Dosimetric Improvements Utilising Intensity Modulated Radiation Therapy for Patients with Glioblastoma Multiforme

Abstract

Aims: The EORTC-NCI study investigating the addition of temozolomide trial to standard radiation therapy has demonstrated improved duration of survival in patients with Glioblastoma multiforme (GBM). With longer survival duration, there is the potential for latent RT morbidity, not previously seen in historical patients. This study evaluates the potential dosimetric advantages of utilising IMRT over 3D-conformal RT in such patients. Methods: 10 consecutive patients with GBM formally screened for a clinical study over a two-month period were planned and treated with IMRT utilising daily on-board imaging (OBI). The EORTC protocol dosimetric criteria and constraints were used in target delineation and planning. For each patient, a 3DCRT plan was also produced. Endpoints for dosimetric evaluation analysed related to tumour dose: mean PTV60 dose (mPTV60Dose), Conformity Index (CI); and normal tissue dose: mean normal brain dose (mBrainDose) and V40 Brain (Brainv40). IGRT endpoints were the median isocentre shifts required in 3 axes measured in one direction. The variation between the IMRT and 3DCRT dosimetric endpoints was examined using Wilcoxon analysis. Results: The 10 patients had tumours located in temporal (3), parietal (3), occipital (2) and callosal (2) regions. The median PTV and normal brain volumes were 308.1 cm3 and 1077.5 cm3 respectively. The IMRT dosimetry was significantly improved in all endpoints specifically CI (p = 0.002), mPTV60Dose (p = 0.004), mBrainDose (p = 0.002) and Brainv40 (p = 0.019). OBI directed isocentre measurements in the patient group were available for 230 treatments. The median shifts (and 95% C.I.s) were 0.1 cm vertical (0.1 - 0.2), 0.1 cm longitudinal (0.1 - 0.2) and 0.2 cm lateral (0.2 - 0.2). At a minimum follow-up of 2 years post diagnosis, the median survival of the group is 18.0 months (95% CI: 13.4 - 22.6 months). Conclusion: IMRT for GBM produces significant dosimetric advantages in relation to planning target volume and normal tissue dose compared with 3D conformal plans. The data also confirm the accuracy of IMRT technique for CNS with IGRT delivery utilising OBI demonstrating minimal deviation from planned to treated isocentre.

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M. Back, S. Clifford, H. Wheeler and T. Eade, "Dosimetric Improvements Utilising Intensity Modulated Radiation Therapy for Patients with Glioblastoma Multiforme," Journal of Cancer Therapy, Vol. 4 No. 11A, 2013, pp. 18-24. doi: 10.4236/jct.2013.411A003.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] R. Stupp, W. Mason, M. van den Bent, et al., “Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma,” New England Journal of Medicine, Vol. 352, No. 10, 2005, pp. 987-996. http://dx.doi.org/10.1056/NEJMoa043330
[2] R. Stupp, M. E. Hegi, W. P. Mason, et al., “Effects of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy Alone on Survival in Glioblastoma in a Randomised Phase III Study: 5-Year Analysis of the EORTC-NCIC Trial,” Lancet Oncology, Vol. 10, No. 5, 2009, pp. 459-466. http://dx.doi.org/10.1016/S1470-2045(09)70025-7
[3] P. Brown, M. Maurer, T. Rummans, et al., “A Prospective Study of Quality of Life in Adults with Newly Diagnosed High-Grade Gliomas: The Impact of the Extent of Resection on Quality of Life and Survival,” Neurosurgery, Vol. 57, No. 3, 2005, pp. 495-504. http://dx.doi.org/10.1227/01.NEU. 0000170562.25335.C7
[4] S. L. Wolden, W. C. Chen, D. G. Pfister, et al., “IntensityModulated Radiation Therapy (IMRT) for Nasopharynx Cancer: Update of the Memorial Sloan-Kettering Experience,” International Journal of Radiation Oncology Biology Physics, Vol. 64, No. 1, 2006, pp. 57-62. http://dx.doi.org/10.1016/ j.ijrobp.2005.03.057
[5] A. Pollack, A. Hanlon, E. M. Horwitz, et al., “Radiation Therapy Dose Escalation for Prostate Cancer: A Rationale for IMRT,” World Journal of Urology, Vol. 21, No. 4, 2003, pp. 200-208. http://dx.doi.org/10. 1007/s00345-003-0356-x
[6] M. Back, T. Eade, M. Kastelan, et al., “Progress in Multidisciplinary Management of Glioblastoma Multiforme Translating to Improvement in Median Survival,” APJCO, Vol. 7, No. S4, 2011, p. 112.
[7] M. Klein, J. J. Heimans, N. K. Aaronson, et al., “Effect of Radiotherapy and Other Treatment-Related Factors on Mid-Term to Long-Term Cognitive Sequelae in LowGrade Gliomas: A Comparative Study,” Lancet, Vol. 360, No. 9343, 2002, pp. 1361-1268. http://dx.doi.org/10.1016/S0140-6736(02)11398-5
[8] R. Henriksson, A. Bottomley, W. Mason, et al., “Progression-Free Survival (PFS) and Health-Related Quality of Life (HRQoL) in AVAglio, a Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma (GBM),” Journal of Clinical Oncology, Vol. 31, 2013.
[9] R. Stupp, M. E. Hegi, B. Neyns, et al., “Phase I/IIa Study of Cilengitide and Temozolomide with Concomitant Radiotherapy Followed by Cilengitide and Temozolomide Maintenance Therapy in Patients with Newly Diagnosed Glioblastoma,” Journal of Clinical Oncology, Vol. 28, No. 16, 2010, pp. 2712-2718. http://dx.doi.org/10.1200/JCO.2009.26.6650
[10] M. Gilbert, J. Dignam, M. Won, et al., “RTOG 0825: Phase III Double-Blind Placebo-Controlled Trial Evaluating Bevacizumab in Patients with Newly Diagnosed Glioblastoma,” Journal of Clinical Oncology, Vol. 31, 2013.
[11] D. Amelio, S. Lorentini, M. Schwartz and M. Amichetti, “Intensity-Modulated Radiation Therapy in Newly Diagnosed Glioblastoma. A Systematic Review on Clinical and Technical Issues,” Radiotherapy Oncology, Vol. 97, No. 3, 2010, pp. 361-369. http://dx.doi.org/10.1016/j.radonc.2010.08.018
[12] R. Cardinale, M. Won, A. Choucair, et al., “A Phase II Trial of Accelerated Radiotherapy Using Weekly Stereotactic Conformal Boost for Supratentorial Glioblastoma Multiforme: RTOG 0023,” International Journal of Radiation Oncology Biology Physics, Vol. 65, No. 5, 2006, pp. 1422-1428.
http://dx.doi.org/10.1016/j.ijrobp.2006.02.042
[13] L. Souhami, W. Seiferheld, D. Brachman, et al., “Randomized Comparison of Stereotactic Radiosurgery Followed by Conventional Radiotherapy with Carmustine to Conventional Radiotherapy with Carmustine for Patients with Glioblastoma Multiforme: Report of Radiation Therapy Oncology Group 93-05 Protocol,” International Journal of Radiation Oncology Biology Physics, Vol. 60, No. 3, 2004, pp. 853-860. http://dx.doi.org/10.1016/j.ijrobp.2004.04.011
[14] N. J. Laperriere, P. M. Leung, S. McKenzie, et al., “Randomized Study of Brachytherapy in the Initial Management of Patients with Malignant Astrocytoma,” International Journal of Radiation Oncology Biology Physics, Vol. 41, No. 5, 1998, pp. 1005-1011. http://dx.doi.org/10.1016/S0360-3016 (98)00159-X
[15] M. D. Piroth, M. Pinkawa, R. Holy, et al., “Integrated Boost IMRT with FET-PET-Adapted Local Dose Escalation in Glioblastomas. Results of a Prospective Phase II Study,” Strahlentherapy Onkology, Vol. 188, No. 4, 2012, pp. 334-339. http://dx.doi.org/10.1007/s00066-011-0060-5
[16] M. Massaccesi, M. Ferro, S. Cilla, et al., “Accelerated Intensity-Modulated Radiotherapy plus Temozolomide in Patients with Glioblastoma: A Phase I Dose-Escalation Study (ISIDE-BT1),” International Journal of Clinical Oncology, 2012.
[17] K. Reddy, D. Damek, L. E. Gaspar, et al., “Phase II Trial of Hypofractionated IMRT with Temozolomide for Patients with Newly Diagnosed Glioblastoma Multiforme,” International Journal of Radiation Oncology Biology Physics, Vol. 84, No. 3, 2012, pp. 655-660. http://dx.doi.org/10.1016/j.ijrobp. 2012.01.035
[18] M. Matsuo, K. Miwa, O. Tanaka, et al., “Impact of [11C]Methionine Positron Emission Tomography for Target Definition of Glioblastoma Multiforme in Radiation Therapy Planning,” International Journal of Radiation Oncology Biology Physics, Vol. 82, No. 1, 2012, pp. 83-89. http://dx.doi.org/10.1016/j. ijrobp.2010.09.020

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