Improvement of Treatment Plans Developed with Intensity-modulated Radiation Therapy for Concave-shaped Head and Neck Tumors1

1. 2. 3. 4. 5. Nesrin Dogan, PhD, Leonid B. Leybovich, PhD, Stephanie King, CMD, Anil Sethi, PhD and Bahman Emami, MD

+ Author Affiliations 1.
1

From the Department of Radiation Oncology, Loyola University Chicago Medical Center, 2160 S First Ave, Maywood, IL 60153. Received May 29, 2001; revision requested June 25; revision received August 23; accepted September 20. Address correspondence to N.D. (e-mail: ndogan@rdth.rdth.luhs.org).

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Abstract
PURPOSE: To improve dose conformity and normal tissue sparing in patients with concave-shaped head and neck cancers by using tomotherapy and static step-and-shoot intensity-modulated radiation therapy (IMRT) and by comparing results with those of three-dimensional (3D) conformal radiation therapy (CRT) and two-dimensional (2D) radiation therapy. MATERIALS AND METHODS: Treatment planning in 10 patients with concaveshaped head and neck tumors was performed by using tomotherapy and step-and-shoot IMRT, 3D CRT, and 2D techniques. IMRT plans were modified by placing virtual critical structures in regions outside the target where hot spots occurred. These modified plans were used for comparison because they provided better dose conformity. Critical structures were the spinal cord, the parotid glands, and the mandible. Comparisons were performed by means of dose-volume histograms, clinical target volume (CTV), target covered by 95% isodose (D95%), dose received by 5% of the critical structure volume (D5%), maximum dose, mean dose, and normal tissue complication probability for critical structures. RESULTS: Original IMRT plans showed more conformal dose distributions than those in 3D CRT and 2D plans. However, hot spots developed in the posterior and anterior neck. Introduction of virtual critical structures in IMRT plans resulted in removal of these

hot spots without affecting target coverage. Modified IMRT plans also demonstrated better CTV coverage than that in 3D CRT and 2D plans. The average D95% was 97.3% with tomotherapy, 97.1% with step-and-shoot IMRT, 84.7% with 3D CRT, and 69.4% with 2D techniques. D5% for the spinal cord changed from approximately 45 Gy with 3D plans and 46 Gy with 2D plans to approximately 28 Gy with IMRT. CONCLUSION: IMRT demonstrated better target coverage and sparing of critical structures than that of 3D CRT and 2D techniques. Use of virtual critical structures resulted in removal of hot spots around the spinal cord. RSNA, 2002 Previous SectionNext Section RSNA, 2002 Because of the complex anatomy and large number of sensitive normal structures in the vicinity of a target, treatment planning for head and neck cancers is a challenging task. The clinical target volume (CTV) includes the gross tumor volume and regions of suspected microscopic disease. These regions usually surround the spinal cord. The need to spare the spinal cord from excessive radiation dose results in concave-shaped clinical and planning target volumes. Moreover, the parotid glands also have to be spared because xerostomia considerably affects a patients quality of life (1). In conventional forward planning techniques, sparing of the spinal cord with two-dimensional (2D) techniques and three-dimensional (3D) conformal radiation therapy (CRT) is usually achieved by combining photon and electron beams. However, matching of photon and electron beams produces areas of highly nonuniform dose distribution (24). Although the dose to the spinal cord may not exceed the tolerance level with these techniques, very high doses are usually delivered to the parotid glands (5). When intensity-modulated beams are used, more conformal dose distributions may be achieved (68). Development of optimal intensity-modulated radiation therapy (IMRT) plans, however, is practically impossible with conventional forward 3D treatment techniques. Inverse treatment planning systems that automatically create IMRT plans are now commercially available (9,10). In the optimization process, the purpose of these systems is to satisfy treatment goals, such as assigning prescription dose to the target(s) and dosevolume constraints to the critical structures. Even though treatment goals may be met, however, dose distributions developed by IMRT planning systems are usually far from desired. For example, for aforementioned concave CTV of the head and neck, treatment plans demonstrate acceptable doses to the spinal cord but high doses to regions around the cord. Posner et al (11) also reported a similar problem. Several planning techniques that might alleviate this problem have been reported in the literature (12,13). De Neve et al (12) developed a method involving beam intensity

modulation that uses a static technique of beam segmentation in the lower neck and upper mediastinal regions. Esik et al (13) used a triangle-shaped dummy organ that was positioned in the posterior neck region. They were able to avoid assigning high doses to areas surrounding the spinal cord. However, the treatment plans were developed for a simplified phantom-based case that used only the step-and-shoot IMRT method of delivery. Wu et al (14) used distention of the original spinal cord contours by 0.5 cm. This technique pushed the high-dose region somewhat away from the spinal cord. However, the high-dose regions still remained in the posterior neck and around the spinal cord. The purpose of our study was to improve dose conformity and normal tissue sparing in patients with concave-shaped head and neck cancers by using tomotherapy and step-andshoot IMRT and by comparing results with those of 3D CRT and 2D radiation therapy. Previous SectionNext Section

MATERIALS AND METHODS

Ten patients with head and neck cancer and cervical node involvement (node levels 15) were selected for this study. Patients underwent computed tomography (CT) with a 35mm section thickness from the top of the head to the lower portion of the neck. The scans were transferred to the AcQSIM system (Marconi Medical Systems, Cleveland, Ohio) for contouring. CTV volumes, prescription doses, and dose constraints to the critical structures were specified according to ICRU50 recommendations (15). Eight patients received radiation after resection of the primary lesion. In all cases, CTV1 included lymph node station levels 15, and prescription dose was 44 Gy. The shape of CTV1 was concave. CTV2 included all subclinical and microscopic disease around the primary tumor and within the lymph node drainage area at risk, and prescription dose was 60 Gy. CTV3 included the tumor bed in eight patients, and prescription dose varied from 64 to 66 Gy. In two patients who had an intact tumor, CTV3 included the primary tumor, and prescription dose was 70 Gy. The critical structures considered in this study were the spinal cord, the parotid glands, and the mandible. The shape of the CTV was used as the only criterion for inclusion of patients in the study. Figure 1 shows the 3D volumetric and 2D representations of the target and normal structures in one patient included in the study.

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Figure 1. Target and critical structure representations are shown in 3D volumetric (top) and transverse (bottom) CT images. Yellow = parotid glands, light blue = mandible, dark blue = target, green = spinal cord. The treatment of all patients was planned and performed with 3D CRT because it is used routinely in our clinic for patients with head and neck tumors. For comparison, however, treatment for these patients was also planned with 2D and IMRT techniques. 3D CRT and 2D planning was performed on a FOCUS treatment planning system (CMS, St Louis, Mo). IMRT plans were developed with a NOMOS-CORVUS treatment planning system (NOMOS, Sewickley, Pa). All plans were generated by an experienced dosimetrist (S.K.) in collaboration with two physicists (N.D., L.B.L.) who coauthored this article. The same two physicists analyzed the plans for the presence of hot spots, selected and compared IMRT plans with 3D CRT and 2D plans, and performed all relevant calculations. Our institutional review board did not require its approval or patient informed consent, since no patient-specific information was used. A combination of 6-MV photon beams and 612-MeV electron beams were used in 3D CRT and 2D treatment plans when necessary. Coned-down fields were used to boost the gross tumor volume. 2D plans were developed by performing CT through the center of the target. 2D plans used mostly parallel-opposed lateral beams with Ellis compensating filters. An anterior field was used to treat the lower portion of the neck. To evaluate the true target coverage and critical structure sparing, volumetric dose distributions corresponding to the beam arrangements developed for 2D treatment plans were also calculated. In 3D CRT plans, the wedge angles, number of beams, and their orientations and weightings were varied until acceptable volumetric dose distributions were obtained. Most of the 3D CRT plans used a four-field technique with right and left lateral, anterior, and lower-anterior neck fields. Non-coplanar beams were also used as needed.

IMRT plans were developed for both tomotherapy and static step-and-shoot techniques. Tomotherapy plans were developed by using 1-cm MIMiC mode (NOMOS) (16) with no couch angulation. The step-and-shoot IMRT plans included eight coplanar nonopposing 6-MV photon beams. This beam arrangement was selected because our preliminary studies demonstrated that further increase in the number of beams did not noticeably improve treatment plans. Multileaf collimator field segments and number of segments were determined with the NOMOS-CORVUS planning software. For each case, the number of multileaf collimator segments for each field varied between 30 and 50. After IMRT plans were developed, they were analyzed for the presence of hot spots outside the target. Two methods were used to reduce the magnitude of hot spots. The first method made use of an external avoidance feature, available with the NOMOS-CORVUS system, in which the system tried to eliminate beams that passed through locations of external avoidance structures. The second method consisted of the creation of virtual critical structures (17) in areas that needed dose reduction. Dose constraints to virtual critical structures were determined interactively during the optimization process. Dose constraints that resulted in the desired dose reduction without affecting target coverage were used to produce the final IMRT plan. For each patient, an IMRT plan that demonstrated superior dose distribution was selected for comparison with 3D CRT and 2D plans. The planning goals were to cover 95% of the target volume with 95% of the prescribed dose and to keep the critical structure doses at or below the known tolerance limits. For the spinal cord, the tolerance dose was 45 Gy. For the parotid glands, the goal was to limit the volume that received a dose greater than 30 Gy to 33%. For the mandible, the volume that received a dose greater than 60 Gy was limited to 15%. Treatment plans were compared by means of dose-volume histograms, maximum dose (Dmax), dose received by 5% of the critical structure volume (D5%), mean dose (Dmean), and target volume covered by 95% of the prescription dose (D95%). In addition, doses received by 33% and 50% of the parotid glands (D33% and D50%, respectively), the mandible volume that received 60 Gy or more (V60Gy), and the dose received by 50% of the mandible (D50%) were evaluated. Standard deviations for the mean values of all parameters were calculated. Normal tissue complication probability (NTCP) was calculated for all critical structures by using the Lyman model (18) with the Kutcher-Burman histogram reduction method (19,20). The parameters for NTCP calculations (volume effect [n], slope [m], and dose that will cause 50% complication probability [TD50]) were selected according to Emami et al (21). The following NTCP parameters were used: TD50 = 66.5 Gy, n = 0.05, and m = 0.17 for the spinal cord; TD50 = 46.0 Gy, n = 0.70, and m = 0.18 for the parotid glands; and TD50 = 72.0 Gy, n = 0.07, and m = 0.10 for the mandible. NTCP values were used only to assist in comparison between rival plans. If two plans had similar dose distributions but different NTCP values, then the plan with the lower NTCP was

considered more beneficial. However, clinical use of the NTCP concept is limited until improved NTCP models are developed and enough clinical data are obtained. Previous SectionNext Section

RESULTS
For both tomotherapy and step-and-shoot IMRT plans, high-dose regions (receiving 80%110% of the prescribed target dose) surrounded the spinal cord and extended to the posterior and superior portion of the neck (Fig 2). The addition of the external avoidance structure had a limited effect in removing these hot spots. Moreover, use of the external avoidance feature increased dose inhomogeneity in the target (Fig 3). On the other hand, use of virtual critical structures (Fig 4) removed the aforementioned hot spots in all cases. On average, the maximum and mean doses to the posterior neck were reduced by 22% 8 and 49% 10, respectively.

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Figure 2. Original tomotherapy dose distributions shown in the sagittal (top left), coronal (top right), superior transverse (bottom left), and inferior transverse planes (bottom right).

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Figure 3. Tomotherapy dose distributions shown in the transverse plane with no external avoidance (top) and with the addition of the external avoidance structure (bottom). Orange = external avoidance.

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Figure 4. Modified tomotherapy treatment plan shows how anterior (orange) and posterior (purple) virtual critical structures are introduced in hot spot locations. Dose distributions are shown in the sagittal (top), superior transverse (middle), and inferior transverse planes (bottom). Introduction of virtual critical structures resulted in a slight increase (approximately 2% on average) of maximum dose to nontarget tissue. Figure 5 demonstrates dose-volume

histograms for anterior and posterior neck regions in one patient. A marked dose reduction was observed after introduction of virtual critical structures. To achieve this dose reduction, the dose constraint to the virtual critical structure should be 30% of the target prescription dose. Because the IMRT plans developed with the use of virtual critical structures demonstrated better sparing of normal structures (eg, introduction of virtual critical structures reduced spinal cord D5% from approximately 45 Gy to approximately 28 Gy) without compromising target coverage (variation of D95% was 2%), they were selected for comparison with 3D CRT and 2D plans.

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Figure 5. Dose-volume histograms developed for the anterior and posterior neck regions allow comparison of doses received with original and modified IMRT plans. It was found that the average D95% varied from 69.4% 10.3 with 2D treatment plans to 84.7% 9.0 with 3D CRT to 97.1% 1.3 with tomotherapy to 97.3% 2.7 with stepand-shoot IMRT. The Table shows the average dose parameters received by critical structures with different treatment planning techniques. As seen from the Table, the maximum spinal cord dose was reduced from 47.01 Gy 1.33 to approximately 39 Gy as the complexity of the treatment technique increased (from 2D to IMRT). The maximum dose to the spinal cord was similar with both IMRT techniques (39.77 Gy 5.20 for tomotherapy and 38.99 Gy 6.07 for step-and-shoot IMRT). A noticeable reduction in D5% was observed in the spinal cord with IMRT. The average D5% to the spinal cord changed from 46.17 Gy 1.06 with 2D treatment plans to 45.18 Gy 4.86 with 3D CRT to 28.61 Gy 3.67 with tomotherapy to 27.51 Gy 3.51 with step-and-shoot IMRT. Even greater reduction in mean dose to the spinal cord (approximately 50%) was observed when IMRT was used. IMRT also resulted in a reduction of spinal cord NTCP from 2.2% (with 3D CRT and 2D techniques) to 0.049%. View this table:

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Comparison of Average Doses to Critical Structures with Different Treatment Techniques 2D and 3D treatment plans demonstrated comparable maximum doses to the parotid glands (approximately 6769 Gy). IMRT reduced the maximum dose to the parotid glands by approximately 10 Gy. The average D5% showed more variation in doses to the parotid glands. D5% for the parotid glands was reduced from approximately 68 Gy with 2D plans to 66 Gy with 3D CRT to 52 Gy with tomotherapy to 50 Gy with step-andshoot IMRT. Much greater variation was observed in mean dose to the parotid glands: approximately 62 Gy with 2D techniques, approximately 53 Gy with 3D CRT, and approximately 30 Gy with IMRT. A great reduction was observed in D33% to the parotid glands: approximately 64 Gy with 2D plans, 58 Gy with 3D CRT, 35 Gy with tomotherapy, and 34 Gy with step-and-shoot IMRT. D50% for parotid glands showed a similar behavior. NTCPs for parotid glands were reduced from approximately 89% with 2D plans to approximately 67% with 3D CRT and 7.5% with tomotherapy and 6% with step-and-shoot IMRT. The average maximum dose to the mandible was comparable between 2D and 3D plans (67.53 Gy 5.25 vs 68.68 Gy 5.34, respectively). Dmax in the mandible practically did not change when IMRT was used (63.86 Gy 3.19 with tomotherapy vs 65.33 Gy 3.91 with step-and-shoot IMRT). Again, D5% for the mandible was similar between 2D plans and 3D CRT (66.15 Gy 5.18 vs 67.11 Gy 5.83, respectively). However, some reduction in D5% was observed with IMRT (57.31 Gy 4.91 for tomotherapy and 56.43 Gy 1.80 for step-and-shoot IMRT). The average mean dose varied as follows: 42.65 Gy 9.79 with 2D plans, 46.58 Gy 9.60 with 3D CRT, 39.83 Gy 5.43 with tomotherapy, and 40.93 Gy 5.18 with step-and-shoot IMRT. The reduction in D50% in the mandible was not conclusive in 2D versus 3D CRT plans (from 58.34 Gy 7.86 to 52.66 Gy 14.2, respectively) and was somewhat noticeable with IMRT (approximately 43 Gy). V60Gy for the mandible decreased from 48.0% with 2D plans to 30.0% with 3D CRT to 3.8%5.5% with IMRT. Although NTCP values for the mandible increased from 7.6% with 2D to 12.0% with 3D CRT, IMRT plans reduced the NTCP value to a fraction of a percent. As expected, the mean dose to nontarget tissue increased with the complexity of the treatment plans: The lowest value (approximately 6.9 Gy) was observed with 2D plans. In 3D CRT plans, the mean dose became approximately 9.3 Gy, and in IMRT plans, the dose increased to 11.4 Gy for tomotherapy and 12.8 Gy for step-and-shoot techniques. Figures 6 and 7 show comparisons of dose distributions and dose-volume histograms for the target, spinal cord, parotid glands, and mandible in one patient by using all four radiation delivery techniques. These figures clearly demonstrate that IMRT plans with the use of virtual critical structures produced more conformal target coverage and better sparing of critical structures than that of 3D CRT and 2D techniques.

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Figure 6. Comparison of isodose distributions with (top left) tomotherapy, step-andshoot IMRT (top right), 3D CRT (bottom left), and 2D (bottom right) techniques.

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Figure 7a. Comparison of dose-volume histograms for (a) target, (b) left parotid gland, (c) mandible, and (d) spinal cord with tomotherapy (dashed and dotted line), step-andshoot IMRT (dashed line), 3D CRT (solid line), and 2D (dotted line) techniques. IMRT plans were developed with the use of virtual critical structures. Target coverage was more conformal and critical structure sparing was improved in both IMRT plans when compared with 3D CRT and 2D plans. The parotid glands received noticeably lower dose with step-and-shoot IMRT than with tomotherapy.

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Figure 7b. Comparison of dose-volume histograms for (a) target, (b) left parotid gland, (c) mandible, and (d) spinal cord with tomotherapy (dashed and dotted line), step-andshoot IMRT (dashed line), 3D CRT (solid line), and 2D (dotted line) techniques. IMRT plans were developed with the use of virtual critical structures. Target coverage was more conformal and critical structure sparing was improved in both IMRT plans when compared with 3D CRT and 2D plans. The parotid glands received noticeably lower dose with step-and-shoot IMRT than with tomotherapy.

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Figure 7c. Comparison of dose-volume histograms for (a) target, (b) left parotid gland, (c) mandible, and (d) spinal cord with tomotherapy (dashed and dotted line), step-andshoot IMRT (dashed line), 3D CRT (solid line), and 2D (dotted line) techniques. IMRT plans were developed with the use of virtual critical structures. Target coverage was more conformal and critical structure sparing was improved in both IMRT plans when compared with 3D CRT and 2D plans. The parotid glands received noticeably lower dose with step-and-shoot IMRT than with tomotherapy.

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Figure 7d. Comparison of dose-volume histograms for (a) target, (b) left parotid gland, (c) mandible, and (d) spinal cord with tomotherapy (dashed and dotted line), step-andshoot IMRT (dashed line), 3D CRT (solid line), and 2D (dotted line) techniques. IMRT plans were developed with the use of virtual critical structures. Target coverage was more conformal and critical structure sparing was improved in both IMRT plans when compared with 3D CRT and 2D plans. The parotid glands received noticeably lower dose with step-and-shoot IMRT than with tomotherapy. Previous SectionNext Section

DISCUSSION
Because head and neck tumors are surrounded by many critical structures, radiation treatment for these tumors requires the use of complex treatment planning. The target volume is usually concave in shape and surrounds the spinal cord. Moreover, parotid glands are usually near the target. With 2D treatment plans, parotid glands receive doses higher than the tolerance level. This leads to xerostomia that may cause discomfort for a patient. Sparing of these organs while delivering the curative dose of radiation presents an intractable problem for 2D treatment planning. Although 3D CRT provided the means to create more conformal dose distributions through the use of complex beam arrangements, development of satisfactory treatment plans was time consuming and was not always possible. Even in plans that were considered satisfactory, doses to critical structures often came close to or exceeded tolerance levels. IMRT may provide more conformal dose distributions and better sparing of critical structures. Although the development of treatment plans is performed automatically by the computer, several attempts are usually necessary because many modifications in target prescription doses and dose-volume constraints to critical structures are required until treatment goals are achieved. While goals may be achieved in optimized IMRT treatment plans, the dose distributions may not be satisfactory. According to the results of

our study, both tomotherapy and step-and-shoot IMRT plans demonstrated high-dose regions in the posterior portion of the neck that surrounded the spinal cord. Moreover, high-dose regions occurred in the anterior portion of the neck. This problem has also been reported elsewhere (11,13). The use of virtual critical structures markedly reduced doses in the posterior and anterior neck regions. This technique reduced the integral dose received by normal tissues; moreover, it removed hot spots near (within 510 mm of) the spinal cord. The presence of hot spots in the vicinity of the spinal cord or other sensitive structures presents a concern because of uncertainties in critical structure localization, dose calculation algorithm, and patient immobilization. These uncertainties may cause occurrence of highdose levels in the critical structures. Besides removing hot spots from posterior and anterior neck regions, the introduction of virtual critical structures resulted in some reduction (5%6%) of mean dose to the spinal cord compared with that observed in original IMRT plans (without use of virtual critical structures). Esik et al (13) used a similar technique to reduce hot spots in the posterior neck region. They positioned a triangle-shaped at-risk dummy organ in the area that needed dose reduction. However, the method was tested for a simplified phantom-based case with the step-and-shoot IMRT method of delivery. Our technique used more realistically shaped virtual critical structures to reduce the hot spots in both anterior and posterior neck regions in real clinical cases. The use of the external avoidance structure available with the NOMOS-CORVUS system did not reduce the magnitude of hot spots in either anterior or posterior neck regions. It seems that the external avoidance structure has a lower priority in the optimization of dose distributions. If avoiding radiation by means of the external avoidance structure compromises target coverage, then the limitations imposed by this structure are ignored by the NOMOS-CORVUS system. This may explain the ineffectiveness of the external avoidance technique in the elimination of hot spots in the anterior neck region. As expected, target coverage that was characterized by D95% was poor in 2D plans (69.4%), was noticeably improved in 3D CRT plans (84.7%), and was further improved (by an additional 15%) in IMRT plans. Even though the average D95% for 3D CRT plans was lower than the set treatment goal, these plans were used for treatments because it was not technically possible to increase D95% without exceeding the tolerance of critical structures. However, 3D CRT plans were approved for treatments because the target areas that received less than 95% of the prescribed dose were medically considered to be at low risk for tumor recurrence in these sets of patients. Both IMRT plans reached the prescribed goal of target coverage; however, the most pronounced effect of the IMRT plans was the sparing of critical structures. Mean dose to the spinal cord was reduced by 50%. Although 3D CRT exhibited improved target coverage when compared with 2D techniques, it did not reduce doses to the spinal cord. When compared with 2D techniques, 3D CRT reduced the mean dose to the parotid glands by only 15%, and IMRT techniques reduced this dose by more than 50%. This result may be important in preserving function of the parotid glands. IMRT techniques also noticeably reduced the

dose to the mandible: Volume of the mandible that received 60 Gy or more was reduced from 48.0% with 2D techniques and 30.0% with 3D CRT to approximately 5% with IMRT. This resulted in the reduction of NTCP values to a fraction of a percent. Reduction in the daily dose received by critical structures with IMRT techniques should provide an extra biologic benefit in the prevention of late complications and potential for dose escalation. NTCP calculations in this study also demonstrated potential reduction in morbidity when head and neck tumors were treated with the use of IMRT. However, NTCP values cannot be used for accurate prediction of complications until both data and models required for these calculations become more reliable. In conclusion, it seems that both tomotherapy and static step-and-shoot IMRT techniques will provide visible improvement in target coverage and in the sparing of normal structures, especially when the virtual critical structure method is used. This should result in the reduction of acute and late complications in patients with head and neck cancers. In our department, the virtual critical structure method is currently used for the development of IMRT treatment plans for targets in various sites. Previous SectionNext Section Previous SectionNext Section

Acknowledgments
The authors thank Andrew Kahn, DO, for editing the manuscript. Previous SectionNext Section

Footnotes

Abbreviations: CRT = conformal radiation therapy, CTV = clinical target volume, IMRT = intensity-modulated radiation therapy, NTCP = normal tissue complication probability, 3D = three-dimensional, 2D = two-dimensional Author contributions: Guarantors of integrity of entire study, all authors; study concepts and design, all authors; literature research, N.D.; clinical studies, N.D., B.E.; data acquisition, N.D., L.B.L., B.E., S.K.; data analysis/interpretation, all authors; statistical analysis, N.D.; manuscript preparation and definition of intellectual content, all authors; manuscript editing, revision/review, and final version approval, N.D., L.B.L., B.E.

Index terms: Head and neck neoplasms, therapeutic radiology, 10.1299, 20.1299; Therapeutic radiology, comparative studies Previous Section

References

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