AANS Neurosurgeon : Features
Volume 20, Number 3, 2011
Point-Counterpoint: The Role of Stereotactic Radiosurgery Versus Whole Brain Radiotherapy in the Treatment of Central Nervous System Metastatic Disease
Timothy Ryken, MD, MS, FAANS, FACS
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Editor’s Note: For this issue focusing on stereotactic radiosurgery, Timothy Ryken, MD, MS, FAANS, FACS, presents several cases highlighting central nervous system metastatic disease. John Buatti, MD, then offers the “point” that stereotactic radiosurgery (SRS) is the treatment of choice, while Casandra Foens, MD, offers the “counterpoint” that whole brain radiotherapy (WBRT) is the treatment of choice. Readers also are encouraged to take a brief survey at the end of the feature regarding the cases presented below.
Background
Central nervous system metastatic disease remains a significant cause of morbidity (and less often mortality) despite advances in many forms of systemic therapy. The blood-brain barrier hinders the ability of many of the more active and specific agents to target malignant cells that have passed into the central nervous system. The management of these patients has generally involved a discussion of radiation with or without surgical resection. Over the last decade, there has been increasing debate over the role of stereotactic radiosurgery (SRS) and its impact on the more traditional treatment options. The American Association of Neurological Surgeons and Congress of Neurosurgeons have endorsed and published Guidelines for the Management of Central Nervous System Metastatic Disease. These guidelines address the role of SRS and whole brain radiotherapy (WBRT) in the management of central nervous system metastases using evidence-based technique, and represent the benchmark of current recommendations. However, the lack of definitive high-quality studies leaves the question of optimal management open to debate in many cases (Gaspar et al 2009, Linskey et al 2009). In the absence of high-level recommendations, we may resort to opinion to generate treatment options. Consider the following three cases:
In Case 1, a solitary lesion in a surgically accessible site, assuming stable systematic disease, is likely a candidate for surgical resection. In Case 3, widespread central nervous system disease, even assuming stable systemic disease, is not a suitable candidate for surgery. Case 2, with two surgically accessible lesions, is representative of one of the more controversial situations. There are a variety of treatment choices for the patient with one to four intracranial lesions. Some centers have even advocated for surgical resection followed by WBRT in this situation. Other options would include WBRT alone; WBRT followed by SRS; or SRS alone. The most controversial topic for the more common scenarios regarding the role of SRS is: Can SRS replace WBRT in the treatment of one to four metastatic lesions either post-operatively or as a stand-alone treatment? For the purposes of our debate we will consider Case 2 and assume that the patient is not a candidate for craniotomy; and that the treatment choices are SRS or WBRT. Based on this outline, we now ask our experts to comment.
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Timothy Ryken, MD, MS, FAANS, FACS, is a neurosurgeon and chair of the Iowa Spine and Brain Institute in Waterloo, Iowa. He holds a master’s degree in clinical epidemiology, and is chair-elect of the American Association of Neurological Surgeons and Congress of Neurological Surgery Joint Guidelines Committee. Dr. Ryken maintains an active clinical and translational research program, and lectures extensively on central nervous system tumor management. He reported no conflicts for disclosure.
Point:
Stereotactic Radiosurgery Is the Treatment of Choice
John Buatti, MD
In the setting of one to four lesions, we have more recently favored an approach using upfront SRS and withholding WBRT until widespread dissemination occurs. This is done in an attempt to limit the cognitive decline associated with WBRT treatments. Admittedly the role of SRS in metastatic disease remains under study, with the combination of WBRT followed by a stereotactic radiosurgical boost becoming a popular option. In a large, randomized study, the combination of WBRT and SRS did appear to benefit patients with solitary lesions and patients with a better performance status at presentation (RPA Class I and under 50 years of age).
Although a mainstay of treatment, the outcomes following WBRT remain suboptimal, with up to 50 percent of patients experiencing neurological decline and death secondary to central nervous system progression despite WBRT. These rather dismal results have driven efforts toward alternative modalities in an attempt to improve quality of life through better local control, as well as overall survival.
SRS has a number of advantages. Unlike craniotomy, which is really best focused on single lesions, SRS can treat multiple lesions in each session. And with the use of modern imaging, the majority of metastatic lesions detected are relatively small — greatly increasing the likelihood they will be well-controlled by radiosurgery. Obviously, SRS also has the ability to treat lesions that may not be safely resectable. There is lower-level data that suggests single lesions, treated with either surgery or radiosurgery, have essentially equivalent outcomes in terms of local control and overall survival without the additional risk of a general anesthesia. In addition, the higher intensity dose of radiation delivered with SRS may result in superior local control rates for radioresistant lesions, such as renal cell carcinoma or melanoma, allowing WBRT to be deferred as a subsequent treatment without adverse sequelae.
Although much work needs to be done, it is clear the future lies with more targeted delivery. WBRT exposes a large volume of well-functioning brain tissue to potential injury — in essence putting many “innocent bystanders” at possible risk while SRS is a targeted, tumor-specific approach that spares most normal tissue.
John Buatti, MD, is professor and chair of the Department of Radiation Oncology and Deputy Director for Clinical Care in the Holden Comprehensive Cancer Center at the University of Iowa in Iowa City, Iowa. He is co-director of the Tumor Imaging Program at the NCI-funded Comprehensive Cancer Center. Dr. Buatti maintains an active research program evaluating quantitative imaging for response assessment in cancer clinical trials and is vice chair of University of Iowa Physicians. He reported no conflicts for disclosure.
Counterpoint:
Whole Brain Radiotherapy Is the Treatment of Choice
Casandra Foens, MD
Despite growing enthusiasm for limited therapy and increasingly targeted treatments, the fact is that metastatic cancer is a disseminating process. How does it make any sense to pursue increasingly targeted therapies in the setting of widespread dissemination? The metastatic CNS lesion did not start in the CNS, so it only stands to reason that microscopic disease throughout the CNS remains a significant concern once one or more lesions are detected. At present there is minimal evidence that the targeted therapy and careful surveillance strategy adds anything to either the quality of life or survival in patients with metastatic brain tumors. In fact, by not treating the whole brain in order to try to prevent a cognitive decline that may or may not occur, or even become noticeable in the remaining life span in these patients, do we not subject the patient to an even greater risk? The AANS/CNS guideline on central nervous system metastatic disease management has at least three top-level (Level 1) recommendations supporting WBRT in various situations and basically none that involve SRS. That is the current state of affairs and must be taken into account when recommending treatment options.
WBRT has been the mainstay in the treatment of metastatic disease to the brain for many years. In the United States, the usual dose regimen is 30-35 Gy given in 10-14 fractions, and may be the only choice in patients with widely metastatic disease. Historically, overall response rates vary from 40 percent to 60 percent, depending on the tumor type, and generally are associated with median survivals ranging from three to six months. Randomized data supports the use of WBRT, although most of these trials are not recent due to the expansion of SRS in the management of brain metastases. In a randomized trial of 95 patients undergoing surgical resection either with or without WBRT, there was a reduction of local recurrence with the addition of radiation with 18 percent of irradiated patients versus 70 percent of those having surgery alone sustaining local tumor recurrence. However, there was no impact on median survival, with 12 months for patients having surgery alone compared to 10.7 months to those having surgery plus radiation.
Limited information directly comparing WBRT to SRS exists. This is likely due to the fact that patients with three or fewer brain metastases are routinely receiving surgery and/or SRS and only patients with widespread brain metastases are receiving WBRT alone — therefore the groups are not comparable for outcomes. A few recent studies do show a superiority of WBRT plus SRS boost as compared to WBRT alone, but again, these are trials limited to patients with good performance status and limited amount of metastatic disease, and so it is not surprising that more radiation (WBRT+SRS) results in more favorable outcomes. However, WBRT will remain the mainstay of treatment for many patients with brain metastases as they will not meet criteria for either surgery and/or SRS because they have multiple brain metastases; multiple other sites of uncontrolled metastatic disease; or poor performance status.
Casandra Foens, MD, is medical director of radiation oncology at Covenant Cancer Treatment Center in Waterloo, Iowa. She currently serves on the American College of Radiology Board of Chancellors, and has participated in the development of many of the ACR Practice Guidelines and Technical Standards for Radiation Oncology. She reported no conflicts for disclosure.
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