Abstract
Purpose
The purpose of our study was to show the feasibility and potential benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model.
Methods
Twenty-one prostate cancer patients (70 years average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations.
Results
Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2 ± 0.5%) for an integrated boost with 75.6 Gy, (98.1 ± 0.3%) for an integrated boost with 80 Gy, (94.7 ± 0.8%) for treatment of PET-positive volume with 75 Gy, and to (99.4 ± 0.1%) for treating PET-positive volume with 95 Gy (all p < 0.0001). For the integrated boost with 80 Gy, a significant increase of the median NTCP of the rectum was found, for all other plans no statistical significant increase in the NTCP neither of the rectum nor the bladder was found.
Conclusions
Our study demonstrates that the use of 68Ga-PSMA-PET/CT image information allows for more individualized prostate treatment planning. TCP values of identified active tumor volumes were increased, while rectum and bladder NTCP values either remained the same or were even lower. However, further studies need to clarify the clinical benefit for the patients applying these techniques.
Similar content being viewed by others
References
Lei JH, Liu LR, Wei Q, Yan SB, Song TR, Lin FS, et al. Systematic review and meta-analysis of the survival outcomes of first-line treatment options in high-risk prostate cancer. Sci Rep. 2014;5:7713.
Ohri N, Dicker AP, Showalter TN. Late toxicity rates following definitive radiotherapy for prostate cancer. Can J Urol. 2012;19:6373–80.
Viani GA, Stefano EJ, Afonso SL. Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys. 2009;74:1405–18.
Bentzen SM, Gregoire V. Molecular imaging-based dose painting: a novel paradigm for radiation therapy prescription. Semin Radiat Oncol. 2011;21:101–10.
van Lin EN, Futterer JJ, Heijmink SW, van der Vight LP, Hoffmann AL, van Kollenburg P, et al. IMRT boost dose planning on dominant intraprostatic lesions: gold marker-based three-dimensional fusion of CT with dynamic contrast-enhanced and 1H-spectroscopic MRI. Int J Radiat Oncol Biol Phys. 2006;65:291–303.
Pinkawa M, Piroth MD, Holy R, Klotz J, Djukic V, Corral NE, et al. Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost. Radiat Oncol (London, England). 2012;7:14.
Chang JH, Lim Joon D, Lee ST, Gong SJ, Anderson NJ, Scott AM, et al. Intensity modulated radiation therapy dose painting for localized prostate cancer using (1)(1)C-choline positron emission tomography scans. Int J Radiat Oncol Biol Phys. 2012;83:e691–6.
Feng Y, Welsh D, McDonald K, Carruthers L, Cheng K, Montgomery D, et al. Identifying the dominant prostate cancer focal lesion using image analysis and planning of a simultaneous integrated stereotactic boost. Acta Oncol (Stockholm, Sweden). 2015;54:1543–50.
Bundschuh RA, Wendl CM, Weirich G, Eiber M, Souvatzoglou M, Treiber U, et al. Tumour volume delineation in prostate cancer assessed by [(11)C]choline PET/CT: validation with surgical specimens. Eur J Nucl Med Mol Imaging. 2013;40:824–31.
Wibmer AG, Burger IA, Sala E, Hricak H, Weber WA, Vargas HA. Molecular imaging of prostate cancer. Radiographics. 2016;36:142–59.
Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid (6)(8)Ga-PSMA Ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.
Maurer T, Beer AJ, Wester HJ, Kubler H, Schwaiger M, Eiber M. Positron emission tomography/magnetic resonance imaging with 68gallium-labeled ligand of prostate-specific membrane antigen: promising novel option in prostate cancer imaging? Int J Urol. 2014;21:1286–8.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic Efficacy of Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging in Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. J Urol. 2015.
Eiber M, Nekolla SG, Maurer T, Weirich G, Wester HJ, Schwaiger M. (68)Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer. Abdom Imaging. 2015;40:1769–71. https://doi.org/10.1007/s00261-014-0301-z.
Dewes S, Schiller K, Sauter K, Eiber M, Maurer T, Schwaiger M, et al. INtegration of (68)Ga-PSMA-PET imaging in planning of primary definitive radiotherapy in prostate cancer: a retrospective study. Radiat Oncol (London, England). 2016;11:73. https://doi.org/10.1186/s13014-016-0646-2.
Giesel FL, Sterzing F, Schlemmer HP, Holland-Letz T, Mier W, Rius M, et al. Intra-individual comparison of (68)Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:1400–6. https://doi.org/10.1007/s00259-016-3346-0.
Zamboglou C, Wieser G, Hennies S, Rempel I, Kirste S, Soschynski M, et al. MRI versus (6)(8)Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:889–97. https://doi.org/10.1007/s00259-015-3257-5.
Rahbar K, Weckesser M, Huss S, Semjonow A, Breyholz HJ, Schrader AJ, et al. Correlation of Intraprostatic tumor extent with Ga-68-PSMA distribution in patients with prostate cancer. J Nucl Med. 2016;57:563–7. https://doi.org/10.2967/jnumed.115.169243.
Zamboglou C, Schiller F, Fechter T, Drendel V, Mix M, Meyer PT, et al. A voxel-wise comparison of (68)ga-Hbed-CC-PSMA PET/CT versus histopathology in primary localized prostate cancer: implementations for radiation therapy treatment planning. Int J Radiat Oncol. 2016;96:E253–E4.
Zschaeck S, Wust P, Beck M, Wlodarczyk W, Kaul D, Rogasch J, et al. Intermediate-term outcome after PSMA-PET guided high-dose radiotherapy of recurrent high-risk prostate cancer patients. Radiat Oncol (London, England). 2017;12:140.
Gay HA, Niemierko A. A free program for calculating EUD-based NTCP and TCP in external beam radiotherapy. Phys Med. 2007;23:115–25. https://doi.org/10.1016/j.ejmp.2007.07.001.
Wu Q, Mohan R, Niemierko A, Schmidt-Ullrich R. Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose. Int J Radiat Oncol Biol Phys. 2002;52:224–35.
Ahmed HU, Pendse D, Illing R, Allen C, van der Meulen JH, Emberton M. Will focal therapy become a standard of care for men with localized prostate cancer? Nat Clin Pract. 2007;4:632–42.
Zamboglou C, Schiller F, Fechter T, Wieser G, Jilg CA, Chirindel A, et al. (68)Ga-HBED-CC-PSMA PET/CT versus histopathology in primary localized prostate cancer: a voxel-wise comparison. Theranostics. 2016;6:1619–28. https://doi.org/10.7150/thno.15344.
Nestle U, Schaefer-Schuler A, Kremp S, Groeschel A, Hellwig D, Rube C, et al. Target volume definition for 18F-FDG PET-positive lymph nodes in radiotherapy of patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2007;34:453–62.
Daisne JF, Duprez T, Weynand B, Lonneux M, Hamoir M, Reychler H, et al. Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen. Radiology. 2004;233:93–100.
Funding
This project was funded in part by the Deutsche Forschungsgemeinschaft (BU 3395/1–1).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
RB has a research contract with Mediso GmbH Germany. Mediso GmbH Germany provided the Mediso Interview Fusion Tool for image analysis within this project. RB and ME are members of the advisory board of Bayer Healthcare, Leverkusen, Germany. All other authors declare that they have no conflicts of interest.
Ethical approval
Due to the retrospective character of the study, ethical approval was waived by the institutional ethics committee.
Informed consent
All patients gave written informed consent about the performed procedures and the fact that all data may be used for retrospective scientific analyses.
Rights and permissions
About this article
Cite this article
Thomas, L., Kantz, S., Hung, A. et al. 68Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for intensity modulated radiation therapy treatment planning with integrated boost. Eur J Nucl Med Mol Imaging 45, 1170–1178 (2018). https://doi.org/10.1007/s00259-018-3954-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-018-3954-y