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The Oncologist, Vol. 9, No. 4, 442–450, July 2004
© 2004 AlphaMed Press

Conformal Radiation Therapy for Childhood CNS Tumors

David G. Kirsch, Nancy J. Tarbell

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Nancy J. Tarbell, M.D., Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 360, Boston, Massachusetts 02114, USA. Telephone: 617-724-1836; Fax: 617-724-4808; e-mail: ntarbell{at}partners.org


   LEARNING OBJECTIVES
Top
 Learning Objectives
Abstract
 Introduction
 Late Effects of Radiation...
 Conformal Radiation Therapy
 Conclusions
 References
 
After completing this course, the reader will be able to:

  1. Describe the difference between conventional and conformal radiation therapy.
  2. Explain why conformal radiation therapy may decrease the long-term side effects of treatment.
  3. Compare the potential risks for a radiation-induced malignancy from proton radiation therapy and intensity-modulated radiation therapy with photons (x-rays).

Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com


   ABSTRACT
Top
 Learning Objectives
 Abstract
Introduction
 Late Effects of Radiation...
 Conformal Radiation Therapy
 Conclusions
 References
 
Radiation therapy plays a central role in the management of many childhood brain tumors. By combining advances in brain tumor imaging with technology to plan and deliver radiation therapy, pediatric brain tumors can be treated with conformal radiation therapy. Through conformal radiation therapy, the radiation dose is targeted to the tumor, which can minimize the dose to normal brain structures. Therefore, by limiting the radiation dose to normal brain tissues, conformal radiation therapy offers the possibility of limiting the long-term side effects of brain irradiation.

In this review, we describe different approaches to conformal radiation therapy for pediatric central nervous system tumors including: A) three-dimensional conformal radiation therapy; B) stereotactic radiation therapy with arc photons; C) intensity-modulated radiation therapy; and D) proton beam radiation therapy. We discuss the merits and limitations of these techniques and describe clinical scenarios in which conformal radiation therapy offers advantages over conventional radiation therapy for treating pediatric brain tumors.

Key Words. Pediatrics • Radiation therapy • Central nervous system neoplasms • Protons • IMRT • Side effects


   INTRODUCTION
Top
 Learning Objectives
 Abstract
 Introduction
Late Effects of Radiation...
 Conformal Radiation Therapy
 Conclusions
 References
 
In comparison to adult cancers, pediatric malignancies are relatively rare, with an incidence of approximately 8,000 cases in the U.S. each year [1]. Nearly one in five pediatric cancers is located in the central nervous system (CNS) (Table 1Go) [1]. Although many childhood malignancies are cured, the acute toxicity of therapy and significant late treatment effects [2] make these cancers a substantial burden for patients, their families, and society. Therefore, a major goal of pediatric cancer therapy is to maintain or improve cancer cure rates, while decreasing treatment sequelae.


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  		Table 1. Distribution of childhood cancers
 
For many childhood CNS tumors, radiation therapy plays an essential role in cancer management. Frequently, these tumors cannot be entirely removed with surgery due to location or because of microscopic tumor spread. Moreover, for most childhood brain tumors, chemotherapy cannot eliminate all cancer cells. Therefore, radiation therapy is frequently employed alone or as part of a multimodality treatment approach in combination with surgery and/or chemotherapy [1]. Since the long-term side effects of conventional radiation therapy for pediatric brain tumors may be limited by conformal radiation therapy [3], this review focuses on different approaches to delivering conformal radiation therapy, with an emphasis on how these techniques may limit the late effects of therapy.


   LATE EFFECTS OF RADIATION THERAPY
Top
 Learning Objectives
 Abstract
 Introduction
 Late Effects of Radiation...
Conformal Radiation Therapy
 Conclusions
 References
 
Some of the long-term side effects of conventional radiation therapy to the brain were reviewed previously in The Oncologist [2]. Cranial irradiation can cause hearing loss, interfere with intellectual development, and affect the hypothalamic-pituitary axis. For example, for some cancer survivors, physical growth is limited by growth hormone deficiency [4]. In addition, radiation therapy to the brain can cause a second malignancy years after treatment, which can be fatal [5].

Interestingly, effects of cranial irradiation can also be documented by magnetic resonance imaging (MRI) of the brain. Three months after receiving a radiation dose of 20 Gy (1 Gy or Gray = 100 rad or cGy), previously normal white matter shows changes on T1-weighted MRI scans [6]. Furthermore, radiation therapy can have profound effects on tumor imaging as well. Nine to 12 months after radiation therapy for low-grade astrocytomas, MRI scans frequently reveal tumors that have increased in size, often with large cystic areas that demonstrate increased enhancement [7]. Most patients will have no clinical deterioration despite these MRI changes that may be mistaken for tumor progression. Since these MRI abnormalities usually resolve without intervention within 6–12 months [7], radiation therapy-related MRI changes in low-grade astrocytomas, which arise in the absence of clinical deterioration, should not prompt biopsy or unnecessary salvage therapy.

The late effects of cranial irradiation are affected by a number of critical factors, including total radiation dose to each normal structure, radiation dose for each daily radiation treatment (daily fraction), the combination of radiation therapy with other treatment modalities (chemotherapy and surgery), and patient age during brain irradiation [1].

Younger patients typically have more pronounced developmental effects from radiation therapy to the brain. The long-term effects of cranial irradiation in young children (median age 4.5 years), who were cured of acute lymphoblastic lymphoma, were recently reported [8]. For children that received 18–24 Gy of whole-brain irradiation, the risk for unemployment as an adult was three to seven times the national average and, for girls, the relative risk of never marrying was one-third higher. Importantly, the actuarial risk of a second malignancy 30 years after cranial or craniospinal irradiation was 20%. However, most of these second malignancies were benign or of low malignant potential and included basal cell skin cancers [8].

Children below the age of 36 months can have the most severe cognitive effects from brain irradiation, which is probably in part due to incomplete myelinization of the white matter at the time of radiation therapy [9]. For many of these young patients, postoperative chemotherapy can delay tumor recurrence for 1–2 years [9]. Therefore, for very young patients, chemotherapy should be considered to try to prevent tumor progression and thereby delay radiation therapy until a developmental stage (after 36 months) when the late effects of radiation therapy will not be as severe.

In older children, the late effects of brain irradiation are less severe and usually do not delay the delivery of radiation therapy. For example, a prospective study of 19 children treated with whole-brain irradiation for brain tumors found that IQ did not decline 2 years after irradiation in children who were at least 7 years old at diagnosis, while IQ declined by 27 points for children diagnosed before the age of 7 [10]. Another prospective study in 12 patients (median age 12, range 9–16 years) with CNS germinomas found no significant difference between pre- and postirradiation IQ values after a median 69 months of follow-up [11]. Interestingly, in that study, pretreatment morbidity was substantial, thereby underscoring the importance of prospective studies to measure late effects, so that morbidity is not inappropriately attributed to radiation therapy.

Germinomas typically present in the CNS during the second decade of life and are routinely cured (90%–95% of patients) with radiation therapy alone, with a dose of 45–54 Gy to the primary tumor [11–13]. However, out of concern for the potential late effects of radiation therapy, investigators have attempted to treat germinomas with carboplatin, etoposide, and bleomycin chemotherapy alone [14]. With this chemotherapy-only regimen, 10% of patients died due to toxicities from chemotherapy, and failure-free survival for germinomas was only 43% after a median follow-up of 31 months [14]. Another approach to limit radiation therapy-related toxicity has been to combine etoposide and cisplatin chemotherapy with involved-field radiation therapy [15]. In a phase II trial in which the dose of radiation depended on the response to chemotherapy, the combination of chemotherapy with 30.6–50.4 Gy of radiation to the primary tumor showed similar survival and disease control to those achieved with radiation therapy alone [15]. Long-term follow-up is necessary to measure the late effects of combined chemotherapy and cranial irradiation. However, it is possible that the risk for certain late effects, such as second malignancies, can be increased after the combination of cranial irradiation with certain types of chemotherapy [16]. Therefore, in the absence of a prospective trial comparing combined chemotherapy and reduced-dose radiation therapy with radiation therapy alone for germinomas, we continue to treat our adolescent patients with germinomas using radiation therapy alone. These patients are treated with a radiation field that initially includes the whole brain, or at least the whole ventricular system, and subsequently focuses on the germinoma by conformal radiation therapy techniques.


   CONFORMAL RADIATION THERAPY
Top
 Learning Objectives
 Abstract
 Introduction
 Late Effects of Radiation...
 Conformal Radiation Therapy
Conclusions
 References
 
Conformal radiation therapy describes any technique in which radiation dose conforms to the tumor target, while dose is limited to normal tissues. Since the total radiation dose to normal brain tissue is an important factor that determines the late effects from radiation therapy, conformal radiation therapy techniques, which limit radiation dose to normal tissues, may decrease long-term treatment-related side effects.

Conformal radiation therapy for childhood CNS malignancies requires brain imaging with computed tomography (CT) or MRI so that the tumor target and critical normal structures can be accurately defined. With greater definition of tumor location, radiation therapy field sizes can be limited to the size that adequately covers the target. At the same time, the proposed dose to critical normal brain structures can be analyzed prior to treatment, so that normal tissue tolerances for radiation can be respected.

Conformal radiation therapy for CNS tumors also requires reproducible patient immobilization. Since the target size must be expanded in radiation therapy planning to account for daily patient set-up error, with less variability in patient positioning, smaller radiation fields are required to adequately cover the target. For example, thermoplastic masks, which are individually molded to each patient and then fixed to the couch during treatment, are often used to immobilize the head and provide reproducible patient positioning [17]. Even more precise patient positioning can be obtained with relocatable head frames [18]. These noninvasive frames are maintained in the appropriate anatomic relation to the tumor via a dental appliance or, for young patients who require general anesthesia, attachments are inserted into the ear canals [18]. With these approaches, the patient and tumor target are reliably positioned for each treatment. Therefore, the radiation field size that is required to adequately cover the target and account for day-to-day variations in tumor position is smaller, so less dose reaches nontarget tissues.

After the patient has been appropriately immobilized and the tumor has been accurately defined by CT or MRI, conformal radiation therapy can be delivered by a variety of techniques (Table 2Go) that use high-energy x-rays (photons), such as three-dimensional (3D) conformal radiation therapy with fixed fields, stereotactic radiation therapy (SRT) using arc therapy, and intensity-modulated radiation therapy (IMRT). Brachytherapy, in which a radioactive isotope is implanted into a cystic cavity, has been used in limited situations as well. Finally, another approach to conformal radiation therapy for childhood brain tumors uses proton beams, which have physical advantages over photons that make this an attractive modality for pediatric brain tumors.


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  		Table 2. Types of conformal radiation therapy
 
3D Conformal Radiation Therapy: Fixed Photon Fields
The technique of 3D conformal radiation therapy with several fixed photon radiation fields achieves conformality through the intersection of the fields at the tumor target (Fig. 1Go). High energy x-rays (photons) enter the normal brain and deposit energy according to a parabolic curve (Fig. 2Go). Energy is deposited into the tumor and then the radiation beam exits through the normal brain. By using fields from several directions that overlap at the tumor, the target receives a relatively homogenous and high radiation dose while surrounding normal brain tissue receives a relatively lower dose from a single beam as it enters the brain and exits beyond the target. Since conventional radiation therapy uses identical high-energy photons, the advantage of 3D conformal radiation therapy derives entirely from better radiation treatment planning. Since 3D treatment planning employs more accurate target identification, smaller radiation fields can be selected and, as a result, less normal brain tissue is treated. Also, while conventional planning usually calculates the doses to the tumor and normal structures in a single plane, 3D treatment planning identifies the radiation dose at every axial slice of the CT scan used for radiation treatment planning. Therefore, this approach identifies the radiation dose to each normal structure prior to treatment and allows more selective shielding of normal structures [19].



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  		Figure 1. 3D conformal radiation therapy to treat a brain stem glioma. The tumor (central object outlined in blue) receives a greater dose than the surrounding tissue through the intersection of two lateral fixed photon fields. Radiation dose distribution is displayed on a sagittal CT slice with the dose that surrounds each area indicated by the color in the legend.

 


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  		Figure 2. Comparison of tumor coverage by high-energy photons and protons. The hypothetical tumor is the red rectangle. The relative dose on the y axis is shown for the different depths of penetration into the patient represented on the x axis. For the photon field, a high radiation dose is deposited in front of the tumor target and additional radiation is deposited after the beam passes the target until the beam exits the patient. In contrast, with protons, the beam deposits relatively less radiation dose in front of the target. When the beam arrives at the target, the remaining dose is deposited at the target and no radiation dose exits beyond the target.

 
Conformal radiation therapy with four fixed photon fields was employed to treat 14 children with progressive or inoperable low-grade gliomas to a dose of 50–55 Gy [20]. In this retrospective review, treatment fields encompassed the enhancing tumor plus a 5–10 mm margin [20]. Three-year progression-free (87%) and overall survival (100%) rates were similar to those of historic controls in which larger radiation therapy fields were used [20].

Preliminary results of a phase II trial of conformal radiation therapy for 102 pediatric patients with localized low-grade astrocytomas and ependymomas have been reported from St. Jude Children’s Research Hospital [21]. In that prospective study, the tumor volume plus 1.5 cm was targeted with fixed photon fields to deliver 54–59.4 Gy of radiation. With a median follow-up of 17 months, 10 failures were reported. When the locations of the treatment failures were examined, eight were, at least in part, within the target volume, one was metastatic disease alone, and only one failure was isolated to an area immediately adjacent to the conformal target [21].

In these studies, longer follow-up is needed to assess the late effects of 3D conformal radiation therapy. Since these treatments employed sophisticated target definition and treatment planning, patients received relatively small radiation fields, compared to those used in conventional radiation therapy. Since less normal brain is irradiated, the long-term side effects of 3D conformal radiation therapy may be smaller. Moreover, these studies indicate that, with careful radiation therapy planning and delivery, smaller radiation fields do not compromise tumor control.

In addition to using smaller fields, this approach allows the radiation oncologist to identify critical normal structures, which can then be more easily avoided during radiation treatment planning. For example, for patients with medulloblastoma, who can develop hearing loss from chemotherapy and radiation therapy, 3D conformal radiation therapy can limit the dose of radiation to the cochlea [22]. By identifying the cochlea and posterior fossa with a combination of brain MRI and CT scans, investigators designed a treatment plan to boost the radiation dose to the entire posterior fossa but limit the radiation dose to the cochlea to 65% of that in the conventional plan [22]. Investigators from Memorial Sloan-Kettering Cancer Center reported on a series of 32 patients with medulloblastomas (27 patients with standard risk) [23]. Those patients each received a boost dose to the tumor bed instead of the entire posterior fossa using 3D conformal radiation therapy (20 patients) or IMRT (12 patients) [23]. The 5-year actuarial disease-free survival rate was 84% and the rate of freedom from posterior fossa failure at 10 years was 86% [23]. By limiting the boost target volume to the tumor bed with conformal radiation therapy, the dose to the cochlea was limited, but tumor control within the posterior fossa was similar to that seen in other series in which the entire posterior fossa received boost irradiation. The optimal volume for boost irradiation (tumor bed versus entire posterior fossa) for patients with medulloblastomas is currently the focus of a cooperative group trial.

Stereotactic Radiation Therapy: Arc Photon Fields
Another approach to delivering conformal radiation therapy involves arc therapy with photons [24]. With this technique, the gantry that delivers the photons moves in an arc around the patient, with the tumor at the center of the arc (Fig. 3Go). By using multiple arcs of photons, the high-dose radiation region more closely matches the shape of most tumor targets than when fixed photons fields are used. The same daily radiation dose (fraction size) and total radiation dose are delivered as with conformal radiation therapy using fixed fields. We routinely use SRT with arc fields to deliver a boost radiation dose to the primary tumor in adolescents with intracranial germ cell tumors [12]. Thirteen patients with germinomas were treated with this boost technique to bring the median total radiation dose to 51.2 Gy. After a median follow-up of 40 months, no local or marginal recurrences were seen [12].



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  		Figure 3. Stereotactic radiation therapy with arc photons to treat a craniopharyngioma. Arc photon therapy conforms the high-dose region of the radiation field more closely to the target (shaded in red). Radiation dose distribution is indicated according to the matched color of the circle in the sagittal CT slice.

 
Gamma-Knife and Linear Accelerator-Based Radiosurgery
Radiosurgery is a technique in which a relatively large dose of SRT is delivered in a single treatment to a conformal target. Radiosurgery can be delivered from 201-cobalt sources in a gamma-knife or with arc photon fields from a linear accelerator. The use of gamma-knife radiosurgery was reported in a study of 12 children with tumors in the cerebral or base of skull regions that included pilocytic astrocytomas and craniopharyngiomas [25]. The mean tumor margin dose was 13.8 Gy in a single treatment. Seven of the patients had stable disease after a median follow-up of 78.6 months [25]. Other investigators reported on 12 children with craniopharyngiomas treated with radiosurgery using a gamma-knife [26]. The mean minimum dose at the tumor margin was 14 Gy and only two of the patients required retreatment in order to obtain disease control [26].

A limitation of radiosurgery versus other radiation therapy approaches for childhood CNS tumors (in which the dose is fractionated over many days) is that some late effects from a single large dose of irradiation are more significant than those from even larger total doses that are delivered with small daily doses (2 Gy) over the course of many treatment days. Therefore, we generally reserve radiosurgery for children who require additional therapy after a full course of fractionated radiation therapy [27]. Linear accelerator-based radiosurgery was given to 90 children with recurrent (62 patients) or residual (28 patients) CNS tumors, and the median progression-free survival time for all patients was 13 months [27]. The 3-year actuarial local control rate varied by histology and ranged from 29% for ependymoma to 57% for medulloblastoma [27]. Nineteen patients in that cohort required subsequent reoperation for radiation necrosis and progressive neurological decline. Therefore, radiosurgery can provide effective salvage therapy for selected patients, but with an increased risk for late effects from treatment.

Brachytherapy
Brachytherapy refers to radiation therapy delivered at a short distance and is another method to deliver conformal radiation therapy in a limited number of situations for childhood brain tumors. Brachytherapy is usually accomplished by implantation of a radioactive source. For example, radioactive phosphorous (32P) was injected into the cystic component of craniopharyngiomas in five children at the University of Pittsburgh [28]. The advantage of brachytherapy is that the radiation only travels a very limited distance, so that most normal brain structures are spared toxicity. However, this treatment requires that the tumor be predominantly cystic, which is not common except for a subset of craniopharyngiomas. Moreover, the precision of the dosimetry for intracavitary irradiation with 32P is also limited. Therefore, the dose to structures adjacent to the cyst, such as the optic chiasm, can be difficult to quantitate. Therefore, for our patients with craniopharyngiomas that are 3 cm or smaller, we routinely use SRT with arc photons. For larger craniopharyngiomas, and especially in younger children, we prefer to use proton radiation therapy.

Proton Radiation Therapy
Conformal radiation therapy can also be delivered with proton radiation therapy. This approach takes advantage of the relatively large size and positive charge of protons that provide the physical advantage of proton therapy over photon therapy: there is no exit dose with protons [29]. Therefore, unlike photons, which enter the patient at a relatively high dose and deposit radiation at and beyond the target, protons enter the patient with a relatively low dose and, once the proton beam reaches the tumor target, all the remaining energy is absorbed by the tumor; no normal tissues distal to the target are irradiated (Fig. 2Go).

The differences between proton and photon irradiation for medulloblastoma are illustrated in Figure 4Go and Figure 5Go. The treatment volumes for medulloblastoma include: A) a posterior fossa boost, and B) the whole brain and spine (craniospinal field). The posterior fossa boost with conventional photons delivers a substantial dose to the cochlea, but with proton radiation therapy, the posterior fossa boost spares the cochlea (Fig. 4Go). Therefore, proton radiation therapy should limit radiation-induced ototoxicity [30].



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  		Figure 4. Comparison of the doses to the cochlea with protons versus conventional photon radiation therapy for a patient with medulloblastoma. Dose to the posterior fossa after whole-brain irradiation and posterior fossa boost is displayed by the color in the inset. The proton posterior fossa boost (left) significantly spares the cochlea outlined in blue.

 


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  		Figure 5. Comparison of spinal fields for medulloblastoma: photons (upper panels) versus protons (lower panels). The radiation dose gradient is displayed over the scan, with pink representing 100% of the prescribed dose. The proton treatment avoids an exit dose and thereby spares the contents of the mediastinum and anterior chest from irradiation.

 
The advantage of proton radiation therapy for medulloblastoma is also seen in the craniospinal field. The posterior spinal field with photons exits beyond the spine, and normal tissues such as the heart, lungs, and breasts are irradiated (Fig. 5Go, upper panels). Therefore, these nontarget tissues are at risk for late effects from radiation therapy, including a second malignancy. In contrast, the posterior spinal field with protons does not exit beyond the spine (Fig. 5Go, lower panels). Therefore, normal tissues anterior to the spine are spared from the potential late effects of radiation therapy. The potential lower risk for radiation-induced tumors after proton irradiation, compared with photon craniospinal irradiation, has been estimated to be a factor of 15 [31]. We, therefore, treat our medulloblastoma patients with proton irradiation at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital.

Proton radiation therapy is also currently available in the U.S. at Loma Linda University Medical Center in California. Investigators at Loma Linda recently reported outcomes for the first 27 children treated with proton radiation therapy for intracranial low-grade astrocytomas [32]. Almost all of the children were treated for either unresectable tumors or residual or progressive disease after subtotal resection. Tumors were treated to a mean dose of 55.2 cobalt gray equivalents (CGE) with standard fractionation (1.8 CGE/day). At a mean follow-up of 3.3 years, only 6 of 27 patients failed locally within the irradiated field.

Proton radiation therapy for pediatric CNS tumors is also available in three countries in Western Europe. The French experience with proton radiation therapy for childhood brain tumors was recently reported from the Centre de Protontherapie d’Orsay [33]. Children with benign (6 patients) and malignant (11 patients) brain tumors were treated with combined photon (median dose 40 Gy) and proton (20 CGE) radiation therapy. With a mean follow-up of 27 months, local control was 92%. Long-term follow-up from this and other studies of proton radiation therapy is needed to document the expected reduction in late effects with proton radiation therapy.

Intensity-Modulated Radiation Therapy
IMRT is another method to deliver conformal radiation therapy and it was reviewed previously in The Oncologist [34]. IMRT is usually delivered with high-energy photons from a linear accelerator. IMRT treats tumors with multiple fixed photon fields that travel through a collimator made up of mobile leaves of metal. During treatment, individual leaves move in and out of the radiation field to sculpt the radiation dose around particular structures. IMRT was used to treat a cohort of children with medulloblastomas at Baylor College of Medicine [35]. Those investigators retrospectively evaluated a group of 26 patients with medulloblastomas and grouped the patients by whether they received conventional radiation therapy or IMRT [36]. In that study, the dose to the cochlea was limited to 68% of the dose given with conventional radiation therapy. Retrospective audiometric evaluation revealed better hearing for the group treated with IMRT without any posterior fossa failures at a median follow-up of 35 months [36].

Although IMRT with photons can be an elegant way to deliver radiation therapy to a target and limit radiation dose to a limited number of normal structures, this benefit is achieved at the cost of increasing the total radiation dose to other normal tissues. For example, when comparing different treatment plans for medulloblastoma, both IMRT with photons and proton radiation therapy plans spare the cochlea (Fig. 6Go). However, in order to spare the cochlea in the IMRT plan, the temporal lobes receive an additional radiation dose (Fig. 6Go). Therefore, it is possible that IMRT with photons will spare the cochlea and preserve hearing at the cost of a greater dose to other structures, such as the temporal lobe, which may cause more cognitive deficits. Even if the additional radiation dose is below the threshold required to cause clinically relevant effects, the additional radiation dose to normal tissues with IMRT has been estimated to almost double the risk of radiation-induced malignancies [37]. Therefore, we believe that the most appropriate place for IMRT in the treatment of childhood brain tumors is in prospective clinical trials where the long-term benefits and toxicities of this approach can be documented.



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  		Figure 6. Comparison of whole-brain irradiation and posterior fossa boost using protons with IMRT. Both treatments limit the dose to the cochlea (outlined in blue), but the IMRT treatment with photons accomplishes this by increasing the dose to the temporal lobes.

 

   CONCLUSIONS
Top
 Learning Objectives
 Abstract
 Introduction
 Late Effects of Radiation...
 Conformal Radiation Therapy
 Conclusions
References
 
Childhood CNS tumors are frequently treated with radiation therapy. Since late effects from radiation therapy can be substantial, a variety of conformal radiation therapy techniques have been developed to try to limit the high radiation dose region to the tumor target. These strategies appear to provide similar tumor control as conventional radiation therapy. Prospective trials that monitor the late effects from these treatments are needed to confirm the expected reduction in long-term side effects with conformal radiation therapy.


   ACKNOWLEDGMENT
Top
 Learning Objectives
 Abstract
 Introduction
 Late Effects of Radiation...
 Conformal Radiation Therapy
 Conclusions
 References
 
We thank Judy Adams and Karen Doppke for providing the figures.


   References
Top
 Learning Objectives
 Abstract
 Introduction
 Late Effects of Radiation...
 Conformal Radiation Therapy
 Conclusions
 References
 

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Received February 17, 2004; accepted for publication April 7, 2004.




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