Dosimetric Evaluation of PSMA PET-Delineated Dominant Intraprostatic Lesion Simultaneous Infield Boosts

Christopher D Goodman, Hatim Fakir, Stephen Pautler, Joseph Chin, Glenn S Bauman, Christopher D Goodman, Hatim Fakir, Stephen Pautler, Joseph Chin, Glenn S Bauman

Abstract

Purpose: Prostate cancer is multifocal. However, there often exists a single dominant focus in the gland responsible for driving the biology of the disease. Dose escalation to the dominant lesion is a proposed strategy to increase tumor control. We applied radiobiological modeling to evaluate the dosimetric feasibility and benefit of dominant intraprostatic lesion simultaneous in-field boosts (DIL-SIB) to the gross tumor volume (GTV), defined using a novel molecular positron emission tomography (PET) probe (18F-DCFPyL) directed against prostate specific membrane antigen (PSMA).

Methods and materials: Patients with clinically localized, biopsy-proven prostate cancer underwent preoperative [18F]-DCFPyL PET/computed tomography (CT). DIL-SIB plans were generated by importing the PET/CT into the RayStation treatment planning system. GTV-PET for the DIL-SIB was defined by the highest %SUVmax (percentage of maximum standardized uptake value) that generated a biologically plausible volume. Volumetric arc-based plans incorporating prostate plus DIL-SIB treatment were generated. Tumor control probability (TCP) and normal tissue complication probability (NTCP) with fractionation schemes and boost doses specified in the FLAME (Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer; NCT01168479), PROFIT (Prostate Fractionated Irradiation Trial; NCT00304759), PACE (Prostate Advances in Comparative Evidence; NCT01584258), and hypoFLAME (Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0; NCT02853110) protocols were compared.

Results: Comparative DIL-SIB plans for 6 men were generated from preoperative [18F]-DCFPyL PET/CT. Median boost GTV volume was 1.015 cm3 (0.42-1.83 cm3). Median minimum (D99%) DIL-SIB dose for F35BS, F20BS, F5BS, and F5BSH were 97.3 Gy, 80.8 Gy, 46.5 Gy, and 51.5Gy. TCP within the GTV ranged from 84% to 88% for the standard plan and 95% to 96% for the DIL-SIB plans. Within the rest of the prostate, TCP ranged from 89% to 91% for the standard plans and 90% to 92% for the DIL-SIB plans. NTCP for the rectum NTCP was similar for the DIL-SIB plans (0.3%-2.7%) compared with standard plans (0.7%-2.6%). Overall, DIL-SIB plans yielded higher uncomplicated TCP (NTCP, 90%-94%) versus standard plans (NTCP, 83%-85%).

Conclusions: PSMA PET provides a novel approach to define GTV for SIB-DIL dose escalation. Work is ongoing to validate PSMA PET-delineated GTV through correlation to coregistered postprostatectomy digitized histopathology.

© 2019 The Author(s).

Figures

Figure 1
Figure 1
Dose distributions (sagittal projections) and corresponding DVHs for different fractionations for patient 4. The first and second rows represent standard and DIL boost plans, respectively. The third row contains comparative DVHs for the CTV, GTV, rectum, and bladder. The DVH for the 5 fractions regimen (F5BS) includes the higher dose Hypo-FLAME (F5BSH) plan results as well (dotted lines). Abbreviations: CTV = clinical target volume; DIL = dominant intraprostatic lesion; DVH = dose-volume histogram; GTV = gross tumor volume; Hypo-FLAME = Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0.
Figure 2
Figure 2
Average EQD2Gy dose-volume histogram of the GTV, PROS-GTV, rectum, and bladder for all fractionations. Abbreviations: GTV = gross tumor volume; PROS-GTV = prostate excluding GTV.
Figure 3
Figure 3
Tumor control probability (TCP) for the GTV and PROS-GTV, NTCP for bladder and rectum, and probability of uncomplicated tumor control (P+) relative to rectal toxicity. Abbreviations: GTV = gross tumor volume; PROS-GTV = prostate excluding GTV.

References

    1. Cooper C.S., Eeles R., Wedge D.C. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue. Nat Genet. 2015;47:367–372.
    1. Viani G.A., Stefano E.J., Afonso S.L. Higher-than-conventional radiation doses in localized prostate cancer treatment: A meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys. 2009;74:1405–1418.
    1. Spratt D.E., Zumsteg Z.S., Ghadjar P. Comparison of high-dose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate-risk prostate cancer. BJU Int. 2014;114:360–367.
    1. Cellini N., Morganti A.G., Mattiucci G.C. Analysis of intraprostatic failures in patients treated with hormonal therapy and radiotherapy: Implications for conformal therapy planning. Int J Radiat Oncol Biol Phys. 2002;53:595–599.
    1. Martinez A.A., Gonzalez J., Ye H. Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy. Int J Radiat Oncol Biol Phys. 2011;79:363–370.
    1. Mouraviev V., Villers A., Bostwick D.G. Understanding the pathological features of focality, grade and tumour volume of early-stage prostate cancer as a foundation for parenchyma-sparing prostate cancer therapies: Active surveillance and focal targeted therapy. BJU Int. 2011;108:1074–1085.
    1. Pucar D., Hricak H., Shukla-Dave A. {A figure is presented} Clinically significant prostate cancer local recurrence after radiation therapy occurs at the site of primary tumor: Magnetic resonance imaging and step-section pathology evidence. Int J Radiat Oncol Biol Phys. 2007;69:62–69.
    1. Arrayeh E., Westphalen AC, Kurhanewicz J. Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys. 2012;82:e787–e793.
    1. Von Eyben F.E., Kiljunen T., Kangasmaki A. Radiotherapy boost for the dominant intraprostatic cancer lesion - a systematic review and meta-analysis. Clin Genitourin Cancer. 2016;14:189–197.
    1. Haffner M.C., Mosbruger T., Esopi D.M. Tracking the clonal origin of lethal prostate cancer. J Clin Invest. 2013;123:4918–4922.
    1. Zamboglou C., Klein C.M., Thomann B. The dose distribution in dominant intraprostatic tumour lesions defined by multiparametric MRI and PSMA PET/CT correlates with the outcome in patients treated with primary radiation therapy for prostate cancer. Radiat Oncol. 2018;13:1–8.
    1. Bauman G., Haider M., Van Der Heide U.A. Boosting imaging defined dominant prostatic tumors: A systematic review. Radiother Oncol. 2013;107:274–281.
    1. Bauman G, Martin P, Thiessen JD. [18F]-DCFPyL positron emission tomography/magnetic resonance imaging for localization of dominant intraprostatic foci: First experience. Eur Urol Focus. 2016;4:5–9.
    1. Rhee H., Thomas P., Shepherd B. Prostate specific membrane antigen positron emission tomography may improve the diagnostic accuracy of multiparametric magnetic resonance imaging in localized prostate cancer. J Urol. 2016;196:1261–1267.
    1. Eiber M., Weirich G., Holzapfel K. Simultaneous 68Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70:829–836.
    1. Zamboglou C., Drendel V., Jilg C.A. Comparison of 68Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology. Theranostics. 2017;7:228–237.
    1. Parliament M., Winter K., Seider M. Effect of standard vs dose-escalated radiation therapy for patients with intermediate-risk prostate cancer. JAMA Oncol. 2018;4:e180039.
    1. Oehler C., Lang S., Dimmerling P. PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers. Radiat Oncol. 2014;9:229.
    1. Lips I.M., van der Heide U.A., Haustermans K. Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): Study protocol for a randomized controlled trial. Trials. 2011;12:255.
    1. Catton C.N., Lukka H., Gu C.-S. Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer. J Clin Oncol. 2017;35:1884–1890.
    1. Morrison K, Tree A, Khoo V. The PACE trial: International randomised study of laparoscopic prostatectomy vs. stereotactic body radiotherapy (SBRT) and standard radiotherapy vs. SBRT for early stage organ-confined prostate cancer. J Clin Oncol. 2018;36(6_suppl):TPS153.
    1. Mouraviev V., Madden J.F., Broadwater G. Use of 111In-capromab pendetide immunoscintigraphy to image localized prostate cancer foci within the prostate gland. J Urol. 2009;182:938–948.
    1. Barentsz J.O., Richenberg J., Clements R. ESUR prostate MR guidelines 2012. Eur Radiol. 2012;22:746–757.
    1. Chan J., Syndikus I., Mahmood S. Is choline PET useful for identifying intraprostatic tumour lesions? A literature review. Nucl Med Commun. 2015;36:871–880.
    1. Piert M, Shankar PR, Montgomery J. Accuracy of tumor segmentation from multi-parametric prostate MRI and 18F-choline PET/CT for focal prostate cancer therapy applications. EJNMMI Res. 2018;8:1–14.
    1. Koerber S.A., Utzinger M.T., Kratochwil C. 68Ga-PSMA11-PET/CT in newly diagnosed carcinoma of the prostate: correlation of intraprostatic PSMA uptake with several clinical parameters. J Nucl Med. 2017;58:1943–1948.
    1. Kuang Y., Wu L., Hirata E. Volumetric modulated arc therapy planning for primary prostate cancer with selective intraprostatic boost determined by18f-choline pet/ct. Int J Radiat Oncol Biol Phys. 2015;91:1017–1025.
    1. Zamboglou C., Sachpazidis I., Koubar K. Evaluation of intensity modulated radiation therapy dose painting for localized prostate cancer using68Ga-HBED-CC PSMA-PET/CT: A planning study based on histopathology reference. Radiother Oncol. 2017;123:472–477.
    1. Gibson E., Bauman G.S., Romagnoli C. Toward prostate cancer contouring guidelines on magnetic resonance imaging: Dominant lesion gross and clinical target volume coverage via accurate histology fusion. Int J Radiat Oncol Biol Phys. 2016;96:188–196.
    1. Clemente S., Nigro R., Oliviero C. Role of the technical aspects of hypofractionated radiation therapy treatment of prostate cancer: A review. Int J Radiat Oncol Biol Phys. 2015;91:182–195.
    1. Abdellatif A., Craig J., Jensen M. Experimental assessments of intrafractional prostate motion on sequential and simultaneous boost to a dominant intraprostatic lesion. Med Phys. 2012;39:1505–1517.
    1. Kim J.-H., Nguyen D.T., Booth J.T. The accuracy and precision of kilovoltage intrafraction monitoring (KIM) six degree-of-freedom prostate motion measurements during patient treatments. Radiother Oncol. 2018;126:236–243.
    1. Benedek H., Lerner M., Nilsson P. The effect of prostate motion during hypofractionated radiotherapy can be reduced by using flattening filter free beams. Phys Imaging Radiat Oncol. 2018;6:66–70.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe