Phase I/II study on stereotactic hypofractionated once-weekly radiation therapy (SHORT) for localized prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 130-130 ◽  
Author(s):  
Indranil Mallick ◽  
Moses Arunsingh ◽  
Sriram Prasath ◽  
B Arun ◽  
Paromita Roy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Phase I ◽  
Treatment Time ◽  
Late Toxicity ◽  
Biochemical Control ◽  
Overall Treatment Time ◽  
Risk Patients ◽  
Prescription Dose

130 Background: The low α/β ratio of prostate cancer (PrCa) is well established. However, stereotactic hypofractionated radiotherapy (SRT) has been investigated primarily in highly selected patient populations with low-intermediate risk disease. We performed a clinical trial of SRT delivered in once-weekly fractions on an unselected cohort of patients with non-metastatic PrCa. Methods: In this Phase I/II study 30 patients with non-metastatic PrCa (multiparametric MRI cT1-4N0, M0, Gleason 6-10, PSA < = 60 ng/ml) were treated with SRT to a prescription dose of 35Gy in 5 fractions delivered once a week (overall treatment time 29 days). Elective nodal RT at 25Gy/5Fr was delivered in patients high-risk by NCCN criteria, and androgen deprivation therapy given to intermediate and high-risk patients. SRT was planned using volumetric intensity modulated arc therapy (VMAT) or Helical Tomotherapy (HT) with pre-defined dose-criteria. The primary endpoint was acute toxicity NCI CTC v4, and secondary endpoints were biochemical control and late toxicity. Results: Thirty patients completed treatment per-protocol. Stage T3, Gleason 8-10, and PSA > 10 was seen in 18 (60%), 7 (23%) and 24 (80%) respectively. Overall 20 (66.7%) were high-risk. Median of Mean PTV dose was 36Gy, and normal tissue constraints could be met in all patients (Table). Acute urinary toxicities (Gr 0: 1; Gr 1: 27; Gr 2: 1; Gr 3-4: 0) and acute rectal toxicities (Gr 0: 20; Gr 1: 10; Gr 2: 0; Gr 3-4: 0) were very modest. The mean IPSS scores at baseline, end of treatment and 3 months after treatment were 8.8, 14.7, and 9.9. With a median follow up of 23.7 months, the 2 year biochemical control was 96%. Late grade 2 rectal bleeding developed in 1 patient. Conclusions: Carefully planned stereotactic VMAT/HT based once-weekly SRT to a predominantly high-risk non-metastatic PrCa cohort was very well tolerated and found to be safe for clinical use. Preliminary biochemical control and late toxicity profiles are encouraging. Clinical trial information: CTRI/2016/02/006671. [Table: see text]

scholarly journals Randomized Trial of Hypofractionated External-Beam Radiotherapy for Prostate Cancer

2013 ◽  
Vol 31 (31) ◽  
pp. 3860-3868 ◽  
Author(s):  
Alan Pollack ◽  
Gail Walker ◽  
Eric M. Horwitz ◽  
Robert Price ◽  
Steven Feigenberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
External Beam Radiotherapy ◽  
Intensity Modulated Radiation Therapy ◽  
Late Toxicity ◽  
Urinary Function ◽  
Conventional Fractionation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Risk Patients

Purpose To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. Patients and Methods Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed. Results There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT. Conclusion The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.

scholarly journals Value of 68Ga-labeled Bombesin Antagonist (RM2) in the Detection of Primary Prostate Cancer Comparing With [18F]fluoromethylcholine PET/CT and mpMRI – a Phase I/II Study

2021 ◽  
Author(s):  
Mohsen Beheshti ◽  
Pekka Taimen ◽  
Jukka Kemppainen ◽  
Ivan Jambor ◽  
Andre Müller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase I ◽  
Risk Group ◽  
Lesion Detection ◽  
Abnormal Finding ◽  
High Risk Patients ◽  
Pet Ct ◽  
Significant Difference ◽  
Risk Patients

Abstract Purpose: Overexperssion of Gastrin-releasing-peptide receptor (GRPr) in prostate carcinoma (PCa) suggests new means in the detection of prostate cancer foci. The bombesin derivative RM2 (DOTA-4-amino-1-carboxy­methyl­piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) is a GRPr antagonist with strong binding affinity. Based on promising results from a first-in-man study on PCa detection in patients with local disease, a Phase I/II study was initiated and the ability of [68Ga]Ga-RM2 PET/CT to detect PCa lesions was compared with [18F]fluoromethylcholine ([18F]FCH) PET/CT and multiparameteric prostate Magnetic Resonance Imaging (mpMRI).Methods: This Phase I/II study was conductedwith a pre-specified interim analysis following the enrollment of 30 biopsy-positive PCa subjects, stratified into low, intermediate and high pretreatment risk of extra-glandular metastases with reference to NCCN criteria. Each subject had PCa detected by transrectal ultrasound guided prostate biopsy and subjects were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate and high risk patients. Following administration of an intravenous dose of 140 MBq of [68Ga]Ga-RM2,imaging was conducted at 60 min. p.i.. Twenty-five (25/30) subjects had concomitant [18F]FCH PET/CT imaging. All patients underwent mpMRI. Intra-prostatic and pelvic nodal PET/CT findings were correlated with histopathologic results.Results: High uptake of [68Ga]Ga-RM2 was seen in pancreas and the urinary system with very low background uptake in the rest of the abdomen or thorax. Despite of high bladder activity, focal intraprostatic uptake was readily well detectable. Of overall 312 analyzed regions, 120 regions (4 to 8 lesions per-patient) showed abnormal finding in the prostate gland. In a region-based analysis overall sensitivity and specificity of [68Ga]Ga-RM2 PET/CT in the detection of primary tumor were 74% and 90%, respectively; while it was 60% and 80% for [18F]FCH PET/CT and 72% and 89% for mpMRI. Although, the overall sensitivity of [68Ga]Ga-RM2 PET/CT was higher comparing to [18F]FCH PET/CT and mpMRI; however, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET/CT and [18F]FCH PET/CT in intermediate-risk group (P=0.01) and [68Ga]Ga-RM2 PET/CT and mpMRT in high-risk group (p=0.03). [68Ga]Ga-RM2 PET/CT correctly detected 2 histopathologically verified LN metastases in 2 high risk patients; while 18F-FCH PET/CT only identified the LN lesion in 1 patient.Conclusion: [68Ga]Ga-RM2 is a promising new PET-tracer with a high detection rate for intraprostatic PCa. While index lesion detection rates were similar in both PET/CT studies, the improved specificity of [68Ga]Ga-RM2 for canver versus BPH renders it notably better than [18F]FCH in the detection of intraprostatic lesions. In addition, GRP-R-based imaging seems to play a complementary role to Choline-based imaging for full characterization of PCa extent, biopsy guidance in low and intermediate metastatic risk PCa patients and has the potential to discriminate them from whom of those at higher risks.Trial Registeration number: EudraCT-Nr.: 2014-003027-21, Date: 10 June, 2014

Update of the HIPRO study: Late toxicity and outcome at seven years.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 81-81
Author(s):  
D. Thomson ◽  
S. Merrick ◽  
R. Swindell ◽  
J. Coote ◽  
P. A. Elliott ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Control ◽  
Dose Escalation ◽  
Treatment Time ◽  
Intensity Modulated Radiotherapy ◽  
Late Toxicity ◽  
Urinary Symptoms ◽  
Overall Treatment Time ◽  
Intensity Modulated ◽  
Pre Treatment

81 Background: Dose-escalated radiotherapy for localised prostate cancer improves disease control but at the expense of increased overall treatment time and late toxicity. Given the low alpha-beta ratio for prostate cancer, treatment with hypofractionation should be biologically advantageous. Intensity-modulated radiotherapy (IMRT) allows dose escalation with hypofractionation, while achieving acceptable levels of toxicity. We report our 7 year late toxicity data in patients treated with two such regimens within the Hypofractionated Dose Escalation utilising Intensity-modulated Radiotherapy in Carcinoma of the Prostate (HIPRO) study. Methods: Sixty men, median age 75 years (50-87), with localised adenocarcinoma of prostate (T1-3NOMO) and either Gleason score ≥7 or PSA 20-50ng/L received 57Gy in 19 fractions (n=30) or 60Gy in 20 fractions (n=30) using 5-field inverse-planned IMRT. All patients received neoadjuvant hormone therapy, continuing for up to 6 months after treatment. Late toxicity was assessed at 7 years follow-up using RTOG criteria and LENT/SOMA questionnaire. Results: Forty-four (73%) patients were alive at 7 years. Nine patients (21%) reported RTOG grade 1 bowel or bladder toxicity; there was no grade 2 toxicity or above and no difference between the fractionation schedules. LENT/SOMA questionnaires were returned by 31/44 patients. Mean and median scores were less than one for bowel and urinary symptoms. When compared with pre-treatment, the proportion of patients with significant (maximum LENT/SOMA ≥2) urinary symptoms remained similar (75% vs. 76%), problems with sexual function had decreased (84% vs. 98%) but bowel symptoms increased (62% vs. 25%). At 5 years, overall survival was 83% and 74% and cause-specific survival was 83% and 84% in the 57Gy and 60Gy groups respectively. Conclusions: Dose-escalated hypofractionated IMRT for prostate cancer appears well tolerated with acceptable levels of late toxicity. Studies to assess long term disease control with these regimens are on-going. No significant financial relationships to disclose.

The impact of neoadjuvant weekly ixabepilone for high-risk prostate cancer: A phase I/II clinical trial.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 158-158 ◽  
Author(s):  
Jodi Lyn Layton ◽  
Angela Marie Plette ◽  
Joseph F. Renzulli ◽  
E. Bradley Miller ◽  
Howard Safran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Phase I ◽  
High Risk Prostate Cancer ◽  
Post Surgery ◽  
Risk Prostate Cancer ◽  
Psa Response ◽  
The Impact

158 Background: Potential benefits of neoadjuvant chemotherapy are tumor downstaging and treatment of micrometastatic disease. A prior study using docetaxel yielded no pathologic complete responses and concerns for increased operative morbidity. In Phase II studies, ixabepilone has promising activity in metastatic prostate cancer. Our study is a Phase I/II clinical trial evaluating neoadjuvant, weekly ixabepilone in men with high-risk prostate cancer opting for radical prostatectomy. Methods: Men with high risk prostate cancer defined as either Gleason 8-10, cT3 disease, high volume Gleason 4+3 and a palpable nodule or a PSA>20 ng/ml were eligible. Men received weekly ixabepilone 16-20/m2 for 12-16 weeks prior to surgery. Fifteen men underwent robotic prostatectomy; one patient who had an open prostatectomy. Initial PSA response, post-operative PSA values, pathology, and evaluation of adverse events were recorded. Results: We enrolled 16 men with a mean follow-up of 15.25 months at time of review. All had pretreatment Gleason scores of 4+3 or higher. With neoadjuvant treatment, PSA values decreased in 14/16 men (mean 46.8%); increased in 2/16 men. None reached an undetectable pre-operative PSA. Nine men experienced an adverse event requiring dose modification or cessation of chemotherapy (neuropathy or allergic reaction). Only 5/16 men completed planned treatment. Mean operative time, EBL, and hospital stay were 189 minutes, 184mL, and1.5 days, respectively; all consistent with institutional and national norms. Post surgery 15/16 (94%) had pT3 disease, 8/16 (50%) had a positive surgical margin and 2/16 (12.5%) had positive regional lymph nodes. There were no pathologic complete responses. Only 1/16 (6.25%) had a biochemical relapse. Conclusions: While a PSA response is achieved, there is substantial toxicity with neoadjuvant weekly ixabepilone. Men were able to undergo prostatectomy without increased morbidity after neoadjuvant therapy. Extracapsular extension and positive surgical margins remained common in this population with high-risk disease. Assessment of biochemical recurrence rates and time to treatment failure will require longer, planned follow-up.

Stereotactic radiotherapy +/- HDR boost for unfavorable-risk prostate cancer: Comparison of efficacy, survival, and late toxicity outcomes.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 372-372
Author(s):  
Andrew Loblaw ◽  
Patrick Cheung ◽  
Danny Vesprini ◽  
Stanley K. Liu ◽  
William Chu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Randomized Study ◽  
Late Toxicity ◽  
Similar Efficacy ◽  
Risk Prostate Cancer ◽  
Brachytherapy Boost ◽  
Risk Patients ◽  
Cause Specific Survival

372 Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. Stereotactic body radiotherapy (SBRT) is an emerging treatment for prostate cancer but its use in high risk disease is limited. We compare efficacy, survival and late toxicity outcomes in patients treated on 2 prospective, phase 2 protocols that both use pelvic SBRT and androgen deprivation therapy (ADT). One used MR-guided HDR brachytherapy boost (SPARE) and the other uses a SBRT boost (SATURN). Methods: SPARE was a phase I/II study where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis. ADT was used for 6-18 months. SATURN was a phase II study where high risk patients received 40Gy to prostate and 25Gy to pelvis along in 5 weekly fractions with 12-18 months ADT. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA < 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival were calculated. Day 0 was first day of RT for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR (UIR), 50% HR) completed SPARE while 30 patients (7% UIR, 93% HR) completed SATURN. Median follow-up of 50 and 48 months, respectively. Actuarial 4-year BF was 11.5% and 0%. Median nPSA was 0.02 ng/ml for both studies. 4yPSARR was 69% and 93%. 4-year cause-specific survival was 96% and 100%. Toxicities are listed in Table. Conclusions: In the context of SBRT pelvis and ADT, SBRT boost provides similar efficacy for unfavorable risk prostate cancer with acceptable but worse toxicities compared to HDR boost. A randomized study is recommended to answer this question. Clinical trial information: 01953055. [Table: see text]

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