Sylvia van Dyk

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.

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.

Conformal Brachytherapy Planning for Cervical Cancer Using Transabdominal Ultrasound

PURPOSE To determine if transabdominal ultrasound (US) can be used for conformal brachytherapy in cervical cancer patients. MATERIALS AND METHODS Seventy-one patients with locoregionally advanced cervix cancer treated with chemoradiation and brachytherapy were included in this study. The protocol consisted of US-assisted tandem insertion and conformal US-based planning. Orthogonal films for applicator reconstruction were also taken. A standard plan was modified to suit the US-based volume and treatment was delivered. The patient then underwent a magnetic resonance imaging (MRI) scan with the applicators in situ. Retrospectively, individual standard (STD), US, and MRI plans were extrapolated for five fractions and superimposed onto the two-dimensional sagittal MRI images for comparison. Doses to Point A, target volume, International Commission on Radiation Units and Measurements (ICRU) 38 bladder and rectal points, and individualized bowel points were calculated on original implant geometry on Plato for each planning method. RESULTS STD (high-dose-rate) plans reported higher doses to Point A, target volume, ICRU 38 bladder and rectal points, and individualized bowel point compared with US and MRI plans. There was a statistically significant difference between standard plans and image-based plans-STD vs. US, STD vs. MRI, and STD vs. Final-having consistent (p <or= 0.001) respectively for target volume, Point A, ICRU 38 bladder, and bowel point. US plan assessed on two-dimensional MRI image was comparable for target volume (p = 0.11), rectal point (p = 0.8), and vaginal mucosa (p = 0.19). Local control was 90%. Late bowel morbidity (G3, G4) was <2%. CONCLUSIONS Transabdominal ultrasound offers an accurate, quick, accessible, and cost-effective method of conformal brachytherapy planning.

Comparative Study of LDR (Manchester System) and HDR Image-guided Conformal Brachytherapy of Cervical Cancer: Patterns of Failure, Late Complications, and Survival

PURPOSE To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. MATERIALS AND METHODS A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. RESULTS Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. CONCLUSIONS Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

Ultrasound guided conformal brachytherapy of cervix cancer: survival, patterns of failure, and late complications

Objective The aim of this study was to report on the long-term results of transabdominal ultrasound guided conformal brachytherapy in patients with cervical cancer with respect to patterns of failures, treatment related toxicities and survival. Methods Three hundred and nine patients with cervical cancer who presented to Institute between January 1999 and December 2008 were staged with magnetic resonance imaging and positron emission tomography and treated with external beam radiotherapy and high dose rate conformal image guided brachytherapy with curative intent. Follow-up data relating to sites of failure and toxicity was recorded prospectively. Results Two hundred and ninety-two patients were available for analyses. The median (interquantile range) follow-up time was 4.1 years (range, 2.4 to 6.1 years). Five-year failure free survival and overall survival (OS) were 66% and 65%, respectively. Primary, pelvic, para-aortic, and distant failure were observed in 12.5%, 16.4%, 22%, and 23% of patients, respectively. In multivariate analysis, tumor volume and nodal disease related to survival, whereas local disease control and point A dose did not. Conclusion Ultrasound guided conformal brachytherapy of cervix cancer has led to optimal local control and OS. The Melbourne protocol compares favorably to the more technically elaborate and expensive GEC-ESTRO recommendations. The Melbourne protocols technical simplicity with real-time imaging and treatment planning makes this a method of choice for treating patients with cervical cancer.

Comparison of Measurements of the Uterus and Cervix Obtained by Magnetic Resonance and Transabdominal Ultrasound Imaging to Identify the Brachytherapy Target in Patients With Cervix Cancer

PURPOSE To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. METHODS AND MATERIALS Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. RESULTS A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (± SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (± 3.353) mm to 3.7 (± 3.856) mm, and -1.46 (± 3.308) mm to 0.47 (± 3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. CONCLUSION Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer.

Ultrasound use in gynecologic brachytherapy: Time to focus the beam

There is wide disparity in the practice of brachytherapy for cervical cancer around the world. Although select well-resourced centers advocate use of MRI for all insertions, planar X-ray imaging remains the most commonly used imaging modality to assess intracavitary implants, particularly where the burden of cervical cancer is high. Incorporating soft tissue imaging into brachytherapy programs has been shown to improve the technical accuracy of implants, which in turn has led to improved local control and decreased toxicity. These improvements have a positive effect on the quality of life of patients undergoing brachytherapy for cervical cancer. Finding an accessible soft tissue imaging modality is essential to enable these improvements to be available to all patients. A modality that has good soft tissue imaging capabilities, is widely available, portable, and economical, is needed. Ultrasound fulfils these requirements and offers the potential of soft tissue image guidance to a much wider brachytherapy community. Although use of ultrasound is the standard of care in brachytherapy for prostate cancer, it only seems to have limited uptake in gynecologic brachytherapy. This article reviews the role of ultrasound in gynecologic brachytherapy and highlights the potential applications for use in brachytherapy for cervical cancer.

Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer.

This study aims to evaluate the feasibility and outcomes of intraoperative radiotherapy (IORT) using high‐dose‐rate (HDR) brachytherapy for locally advanced or recurrent rectal cancers. Despite preoperative chemoradiation, patients with locally advanced or recurrent rectal cancers undergoing surgery remain at high risk of local recurrence. Intensification of radiation with IORT may improve local control.

PATTERNS OF FAILURE AND TREATMENT-RELATED TOXICITY IN ADVANCED CERVICAL CANCER PATIENTS TREATED USING EXTENDED FIELD RADIOTHERAPY WITH CURATIVE INTENT

PURPOSE The purpose of this study was to evaluate the patterns of failure and overall survival (OS) and disease-free survival (DFS) rates in cervical cancer patients who had metastatic disease in common iliac or para-aortic lymph nodes and were treated with curative intent, using extended field radiotherapy (EFRT). METHODS AND MATERIALS This was a retrospective study involving 39 patients treated from January 1996 to June 2007, using EFRT with concurrent chemotherapy and intracavitary brachytherapy. EFRT consisted of 45 Gy in 1.8-Gy fractions. Radiation to involved nodes was boosted to a total dose of 50.4 to 54 Gy. Primary tumor radiation was boosted to a dose of 80 Gy using brachytherapy. RESULTS Overall, 30 patients (77%) have relapsed. The 5-year OS rate was 26% (95% confidence interval [CI], 11-44). The 5-year DFS rate was 19.4% (95% CI, 8-35). Only 3 patients (7.5%) experienced treatment failure exclusively within the treatment field, and 2 patients underwent salvage treatment. Grade 3 to 4 acute bone marrow and gastrointestinal toxicities were observed in 10 (26%) and 7 (18%) patients, respectively. CONCLUSIONS Concurrent chemotherapy and EFRT treatment was well tolerated. Most patients showed failure at multiple sites and outside the treatment field. Only 3/39 patients had failures exclusively within the treatment field, and 2 underwent salvage treatment.

Assessing changes to the brachytherapy target for cervical cancer using a single MRI and serial ultrasound

PURPOSE To assess changes to the brachytherapy target over the course of treatment and the impact of these changes on planning and resources. METHODS AND MATERIALS Patients undergoing curative treatment with radiotherapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were positioned in the uterine canal while patients were under anesthesia. Images were obtained by MRI and ultrasound at Fraction 1 and ultrasound alone at Fractions 2, 3, and 4. Cervix and uterine dimensions were measured on MRI and ultrasound and compared using Bland-Altman plots and repeated measures one-way analysis of variance. RESULTS Of 192 patients who underwent three fractions of brachytherapy, 141 of them received four fractions. Mean differences and standard error of differences between MRI at Fraction 1 and ultrasound at Fraction 4 for anterior cervix measurements were 2.9 (0.31), 3.5 (0.25), and 4.2 (0.27) mm and for posterior cervix 0.8 (0.3), 0.3 (0.3), and 0.9 (0.3) mm. All differences were within clinically acceptable limits. The mean differences in the cervix over the course of brachytherapy were less than 1 mm at all measurement points on the posterior surface. Replanning occurred in 11 of 192 (5.7%) patients, although changes to the cervix dimensions were not outside clinical limits. CONCLUSIONS There were small changes to the cervix and uterus over the course of brachytherapy that were not clinically significant. Use of intraoperative ultrasound as a verification aid accurately assesses the target at each insertion, reduces uncertainties in treatment delivery, and improves efficiency of the procedure benefiting both the patient and staff.