Frontiers of Radiation Therapy and Oncology最新文献

The clinical advantage for proton radiotherapy over photon approaches is the marked reduction in integral dose to the patient, due to the absence of exit dose beyond the proton Bragg peak. The integral dose with protons is approximately 60% lower than that with any external beam photon technique. Pediatric patients, because of their developing normal tissues and anticipated length of remaining life, are likely to have the maximum clinical gain with the use of protons. Proton therapy may also allow treatment of some adult tumors to much more effective doses, because of normal tissue sparing distal to the tumor. Currently, the most commonly available proton treatment technology uses 3D conformal approaches based on (a) distal range modulation, (b) passive scattering of the proton beam in its x- and y-axes, and (c) lateral beam-shaping. It is anticipated that magnetic pencil beam scanning will become the dominant mode of proton delivery in the future, which will lower neutron scatter associated with passively scattered beam lines, reduce the need for expensive beam-shaping devices, and allow intensity-modulated proton radiotherapy. Proton treatment plans are more sensitive to variations in tumor size and normal tissue changes over the course of treatment than photon plans, and it is expected that adaptive radiation therapy will be increasingly important for proton therapy as well. While impressive treatment results have been reported with protons, their cost is higher than for photon IMRT. Hence, protons should ideally be employed for anatomic sites and tumors not well treated with photons. While protons appear cost-effective for pediatric tumors, their cost-effectiveness for treatment of some adult tumors, such as prostate cancer, is uncertain. Comparative studies have been proposed or are in progress to more rigorously assess their value for a variety of sites. The utility of proton therapy will be enhanced by technological developments that reduce its cost. Combinations of 3D protons with IMRT photons may offer improved treatment plans at lower cost than pure proton plans. Hypofractionation with proton therapy appears to be safe and cost-effective for many tumor sites, such as for selected liver, lung and pancreas cancers, and may yield significant reduction in the cost of a therapy course. Together, these offer practical strategies for expanding the clinical availability of proton therapy.

Advanced technologies have facilitated the development of stereotactic body radiation therapy (SBRT) programs capable of delivering ablative radiation doses for the control of lung cancers. To date, experience with these programs has been highly favorable, as reflected in the results of careful clinical trials. The medically inoperable lung cancer patient, lacking more effective options, has served as the initial clinical base to test SBRT; the therapeutic outcomes have confirmed a significant role for this approach. For many patient groups, SBRT may become a noninvasive alternative to some thoracic surgeries, especially ones with more limited therapeutic goals such as wedge resection. Despite these results, long-term evaluation of the cases treated is required to allow greater understanding of the limitations and contributions of this new modality. The successful delivery of SBRT requires the development of a comprehensive, specialized clinical program providing advanced technology and the technical expertise of physicians, physicists and therapists specially trained in SBRT applications. To achieve successful clinical outcomes, careful patient selection and attention to therapy design and delivery are required since exacting clinical procedures are involved. This chapter will outline many details essential for establishing an effective SBRT program in clinical practice.

The hypofractionation of stereotactic body radiotherapy (SBRT) for prostate cancer has become a broad topic, and there are many aspects to consider before accepting this treatment into our clinics. Among the considerations are the data from the Stanford phase II trial, a seminal investigation into this area, which will be presented and reviewed here. A single-arm, prospective phase II trial was initiated at Stanford in December of 2003. This trial uses SBRT as monotherapy for 'low-risk' prostate cancer patients, and 69 patients have been entered to date. We have analyzed the patient data for the first 5 years of this study. For study entry, patients were required to have clinical stage T1c or T2a disease, prostate-specific antigen (PSA) ≤ 10 and a Gleason score of 3 + 3 (or 3 + 4 if the higher grade portion was of small volume, usually <25% of the cores involved). No prior treatment was permitted, including the use of transurethral resections or androgen deprivation therapies. A low urinary IPSS score of < 20 was required for study entry as well. The prescription dose was 7.25 Gy for 5 fractions for a total dose of 36.25 Gy. This was normalized to cover ≥ 95% of the planning target volume with 100% of the prescription dose. Patients were treated using CyberKnife technology. To date, excellent PSA responses have been observed in patients with lower-risk disease selected for treatment and receiving 36.25 Gy in 5 fractions. To date, sexual quality of life outcomes have also been approximately comparable to other radiotherapy approaches. Rates of late GI and GU toxicity have been relatively low and generally comparable to dose-escalated approaches using conventional fractionation.

The range of clinical applications for stereotactic body radiation therapy (SBRT) continues to expand based on clinical outcomes data from prospective trials and carefully analyzed institutional experiences. As a result of this strong scientific foundation, there has been burgeoning implementation of SBRT and other forms of hypofractionated radiation therapy in the practice of radiation oncology worldwide. In spite of the clinical successes achieved thus far - or, perhaps, because of them - fundamental questions about SBRT remain and have come into greater focus. Where and when is SBRT optimally integrated into the range of evolving modern multidisciplinary cancer treatment programs? What scientific insights (biological, technical and medical) might lead to further improvements in the efficacy of SBRT? What efficiencies are needed to achieve greater availability of SBRT? These and many other questions, fueled by the clinical accomplishments of SBRT to date, provide compelling directions for further exploration in scientific and clinical studies and further contributes to discoveries already transforming the practice of radiation oncology.

As advanced radiotherapy approaches for targeting the tumor and sparing the normal tissues have been developed, the image guidance of therapy has become essential to directing and confirming treatment accuracy. To approach these goals, image guidance devices now include kV on-board imagers, kV/MV cone-beam CT systems, CT-on-rails, and mobile and in-room radiographic/fluoroscopic systems. Nonionizing sources, such as ultrasound and optical systems, and electromagnetic devices have been introduced to monitor or track the patient and/or tumor positions during treatment. In addition, devices have been designed specifically for monitoring and/or controlling respiratory motion. Optimally, image-guided radiation therapy systems should possess 3 essential elements: (1) 3D imaging of soft tissues and tumors, (2) efficient acquisition and comparison of the 3D images, and (3) an efficacious process for clinically meaningful intervention. Understanding and using these tools effectively is central to current radiotherapy practice. The implementation and integration of these devices continue to carry practical challenges, which emphasize the need for further development of the technologies and their clinical applications.

The CyberKnife system deploys a linac mounted on an agile robot and directed under image guidance for stereotactic radiotherapy using nonisocentric beam delivery. A design advantage of the CyberKnife system is its method of active image guidance during treatment delivery. Recent developments in the hardware and software of the system have significantly enhanced its functionality: (a) an optimized path traversal process significantly reduces the robot motion time, resulting in reductions of overall treatment times of at least 5-10 min; (b) to optimize the accuracy of dose calculation in CyberKnife planning/delivery, Monte Carlo algorithms have been introduced; (c) the new IRIS collimator reduces the monitor units required, increases treatment speed and improves conformality and homogeneity of treatment plans; (d) XSight lung tracking, an algorithm for fiducial-less lung tracking, has been developed for peripheral, radio-dense lung tumors with diameters >15 mm; and (e) a sequential optimization planning process incorporates a more flexible approach to optimize the multiple, complex treatment planning criteria used today. The clinical efficacy of CyberKnife radiosurgery for brain/head lesions such as metastases, arteriovenous malformations, acoustic neuromas and meningiomas is well established. Since there is no need for skeletal fixation with the CyberKnife, radiosurgery can be applied to targets beyond the brain, and the technology has been extensively used for stereotactic body radiotherapy, treating targets in many anatomic sites. Currently, clinical studies have been completed or are ongoing for common malignancies including tumors involving the spine, lung, pancreas, liver and prostate.

Intensity-modulated radiotherapy (IMRT) can improve dose distributions through the treated breast and also reduce radiation doses to adjacent normal tissues including the contralateral breast, heart and lung with appropriate planning. Analyses demonstrate that the quality of radiation dose distribution does affect clinical results, and that outcomes are enhanced through improved planning and dose delivery methods. To achieve these results, it is essential to carefully define tissue volumes for treatment or avoidance, select technologies that can potentially conform fields to those volumes, use comprehensive planning methods, and assess their results in terms of objective dose constraints. IMRT can also be used to boost the region of tumor excision concurrently with whole breast treatment, an approach now being evaluated in on-going clinical studies. Partial breast irradiation (PBI) has been proposed as an alternative to irradiation of the entire breast for early-stage breast cancer patients undergoing breast conservation treatment. Numerous single institution phase II studies have demonstrated promising results, and the American Society of Radiation Oncology (ASTRO) has defined a suitable group of low-risk patients for PBI treatment off protocol at this time. IMRT has been proposed as an alternative to 3D conformal radiotherapy (3DCRT) for external beam PBI to improve the dose conformality to target volumes and the sparing of normal tissues. There are an increasing number of institutions evaluating and using IMRT instead of 3DCRT for PBI because of the potential treatment advantages for the breast cancer patient.

Organ motion due to breathing, peristalsis and deformation presents challenging problems for the delivery of highly conformal radiotherapy to upper abdominal targets, despite the many advancements in the technology of radiation planning and delivery. It is important to understand and account for this motion to avoid treatment inaccuracies, especially systematic errors that could potentially impact the probability of tumor control or increase the risk of normal tissue toxicity. Various image guidance tools can be utilized from the outset of radiation planning through treatment to minimize introducing such errors. These strategies include: assessment of breathing motion (with or without breath hold) prior to simulation, 4D CT simulation and cine MRI to evaluate tumor/organ motion, and image guidance on the treatment unit using kV fluoroscopy and 4D cone-beam CT. Together, image guidance methods can provide greater assurance that concordance exists between planned and delivered doses during a course of radiotherapy.

The development and acceptance of new image-guided radiotherapy (IGRT) technologies have often been initiated with the treatment of prostate cancer. Imaging and tracking of the prostate during a treatment course has yielded a great deal of information about the motion and deformation of the gland during radiotherapy, and has led the way toward the development of more accurate treatment methods including dose-guided and adaptive strategies. Now, there is long-term experience with the use of fiducials and electromagnetic implantable beacons that give high-quality tracking of prostate motion. From analyzing these extensive tracking data sets, a clear understanding of prostate motion and its dosimetric significance has developed. This knowledge can now be used to define current expectations and guidelines for clinical care. The random nature of prostate motion requires daily localization if treatment is to be delivered with small margins. Interfraction motion can have a significant impact on prostate gland dosimetry, and even more of an impact on the seminal vesicles and possibly intraprostatic tumor areas. The dosimetric impact on normal structures (bladder/rectum) is less clear, and there are significant individual variations. Interfraction and intrafraction rotations and deformations of the prostate are routinely detected. The dosimetric impact of these motions of the prostate gland is minimal when daily localization is used, even when the treatment margins are small. However, deformations of the seminal vesicles, rectum and bladder are much more pronounced. The dosimetric impact of deformation of the rectum and bladder is highly variable among patients, and the clinical consequences remain unclear. Daily volumetric imaging and dosimetry may become quite important for these volumes. Due to the random nature of motion/deformation during prostate radiotherapy, adaptive radiotherapy ideally would be performed as an on-line process. On-line adaptive radiotherapy requires robust deformable registration and replanning programs. These are beginning to emerge in useful clinic applications.

Stereotactic body radiotherapy (SBRT) is an emerging treatment for pancreas cancer and liver tumors. Early data suggest excellent control rates for locally advanced pancreas cancer. However, due to the close proximity of the duodenum and stomach, steps to effectively minimize toxicities must be taken through image guidance of treatments. SBRT for liver tumors has also shown high rates of local control with low risks for hepatic toxicity. Careful selection of cases for SBRT is essential to achieve disease control and to minimize toxicity for patients. In treatment, attention must be paid to minimizing exposure of nearby normal tissues, including ribs, skin and bowel as well as the functioning organs surrounding the tumors. There is no accepted standard for the SBRT dose/fractionation schedule for these cases and the optimal strategy will likely depend on the size, number and location of lesions for each patient. However, the published data seem to suggest an overall dose-response effect. To realize the clinical potential of SBRT for these tumors, investigations are needed to determine optimum fractionation schedules and to integrate its use with systemic chemotherapy programs.