Stereotactic Body Radiotherapy: A Review

doi:10.1016/j.clon.2009.12.003

Clinical Oncology

Volume 22, Issue 3, April 2010, Pages 157-172

https://doi.org/10.1016/j.clon.2009.12.003 Get rights and content

Abstract

Stereotactic body radiotherapy (SBRT) combines the challenge of meeting the stringent dosimetric requirements of stereotactic radiosurgery with that of accounting for the physiological movement of tumour and normal tissue. Here we present an overview of the history and development of SBRT and discuss the radiobiological rationale upon which it is based. The published results of SBRT for lung, liver, pancreas, kidney, prostate and spinal lesions are reviewed and summarised. The current evidence base is appraised and important ongoing trials are identified.

Section snippets

Statement of Search Strategies Used and Sources of Information

A search for the published results of stereotactic body radiotherapy for lung, liver, pancreas, kidney, prostate and spinal lesions was carried out using Ovid Online via the Athens website. Medline and Embase databases were selected, and the following terms were searched for, in all fields: ‘radiosurgery’, ‘stereotactic radiosurgery’, ‘stereotactic body radiotherapy’, ‘stereotactic body radiation therapy’ and ‘cyberknife’. Appropriate publications were selected from the lists generated, and

History

Stereotactic surgery was first described by Horsley and Clarke in 1906. They developed a method of locating deep-seated brain lesions by assigning coordinates in three planes to neuroanatomical structures, based on cranial landmarks [1]. In 1947, Spiegel et al. [2] introduced frame-based stereotaxy using a plaster head cap known as a stereoencephalatome, and a three-dimensional coordinate system relative to this.

Lars Leksell, a Swedish neurosurgeon, was the first person to marry the two

Fractionation and Radiobiology

In CFR, the tumour volume is irradiated together with a margin to account for tumour and organ motion, and inaccuracies of planning, set-up and delivery. The total dose is limited by the tolerance of normal tissue within, or close to, the planning target volume (PTV). The therapeutic benefit achieved with dose fractionation has been recognised for over 100 years. Conventional fractionation has emerged as a result of these early clinical observations, and subsequent changes have been driven

Overview of Stereotactic Body Radiotherapy Systems

A number of modern linacs with on-board imaging capabilities meet the basic image guidance requirements for delivering SBRT, e.g. Varian Trilogy (Varian Medical Systems, Palo Alto, CA, USA) and Elekta Synergy (Elekta, Stockholm, Sweden). A micro multileaf collimator can be added to produce the required degree of conformality for stereotactic plans.

More recently there has been the introduction of linacs fully adapted as integrated stereotactic delivery systems. Novalis TX has a Varian Trilogy

Lung

Lung SBRT is additionally challenging because of the problems of accounting for intrafraction target movement with breathing. Most of the published data come from centres using gantry-based linacs with vacuum and/or frame body immobilisation, and diaphragmatic pressure to reduce breathing movement.

Four-dimensional computed tomography planning allows the construction of a volume that takes into account the tumour position at all phases of the respiratory cycle. It has been shown to increase

Primary Non-small Cell Lung Cancer

Surgery remains the standard of care for early stage NSCLC. A 5-year survival rate of 65% has been reported for pathological stage I patients [17], and a recent analysis of 975 patients (85% stage I) revealed a 5-year local control of 78% [18].

However, the preferred procedure (lobectomy) results in a significant loss of functional pulmonary reserve and is associated with operative morbidity and mortality. Also, a large number of surgically resectable patients are medically inoperable (mainly

Lung Metastases

The term ‘oligometastases’ refers to a finite small number of metastases confined to a single or limited number of organs [32]. Long-term follow-up of patients after surgical resection of lung and liver metastases has shown that some of these patients are effectively cured after surgery [33], [34]. For example, in an analysis of over 5000 patients with lung metastases, survival after complete surgical resection was 36% at 5 years and 22% at 15 years [33]. Thus, in some cancers there seems to be

Liver Metastases

As with lung metastases, surgical series of metastectomy for liver metastases have shown a proportion of long-term survivors. In a series of 1000 patients from Memorial Sloan-Kettering Cancer Center with resectable liver-only metastases from colorectal cancer, survival was 37% at 5 years and 22% at 10 years [34]. Surgery remains the gold standard for resectable disease, but many patients are unresectable, either due to the extent of metastatic disease, insufficient functional liver reserve or

Primary Liver Tumours

Wherever possible, surgery is the treatment of choice for primary hepatocellular carcinoma (HCC), but a significant number of patients are not suitable for either resection or liver transplantation [52]. Studies have shown radiofrequency ablation and transarterial chemoembolisation to be effective treatments, but again not all patients are suitable. In primary liver disease, SBRT has been used predominantly in patients in whom other local treatments are not suitable, or who have recurred after

Pancreas

Surgery is the standard of care for pancreatic cancer, but unfortunately only 20% of patients are diagnosed with resectable disease [57]. Patients with metastatic disease at diagnosis proceed directly to systemic therapy. For locally advanced non-metastatic (or medically inoperable) patients, the optimum treatment is less clear. Trials have shown chemoradiotherapy to improve survival compared with radiotherapy alone [58], [59], but there is conflicting evidence as to whether chemoradiotherapy

Kidney

Renal cell carcinoma (RCC) has traditionally been viewed as a radioresistant tumour, as the results of CFR on primary [67] and metastatic [68] lesions have been disappointing. However, published series of radiosurgery for metastatic RCC in the brain have shown that the tumour is sensitive to extreme hypofractionated treatment [69], [70]. This has led to interest in the use of SBRT for primary RCC, and for extracranial oligometastatic RCC.

Beitler et al. [71] were the first to report an exclusive

Prostate

There is randomised evidence showing that dose escalation in CFR for localised prostate cancer results in improved biochemical progression-free survival, at the expense of an increased risk of late rectal toxicity [76], [77]. There is also increasing evidence to suggest that the α/β of prostate cancer is considerably lower than many other cancers, and indeed lower than that of the surrounding organs at risk [78]. The precise value is still uncertain, although it has been estimated to be as low

Spine Metastases

Conventional radiotherapy is widely used in the management of spine metastases, for local control, palliation of pain and treatment of spinal cord compression [87], [88], [89]. However, the prescribed dose is limited by spinal cord and cauda equina radiation tolerance [87], [90], [91]. The steep dose falloff seen with SBRT allows the delivery of a higher dose to the tumour, while staying within cord tolerance. This will increase the probability of long-term tumour control and effective

Primary Spine Tumours

Microsurgical resection is a safe and effective treatment for benign spinal tumours [106]. However, surgery may not always be possible, for example with post-surgical recurrence or medical co-morbidity. SBRT is a useful treatment in these situations.

Several series of CyberKnife SBRT for benign intradural tumours have been published [107], [108], [109], [110]. From Stanford University, Dodd et al. [107] treated 55 tumours in 51 patients in whom surgery was contraindicated. Doses ranged from 16

Conclusion

Advances in image guidance and radiotherapy planning software, together with improved accuracy of treatment delivery, have led to the successful use of stereotactic radiotherapy for extracranial targets. Careful patient selection is especially important. As the volume of normal tissue within the target periphery is related to the cube of the target's radius, smaller lesions are preferable. The steep dose falloff outside the target volume means that lesions with unclear, infiltrative margins

Conflict of Interest

A. Martin is currently employed as a research fellow at the CyberKnife Centre, The Harley Street Clinic, London, UK. There is no association with Accuray Inc.

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OverviewStereotactic Body Radiotherapy: A Review

Abstract

Section snippets

Statement of Search Strategies Used and Sources of Information

History

Fractionation and Radiobiology

Overview of Stereotactic Body Radiotherapy Systems

Lung

Primary Non-small Cell Lung Cancer

Lung Metastases

Liver Metastases

Primary Liver Tumours

Pancreas

Kidney

Prostate

Spine Metastases

Primary Spine Tumours

Conclusion

Conflict of Interest

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Ann Thorac Surg

Lung Cancer

J Thorac Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Thorac Oncol

Clin Lung Cancer

Int J Radiat Oncol Biol Phys

J Thorac Cardiovasc Surg

Radiother Oncol

Lung Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lancet

Am J Surg

Lancet

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Lancet Oncol

Int J Radiat Oncol Biol Phys

Clin Oncol

Int J Radiat Oncol Biol Phys

Clin Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Urol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clin Neurol Neurosurg

The structure and functions of the cerebellum examined by a new method

Brain

Stereotactic apparatus for operations on the human brain

Science

The stereotactic method and radiosurgery of the brain

Acta Chir Scand

Accuracy and stability of positioning in radiosurgery: long-term results of the Gamma Knife system

Med Phys

Preliminary clinical experience with linear accelerator-based spinal stereotactic radiosurgery

Neurosurgery

Stereotactic radiotherapy of malignancies in the abdomen: methodological aspects

Acta Oncol

Radical cyberknife radiosurgery with tumor tracking: an effective treatment for inoperable small peripheral stage I non-small cell lung cancer

J Hematol Oncol

Overview
Stereotactic Body Radiotherapy: A Review