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.     

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.     

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%.     

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.     

Image-guided interstitial high-dose-rate brachytherapy for dose escalation in the radiotherapy treatment of locally advanced lung cancer: A single-institute experience

PurposeTo evaluate the clinical outcome after CT-guided interstitial high-dose-rate (HDR) brachytherapy for dose escalation in the radiotherapy treatment of inoperable locally advanced non–small-cell lung cancer (NSCLC).Methods and MaterialsFrom 2005 to 2015, 16 patients with unresectable NSCLC were treated. Median age was 65.7 years (range, 52–86). The median tumor volume was 95.3 cm³ (range, 20.0–2000.0). The median prescribed HDR was 15.0 Gy (range, 7.0–32.0) delivered in twice-daily fractions of 6.0–8.0 Gy in 4 patients and in once-daily fractions of 7.0–15.0 Gy in 12 patients, respectively.ResultsAfter a median followup of 12.5 months, median overall survival and local control was 12.9 and 24.9 months, respectively. The corresponding median overall survival and local control rates at 1, 2, and 3 years were 56.2%, 37.5%, and 12.5% as well as 68.9%, 57.4%, and 43%, respectively. Apart from one Grade 1 cough episode persisting for 1 week and one patient developing a minor hemopneumothorax requiring no postprocedural drainage, no other adverse events were recorded.ConclusionsCT-guided interstitial HDR brachytherapy is a safe modality for radiation dose escalation which may play a role in the definitive radiotherapy treatment of locally advanced NSCLC.     

High-dose-rate vs. low-dose-rate interstitial brachytherapy boost for anal canal cancers

PurposeThe purpose of this study was to analyze and compare clinical outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after EBRT or radio chemotherapy for the treatment of anal canal cancers.Methods and MaterialsOne hundred patients with anal canal cancers were treated at our institution by ISBT [LDR (n = 50); HDR (n = 50)]. Chronic toxicity rates, local control, disease-free survival, overall survival, and colostomy-free survival of the two different dose-rate brachytherapy modalities were analyzed and compared.ResultsWith a median followup of 42.2 months (95% CI, [34.5–48.8]), 9 (9% [4.8–16.2%]) local recurrences were observed, 4 (8% [3.2–18.8%]) in LDR vs. 5 (10% [4.4–21.4%]) in HDR group (odds ratio [OR] = 1.28 [0.32–5.07], p = 0.73). The 5-year rate of local control for the entire population was 90% [81–95%], 93% [79–98%] vs. 86% [69–94%] for LDR and HDR, respectively (p = 0.38). The 5-year disease-free survival rate for all patients was 82% [71–90%], 88% [73–95%] vs. 72% [44–88%] for LDR and HDR, respectively (p = 0.21). The 5-year overall survival rate for global population was 94% [84–98%], with no significant differences between LDR (97% [79–100%]) and HDR (93% [80–98%]) (p = 0.27). The 5-year colostomy-free survival rate was 92% [83–96%], respectively, 95% [83–99%] vs. 86% [69–94%] for LDR and HDR (p = 0.21). Significant differences were found in terms of chronic toxicity rates, with 28 (56% [42.3–68.8%]) patients concerned in low-dose-rate brachytherapy vs. 17 (34% [22.4–47.9%]) in high-dose-rate brachytherapy (OR = 0.40 [0.18–0.91], p = 0.03).ConclusionsLocal recurrence rates were comparable between both groups; HDR brachytherapy seem to have a better toxicity profile. Our data confirmed the finding that HDR can be used to safely administer ISBT without increasing chronic toxicity.     

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%.     

Long-term efficacy and urological toxicity of low-dose-rate brachytherapy (LDR-BT) as monotherapy in localized prostate cancer

PurposeThe purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa).Methods and MaterialsDuring the years 1999–2008, 241 patients with PCa who underwent LDR-BT with I¹²⁵ and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed.ResultsAll D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores (p = 0.016) and higher initial urine residual volumes (p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively.ConclusionsThe treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.     

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.     

Changes in ADC and T2-weighted MRI-derived radiomic features in patients treated with focal salvage HDR prostate brachytherapy for local recurrence after previous external-beam radiotherapy

PurposeTo explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.Materials and MethodsEligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance.ResultsPre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p < 0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p < 0.05).ConclusionsExploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB.     

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.     

Permanent breast seed implant for partial breast radiotherapy after partial mastectomy for favorable breast cancer: Technique,results, and applications to various seroma presentations

PurposeAdjuvant partial breast radiotherapy is the standard of care for early-stage favorable breast cancer. We report dosimetry, acute and late tolerance for 67 permanent breast seed implants.Materials and MethodsFrom July 2012 to October 2018, 67 postmenopausal women with unifocal pT1pN0 invasive ductal or ductal carcinoma in situ received partial breast radiotherapy using stranded Pd-103 seeds after breast-conserving surgery, delivering 90 Gy to the seroma + margin (1.25–1.5 cm), planned with computed tomography simulation and performed as an ultrasound-guided outpatient procedure. The planning and postimplant computed tomography images were fused for seroma delineation for postimplant dosimetry. Evaluations were performed at 1, 2, 6, and 12 months and then annually.ResultsAlthough patient acceptance is high, only 40% met technical requirements of seroma volume, location, and visibility. For 67 patients, the median seroma volume was 6.6 cc, PTV 61 cc, and number of needles 18. In day 0 dosimetry, median seroma D90 dose was 132 Gy; seroma + 5 mm, 106 Gy; and seroma + 10 mm, 80 Gy. Peak reaction at 6 weeks is limited to the implant site: 51% grade 1 erythema and 12% focal desquamation. Late reactions (>2 years) are generally minimal: 35% no sequelae, 43% localized fibrosis, 20% mild telangiectasia (6% moderate but asymptomatic), 22% contour change. At minimum 6-month follow-up, 94% were “very or totally satisfied.” Recurrences (median follow-up: 3.3 years) were one in breast (different quadrant) and 2 contralateral. Three patients have had biopsies of fibrosis, all negative for malignancy.ConclusionsOur experience with permanent breast seed implant is favorable with a high patient acceptance and satisfaction, excellent early efficacy, and very satisfactory cosmesis.     

Feasibility of an MRI-only workflow for postimplant dosimetry of low-dose-rate prostate brachytherapy: Transition from phantoms to patients

PurposeThe lack of positive contrast from brachytherapy seeds in conventional MR images remains a major challenge toward an MRI-only workflow for postimplant dosimetry of low-dose-rate brachytherapy. In this work, the feasibility of our recently proposed MRI-only workflow in clinically relevant scenarios is investigated and the necessary modifications in image acquisition and processing pipeline are proposed for transition to the clinic.Methods and MaterialsFour prostate phantoms with a total of 321 I-125 implanted dummy seeds and three patients with a total of 168 implanted seeds were scanned using a gradient echo sequence on 1.5 T and 3T MR scanners. Quantitative susceptibility mapping (QSM) was performed for seed visualization. Before QSM, the seed-induced distortion correction was performed followed by edge enhancement. Seed localization was performed using spatial clustering algorithms and was compared with CT. In addition, feasibility of the proposed method on detection of prostatic calcifications was studied.ResultsThe proposed susceptibility-based algorithm generated consistent positive contrast for the seeds in phantoms and patients. All the 321 seeds in the four phantoms were correctly identified; the MR-derived seeds centroids agreed well with CT-derived positions (average error = 0.5 ± 0.3 mm). The proposed algorithm for seed visualization was found to be orientation invariant. In patient cases, all seeds were visualized and correctly localized (average error = 1.2 ± 0.9 mm); no significant differences between dose volume histogram parameters were found. Prostatic calcifications were depicted with negative contrast on QSM and spatially agreed with CT.ConclusionsThe proposed MRI-based approach has great potential to replace the current CT-based practices. Additional patient studies are necessary to further optimize and validate the workflow.     

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.