Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: The Triumph of Radiobiology

2021 ◽  
Vol 16 ◽  
Author(s):  
Andromachi Kougioumtzopoulou ◽  
Kalliopi Platoni ◽  
Anna Zygogianni ◽  
George Kounadis ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Late Toxicity ◽  
Phase Iii ◽  
Hypofractionated Radiotherapy ◽  
Phase Ii Studies ◽  
Risk Prostate Cancer ◽  
Prospective Phase ◽  
Moderate Hypofractionation ◽  
Meta Analyses ◽  
Phase Iii Studies

Background: Radiotherapy represents one of the main therapeutic modalities for localized prostate cancer. In the last two decades, emerging data regarding the radiobiology of prostate cancer suggests a very low α/β value which has led the scientific community to evaluate the potential advantage of hypofractionation. Objective: The aim of this manuscript is to present the rationale of prostate radiobiology and the medical evidence of moderate hypofractionation for prostate cancer. Methods: Existing literature was reviewed, including data from prospective clinical trials dealing with the efficacy and toxicity of hypofractionated radiotherapy. Fifteen prospective phase II studies, nine randomized phase III studies, and ten meta-analyses were selected. For every study included, the equivalent dose was calculated for both biochemical control and late toxicity. Results: The efficacy of hypofractionated radiotherapy, compared to conventional radiotherapy, regarding biochemical control, was evaluated in five superiority and four non-inferiority randomized phase III studies. The majority of participants in these studies were patients with low- and intermediate-risk prostate cancer. Even though the superiority criterion of the hypofractionation was not met in all studies, the non-inferiority criterion was. Prospective phase II studies of hypofractionation reported a low rate of acute and late toxicity. In randomized phase III studies, acute and late toxicity grade 3 and higher for the bowel and bladder were comparable between hypofractionated and conventional radiotherapy. The included meta-analyses showed no difference in efficacy and toxicity. Conclusion: Moderate hypofractionation is feasible and safe and may be considered an alternative option in low- and intermediate-risk prostate cancer patients.

Baseline albumin (b-alb) as a potential predictive biomarker for the efficacy of bevacizumab (B) therapy (tx) in patients (pts) with advanced pancreas cancer (APCA): A comparative analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4039-4039
Author(s):  
Ludmila Katherine Martin ◽  
Susan Michelle Geyer ◽  
Anissa Bingman ◽  
Mark M. Zalupski ◽  
Tanios S. Bekaii-Saab
Keyword(s):  
Pancreas Cancer ◽  
Stage Iv ◽  
Predictive Biomarker ◽  
Phase Iii ◽  
Phase Ii Studies ◽  
Prospective Phase ◽  
Prospective Trials ◽  
Phase Iii Studies ◽  
Background Phase

4039 Background: Phase III studies of B in unselected pts with APCA have demonstrated no improvement in outcome. Recent data suggest certain subsets of APCA patients may benefit from B. Lower b- alb results in a 15-20% increased rate of B clearance that may decrease exposure to B. The resulting clinical implications are not well understood. We evaluated the potential predictive and prognostic role of b-alb in pts with APCA receiving gemcitabine (G)-based tx with or without B. Methods: Relevant data were collected from 3 prospective phase II studies of G-based tx. Pts were grouped according to exposure to B (Gr 1) or no B (Gr 2) and by b-alb < 3.4 g/dL (< LLN) or > 3.4 g/dL (>LLN). Univariate and multivariate analyses of clinical outcome (OS, TTP) were conducted for each group and all pts. Results: 100 pts (46M, 54F) with median age 63 (range 28-82) were included. 94% had stage IV. Median b-alb was similar in both groups. Clinical outcomes by alb are outlined in the table. In Gr 1 but not Gr 2, b-alb > 3.4 g/dL was significantly associated with improved OS and TTP. For pts with b-alb >3.4 g/dL, maintenance of alb >3.4 g/dL throughout tx was significantly associated with improved survival in Gr 1 but not Gr 2. Multivariate analysis revealed significant association between alb > 3.4 and OS regardless of B status (p=0.004) although this was strongly influenced by the survival differential in Gr 1. Conclusions: APCA pts with b-alb > 3.4 g/dL appear to derive significant benefit from B and this benefit is most pronounced in pts who maintain alb > 3.4 g/dL throughout B tx. This finding was not observed in pts treated without B. b-alb > 3.4 g/dL including maintenance of alb > 3.4 g/dL during B tx may predict for improved efficacy of B in APCA. These findings require further investigation in larger prospective trials. [Table: see text]

scholarly journals Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Maurizio Valeriani ◽  
Alessia Carnevale ◽  
Linda Agolli ◽  
Paolo Bonome ◽  
Adelaide Montalto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Late Toxicity ◽  
Low Risk ◽  
Hypofractionated Radiotherapy ◽  
Low Grade ◽  
Image Guided ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT).Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions.Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P=0.04) in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P<0.001) for HFRT patients.Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

Moderate Hypofractionation in High-Risk, Organ-Confined Prostate Cancer: Final Results of a Phase III Randomized Trial

2017 ◽  
Vol 35 (17) ◽  
pp. 1891-1897 ◽  
Author(s):  
Giorgio Arcangeli ◽  
Biancamaria Saracino ◽  
Stefano Arcangeli ◽  
Sara Gomellini ◽  
Maria Grazia Petrongari ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Randomized Trial ◽  
Gleason Score ◽  
Late Toxicity ◽  
Phase Iii ◽  
Hypofractionated Radiotherapy ◽  
Significant Prognostic Factor ◽  
Prognostic Variables ◽  
Genitourinary Toxicity

Purpose To report the final results on treatment outcomes of a randomized trial comparing conventional and hypofractionated radiotherapy in high-risk, organ-confined prostate cancer (PCa). Patients and Methods This single-institution, randomized clinical trial, conducted from January 2003 to December 2007, enrolled 168 patients with high-risk PCa who were randomly assigned in a 1:1 ratio to conventional (80 Gy in 40 fractions in 8 weeks) or hypofractionated radiotherapy (62 Gy in 20 fractions in 5 weeks) to prostate and seminal vesicles. The primary outcome measure was late toxicity. Additional outcomes were freedom from biochemical failure (FFBF), prostate cancer–specific survival (PCaSS), and overall survival (OS), evaluated on an intention-to-treat basis. Results A total of 85 patients were assigned to conventional and 83 to hypofractionated radiotherapy. At a median follow-up of 9 years (interquartile range, 7.5 to 10.1 years), no differences was observed in physician-assessed late gastro intestinal and genitourinary toxicity greater than or equal to grade 2 ( P = .68 and .57, respectively) were found between the two arms. The 10-year FFBF rate was 72% in the hypofractionation group and 65% in the conventional fractionation group ( P = .148). Ten-year OS rates were 75% in the hypofractionation group and 64% in the conventional group, respectively ( P = .22). The same features for 10-year PCaSS were 95% and 88%, respectively ( P = .066). Hypofractionation, pretreatment prostate-specific antigen level, Gleason score, and clinical tumor stage for FFBF, and hypofractionation and Gleason score for PCaSS were significant prognostic variables on the multivariate analysis. Conclusion Long-term findings showed that hypofractionated radiotherapy failed the intent of either reducing physician-assessed late toxicity or maintaining the same efficacy. A postrandomization analysis, however, revealed that hypofractionation was a significant prognostic factor for FFBF and PCaSS, when adjusted for clinical prognostic variables.

scholarly journals Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
David Thomson ◽  
Sophie Merrick ◽  
Ric Swindell ◽  
Joanna Coote ◽  
Kay Kelly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Intensity Modulated Radiotherapy ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Hypofractionated Radiotherapy ◽  
Intensity Modulated ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

Background. The benefit of dose-escalated hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) in prostate cancer is not established. We report 5-year outcome and long-term toxicity data within a phase II clinical trial.Materials and Methods. 60 men with predominantly high-risk prostate cancer were treated. All patients received neoadjuvant hormone therapy, completing up to 6 months in total. Thirty patients were treated with 57 Gy in 19 fractions and 30 patients with 60 Gy in 20 fractions. Acute and 2-year toxicities were reported and patients followed longitudinally to assess 5 year outcomes and long-term toxicity. Toxicity was measured using RTOG criteria and LENT/SOMA questionnaire.Results. Median followup was 84 months. Five-year overall survival (OS) was 83% and biochemical progression-free survival (bPFS) was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction.Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

Eight-year outcomes of a phase III randomized trial of conventional versus hypofractionated high-dose intensity modulated radiotherapy for prostate cancer (CRUK/06/016): Update from the CHHiP Trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 325-325 ◽  
Author(s):  
David P. Dearnaley ◽  
Clare Griffin ◽  
Isabel Syndikus ◽  
Vincent Khoo ◽  
Alison Jane Birtle ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Dose Intensity ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Phase Iii ◽  
High Dose ◽  
Moderate Hypofractionation

325 Background: CHHiP is a non-inferiority trial to determine efficacy and safety of hypofractionated radiotherapy for localised prostate cancer (PCa). Five year results indicated that moderate hypofractionation of 60 Gray (Gy)/20 fractions (f) was non-inferior to 74Gy/37f (Lancet Oncology, 2016). Moderate hypofractionation is now an international standard of care but with patients remaining at risk of recurrence for many years, information on long-term outcomes is important. Here we report pre-planned analysis of 8 year outcomes. Methods: Between October 2002 and June 2011, 3216 men with node negative T1b-T3a localised PCa with risk of seminal vesical involvement ≤30% were randomised (1:1:1 ratio) to 74Gy/37f (control), 60Gy/20f or 57Gy/19f. Androgen deprivation began at least 3 months prior to radiotherapy (RT) and continued until end of RT. The primary endpoint was time to biochemical failure (Phoenix consensus guidelines) or clinical failure (BCF). The non-inferiority design specified a critical hazard ratio (HR) of 1.208 for each hypofractionated schedule compared to 74Gy/37f. Late toxicity was assessed at 5 years by RTOG and LENT-SOM scales. Analysis was by intention-to-treat. Results: With a median follow up of 9.2 years, 8 year BCF-free rates (95% CI) were 74Gy: 80.6% (77.9%, 83.0%); 60Gy: 83.7% (81.2%, 85.9%) and 57Gy: 78.5% (75.8%, 81.0%). For 60Gy/20f, non-inferiority was confirmed: HR60=0.84 (90% CI 0.71, 0.99). For 57Gy/19f, non-inferiority could not be declared: HR57=1.17 (90% CI 1.00, 1.37). Clinician assessments of late toxicity were similar across groups. At 5 years, RTOG grade≥2 (G2+) bowel toxicity was observed in 14/879 (1.6%), 18/908 (2.0%) and 17/904 (1.9%) of the 74Gy, 60Gy and 57Gy groups respectively. RTOG G2+ bladder toxicity was observed in 17/879 (1.9%), 14/908 (1.5%) and 17/904 (1.9%) of the 74Gy, 60Gy and 57Gy groups respectively. Conclusions: With BCF rates over 80%, long-term follow-up confirms that 60Gy/20f is non-inferior to 74Gy/37f. Late side effects were very low across all groups. These results support the continued use of 60Gy/20f as standard of care for men with localised PCa. Clinical trial information: 97182923.

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