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Use of volumetric-modulated arc therapy for treatment of Hodgkin lymphoma
Medical Dosimetry 38 (2013) 372–375
Medical Dosimetry journal homepage: www.meddos.org
Use of volumetric-modulated arc therapy for treatment of Hodgkin lymphoma Young K. Lee, Ph.D.,* James L. Bedford, Ph.D.,* Mary Taj, M.D.,† and Frank H. Saran, M.D., F.R.C.R.‡ *Joint Department of Physics, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK; †Paediatric Oncology, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK; and ‡ Radiotherapy Department, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 July 2012 Accepted 8 April 2013
To evaluate volumetric-modulated arc therapy (VMAT) for treatment of Hodgkin lymphoma (HL) in patients where conventional radiotherapy was not deliverable. A planning computed tomography (CT) scan was acquired for a twelve-year-old boy with Stage IIIB nodular sclerosing HL postchemotherapy with positive positron emission tomography scan. VMAT was used for Phase 1 (19.8 Gy in 11 fractions) and Phase 2 (10.8 Gy in 6 fractions) treatment plans. Single anticlockwise arc plans were constructed using SmartArc (Philips Radiation Oncology Systems, Fitchburg, WI) with control points spaced at 41. The inverse-planning objectives were to uniformly irradiate the planning target volume (PTV) with the prescription dose while keeping the volume of lung receiving greater than 20 Gy (V20 Gy) to less than 30% and minimize the dose to the other adjacent organs at risk (OAR). Pretreatment verification was conducted and the treatment delivery was on an MLCi Synergy linear accelerator (Elekta Ltd, Crawley, UK). The planning results were retrospectively confirmed in a further 4 patients using a single PTV with a prescribed dose of 19.8 Gy in 11 fractions. Acceptable dose coverage and homogeneity were achieved for both Phase 1 and 2 plans while keeping the lung V20 Gy at 22.5% for the composite plan. The beam-on times for Phase 1 and Phase 2 plans were 109 and 200 seconds, respectively, and the total monitor units were 337.2 MU and 292.5 MU, respectively. The percentage of measured dose points within 3% and 3 mm for Phase 1 and Phase 2 were 92% and 98%, respectively. Both plans were delivered successfully. The retrospective planning study showed that VMAT improved PTV dose uniformity and reduced the irradiated volume of heart and lung, although the volume of lung irradiated to low doses increased. Twophased VMAT offers an attractive option for large volume sites, such as HL, giving a high level of target coverage and significant OAR sparing together with efficient delivery. & 2013 American Association of Medical Dosimetrists.
Keywords: Dynamic arc therapy Hodgkin lymphoma Radiotherapy VMAT Volumetric-modulated arc therapy
Introduction Radiotherapy is part of a standard course of treatment for many patients with Hodgkin lymphoma (HL). For supradiaphragmatic disease, the thoracic organs are irradiated to the prescription dose with conventional modified mantle fields that are often used. When a higher dose is required for a sclerosing mass, the prescription dose is limited by the organs at risk (OAR) that are in the radiotherapy fields.1,2 We investigate the use of volumetricmodulated arc therapy (VMAT) in large volumes, such as HL, where the OAR doses cannot be met using conventional methods. Methods and Materials A twelve-year-old boy with Stage IIIB nodular sclerosing HL had presented with a positive positron emission tomography scan after 2 courses of chemotherapy to
Reprint requests to: Young K. Lee, Ph.D., Joint Department of Physics, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel.: þ44 (0)208 661 3474; fax: þ44(0)208 643 3812. E-mails: [email protected], [email protected]
be treated according to EuroNET-PHL-C1 trial.3 The initial Phase 1 (Ph1) conventional plan consisted of anterior-posterior fields defined by virtual simulation, i.e., with no delineated volumes, and a prescription dose of 19.8 Gy in 11 fractions delivered 5 fractions/wk. The treatment region included all sites of involved disease at diagnosis and multileaf collimators were used to shield noninvolved regions. The residual nodular bulky mediastinal mass was localized to produce a conformal Phase 2 (Ph2) plan with prescription of 10.8 Gy in 6 fractions with the beams arranged anteriorly to minimize the lung dose as much as possible. However, the composite plan showed the treatment was unacceptable as the lung receiving greater than 20 Gy (V20 Gy) exceeded 70% (Table 1). VMAT4,5 was then planned for Ph1 using the same prescription regime. A new computed tomography (CT) scan was acquired from eyes to the pelvis in contiguous 2-mm thickness slices on a Philips Brilliance largebore CT simulator (Philips Medical Systems, Cleveland, OH). The patient was in a supine position with the head and shoulders immobilized in a thermoplastic shell while holding handles that were attached to ropes connected to a foot plate. Contrast was used to aid the volume delineating process. The spleen, hilum lymph node, involved left neck nodes, and the postchemotherapy residual mediastinal mass were localized as the clinical target volumes (CTVs). The Ph1 planning target volume (PTV) included all CTVs with a uniform 1-cm margin except the neck nodal volume where a 0.3-cm margin was used (1820.0 cm3). The Ph2 PTV was the mediastinal CTV with a uniform 1-cm margin (828.0 cm3). The lungs, heart, thyroid, liver, and left and right kidneys were also delineated. The density in the delineated organs that were affected by the contrast was overridden.
0958-3947/$ – see front matter Copyright Ó 2013 American Association of Medical Dosimetrists http://dx.doi.org/10.1016/j.meddos.2013.04.004
Y. K. Lee et al. / Medical Dosimetry 38 (2013) 372–375 The primary objective of the VMAT plans was to deliver an adequate dose to the PTV while keeping the lung V20 Gy less than 30%. The secondary objective was to meet the currently accepted dose-volume restrictions in the OAR. The 6-MV VMAT plans were inversely planned using Pinnacle SmartArc v9.0 (Philips Healthcare, Fitchburg, WI). For Ph1, a single arc from gantry angle of 1711 to 1811 (according to the International Electrotechnical Commission 61217) around the isocenter with a collimator rotation of 21 to minimize planes of interleaf leakage was used. The control point spacing was 41 and the leaf motion was constrained to 0.46 cm/deg. Τhe plan was initially optimized with high weightings for PTV coverage and homogeneity, and low weightings for OAR objectives. An annulus was used to conform high dose to the PTV. The weights to the OAR and annulus objectives were increased on subsequent optimizations and priority was given to the lung objectives. The plan was seen to have reached optimality when the dose to the lung could not be improved further without a large reduction in PTV coverage. The Ph1 OAR dose-volume histograms (DVH) were used to estimate an acceptable OAR DVH for Ph2. For Ph2, a single arc from gantry angle of 1791 to 1811 around the same isocenter with a collimator rotation of 21 was used. A similar inverseplanning strategy to that used for Ph1 was used to plan Ph2 VMAT but only using the involved OAR objectives as the Ph2 PTV was contained in the mediastinal region. The plans were verified using Delta4 (ScandiDos, Uppsala, Sweden), and greater than 90% gamma agreement between the dose calculated by Pinnacle3 and the dose measured by the phantom for 3%-dose and 3-mm distance was deemed clinically acceptable. All measurement points receiving more than 20% of the dose were included in the gamma analysis. The patient was treated on MLCi Synergy digital linear accelerator (Elekta Ltd, Crawley, UK) and cone-beam CT images were used for patient setup verification. To confirm the observations in this patient, a further 4 patients were retrospectively studied, creating a cohort of 5 patients. A single phase of treatment was considered, with a prescribed dose of 19.8 Gy in 11 fractions. The planning technique was as described previously. The mean statistics for PTV, lung, and heart were evaluated and statistical significance was assessed using a two-tailed Wilcoxon signed rank test.
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Fig. 1. Homogeneous dose coverage of PTV was achieved in both conventional and VMAT plans. A clinically acceptable coverage of the PTVs was also achieved (Fig. 2a). Coverage of the Ph2 PTV was lower than the 95% dose normally achieved, but as the PTV overlapped with the low-density lung, where coverage was expected to be difficult, this was accepted. The lung V20 Gy and mean dose were well within the acceptable levels for VMAT. These levels were not achievable with conventional planning methods (see Table 1 and lung DVH in Fig. 2b). Note, however, that the lung V5 Gy is higher with VMAT owing to the spreading of the dose with this technique. Clinically acceptable dose levels were met for the heart even with greater than 17%
105% 100% 95% comp 90% 105% 100% 95% 90%
Ph1
Results Dose-volume statistics for composite conventional and VMAT plans are shown in Table 1 and the dose distribution can be seen in Table 1 Dose-volume statistics on organs at risk for the composite conventional and VMAT plans. The overlap between named organs and Ph1 PTV are also shown Organ at risk (% Ph1 PTV overlap)
DxVx
Composite plans Dx(Gy) Vx(%) Conventional
Clinically acceptable level VMAT
105% 100% 95% comp 90%
Ph1 PTV (Ph1 plan)
D2% D98% V95%
21.0 9.7 91.6
20.7 17.4 92.5
Ph2 PTV
D2% D98% V95%
32.0 29.0 98.0
31.8 26.2 89.8
Lungs (15.6%)
Dmean V20 Gy V10 Gy V5 Gy
21.6 72.5 82.7 93.5
15.6 22.5 80.8 99.3
o 18 Gy o 30% – –
Heart (17.2%)
Dmean D30% D33% D50% V20 Gy V10 Gy
27.2 29.9 29.8 29.1 99.6 100
23.5 29.1 28.8 25.3 68.9 95.4
– o 40 Gy o 30 Gy o 25 Gy – –
Thyroid (39.8%)
Dmean
21.4
17.6
o 30 Gy
Ipsilateral kidney*
Dmean D50%
14.0 19.2
16.1 17.3
– o 20 Gy
Contralateral kidney*
Dmean D50%
2.1 1.6
3.7 3.3
– o 20 Gy
Kidneys* (8.4%)
Dmean
8.0
9.8
o 18 Gy
Liver* (0.5%)
Dmean V20 Gy V10 Gy
7.8 11.6 33.7
8.1 0 31.8
o 25 Gy – –
105% 100% 95% 90%
n Indicates organs that were fully shielded while compromising the PTV in conventional planning owing to the simple planning methods.
Ph1
Fig. 1. Sagittal (left) and coronal (right) slices with vertical lines indicating the corresponding planes from conventional (top) and VMAT (bottom) plans. Ph1 PTV is in pink and Ph2 PTV is in purple. The yellow ruler on the right indicates a centimeter scale. The isodose lines are indicated in the legend. (Color version of the figure is available online.)
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Y. K. Lee et al. / Medical Dosimetry 38 (2013) 372–375
Fig. 2. (a) Phase 1 PTV and Phase 2 PTV composite dose-volume histograms from VMAT (solid) and conventional (dashed) plans. (b) The lung, heart, and thyroid composite dose-volume histograms from VMAT (solid) and conventional (dashed) plans. (Color version of the figure is available online.)
overlap to the PTV and were lower than what were achievable with conventional plans (see Table 1 and heart DVH in Fig. 2). The thyroid mean dose was well within 30 Gy, which is the level associated with increased risk of abnormal activity. The involved regions near the kidneys that would have been fully shielded with conventional plans were treated with VMAT while maintaining acceptable dose levels for the kidneys (Table 1 and Fig. 1). The planning system–estimated beam-on times for Ph1 and Ph2 plans were 109 and 200 seconds, respectively, and the total number of monitor units were 337.2 MU and 292.5 MU, respectively, which were relatively efficient for delivering 1.8 Gy/fraction to such large treatment volumes. The percentage of measured points with a Gamma Index o 1 with 3% dose difference and 3mm distance to agreement6 for Ph1 and Ph2 were 92% and 98%, respectively. However, the measured dose was 5% to 7% lower than planned dose in regions below the diaphragm for Ph1. An ionization chamber measurement in the region concerned confirmed that the dose was 4.8% low. This was discussed and was considered clinically acceptable as the planned dose in this region was 4 100% of the prescription dose. For Ph2 verification, measured dose was 4% lower than planned dose in small sections of the PTV. Again this was in a high-dose region and was deemed clinically acceptable. The treatment was delivered without problems. The mean results for the complete cohort of 5 patients (Table 2) showed that the PTV dose uniformity was improved slightly with VMAT compared with the conventional treatment, with statistically significant reduction in D2%. The lung V18 Gy was reduced significantly with VMAT, although lung V5 Gy was increased. This indicated that overall, it was likely that the lung would be spared beneficially for patients treated to higher prescribed doses. Heart was also spared significantly using VMAT.
Discussion With low-grade HL, as well as solid tumors, there is evidence for minimizing the use of adjuvant radiotherapy owing to radiation-associated complications. However, in this case, a large mass is present with an incomplete positron emission tomography response after 2 cycles of chemotherapy for which more than the standard 19.8 Gy in 11 fractions is required. A conventional plan cannot deliver adequate dose to the diseased volumes while meeting the OAR constraints. A simultaneous boost technique is not employed here as there are no data to support change in prescription.
Table 2 Mean ⫾ 1 SD dose-volume statistics for the conventional and VMAT plans in the complete cohort of 5 patients. Statistically significant results are shown in bold PTV/organ at risk
DxVx
Composite plans Dx(Gy) Vx(%) Conventional
VMAT 20.5 ⫾ 0.2 18.5 ⫾ 0.7 96.7 ⫾ 2.7
p-Value
PTV
D2% D98% V95%
20.9 ⫾ 0.2 15.8 ⫾ 3.8 90.0 ⫾ 7.5
Lungs
Dmean V18 Gy V10 Gy V5 Gy
9.4 31.7 44.2 51.4
⫾ ⫾ ⫾ ⫾
3.7 21.7 19.8 19.0
9.4 13.1 41.3 72.1
⫾ ⫾ ⫾ ⫾
1.5 4.7 12.2 17.2
0.50 0.04 0.89 0.04
Heart
Dmean D30% V18 Gy V10 Gy
13.3 17.6 49.9 65.6
⫾ ⫾ ⫾ ⫾
4.5 3.4 31.3 25.4
11.0 15.2 27.9 52.6
⫾ ⫾ ⫾ ⫾
3.2 3.9 12.6 24.1
0.04 0.07 0.08 0.04
0.04 0.08 0.14
Y. K. Lee et al. / Medical Dosimetry 38 (2013) 372–375
Studies have shown the detrimental side effects associated with lung irradiation.7 With pediatric cases, the recommended threshold doses used in adults may be too high, and hence doses have been kept as low as possible in this case. Furthermore, organs such as the heart, which have large overlap with the PTV, have also been kept within clinically acceptable levels. In this treatment, there are regions, such as the arms, that have been irradiated that would not have been with a simpler technique. Reproducibility of arm position is important as the attenuation of the beams going through the arms can change with movement, and to increase setup accuracy an immobilization device has been utilized here and cone-beam CT has been used for patient-position verification. With VMAT, there is an increase in volumes receiving low dose due to the delivery of highly modulated dose through a rotational geometry, which could increase the risk of secondary malignancies. This study evaluates the use of VMAT for treatment of HL, but similar results are expected with intensity-modulated radiation therapy using static beam directions. A number of studies have shown that VMAT provides very similar dose distributions to intensity-modulated radiation therapy, but with significantly shorter delivery time.8 Thus, 7 beams spaced approximately evenly around the patient should give very similar dosimetric results to those presented here, although the beams would take considerably longer to deliver. An alternative is to use proton therapy. Hoppe et al.9 show that reduction in dose to OAR and healthy tissue is possible with proton therapy when compared with conventional and intensitymodulated radiotherapy. However, it is highlighted that in some instances, intensity-modulated radiotherapy achieves greater reductions than proton therapy in the OAR receiving high radiation doses. Furthermore, setup imaging and dose calculation of proton therapy may not be as accurate as they are in photon therapy.10 It should also be noted that proton therapy machines are not readily available and a solution is required to treat such patients in many centers.
Conclusions VMAT has allowed radiotherapy to be delivered according to protocol for this patient. Without VMAT, local control may have
375
been reduced. This study shows that VMAT is a valuable technique for treatment of large PTVs, such as in HL, giving high target coverage and low OAR dose and efficient delivery.
Acknowledgments The authors would like to thank Matthew James for his assistance with the verification and the Royal Marsden NHS Foundation Trust simulation and radiotherapy staff for the treatment of the patient. We are grateful to Elekta Ltd for their collaboration on VMAT and to Philips Medical Systems for their collaboration on adaptive radiotherapy. References 1. Eich, H.T.; Gossmann, A.; Engert, A.; et al. German Hodgkin Study Group A Contribution to solve the problem of the need for consolidative radiotherapy after intensive chemotherapy in advanced stages of Hodgkin's lymphoma— Analysis of a quality control program initiated by the radiotherapy reference center of the German Hodgkin Study Group (GHSG). Int. J. Radiat. Oncol. Biol. Phys. 69:1187–92; 2007. 2. Capra, M.; Hewitt, M.; Radford, M.; et al. Children's Cancer and Leukaemia Group. Long-term outcome in children with Hodgkin's lymphoma: The United Kingdom Children's Cancer Study Group HD82 trial. Eur. J. Cancer 43:1171–9; 2007. 3. EuroNet-Paediatric Hodgkin's Lymphoma Group (EuroNet-PHL-C1): First international inter-group study for classical Hodgkin's lymphoma in children and adolescents. ClinicalTrials.gov, A service of the U.S. National Institutes of Health. Available at: http://clinicaltrials.gov/ct2/show/NCT00433459?term=euro net-phl-c1&rank=1. Published February 8, 2007. Accessed December 6, 2011. 4. Otto, K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med. Phys. 35:310–7; 2008. 5. Bedford, J.L.; Warrington, A.P. Commissioning of volumetric modulated arc therapy (VMAT). Int. J. Radiat. Oncol. Biol. Phys. 73:537–45; 2009. 6. Low, D.A.; Harms, W.B.; Mutic, S.; et al. A technique for the quantitative evaluation of dose distributions. Med. Phys. 25:656–61; 1998. 7. Schoenfeld, J.D.; Mauch, P.M.; Das, P.; et al. Lung malignancies after Hodgkin lymphoma: Disease characteristics, detection methods and clinical outcome. Ann. Oncol. 23:1813–8; 2012. 8. Teoh, M.; Clark, C.H.; Wood, K.; et al. Volumetric modulated arc therapy: A review of current literature and clinical use in practice. Br. J. Radiol. 84:967–96; 2011. 9. Hoppe, B.S.; Flampouri, S.; Su, Z.; et al. Consolidative involved-node proton therapy for Stage IA-IIIB mediastinal Hodgkin lymphoma: Preliminary dosimetric outcomes from a Phase II study. Int. J. Radiat. Oncol. Biol. Phys. 83:260–7; 2012. 10. Hodgson, D.C.; Dong, L. Proton therapy for Hodgkin lymphoma: Does a case report make the case? Leuk Lymphoma 51:1397–8; 2010.
Medical Dosimetry journal homepage: www.meddos.org
Use of volumetric-modulated arc therapy for treatment of Hodgkin lymphoma Young K. Lee, Ph.D.,* James L. Bedford, Ph.D.,* Mary Taj, M.D.,† and Frank H. Saran, M.D., F.R.C.R.‡ *Joint Department of Physics, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK; †Paediatric Oncology, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK; and ‡ Radiotherapy Department, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 July 2012 Accepted 8 April 2013
To evaluate volumetric-modulated arc therapy (VMAT) for treatment of Hodgkin lymphoma (HL) in patients where conventional radiotherapy was not deliverable. A planning computed tomography (CT) scan was acquired for a twelve-year-old boy with Stage IIIB nodular sclerosing HL postchemotherapy with positive positron emission tomography scan. VMAT was used for Phase 1 (19.8 Gy in 11 fractions) and Phase 2 (10.8 Gy in 6 fractions) treatment plans. Single anticlockwise arc plans were constructed using SmartArc (Philips Radiation Oncology Systems, Fitchburg, WI) with control points spaced at 41. The inverse-planning objectives were to uniformly irradiate the planning target volume (PTV) with the prescription dose while keeping the volume of lung receiving greater than 20 Gy (V20 Gy) to less than 30% and minimize the dose to the other adjacent organs at risk (OAR). Pretreatment verification was conducted and the treatment delivery was on an MLCi Synergy linear accelerator (Elekta Ltd, Crawley, UK). The planning results were retrospectively confirmed in a further 4 patients using a single PTV with a prescribed dose of 19.8 Gy in 11 fractions. Acceptable dose coverage and homogeneity were achieved for both Phase 1 and 2 plans while keeping the lung V20 Gy at 22.5% for the composite plan. The beam-on times for Phase 1 and Phase 2 plans were 109 and 200 seconds, respectively, and the total monitor units were 337.2 MU and 292.5 MU, respectively. The percentage of measured dose points within 3% and 3 mm for Phase 1 and Phase 2 were 92% and 98%, respectively. Both plans were delivered successfully. The retrospective planning study showed that VMAT improved PTV dose uniformity and reduced the irradiated volume of heart and lung, although the volume of lung irradiated to low doses increased. Twophased VMAT offers an attractive option for large volume sites, such as HL, giving a high level of target coverage and significant OAR sparing together with efficient delivery. & 2013 American Association of Medical Dosimetrists.
Keywords: Dynamic arc therapy Hodgkin lymphoma Radiotherapy VMAT Volumetric-modulated arc therapy
Introduction Radiotherapy is part of a standard course of treatment for many patients with Hodgkin lymphoma (HL). For supradiaphragmatic disease, the thoracic organs are irradiated to the prescription dose with conventional modified mantle fields that are often used. When a higher dose is required for a sclerosing mass, the prescription dose is limited by the organs at risk (OAR) that are in the radiotherapy fields.1,2 We investigate the use of volumetricmodulated arc therapy (VMAT) in large volumes, such as HL, where the OAR doses cannot be met using conventional methods. Methods and Materials A twelve-year-old boy with Stage IIIB nodular sclerosing HL had presented with a positive positron emission tomography scan after 2 courses of chemotherapy to
Reprint requests to: Young K. Lee, Ph.D., Joint Department of Physics, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel.: þ44 (0)208 661 3474; fax: þ44(0)208 643 3812. E-mails: [email protected], [email protected]
be treated according to EuroNET-PHL-C1 trial.3 The initial Phase 1 (Ph1) conventional plan consisted of anterior-posterior fields defined by virtual simulation, i.e., with no delineated volumes, and a prescription dose of 19.8 Gy in 11 fractions delivered 5 fractions/wk. The treatment region included all sites of involved disease at diagnosis and multileaf collimators were used to shield noninvolved regions. The residual nodular bulky mediastinal mass was localized to produce a conformal Phase 2 (Ph2) plan with prescription of 10.8 Gy in 6 fractions with the beams arranged anteriorly to minimize the lung dose as much as possible. However, the composite plan showed the treatment was unacceptable as the lung receiving greater than 20 Gy (V20 Gy) exceeded 70% (Table 1). VMAT4,5 was then planned for Ph1 using the same prescription regime. A new computed tomography (CT) scan was acquired from eyes to the pelvis in contiguous 2-mm thickness slices on a Philips Brilliance largebore CT simulator (Philips Medical Systems, Cleveland, OH). The patient was in a supine position with the head and shoulders immobilized in a thermoplastic shell while holding handles that were attached to ropes connected to a foot plate. Contrast was used to aid the volume delineating process. The spleen, hilum lymph node, involved left neck nodes, and the postchemotherapy residual mediastinal mass were localized as the clinical target volumes (CTVs). The Ph1 planning target volume (PTV) included all CTVs with a uniform 1-cm margin except the neck nodal volume where a 0.3-cm margin was used (1820.0 cm3). The Ph2 PTV was the mediastinal CTV with a uniform 1-cm margin (828.0 cm3). The lungs, heart, thyroid, liver, and left and right kidneys were also delineated. The density in the delineated organs that were affected by the contrast was overridden.
0958-3947/$ – see front matter Copyright Ó 2013 American Association of Medical Dosimetrists http://dx.doi.org/10.1016/j.meddos.2013.04.004
Y. K. Lee et al. / Medical Dosimetry 38 (2013) 372–375 The primary objective of the VMAT plans was to deliver an adequate dose to the PTV while keeping the lung V20 Gy less than 30%. The secondary objective was to meet the currently accepted dose-volume restrictions in the OAR. The 6-MV VMAT plans were inversely planned using Pinnacle SmartArc v9.0 (Philips Healthcare, Fitchburg, WI). For Ph1, a single arc from gantry angle of 1711 to 1811 (according to the International Electrotechnical Commission 61217) around the isocenter with a collimator rotation of 21 to minimize planes of interleaf leakage was used. The control point spacing was 41 and the leaf motion was constrained to 0.46 cm/deg. Τhe plan was initially optimized with high weightings for PTV coverage and homogeneity, and low weightings for OAR objectives. An annulus was used to conform high dose to the PTV. The weights to the OAR and annulus objectives were increased on subsequent optimizations and priority was given to the lung objectives. The plan was seen to have reached optimality when the dose to the lung could not be improved further without a large reduction in PTV coverage. The Ph1 OAR dose-volume histograms (DVH) were used to estimate an acceptable OAR DVH for Ph2. For Ph2, a single arc from gantry angle of 1791 to 1811 around the same isocenter with a collimator rotation of 21 was used. A similar inverseplanning strategy to that used for Ph1 was used to plan Ph2 VMAT but only using the involved OAR objectives as the Ph2 PTV was contained in the mediastinal region. The plans were verified using Delta4 (ScandiDos, Uppsala, Sweden), and greater than 90% gamma agreement between the dose calculated by Pinnacle3 and the dose measured by the phantom for 3%-dose and 3-mm distance was deemed clinically acceptable. All measurement points receiving more than 20% of the dose were included in the gamma analysis. The patient was treated on MLCi Synergy digital linear accelerator (Elekta Ltd, Crawley, UK) and cone-beam CT images were used for patient setup verification. To confirm the observations in this patient, a further 4 patients were retrospectively studied, creating a cohort of 5 patients. A single phase of treatment was considered, with a prescribed dose of 19.8 Gy in 11 fractions. The planning technique was as described previously. The mean statistics for PTV, lung, and heart were evaluated and statistical significance was assessed using a two-tailed Wilcoxon signed rank test.
373
Fig. 1. Homogeneous dose coverage of PTV was achieved in both conventional and VMAT plans. A clinically acceptable coverage of the PTVs was also achieved (Fig. 2a). Coverage of the Ph2 PTV was lower than the 95% dose normally achieved, but as the PTV overlapped with the low-density lung, where coverage was expected to be difficult, this was accepted. The lung V20 Gy and mean dose were well within the acceptable levels for VMAT. These levels were not achievable with conventional planning methods (see Table 1 and lung DVH in Fig. 2b). Note, however, that the lung V5 Gy is higher with VMAT owing to the spreading of the dose with this technique. Clinically acceptable dose levels were met for the heart even with greater than 17%
105% 100% 95% comp 90% 105% 100% 95% 90%
Ph1
Results Dose-volume statistics for composite conventional and VMAT plans are shown in Table 1 and the dose distribution can be seen in Table 1 Dose-volume statistics on organs at risk for the composite conventional and VMAT plans. The overlap between named organs and Ph1 PTV are also shown Organ at risk (% Ph1 PTV overlap)
DxVx
Composite plans Dx(Gy) Vx(%) Conventional
Clinically acceptable level VMAT
105% 100% 95% comp 90%
Ph1 PTV (Ph1 plan)
D2% D98% V95%
21.0 9.7 91.6
20.7 17.4 92.5
Ph2 PTV
D2% D98% V95%
32.0 29.0 98.0
31.8 26.2 89.8
Lungs (15.6%)
Dmean V20 Gy V10 Gy V5 Gy
21.6 72.5 82.7 93.5
15.6 22.5 80.8 99.3
o 18 Gy o 30% – –
Heart (17.2%)
Dmean D30% D33% D50% V20 Gy V10 Gy
27.2 29.9 29.8 29.1 99.6 100
23.5 29.1 28.8 25.3 68.9 95.4
– o 40 Gy o 30 Gy o 25 Gy – –
Thyroid (39.8%)
Dmean
21.4
17.6
o 30 Gy
Ipsilateral kidney*
Dmean D50%
14.0 19.2
16.1 17.3
– o 20 Gy
Contralateral kidney*
Dmean D50%
2.1 1.6
3.7 3.3
– o 20 Gy
Kidneys* (8.4%)
Dmean
8.0
9.8
o 18 Gy
Liver* (0.5%)
Dmean V20 Gy V10 Gy
7.8 11.6 33.7
8.1 0 31.8
o 25 Gy – –
105% 100% 95% 90%
n Indicates organs that were fully shielded while compromising the PTV in conventional planning owing to the simple planning methods.
Ph1
Fig. 1. Sagittal (left) and coronal (right) slices with vertical lines indicating the corresponding planes from conventional (top) and VMAT (bottom) plans. Ph1 PTV is in pink and Ph2 PTV is in purple. The yellow ruler on the right indicates a centimeter scale. The isodose lines are indicated in the legend. (Color version of the figure is available online.)
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Y. K. Lee et al. / Medical Dosimetry 38 (2013) 372–375
Fig. 2. (a) Phase 1 PTV and Phase 2 PTV composite dose-volume histograms from VMAT (solid) and conventional (dashed) plans. (b) The lung, heart, and thyroid composite dose-volume histograms from VMAT (solid) and conventional (dashed) plans. (Color version of the figure is available online.)
overlap to the PTV and were lower than what were achievable with conventional plans (see Table 1 and heart DVH in Fig. 2). The thyroid mean dose was well within 30 Gy, which is the level associated with increased risk of abnormal activity. The involved regions near the kidneys that would have been fully shielded with conventional plans were treated with VMAT while maintaining acceptable dose levels for the kidneys (Table 1 and Fig. 1). The planning system–estimated beam-on times for Ph1 and Ph2 plans were 109 and 200 seconds, respectively, and the total number of monitor units were 337.2 MU and 292.5 MU, respectively, which were relatively efficient for delivering 1.8 Gy/fraction to such large treatment volumes. The percentage of measured points with a Gamma Index o 1 with 3% dose difference and 3mm distance to agreement6 for Ph1 and Ph2 were 92% and 98%, respectively. However, the measured dose was 5% to 7% lower than planned dose in regions below the diaphragm for Ph1. An ionization chamber measurement in the region concerned confirmed that the dose was 4.8% low. This was discussed and was considered clinically acceptable as the planned dose in this region was 4 100% of the prescription dose. For Ph2 verification, measured dose was 4% lower than planned dose in small sections of the PTV. Again this was in a high-dose region and was deemed clinically acceptable. The treatment was delivered without problems. The mean results for the complete cohort of 5 patients (Table 2) showed that the PTV dose uniformity was improved slightly with VMAT compared with the conventional treatment, with statistically significant reduction in D2%. The lung V18 Gy was reduced significantly with VMAT, although lung V5 Gy was increased. This indicated that overall, it was likely that the lung would be spared beneficially for patients treated to higher prescribed doses. Heart was also spared significantly using VMAT.
Discussion With low-grade HL, as well as solid tumors, there is evidence for minimizing the use of adjuvant radiotherapy owing to radiation-associated complications. However, in this case, a large mass is present with an incomplete positron emission tomography response after 2 cycles of chemotherapy for which more than the standard 19.8 Gy in 11 fractions is required. A conventional plan cannot deliver adequate dose to the diseased volumes while meeting the OAR constraints. A simultaneous boost technique is not employed here as there are no data to support change in prescription.
Table 2 Mean ⫾ 1 SD dose-volume statistics for the conventional and VMAT plans in the complete cohort of 5 patients. Statistically significant results are shown in bold PTV/organ at risk
DxVx
Composite plans Dx(Gy) Vx(%) Conventional
VMAT 20.5 ⫾ 0.2 18.5 ⫾ 0.7 96.7 ⫾ 2.7
p-Value
PTV
D2% D98% V95%
20.9 ⫾ 0.2 15.8 ⫾ 3.8 90.0 ⫾ 7.5
Lungs
Dmean V18 Gy V10 Gy V5 Gy
9.4 31.7 44.2 51.4
⫾ ⫾ ⫾ ⫾
3.7 21.7 19.8 19.0
9.4 13.1 41.3 72.1
⫾ ⫾ ⫾ ⫾
1.5 4.7 12.2 17.2
0.50 0.04 0.89 0.04
Heart
Dmean D30% V18 Gy V10 Gy
13.3 17.6 49.9 65.6
⫾ ⫾ ⫾ ⫾
4.5 3.4 31.3 25.4
11.0 15.2 27.9 52.6
⫾ ⫾ ⫾ ⫾
3.2 3.9 12.6 24.1
0.04 0.07 0.08 0.04
0.04 0.08 0.14
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Studies have shown the detrimental side effects associated with lung irradiation.7 With pediatric cases, the recommended threshold doses used in adults may be too high, and hence doses have been kept as low as possible in this case. Furthermore, organs such as the heart, which have large overlap with the PTV, have also been kept within clinically acceptable levels. In this treatment, there are regions, such as the arms, that have been irradiated that would not have been with a simpler technique. Reproducibility of arm position is important as the attenuation of the beams going through the arms can change with movement, and to increase setup accuracy an immobilization device has been utilized here and cone-beam CT has been used for patient-position verification. With VMAT, there is an increase in volumes receiving low dose due to the delivery of highly modulated dose through a rotational geometry, which could increase the risk of secondary malignancies. This study evaluates the use of VMAT for treatment of HL, but similar results are expected with intensity-modulated radiation therapy using static beam directions. A number of studies have shown that VMAT provides very similar dose distributions to intensity-modulated radiation therapy, but with significantly shorter delivery time.8 Thus, 7 beams spaced approximately evenly around the patient should give very similar dosimetric results to those presented here, although the beams would take considerably longer to deliver. An alternative is to use proton therapy. Hoppe et al.9 show that reduction in dose to OAR and healthy tissue is possible with proton therapy when compared with conventional and intensitymodulated radiotherapy. However, it is highlighted that in some instances, intensity-modulated radiotherapy achieves greater reductions than proton therapy in the OAR receiving high radiation doses. Furthermore, setup imaging and dose calculation of proton therapy may not be as accurate as they are in photon therapy.10 It should also be noted that proton therapy machines are not readily available and a solution is required to treat such patients in many centers.
Conclusions VMAT has allowed radiotherapy to be delivered according to protocol for this patient. Without VMAT, local control may have
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been reduced. This study shows that VMAT is a valuable technique for treatment of large PTVs, such as in HL, giving high target coverage and low OAR dose and efficient delivery.
Acknowledgments The authors would like to thank Matthew James for his assistance with the verification and the Royal Marsden NHS Foundation Trust simulation and radiotherapy staff for the treatment of the patient. We are grateful to Elekta Ltd for their collaboration on VMAT and to Philips Medical Systems for their collaboration on adaptive radiotherapy. References 1. Eich, H.T.; Gossmann, A.; Engert, A.; et al. German Hodgkin Study Group A Contribution to solve the problem of the need for consolidative radiotherapy after intensive chemotherapy in advanced stages of Hodgkin's lymphoma— Analysis of a quality control program initiated by the radiotherapy reference center of the German Hodgkin Study Group (GHSG). Int. J. Radiat. Oncol. Biol. Phys. 69:1187–92; 2007. 2. Capra, M.; Hewitt, M.; Radford, M.; et al. Children's Cancer and Leukaemia Group. Long-term outcome in children with Hodgkin's lymphoma: The United Kingdom Children's Cancer Study Group HD82 trial. Eur. J. Cancer 43:1171–9; 2007. 3. EuroNet-Paediatric Hodgkin's Lymphoma Group (EuroNet-PHL-C1): First international inter-group study for classical Hodgkin's lymphoma in children and adolescents. ClinicalTrials.gov, A service of the U.S. National Institutes of Health. Available at: http://clinicaltrials.gov/ct2/show/NCT00433459?term=euro net-phl-c1&rank=1. Published February 8, 2007. Accessed December 6, 2011. 4. Otto, K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med. Phys. 35:310–7; 2008. 5. Bedford, J.L.; Warrington, A.P. Commissioning of volumetric modulated arc therapy (VMAT). Int. J. Radiat. Oncol. Biol. Phys. 73:537–45; 2009. 6. Low, D.A.; Harms, W.B.; Mutic, S.; et al. A technique for the quantitative evaluation of dose distributions. Med. Phys. 25:656–61; 1998. 7. Schoenfeld, J.D.; Mauch, P.M.; Das, P.; et al. Lung malignancies after Hodgkin lymphoma: Disease characteristics, detection methods and clinical outcome. Ann. Oncol. 23:1813–8; 2012. 8. Teoh, M.; Clark, C.H.; Wood, K.; et al. Volumetric modulated arc therapy: A review of current literature and clinical use in practice. Br. J. Radiol. 84:967–96; 2011. 9. Hoppe, B.S.; Flampouri, S.; Su, Z.; et al. Consolidative involved-node proton therapy for Stage IA-IIIB mediastinal Hodgkin lymphoma: Preliminary dosimetric outcomes from a Phase II study. Int. J. Radiat. Oncol. Biol. Phys. 83:260–7; 2012. 10. Hodgson, D.C.; Dong, L. Proton therapy for Hodgkin lymphoma: Does a case report make the case? Leuk Lymphoma 51:1397–8; 2010.