Stereotactic radiotherapy with focal boost for intermediate and high-risk prostate cancer: Initial results of the SPARC trial

Nicholls, Luke; Suh, Yae-eun; Chapman, E.; Henderson, Daniel R.; Jones, Caroline L.; Morrison, Kirsty; Sohaib, Aslam; Taylor, H.; Tree, A.; As, Nicholas van

doi:10.1016/j.ctro.2020.10.004

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…In the experimental arm of the HypoFocal-SBRT study, a dose of 35 Gy will be applied to the entire prostate [ 18 ]. Compared to other SBRT focal-dose escalation studies [ 32 , 34 ], the applied dose to the ITM in our study is lower (40–42 Gy), considering an improved tumor coverage due to the implementation of advanced medical imaging. All previous studies performed ITM definition based on mpMRI information.…”

Section: Methods and Designmentioning

confidence: 77%

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PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

Zamboglou

Spohn

Adebahr

et al. 2021

Cancers

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Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose–response relationship for patients with primary PCa and especially in patients with high-risk features, as dose escalation leads to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography targeting prostate-specific-membrane antigen (PSMA-PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time. The HypoFocal-SBRT study combines ultra-hypofractionated RT/stereotactic body RT, with focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts. This novel strategy will be compared with moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide. We suspect an increase in relapse-free survival (RFS), and we will assess quality of life in order to detect potential changes.

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Section: Methods and Designmentioning

confidence: 77%

“…No grade 3 toxicities were reported up to 90 days after treatment. The SPARC trial delivered 44.85–48.25 Gy in 5 fractions to the ITM [ 34 ]. An interim safety analysis was performed on the first 8 patients after a median follow-up of 56 months.…”

Section: Methods and Designmentioning

confidence: 99%

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

Zamboglou

Spohn

Adebahr

et al. 2021

Cancers

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“…Moreover, focal dose escalated MHRT was investigated in a pilot study by Onjukka et al [ 35 ] and the phase II DELINEATE trial [ 36 ] with acceptable toxicitiy profiles. Results regarding focal dose escalated SBRT were reported by the phase II hypo-FLAME trial [ 37 ], a phase 1a/1b trial by Herrara et al [ 38 ] and the SPARC trial [ 39 ]. The interim analysis of the Italian AIRC-IG-13218 phase II trial did not report any grade 3 or 4 toxicities after a median follow up of 17 months [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients

et al. 2022

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Objective Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). Materials and methods The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients’ representatives and patients’ self-help groups addressing the patients’ willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. Results (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. Conclusion The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

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“…Only, the HYPO-RT-PC trial and 1 older study from South Korea deviated from this approach. Most trials prescribed 5 × 7.25–7.5 Gy and there is little evidence for the safety and efficacy of further increased single-fraction doses [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review

Forster

Zwahlen

Buchali

et al. 2021

Cancers

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Background: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome. Stereotactic body radiotherapy (SBRT) is a highly conformal RT technique enabling ultra-hypofractionation which has been shown to be safe and efficient in patients with low- and intermediate-risk PCA. There is a paucity of data on the role of SBRT in HR PCA. In particular, the need for pelvic elective nodal irradiation (ENI) needs to be addressed. Therefore, we conducted a systematic review to analyze the available data on observed toxicities, ADT prescription practice, and oncological outcome to shed more light on the value of SBRT in HR PCA. Methods: We searched the PubMed and Embase electronic databases for the terms “prostate cancer” AND “stereotactic” AND “radiotherapy” in June 2020. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Results: After a rigorous selection process, we identified 18 individual studies meeting all selection criteria for further analyses. Five additional studies were included because their content was judged as relevant. Three trials have reported on prostate SBRT including pelvic nodes; 2 with ENI and 1 with positive pelvic nodes only. The remaining studies investigated SBRT of the prostate only. Grade 2+ acute genitourinary (GU) toxicity was between 12% and 46.7% in the studies investigating pelvic nodes irradiation and ranged from 0% to 89% in the prostate only studies. Grade 2+ chronic GU toxicity was between 7% and 60% vs. 2% and 56.7%. Acute gastrointestinal (GI) grade 2+ toxicity was between 0% to 4% and 0% to 18% for studies with and without pelvic nodes irradiation, respectively. Chronic GI grade 2+ toxicity rates were between 4% and 50.1% vs. 0% and 40%. SBRT of prostate and positive pelvic nodes only showed similar toxicity rates as SBRT for the prostate only. Among the trials that reported on ADT use, the majority of HR PCA patients underwent ADT for at least 2 months; mostly neoadjuvant and concurrent. Biochemical control rates ranged from 82% to 100% after 2 years and 56% to 100% after 3 years. Only a few studies reported longer follow-up data. Conclusion: At this point, SBRT with or without pelvic ENI cannot be considered the standard of care in HR PCA, due to missing level 1 evidence. Treatment may be offered to selected patients at specialized centers with access to high-precision RT. While concomitant ADT is the current standard of care, the necessary duration of ADT in combination with SBRT remains unclear. Ideally, all eligible patients should be enrolled in clinical trials.

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Stereotactic radiotherapy with focal boost for intermediate and high-risk prostate cancer: Initial results of the SPARC trial

Abstract: Highlights Dose escalation to MRI-defined prostate lesions using SABR is feasible and safe. After an extended follow up, rates of Grade 2 + GU and GI toxicities were low. No biochemical relapse was observed. 10 minor dose variations were reported out of 80 ideal dose constraints.

Cited by 12 publications

References 28 publications

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review

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