Magnetic Resonance Image-guided Brachytherapy Research Articles

Feasibility of quantitative diffusion-weighted imaging during intra-procedural MRI-guided brachytherapy of locally advanced cervical and vaginal cancers

PurposeTo determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI). Methods and MaterialsT2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were compared between timepoints using repeated measures ANOVA. ResultsssEPI-DWI mean ADC increased between baseline and prebrachytherapy from 1.03 ± 0.18 10−3 mm2/s to 1.34 ± 0.28 10−3 mm2/s for the GTV (p = 0.06) and from 0.84 ± 0.13 10−3 mm2/s to 1.26 ± 0.25 10−3 mm2/s at the level of the GTVcenter (p = 0.03), consistent with early treatment response. rFOV-DWI during MRgBT demonstrated mean ADC values of 1.28 ± 0.14 10−3 mm2/s and 1.28 ± 0.19 10−3 mm2/s for the GTV and GTVcenter, respectively (p = 0.02 and p = 0.03 relative to baseline). No significant differences were observed between ssEPI-DWI and rFOV-DWI ADC measurements. ConclusionsQuantitative ADC measurement in the setting of MRI guided brachytherapy implant placement for cervical and vaginal cancers is feasible using rFOV-DWI, with comparable mean ADC comparable to prebrachytherapy ssEPI-DWI, and may enable MRI-guided radiotherapy targeting of low ADC, radiation resistant sub-volumes of tumor.

Risk Factors for Late Persistent Fatigue After Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Analysis From the EMBRACE-I Study

This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study. Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradiotherapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade ≥1 or ≥2 was scored in at least half of the follow ups. The median follow-up time was 57 months. Baseline fatigue grade ≥1/≥2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade ≥1/≥2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT+brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade ≥2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade ≥1 increased by 7% and 4% with V43Gy <2000 cm³ versus >3000 cm³ in patients with and without baseline fatigue, respectively. Late persistent grade ≥1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively. Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques.

Comparison of impact of target delineation of computed tomography- and magnetic resonance imaging-guided brachytherapy on dose distribution in cervical cancer.

PurposeThe dose distributions obtained from three imaging approaches for target delineation in cervical cancer using high-dose-rate (HDR) brachytherapy were investigated.Material and methodsTen cervical cancer patients receiving four fractions of HDR brachytherapy were enrolled. Based on different imaging approaches, three brachytherapy plans were developed for each patient: with the high-risk clinical target volume (HRCTV) delineated on magnetic resonance (MRI) images for every fraction (approach A; MRI-only); on MRI for the first fraction and computed tomography (CT) images for the subsequent fractions (approach B; MRI1st/CT); and on CT images for all fractions (approach C; CT-only). The volume, height, width at point A, width at maximum level, and dosimetric parameters (D100, D98, D95, and D90 of the HRCTV; and D0.1cc, D1cc, and D2cc of all organs at risk, or organ at risk – OAR: bladder, rectum, sigmoid colon, and bowel) provided by each approach were compared.ResultsThe mean HRCTV volume, width, and height obtained from approach C (CT-only) were overestimated compared to those from approaches A (MRI-only) and B (MRI1st/CT). The doses to the HRCTV for approaches A and B were similar. However, the HRCTV doses for approach C were significantly lower than those for approaches A and B for all parameters (D95-D100). As to the OAR, the three approaches showed no differences.ConclusionsA combination of MRI and CT is a safe alternative approach for cervical cancer HDR brachytherapy. The technique provides comparable dosimetric outcomes to MRI-based planning, while being more cost-effective.

Throwing the dart blind-folded: comparison of computed tomography versus magnetic resonance imaging-guided brachytherapy for cervical cancer with regard to dose received by the 'actual' targets and organs at risk.

PurposeComputed tomography (CT) is inferior to magnetic resonance imaging (MRI) in cervical tumor delineation, but similar in identification of organs at risk (OAR). The trend to over-estimate high-risk and low-risk clinical target volume (HRCTV, IRCTV) on CT can lead to under-estimation of dose received by 90% (D90) of the ‘actual’ CTV. This study aims to evaluate whether CT-guided planning delivers adequate dose to the ‘actual’ targets while spares the OAR similarly.Material and methodsMRI-guided high-dose-rate image-guided brachytherapy (IGBT) was performed in 11 patients. The pre-brachytherapy CTs were retrospectively contoured to generate CT-guided plans. MRI-based contours (HRCTVmri, IRCTVmri, bladdermri, rectummri, and sigmoidmri) were fused to CT plans for dosimetric comparison with MRI-guided plans. Paired 2-tailed t-test and Wilcoxon signed-rank test were used to analyze data.Results63.6% of CT plans achieved the HRCTVmriD90 constraint (≥ 7.2 Gy in one fraction), compared with 90.9% for MRI plans. > 90% of both modalities achieved the OAR’s constraints (EMBRACE). The percentage of CT and MRI plans that achieved the aims (EMBRACE II) for bladder, rectum, and sigmoid were 36.4% vs. 81.8%, 63.6% vs. 63.6%, and 72.7% vs. 72.7%, respectively. There were no statistically significant differences in HRCTVmriD90, IRCTVmriD90, or dose received by the most exposed 2 cm3 (D2cc) of OARmri between the modalities. Excluding the CT plans not achieving HRCTVmriD90 constraint, there were significant increase in bladdermriD2cc, rectummriD2cc, and sigmoidmriD2cc, compared with MRI plans (0.9 Gy/Fr, 95% CI 0.2-1.5, p = 0.018; 0.9 Gy/Fr, 95% CI 0.3-1.4, p = 0.009; 0.5 Gy/Fr, 95% CI 0.2-0.9, p = 0.027, respectively).ConclusionsMRI-based IGBT remains the gold standard. CT planning may compromise HRCTVmriD90 or increase OARmriD2cc, which could decrease local control or increase treatment toxicity.

Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience

ABSTRACTBackground. To evaluate efficacy and toxicity of radio-chemotherapy (RCT) and MR-guided pulsed-dose-rate (PDR) adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC).Material and methods. Between 2007 and 2014 85 patients with FIGO stage 1B1 N+ or ≥ 1B2 cervical cancer were treated with RCT+ IGABT. The treatment consisted of a pelvic± paraaortic external beam radiotherapy (EBRT) (45–50.4 Gy ± 10 Gy boost to primary tumor and/or to pathologic lymph nodes) with concurrent cisplatin followed by 25–35 Gy of PDR IGABT in 30–50 pulses. The ratio of 3D-CFRT/IMRT was 61/24 patients. Dose-volume parameters of high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and D2cm3 organs at risk (OARs) were reported. Local control (LC), cancer-specific survival (CCS) and overall survival (OS) were analyzed actuarially and morbidity crude rates were scored using CTCAEv4.0.Results. Mean follow-up was 36 months (range 6–94). The mean D90 and D98 for HR-CTV was 84.4 ± 9 Gy and 77 ± 8.1 Gy, while for IR-CTV was 69.1 ± 4.3 Gy and 64.8 ± 4.3 Gy, respectively. The mean D2cm3 for OARs was the following: bladder: 77.3 ± 10.5 Gy, rectum: 65 ± 6.8 Gy, sigmoid: 63 ± 7.9 Gy and intestine: 64.0 ± 9.1 Gy. Three year LC, CSS and OS were: 94%, 85% and 81%. The three-year regional- and distant control rates were 95% and 74%. Node negative patients had significantly higher three-year CSS (100 vs. 72%, p = 0.016) and OS (92 vs. 72%, p = 0.001) compared to node positive ones. Three-year actuarial late Grade ≥ 3 morbidity was the following: GI: 8%, GU: 5%, Vaginal: 8%. The frequency of Grade ≥ 3 hematological toxicities including anemia/leukopenia/neutropenia/thrombocytopenia were 8.6%/34.7%/24.3%/24.3%, respectively.Conclusion. This large mono-institutional experience builds up further evidences that IGABT in conjunction with RCT should be the standard of care for patients suffering LACC.

Magnetic resonance imaging-guided brachytherapy for cervical cancer: initiating a program.

Over the past decade, the application of magnetic resonance imaging (MRI) has increased, and there is growing evidence to suggest that improvements in accuracy of target delineation in MRI-guided brachytherapy may improve clinical outcomes in cervical cancer. To implement a high quality image guided brachytherapy program, a multidisciplinary team is required with appropriate expertise as well as an adequate patient load to ensure a sustainable program. It is imperative to know that the most important source of uncertainty in the treatment process is related to target delineation and therefore, the necessity of training and expertise as well as quality assurance should be emphasized. A short review of concepts and techniques that have been developed for implementation and/or improvement of workflow of a MRI-guided brachytherapy program are provided in this document, so that institutions can use and optimize some of them based on their resources to minimize their procedure times.

Clinical Use of the Utrecht Applicator for Combined Intracavitary/Interstitial Brachytherapy Treatment in Locally Advanced Cervical Cancer

The aims of this study were to investigate the benefit of the Utrecht interstitial CT/MR applicator for combined intracavitary/interstitial (IC/IS) approach, using magnetic resonance imaging-guided brachytherapy, over the intracavitary approach alone in patients with locally advanced cervical cancer and to analyze the clinical use of needles. This study includes the first 20 patients treated with the new applicator. Brachytherapy consisted of two pulsed dose rate applications, and the second application was performed with the IC/IS approach. The number of needles, chosen guiding holes through the ovoids, and insertion depths were based on the dose distribution and dosimetric shortcomings of the first application (IC alone). We investigated the dosimetric gain by comparing the clinical interstitial optimized plan (IC/IS(clinical)) with an additionally generated optimized plan without needle use (IC(study)). Furthermore, we studied the relation of the inserted needles and their source loading patterns with the high-risk clinical target volume (HR-CTV). A total of 54 needles (range, 1-6 per application) were applied with an average depth of 25 mm. The chosen needle positions corresponded with the location of the HR-CTV extensions. The total and individual needle treatment times per application were on average 19% (range, 4-35%) and 7% (range, 2-14%) of the implant treatment time, respectively. The total (external-beam radiotherapy+ brachytherapy) D90 HR-CTV for the IC(study) and the IC/IS(clinical) were on average 79.5 (SD 7.4) Gy(α/β10) and 83.9 (SD 6.7) Gy(α/β10), respectively, with an average gain of 4.4 (SD 2.3) Gy(α/β10) for the second application. Needle placement was feasible in all patients and resulted in a gain in dose and better coverage of HR-CTV. Defining the location of HR-CTV protrusions and analyzing the associated needles has given us deeper understanding of the possibilities in magnetic resonance imaging-guided (pre)treatment planning with the IC/IS Utrecht applicator.

Dose–effect relationship for local control of cervical cancer by magnetic resonance image-guided brachytherapy

Background and purpose To analyse dose–response relationships for local control of cervical cancer after MR image-guided brachytherapy (IGBT) based on dose–volume histogram parameters. Methods and materials The analysis includes 141 patients with cervix cancer (stages IB–IVA) treated with 45–50.4 Gy EBRT ± cisplatin plus 4 × 7 Gy IGBT. Gross tumour volume (GTV), high risk clinical target volume (HR CTV) and intermediate risk CTV (IR CTV) were delineated and DVH parameters (D90, D100) were assessed. Doses were converted to the equivalent dose in 2 Gy (EQD2) using linear-quadratic model ( α/ β = 10 Gy). Groups of patients were formed according to tumour size at diagnosis (GTV D) of 2–5 cm (group 1) or >5 cm (2), with subgroups of the latter for HR CTV size at first IGBT 2–5 cm (2a) or >5 cm (2b). Dose–response dependence for local recurrence was evaluated by logit analysis. Results Eighteen local recurrences in the true pelvis were observed. Dose–response analyses revealed a significant effect of HR CTV D100 ( p = 0.02) and D90 ( p = 0.005). The ED50-values for tumour control were 33 ± 15 Gy (D100) and 45 ± 19 Gy (D90). ED90-values were 67 Gy (95% confidence interval [50;104]) and 86 Gy [77;113], respectively. Conclusions A significant dependence of local control on D100 and D90 for HR CTV was found. Tumour control rates of >90% can be expected at doses >67 Gy and 86 Gy, respectively.

Comparing PSA outcome after radical prostatectomy or magnetic resonance imaging-guided partial prostatic irradiation in select patients with clinically localized adenocarcinoma of the prostate

Objectives To determine whether high-dose radiation delivered to a subvolume of the prostate gland (peripheral zone) using intraoperative magnetic resonance imaging-guided brachytherapy provided comparable 5-year prostate-specific antigen (PSA) control rates to radical prostatectomy (RP) in select patients compared prospectively but in a nonrandomized setting. Methods Between 1997 and 2002, 322 and 196 patients with clinical Stage T1c, PSA less than 10 ng/mL, biopsy Gleason score 3 + 4 or less, and without perineural invasion underwent RP or intraoperative magnetic resonance imaging-guided brachytherapy, respectively, and had a 2-year minimal follow-up. Cox regression multivariable analysis was used to evaluate whether the initial therapy, pretreatment PSA level, biopsy Gleason score, percentage of positive biopsies, or prostate gland volume were predictors of the time to post-therapy PSA failure. PSA failure was estimated using the Kaplan-Meier method and defined using the American Society for Therapeutic Radiology Oncology consensus definition. Results Only the percentage of positive prostate biopsies ( P Cox = 0.02) was a significant predictor of the time to post-treatment PSA failure. However, the distribution of this parameter between RP and brachytherapy-treated patients was not significantly different ( P chi-square = 0.25). The initial therapy did not predict for the time to post-therapy PSA failure ( P Cox = 0.18). The 5-year estimate of PSA control was 93% versus 95% ( P log-rank = 0.16) for the RP and brachytherapy patients, respectively. Conclusions Despite only partial prostatic irradiation using intraoperative magnetic resonance imaging-guided brachytherapy, similar 5-year estimates of PSA control were found for both brachytherapy and RP-managed patients.

Real-time magnetic resonance imaging-guided brachytherapy in the treatment of selected patients with clinically localized prostate cancer.

A real-time three-dimensional magnetic resonance imaging (MRI)-guided implant technique has been designed and implemented. This report summarizes the dosimetry achieved and the acute morbidity in the first patients. To date, 43 patients with clinical stage T(1c)N(X)M(0) prostate cancer, serum prostate specific antigen <10 ng/mL, and biopsy Gleason score no higher than 3 + 4 have been treated. The procedure was performed using an open magnet, with axial T1-weighted and fast spin echo images. The prescribed minimum radiation dose to the peripheral zone was 160 Gy. The total activity implanted ranged from 18.8 to 47.5 mCi using 43 to 120 (median 80) (125)I seeds. Dosimetric analyses were performed intraoperatively in real time for the tumor, anterior rectal wall, and prostatic urethra. The percent of the clinical target volume receiving the prescription dose was 89% to 99% (median 96%). Using a conservative estimate of 164 Gy, no more than 9% of the urethral volume exceeded the tolerated dose. Using an estimated tolerated dose of 82 Gy, 30% to 100% (median 68%) of the anterior rectal wall volume was within the dose limit. Thirty-nine patients voided spontaneously within 3 hours of Foley catheter discontinuation, although four patients required recatheterization for a period. No patient reported gastrointestinal or sexual dysfunction during the first postoperative month. A real-time MR-guided technique can achieve a minimum of 89% coverage of the tumor volume while maintaining the prostatic urethra and most of the anterior rectal wall below tolerance levels. Acute morbidity was minimal. Further follow-up is needed to ascertain the impact on cancer control and quality of life.