Infection after prostatic transrectal fiducial marker implantation for image guided radiation therapy.

PURPOSE: The aim of this retrospective study is to assess the risk of infection after transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy of prostate cancer. MATERIAL AND METHODS: Between January 2016 and December 2020, 829 patients scheduled for intensity-modulated radiotherapy for prostate cancer had an intraprostatic fiducial marker transrectal implantation under ultrasound guidance by radiation-oncologists specialized in brachytherapy. Patients received standard oral prophylactic antibiotic with quinolone. If Gram negative bacteria resistant to quinolone were detected at the time of the prostate cancer biopsies, the antibioprophylaxis regimen was modified accordingly. The resistance to quinolone screening test was not repeated before fiducial marker insertion. Infectious complications were assessed with questionnaires at the time of CT-planning and medical record reviewed. Toxicity was evaluated according to CTCAE v5.0. RESULTS: The median time between fiducial marker implantation and evaluation was 10 days (range: 0-165 days). Four patients (0.48%) developed urinary tract infection related to the procedure, mostly with Gram-negative bacteria resistant to quinolone (75%). Three had a grade 2 infection, and one patient experienced a grade 3 urosepsis. The quinolone-resistance status was known for two patients (one positive and one negative) and was unknown for the other two patients prior to fiducial marker implantation. CONCLUSION: Intraprostatic transrectal fiducial marker implantation for image-guided radiotherapy is well tolerated with a low rate of infection. With such a low rate of infection, there is no need to repeat the search of Gram-negative bacteria resistant to quinolone before fiducial marker implantation if it was done at the time of prostate biopsies. Optimal antibioprophylaxis should be adapted to the known status of Gram-negative bacteria resistant to quinolone.

Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial.

Purpose/Objectives: To analyze the long term efficacy and safety of an ultra-hypofractionated (UHF) radiation therapy prostate treatment regimen with HDR brachytherapy boost (BB) and compare it to moderate-hypofractionated regimens (MHF). Materials/Methods: In this single arm, prospective monocentric study, 28 patients with intermediate risk prostate cancer were recruited in an experimental treatment arm of 25 Gy in 5 fractions plus a 15 Gy HDR BB. They were then compared to two historical control groups, treated with either 36 Gy in 12 fractions or 37.5 Gy in 15 fractions with a similar HDR BB. The control groups included 151 and 311 patients respectively. Patient outcomes were reported using the International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC-26) questionnaires at baseline and at each follow-up visit. Results: Median follow-up for the experimental arm was 48.5 months compared to 47 months and 60 months compared to the 36/12 and 37,5/15 groups respectively. The IPSS and EPIC scores did not demonstrate any significant differences in the gastrointestinal or genitourinary domains between the three groups over time. No biochemical recurrence occurred in the UHF arm as defined by the Phoenix criterion. Conclusion: The UHF treatment scheme with HDR BB seems equivalent to standard treatment arms in terms of toxicities and local control. Randomized control trials with larger cohorts are ongoing and needed to further confirm our findings.

Focal HDR brachytherapy boost to stereotactic radiotherapy (fBTsRT) for prostate cancer: a phase II randomized controlled trial.

BACKGROUND: For patients with a higher burden of localized prostate cancer, radiation dose escalation with brachytherapy boosts have improved cancer control outcomes at the cost of urinary toxicity. We hypothesize that a focal approach to brachytherapy boosts targeting only grossly visualized tumor volumes (GTV) combined with stereotactic radiotherapy will improve quality of life (QoL) outcomes without compromising cancer control. METHODS: 150 patients with intermediate or high-risk prostate cancer will be enrolled and randomized 1:1 in a cohort multiple randomized clinical trial phase 2 design. Patients are eligible if planned for standard-of-care (SOC) high dose rate (HDR) brachytherapy boost to radiotherapy (RT) with GTVs encompassing < 50% of the prostate gland. Those randomly selected will be offered the experimental treatment, consisting of focal HDR brachytherapy boost (fBT) of 13-15 Gy in 1 fraction followed by stereotactic radiotherapy (sRT) 36.25-40 Gy in 5 fractions to the prostate (+/- 25 Gy to the elective pelvis) delivered every other day. The primary endpoint is to determine if fBTsRT is superior to SOC by having fewer patients experience a minimally important decline (MID) in urinary function as measured by EPIC-26 at 1 and 2 years. Secondary endpoints include rates of toxicity measured by Common Terminology Criteria for Adverse Events (CTCAE), and failure-free survival outcomes. DISCUSSION: This study will determine whether a novel approach for the treatment of localized prostate cancer, fBTsRT, improves QoL and merits further evaluation. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04100174 as a companion to registry NCT03378856 on September 24, 2019.

Employment outcomes for recent Canadian radiation oncology graduates.

Introduction: Radiation oncology (ro) is one of several specialties identified by the Royal College of Physicians and Surgeons of Canada with employment difficulties for graduating trainees. The purpose of the present study was to determine the employment status and location of recent Canadian ro trainees within 2 years after graduation, to monitor workforce recruitment trends over time, and to capture the opinions of program directors about employment difficulty for graduates and resident morale. Visa trainee graduates were excluded. Methods: Results of the survey administered to ro program directors in 2016 and again in 2018, both with 100% response rates, are presented here. Results: In both surveys, approximately 57% of ro graduates had attained staff or locum employment in Canada or abroad within 2 years from graduation (p = 0.92). However, graduates with Canadian staff employment increased by 46% to 32 in 2018 from 22 in 2016, while the proportion of graduates with staff positions abroad decreased to 6% from 27% (p = 0.04). Most trainees without staff positions were employed as fellows. The proportion of program directors reporting employment difficulties for graduates in the Canadian labour market declined to 38% from 85% (p = 0.04), and the morale of residents in training programs remained high. Conclusions: Employment challenges for newly certified Canadian-trained radiation oncologists continue. However, compared with the situation 2 years ago, trends in the Canadian ro job market suggest a modest improvement, with more staff employment in Canada and lower emigration rates for jobs abroad.

Randomised Phase II Feasibility Trial of Image-guided External Beam Radiotherapy With or Without High Dose Rate Brachytherapy Boost in Men with Intermediate-risk Prostate Cancer (CCTG PR15/ NCT01982786).

AIMS: We conducted a multicentre feasibility study to assess the ability to randomise patients between image-guided radiotherapy (IGRT) and IGRT + high dose rate (HDR) brachytherapy boost and to adhere to appropriate radiation quality assurance standards. MATERIALS AND METHODS: The primary end point was to determine the ability to randomise 60 patients over an 18 month period. Arm 1 (IGRT) patients received 78 Gy in 39 fractions or 60 Gy in 20 fractions (physician's preference), whereas arm 2 (IGRT + HDR) received 37.5 Gy in 15 fractions with HDR boost of 15 Gy. The secondary end points included >grade 3 acute genitourinary and gastrointestinal toxicity, using Common Terminology Criteria for Adverse Events version 4.0 at 3 months, validation of a prospectively defined radiation oncology quality assurance to assess treatment compliance. All analyses were descriptive; no formal comparisons between treatment arms were carried out. RESULTS: Between April 2014 and September 2015, 57 National Comprehensive Cancer Network (NCCN)-defined intermediate-risk prostate cancer patients were randomised between IGRT alone (arm 1; n = 29) and IGRT plus HDR brachytherapy boost (arm 2; n = 28). Overall, 93% received the treatment as randomised. There were four patients (one on IGRT arm 1 and three patients on the IGRT + HDR arm 2) who were treated differently from randomisation assignment. For the 29 patients receiving IGRT (arm 1), there were 14 cases reported with minor deviations and three with major deviations. For patients on IGRT + HDR (arm 2), there were 18 cases reported with minor deviations and two with major deviations. At 3 months in the IGRT group (arm 1), one patient reported grade 3 diarrhoea, whereas in the IGRT + HDR group (arm 2), two patients reported grade 3 haematuria. No other gastrointestinal and genitourinary toxicities were reported. CONCLUSION: The pilot study showed the feasibility of randomisation between treatment with IGRT alone versus IGRT + HDR boost. Treatment compliance was good, including adherence to quality assurance standards.

Stereotactic Ablative Radiotherapy Versus Low Dose Rate Brachytherapy or External Beam Radiotherapy: Propensity Score Matched Analyses of Canadian Data.

AIMS: To compare biochemical failure-free survival (BFFS) and overall survival for prostate cancer treated with stereotactic ablative radiotherapy (SABR), low dose rate (LDR) brachytherapy or external beam radiotherapy (EBRT) using a large Canadian multi-institutional database. MATERIALS AND METHODS: Patients with low risk localised prostate cancer treated with SABR, LDR or EBRT and no androgen deprivation therapy were selected. Propensity score matching was used to create two sets of matched cohorts with LDR and EBRT serving as control groups. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare differences in BFFS and overall survival between treatment groups. RESULTS: The pre-matched cohort contained 602 patients; the median follow-up was >5.0 years. There were no significant differences in BFFS before or after matching for SABR versus LDR but the prostate-specific antigen (PSA) nadir was lower after LDR. For the SABR versus EBRT, SABR had a BFFS trend before matching (P = 0.08), which became significant after matching (P < 0.001). CONCLUSIONS: Using the Genitourinary Radiation Oncologists of Canada Prostate Cancer Risk Stratification database, low risk prostate cancer patients receiving SABR had similar BFFS compared with patients receiving LDR but better BFFS than EBRT patients. Further comparative studies of efficacy, quality of life and economic outcomes using a broader risk of patients are warranted.

Prospective Phase II Trial of Once-weekly Hypofractionated Radiation Therapy for Low-risk Adenocarcinoma of the Prostate: Late Toxicities and Outcomes.

AIMS: To report the long-term toxicities and sexual quality of life of a once-weekly hypofractionated radiation therapy schedule for low-risk prostate cancer. MATERIALS AND METHODS: A multi-institutional phase II trial was conducted, using a three-dimensional conformal radiation therapy (3D-CRT) approach for low-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and prostate-specific antigen ≤ 10 ng/ml). Forty-five Gray (Gy) were delivered in nine fractions of 5 Gy given on a weekly basis. Acute and late genitourinary and gastrointestinal toxicities were graded according to the Radiation Therapy Oncology Group toxicity scale. Sexual function and sexual bother were assessed with the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. RESULTS: Between March 2006 and August 2008, 80 patients were treated, with a median age of 69 years (interquartile range 64-72). The median follow-up was 83 months (interquartile range 73-85 months). At 7 years, overall survival was 88%. No patients died of prostate cancer. Cumulative grade ≥2 genitourinary and gastrointestinal late toxicity was reported for 31.3% and 30% of our patients, respectively. Cumulative grade ≥3 genitourinary and gastrointestinal late toxicity was seen in 3.8% and 12.5% of cases, respectively. Late genitourinary grade 2 toxicity was correlated with the occurrence of acute genitourinary grade 2 toxicity (P = 0.006). The occurrence of late gastrointestinal toxicity was not correlated with acute gastrointestinal toxicity. Pre-treatment EPIC sexual function was low (37.5%) and the mean EPIC sexual function score at 7 years after treatment was 14%. On the other hand, pre-treatment EPIC sexual bother reached 80.5%, meaning little bother, and remained stable during follow-up. CONCLUSIONS: Once-weekly 3D-CRT leads to excellent biochemical disease-free survival and acceptable toxicities. Pre-treatment EPIC sexual function dropped by 42% at 5 years of follow-up. This functional deficit did not bother patients, possibly due to the already low sexual function at baseline.

[Clinical outcome of intermediate risk prostate cancer treated with iodine 125 monotherapy: The Hotel-Dieu of Quebec experience]. / Evolution clinique des patients atteints d'un cancer prostatique de risque intermédiaire traités par implants permanents d'iode-125 : l'expérience de l'Hôtel-Dieu de Québec.

PURPOSE: To describe the biochemical failure-free survival (BFFS), GU toxicity and erectile dysfunction in intermediate risk prostate cancer treated with iodine 125 monotherapy (I125). PATIENTS AND METHODS: Between October 1994 and October 2007, 1282 patients were treated with I125 at the Hotel Dieu de Quebec. Two hundred patients were intermediate risk prostate cancer. One hundred and fifty-seven had enough follow-up to be evaluated in this study. Biochemical failure-free survival is reported using Phoenix definition. Acute and late GU toxicity was described using the International Prostate Symptoms Score (IPSS) as well as with the rate of bladder catheter. Erectile dysfunction was also reported. RESULTS: The mean age of the patients was 65.6 years (S.D.=6 years) and the mean pretreatment PSA was 8.7ng/ml. About half of the patients (51%) were T2b/T2c. About 44.6% had a PSA greater than 10 and 4.5% had Gleason score of 7/10. More than half of the patients received a short course of hormones of less than 6 months for cytoreduction (57.4%). The median follow-up was 60 months. Biochemical failure-free survival at 60-month and 96-month were 87.1% and 81% according to Phoenix definition. The mean IPSS rose from 5 immediately after the implant to 15 1 month after and then slowly decreased to 8 at 24 months. Acute urinary retention with bladder catheter occurred in 10.9% of patients. Only 4.3% presented erectile dysfunction at 5 months post-implant. CONCLUSION: I125 monotherapy for intermediate risk prostate implant gives biochemical failure-free survivals at 5 years and 8 years comparable to those obtained with high dose external beam radiotherapy. GU toxicity and erectile dysfunction were low and acceptable. Therefore, the use of I125 alone in this group of patients could be presented and discussed with the patient in the waiting of phase III validation.

[The impact of 3D image guided prostate brachytherapy on therapeutic ratio: the Quebec University Hospital experience]. / Le rôle de la curiethérapie prostatique guidée par imagerie 3D sur le ratio thérapeutique: l'expérience du CHU de Québec.

PURPOSE: To evaluate the impact of adaptative image-guided brachytherapy on therapeutic outcome and toxicity in prostate cancer. MATERIALS AND METHODS: The 1,110 first patients treated at the CHUQ-l'Hôtel-Dieu de Québec were divided in five groups depending on the technique used for the implantation, the latest being intra operative treatment planning. Biochemical disease free survival (5-bDFS), toxicities and dosimetric parameters were compared between the groups. RESULTS: 5-bDFS (ASTRO+Houston) were of 88.5% and 90.5% for the whole cohort. The use of intra operative treatment planning resulted in better dosimetric parameters. Clinically, this resulted in a decreased use of urethral catheterism, from 18.8% in group 1 to 5.2% in group 5, and in a reduction in severe acute urinary side effects (21.3 vs 33.3% P=0.01) when compared with preplanning. There was also less late gastrointestinal side effects (groups 5 vs 1: 26.6 vs 43.2% P<0.05). Finally, when compared with preplanning, intra operative treatment planning was associated with a smaller reduction between planned D90 and the dose calculated at the CT scan 1 month after the implant (38 vs 66 Gy). CONCLUSION: The evolution of prostate brachytherapy technique toward intra operative treatment planning allowed dosimetric gains which resulted in significant clinical benefits by increasing the therapeutic ratio mainly through a decreased urinary toxicity. A longer follow-up will answer the question whether there is an impact on 5-bDFS.

Robustness and precision of an automatic marker detection algorithm for online prostate daily targeting using a standard V-EPID.

An algorithm for the daily localization of the prostate using implanted markers and a standard video-based electronic portal imaging device (V-EPID) has been tested. Prior to planning, three gold markers were implanted in the prostate of seven patients. The clinical images were acquired with a BeamViewPlus 2.1 V-EPID for each field during the normal course radiotherapy treatment and are used off-line to determine the ability of the automatic marker detection algorithm to adequately and consistently detect the markers. Clinical images were obtained with various dose levels from ranging 2.5 to 75 MU. The algorithm is based on marker attenuation characterization in the portal image and spatial distribution. A total of 1182 clinical images were taken. The results show an average efficiency of 93% for the markers detected individually and 85% for the group of markers. This algorithm accomplishes the detection and validation in 0.20-0.40 s. When the center of mass of the group of implanted markers is used, then all displacements can be corrected to within 1.0 mm in 84% of the cases and within 1.5 mm in 97% of cases. The standard video-based EPID tested provides excellent marker detection capability even with low dose levels. The V-EPID can be used successfully with radiopaque markers and the automatic detection algorithm to track and correct the daily setup deviations due to organ motions.

Forward or inversely planned segmental multileaf collimator IMRT and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy.

PURPOSE: To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS: A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS: All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS: Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.

3D conformal radiation therapy (3DCRT) for high grade prostate cancer: a multi-institutional review.

PURPOSE: To evaluate the results of 3DCRT and the effect of higher than traditional doses in patients with high grade prostate cancer, we compiled data from three institutions and analyzed the outcome of this relatively uncommon subset of prostate cancer patients. METHODS AND MATERIALS: The 180 patients with Gleason score 8- 10 adenocarcinoma of the prostrate were treated with 3DCRT at the Univer sity of Michigan Health System, University of California-San Francisco, or Fox Chase Cancer. Eligible patients had T1-T4 NO or NX MO adenocarci noma with a pretreatment PSA. Pretreatment characteristics included: me dian age 72 years, 60.6% Gleason score 8 tumors, 57.6% T1-T2, and median pretreatment PSA 17.1 ng/ml (range 0.3-257.1). The total dose received was <70 Gy in 30%, 70-75 Gy in 37%, and >75 Gy in 33%, 27% received adju vant or neoadjuvant hormonal therapy. The median follow-up was 3.0 years for all patients and 16% of patients were followed up for at least 5 years. RESULTS: The 5-year freedom from PSA failure was 62.5% for all patients and 79.3% in T1-T2 patients. Univariate analysis revealed that T-stage (T1-T2 vs. T3-T4), pretreatment PSA, and RT dose predicted for freedom from PSA failure. A 5-year overall survival for all patients was 67.3%. Only RT dose was predictive of 5-year overall survival on univariate analysis. Because a significant association was seen between T-stage and RT dose, the Cox proportional hazards model was performed separately for T1-T2 and T3-T4 tumors. None of the prognostic factors reached statistical significance for overall survival or freedom from PSA failure in T3-T4 patients or for overall survival in T1-T2 patients. Lower RT dose and higher pretreatment PSA predicted for PSA failure on multivariate analysis in T1-T2 patients. CONCLUSION: This retrospective study from three institutions with experience in dose escalation suggests a dose effect for PSA control above 70 Gy in patients with T1-T2 high grade prostate cancer. These results are superior to surgery and emphasize the need for dose escalation in treating Gleason 8-10 prostate cancer.

Static field intensity modulation to treat a dominant intra-prostatic lesion to 90 Gy compared to seven field 3-dimensional radiotherapy.

PURPOSE/OBJECTIVE: Recent studies supported by histopathological correlation suggest that the combined use of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) allows differentiation of normal and carcinomatous prostate. The goal of this study was to use static field intensity modulated three-dimensional conformal radiotherapy (SF-IMRT) to treat the entire prostate to a total dose of >70 Gy, while concurrently treating a dominant intraprostatic lesion (DIL) defined by MRI+MRS to 90 Gy while not exceeding normal tissue tolerances. MATERIALS AND METHODS: For the example chosen, the DIL consisted of a large portion of the peripheral zone of the left lobe of the prostate. University of Michigan (UM-PLAN) three-dimensional treatment planning software was used to design a partially shielded 7 field conformal isodose plan that would treat the entire prostate to >70 Gy at 1.8 Gy per day (80% isodose line), while concurrently treating the DIL to 2.25 Gy per day for a total dose of 90 Gy. Dose volume histograms (DVH) were used to compare the rectal doses to rectum and other adjacent normal tissues using these two techniques. RESULTS: SF-IMRT as described, allowed a total dose of 90 Gy to encompass the DIL, while the rectal dose was slightly lower than that using the standard 7 field technique to the prostate alone. For example, the dose to 30 cm3 of the rectum was 40 Gy using SF-IMRT and 48 Gy for the standard 7 field technique. Because of differences in the dose per fraction the biologic advantages of the SF-IMRT technique are likely to be even greater. CONCLUSIONS: This study demonstrates the feasibility of using SF-IMRT to treat a DIL involving a single lobe of the prostate, as defined by MRI/MRS, to 90 Gy, while simultaneously treating the prostate to >70 Gy without increasing the dose to surrounding normal tissues. A similar approach could be used to treat multifocal disease. This method of treatment is an alternative to dynamic intensity modulation. It is less expensive, and can be adapted to any radiation therapy department without the use of an inverse treatment planning programs.

Electronic portal imaging device detection of radioopaque markers for the evaluation of prostate position during megavoltage irradiation: a clinical study.

PURPOSE: This study was designed to assess daily prostatic apex motion relative to pelvic bone structures during megavoltage irradiation. METHODS AND MATERIALS: Radioopaque markers were implanted under ultrasound guidance near the prostatic apex of 11 patients with localized prostatic carcinoma. Patients were subsequently treated with a four field-box technique at a beam energy of 23 MV. During treatment, on-line images were obtained with an electronic portal imaging device (EPID). The marker was easily identified, even on unprocessed images, and the distance between the marker and a bony landmark was measured. Timelapse movies were also reviewed. After the completion of treatment, a transrectal ultrasound examination was performed in 8 of 11 patients, to verify the position of the marker. RESULTS: We acquired over 900 digital portal images and analyzed posterioanterior and right lateral views. The quality of portal images obtained with megavoltage irradiation was good. It was possible to evaluate pelvic bone structures even without image histogram equalization. Moreover, the radioopaque marker was easily visible on every online portal image. The review of timelapse movies showed important interfraction motion of the marker while bone structures remained stable. We measured the position of the marker for each fraction. Marker displacements up to 1.6 cm were measured between 2 consecutive days of treatment. Important marker motions were predominantly in the posteroanterior and cephalocaudal directions. In eight patients, we verified the position of the marker relative to the prostatic apex with ultrasound at the end of the treatments. The marker remained in the trapezoid zone. Intratreatment images reviewed in two cases showed no-change in marker position. Our results, obtained during the treatment courses, indicate similar or larger prostate motions than previously observed in studies that used intertreatment x-ray films and CT images. Marker implantation under transrectal ultrasound was well tolerated. CONCLUSIONS: Radioopaque marker and the use of electronic portal imaging give a direct evaluation of prostatic motion during radiation treatment. As suggested in previous studies the motions observed are predominantly in the posteroanterior and cephalocaudal directions. Therefore, prostate motion during treatment is important and must be considered especially when using conformal therapy.