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

Overview

Journal Trials

Publisher Biomed Central

Specialties General Medicine
Pharmacology

Date 2011 Dec 7

PMID 22141598

Citations 63

Authors

Irene M Lips

Uulke A van der Heide

Karin Haustermans

Emile N J T van Lin

Floris Pos

Stefan P G Franken

Alexis N T J Kotte

Carla H van Gils

Marco van Vulpen

Affiliations

Soon will be listed here.

Abstract

Background: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer.

Methods/design: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described.

Trial Registration: This study is registered at ClinicalTrials.gov: NCT01168479.

Citing Articles

Microboost in Localized Prostate Cancer: Analysis of a Statewide Quality Consortium.

Regan S, Dykstra M, Yin H, Grubb M, Vaishampayan N, Zaki M Adv Radiat Oncol. 2024; 9(11):101629.

PMID: 39610797 PMC: 11602997. DOI: 10.1016/j.adro.2024.101629.

Stereotactic Body Radiation Therapy (SBRT) in prostate cancer in the presence of hip prosthesis - is it a contraindication? A narrative review.

Dube S, Pareek V, Barthwal M, Antony F, Sasaki D, Rivest R BMC Urol. 2024; 24(1):152.

PMID: 39061006 PMC: 11282858. DOI: 10.1186/s12894-024-01479-8.

Focal Boost in Prostate Cancer Radiotherapy: A Review of Planning Studies and Clinical Trials.

Zhao Y, Haworth A, Rowshanfarzad P, Ebert M Cancers (Basel). 2023; 15(19).

PMID: 37835581 PMC: 10572027. DOI: 10.3390/cancers15194888.

Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group.

Bisgaard A, Keesman R, van Lier A, Coolens C, van Houdt P, Tree A Radiother Oncol. 2023; 186:109803.

PMID: 37437609 PMC: 11197850. DOI: 10.1016/j.radonc.2023.109803.

Radiotherapy planning in a prostate cancer phantom model with intraprostatic dominant lesions using stereotactic body radiotherapy with volumetric modulated arcs and a simultaneous integrated boost.

Skrobala A, Kruszyna-Mochalska M, Graczyk K, Ryczkowski A, Fundowicz M, Milecki P Front Oncol. 2023; 13:1147593.

PMID: 37188175 PMC: 10175813. DOI: 10.3389/fonc.2023.1147593.

References

Scheidler J, Hricak H, Vigneron D, Yu K, Sokolov D, Huang L . Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging--clinicopathologic study. Radiology. 1999; 213(2):473-80. DOI: 10.1148/radiology.213.2.r99nv23473. View

Pollack A, Zagars G, Starkschall G, Antolak J, Lee J, Huang E . Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002; 53(5):1097-105. DOI: 10.1016/s0360-3016(02)02829-8. View

Sandhu A, Zelefsky M, Lee H, Lombardi D, Fuks Z, Leibel S . Long-term urinary toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection. Int J Radiat Oncol Biol Phys. 2000; 48(3):643-7. DOI: 10.1016/s0360-3016(00)00714-8. View

Nout R, van de Poll-Franse L, Lybeert M, Warlam-Rodenhuis C, Jobsen J, Mens J . Long-term outcome and quality of life of patients with endometrial carcinoma treated with or without pelvic radiotherapy in the post operative radiation therapy in endometrial carcinoma 1 (PORTEC-1) trial. J Clin Oncol. 2011; 29(13):1692-700. DOI: 10.1200/JCO.2010.32.4590. View

Vickers A, Altman D . Statistics notes: Analysing controlled trials with baseline and follow up measurements. BMJ. 2001; 323(7321):1123-4. PMC: 1121605. DOI: 10.1136/bmj.323.7321.1123. View

Pickett B, Vigneault E, Kurhanewicz J, Verhey L, Roach M . Static field intensity modulation to treat a dominant intra-prostatic lesion to 90 Gy compared to seven field 3-dimensional radiotherapy. Int J Radiat Oncol Biol Phys. 1999; 44(4):921-9. DOI: 10.1016/s0360-3016(98)00502-1. View

Gaudet M, Vigneault E, Aubin S, Varfalvy N, Harel F, Beaulieu L . Dose escalation to the dominant intraprostatic lesion defined by sextant biopsy in a permanent prostate I-125 implant: a prospective comparative toxicity analysis. Int J Radiat Oncol Biol Phys. 2009; 77(1):153-9. DOI: 10.1016/j.ijrobp.2009.04.049. View

Fonteyne V, Villeirs G, Speleers B, De Neve W, De Wagter C, Lumen N . Intensity-modulated radiotherapy as primary therapy for prostate cancer: report on acute toxicity after dose escalation with simultaneous integrated boost to intraprostatic lesion. Int J Radiat Oncol Biol Phys. 2008; 72(3):799-807. DOI: 10.1016/j.ijrobp.2008.01.040. View

Ash D, Flynn A, Battermann J, de Reijke T, Lavagnini P, Blank L . ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol. 2000; 57(3):315-21. DOI: 10.1016/s0167-8140(00)00306-6. View

10.

Rijkhorst E, Lakeman A, Nijkamp J, de Bois J, Van Herk M, Lebesque J . Strategies for online organ motion correction for intensity-modulated radiotherapy of prostate cancer: prostate, rectum, and bladder dose effects. Int J Radiat Oncol Biol Phys. 2009; 75(4):1254-60. DOI: 10.1016/j.ijrobp.2009.04.034. View

11.

Borghede G, Sullivan M . Measurement of quality of life in localized prostatic cancer patients treated with radiotherapy. Development of a prostate cancer-specific module supplementing the EORTC QLQ-C30. Qual Life Res. 1996; 5(2):212-22. DOI: 10.1007/BF00434743. View

12.

Kotte A, Hofman P, Lagendijk J, van Vulpen M, van der Heide U . Intrafraction motion of the prostate during external-beam radiation therapy: analysis of 427 patients with implanted fiducial markers. Int J Radiat Oncol Biol Phys. 2007; 69(2):419-25. DOI: 10.1016/j.ijrobp.2007.03.029. View

13.

Rouviere O . MR assessment of recurrent prostate cancer after radiation therapy. Radiology. 2007; 242(2):635-6. DOI: 10.1148/radiol.2422060215. View

14.

Xia P, Pickett B, Vigneault E, Verhey L, Roach 3rd M . Forward or inversely planned segmental multileaf collimator IMRT and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy. Int J Radiat Oncol Biol Phys. 2001; 51(1):244-54. DOI: 10.1016/s0360-3016(01)01643-1. View

15.

Lips I, Dehnad H, van Gils C, Boeken Kruger A, van der Heide U, van Vulpen M . High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients. Radiat Oncol. 2008; 3:15. PMC: 2430572. DOI: 10.1186/1748-717X-3-15. View

16.

Oken M, Creech R, Tormey D, Horton J, Davis T, McFadden E . Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6):649-55. View

17.

Inoue S, Shiina H, Hiraoka T, Wake K, Sumura M, Honda S . Five-year longitudinal effect of radical perineal prostatectomy on health-related quality of life in Japanese men, using general and disease-specific measures. BJU Int. 2009; 104(8):1077-84. DOI: 10.1111/j.1464-410X.2009.08491.x. View

18.

Miralbell R, Molla M, Rouzaud M, Hidalgo A, Toscas J, Lozano J . Hypofractionated boost to the dominant tumor region with intensity modulated stereotactic radiotherapy for prostate cancer: a sequential dose escalation pilot study. Int J Radiat Oncol Biol Phys. 2009; 78(1):50-7. DOI: 10.1016/j.ijrobp.2009.07.1689. View

19.

Zelefsky M, Chan H, Hunt M, Yamada Y, Shippy A, Amols H . Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol. 2006; 176(4 Pt 1):1415-9. DOI: 10.1016/j.juro.2006.06.002. View

20.

Zelefsky M, Fuks Z, Hunt M, Yamada Y, Marion C, Ling C . High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys. 2002; 53(5):1111-6. DOI: 10.1016/s0360-3016(02)02857-2. View