C. Udrescu

Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

PURPOSE The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. METHODS AND MATERIALS In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). RESULTS The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. CONCLUSIONS The injection of HA significantly limited radiation doses to the rectal wall.

Evaluation of the respiratory prostate motion with four-dimensional computed tomography scan acquisitions using three implanted markers

BACKGROUND AND PURPOSE During the irradiation of the prostate cancer, it is crucial to take into account the possible displacements in defining the planning target volume. The objective of this study was to specifically analyze the respiratory-induced prostate motion using a four-dimensional CT scan (4DCT). MATERIALS AND METHODS Ten patients have been treated for prostate cancer in the supine position and with three implanted gold markers; they underwent a 4DCT using a GE LightSpeed16 CT scan (slice thickness 2.5mm). This acquisition was divided into 10 phases over the respiratory cycle using the Advantage4D software. For each phase, digitally-reconstructed radiographs (DRRs) were created at 0° and 90° with the view of the markers. The coordinates of each marker center were generated from the scan isocenter. The motion amplitude was: visually analyzed on the dynamic 4DCT sequences and then more precisely calculated by comparing the marker coordinates on the 10 scans. RESULTS There was not any difficulty in defining the coordinates of the markers on each series. No prostate motion was observed on a simple visual analysis of the dynamic 4DCT sequences. After a more specific analysis, using the coordinates of the fiducials on the 10 phases, the prostate motion remained below 1mm in all directions, except for the cranio-caudal, where it was undetectable (thereby below the slice thickness of 2.5mm). CONCLUSIONS To our knowledge, this is the first study that evaluates the respiratory-induced prostate motion, using a 4DCT scan. Even if important prostate displacement can occur during the prostate treatment, because of the bladder or rectum filling, in the present study no respiratory-induced prostate motion was observed.

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

PURPOSE Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. METHODS AND MATERIALS The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. RESULTS From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. CONCLUSIONS The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

Does hormone therapy modify the position of the gold markers in the prostate during irradiation? A daily evaluation with kV-images

PURPOSE Gold markers are frequently used for a better daily repositioning of the prostate before irradiation. The purpose of this work was to analyze if the combination of an androgen deprivation with the external irradiation could modify the position of the gold markers in the prostate. PATIENTS AND METHODS Ten patients have been treated for a prostate cancer, using three implanted gold markers. The variations of the intermarker distances in the prostate were measured and collected on daily OBI(®) kilovoltage images acquired at 0° and 90°. Five patients had a 6-month androgen deprivation started before the external irradiation (H group) and five did not (NH group). RESULTS A total number of 1062 distances were calculated. No distance variation greater than 3.7mm was seen between two markers, in any of the two groups. The median standard deviations of the daily intermarker distance differences were 0.7mm (range 0.3-1.2mm) for the H group and 0.6mm (range 0.2-1.2mm) for the NH group. The intermarker distances variations were noted as greater than -2mm, between -2mm and 2mm and greater than 2mm in 16.4, 83.4 and 0.2% for the H group and 1.3, 98.5 and 0.2% for the NH group, respectively. CONCLUSION The distance variations remained less than 4mm in both groups and for all the measurements. In the NH group, the variation of the distance between two markers remained below 2mm in 98.5%. In the H group, the presence of a reduction of distance above 2mm in 16.4% of measurements could indicate the shrinkage of the prostate volume.

Accuracy of Elastic Fusion of Prostate Magnetic Resonance and Transrectal Ultrasound Images under Routine Conditions: A Prospective Multi-Operator Study

Purpose To evaluate in unselected patients imaged under routine conditions the co-registration accuracy of elastic fusion between magnetic resonance (MR) and ultrasound (US) images obtained by the Koelis Urostation™. Materials and Methods We prospectively included 15 consecutive patients referred for placement of intraprostatic fiducials before radiotherapy and who gave written informed consent by signing the Institutional Review Board-approved forms. Three fiducials were placed in the prostate under US guidance in standardized positions (right apex, left mid-gland, right base) using the Koelis Urostation™. Patients then underwent prostate MR imaging. Four operators outlined the prostate on MR and US images and an elastic fusion was retrospectively performed. Fiducials were used to measure the overall target registration error (TRE3D), the error along the antero-posterior (TREAP), right-left (TRERL) and head-feet (TREHF) directions, and within the plane orthogonal to the virtual biopsy track (TRE2D). Results Median TRE3D and TRE2D were 3.8–5.6 mm, and 2.5–3.6 mm, respectively. TRE3D was significantly influenced by the operator (p = 0.013), fiducial location (p = 0.001) and 3D axis orientation (p<0.0001). The worst results were obtained by the least experienced operator. TRE3D was smaller in mid-gland and base than in apex (average difference: -1.21 mm (95% confidence interval (95%CI): -2.03; -0.4) and -1.56 mm (95%CI: -2.44; -0.69) respectively). TREAP and TREHF were larger than TRERL (average difference: +1.29 mm (95%CI: +0.87; +1.71) and +0.59 mm (95%CI: +0.1; +0.95) respectively). Conclusions Registration error values were reasonable for clinical practice. The co-registration accuracy was significantly influenced by the operator’s experience, and significantly poorer in the antero-posterior direction and at the apex.

Potential interest of developing an integrated boost dose escalation for stereotactic irradiation of primary prostate cancer

INTRODUCTION The stereotactic irradiation is a new approach for low-risk prostate cancer. The aim of the present study was to evaluate a schema of stereotactic irradiation of the prostate with an integrated-boost into the tumor. MATERIAL AND METHODS The prostate and the tumor were delineated by a radiologist on CT/MRI fusion. A 9-coplanar fields IMRT plan was optimized with three different dose levels: 1) 5 × 6.5 Gy to the PTV1 (plan 1), 2) 5 × 8 Gy to the PTV1 (plan 2) and 3) 5 × 6.5 Gy on the PTV1 with 5 × 8 Gy on the PTV2 (plan 3). The maximum dose (MaxD), mean dose (MD) and doses received by 2% (D2), 5% (D5), 10% (D10) and 25% (D25) of the rectum and bladder walls were used to compare the 3 IMRT plans. RESULTS A dose escalation to entire prostate from 6.5 Gy to 8 Gy increased the rectum MD, MaxD, D2, D5, D10 and D25 by 3.75 Gy, 8.42 Gy, 7.88 Gy, 7.36 Gy, 6.67 Gy and 5.54 Gy. Similar results were observed for the bladder with 1.72 Gy, 8.28 Gy, 7.01 Gy, 5.69 Gy, 4.36 Gy and 2.42 Gy for the same dosimetric parameters. An integrated SBRT boost only to PTV2 reduced by about 50% the dose difference for rectum and bladder compared to a homogenous prostate dose escalation. Thereby, the MD, D2, D5, D10 and D25 for rectum were increased by 1.51 Gy, 4.24 Gy, 3.08 Gy, 2.84 Gy and 2.37 Gy in plan 3 compared to plan 1. CONCLUSIONS The present planning study of an integrated SBRT boost limits the doses received by the rectum and bladder if compared to a whole prostate dose escalation for SBRT approach.

ExacTrac Snap Verification: A New Tool for Ensuring Quality Control for Lung Stereotactic Body Radiation Therapy

PURPOSE The intrafraction verification provided by ExacTrac X-ray 6D Snap Verification (ET-SV) allows the tracking of potential isocenter displacements throughout patient position and treatment. The aims of this study were (1) to measure the intrafraction variations of the isocenter position (random errors); (2) to study the amplitude of the variation related to the fraction duration; and (3) to assess the impact of the table movement on positioning uncertainties. METHODS AND MATERIALS ET-SV uses images acquired before or during treatment delivery or both to detect isocenter displacement. Twenty patients treated with stereotactic body radiation therapy (SBRT) for lung tumors underwent SV before or during each beam. Noncoplanar beams were sometimes necessary. The time between the setup of the patient and each SV was noted, and values of deviations were compiled for 3 SV time groups: SV performed at ≤10 min (group 1), between 11 and 20 min (group 2), and ≥21 min (group 3). Random errors in positioning during the use of noncoplanar fields were noted. RESULTS The mean isocenter deviation±SD was 2±0.5 mm (range, 1-8 mm). The average deviations±SD increased significantly from 1.6±0.5 mm to 2.1±0.8 mm and 2.2±0.6 mm for groups 1, 2, and 3 (P=.002), respectively. Percentages of deviation≥3 mm were 7.06%, 22.83%, and 28.07% and 1.08%, 4.15%, and 8.4% for ≥5 mm (P<.0001). For 11 patients, table rotation was necessary. The mean isocenter deviation±SD increased significantly from 1.9±0.5 mm before table rotation to 2.7±0.5 mm (P=.001) for the first beam treated after rotation. CONCLUSIONS SV detects isocenter deviations, which increase in amplitude and frequency with the fraction duration, and enables intrafraction verification for SBRT (taking into account clinical condition and technical issues). SV gives accurate targeting at any time during irradiation and may raise confidence to escalate the dose. SV appears to be an important tool for ensuring the quality control of SBRT.

Technique of Injection of Hyaluronic Acid as a Prostatic Spacer and Fiducials Before Hypofractionated External Beam Radiotherapy for Prostate Cancer

OBJECTIVE To describe a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity after an image-guided external beam radiotherapy (EBRT) with hypofractionation for prostate cancer and to assess the tolerance and the learning curve of the procedure. MATERIALS AND METHODS Thirty patients with prostate cancer at low or intermediate risk were included in a phase II trial: image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with intensity-modulated radiotherapy. A transrectal implantation of 3 fiducials and transperineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was performed by 1 operator. The thickness of HA was measured at 10 points on magnetic resonance imaging to establish a quality score of the injection (maximum score = 10) and determine the learning curve of the procedure. RESULTS The quality score increased from patients 1-10, 11-20, to 21-30 with respective median scores: 7 [2-10], 5 [4-7], and 8 [3-10]. The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4-29], 9.8 mm [5-21.2], and 9.9 mm [3.2-21.5]. The injection of the HA induced a median pain score of 4 [1-8] and no residual pain at mid-long term. CONCLUSION Creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before a hypofractionated EBRT for prostate cancer.

Transrectal implantation and stability of gold markers in prostate bed for salvage radiotherapy of macroscopic recurrences

BACKGROUND AND PURPOSE The objective of the study was to verify the stability of gold markers in the prostatic bed (PB) during salvage radiotherapy. MATERIAL AND METHODS Seven patients, diagnosed with a macroscopic nodule visible on MRI, underwent targeted MRI-guided biopsies. Three gold markers were implanted into the PB close to the relapsing nodule for CT/MRI fusion. A dose of 60Gy was delivered using IMRT to the PB followed by a dose escalation up to 72Gy to the macroscopic nodule. Daily anterior and left-lateral kV-images were acquired for repositioning. The coordinates of the center of each marker were measured on the two kV-images. The distance variations (Dvar) of the markers in the first session and the subsequent ones were compared. RESULTS No marker was lost during treatment. The average distance between markers was 7.8mm. The average Dvar was 0.8mm, in absolute value. A total of 380/528 (72%) Dvar were ⩽1mm. A Dvar greater than 2mm was observed in 5.7% of measurements, with a maximum value of 4.8mm. CONCLUSIONS Despite the absence of the prostate, the implantation of gold markers in the PB remains feasible, with Dvar often less than 2mm, and could be used to develop new approaches of salvage focal radiotherapy on the macroscopic relapse after prostatectomy.

Prospective evaluation of a specific technique of sexual function preservation in external beam radiotherapy for prostate cancer

OBJECTIVE Sexual preservation is an important issue in the treatment of localized prostate cancer. A technique of irradiation was developed to better preserve this function and has been evaluated. METHODS Eleven patients, with no erectile dysfunction (ED), were treated with daily IMRT-IGRT (total dose: 76-78 Gy). The pudendal arteries, penile bulb and cavernous body were delineated on the planning CT scan. The doses to these structures (with a 5 mm margin) were optimized to be as low as possible. The erectile function was documented using IIEF-5 scores at baseline, 6 months, 1 and 2 years. No ED was defined by an IIEF5 ≥ 20/25, a mild ED by an IIEF5 score of 17-19 and an important ED by a score <17. RESULTS The mean age was 68.4 years. At the median follow-up of 36 months, there was no biochemical relapse. Before RT, the mean IIEF5 score in all 11 patients was 23.4 (range, 20-25). At 6, 12, 18 and 24 months after RT, the mean IIEF scores were 21.2 (14-25), 21.3 (14-25), 21.8 (16-25) and 21.8 (16-25), respectively. At 2 years, 8 patients (72.7%) had no ED and 2 patients (18.2%) experienced a mild ED. The only patient with an important ED had a medical treatment and recovered a satisfactory IIEF score from 16 to 24. CONCLUSION The results of this technique of optimisation for sexual preservation are encouraging. Despite a mean age close to 70 years at the time of treatment, 90.9% of the patients had no to mild ED at 2 years. This rate increases at 100% with medical treatment. Advances in knowledge: Dose optimization on sexual organs is possible and could decrease the ED rates.