Comparison of hypofractionated high-dose intensity-modulated radiotherapy schedules for prostate cancer: Results from the phase III randomized CHHiP trial (CRUK/06/016).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
David P. Dearnaley ◽  
Isabel Syndikus ◽  
Helen Mossop ◽  
Alison J. Birtle ◽  
DJ Bloomfield ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Dose Intensity ◽  
Late Toxicity ◽  
Phase Iii ◽  
High Dose ◽  
Significant Difference ◽  
Patient Reported ◽  
Free Rate

2 Background: We aimed to explore the dose response relationship for two 3 Gray (Gy) hypofractionated radiotherapy (hRT) schedules for localised prostate cancer (PCa). Methods: hRT schedules of 60Gy/20 fractions (f) and 57Gy/19f were compared with conventional RT (cRT) 74Gy/37f; iso-effective for alpha-beta ratios of 2.5Gy and 1.5Gy respectively. The trial was powered to demonstrate non-inferiority between each hRT schedule and cRT, with 3,213 patients (pt) needed to rule out 5% inferiority (80% power, 1-sided alpha 5%) assuming 70% event-free rate in cRT, corresponding to a critical hazard ratio (HR) of 1.21. The trial was not formally powered to directly compare the two hRT schedules. Pt with N0 T1b-T3a localised PCa were randomized (1:1:1 ratio). The primary endpoint was PCa progression (freedom from biochemical failure by Phoenix consensus guidelines or PCa recurrence). Acute toxicity was assessed up to 18 weeks post treatment and late side effects to 5 years (yr) by RTOG, LENT-SOM and patient reported outcomes (PROs). Results: 3,216 pts were randomized between 2002 and 2011; 1,065 (74Gy), 1,074 (60Gy), 1,077 (57Gy). Baseline characteristics were well balanced across groups: median age 69 yr; NCCN risk group 15% low, 73% intermediate, 12% high. With median follow up 5.2yr, 5yr progression-free rate (95% CI) was 74Gy: 88.3% (86.0%, 90.2%); 60Gy: 90.6% (88.5%, 92.3%), 57Gy: 85.9 (83.4, 88.0); HR60/74: 0.83, 90% CI (0.68, 1.03), HR57/74: 1.20, 90% CI (0.99, 1.45). Significantly more events were observed with 57Gy compared to 60Gy; HR57/60: 1.44, 90% CI (1.18, 1.75), log-rank p=0.003. No significant difference in acute RTOG bladder or bowel toxicity was observed between hRT schedules. Late toxicity profile was favorable; with grade 2+ RTOG bladder (60Gy: 16/960 (1.7%); 57Gy: 11/962 (1.1%), p=0.34) and bowel (60Gy: 28/960 (2.9%); 57Gy: 17/962 (1.8%), p=0.10) toxicity at 2yr. Analysis of LENT-SOM and PROs supported these results. Conclusions: With 5 yr follow-up treatment with a 3Gy schedule of 60Gy/20f shows improved treatment efficacy compared to 57Gy/19f and is non-inferior to 74Gy/37f with a similar low level of acute and late normal tissue damage. Clinical trial information: ISRCTN97182923.

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.

Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 945-945
Author(s):  
Roland Fenk ◽  
Peter Schneider ◽  
Martin Kropff ◽  
Ali-Nuri Huenerlituerkoglu ◽  
Ulrich Steidl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Significant Difference

Abstract High-dose chemotherapy (HDT) improves the outcome of patients with multiple myeloma (MM) in comparison to conventional chemotherapy. Dose-escalating strategies including tandem HDT are currently evaluated to further improve remission rates and survival of patients. Therefore we conducted a randomized multicenter trial to compare an intensified conditioning regimen with the current standard high-dose melphalan. The primary study endpoint was response rate, with overall survival (OS), event-free survival (EFS) and toxicity analysed as secondary endpoints. Between 1997 and 1999 a total of 56 patients with stage II and III disease, who were matched for age (median 56 years), number of previous therapies (median time from diagnosis to transplant 7 months) and different risk factors (beta2-microglobulin, LDH, CRP, cytogentic abnormalities, chemoresistant disease, IgA-subtype, renal impairment), were randomized. All patients received 2 courses of oral idarubicine/dexamethasone and 2 courses of intravenous cyclophosphamide/adriamycine in combination with G-CSF followed by peripheral stem cell collection. Thirty patients were treated with melphalan 200mg/m2 (HD-M) whereas 26 patients received idarubicine 42mg/m2, melphalan 200mg/m2 and cyclophosphamide 120mg/kg (HD-IMC) followed by autologous blood stem cell transplantation. Acute toxicity was higher with HD-IMC, including 5 (20%) treatment-related deaths due to infections versus none (0%) in the HD-M group. This lead to early termination of the study. Severity of mucositis (grade III-IV 19 vs. 8 pts., p=0.001), CRP (20 vs. 7 mg/dl, p<0.001), days of fever (11 vs. 3, p<0.001), days with iv-antibiotics (13 vs. 4, p<0.001), number of erythrocyte-transfusions (6 vs. 2, p<0.001), number of platelet-transfusions (16 vs. 4, p<0.001) and days to granulocyte engraftment (18 vs. 11, p=0.007) were significantly higher after HD-IMC. After a follow-up of 5 years analysis restricted to patients surviving the first 30 days after HDT showed a trend to higher response rates (CR+vgPR: 47% (95%CI 24–72%) vs. 35% (95%CI 18–56%), PR 37% (95%CI 17–63%) vs. 48% (95%CI 29–68%) and time-to-progression (median 31 vs. 15 months, p=0.1) in the HD-IMC treatment arm in comparison to HD-M, but there was no significant difference in EFS and OS (median 22 vs. 30, p= 0.31 and 66 vs. 66 months, p=0.8, respectively). Univariate analysis demonstrated that LDH levels > 200 U/L (p=0.04) and chemoresistant disease (p=0.05) were a bad prognostic factor for EFS. Beta2-Microglobulin levels > 5mg/dl (p=0.01), abnormal conventional cytogenetics (p=0.02) and LDH levels > 200 U/L (p=0.03) were predictive for an inferior OS. In conclusion intensified conditioning for HDT had an intolerable high treatment-related mortality and did not improve EFS and OS in patients with multiple myeloma.

Patient-reported quality of life in men with TURP undergoing proton therapy for prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 220-220 ◽  
Author(s):  
Derek Lee ◽  
Bradford S. Hoppe ◽  
Tamara L. Smith ◽  
Christopher G. Morris ◽  
Romaine Charles Nichols ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Proton Therapy ◽  
Toxicity Assessment ◽  
Gu Toxicity ◽  
Significant Difference ◽  
Patient Reported ◽  
Grade 3

220 Background: We report on quality of life (QOL) and early toxicity following proton therapy (PT) among men with prostate cancer who underwent transurethral resection of the prostate (TURP) prior to treatment. Methods: Between 2006 and 2010, 1,540 patients were treated definitively with PT for prostate cancer at UFPTI and enrolled on a prospective IRB-approved outcomes protocol. One hundred of the men had received a TURP before PT. Baseline comorbidities, medications, expanded prostate index composite (EPIC) score, international prostate symptom score (IPSS), and CTCAE vs.3 toxicity assessment were collected prospectively. The Kaplan-Meier product limit method was used to estimate freedom from toxicity. Results: Men who had TURP prior to PT had lower EPIC scores at baseline and at all followup points for urinary function, urinary incontinence, and urinary summary (Table). The TURP group also had lower EPIC bowel bother, bowel function, and bowel summary at baseline, 6-month, and 1-year followup. EPIC urinary bother, urinary irritation/obstruction, and subscales did not show a statistically significant difference at baseline, but they did show lower scores for the TURP group at variable follow-up time points. The IPSS scores among the TURP group did not show a statistical difference from the non-TURP group, except at the 6-month follow-up time point. Toxicity assessment showed that the 2-year and 3-year cumulative incidence of grade 3 GU toxicity rate in the pretreatment TURP group were 14% and 18%, respectively. Conclusions: Pretreatment TURP was associated with both a high incidence of physician-assessed toxicity and inferior patient-reported QOL scores both before and after PT treatment. Studies investigating QOL and toxicity after specific prostate cancer therapies should stratify patients by pretreatment TURP. Longer follow-up and further evaluation of risk factors for grade 3 GU toxicity among this cohort are needed. [Table: see text]

Late toxicity described using patient reported outcomes measures (PROMS) in men treated with salvage radiation following primary high intensity focal ultrasound (HIFU) for localized prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 131-131 ◽  
Author(s):  
Reena Davda ◽  
Clement Orczyk ◽  
Mark Prentice ◽  
Aylin Sarova ◽  
Manit Arya ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Minimally Invasive ◽  
Symptom Score ◽  
Late Toxicity ◽  
Salvage Radiotherapy ◽  
Small Problem ◽  
Ablative Therapies ◽  
Number Of Patients ◽  
Patient Reported

131 Background: In primary treatment of localised prostate cancer, minimally invasive ablative therapies such as HIFU aim to achieve cancer control whilst offering a potentially favourable toxicity profile. At 5 years median follow up, 12% of patients treated with focal HIFU require salvage therapy. PROMS using Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC‐CP) provide a validated and clinically relevant tool to assess and quantify side effects from pelvic radiotherapy. There is limited data on late toxicity using PROMs with salvage radiotherapy in this setting. Methods: Retrospective analysis from prospectively collected data of 28 patients who received salvage radiotherapy at our institution 2010-2018 was performed. Late bowel and urinary toxicity measured by EPIC-CP is reported. Results: Gleason score at diagnosis: 3+3 4/28; 3+4 22/28; 4+3 2/28. HIFU treatment received: focal: 9/28; whole gland: 6/28; focal and redo focal: 7/28; focal and redo whole gland: 1/28; whole gland and redo: 5/28. All patients had mpMRI and biopsy proven recurrence with median PSA 6.6 ng/ml (0.57- 30.89). Median age at radiation was 67 years (55-80). Patients received 74 Gy to the prostate and 4 patients received additional pelvic lymph node irradiation. Three men received conformal radiotherapy (multiphase technique) and 25 arcing intensity modulated radiotherapy with hormone therapy as per risk stratification. Cumulative incidence of toxicity is reported at median follow-up of 43 months (7-99). Overall urinary function: no problem 8/28; very small problem 4/28; small problem 7/28; moderate problem 5/28; big problem 4/28 Urinary Incontinence Symptom Score: 2.5/12 (0-12) Urinary Irritation /Obstructive Symptom Score: 3.1/12 (0-12) Bowel Symptom Score: 3.5/12 (0-11) Biochemical relapse has occurred in 2/28 patients. Conclusions: Functional and oncological outcomes for a greater number of patients treated with minimally invasive ablative therapies followed by salvage radiation are required, however this data suggests radiation is a well-tolerated and effective salvage option following primary HIFU.

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