Towards tumour hypoxia imaging: Incorporating relative oxygen extraction fraction mapping of prostate with multi-parametric quantitative MRI on a 1.5T MR-linac.

Hypoxia plays a central role in tumour radioresistance. Reliable tumour hypoxia imaging would allow the monitoring of tumour response and a more personalized adaptation of radiotherapy planning. Here, we showed a proof of concept of the feasibility and repeatability of relative oxygen extraction fraction (rOEF) mapping of prostate using multi-parametric quantitative MRI (qMRI) achieved for the first time on a 1.5T MR-linac. T2, T2* relaxation times maps, and intra-voxel incoherent motion (IVIM) parametric maps mapping were computed on a 29 years old healthy volunteer. R2' and rOEF maps were calculated based on a multi-parametric model. Long-term repeatability and repeatability coefficient (RC) were determined for each parameter according to QIBA recommendations. Mean values for the entire healthy prostate were 0.99 ± 0.14 × 10-3 mm/s2, 81 ± 2.1 × 10-3 mm/s2, 21.6 ± 3.6%, 92.7 ± 19.7 ms and 62.4 ± 17.3 ms for Dslow, Dfast, f, T2 and T2*, respectively. R2' and rOEF in the prostate were 6.1 ± 3.4 s-1 and 18.2 ± 10.1% respectively. The RC of rOEF was 4.43%. Long-term repeatability of quantitative parameters based on a test-retest ranged from 2 to 18%. qMRI parameters are measurable and repeatable on 1.5T MR LINAC. From T2, T2* and IVIM parameters maps, we were able to obtain a rOEF mapping of the prostate. These results are the first step to a non-invasive imaging of tumour hypoxia during radiotherapy leading to a biological image-guided adaptive radiotherapy.

Intravoxel incoherent motion magnetic resonance imaging to assess early tumor response to radiation therapy: Review and future directions.

Early prediction of radiation response by imaging is a dynamic field of research and it can be obtained using a variety of noninvasive magnetic resonance imaging methods. Recently, intravoxel incoherent motion (IVIM) has gained interest in cancer imaging. IVIM carries both diffusion and perfusion information, making it a promising tool to assess tumor response. Here, we briefly introduced the basics of IVIM, reviewed existing studies of IVIM in various type of tumors during radiotherapy in order to show whether IVIM is a useful technique for an early assessment of radiation response. 31/40 studies reported an increase of IVIM parameters during radiotherapy compared to baseline. In 27 studies, this increase was higher in patients with good response to radiotherapy. Future directions including implementation of IVIM on MR-Linac and its limitation are discussed. Obtaining new radiologic biomarkers of radiotherapy response could open the way for a more personalized, biology-guided radiation therapy.

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.

Managing postoperative biochemical relapse in prostate cancer, from the perspective of the Francophone group of Urological radiotherapy (GFRU).

Up to 50% of patients treated with radical surgery for localized prostate cancer may experience biochemical recurrence that requires appropriate management. Definitions of biochemical relapse may vary, but, in all cases, consist of an increase in a PSA without clinical or radiological signs of disease. Molecular imaging through to positron emission tomography has taken a preponderant place in relapse diagnosis, progressively replacing bone scan and CT-scan. Prostate bed radiotherapy is currently a key treatment, the action of which should be potentiated by androgen deprivation therapy. Nowadays perspectives consist in determining the best combination therapies, particularly thanks to next-generation hormone therapies, but not exclusively. Several trials are ongoing and should address these issues. We present here a literature review aiming to discuss the current management of biochemical relapse in prostate cancer after radical surgery, in lights of recent findings, as well as future perspectives.

Sexual Structure Sparing for Prostate Cancer Radiotherapy: A Systematic Review.

CONTEXT: Erectile dysfunction represents a major side effect of prostate cancer (PCa) treatment, negatively impacting men's quality of life. While radiation therapy (RT) advances have enabled the mitigation of both genitourinary and gastrointestinal toxicities, no significant improvement has been showed in sexual quality of life over time. OBJECTIVE: The primary aim of this review was to assess sexual structures' dose-volume parameters associated with the onset of erectile dysfunction. EVIDENCE ACQUISITION: We searched the PubMed database and ClinicalTrials.gov until January 4, 2023. Studies reporting the impact of the dose delivered to sexual structures on sexual function or the feasibility of innovative sexual structure-sparing approaches were deemed eligible. EVIDENCE SYNTHESIS: Sexual-sparing strategies have involved four sexual organs. The mean penile bulb doses exceeding 20 Gy are predictive of erectile dysfunction in modern PCa RT trial. Maintaining a D100% of ≤36 Gy on the internal pudendal arteries showed preservation of erectile function in 88% of patients at 5 yr. Neurovascular bundle sparing appears feasible with magnetic resonance-guided radiation therapy, yet its clinical impact remains unanswered. Doses delivered to the testicles during PCa RT usually remain <2 Gy and generate a decrease in testosterone levels ranging from -4.6% to -17%, unlikely to have any clinical impact. CONCLUSIONS: Current data highlight the technical feasibility of sexual sparing for PCa RT. The proportion of erectile dysfunction attributable to the dose delivered to sexual structures is still largely unknown. While the ability to maintain sexual function over time is impacted by factors such as age or comorbidities, only selected patients are likely to benefit from sexual-sparing RT. PATIENT SUMMARY: Technical advances in radiation therapy (RT) made it possible to significantly lower the dose delivered to sexual structures. While sexual function is known to decline with age, the preservation of sexual structures for prostate cancer RT is likely to be beneficial only in selected patients.

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Cancer: 24-Month Results of the RSR1 Phase 1 Dose Escalation Study.

PURPOSE: Stereotactic body radiation therapy (SBRT) has become a new therapeutic option for primary renal cell carcinoma. However, treatment doses lack consistency in the literature. The primary objective of this study was to determine the maximum tolerated dose for renal cancer SBRT. METHODS AND MATERIALS: This phase 1 multicentric dose-escalation study assessed 4 dose levels: 8 Gy × 4, 8 Gy × 5, 10 Gy × 4, and 12 Gy × 4. The primary objective of this study was to determine the maximal tolerated dose, defined by the occurrence of dose-limiting toxicity was defined as any acute side effect of grade ≥4 based on the Common Terminology Criteria for Averse Events, version 4.0. RESULTS: From October 2010 to September 2017, 13 patients were enrolled. The median follow-up was 23 months. There was no dose-limiting toxicity in our study, and the highest dose was reached successfully. No acute or late toxic effects above grade 2 were seen. There was no significant alteration of renal function after treatment. At 24 months, 2 patients had partial response and the others had stable disease. CONCLUSIONS: After 24 months of follow-up, no dose-limiting toxicity was seen at any of the prescribed dose levels in our study. The findings suggest that our last dose level of 48 Gy in 4 12-Gy fractions can be considered safe and can be used in further studies.

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group.

Stereotactic body radiotherapy (SBRT) has become treatment option for localized prostate cancer but the evidence base remains incomplete. Several clinical studies, both prospective and retrospective, have been published. However, treatment techniques, target volumes and dose constraints lack consistency between studies. Based on the current available literature, the French Genito-Urinary Group (GETUG) suggests that.

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.

Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder.

PURPOSE: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations. METHODS AND MATERIALS: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy. RESULTS: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence. CONCLUSION: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.

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.

Adjuvant radiotherapy after radical cystectomy for muscle-invasive bladder cancer: A retrospective multicenter study.

OBJECTIVES: Radical cystectomy (RC) and pelvic lymph-node dissection (LND) is standard treatment for non-metastatic muscle-invasive urothelial bladder cancer (MIBC). However, loco-regional recurrence (LRR) is a common early event associated with poor prognosis. We evaluate 3-year LRR-free (LRRFS), metastasis-free (MFS) and overall survivals (OS) after adjuvant radiotherapy (RT) for pathological high-risk MIBC. MATERIAL AND METHODS: We retrospectively reviewed data from patients in 3 institutions. Inclusion criteria were MIBC, histologically-proven urothelial carcinoma treated by RC and adjuvant RT. Patients with conservative surgery were excluded. Outcomes were evaluated by Kaplan-Meier method. Acute toxicities were recorded according to CTCAE V4.0 scale. RESULTS: Between 2000 and 2013, 57 patients [median age 66.3 years (45-84)] were included. Post-operative pathological staging was ≤pT2, pT3 and pT4 in 16%, 44%, and 39%, respectively. PLND revealed 28% pN0, 26% pN1 and 42% pN2. Median number of lymph-nodes retrieved was 10 (2-33). Forty-eight patients (84%) received platin-based chemotherapy. For RT, clinical target volume 1 (CTV 1) encompassed pelvic lymph nodes for all patients. CTV 1 also included cystectomy bed for 37 patients (65%). CTV 1 median dose was 45 Gy (4-50). A boost of 16 Gy (5-22), corresponding to CTV 2, was administered for 30 patients, depending on pathological features. One third of patients received intensity-modulated RT. With median follow-up of 40.4 months, 8 patients (14%) had LRR. Three-year LRRFS, MFS and OS were 45% (95%CI 30-60), 37% (95%CI 24-51) and 49% (95%CI 33-63), respectively. Five (9%) patients had acute grade ≥3 toxicities (gastro-intestinal, genito-urinary and biological parameters). One patient died with intestinal fistula in a septic context. CONCLUSIONS: Because of poor prognosis, an effective post-operative standard of care is needed for pathological high-risk MIBC. Adjuvant RT is feasible and may have oncological benefits. Prospective trials evaluating this approach with current RT techniques should be undertaken.

Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients.

OBJECTIVE: To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. PATIENTS AND METHODS: This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. RESULTS: In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. CONCLUSION: S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure.

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.

Pathologic Response, When Increased by Longer Interval, Is a Marker but Not the Cause of Good Prognosis in Rectal Cancer: 17-year Follow-up of the Lyon R90-01 Randomized Trial.

PURPOSE: The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years. METHODS AND MATERIALS: Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery. RESULTS: LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SI group (26% vs 10.3%, P=.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P=.0293 and pN: P=.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival (P=.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P=.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients). CONCLUSIONS: The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence treatment decisions in adults.