Treatment Delivery Technology Research Articles

Resource Allocations for Common Radiation Oncology Procedures

Radiation Oncology is a complex, resource-intensive discipline. The complexity of the radiation oncology treatment process has increased significantly in recent years with the introduction of more advanced imaging, planning, and treatment delivery technology and enhanced use of multidisciplinary care paths. We conducted a multi-institutional study to estimate the average time by functional unit for a wide range of modern radiation oncology treatment regimens. Structured process mapping was performed for 24 treatment categories, and average time estimates for 6 functional groups were obtained for each process step through consultation with the full clinical team at each institution. Six geographically dispersed institutions participated in the study. Significant effort was invested in aggregate data analysis and clarification of assumptions. The findings show significant variability in the resources expended for many treatment categories as well as the distribution of workload between functional units. Major factors in the variability include the rate of adoption of hypofractionation in external beam therapy, adoption of automation tools and standardization, and the transition to multimodality image-based planning in brachytherapy. The data obtained from this study may be useful in designing institution-specific staffing models appropriate to the scope of radiation therapy services provided at each institution.

Carmustine: Promising Drug for Treatment of Glioma

Background: The treatment for glioma has challenging and survival rate is not more than one year after diagnosis. Carmustine is a non-specific antineoplastic agent that belongs to the nitrosourea group of compounds (bischlo-roethyl nitrosourea) and has various mechanisms of tumor cytotoxicity. Main body: It can alkylate reactive sites on nucleoproteins as an alkylating agent, interfering with DNA and RNA synthesis and DNA repair. It can create interstrand crosslink’s in DNA, preventing DNA replication and transcription. Under physiological conditions, carmustine undergoes spontaneous nonenzymatic decomposition, releasing reactive intermediates with alkylating and carbamoylating activities, which are thought to be responsible for carmustine’s anticancer and cytotoxic properties. Human gliomas are the for the most part kind of tumor for brain. Gliomas can be treated with a variety of chemotherapeutics, but carmustine has recently emerged as a promising treatment option. Conclusion: The adoption of a nose-to-brain medication delivery method has several advantages over efforts that try to breach the blood-brain barrier. The focused strategy also lowers the risk of cardiovascular harm. A significant advantage of nose to brain administration is the relatively high patient compliance. Research into new chemotherapeutic compounds and treatment delivery technologies is crucial for present and future patients

Three discipline collaborative radiation therapy (3DCRT) special debate: FLASH radiotherapy needs ongoing basic and animal research before implementing it to a large clinical scale.

Three discipline collaborative radiation therapy (3DCRT) special debate: FLASH radiotherapy needs ongoing basic and animal research before implementing it to a large clinical scale.

From neuroscience to evidence based psychological treatments – The promise and the challenge, ECNP March 2016, Nice, France

This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches are not fully satisfactory, there is an imperative to understand why not. And when psychological therapies do work we need to understand why this is the case, and how we can improve them. We may be able to improve accessibility to treatment without understanding mechanisms. But for treatment innovation and improvement, mechanistic insights may actually help. Applying neuroscience in this way will become an additional mission for ECNP.

Advances in Technology and Its Application: Radiotherapy Treatment Planning.

Treatment planning for radiotherapy has become unthinkable without computer algorithms for dose optimization. Although the need for optimization algorithms originated from the complexity of treatment delivery technology such as intensity-modulated radiotherapy, volumetric-modulated arc therapy, and robotic stereotactic radiotherapy, the focus has shifted to refining goals and methods of optimization itself. Dose optimization chiefly advances in 3 directions: human interface and automation, compensation of changing patient geometries, and diversification/individualization of radiation dose prescription. Traditionally, dose optimization requires the definition of numerical treatment goals, followed by an interactive trial-and-error process to adjust the correct, patient-specific balance of these goals. Being both operator dependent and time consuming, methods are needed that produce high-quality treatments efficiently, with the long-term objective of autonomous dose optimization. Expedient treatment planning is also key to treatment adaptation to changes in patient geometry. Despite all efforts to image and adapt at treatment time, some residual uncertainties remain and must be compensated via treatment planning. Reformulations of the dose optimization problem are joined with various image-based 4D patient models to ensure treatment robustness against geometric uncertainties. Robust optimization leads to a deviation from customary dose prescription in favour of more predictable dose delivery. The dose distribution can be individualized further by additional functional image information, aiming to guide the dose towards undertreated volumes and away from overtreated ones, also known as dose-painting. Multimodal imaging is increasingly integrated into treatment planning, making it a natural consequence to supplant computed tomography by magnetic resonance imaging to establish MR-based radiotherapy.

Radiation oncology: a snapshot in time, 2014.

This special series issue of Journal of Clinical Oncology is devoted to the field of radiation oncology. The intention is to apprise our multidisciplinary readership of the latest developments and potential future directions in this field. The contents of this issue represent a snapshot in time, highlighting carefully selected topics in radiation oncology circa 2014. The editors enjoyed the process of considering what to record, given that we had such a broad and exciting assortment of choices available. We regret that we could not cover every aspect of the field. For example, we did not include a piece on lymphomas, although there have been significant changes in recent years with respect to the role of radiotherapy in managing that group of malignancies. Likewise, we did not specifically spotlight brachytherapy, or the contributions of the engineers and medical physicists whose work is the technologic basis of modern radiation oncology. The latter point is worth extra emphasis: the marriage of computed tomography, magnetic resonance, and positron emission tomography imaging to treatment planning, the consequential advent of three-dimensional (3D) conformal radiation therapy, the development of inverse planning software and intensity-modulated radiation therapy delivery hardware, the invention of near real-time image guidance of treatment delivery using cone-beam computed tomography and other techniques, and the adaptation of motion management strategies and 4D treatment planning (3D with a breathing motion component) are just some of the marvelous inventions that are the sine qua non on which the field is now based. Radiation oncology is not alone as a medical specialty that has benefited greatly from computerization and other applied modern technology, but we radiation oncologists owe a particularly large debt to our medical physics colleagues, who work alongside us in the clinic every day. Some of the articles that are included in this special series issue do, in fact, address clinical gains that are enabled by technologic progress (articles on stereotactic radiosurgery, stereotactic body radiation therapy, particle therapy, and novel paradigms for early-stage breast cancer, for example). These high-tech treatments are sometimes highly resource intensive, and we must be mindful of whether we are providing good value to patients and society with these sophisticated innovations—hence the thoughtful contribution by Teckie et al1 concerning how we begin to frame that question. The laws of physics are not changing, nor is human anatomy likely to evolve noticeably in this millennium. Consequently, as pointed out by Giaccia,2 it could be that we are reaching the limits of how far we can go on the basis of advances in treatment delivery technology alone. For further progress we will likely need to emphasize tumor biology from perspectives that vary from the genome to growth factor signaling to the tumor-immune system interface. Morris and Harari3 discuss pioneering efforts to translate such knowledge to the clinic. The ultimate measure of any success in oncology is how patients regard their own outcomes, and a fine discussion of the methodology of analyzing patient-reported outcomes is provided by Siddiqui et al,4 who also discuss important issues to consider in the long-term post-treatment survivorship phase of life—a state that is gratifyingly becoming more and more common. Whereas Salama and Milano5 describe the virtue of maintaining an aggressive approach for many patients with limited metastatic disease, Lutz et al6 offer insights into how radiotherapy is best integrated into the end-of-life phase of care for patients with cancer. In a few contributions in this issue, there are passages that provide background information of a historical nature on the development of treatment strategies and methods that are now in routine clinical use. The value of these sections is twofold: first, they recognize important individuals and schools of thought from the past that have helped to shape our modern approaches; and second, they remind us that future readers of material published today might look back on treatments given in 2014 and consider many to be outdated. Indeed, we hope that this will be the case. Although we are proud of how the field of radiation oncology has progressed, there remain many challenges to overcome before the problem of cancer is a thing of the past.

WE‐D‐BRD‐01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF‐beam based IMRT and VMAT, respiration‐gated VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted.Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.

DNA topoisomerase I drugs and radiotherapy for lung cancer.

Lung cancer represents the most common cause of cancer-related mortality in the United States and around the world. DNA topoisomerase I (TOP1) drugs such as irinotecan and topotecan represent a unique class of chemotherapeutic agents that exhibit not only potent cytotoxic effect, but also tumor-selective radiation-sensitizing effect. The mechanism of cytotoxicity and radiation sensitization by TOP1 drugs has been intensely investigated. Modern radiotherapy, aided by improved imaging and treatment delivery technology, is capable of targeting tumors more precisely, while sparing surrounding critical structures. Clinical trials with camptothecin derivatives and radiotherapy have been conducted in lung cancers. Combined modality therapy with TOP1 drugs and radiotherapy offers a new frontier for lung cancer therapy. We review the present state of TOP1-targeted chemotherapy and modern radiotherapy for lung cancer.

TH-A(SAM)-BRC-01: Physics and Dosimetry of SBRT

SBRT is a novel cancer treatment strategy where ultra-high doses per fraction are used, generally in the range of 6 to 20 Gy per fraction, in a hypofractionated regimen of 5 or fewer fractions. Such high doses per treatment were inconceivable in the past because of concerns about radiation-induced injury to normal tissue if large volumes of OARs were irradiated to high doses. However, with recent technical advancements in highly-conformal treatment planning, image-guided radiotherapy, and delivery technologies, it has become possible to deliver safely very large fractional doses of radiation to lesions in the lung, liver, spine, and prostate. Since SBRT involves technically sophisticated patient repositioning and treatment delivery procedure, it is not uncommon for a treatment to last 40 minutes. Clinicians are usually concerned of a possible compromise in treatment efficacy for individual fractions that require long treatment time because of tumor intra-fraction motion and patient involuntary movement during radiation delivery, as well as a theoretical risk of intra-fractional radiation damage repair within tumor cells in the context of prolonged fractional delivery time. In this session, methods for effective, optimal and accurate planning, and efficiency and robustness in the delivery of SBRT, including QA, will be presented so that these concerns are minimized. Furthermore, the technical challenges associated with the clinical implementation of SBRT will be discussed, thereby allowing the wide application of SBRT using current treatment planning and delivery technologies (fixed-field 3DCRT/IMRT, dynamic arcs, rotational IMRT). The specific objectives of the session are to: 1. Describe secure and comfortable immobilization techniques to minimize patient movement, techniques accounting for internal organ motion, and accurate patient repositioning methods using online imaging 2. Discuss treatment planning methods to ensure coverage of tumor volume within high dose regions with very rapid fall-off to surrounding OARs, including the use of Monte Carlo algorithms 3. Describe quality assurance and verification techniques for fixed-field (3DCRT, IMRT) and rotational (static/dynamic arcs, VMAT/Rapid Arc/Tomo) delivery, usually characterized by many small beam segments, and the assessment of target conformity coverage, and high dose “spillage” region

TU-A-BRB-01: Physics and Dosimetry of SBRT

SBRT is a novel cancertreatment strategy where ultra‐high doses per fraction are used, generally in the range of 10 to 20 Gy per fraction, in a hypofractionated regimen of 5 or fewer fractions. Such high doses per treatment were inconceivable in the past because of concerns about radiation‐induced injury to normal tissue if large volumes of OARs were irradiated to high doses. However, with recent technical advancements in highly‐conformal treatment planning,image‐guidedradiotherapy, and delivery technologies, it has become possible to deliver safely very large fractional doses of radiation to lesions in the lung, liver, spine, and prostate. Since SBRT involves technically sophisticated patient repositioning and treatment delivery procedure, it is not uncommon for a treatment to last up to 40–50 minutes. Clinicians are usually concerned of a possible compromise in treatment efficacy for individual fractions that require long treatment time because of tumor intra‐fraction motion and patient involuntary movement during radiation delivery, as well as a theoretical risk of intra‐fractional radiation damage repair within tumor cells in the context of prolonged fractional delivery time. In this session, methods for effective, optimal and accurate planning, and efficiency and robustness in the delivery of SBRT, including QA, will be presented so that these concerns are minimized. Furthermore, the technical challenges associated with the clinical implementation of SBRT will be discussed, thereby allowing the wide application of SBRT using current treatment planning and delivery technologies (fixed‐field 3DCRT/IMRT, dynamic arcs, rotational IMRT). The specific objectives of the session are to: 1. Describe secure and comfortable immobilization techniques to minimize patient movement, techniques accounting for internal organ motion, and accurate patient repositioning methods using online planning 2. Discuss treatment planning methods to ensure coverage of tumor volume within high dose regions with very rapid fall‐off to surrounding OARs, including the use of Monte Carlo algorithms 3. Describe quality assurance and verification techniques for fixed‐field (3DCRT, IMRT) and rotational (static/dynamic arcs, VMAT/Rapid Arc/Tomo) delivery, usually characterized by many small beam segments, and the assessment of target conformity coverage, and high dose “spillage” region

MO‐SAM‐BRB‐02: Proton Physics and Technology

The dose localization advantages of proton beams derive primarily from the Bragg peak in the proton stopping distribution. Therefore, the potential clinical gains expected form proton beams are based on physical, rather than biological, considerations. The rationale for proton therapy is based on the hypothesis that the superior dose distributions of proton beams will lead to increased local control; increased disease‐free survival; decreased treatment‐related morbidity; and improved quality of life. The degree to which each of these end‐points can be changed by proton therapy will depend upon the particular disease site, patient population, and other factors. In the last few years there has been a significant increase in interest in proton therapy and as a consequence, many new facilities are being planned and built. There are currently over 25 institutions worldwide treating patients with proton beams and over 55,000 patients have been treated. There are at least 25 new facilities in various stages of planning and building. We will discuss the rationale for proton therapy, the current status of proton therapy, proton physics and dosimetry, and technology for the acceleration and delivery of proton beams. We will also discuss new developments in proton therapy accelerators and treatment delivery systems. Technologies for carbon ion therapy will also be discussed. We will address issues related to the cost of proton treatments relative to the cost of photon treatments and discuss various ways in which the cost of proton therapy can be decreased.Learning Objectives:Understand1. rationale for proton therapy;2. current status of proton therapy;3. physical characteristics of proton beams;4. beam production and treatment delivery technology for proton beams;5. acceptance testing and clinical commissioning of proton therapy beams; and6. QA for proton treatments

MO‐B‐AUD C‐01: Proton Therapy

The clinical advantages of proton beams have become widely recognized and there has recently been a significant increase in interest for building additional proton therapy facilities. There are currently over 25 institutions worldwide treating patients with proton beams and over 55,000 patients have been treated. There are at least 25 new facilities in various stages of planning and building. However, the fraction of patients treated with protons each year remains extremely small compared to the total number of cancer patients treated with external beam photons and electrons. The advantage of proton beams lies primarily in their excellent dose localization as compared to that which can be achieved using photon beams. Due to the Bragg peak characteristic in the depth dose of proton beams, the integral dose from proton therapy is, in general, about two times less that that for photon treatments. This allows higher doses to be delivered to target volumes, resulting in increased probabilities of local control, and lower doses delivered to critical normal tissues, resulting in decreased probabilities of treatment‐related morbidity. There are many challenges associated with increasing the accessibility of proton therapy not the least of which is the very limited number of clinical staff with knowledge of and training in proton therapy. The aim of the present Continuing Education Course is to provide a basic understanding of the rationale for proton therapy, physics of proton beams, technology of proton beam acceleration and transport, delivery of proton treatments, proton treatment planning and clinical results of proton therapy.Educational Objectives:1. Understanding of the physical characteristics of proton beams and interactions in tissues.2. Understanding of the beam production and treatment delivery technology for proton beams.3. Understanding of the clinical commissioning of proton therapy beams.4. Understanding of the basic principles of proton treatment planning.5. Understanding of the clinical results for proton therapy.

Controlling the dose distribution with gEUD-type constraints within the convex radiotherapy optimization framework

Radiation therapy is an important modality in treating various cancers. Various treatment planning and delivery technologies have emerged to support intensity modulated radiation therapy (IMRT), creating significant opportunities to advance this type of treatment. However, one of the fundamental questions in treatment planning and optimization, ‘can we produce better treatment plans relying on the existing delivery technology?’ still remains unanswered, in large part due to the underlying computational complexity of the problem, which, in turn, often stems from the optimization model being non-convex. We investigate the possibility of including the dose prescription, specified by the dose–volume histogram (DVH), within the convex optimization framework for inverse radiotherapy treatment planning. Specifically, we study the quality of approximating a given DVH with a superset of generalized equivalent uniform dose (gEUD)-based constraints, the so-called generalized moment constraints (GMCs). As a bi-product, we establish an analytic relationship between a DVH and a sequence of gEUD values. The newly proposed approach is promising as demonstrated by the computational study where the rectum DVH is considered. Unlike the precise partial-volume constraints formulation, which is commonly based on the mixed-integer model and necessitates the use of expensive computing resources to be solved to global optimality, our convex optimization approach is expected to be feasible for implementation on a conventional treatment planning station.

The North American Experience with Stereotactic Body Radiation Therapy in Non-small Cell Lung Cancer

In North America, the majority of prospective investigation using stereotactic body radiation therapy (SBRT) for thoracic targets has been carried out treating medically inoperable patients with non-small cell lung cancer. Because SBRT involves constructing very compact high-dose volumes within the lung for targeting cancer deposits, tumor position must be accurately assessed throughout the respiratory cycle. Measures to account for this motion, either by tracking (chasing), gating, or inhibition (breath hold and abdominal compression) must be used to avoid large margins of error that would expose uninvolved normal tissues. Sophisticated image guidance and related treatment delivery technology have been used primarily for the purpose of targeting the tumor with as low a radiation dose to the surrounding normal tissue as possible. Phase I dose escalation trials have been carried out in North America to achieve potent tumorcidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. While late toxicity requires further careful assessment, acute and subacute toxicity are generally acceptable. Radiographic and local tissue effects consistent with bronchial or vascular damage and downstream collapse with fibrosis are common. While such radiographic changes are most often asymptomatic, more frequent and sometimes debilitating toxicity has been observed for patients with tumors near the central airways. Prospective trials using SBRT in North America have been able to identify potent tolerant dose levels and confirm their efficacy in patients with medically inoperable disease. Although mechanisms of this injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in treating pulmonary targets.

MO‐B‐M100F‐01: Proton Therapy

The clinical advantages of proton beams have become widely recognized and there has recently been a significant increase in interest for building additional proton therapy facilities. There are currently over 25 institutions worldwide treating patients with proton beams and over 50,000 patients have been treated. There are at least 25 new facilities in various stages of planning and building. However, the fraction of patients treated with protons each year remains extremely small compared to the total number of cancer patients treated with external beam photons and electrons. The advantage of proton beams lies primarily in their excellent dose localization as compared to that which can be achieved using photon beams. Due to the Bragg peak characteristic in the depth dose of proton beams, the integral dose from proton therapy is significantly less that that for photon treatments. This allows higher doses to be delivered to target volumes, resulting in increased rates of local control, and lower doses delivered to critical normal tissues, resulting in decreased rates of treatment‐related morbidity. There are many challenges associated with increasing the accessibility of proton therapy not the least of which is the very limited number of clinical staff with knowledge of and training in proton therapy. The aim of the present Continuing Education Course is to provide a basic understanding of the rationale for proton therapy, physics of proton beams, technology of proton beam acceleration and transport, delivery of proton treatments, proton treatment planning and clinical results of proton therapy.Educational Objectives:Understanding of1. the physical characteristics of proton beams and interactions in tissues.2. the beam production and treatment delivery technology for proton beams.3. the clinical commissioning of proton therapy beams.4. the basic principles of proton treatment planning.5. the clinical results for proton therapy.

Treatment plan comparison between helical tomotherapy and MLC-based IMRT using radiobiological measures

The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose–volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose is applied together with the complication-free tumour control probability (P+). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using as the common prescription point of the treatment plans and plotting the tissue response probabilities versus for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome (P+ of 62.2% and 46.0%, to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P+ of 66.9% and 72.9%, to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P+ of 68.7% and 72.2%, to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose–response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of diagrams to effectively evaluate and compare treatment plans.

Stereotactic Body Radiation Therapy in Multiple Organ Sites

Stereotactic body radiation therapy (SBRT) uses advanced technology to deliver a potent ablative dose to deep-seated tumors in the lung, liver, spine, pancreas, kidney, and prostate. SBRT involves constructing very compact high-dose volumes in and about the tumor. Tumor position must be accurately assessed throughout treatment, especially for tumors that move with respiration. Sophisticated image guidance and related treatment delivery technologies have developed to account for such motion and efficiently deliver high daily dose. All this serves to allow the delivery of ablative dose fractionation to the target capable of both disrupting tumor mitosis and cellular function. Prospective phase I dose-escalation trials have been carried out to reach potent tumoricidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. Prospective phase II studies have been reported from several continents consistently showing very high levels of local tumor control. Although late toxicity requires further careful assessment, acute and subacute toxicities are generally acceptable. Patterns of toxicity, both clinical and radiographic, are distinct from those observed with conventionally fractionated radiotherapy as a result of the unique biologic response to ablative fractionation. Prospective trials using SBRT have confirmed the efficacy of treatment in a variety of patient populations. Although mechanisms of ablative-dose injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in the treatment arsenal.

Intracranial and extracranial stereotactic radiosurgery and radiotherapy

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are both flourishing, potent, noninvasive methods of precise high-dose RT for localized benign and malignant tumor in cranial or extracranial locations (stereotactic body radiotherapy [SBRT]). Both have in common the use of image guidance and related treatment delivery technology for escalating the radiation dose to the tumor with as little radiation dose to the surrounding normal tissue as possible. The advent and implementation of SRT and SBRT are novel, but they are a natural progression of the clinical implementation of SRS technologies that has occurred during the previous decades.

Repetitive transcranial magnetic stimulation as add-on antidepressant treatment. The applicability of the method in a clinical setting

Recent research indicates that repetitive transcranial magnetic stimulation (rTMS) over the frontal cortex has an antidepressant effect. The aim of the present pilot study was to assess the antidepressant effect, side-effects and the applicability in daily clinical practice of left prefrontal high-frequency rTMS. Fifteen inpatients with major depression (ICD-10 and DSM-IV) were randomized to receive 15 days of real left prefrontal high-frequency rTMS (20 trains of 10 s, 60-s interval, 10 Hz, 90% of motor threshold) or sham rTMS as add on to conventional antidepressant treatment. Depressive symptoms and side-effects were evaluated blindly during the treatment period. Five out of eight patients receiving real rTMS suffered from local discomfort during treatment. Three of them dropped out and the project was closed for that reason. Real rTMS did not add efficacy to standard antidepressant medication. This pilot study did not confirm the antidepressant effect of left frontal high-frequency rTMS.Unwanted effects led to considerable patient drop-out and premature termination of the study. The result suggests that alternative treatment delivery technology should be considered.

High-tech in radiation oncology: should there be a ceiling?

Purpose To analyze some of the limitations to improvement of the outcome of radiotherapy (RT) expected from the introduction of sophisticated treatment planning and delivery technology. Methods and materials Several recent examples from the literature were analyzed in some detail. Mathematical modeling techniques were used to assess the likely clinical impact of new technologies or biologic principles. The findings of recent randomized controlled trials of RT for prostate, breast, and rectal cancer were analyzed from the perspective of cost-effectiveness and therapeutic gain. Results The main findings of the analyses may be summarized as follows. Dosimetric precision should aim for a <2% patient-to-patient variability in the delivered dose. Imprecision in clinical target volume definition remains an obstacle for high-precision RT. Functional imaging and novel biologic assays may facilitate a move from a clinical target volume to the real target volume. Improved target volume coverage is mainly important if RT has high effectiveness. Radiation oncology is increasingly becoming evidence based. However, there is still a long way to go. Hypofractionation in adjuvant RT for breast cancer may represent a favorable balance between cost and benefit. Treatment complications are potentially associated with both suffering and high cost. The identification of high-risk patients would improve the cost-effectiveness of high-tech RT aimed at avoiding complications. Conformal RT may allow the introduction of hypofractionation, which, again, could potentially save resources. With improvement in surgery and more screening-detected cancer cases, the number needed to treat increases, and this will directly affect the cost-effectiveness of high-tech RT unless efficient patient selection can be developed. Conclusion Sustained technological refinement is only likely to be cost-effective if the clinical and biologic understanding of patient-to-patient variability in the risk of specific types of failure and the optimal multimodality approach to handle these risks is developed at the same time. Mathematical modeling together with methods from health technology assessment and health economics are useful complements to standard methods from evidence-based medicine. Progress in functional imaging and in basic and clinical cancer biology is likely to provide the tools required for individualized risk-adapted RT.