Prostate cancer and hypofractionation: reflections on recent randomised phase III clinical trial results

Dearnaley, David P.; Hall, Emma

doi:10.21037/tau.2017.01.05

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…An increase in late toxicity rates for MHRT was observed in RTOG 0415. This may be expected as Dearnaley points out that EQD2 was higher for the patients receiving MHRT [37] (see Table 5). No difference in late toxicities was observed in CHHiP.…”

Section: Discussionmentioning

confidence: 60%

“…An increase in acute GI toxicity was observed with MHRT compared with conventionally fractionated radiation therapy in the CHHiP and PROFIT studies. Only 30% of the patients in CHHiP received image-guided radiation therapy (IGRT), which may explain the relative larger toxicity observed here compared with PROFIT where treatment was delivered with daily image guidance [37]. Image-guided radiation therapy may improve toxicity rates [41].…”

Section: Discussionmentioning

confidence: 91%

“…However, the impact of ADT on the α/β ratio remains unknown [36]. Ninety seven percent of the patients in CHHiP received ADT compared with 5% of the patients in PROFIT, which likely accounts for the observed difference in biochemical control at 5-years (91% vs. 85%) [37]. A similar increase (13%) in 5-year PSA-control with 6 months ADT has been detected in the EORTC 22991 study, which investigated the use of adjuvant ADT to radiation therapy [38].…”

Section: Discussionmentioning

confidence: 99%

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Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials

Lilleby

Petersen

Daugaard

et al. 2023

SJU

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Problem: A low α/β ratio for prostate cancer (PCa) compared to surrounding normal tissue theoretically implies therapeutical advantages with hypofractionated treatment. Data from large randomised control trials (RCTs) comparing moderate hypofractionated (MHRT, 2.4–3.4 Gray/fraction (Gy/fx)) and ultra-hypofractionated (UHRT, >5 Gy/fx) with conventionally fractionated radiation therapy (CFRT, 1.8–2 Gy/fx) and the possible clinical implications have been reviewed.Materials and method: We searched PubMed, Cochrane and Scopus for RCT comparing MHRT/UHRT with CFRT treatment of locally and/or locally advanced (N0M0) PCa. We found six RCTs, which compared different radiation therapy regimes. Tumour control and acute and late toxicities are reported.Results: MHRT was non-inferior to CFRT for intermediate-risk PCa, non-inferior for low-risk PCa and not superior in terms of tumour control for high-risk PCa. Acute toxicity rates were increased compared to CFRT, especially an increase in acute gastrointestinal adverse effects was seen. Late toxicity related to MHRT seems to be comparable. UHRT was non-inferior in terms of tumour control in one RCT, with increased acute toxicity, but with comparable late toxicity. One trial, however, indicated increased late toxicity rates with UHRT.Discussion and conclusion: MHRT delivers similar therapeutic outcomes compared to CFRT in terms of tumour control and late toxicity for intermediate-risk PCa patients. Slightly more acute transient toxicity could be tolerated in favour of a shorter treatment course. UHRT should be regarded as an optional treatment for patients with low- and intermediate-risk disease applied at experienced centres in concordance with international and national guidelines.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials

Lilleby

Petersen

Daugaard

et al. 2023

SJU

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“…In recent years, in the aim of shortening radiotherapy courses while maintaining excellent treatment outcomes, several randomized phase III trials have evaluated the efficacy of moderately hypofractionated and ultrahypofractionated radiotherapy in various scenarios of localized PCa treatment [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Hypofractionated Radiotherapy in Localized, Low–Intermediate-Risk Prostate Cancer: Current and Future Prospectives

Lo Greco,

Marletta,

Marano

et al. 2023

Medicina

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At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

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“…2,3 Despite receiving the combination, patients can experience a biochemical recurrence (ie, prostate-specific antigen increase), as well as distant metastases and prostate cancer-specific mortality; therefore, there is a need for treatment improvement. 4,5 Without such improvement, the administration of doseescalated RT and long-term ADT will have failed for 45% of patients with high-risk prostate cancer by 6 years. 6 To address the need for treatment intensification, we considered combining RT and ADT with the colonystimulating factor 1 receptor (CSF1R) inhibitor pexidartinib.…”

Section: Introductionmentioning

confidence: 99%

A Phase 1 study Combining Pexidartinib, Radiation Therapy, and Androgen Deprivation Therapy in Men With Intermediate- and High-Risk Prostate Cancer

Hamid

Heilbrun

Maier

et al. 2021

Advances in Radiation Oncology

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This study aimed to evaluate a combination of radiation therapy (RT), androgen deprivation therapy (ADT), and pexidartinib (colony-stimulating factor 1 receptor [CSF1R]) inhibitor in men with intermediate-and high-risk prostate cancer. CSF1R signaling promotes tumor infiltration and survival of tumor-associated macrophages, which in turn promote progression and resistance. Counteracting protumorigenic actions of tumor-associated macrophages via CSF1R inhibition may enhance therapeutic efficacy of RT and ADT for prostate cancer. Methods and Materials: In this phase 1 study, the treatment regimen consisted of pexidartinib (800 mg, administered as a split-dose twice daily) and ADT (both for a total of 6 months), and RT that was initiated at the start of month 3. RT volumes included the prostate and proximal seminal vesicles. The delivered dose was 7920 cGy (180 cGy per fraction) using intensity modulated RT with daily image guidance for prostate localization. The primary objective was to identify the maximum tolerated dose based on dose-limiting toxicities. Results: All 4 enrolled patients who were eligible to receive RT had T 1 stage prostate cancer, 2 were intermediate risk, and 2 were high risk. The median age was 62.5 years, and the prostate-specific antigen levels were in the range 6.4 to 10.7 ng/mL. The patients' individual Gleason scores were 3 þ 3, 4 þ 3, 4 þ 4, and 4 þ 5. All 4 patients reported 1 adverse events before RT. Grade 1

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Prostate cancer and hypofractionation: reflections on recent randomised phase III clinical trial results

Cited by 5 publications

References 13 publications

Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials

Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials

Hypofractionated Radiotherapy in Localized, Low–Intermediate-Risk Prostate Cancer: Current and Future Prospectives

A Phase 1 study Combining Pexidartinib, Radiation Therapy, and Androgen Deprivation Therapy in Men With Intermediate- and High-Risk Prostate Cancer

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