Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer

PurposeOnly scarce data are available on the possibility to include radiobiological optimization as part of the dosimetric process in cervical cancer treated with brachytherapy (BT). We compared dosimetric outcomes of pulse-dose-rate (PDR) and high-dose-rate (HDR)-BT, according to linear-quadratic model.Methods and MaterialsThree-dimensional dosimetric data of 10 consecutive patients with cervical cancer undergoing intracavitary image-guided adaptive PDR-BT after external beam radiation therapy were examined. A new HDR plan was generated for each patient using the same method as for the PDR plan. The procedure was intended to achieve the same D₉₀ high-risk clinical target volume with HDR as with PDR planning after conversion into dose equivalent per 2 Gy fractions (EQD2) following linear-quadratic model. Plans were compared for dosimetric variables.ResultsAs per study's methodology, the D₉₀ high-risk clinical target volume was strictly identical between PDR and HDR plans: 91.0 Gy (interquartile: 86.0–94.6 Gy). The median D₉₈ intermediate-risk clinical target volume was 62.9 Gy_EQD2 with HDR vs. 65.0 Gy_EQD2 with PDR (p < 0.001). The median bladder D_2cc was 65.6 Gy_EQD2 with HDR, vs. 62 Gy_EQD2 with PDR (p = 0.004). Doses to the rectum, sigmoid, and small bowel were higher with HDR plans with a median D_2cc of 55.6 Gy_EQD2 (vs. 55.1 Gy_EQD2, p = 0.027), 67.2 Gy_EQD2 (vs. S 64.7 Gy_EQD2, p = 0.002), and 69.4 Gy_EQD2 (vs. 66.8 Gy_EQD2, p = 0.014), respectively. For organs at risk (OARs), the effect of radiobiological weighting depended on the dose delivered. When OARs BT contribution to D_2cc doses was <20 Gy_EQD2, both BT modalities were equivalent. OARs EQD2 doses were all higher with HDR when BT contribution to D_2cc was ≥20 Gy_EQD2.ConclusionBoth BT modalities provided satisfactory target volume coverage with a slightly higher value with the HDR technique for OARs D2_cc while intermediate-risk clinical target volume received higher dose in the PDR plan. The radiobiological benefit of PDR over HDR was predominant when BT contribution dose to OARs was >20 Gy.     

Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy

PURPOSETo report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution.METHODSSeventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3–3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4–7 Gy given once or twice a week).RESULTSMedian follow-up was 76 months (7–204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9–54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation.CONCLUSIONSHDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.     

Understanding the underutilization of cervical brachytherapy for locally advanced cervical cancer

PurposeTo understand the reasons behind current low utilization of brachytherapy for locally advanced cervical cancer in the United States.Methods and MaterialsA 17-item survey was e-mailed to the American Brachytherapy Society (ABS) listserv of active members in 2018. Responses of attending physicians in the United States were included in the analysis.ResultsAmong a total of 135 respondents, 81 completed the survey. Eighty-four percent agree/strongly agree that cervical brachytherapy is underutilized, and 46.9% disagree/strongly disagree that residents are receiving adequate training for brachytherapy; 75.3% agree/strongly agree that inadequate maintenance of brachytherapy skills is a major obstacle to brachytherapy use; and 71.6% agree/strongly agree that increased time requirement constitutes a major obstacle. Over 97% will recommend brachytherapy for most patients with cervical cancer if given access/time; 72.8% always perform their own brachytherapy, whereas 29.6% reported some type of barrier exists in performing brachytherapy themselves, with time required to perform brachytherapy (9.9%) being a leading factor. A quarter (24.7%) routinely refer to other radiation oncologists for brachytherapy. Even among ABS members, 37.0% reported that they would perform an intensity-modulated radiation therapy or stereotactic body radiation therapy boost in specific scenarios in potentially curable patients. The most common scenario is inability to place a uterine tandem (56.7%).ConclusionsThe underutilization of brachytherapy in cervical cancer is widely recognized by ABS members with inadequate training during residency and inadequate maintenance of skills being possible major contributing factors. Even among ABS members, there are identifiable barriers. Continued advocacy and future initiatives in enhancing access to brachytherapy training and efficiency are needed.     

Single-fraction brachytherapy as monotherapy for early-stage prostate cancer: The UCSF experience

PurposeHigh-dose-rate (HDR) brachytherapy as monotherapy is an effective treatment option for localized prostate cancer, but experience with single-fraction brachytherapy is limited by studies with small sample size. We report a large single-institution experience with single-fraction HDR brachytherapy as monotherapy for early-stage prostate cancer.Methods and MaterialsRetrospective chart review was performed for men treated with HDR brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Competing risk analyses were performed to estimate subdistribution hazard ratio and cumulative incidence of biochemical recurrence (BCR) and prostate cancer–specific mortality.ResultsWe identified 124 men with a median followup of 2.2 years (interquartile range 25th to 75th percentile: 1.8–3). Overall, 21.0% of patients (n = 26) were low risk, 44.4% (n = 55) were favorable intermediate risk, and 34.7% (n = 43) were unfavorable intermediate risk. At 2 years, the cumulative incidence of BCR was 3.5%: 0% for low risk, 4.0% for favorable intermediate risk patients, and 4.5% for unfavorable intermediate risk patients. In total, 12 BCRs were observed (9.7%) and approximately half occurred after median followup of 2.2 years. Compared with low-risk and favorable intermediate-risk disease, unfavorable intermediate-risk disease was significantly associated with BCR (subdistribution hazard ratio: 3.6, 95% CI: 1.1 to 11.1, p = 0.03). Prostate cancer–specific mortality was 0%. No patient experienced Grade 3 or higher acute or late genitourinary toxicity.ConclusionsSingle-fraction brachytherapy for early-stage prostate cancer was safe with promising short-term disease control rates, especially for low-risk patients. Longer term followup is needed as we observed an overall BCR rate of 9.7%.     

Influence of transitioning of planning techniques in high-dose-rate brachytherapy monotherapy for clinically localized prostate cancer from two- to three-dimensional planning

PurposeThe purpose of this study was to examine the influence of transitioning treatment planning techniques in high-dose-rate interstitial brachytherapy monotherapy for localized prostate cancer.Methods and MaterialsWe compared 113 patients treated with initial two-dimensional treatment planning (2D: 74% received 54 Gy/nine fractions) to 240 patients treated with three-dimensional planning (3D: 70 CT image-guided 3D [CT-3D]: 84% 45.5 Gy/seven fractions and 170 MRI image-guided [MRI-3D]: 87% received 49 Gy/nine fractions).ResultsThe actuarial 5-year biochemical failure-free survival rates for 2D and 3D planning were 88.4% and 95.1% (p = 0.0285 between 2D and 3D) (89.4% in CT-3D and 97.5% in MRI-3D), respectively; the rates for 2D and 3D planning were not available and 100% in the low-risk group (100% and 100%), 97.7% and 94.5% (p = 0.7626) (85.1% and 100%) in the intermediate-risk group, and 82.5% and 94.4% (p = 0.0507) (93.8% and 94.7%) for the high-risk group. Late gastrointestinal (GI) toxicity Grade 1, Grade 2, and Grade 3 was found in 13%, 4%, and 1% in 2D, whereas 8%, 2%, and 0% in 3D group (p = 0.0699), respectively. 3D decreased GI toxicity Grade 2 ≤ than 2D (19% and 10%, p = 0.0169). Late genitourinary toxicity Grade 1, Grade 2, and Grade 3 was 21%, 12%, and 3% for 2D and 32%, 18%, and 3% for 3D, respectively (p = 0.0217).ConclusionsThe 3D technique has the potential to reduce GI toxicity and improve biochemical control rate compared to 2D planning, whereas 3D resulted in increased mild genitourinary toxicity.     

Cosmetic assessment in brachytherapy (interventional radiotherapy) for breast cancer: A multidisciplinary review

PurposeThis review was to focus on breast brachytherapy cosmetic assessment methods state of the art and to define the advantages and disadvantages related to.Methods and MaterialsWe conducted a literature review of the major experience on breast brachytherapy cosmetic assessment methods in several databases (PubMed, Scopus, and Google Scholar databases). To identify the relevant works, a task force screened citations at title and abstract level to identify potentially relevant paper. An expert board reviewed and approved the text. The assessment systems were classified into three main groups: (1) the Oncological Toxicity Scales, (2) the Independent Patients Perspective Measures, (3) the Patient-Related Outcome Measures. Each cosmetic assessment method was evaluated following six parameters: (1) anatomical site, (2) advantages, (3) disadvantages, (4) subjective/objective, (5) quantitative/qualitative, (6) computers or pictures needs.ResultsEleven assessment methods were selected. Three methods were classified as Oncological Toxicity Scale, six in the Independent Patients Perspective Measures classification, and two as Patient-Related Outcome Measures. Six methods are subjective, while eight are objective. Four systems are classified as quantitative, four as qualitative while three both. Five systems need informatics support. Moreover, each method was discussed individually reporting the main characteristics and peculiarities.ConclusionsCosmesis is one major end point for the patient who has a malignancy of low lethal potential. In modern personalized medicine, there is a need for standardized cosmetic outcome assessments to analyze and compare the results of treatments. No gold standard methods currently exist. The result of this review is to summarize the various cosmesis methods, defining the strengths and weaknesses of each one and giving a line in research and clinical practice.     

Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy

PurposeTo compare clinical outcomes between low-dose-rate (LDR) brachytherapy and high-dose-rate (HDR) brachytherapy for cervical cancer patients.Methods and MaterialsAll consecutive newly diagnosed cervical cancer patients undergoing pretreatment 18-fluorodeoxyglucose positron emission tomography imaging and treated with curative-intent definitive chemoradiation from 1997 to 2016 at a U.S. academic center were included. Brachytherapy boost was LDR or HDR 2D treatment planning from 1997 to 2005 and HDR with MR-based 3D planning from 2005 to 2016. Local control (LC), cancer-specific survival (CSS), and late bowel/bladder complications were evaluated.ResultsTumor stages were International Federation of Gynecology and Obstetrics IB1-IIB (n = 457; 75%) and III-IVA (n = 152; 25%). Brachytherapy was LDR for 104 patients and HDR for 505 patients. Concurrent weekly cisplatin was administered to 536 patients (88%). With median followup of 9.4 years, there was no difference in LC (p = 0.24) or CSS (p = 0.50) between LDR and HDR brachytherapy. Cox multivariable regression showed that only International Federation of Gynecology and Obstetrics stage III-IVA (HR=2.4, p = 0.004) was associated with worse LC. A propensity-matched cohort (90 LDR vs. 90 HDR) was created, and the 5-year LC rates were 88% LDR and 82% HDR, p = 0.26; 5-year CSS rates were 66% LDR and 58% HDR, p = 0.19; 5-year grade ≥3 bowel/bladder toxicities were 23% LDR and 16% HDR, p = 0.44. For all patients, the 5-year late toxicity in stage III-IVA patients was higher with LDR 47% vs. HDR 15%, p = 0.03, with no difference in LC, 86% and 75%, respectively (p = 0.09).ConclusionsThere was no difference in LC with either LDR or HDR brachytherapy. The late complication rate was reduced with HDR and 3D-planned brachytherapy compared to LDR and 2D-planned brachytherapy.     

Mechanical evaluation of the Bravos afterloader system for HDR brachytherapy

PurposeThe Bravos afterloader system was released by Varian Medical Systems in October of 2018 for high-dose-rate brachytherapy with ¹⁹²Ir sources, containing new features such as the CamScale (a new device for daily quality assurance and system recalibration), channel length verification, and different settings for rigid and flexible applicators. This study mechanically evaluated the Bravos system precision and accuracy for clinically relevant scenarios, using dummy sources.Methods and MaterialsThe system was evaluated after three sets of experiments: (1) The CamScale was used to verify inter- and intra-channel dwelling variability and system calibration; (2) A high-speed camera was used to verify the source simulation cable movement inside a transparent quality assurance device, where dwell positions, dwell times, transit times, speed profiles, and accelerations were measured; (3) The source movement inside clinical applicators was captured with an imaging panel while being exposed to an external kV source. Measured and planned dwell positions and times were compared.ResultsMaximum deviations between planned and measured dwell positions and times for the source cable were 0.4 mm for the CamScale measurements and 0.07 seconds for the high-speed camera measurements. Mean dwell position deviations inside clinical applicators were below 1.2 mm for all applicators except the ring that required an offset correction of 1 mm to achieve a mean deviation of 0.4 mm.ConclusionsFeatures of the Bravos afterloader system provide a robust and precise treatment delivery. All measurements were within manufacturer specifications.     

Monte Carlo study of the relationship between skin dose and optically stimulated luminescence dosimeter dose in Pd-103 permanent breast seed implant brachytherapy

PurposeTo establish a method for estimating skin dose for patients with permanent breast seed implant based on in vivo optically stimulated luminescence dosimeters (OSLDs) measurements.Methods and MaterialsMonte Carlo simulations were performed in a simple breast phantom using the EGSnrc user code egs_brachy. Realistic models of the IsoAid Advantage Pd-103 brachytherapy source and Landauer nanoDot OSLD were created to model in vivo skin dose measurements where an OSLD would be placed on the skin of a patient with permanent breast seed implant following implantation. Doses to a 0.2 cm³ volume of skin beneath the OSLD and to the sensitive volume within the OSLD were calculated, and the ratio of these values was found for various seed positions inside the breast phantom. The maximum value of this ratio may be used as a conversion factor that would allow skin dose to be estimated from in vivo OSLD measurements.ResultsConversion factors of 0.5 and 1.44 are recommended for OSLDs calibrated to dose to Al₂O₃ and water, respectively, at the point of measurement in the OSLD. These factors were not significantly affected by the addition of extra seeds in the dose calculations.ConclusionsA method for estimating skin dose from OSLD measurements was proposed. Individual institutions should calibrate OSLDs to Pd-103 seeds to apply the results of this work clinically.     

Detection of air gaps around the cylinder by postinsertion computed tomography in vaginal cuff brachytherapy: A prospective series,systematic review,and meta-analysis

PurposePostinsertion computed tomography (CT) can identify air gaps (AGs) around the cylinder in vaginal cuff brachytherapy (VCB). This study investigates the incidence and location of AGs.Methods and MaterialsPlanning CTs of 22 prospectively recruited patients (NCT02091050) treated with 2.6 cm (n = 8) and 3.0 cm (n = 14) cylinders were evaluated. In addition, a systematic literature review and meta-analysis was performed (PubMed and EMBASE). The pooled incidence of AGs was calculated by using the random-effects model weighted by inverse variance.ResultsIn 18 cases (82%), a total of 45 AGs were found: 26 within the 2 cm cranial length and 19 between 2 and 4 cm of the cylinder. The mean AG diameter was 3.7 mm (range: 1.3–11.8). Cylinder diameter, primary tumor site, and use of external beam radiotherapy were not associated with AG incidence. Systematic literature review revealed nine additional relevant studies, totaling 657 patients. The pooled incidence of patients with ≥1 AG was 67% (95% confidence interval: 50–83). AGs were located at the apex in 43.4%–94.4% of cases. In patients with ≥1 AG (n = 244), the pooled mean number of AGs was 2.18 per patient. The mean dose reduction varied from 9.6% to 29.3%.ConclusionMore than two-thirds of VCB cases present with AGs, which are most commonly at the apex and can potentially reduce mucosal dose. By identifying AGs, postinsertion CT can facilitate selection of optimal cylinder size in VCB.