Can we reduce dose to ureters as avoidance organs for MRI based brachytherapy for cervical cancer? A dosimetric feasibility study

BACKGROUND AND PURPOSEUreteral stenosis (US) is an underreported complication of brachytherapy (BT) for cervical cancer (CC), with limited data on toxicity risk reduction. A previous study demonstrated ureter EQD2 D0.1cc > 77 Gy correlated with US development. We sought to assess feasibility of this constraint while maintaining similar HR-CTV coverage.MATERIALS AND METHODSPatients with locally advanced CC treated with EBRT plus HDR MRI-based brachytherapy boost without hydronephrosis at diagnosis and with ureter dose EQD2 D0.1cc > 77 Gy were included. Replan was attempted to achieve HR-CTV D90 ≥ 80–85 Gy and ureter dose reduction. Ureter distance from lateral margin of HR-CTV and tandem was recorded. t-test was performed to compare ureteral dose and HR-CTV D90.RESULTsOf 25 patients were identified. Hundred percent received 45 Gy in 25 fractions to the pelvis ± paraaortic lymph nodes and 80% receiving median additional parametrial dose of 5.4 Gy. Replan meeting ureteral dose of ≤77 Gy was feasible in 18 of 25 patients, with a reduction in median ureter D0.1cc from 82.3 to 76.8 Gy (p < 0.001). Median HR-CTV D90 was similar (84.7 vs. 85.0 Gy). Replan achieved D0.1cc ≤77 Gy in 56% of patients who experienced US. All unilateral US cases occurred in the ureter closest to HR-CTV.CONCLUSIONSOptimization to reduce ureter dose to ≤77 Gy is feasible when ureters are visible and contoured. Ureters may be considered as potential OAR during MRI-based brachytherapy treatment. Reduced ring to tandem total reference air kerma (TRAK) ratio may provide an additional metric by which to lower US risk.     

Dose–effect response in image-guided adaptive brachytherapy for cervical cancer: A systematic review and meta-regression analysis

PurposeThis study aimed to integrate and update the dose–effect relationship between volumetric dose and local control for cervical cancer brachytherapy.Methods and MaterialsWe identified studies that reported high-risk clinical target volume (HR-CTV) D₉₀ and local control probability by searching PubMed, Web of Science, and the Cochrane Library databases through Oct 27, 2019. The regression analyses were performed using a probit model between HR-CTV D₉₀, D₁₀₀, intermediate-risk clinical target volume (IR-CTV) D₉₀, and dose to Point A vs. local control probability. Subgroup analyses were performed according to stratification: time of local control, income level of the country or region, stage of cancer, pathology, mean volume of HR-CTV, dose rate, image modality, concurrent chemoradiotherapy proportion, interstitial proportion, and mean overall treatment time.ResultsThirty-three studies encompassing 2893 patients were included. The probit model showed a significant relationship between the HR-CTV D₉₀ value and the local control probability, p < 0.0001. The D₉₀ corresponding to a probability of 90% local control was 83.7 Gy_EQD2,10 (80.6–87.8 Gy_EQD2,10). Of the 33 studies included in our analysis, eight studies, including 1172 patients, reported the IR-CTV D₉₀ value, ranging from 59.1 Gy_EQD2,10 to 72.3 Gy_EQD2,10. The probit model also showed a significant relationship between the IR-CTV D₉₀ value and the local control probability, p = 0.0464. The 60 Gy_EQD2,10 for IR-CTV D₉₀ corresponded to an 86.1% local control probability (82.0%–89.8%).ConclusionsA significant dependence of local control on HR-CTV D₉₀ and IR-CTV D₉₀ was found. A tumor control probability of >90% can be expected at doses >84 Gy_EQD2,10 and 69 Gy_EQD2,10, respectively, based on an updated meta-regression analysis.     

Investigation of geometric distortions on magnetic resonance and cone beam computed tomography images used for planning and verification of high–dose rate brachytherapy cervical cancer treatment

PurposeTo measure the amount of geometric distortions present in the three-dimensional imaging modalities—cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI)—used at University of California, San Francisco, CA, for gynecologic high dose rate brachytherapy.Methods and MaterialsAn MRI- and CT–compatible water phantom with two different sets of support structures was designed and built for this study. The support structures were used to precisely position catheters that were filled with either an MRI contrast agent or a string of radio-opaque markers. The first support structure without anatomy was built to test system-based distortions. A second structure included two types of gynecologic applicators as well as several anatomical structures, including bones and rectum to test object-induced distortions. Images were acquired with CT (for reference), kilovoltage CBCT, and MRI (1.5 T with T1- and T2-weighted images). The difference in catheter positions between the images and the CT images was analyzed.ResultsFor CBCT, the mean of the absolute deviations was below 1 mm in all directions. The inherent uncertainty in the measurement of distortion was less than 0.5 mm. MRI presented mean absolute system-based distortions between 0.6 and 1.1 mm in the central region of the image and between 0.7 and 2.3 mm in the outer region. Images with the applicator and anatomy in place created mean absolute distortions of 0.4, 0.8, and 0.8 mm or less for CBCT, MR-T1, and MR-T2 images, respectively.ConclusionsThe distortions measured in the presence of applicators are small enough to validate the use of CBCT and 1.5 T MRI for GYN brachytherapy treatment planning and verification.     

An MRI-based dose–response analysis of urinary sphincter dose and urinary morbidity after brachytherapy for prostate cancer in a phase II prospective trial

PurposeTo compare dose–volume histogram variables for the internal and external urinary sphincters (IUS/EUS) with urinary quality of life after prostate brachytherapy.Methods and MaterialsSubjects were 42 consecutive men from a prospective study of brachytherapy as monotherapy with ¹²⁵I for intermediate-risk localized prostate cancer. No patient received hormonal therapy. Preplanning constraints included prostate V₁₀₀ higher than 95%, V₁₅₀ lower than 60%, and V₂₀₀ lower than 20% and rectal R₁₀₀ less than 1 cm³. Patients completed the Expanded Prostate Cancer Index Composite quality-of-life questionnaire before and at 1, 4, 8, and 12 months after implantation, and urinary domain scores were analyzed. All structures including the IUS and EUS were contoured on T2-weighted MRI at day 30, and doses received were calculated from identification of seeds on CT. Spearman's (nonparametric) rank correlation coefficient (ρ) was used for statistical analyses.ResultsOverall urinary morbidity was worst at 1 month after the implant. Urinary function declined when the IUS V₂₈₅ was 0.4% (ρ = ?0.32, p = 0.04); bother worsened when the IUS V₃₅ was 99% (ρ = ?0.31, p = 0.05) or the EUS V₂₄₀ was 63% (ρ = ?0.31, p = 0.05); irritation increased when the IUS V₃₅ was 95% (ρ = ?0.37, p = 0.02) and the EUS V₂₆₅ was 24% (ρ = ?0.32, p = 0.04); and urgency worsened when the IUS V₃₅ was 99.5% (ρ = ?0.38, p = 0.02). Incontinence did not correlate with EUS or IUS dose.ConclusionsDoses to the IUS and EUS on MRI/CT predicted worse urinary function, with greater bother, irritative symptoms, and urgency. Incorporating MRI-based dose–volume histogram analysis into the treatment planning process may reduce acute urinary morbidity after brachytherapy.     

Interstitial preoperative high-dose-rate brachytherapy for early stage cervical cancer: Dose–volume histogram parameters,pathologic response and early clinical outcome

PurposeTo analyze dose–volume histogram parameters and pathologic response after preoperative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs).Methods and MaterialsFrom June 2007 to December 2011, 32 patients with a histologically proven invasive cervical cancer with high risk of local recurrence (size >2 cm, adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39 Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB.ResultsWith a median clinical target volume of 50 cc (minimum–maximum, 42–74), the median V₁₀₀ was 49 cc (minimum–maximum, 42–50). Median D₉₀ was 45 Gy (equivalent dose at 2 Gy per fraction, 56 Gy_αβ10). Median D_2cc was 34 Gy, 31 Gy, 28 Gy, and 38 Gy_αβ3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histologic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median followup of 24 months (minimum–maximum, 5–48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2–G3 toxicities were noticed.ConclusionsPreoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Dose–volume histogram parameters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs.     

3T multiparametric MRI–guided high-dose-rate combined intracavitary and interstitial adaptive brachytherapy for the treatment of cervical cancer with a novel split-ring applicator

PurposeTo evaluate the role of 3T-MRI–guided adaptive high-dose-rate (HDR) combined intracavitary and interstitial brachytherapy for cervical cancer using a novel intracavitary split-ring (ICSR) applicator adapter.Methods and MaterialsWe retrospectively reviewed all HDR brachytherapy cases from 2013 to 2015 using an ICSR applicator. Initial optimization was performed using 3T multiparametric MRI (mpMRI) series with an applicator in place. The mpMRI series were discretionarily acquired before subsequent fractions for possible target adaptation. When necessary, interstitial needles (ISNs) were inserted through a novel ICSR adapter or freehand. Dosimetric parameters, clinical outcomes, and toxicities were compared between groups.ResultsSeventeen patients were included, with a mean followup of 32 months. An mpMRI series preceded each initial fraction and 52.9% of patients underwent ≥1 additional pretreatment mpMRI. Among these subsequent fractions, the high-risk clinical target volume was reduced in 80% vs. 41% without pretreatment mpMRI. Five patients had ISN placement (seven insertions) to improve extracervical target coverage. Mean D₉₀ (Gy) per fraction to the high-risk clinical target volume and intermediate-risk clinical target volume with and without an ISN were 7.51 ± 1.07 vs. 6.14 ± 0.52 (p = 0.028) and 6.35 ± 0.75 vs. 5.21 ± 0.49 (p = 0.007), respectively. Mean fractional D_2cc (Gy) for organs at risk was comparable. No Grades 3–4 toxicity was reported. Disease-free survival and local control for the ICSR-ISN and ICSR-alone groups were 29.8 months/80.0% and 31.2 months/83.3%, respectively.ConclusionsThe mpMRI acquisition with ICSR applicator in place immediately before HDR brachytherapy for cervical cancer guided successful adaptive treatment optimization and delivery. Our initial experience with a novel interstitial adapter for the split-ring applicator demonstrated excellent target coverage without compromising organs at risk, resulting in good local control and disease-free survival.     

Rectal morbidity after permanent interstitial brachytherapy for prostate cancer—Impact of Day 1 vs. Day 30 computed tomography–based postimplant dosimetry

PurposeThe aim of the study was to evaluate bowel quality-of-life changes after prostate brachytherapy and the impact of Day 1 vs. Day 30 postimplant dosimetry.Methods and MaterialsIn 61 patients, computed tomography (CT) scans were performed at Days 1 and 30 after ¹²⁵I brachytherapy. The patients have been surveyed prospectively before (time A), 1 month (time B), and >1 year after treatment (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Different parameters were tested for their predictive value on bowel quality-of-life changes (bowel bother score decrease >20 points at time B = BB20; bowel bother score decrease >10 points at time C = BC10), including seed displacements.ResultsMean bowel function/bother score decreased 13/13 points at time B (p < 0.01) and 1/4 points at time C (change not significant). BB20 and BC10 were found in 25% and 20% of patients, respectively. Bowel bother score declines at time B correlated well with declines at time C (r = 0.53; p < 0.01). Prostate volume before implantation and the number of seeds per cubic centimeters were found to be predictive for BB20 and BC10. Smaller rectal wall volumes covered by the 60–100% isodoses at Day 1 were (paradoxically) found to be significantly predictive for BC10. Larger posterior seed displacements between Days 1 and 30 were significantly associated with BB20.ConclusionsQuality-of-life scores have not been found to change significantly >1 year after brachytherapy. Larger rectal wall volumes within higher isodoses at Day 1 or 30 were not found to be predisposing for adverse quality-of-life changes.