Patterns of Failure Following External Beam Radiotherapy With or Without an Additional Focal Boost in the Randomized Controlled FLAME Trial for Localized Prostate Cancer

Groen, V.; Haustermans, Karin; Pos, Floris J.; Draulans, Cédric; Isebaert, Sofie; Monninkhof, Evelyn M.; Smeenk, Robert Jan; Kunze-Busch, Martina; Boer, J.C.J. de; Zijp, Jochem van der Voort van; Kerkmeijer, Linda G.W.; Heide, Uulke A. van der

doi:10.1016/j.eururo.2021.12.012

Cited by 47 publications

(26 citation statements)

References 20 publications

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“…1 Both local control and regional/distant metastasis-free survival were also improved. 2 Remarkably, these patient benefits did not come at the cost of additional short-or long-term toxicity. 2,3 However, radiation oncologists' ability to identify prostate tumors on MRI is critical to harnessing the benefits of radiotherapy boost for patients.…”

Section: Manuscriptmentioning

confidence: 97%

ReIGNITE RT Boost: An international study testing the accuracy and feasibility of using restriction spectrum imaging (RSI) MRI to guide intraprostatic tumor target volume for radiotherapy boost

Lui

Kallis

Zhong

et al. 2022

Preprint

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In a phase III randomized trial, adding a radiation boost to visible tumor(s) on MRI improved prostate cancer disease-free and metastasis-free survival without additional toxicity. However, radiation oncologists' ability to identify prostate tumors is critical and represents a major barrier to widely adopting intraprostatic tumor radiotherapy boost for patients. We previously developed a quantitative diffusion MRI biomarker for prostate cancer, called the Restriction Spectrum Imaging restriction score (RSIrs), that has been shown to improve radiologist identification of clinically significant prostate cancer. 42 radiation oncologists (participants) from multiple, international institutions contoured prostate tumors on 40 patient cases using standard MRI with or without RSIrs map, producing 1646 target volumes. Use of RSIrs maps significantly improved all evaluated accuracy metrics, including participants' percent overlap with consensus expert target volume (73% vs. 42%, p<0.001). A mixed effects model confirmed that RSIrs maps were the main variable driving the improvement in all metrics. System Usability Scores indicated RSIrs maps significantly improved the contouring experience (72 vs. 58, p<0.002). The expert-defined tumor was completely missed 158 times on standard MRI alone and only 19 times with RSIrs maps. RSIrs maps improve the accuracy of target delineation for prostate tumor boost.

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Section: Manuscriptmentioning

confidence: 97%

ReIGNITE RT Boost: An international study testing the accuracy and feasibility of using restriction spectrum imaging (RSI) MRI to guide intraprostatic tumor target volume for radiotherapy boost

Lui

Kallis

Zhong

et al. 2022

Preprint

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show abstract

“…Toxicity and QoL were favorable in both arms, and differences were small a not statistically significant. Likewise, a patterns of failure analysis of the FLAME trial demonstrated focal boost decreased both local and regional or distant metastatic failure ( 29 ). Although there was also a clear inverse relationship between achieved dose to the GTV and probability of biochemical failure, there appears to be saturation as the curve starts to plateau beyond 85–90 Gy (96–106 EQD2, α/β of 1.2) ( 28 ).…”

Section: Dose Escalation For High-risk Prostate Cancermentioning

confidence: 99%

“…Although the technical achievement of focal dose escalation to this extreme is commendable, it is unclear whether the risk of increased toxicity is justified from an oncological perspective. The recently published FLAME trial patterns-of-failure analysis suggests that there are diminishing returns to dose escalation to the DIL in excess of 100 Gy EQD2 (α/β of 1.2), both in terms of local failure and regional/distant metastatic failure ( 29 ).…”

Section: Dose Escalation For High-risk Prostate Cancermentioning

confidence: 99%

Stereotactic Body Radiotherapy: Hitting Harder, Faster, and Smarter in High-Risk Prostate Cancer

Correa

Loblaw

2022

Front. Oncol.

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Stereotactic body radiotherapy (SBRT) is a technologically sophisticated form of radiotherapy that holds significant potential to effectively treat high-risk prostate cancer (HRPC). Prostate SBRT has been the subject of intense investigation in the context of low- and intermediate-risk disease, but less so for HRPC. However, emerging data are demonstrating its potential to safely and efficiently delivery curative doses of radiotherapy, both to the prostate and elective lymph nodes. SBRT theoretically hits harder through radiobiological dose escalation facilitated by ultra-hypofractionation (UHRT), faster with only five treatment fractions, and smarter by using targeted, focal dose escalation to maximally ablate the dominant intraprostatic lesion (while maximally protecting normal tissues). To achieve this, advanced imaging modalities like magnetic resonance imaging and prostate specific membrane antigen positron emmission tomography (PSMA-PET) are leveraged in combination with cutting-edge radiotherapy planning and delivery technology. In this focused narrative review, we discuss key evidence and upcoming clinical trials evaluating SBRT for HRPC with a focus on dose escalation, elective nodal irradiation, and focal boost.

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“…Participants were randomly assigned to receive either uniform RT dose to the entire prostate (control arm) or RT to the entire prostate with a focal RT dose boost to gross disease (focal boost arm). Compared to the control arm, participants in the focal boost arm had improved disease-free survival, improved local control, and improved regional/distant metastasis-free survival 1,2 . No difference in toxicity was observed between the two groups 1 .…”

Section: Introductionmentioning

confidence: 99%

Use of focal radiotherapy boost for prostate cancer and perceived barriers toward its implementation: a survey

Zhong

Lui

Katz

et al. 2023

Preprint

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BackgroundIn a recent phase III randomized control trial (FLAME), delivering a focal radiotherapy (RT) boost to tumors visible on MRI was shown to improve outcomes for prostate cancer patients without increasing toxicity. The aim of this study was to assess how widely this technique is being applied in current practices as well as physicians’ perceived barriers toward its implementation.MethodsAn online survey assessing the use of intraprostatic focal boost was conducted on RedCAP in December 2022. The survey link was distributed to radiation oncologists worldwide via email list, group text platform, and social media.ResultsThe survey collected 205 responses from various countries over a two-week period. The majority of respondents worked at an academic medical center (59%) and considered their practice to be at least partially genitourinary (GU)-subspecialized (81%). 51% of participants reported not routinely using intraprostatic focal boost. Even among complete subspecialists, a substantial proportion (38%) do not routinely use focal boost. Less than half of participants in both high-income and low-to-middle-income countries were shown to routinely use focal boost. The most commonly cited barriers overall were challenges to accessing high-quality MRI, concerns about registration accuracy between MRI and CT, and concerns about risk of additional toxicity.ConclusionDespite the promising level 1 results of the FLAME trial, there is substantial evidence that most radiation oncologists are not routinely offering focal RT boost. Adoption of this technique might be accelerated by increased access to high-quality MRI, better registration algorithms of MRI to CT simulation images, physician education on benefit-to-harm ratio, and physician training on contouring prostate lesions on MRI.

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Patterns of Failure Following External Beam Radiotherapy With or Without an Additional Focal Boost in the Randomized Controlled FLAME Trial for Localized Prostate Cancer

Cited by 47 publications

References 20 publications

ReIGNITE RT Boost: An international study testing the accuracy and feasibility of using restriction spectrum imaging (RSI) MRI to guide intraprostatic tumor target volume for radiotherapy boost

ReIGNITE RT Boost: An international study testing the accuracy and feasibility of using restriction spectrum imaging (RSI) MRI to guide intraprostatic tumor target volume for radiotherapy boost

Stereotactic Body Radiotherapy: Hitting Harder, Faster, and Smarter in High-Risk Prostate Cancer

Use of focal radiotherapy boost for prostate cancer and perceived barriers toward its implementation: a survey

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