, typically to the 80-90% isodose line. Eleven of 16 patients have been followed by repeat angiography at least 1 year following treatment. Five of 11 have had complete obliteration of their AVM in 1 year and an additional three patients have achieved complete obliteration by 24 months. There have been no incidences of rebleeding or serious complications in any patient. We conclude that stereotactic radiosurgery using a standard linear accelerator is an effective and safe technique in the treatment of intracranial AVMs and the results compare favorably to the more expensive and elaborate systems that are currently available for stereotactic treatments.     

Prostate localization systems for prostate radiotherapy]

The development of sophisticated conformal radiation therapy techniques for prostate cancer, such as intensity-modulated radiotherapy, implies precise and accurate targeting. Inter- and intrafraction prostate motion can be significant and should be characterized, unless the target volume may occasionally be missed. Indeed, bony landmark-based portal imaging does not provide the positional information for soft-tissue targets (prostate and seminal vesicles) or critical organs (rectum and bladder). In this article, we describe various prostate localization systems used before or during the fraction: rectal balloon, intraprostatic fiducials, ultrasound-based localization, integrated CT/linear accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical benefit in using such prostate localization tools is not proven by randomized studies and the feasibility has just been established for some of these techniques. Nevertheless, these systems should improve local control by a more accurate delivery of an increased prescribed dose in a reduced planning target volume.