Farshad Foroudi

Urethral stricture following high dose rate brachytherapy for prostate cancer.

PURPOSE To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma. METHODS AND MATERIALS Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0. RESULTS At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n=15) or optical urethrotomy (n=20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p=0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p=0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p=0.008). CONCLUSIONS BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

PURPOSE There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. METHODS AND MATERIALS This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. RESULTS Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. CONCLUSIONS HDR brachytherapy as a monotherapy for favorable-risk prostate cancer, administered using a single implant over 2 days, is feasible and has acceptable acute and late toxicities. Further follow-up is still required to better evaluate the efficacy of such treatment.

Online Adaptive Radiotherapy for Muscle-Invasive Bladder Cancer: Results of a Pilot Study

PURPOSE To determine the advantages and disadvantages of daily online adaptive image-guided radiotherapy (RT) compared with conventional RT for muscle-invasive bladder cancer. METHODS AND MATERIALS Twenty-seven patients with T2-T4 transitional cell carcinoma of the bladder were treated with daily online adaptive image-guided RT using cone-beam computed tomography (CBCT). From day 1 daily soft tissue-based isocenter positioning was performed using CBCT images acquired before treatment. Using a composite of the initial planning CT and the first five daily CBCT scans, small, medium, and large adaptive plans were created. Each of these adaptive plans used a 0.5-cm clinical target volume (CTV) to planning target volume expansion. For Fractions 8-32, treatment involved daily soft tissue-based isocenter positioning and selection of suitable adaptive plan of the day. Treating radiation therapists completed a credentialing program, and one radiation oncologist performed all the contouring. Comparisons were made between adaptive and conventional treatment on the basis of CTV coverage and normal tissue sparing. RESULTS All 27 patients completed treatment per protocol. Bladder volume decreased with time or fraction number (p < 0.0001). For the adaptive component (Fractions 8-32) the small, medium, large, and conventional plans were used in 9.8%, 49.2%, 39.5%, and 1.5% of fractions, respectively. For the adaptive strategy, 2.7% of occasions resulted in a CTV V95 <99%, compared with 4.8% of occasions for the conventional approach (p = 0.42). Mean volume of normal tissue receiving a dose >45 Gy was 29% (95% confidence interval, 24-35%) less with adaptive RT compared with conventional RT. The mean volume of normal tissue receiving >5 Gy was 15% (95% confidence interval, 11-18%) less with adaptive RT compared with conventional RT. CONCLUSIONS Online adaptive radiotherapy is feasible in an academic radiotherapy center. The volume of normal tissue irradiated can be significantly smaller without reducing CTV coverage.

A systematic review of stereotactic radiotherapy ablation for primary renal cell carcinoma

Study Type – Therapy (systematic review)

Direct 2-Arm Comparison Shows Benefit of High-Dose-Rate Brachytherapy Boost vs External Beam Radiation Therapy Alone for Prostate Cancer

PURPOSE To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone. METHODS AND MATERIALS From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRT was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed. RESULTS Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed. CONCLUSIONS This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy

BackgroundImage-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically.MethodsBetween 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74Gy in 37 fractions, to 78Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment.ResultsIn the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference.ConclusionsIn this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.

Intra-fraction prostate displacement in radiotherapy estimated from pre- and post-treatment imaging of patients with implanted fiducial markers

PURPOSE To determine intra-fraction displacement of the prostate gland from imaging pre- and post-radiotherapy delivery of prostate cancer patients with three implanted fiducial markers. METHODS AND MATERIALS Data were collected from 184 patients who had two orthogonal X-rays pre- and post-delivery on at least 20 occasions using a Varian On Board kV Imaging system. A total of 5778 image pairs covering time intervals between 3 and 30 min between pre- and post-imaging were evaluated for intra-fraction prostate displacement. RESULTS The mean three dimensional vector shift between images was 1.7 mm ranging from 0 to 25 mm. No preferential direction of displacement was found; however, there was an increase of prostate displacement with time between images. There was a large variation in typical shifts between patients (range 1 +/- 1 to 6 +/- 2 mm) with no apparent trends throughout the treatment course. Images acquired in the first five fractions of treatment could be used to predict displacement patterns for individual patients. CONCLUSION Intra-fraction motion of the prostate gland appears to be a limiting factor when considering margins for radiotherapy. Given the variation between patients, a uniform set of margins for all patients may not be satisfactory when high target doses are to be delivered.

Late toxicity and biochemical control in 554 prostate cancer patients treated with and without dose escalated image guided radiotherapy.

BACKGROUND AND PURPOSE To compare rates of late gastrointestinal toxicity, late genitourinary toxicity and biochemical failure between patients treated for prostate cancer with implanted fiducial marker image guided radiotherapy (FMIGRT), and those treated without FMIGRT. METHODS AND MATERIALS We performed a single institution retrospective study comparing all 311 patients who received 74 Gy without fiducial markers in 2006 versus all 243 patients who received our updated regimen of 78 Gy with FMIGRT in 2008. Patient records were reviewed 27 months after completing radiotherapy. Biochemical failure was defined using the Phoenix definition. Details of late gastrointestinal and genitourinary toxicities were graded according to CTCAEv4. Moderate/severe toxicity was defined as a grade 2 or higher toxicity. Cumulative incidence and prevalence curves for moderate/severe toxicity were constructed and compared using multistate modeling while biochemical failure free survival was compared using the log rank test. A Cox regression model was developed to correct for confounding factors. RESULTS Median follow-up time for both groups was 22 months. The hazard ratio for moderate/severe late gastrointestinal toxicity in the non-FMIGRT group was 3.66 [95% CI (1.63-8.23), p=0.003] compared to patients in the FMIGRT group. There was no difference in the hazard ratio of moderate/severe late genitourinary toxicity between the two groups (0.44 [95% CI (0.19-1.00)]), but patients treated with FMIGRT did have a quicker recovery from their genitourinary toxicities HR=0.24 [95% CI (0.10-0.59)]. We were unable to detect any differences in biochemical failure free survival between the cohorts HR=0.60 [95% CI (0.30-1.20), p=0.143]. CONCLUSION Despite dose escalation, the use of FMIGRT in radical radiotherapy for prostate cancer significantly reduces the incidence of gastrointestinal toxicity and the duration of late genitourinary toxicity when compared to conventional non-FMIGRT techniques.

Patient-reported complications from fiducial marker implantation for prostate image-guided radiotherapy

OBJECTIVES To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy. METHODS 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale. RESULTS Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5). CONCLUSION Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

Estimating the Need for Radiotherapy for Patients With Prostate, Breast, and Lung Cancers: Verification of Model Estimates of Need With Radiotherapy Utilization Data From British Columbia

PURPOSE Estimates of the need for radiotherapy (RT) using different methods (criterion based benchmarking [CBB] and the Canadian [C-EBEST] and Australian [A-EBEST] epidemiologically based estimates) exist for various cancer sites. We compared these model estimates to actual RT rates for lung, breast, and prostate cancers in British Columbia (BC). METHODS AND MATERIALS All cases of lung, breast, and prostate cancers in BC from 1997 to 2004 and all patients receiving RT within 1 year (RT(1Y)) and within 5 years (RT(5Y)) of diagnosis were identified. The RT(1Y) and RT(5Y) proportions in health regions with a cancer center for the most recent year were then calculated. RT rates were compared with CBB and EBEST estimates of RT needs. Variation was assessed by time and region. RESULTS The RT(1Y) in regions with a cancer center for lung, breast, and prostate cancers were 51%, 58%, and 33% compared with 45%, 57%, and 32% for C-EBEST and 41%, 61%, and 37% for CBB models. The RT(5Y) rates in regions with a cancer center for lung, breast, and prostate cancers were 59%, 61%, and 40% compared with 61%, 66%, and 61% for C-EBEST and 75%, 83%, and 60% for A-EBEST models. The RT(1Y) rates increased for breast and prostate cancers. CONCLUSIONS C-EBEST and CBB model estimates are closer to the actual RT rates than the A-EBEST estimates. Application of these model estimates by health care decision makers should be undertaken with an understanding of the methods used and the assumptions on which they were based.