Background
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NCT01859221: A single-institution phase II stereotactic body radiotherapy and stereotactic hypofractionated radiotherapy for oligometastatic hormone sensitive and hormone-resistant prostate cancer
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NCT0219278: SBRT as a treatment of oligometastases of prostate cancer
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NCT01558427: a randomized Phase II Trial comparing salvage treatment (surgery or SBRT) or active clinical surveillance for oligometastatic prostate cancer [15]
Methods/Design
Hypothesis
Study objectives
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In case of decline from starting point: record time from randomization to first PSA increase that is ≥25 % and ≥ 2 ng/ml above the nadir OR that is ≥25 % and rises above the pre-treatment PSA value and which is confirmed by a second value 3 or more weeks later.
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In case of no decline from starting point: PSA increase that is ≥25 % and ≥ 2 ng/ml after 3 months if baseline PSA is ≥2 ng/ml. PSA increase that is ≥25 % after 3 months if starting point PSA is < 2 ng/ml.
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overall survival
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acute and late toxicity: evaluated by CTC-AE v4
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quality of life: EORTC QLQ-C30 and PR25 questionnaires
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site of tumor progression: using fluorocholine PET at biochemical relapse
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Time to start of palliative ADT: ADT will be started at time of polymetastatic disease, local progression or symptoms.
Main inclusion criteria
Main exclusion criteria
Statistics
Statistical justification for the number of inclusions
Level of statistical significance set
Statistical criteria for stopping the study
Detailed description of techniques to be used
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General recommendations
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The use of Intensity-Modulated Radiation Therapy (IMRT) is mandatory.
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Irradiation will be delivered with a non-empty bladder and an empty rectum. It is recommended that the patient empties his bladder and rectum one hour before the planning CT-scan and before each radiotherapy treatment, and then drink at least 1/3 L of water after voiding. The one hour delay will be adapted to the patient’s continence.
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Daily verification of patient’s organ positioning using IGRT is mandatory
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Verification of in vivo dose delivery is mandatory
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The use of a record and verify processing software is mandatory.
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Preparation of treatment
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Planning CT of the pelvic cavity that includes all of the pelvic lymph nodes will be performed in the supine position, with iv injection of contrast agent to help visualize the pelvic vessels. Oral contrast agent will be administered to assist in the the determination of the small bowel volume. The minimum CT resolution will be at least 3 mm thick slices every 3 mm, but thinner slices may be necessary for very small volume lymphadenopathy. Merging the CT with pelvic MRI may help visualize the vascular axes and pelvic lymph nodes.
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Fusion with FCH PET:The FCH PET images will be segmented using a threshold adapted to the size of the lymphadenopathy. These images will be used to locate the pathological lymph nodes, but the tumor volume (GTV) will be contoured on the planning CT.
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Target volumes
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Metastatic lymph nodes
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Whole pelvic lymph node irradiation
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Prostate bed
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Boundaries
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anteriorly: the posterior border of the pubic bone;
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posteriorly: the rectal wall;
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caudally: 8–12 mm below the vesicoureteral anastomosis;
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laterally: the levator ani and internal obturator muscle.
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anteriorly: including 1–2 cm of the posterior wall of the bladder;
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posteriorly: the mesorectal fascia;
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cranially: the end of the vas deferens or 3–4 cm above the pubic symphysis;
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laterally: the sacro-recto-genito-pubic fascia.
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Local relapse in the prostate bed (PBR GTV)It is possible to define a PBR GTV that encompasses the FCH-PET signal in the prostate bed, possibly with the aid of pelvic MRI. RPB CTV will be defined by a 5mm-margin around the PBR GTV. The PBR PTV will include the CTV with an extra margin of 5 mm.
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Organs at risk (OARs)OARs will be contoured as recommended by the RTOG [20]. It is not intended to add margins (PRV) around organs at risk.
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Bladder: the outer contour of the bladder on all sections where it appears. The bladder volume is the volume between the outer contour and an inner contour that is defined 7mm from the outer contour.
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Rectum: the external contour of the rectum from the recto-sigmoid junction to the anal canal. The rectal wall is the volume between the outer contour and an inner contour that is defined 5mm from the outer contour.
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Intestine: the external contours of the sigmoid, colon and the small intestine are defined as an “intestine bag” including the abdominal cavity as a whole. It will be important not to create areas of overlap between the intestine and the CTVs.
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Femoral head.
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Anal canal: 3 cm from its margin.
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PTV1-PTV5: 66 Gy in 30 fractions of 2.2 Gy
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PLN PTV: 54 Gy in 30 fractions of 1.8 Gy
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PB PTV: 60 Gy in 30 fractions of 2 Gy. An additional 6 Gy (3x2 Gy fractions) can be delivered on the entire prostate bed.
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PBR PTV: 72 Gy in 36 fractions of 2 Gy (66 Gy to the PTV prostate bed plus an additional boost of 6 Gy -3x2 Gy)
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Bladder: the bladder volume receiving a dose > 65 Gy will be no greater than 50 %.
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Rectum: V50 < 50 %, V60 < 35 %, V65 < 25 %, V70 < 20 %, and V75 < 15 %.
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Bowel: the volume receiving 45 Gy will be less than 195 ml.
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Femoral head: <5 % of each femoral head should receive a dose > 50 Gy.
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Anal canal: D55 < 100 %.
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Image guidance
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Quality control.
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Quality control of target volumes and critical organs
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CTV and PTV contoured according to protocol;
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organs at risk (bladder and rectal walls and femoral heads) contoured according to protocol;
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DVH for intestine, bladder and rectal wall, PTV and CTV that meet dose constraints;
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a statement that patients will be treated with an approved daily image guidance technique.
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Quality control of IMRTAll IMRT plans will undergo quality assurance evaluation with ion chamber measurements or an equivalent method of dose verification to verify the absolute dose for each IMRT field and film dosimetry to measure the relative dose for each IMRT field, as in standard clinical practice. Independent Monitor Units calculation may be substituted for ion chamber dosimetry when available.
Follow-up
Visits | Inclusion | Treatment period | follow-up | |||
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Visits | Max 2 months prior to RT day 1 | M1 1 month after end of RT | Before progression | After progression | ||
Every 6 months during 2 years | Every 6 months until progression | Every 6 months until death | ||||
Inclusion/exclusion criteria | X | |||||
Signed consent form | X | |||||
Inclusion (max 2 months prior to RT) | X | |||||
FCH PET | X (a) | X (b) | ||||
Physical examination with PS | X | X (d) | X | X | X | X |
Prior history, tumor characteristics | X | |||||
Blood Pressure | X | X (d) | X | X | ||
Acute toxicity during ADT and RT (f) | X (d) | X | ||||
Late toxicity (f) | X | |||||
QLQ-C30 et QLQ-PR25 | X | X | X | |||
PSA | X | X (f) | X (f) | X (f) | ||
Testosterone | X (g) | X | X | X | ||
ADT (c) + RT | X |
Discussion
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Project planning:
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The role of each team
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Project calendarThe study has been submitted and approved by regulatory authorities (ANSM; date of approval: 13/06/14) and ethics committee (Centre de Protection des Personnes Ouest IV - Nantes; date of approval: 3/05/14). The study opened in september 2014. A written informed consent will be obtained from the study participants. Recruitment is planned until the end of 2016. After a two-year minimum follow-up, final results will be presented during the last trimester 2018.
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Project co-ordinationThe project has been extensively discussed and approved by the GETUG. Patient recruitment will be monitored at each quarterly GETUG meeting.