Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.

BACKGROUND: Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. METHODS: The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0-2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0-50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. FINDINGS: Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI -6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3-4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. INTERPRETATION: Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. FUNDING: National Health and Medical Research Council and National Cancer Institute.

Why quality assurance is necessary in gynecologic radiation oncology.

Quality assurance (QA) in radiation oncology involves all checks and processes that ensure that radiotherapy is delivered in an optimal and intended manner. QA is essential for the accurate delivery of brachytherapy and external beam radiotherapy in patients diagnosed with gynecologic malignancies. Inadequate QA can adversely impact clinical outcomes and reduce the reliability of clinical trials. This review highlights the importance of QA in gynecologic radiation oncology and explores the pertinent issues related to its implementation.

Intensification of Local Therapy With High Dose Rate, Intraoperative Radiation Therapy (HDR-IORT) and Extended Resection for Locally Advanced and Recurrent Colorectal Cancer.

BACKGROUND: We report our long-term experience with high dose rate intraoperative radiotherapy (HDR-IORT) in a single, quaternary institution. PATIENTS/METHODS: From 2004 to 2020, 60 HDR-IORT procedures for locally advanced colorectal cancer (LACC) and 81 for locally recurrent colorectal cancer (LRCC) were done in our institution. Preoperative radiotherapy was done prior to majority of the resections (89%, 125/141). Sixty-nine percent (58/84) of the resections involving pelvic exenterations had >3 en bloc organs resected. HDR-IORT was delivered using a Freiburg applicator. A single 10 Gy fraction was delivered. Margin status was R0 and R1 in 54% (76/141) and 46% (65/141) of the resections, respectively. RESULTS: With a median follow-up time of 4 years, 3-, 5-, and 7- year, overall survival (OS) rates were 84%, 58%, and 58% for LACC and 68%, 41%, and 37% for LRCC, respectively. Local progression-free survival (LPFS) rates were 97%, 93%, and 93% for LACC and 80%, 80%, 80% for LRCC, respectively. For the LRCC group, an R1 resection was associated with worse OS, LPFS, and progression-free survival (PFS), preoperative EBRT was associated with improved LPFS and PFS, and ≥2 years disease-free interval was associated with improved PFS. The most common severe adverse events were postoperative abscess (n = 25) and bowel obstruction (n = 11). There were 68 grade 3 to 4 and no grade 5 adverse events. CONCLUSIONS: Favorable OS and LPFS can be achieved for LACC and LRCC with intensive local therapy. In patients with risk factors for poorer outcomes, optimization of EBRT and IORT, surgical resection, and systemic therapy are required.

Reviewing the role of parametrial boost in patients with cervical cancer with clinically involved parametria and staged with positron emission tomography.

OBJECTIVE: Primary objective was to validate the practice of not treating clinically involved parametria by parametrial boost. Secondary objective was to validate the adequacy of nodal boost in node-positive patients regardless of parametrial status. MATERIAL AND METHODS: A retrospective analysis of 193 patients with locoregionally advanced cervical cancer treated with curative intent using external beam radiotherapy and brachytherapy. All patients were staged clinically (International Federation of Gynecology and Obstetrics) and radiologically using magnetic resonance imaging and positron emission tomography. The positron emission tomography positive nodes were boosted to an additional dose of 6 to 10 Gy after 40 Gy to the whole pelvis. Parametrial boost was not used. Patients with stages IB to IIa and stages IIB to IIIB disease were allocated to groups A and B, respectively. RESULTS: The pelvic failure (P = 0.430) and extrapelvic failure (P = 0.437) did not differ significantly between groups A and B. In multifactor analysis, tumor volume was significantly associated with pelvic failure (P = 0.009) and node positivity was significantly associated with extrapelvic failure (P = 0.002). Clinical parametrial involvement in the absence of parametrial boost was not related to either pelvic or extrapelvic failure. None of the node-positive patients had isolated pelvic nodal failure. CONCLUSION: Cervical cancer with clinically involved parametria can be adequately treated without parametrial boost. A dose of 46 to 50 Gy was adequate to avoid isolated pelvic nodal failure.

Patterns of practice survey for brachytherapy for cervix cancer in Australia and New Zealand.

INTRODUCTION: The purpose of this survey was to explore the current patterns of practice for brachytherapy in cervix cancer in Australia and New Zealand. The survey was also intended to explore clinician attitudes towards image-guided adaptive brachytherapy (IGABT) and identify barriers to the implementation of IGABT. METHODS: Electronic surveys were sent to all radiotherapy centres in Australia and New Zealand under collaboration with Australia New Zealand Gynaecology and Oncology Group (ANZGOG), in order to identify patterns of radiotherapy practice. The survey was sent out in December 2013, with a reminder in February 2014. RESULTS: Of the 75 radiotherapy centres in Australia and New Zealand, 23 centres replied (31% response rate). Twenty-two responding departments treat cervix cancer with external beam radiation (EBRT) (22/23; 96%). Fourteen responses were from departments that also use intracavitary brachytherapy (14/22; 64%). The remaining eight departments who do not offer intracavitary brachytherapy referred their patients on to other centres for brachytherapy. Ultrasound was used by 86% for applicator guidance. CT and MRI were used by 79%, and 50% respectively for planning. Optimisation was based on organs at risk (93%) and target volumes (64%). CONCLUSIONS: Brachytherapy remains an integral component of definitive treatment for cervix cancer in Australia and New Zealand. There was increased use of soft tissue imaging modalities with emphasis on verification; high rates of volumetric planning, and adherence to a defined overall treatment period. Brachytherapy was not substituted with other EBRT modalities. Despite this, there remain barriers to implementation of image-guided brachytherapy.

High-risk CTV delineation for cervix brachytherapy: Application of GEC-ESTRO guidelines in Australia and New Zealand.

INTRODUCTION: Image-based brachytherapy for cervical cancer using MRI has been implemented in Australia and New Zealand. The aims of this study were to measure variability in High-risk CTV (HR-CTV) delineation and evaluate dosimetric consequences of this. METHODS: Nine radiation oncologists, one radiation therapist and two radiologists contoured HR-CTV on 3T MRI datasets from ten consecutive patients undergoing cervical brachytherapy at a single institution. Contour comparisons were performed using the Dice Similarity Coefficient (DSC) and Mean Absolute Surface Distance (MASD). Two reference contours were created for brachytherapy planning: a Simultaneous Truth and Performance Level Estimation (STAPLE) and a consensus contour (CONSENSUS). Optimized plans (8 Gy) for both these contours were applied to individual participant's contours to assess D90 and D100 coverage of HR CTV. To compare variability in dosimetry, relative standard deviation (rSD) was calculated. RESULTS: Good concordance (mean DSC≥0.7, MASD≤5 mm) was achieved in 8/10 cases when compared to the STAPLE reference and 6/10 cases when compared to the CONSENSUS reference. Greatest variation was visually seen in the cranio-caudal direction. The average mean rSD across all patients was 27% and 34% for the STAPLE HR-CTV D90 and D100, respectively, and 28% and 35% for the CONSENSUS HR-CTV D90 and D100. Delineation uncertainty resulted in an average dosimetric uncertainty of ±1.5-1.6 Gy per fraction based on an 8 Gy prescribed fraction. CONCLUSIONS: Delineation of HR-CTV for cervical cancer brachytherapy was consistent amongst observers, suggesting similar interpretation of GEC-ESTRO guidelines. Despite the good concordance, there was dosimetric variation noted, which could be clinically significant.

A Phase II study of external-beam radiotherapy and endovascular brachytherapy with PTA and stenting for femoropopliteal artery restenosis.

PURPOSE: To assess the safety and seek evidence of efficacy of combined external-beam radiotherapy (EBRT) and endovascular brachytherapy in the treatment of stenotic vascular lesions. METHODS AND MATERIALS: Seventeen patients with high risk for restenosis of femoropopliteal arteries were enrolled in this study from February 2000 to August 2002. The external beam radiotherapy regimen consisted of 10 Gy in 5 fractions of 2 Gy, starting on Day 0. This was followed on Day 6 by angiography, stent placement, and intraluminal brachytherapy to a dose of 10 Gy at 1.2 mm from stent surface. The EBRT was continued from the same day to another 10 Gy in 2 Gy daily fractions for 5 days. RESULTS: The follow up ranged from 33 months to 60 months. At the time of analysis 15 of 17 patients were alive with patent stents. Of these, 10 were symptom-free. Two patients died of unrelated causes. CONCLUSIONS: The combination of EBRT and endovascular brachytherapy provided adequate dose distribution without any geographical miss or "candy wrapper" restenosis. No incidence of aneurysmal dilation of radiated vascular segment was observed. The treatment was feasible, well tolerated, and achieved 88% stenosis free survival.

Reproducibility and interoperator reliability of obtaining images and measurements of the cervix and uterus with brachytherapy treatment applicators in situ using transabdominal ultrasound.

PURPOSE: To validate interoperator reliability of brachytherapy radiation therapists (RTs) in obtaining an ultrasound image and measuring the cervix and uterine dimensions using transabdominal ultrasound. METHODS AND MATERIALS: Patients who underwent MRI with applicators in situ after the first insertion were included in the study. Imaging was performed by three RTs (RT1, RT2, and RT3) with varying degrees of ultrasound experience. All RTs were required to obtain a longitudinal planning image depicting the applicator in the uterine canal and measure the cervix and uterus. The MRI scan, taken 1 hour after the ultrasound, was used as the reference standard against which all measurements were compared. Measurements were analyzed with intraclass correlation coefficient and Bland-Altman plots. RESULTS: All RTs were able to obtain a suitable longitudinal image for each patient in the study. Mean differences (SD) between MRI and ultrasound measurements obtained by RTs ranged from 3.5 (3.6) to 4.4 (4.23) mm and 0 (3.0) to 0.9 (2.5) mm on the anterior and posterior surface of the cervix, respectively. Intraclass correlation coefficient for absolute agreement between MRI and RTs was >0.9 for all posterior measurement points in the cervix and ranged from 0.41 to 0.92 on the anterior surface. Measurements were not statistically different between RTs at any measurement point. CONCLUSIONS: RTs with variable training attained high levels of interoperator reliability when using transabdominal ultrasound to obtain images and measurements of the uterus and cervix with brachytherapy applicators in situ. Access to training and use of a well-defined protocol assist in achieving these high levels of reliability.

Clinical outcomes from an innovative protocol using serial ultrasound imaging and a single MR image to guide brachytherapy for locally advanced cervix cancer.

PURPOSE: The aim of this study was to report clinical outcomes in a series of patients who underwent serial ultrasound and a single MRI to plan and verify intracavitary brachytherapy. METHODS AND MATERIALS: Data for patients who were referred for curative intent radiotherapy for International Federation of Gynecology and Obstetrics (FIGO) Stage 1-1V cervix cancer between January 2007 and March 2012 were analyzed. All patients received external beam radiotherapy with concurrent chemotherapy and sequential high-dose rate brachytherapy. Brachytherapy was planned and verified using serial ultrasound imaging and a single MRI. RESULTS: Data from 191 patients were available for analyses. The median (range) followup time was 5.08 (0.25-8.25) years. Five-year local control, failure-free survival, cancer-specific survival, and overall survival were 86%, 57.3%, 70% and 63%, respectively. Mean (standard deviation) combined external beam radiotherapy and brachytherapy target doses, equivalent to doses in 2 Gy fractions were 80.4 Gy10 (3.89), median (range) 80 (49-96) Gy10. Grade 3 or greater gastrointestinal, genitourinary, or vaginal late toxicity occurred in 3%, 1.6%, and 2% of patients, respectively. Survival, patterns of failure, and late complication rates were similar to published series of MRI/CT-based brachytherapy practices. CONCLUSIONS: This large study demonstrates that favorable treatment outcomes can be obtained using a pragmatic and innovative combination of ultrasound and MR imaging.

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.

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.

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 protocol's 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.

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.

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

INTRODUCTION: 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. METHODS: This is a prospective non-randomised study. Eligible patients were those with T4 rectal cancer or pelvic recurrence, deemed suitable for radical surgery but at high risk of positive resection margins, without evidence of metastasis. Chemoradiation was followed by radical surgery. Ten gray (Gy) was delivered to tumour bed via an IORT applicator at time of surgery. RESULTS: There were 15% primary and 85% recurrent cancers. The 71% received preoperative chemoradiation. R0, R1 and R2 resections were 70%, 22% and 7%, respectively. IORT was successfully delivered in 27 of 30 registered patients (90% (95% confidence interval (CI) = 73-98) ) at a median reported time of 12 weeks (interquartile range (IQR) = 10-16) after chemoradiation. Mean IORT procedure and delivery times were 63 minutes (range 22-105 minutes). Ten patients (37% (95% CI = 19-58) ) experienced grade 3 or 4 toxicities (three wound, four abscesses, three soft tissue, three bowel obstructions, three ureteric obstructions and two sensory neuropathies). Local recurrence-free, failure-free and overall survival rates at 2.5 years were 68% (95% CI = 52-89), 37% (95% CI = 23-61) and 82% (95% CI = 68-98), respectively. CONCLUSION: The addition of IORT to radical surgery for T4 or recurrent rectal cancer is feasible. It can be delivered safely with low morbidity and good tumour outcomes.

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.

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.

Image-guided brachytherapy for cervix cancer: from Manchester to Melbourne.

Brachytherapy for cervix cancer has evolved rapidly over the last few years through the introduction of image-guided brachytherapy. This has enabled the transition from Manchester-based orthogonal radiograph planning to more conformal treatments, incorporating the concepts of patients' anatomy, tumor characteristics and tumor response with time. The purpose of this article is to outline the evolution of cervix cancer brachytherapy, discuss guidelines and recommendations on image-guided brachytherapy and describe our single-institution conformal image-based brachytherapy experience.