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Where are the at-risk cervical nodes?
Int. J. Radiation Oncology Biol. Phys., Vol. 58, No. 1, pp. 1–2, 2004 Copyright © 2004 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/04/$–see front matter
doi:10.1016/S0360-3016(03)01451-2
EDITORIAL
WHERE ARE THE AT-RISK CERVICAL NODES? ADAM S. GARDEN, M.D. Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
The advent of conformal therapy, and particularly intensitymodulated radiation therapy (IMRT), for the treatment of head-and-neck cancers has led to a re-exploration of defining the subclinical lymph nodes at risk. At first glance, this seems simple. Certainly the nodes at risk haven’t moved. Sixty-five years ago, the famed anatomist Henri Rouvie`re published The Anatomy of the Human Lymphatic System (1), in which he defined the nodal drainage of the skin and mucosal sites of the head and neck. He not only described the finer lymphatic channels, but the nodal basins that drained these lymphatic capillaries. The retropharyngeal nodes were divided into medial and lateral chains. The lateral nodes, sometimes referred to as the nodes of Rouvie`re, lie lateral to the pharyngeal constrictors and medial to the internal carotid artery and superior cervical ganglion. The deep jugular nodes were described as two separate groups, the lateral and anterior groups, defined by their relation to the internal jugular vein. The superior border was described as the posterior belly of the digastric. As a footnote, Rouvie`re described the retrostyloid or subparotid nodes, an inconsistent continuation of the jugular chain extending superiorly behind the digastric muscle. These nodes lie in the area referred to as the carotid space, in front of the internal carotid artery and internal jugular vein just distal from where the latter exits the jugular fossa. The spinal accessory nodes follow the nerve of the same name, and with the transverse cervical nodes, the three chains form a triangle. Nodes at the point of intersection of the deep jugular nodes and the spinal accessory nodes have been called the junctional nodes, though many names have been given to the nodes in this location. The importance of these nodes is their proximity to the parotid gland and the question of whether in differing circumstances they are at risk of harboring subclinical metastases. The confusion of identifying the nodes at risk perhaps is due to the use of numerous synonyms with similar, but not identical, definitions that creates subtle differences in interpretation of where potential nodes at risk may lie. There has been a shift from using the classical terms, including jugular nodes and spinal accessory nodes, to defining the nodes by
specific levels (Levels I–VI). This movement began with otolaryngologists and head-and-neck surgeons, and in a seminal work, Som et al. translated the location of cervical nodes based on surgeons’ descriptions of the anatomic borders to computerized tomographic images (2). The importance of this work for radiation oncologists is that we rely on computerized tomography for our definition of target volumes. Unfortunately, this shift of terminology does not seem to be as simple as the change from the rad to the Gray, because there remain inconsistencies with the use of these levels, particularly Level 2, as well as the difficulty of eliminating the old nomenclature from our vocabulary. Radiation oncologists often make a decision to treat the neck based on a somewhat arbitrary perception of risk of the cervical nodes harboring metastases. This threshold varies, but usually lies between 15% and 25%. Even more complex are the implications, once a commitment is made to treat the neck, of treating only the highest-risk nodes. A survey of radiation textbooks over the years is likely to demonstrate subtle increases in field design. Fletcher (3) felt that coverage of only the subdigastric nodes was adequate for T2N0 tonsil cancer. Over the years, these fields have expanded. Portals extend to the clavicles inferiorly and often with generous coverage of the retropharyngeal and junctional nodes to the base of skull. Thus, even with conventional field arrangements, these differences can have significant implications on the degree of xerostomia a patient will experience. Now, conformal therapy has led to a reexamination of these field designs. One conformal approach is to still treat all these nodes as we have in the past with a conventional approach, and rely on the technology to spare the salivary glands. As a minimum, with this approach we can occasionally give differential consideration to the ipsilateral and contralateral sides of the neck for lateralized disease. For example, in a patient with T2N2b carcinoma of the right tonsil, are the left junctional nodes at risk? With a conventional parallel approach, if the right side is treated, so is the left side, and we would not have to consider this question. Conformal therapy creates an opportunity to allow differential sparing of the glands when one side
Reprint requests to: Adam S. Garden, Professor, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard–Unit 97, Houston, TX 77030. Tel: (713) 563-2321; Fax:
(713) 563-2331; E-mail: [email protected] Received Jun 23, 2003. Accepted for publication Jul 1, 2003. 1
2
I. J. Radiation Oncology
● Biology ● Physics
of the neck may have greater risk for harboring subclinical metastases than the other side. The second approach, which is being led by the groups from Rotterdam and Brussels, is to reevaluate the dogma that has been passed down over the decades. This process has involved literature review, analysis of surgical dissection techniques, and cadaveric evaluation of lymph node location. The current article by Levendag et al. (4) is the latest in a series of works aimed at assisting radiation oncologists in identifying the cervical nodes at risk for harboring microscopic disease. Regarding a review of the literature, the authors make an interesting observation that our understanding of these atrisk nodes is at best based on Class 3 evidence. Much of these data are from surgical series that pathologically have identified these nodes and the levels that harbor malignancy. However, a review of these publications reveals that although the overall number of necks dissected is large, when broken down by head-and-neck mucosal subsites, the numbers diminish remarkably and are fewest for the sites that are more commonly treated with radiation. There is also a relatively sparse body of literature addressing modern radiologic correlates with nodal pathology. The current trial seems to have been successful. Sixty-one patients were irradiated with volumes contoured by specified guidelines. The dosimetry of the contoured volumes was acceptable, and there were only four regional failures, and none outside the contoured volumes. Yet with approximately 30 node-negative patients and 30 node-positive patients, what would have made the trial a failure? Would even one marginal failure have made us skeptical of the process of nodal contouring and volume definitions? How many patients are required to validate the process of adequate contouring of the at-risk nodes? Levendag et al. ask us to follow the surgeons’ lead in defining the nodes at risk. They also allude to following the surgeons who have practiced their own form of conformal therapy. Historically, it was argued that to perform less than a radical neck dissection was inadequate management of the neck. Primarily during the 1970s, surgeons at The University of Texas M. D. Anderson Cancer Center refined and perfected the modified radical neck dissection and described the indications for this procedure. In particular, it was argued that a radical neck dissection was not necessary as elective treatment for any patient clinically staged N0, because the modified procedure provided equivalent cancer control and better functional results. Eventually, the concept of selective or functional
Volume 58, Number 1, 2004
neck dissections arose. These dissections not only aimed at achieving an improved functional outcome, but also proposed dissection of only the nodal beds at risk for harboring micrometastases, rather than dissection of all nodal levels. Ferlito et al. provide a concise review of the evolution of the neck dissection and current considerations (5). One fascinating aspect of this review is the parallel thought processes that surgeons and radiation oncologists are undertaking in their management of the neck with respect to “targets” and function and the fine balance between disease control and morbidity. Whereas radiation oncologists have investigated radiation protectors of normal tissues as well as technology to avoid normal tissue, there has been less of an effort to question how much of the neck requires radiation. O’Sullivan et al. (6), who investigated the common practice in the United States of irradiating the contralateral neck in tonsillar carcinoma, performed one such study. They demonstrated that the risk of contralateral disease recurrence in well-lateralized tonsil cancers arising in patients who were node negative was extremely small. Thus ipsilateral treatment could be performed in this setting, providing contralateral salivary sparing with simple techniques. When patients have disease recur in field, radiation oncologists will often attribute these events to factors beyond their control at the present time, such as intrinsic radiation resistance or adverse features of the tumor environment. Yet disease recurrence at the edge of the field or in untreated nodal beds is within the control of radiation oncologists, and even if a rare event, these failures are often compensated for by an increase in field size for future patients. The radiation oncology community has been cautioned that the use of IMRT may result in geographic tumor misses. However, for head-and-neck cancer, and in particular nasopharyngeal cancer, IMRT potentially provides both improved tumor coverage and more normaltissue sparing. Sophisticated decision analysis may be needed to help us (both physicians and patients) with these issues. The severity of xerostomia as a sequela and its incidence need to be weighed against the potential, albeit small, incidence of nodal recurrence in a location close to a protected salivary gland. Will we increase target definition when we see a carotid space recurrence, or decrease target definition when we cure a patient, but the effects of xerostomia seem devastating? Levendag et al. (4) are starting the process of accumulating more data to answer these questions that should ideally be approached scientifically rather than emotionally.
REFERENCES 1. Rouvie`re H. Anatomy of the human lymphatic system. Ann Arbor, MI: Edward Brothers Inc.; 1938. 2. Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125:388–396. 3. Fletcher GH. Textbook of radiotherapy. 3rd ed. Philadelphia, PA: Lea & Febiger; 1980. 4. Levendag P, Broksmol M, Coche E, et al. Rotterdam and Brussels CT-based neck nodal delineation compared with the
surgical levels as defined by the American Academy of Otolaryngology–Head and Neck Surgery, Int J Radiat Oncol Biol Phys 2004;58:113–123. 5. Ferlito A, Robbins KT, Shaha AR, et al. Current considerations in neck dissection. Acta Otolaryngol 2002;122:323– 329. 6. O’Sullivan B, Warde P, Grice B, et al. The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 2001;51: 332–343.
doi:10.1016/S0360-3016(03)01451-2
EDITORIAL
WHERE ARE THE AT-RISK CERVICAL NODES? ADAM S. GARDEN, M.D. Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
The advent of conformal therapy, and particularly intensitymodulated radiation therapy (IMRT), for the treatment of head-and-neck cancers has led to a re-exploration of defining the subclinical lymph nodes at risk. At first glance, this seems simple. Certainly the nodes at risk haven’t moved. Sixty-five years ago, the famed anatomist Henri Rouvie`re published The Anatomy of the Human Lymphatic System (1), in which he defined the nodal drainage of the skin and mucosal sites of the head and neck. He not only described the finer lymphatic channels, but the nodal basins that drained these lymphatic capillaries. The retropharyngeal nodes were divided into medial and lateral chains. The lateral nodes, sometimes referred to as the nodes of Rouvie`re, lie lateral to the pharyngeal constrictors and medial to the internal carotid artery and superior cervical ganglion. The deep jugular nodes were described as two separate groups, the lateral and anterior groups, defined by their relation to the internal jugular vein. The superior border was described as the posterior belly of the digastric. As a footnote, Rouvie`re described the retrostyloid or subparotid nodes, an inconsistent continuation of the jugular chain extending superiorly behind the digastric muscle. These nodes lie in the area referred to as the carotid space, in front of the internal carotid artery and internal jugular vein just distal from where the latter exits the jugular fossa. The spinal accessory nodes follow the nerve of the same name, and with the transverse cervical nodes, the three chains form a triangle. Nodes at the point of intersection of the deep jugular nodes and the spinal accessory nodes have been called the junctional nodes, though many names have been given to the nodes in this location. The importance of these nodes is their proximity to the parotid gland and the question of whether in differing circumstances they are at risk of harboring subclinical metastases. The confusion of identifying the nodes at risk perhaps is due to the use of numerous synonyms with similar, but not identical, definitions that creates subtle differences in interpretation of where potential nodes at risk may lie. There has been a shift from using the classical terms, including jugular nodes and spinal accessory nodes, to defining the nodes by
specific levels (Levels I–VI). This movement began with otolaryngologists and head-and-neck surgeons, and in a seminal work, Som et al. translated the location of cervical nodes based on surgeons’ descriptions of the anatomic borders to computerized tomographic images (2). The importance of this work for radiation oncologists is that we rely on computerized tomography for our definition of target volumes. Unfortunately, this shift of terminology does not seem to be as simple as the change from the rad to the Gray, because there remain inconsistencies with the use of these levels, particularly Level 2, as well as the difficulty of eliminating the old nomenclature from our vocabulary. Radiation oncologists often make a decision to treat the neck based on a somewhat arbitrary perception of risk of the cervical nodes harboring metastases. This threshold varies, but usually lies between 15% and 25%. Even more complex are the implications, once a commitment is made to treat the neck, of treating only the highest-risk nodes. A survey of radiation textbooks over the years is likely to demonstrate subtle increases in field design. Fletcher (3) felt that coverage of only the subdigastric nodes was adequate for T2N0 tonsil cancer. Over the years, these fields have expanded. Portals extend to the clavicles inferiorly and often with generous coverage of the retropharyngeal and junctional nodes to the base of skull. Thus, even with conventional field arrangements, these differences can have significant implications on the degree of xerostomia a patient will experience. Now, conformal therapy has led to a reexamination of these field designs. One conformal approach is to still treat all these nodes as we have in the past with a conventional approach, and rely on the technology to spare the salivary glands. As a minimum, with this approach we can occasionally give differential consideration to the ipsilateral and contralateral sides of the neck for lateralized disease. For example, in a patient with T2N2b carcinoma of the right tonsil, are the left junctional nodes at risk? With a conventional parallel approach, if the right side is treated, so is the left side, and we would not have to consider this question. Conformal therapy creates an opportunity to allow differential sparing of the glands when one side
Reprint requests to: Adam S. Garden, Professor, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard–Unit 97, Houston, TX 77030. Tel: (713) 563-2321; Fax:
(713) 563-2331; E-mail: [email protected] Received Jun 23, 2003. Accepted for publication Jul 1, 2003. 1
2
I. J. Radiation Oncology
● Biology ● Physics
of the neck may have greater risk for harboring subclinical metastases than the other side. The second approach, which is being led by the groups from Rotterdam and Brussels, is to reevaluate the dogma that has been passed down over the decades. This process has involved literature review, analysis of surgical dissection techniques, and cadaveric evaluation of lymph node location. The current article by Levendag et al. (4) is the latest in a series of works aimed at assisting radiation oncologists in identifying the cervical nodes at risk for harboring microscopic disease. Regarding a review of the literature, the authors make an interesting observation that our understanding of these atrisk nodes is at best based on Class 3 evidence. Much of these data are from surgical series that pathologically have identified these nodes and the levels that harbor malignancy. However, a review of these publications reveals that although the overall number of necks dissected is large, when broken down by head-and-neck mucosal subsites, the numbers diminish remarkably and are fewest for the sites that are more commonly treated with radiation. There is also a relatively sparse body of literature addressing modern radiologic correlates with nodal pathology. The current trial seems to have been successful. Sixty-one patients were irradiated with volumes contoured by specified guidelines. The dosimetry of the contoured volumes was acceptable, and there were only four regional failures, and none outside the contoured volumes. Yet with approximately 30 node-negative patients and 30 node-positive patients, what would have made the trial a failure? Would even one marginal failure have made us skeptical of the process of nodal contouring and volume definitions? How many patients are required to validate the process of adequate contouring of the at-risk nodes? Levendag et al. ask us to follow the surgeons’ lead in defining the nodes at risk. They also allude to following the surgeons who have practiced their own form of conformal therapy. Historically, it was argued that to perform less than a radical neck dissection was inadequate management of the neck. Primarily during the 1970s, surgeons at The University of Texas M. D. Anderson Cancer Center refined and perfected the modified radical neck dissection and described the indications for this procedure. In particular, it was argued that a radical neck dissection was not necessary as elective treatment for any patient clinically staged N0, because the modified procedure provided equivalent cancer control and better functional results. Eventually, the concept of selective or functional
Volume 58, Number 1, 2004
neck dissections arose. These dissections not only aimed at achieving an improved functional outcome, but also proposed dissection of only the nodal beds at risk for harboring micrometastases, rather than dissection of all nodal levels. Ferlito et al. provide a concise review of the evolution of the neck dissection and current considerations (5). One fascinating aspect of this review is the parallel thought processes that surgeons and radiation oncologists are undertaking in their management of the neck with respect to “targets” and function and the fine balance between disease control and morbidity. Whereas radiation oncologists have investigated radiation protectors of normal tissues as well as technology to avoid normal tissue, there has been less of an effort to question how much of the neck requires radiation. O’Sullivan et al. (6), who investigated the common practice in the United States of irradiating the contralateral neck in tonsillar carcinoma, performed one such study. They demonstrated that the risk of contralateral disease recurrence in well-lateralized tonsil cancers arising in patients who were node negative was extremely small. Thus ipsilateral treatment could be performed in this setting, providing contralateral salivary sparing with simple techniques. When patients have disease recur in field, radiation oncologists will often attribute these events to factors beyond their control at the present time, such as intrinsic radiation resistance or adverse features of the tumor environment. Yet disease recurrence at the edge of the field or in untreated nodal beds is within the control of radiation oncologists, and even if a rare event, these failures are often compensated for by an increase in field size for future patients. The radiation oncology community has been cautioned that the use of IMRT may result in geographic tumor misses. However, for head-and-neck cancer, and in particular nasopharyngeal cancer, IMRT potentially provides both improved tumor coverage and more normaltissue sparing. Sophisticated decision analysis may be needed to help us (both physicians and patients) with these issues. The severity of xerostomia as a sequela and its incidence need to be weighed against the potential, albeit small, incidence of nodal recurrence in a location close to a protected salivary gland. Will we increase target definition when we see a carotid space recurrence, or decrease target definition when we cure a patient, but the effects of xerostomia seem devastating? Levendag et al. (4) are starting the process of accumulating more data to answer these questions that should ideally be approached scientifically rather than emotionally.
REFERENCES 1. Rouvie`re H. Anatomy of the human lymphatic system. Ann Arbor, MI: Edward Brothers Inc.; 1938. 2. Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125:388–396. 3. Fletcher GH. Textbook of radiotherapy. 3rd ed. Philadelphia, PA: Lea & Febiger; 1980. 4. Levendag P, Broksmol M, Coche E, et al. Rotterdam and Brussels CT-based neck nodal delineation compared with the
surgical levels as defined by the American Academy of Otolaryngology–Head and Neck Surgery, Int J Radiat Oncol Biol Phys 2004;58:113–123. 5. Ferlito A, Robbins KT, Shaha AR, et al. Current considerations in neck dissection. Acta Otolaryngol 2002;122:323– 329. 6. O’Sullivan B, Warde P, Grice B, et al. The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 2001;51: 332–343.