Stereotactic body radiotherapy for inoperable patients with renal carcinoma.

INTRODUCTION: The objective of this study was to analyze the dose-dependent safety profiles of stereotactic body radiation therapy (SBRT) in patients with inoperable small renal cell carcinoma (RCC). MATERIAL: This is a retrospective study from a single institution including patients with RCC treated between 2011 and 2020 with SBRT on the primary tumor or on a local recurrence after surgery. All patients had been declared inoperable or refused surgery. The patients were divided into two dose level groups: group 1 (BED10<60Gy) and group 2 (BED10≥60Gy). Acute and late toxicities, renal function and local control (LC) were compared between the two groups. RESULTS: A total of 24 patients were analyzed with an average follow-up of 25.1 months. Nine patients (37%) and three patients (14%) reported grade 1-2 acute and late toxicities, respectively. No grade≥3 acute and late toxicities were observed. There was no significant difference in acute and late toxicities between the two groups (P=0.21 and P=0.27, respectively). There was no significant difference in estimated glomerular filtration rate in the 15 patients, eligible for renal toxicity analysis between the pre-radiation and the 12-month follow-up (P=0.1) and the last follow-up (P=0.06). LC at the last follow-up was noted in 19 out of 23 patients (83%) and was based on imaging acquisition. LC was 77.8% for group 1 and 85.7% for group 2 (P=1.95). CONCLUSION: Dose escalation was not associated with an increase in acute and late grade≥2 toxicities. There appears to be a trend towards increased LC at higher doses.

Prostate hypofractionated radiotherapy (62Gy at 3.1Gy per fraction) with injection of hyaluronic acid: final results of the RPAH1 study.

OBJECTIVES: The present multicenter Phase II study evaluated the rate of late grade ≥2 gastrointestinal (GI) toxicities at 3 years, after hypofractionated radiotherapy (HFR) of prostate cancer with injection of hyaluronic acid (HA) between the prostate and the rectum. METHODS: Between 2010 and 2013, 36 patients with low- or intermediate-risk prostate cancer were treated by HFR/IMRT-IGRT. 20 fractions of 3.1 Gy were delivered, 5 days per week for a total dose of 62 Gy. A transperineal injection of 10cc of HA was performed between the rectum and the prostate. Late toxicities were evaluated between 3 and 36 months after the end of treatment (CTCAE v4). RESULTS: Median pretreatment prostate-specific antigen was 8 ng ml-1. Among the 36 included patients, 2 were not evaluated because they withdrew the study in the first 3 months of follow-up, and 4 withdrew between 3 and 36 months, the per protocol population was therefore composed.Late grade ≥2 GI toxicities occurred in 4 (12%) patients with 3 (9%) Grade 2 rectal bleedings and one diarrhoea. Therefore, the inefficacy hypothesis following Fleming one-stage design cannot be rejected. None of the patients experienced late Grade 3-4 toxicities. Among the 30 patients completing the 36 months' visit, none still had a grade ≥2 GI toxicity. Late grade ≥2 genitourinary (GU) toxicities occurred in 14 (41%) patients. The most frequent toxicities were dysuria and pollakiuria. Four patients still experienced a grade ≥2 GU toxicity at 36 months.The biochemical relapse rate (nadir +2 ng ml-1) was 6% (2 patients). Overall, HA was very well tolerated with no pain or discomfort. CONCLUSION: Despite the inefficacy of HA injection was not rejected, we observed the absence of Grade 3 or 4 rectal toxicity as well as a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up. Late urinary toxicities are the most frequent but the rate decreases largely at 3 years. ADVANCES IN KNOWLEDGE: With an injection of HA, hypofractionated irradiation in 4 weeks is well tolerated with no Grade 3 or 4 GI toxicity and a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up.

Dosimetric feasibility of stereotactic irradiation of primary prostate cancer at 5x9 Gy with a method of urethral sparing.

OBJECTIVE: The most commonly used dose for prostate cancer stereotactic body radiotherapy (SBRT) is 5 × 7.25 Gy. The aim of this study was to evaluate the dosimetric feasibility of a 5 × 9 Gy SBRT regimen while still limiting the dose to the urethra to 5 × 7.25 Gy. This dosimetric study is part of the groundwork for a future Phase III randomized trial. METHODS: The prostate, the urethra and the tumors were delineated on 20 dosimetric CT-scans with MRI-registration. The planning target volume (PTVp) was defined as a 5 mm expansion (3 mm posteriorly) of the prostate. The planning at risk volume (PRVu) was defined as a 2 mm expansion of the urethra. The tumors were delineated on the MRI (GTVt) and a 3 mm-margin was added to create a tumoral planning target volume (PTVt). IMRT plans were optimized to deliver 5 × 9 Gy to the PTVp, limiting the dose to the PRVu to 5 × 7.25 Gy. Results are presented using average (range) values. RESULTS: PTVp doses were D98% = 36.2 Gy (35.6-36.8), D2% = 46.9 Gy (46.5-47.5) and mean dose = 44.1 Gy (43.8-44.5). The dose to the PRVu was within tolerance limits for all 20 patients: V34.4Gy = 99.8% (99.2-100) and D5% = 38.7 Gy (38.6-38.8). Dose coverage of PTV-PRVu was D95% = 40.6 Gy (40.5-40.9), D5% = 46.6 Gy (46.2-47.2) and mean dose = 44.6 Gy (44.3-44.9). Dose to the PTVt reached 44.6 Gy (41.2-45.9). Doses to the OAR were respected, except V36Gy ≤1 cc for the rectum. CONCLUSION: A SBRT dose-escalation to 5 × 9 Gy on the prostate while sparing the urethra + 2 mm at 36.25 Gy is feasible without compromising dose coverage to the tumor. This radiation regimen will be used for a Phase-III trial. ADVANCES IN KNOWLEDGE: In prostate SBRT, dose optimization on the urethra is feasible and could decrease urinary toxicities.

Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy.

PURPOSE: Prostate bed (PB) irradiation is considered the standard postoperative treatment after radical prostatectomy (RP) for tumors with high-risk features or persistent prostate-specific antigen, or for salvage treatment in case of biological relapse. Four consensus guidelines have been published to standardize practices and reduce the interobserver variability in PB delineation but with discordant recommendations. To improve the reproducibility in the PB delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked to propose a new and more reproducible consensus guideline for PB clinical target volume (CTV) definition. METHODS AND MATERIALS: A 4-step procedure was used. First, a group of 10 GFRU prostate experts evaluated the 4 existing delineation guidelines for postoperative radiation therapy (European Organization for Research and Treatment of Cancer; the Faculty of Radiation Oncology Genito-Urinary Group; the Radiation Therapy Oncology Group; and the Princess Margaret Hospital) to identify divergent issues. Second, data sets of 50 magnetic resonance imaging studies (25 after RP and 25 with an intact prostate gland) were analyzed to identify the relevant anatomic boundaries of the PB. Third, a literature review of surgical, anatomic, histologic, and imaging data was performed to identify the relevant PB boundaries. Fourth, a final consensus on PB CTV definition was reached among experts. RESULTS: Definitive limits of the PB CTV delineation were defined using easily visible landmarks on computed tomography scans (CT). The purpose was to ensure a better reproducibility of PB definition for any radiation oncologist even without experience in postoperative radiation therapy. CONCLUSIONS: New recommendations for PB delineation based on simple anatomic boundaries and available as a CT image atlas are proposed by the GFRU. Improvement in uniformity in PB CTV definition and treatment homogeneity in the context of clinical trials are expected.

Prostate brachytherapy under hypnosedation: A prospective evaluation.

PURPOSE: Hypnosedation (HS) for brachytherapy has been proposed in patients with prostate cancer and has been evaluated. MATERIALS AND METHODS: 79 patients were treated with brachytherapy under HS. The Visual Analog Scale questionnaire was used to assess comfort and anxiety and the lowest, mean, and highest level of pain. Data for 79 patients who underwent general anesthesia (GA) and 37 patients who underwent spinal anesthesia (SA) treated at the same period were compared with HS group in terms of medication and treatment duration. RESULTS: 11 patients (13.9%) requested a GA, because they did not reach the hypnotic level. For the remaining 68 patients, the mean pain and comfort scores evaluated just after the intervention were 3.1 and 7.4, respectively. At 8 weeks, the scores were 2.8 and 7.5, respectively. 66 patients (97%) would choose this approach again and recommend it to other patients. The patients in the HS group received significant less medications than in the GA (remifentanil, propofol, kétamine, phenylephrine, ephedrine…) or SA (sufentanil, midazolam, morphine, bupivacaine…) groups with mean values of 3.1 vs. 7.9 vs. 5.6 (p < 0.0001), respectively. HS increased the mean time of surgery room occupation by 12 min vs. GA and by 20 min vs. SA. However, the recovery room occupation is avoided with HS (GA = 61 min and SA = 67 min) and a shorter duration of a need for a urinary catheter was noted. CONCLUSIONS: HS is a feasible and comfortable method of anesthesia and a good alternative to GA and SA for patients undergoing prostate brachytherapy, with reduced treatment duration and number of medications.

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.

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.

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.

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.

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.

Dosimetric implications of an injection of hyaluronic acid for preserving the rectal wall in prostate stereotactic body radiation therapy.

PURPOSE: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose-volume histogram, and the prostate-rectum separation was measured at 7 levels of the prostate on the center line of the organ. RESULTS: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). CONCLUSIONS: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

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.

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.

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.