A comparative dosimetric analysis of virtual stereotactic body radiotherapy to high-dose-rate monotherapy for intermediate-risk prostate cancer

PurposeStereotactic body radiotherapy (SBRT) is being used with increasing frequency as definitive treatment of early stage prostate cancer. Much of the justification for its adoption was derived from earlier clinical results using high-dose-rate (HDR) brachytherapy. We determine whether HDR's dosimetry can be achieved by virtual SBRT.Methods and MaterialsPatients with intermediate-risk prostate cancer on a prospective trial evaluating the efficacy of HDR monotherapy treated to dose of 9.5 Gy × 4 fractions were used for this study. A total of 5 patients were used in this analysis. Virtual SBRT plans were developed to reproduce the planning target volume (PTV) HDR dose distributions. Both normal tissue– and PTV-prioritized plans were generated.ResultsFrom the normal tissue–prioritized plan, HDR and virtual SBRT achieved similar PTV V₁₀₀ (93.8% vs. 93.1%, p = 0.20) and V₁₅₀ (40.3% vs. 42.9%, p = 0.69) coverage. However, the PTV V₂₀₀ was not attainable with SBRT (15.2% vs. 0.0%, p < 0.001). The rectal D_max was significantly lower with HDR (94.2% vs. 99.42%, p = 0.05). The rectal D_{2 cc} was also lower (60.8% vs. 71.1%, p = 0.07). Difference in D_{1 cc} urethral dose was not significantly different (87.7% vs. 75.2%, p = 0.33). Comparing the PTV-prioritized plans, the rectal D_max (94.2% vs. 111.1%, p = 0.05) and mean dose (27.1% vs. 33.3%, p = 0.03) were significantly higher using SBRT, and the rectal D_{2 cc} was higher using SBRT (60.8% vs. 81.8%, p = 0.07).ConclusionsHDR achieves significantly higher intraprostatic doses while achieving a lower maximum rectal dose compared with our virtual SBRT treatment planning. Future studies should compare clinical outcomes and toxicity between these modalities.     

Interstitial brachytherapy vs. intensity-modulated radiation therapy for patients with cervical carcinoma not suitable for intracavitary radiation therapy

PurposeInterstitial brachytherapy (IBT) is the standard alternative treatment for patients with cervical carcinoma not suitable for intracavitary radiotherapy. There is an emerging belief that intensity-modulated radiotherapy (IMRT) has the potential to replace IBT. We aimed to compare the dosimetry achieved by IBT and IMRT in such patients.Methods and MaterialsThe CT imaging data, previously used for IBT planning of 12 patients with cervical carcinoma, were transferred to IMRT planning system to generate parallel IMRT plans. Prescribed dose to the planning target volume (PTV) was 20 Gy delivered in 2-weekly high-dose-rate fractions of 10 Gy each with IBT (biologically equivalent dose [BED₁₀] 40 Gy) and 33 Gy/13 fractions/2.5 wk with IMRT (BED₁₀ 41 Gy). For comparison, dose–volume parameters for target and organs at risk were recorded and expressed in terms of BED₁₀ and BED₃, respectively.ResultsFor PTV, the mean D₉₅ (dose received by 95% of PTV) was better with IBT (57.16 Gy vs. 41.47 Gy, p = 0.003). The mean conformity index was 0.94 and 0.90 with IBT and IMRT, respectively (p = 0.034). IBT delivered significantly reduced doses to 1.0 cc (D_max), 5.0 cc (D_{5 cc}), 50% (D₅₀), and 75% (D₇₅) of bladder volume as compared with IMRT. The mean rectal D_max was significantly better with IBT as compared with IMRT (54.64 Gy vs. 62.63 Gy, p = 0.02).ConclusionsIBT provides superior PTV coverage and organs at risk sparing to IMRT. Thus, IBT remains the standard treatment for patients with cervical carcinoma unsuitable for intracavitary radiotherapy.     

Endorectal magnetic resonance imaging for predicting pathologic T3 disease in Gleason score 7 prostate cancer: Implications for prostate brachytherapy

PurposeTo determine the ability of endorectal magnetic resonance imaging (erMRI) and other pretreatment factors to predict the presence and extent of extraprostatic extension (EPE) in men with Gleason score (GS) 7 prostate cancer.Methods and MaterialsWe included patients with clinical stage T1c–T2c, GS = 7 (3 + 4 or 4 + 3), and prostate-specific antigen (PSA) <10 ng/mL who underwent pre-prostatectomy erMRI. We compared pathologic EPE findings with pretreatment factors.ResultsOne hundred seventy-one men were eligible for inclusion. Pretreatment characteristics were: median age = 60 years (42–76); median PSA 4.9 ng/mL (0.4–9.9); GS 3 + 4 = 61%; T1c = 51%; T2a = 25%; T2b = 21%; T2c = 3%; ≥50% positive cores = 46%; EPE-positive (EPE+) erMRI = 28%. Thirty-three percent had pathologic EPE. Increasing T-stage (p < 0.0001) and EPE+ erMRI (p < 0.0001) were significant predictors of pathologic EPE, whereas GS (4 + 3 vs. 3 + 4) (p = 0.14), percentage of positive core biopsies (p = 0.15), and pretreatment PSA (p = 0.41) were not. Median EPE distance was 1.75 mm (range, <1–15 mm). The rates of EPE >5 mm and EPE >3 mm were 11% and 15%, respectively. The odds ratios for erMRI detection of any EPE and of EPE >5 mm were 3.06 and 3.75, respectively.ConclusionsT-stage and EPE+ erMRI predict pathologic EPE in men with GS 7 prostate cancer. The ability of erMRI to detect EPE increases with increasing EPE distance. These findings may be useful in patient selection for prostate brachytherapy monotherapy.     

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PurposeTo determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy.Methods and MaterialsBetween October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5 Gy within 48 h for a total prescribed dose (PD) of 38 Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4–4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria.ResultsAcute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V₁₀₀ (% PTV receiving ≥100% of the PD; p = 0.036), D₉₀ (dose delivered to 90% of the PTV; p = 0.02), and the urethral V₁₂₀ (urethral volume receiving ≥120% of the PD; p = 0.043). The urethral V₁₂₀ was associated with increased PTV V₁₀₀ (p < 0.001) and D₉₀ (p = 0.003).ConclusionsAfter HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V₁₂₀ and the V₁₀₀ and D₉₀ of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.     

Improving prostate brachytherapy quality assurance with MRI–CT fusion–based sector analysis in a phase II prospective trial of men with intermediate-risk prostate cancer

PurposeWe combined sector analysis with MRI–CT fusion to comprehensively assess postimplant dosimetry after prostate brachytherapy.Methods and MaterialsSubjects were 50 men with intermediate-risk prostate cancer treated with ¹²⁵I brachytherapy in a prospective phase II clinical trial. On Day 30 after the implantation, dosimetry was evaluated in the prostate base, midgland, and apex regions on fused MRI–CT scans and CT scans. Volumes of each sector receiving 100% of the prescribed dose (V₁₀₀) and doses to 90% of each sector (D₉₀) were also calculated on the ultrasonogram used for treatment planning and compared with values derived from CT and fused MRI–CT scans.ResultsFused MRI–CT scans revealed lower-than-expected doses for the whole prostate (V₁₀₀ = 91.3%, D₉₀ = 152.9 Gy) compared with CT scans (98.5% and 183.6 Gy, p < 0.0001) and lower doses to the prostate base (V₁₀₀ = 79%, D₉₀ = 130 Gy) vs. CT (96% and 170 Gy, p < 0.0001). However, lower doses to the prostate base did not adversely affect biochemical outcomes in men with biopsy-proven disease at the base. At a median followup time of 42 months, the mean prostate-specific antigen level for all patients was 0.3 ng/mL, and no patient had experienced biochemical or clinical progression or recurrence.ConclusionsMRI–CT fusion–based sector analysis was feasible and revealed significantly lower doses to the prostate base than doses estimated from CT alone, although this did not affect biochemical outcomes. MRI–CT fusion–based sector analysis may be useful for developing MRI-based dosimetric markers to predict disease outcomes and treatment-related morbidity.     

Prostate cancer diagnosis: Efficacy of a simple electromagnetic MRI-TRUS fusion method to target biopsies

ObjectiveTo assess that transrectal ultrasound guidance (TRUS) targeted biopsies (TB) aimed with an easy to use electronic real-time fusion registration device have a higher rate of prostate cancer (PC) detection than standard biopsies (SB).Material and methodsThis prospective study included 130 patients referred for TRUS biopsies after suspicious MRI. They underwent 16-core SB and 2 to 3 cores in each MRI suspicious area, using a fusion software. We noted SB and TB positivity for PC and Gleason score (GS). We used the McNemar test to compare SB and TB, with a statistical significance p < 0.05.ResultsAmong 130 patients, 68.5% had PC. Additional time due to the fusion registration was 3.3 min. One hundred fifteen patients (88.4%) had pathological findings on the histological analysis (prostate cancer n = 89, others n = 26). TB diagnosed PC in 75 patients with negative SB. Positivity rate for PC was significantly higher for TB than SB (p = 0.03). Among highly suspicious MRI lesions, detection rate of histological abnormalities using SB and TB was 96% with 79.7% of PC. Most PC that TB diagnosed alone were clinically significant (86.3%).ConclusionTRUS biopsies performed with a simple MRI and US electronic fusion is an unrestrainedly method to increase PC diagnosis.     

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.     

Circumferential or sectored beam arrangements for stereotactic body radiation therapy (SBRT) of primary lung tumors: Effect on target and normal-structure dose-volume metrics

To compare 2 beam arrangements, sectored (beam entry over ipsilateral hemithorax) vs circumferential (beam entry over both ipsilateral and contralateral lungs), for static-gantry intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques with respect to target and organs-at-risk (OAR) dose-volume metrics, as well as treatment delivery efficiency. Data from 60 consecutive patients treated using stereotactic body radiation therapy (SBRT) for primary non–small-cell lung cancer (NSCLC) formed the basis of this study. Four treatment plans were generated per data set: IMRT/VMAT plans using sectored (-s) and circumferential (-c) configurations. The prescribed dose (PD) was 60 Gy in 5 fractions to 95% of the planning target volume (PTV) (maximum PTV dose ~ 150% PD) for a 6-MV photon beam. Plan conformality, R₅₀ (ratio of volume circumscribed by the 50% isodose line and the PTV), and D_2 cm (D_max at a distance ≥2 cm beyond the PTV) were evaluated. For lungs, mean doses (mean lung dose [MLD]) and percent V₃₀/V₂₀/V₁₀/V₅ Gy were assessed. Spinal cord and esophagus D_max and D₅/D₅₀ were computed. Chest wall (CW) D_max and absolute V₃₀/V₂₀/V₁₀/V_5 Gy were reported. Sectored SBRT planning resulted in significant decrease in contralateral MLD and V₁₀/V_5 Gy, as well as contralateral CW D_max and V₁₀/V_5 Gy (all p < 0.001). Nominal reductions of D_max and D₅/D₅₀ for the spinal cord with sectored planning did not reach statistical significance for static-gantry IMRT, although VMAT metrics did show a statistically significant decrease (all p < 0.001). The respective measures for esophageal doses were significantly lower with sectored planning (p < 0.001). Despite comparable dose conformality, irrespective of planning configuration, R₅₀ significantly improved with IMRT-s/VMAT-c (p < 0.001/p = 0.008), whereas D_2 cm significantly improved with VMAT-c (p < 0.001). Plan delivery efficiency improved with sectored technique (p < 0.001); mean monitor unit (MU)/cGy of PD decreased from 5.8 ± 1.9 vs 5.3 ± 1.7 (IMRT) and 2.7 ± 0.4 vs 2.4 ± 0.3 (VMAT). The sectored configuration achieves unambiguous dosimetric advantages over circumferential arrangement in terms of esophageal, contralateral CW, and contralateral lung sparing, in addition to being more efficient at delivery.     

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent

PurposeTo validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)–based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer.MethodsEight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose–volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program.ResultsThe ASA plans are higher on bladder V_75% and D_2cc (p = 0.034) and lower on rectum V_75% and D_2cc (p = 0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p = 0.034), lower overdose index (p = 0.005), and lower rectum gEUD and normal tissue complication probability (p = 0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose–volume histogram could have different dose distributions.ConclusionsOur optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA.     

Multi-parametric MRI-guided focal tumor boost using HDR prostate brachytherapy: A feasibility study

PurposeThis study investigates the feasibility of delivering focal boost dose to tumor regions, identified with multi-parametric MRI, in high-dose-rate prostate brachytherapy.Methods and MaterialsT2-weighted, diffusion-weighted, and dynamic-contrast-enhanced MRI were acquired the day before treatment and analyzed retrospectively for 15 patients. Twelve patients had hormone therapy before the MRI scan. The tumor was delineated on MRI by a radiologist and registered to treatment planning transrectal ultrasound images. A margin based on analysis of delineation and registration uncertainties was applied to create a focal boost planning target volume (F-PTV). Delivered treatment plans were compared with focal boost plans optimized to increase F-PTV dose as much as allowed by urethral and rectal dose constraints.ResultsTumors were delineated in all patients with volumes 0.4–23.0 cc. The margin for tumor delineation and image registration uncertainties was estimated to be 4.5 mm. For F-PTV, the focal boost treatment plans increased median D₉₀ from 17.6 to 20.9 Gy and median V₁₅₀ from 27.3% to 75.9%.ConclusionsMRI-guided high-dose-rate prostate brachytherapy focal tumor boost is feasible—tumor regions can be identified even after hormone therapy, and focal boost dose can be delivered without violating urethral and rectal dose constraints.     

Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer

Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V₂₀, V₃₀, or V₄₀) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within < 2.5 cm of the CW. We found 260 cases; of these, chronic grade ≥ 2 CW pain was identified in 23 patients. We then selected 10 representative patients from this group and generated proton SBRT treatment plans, using the identical dose of 50 Gy in 4 fractions, and assessed potential differences in CW dose between the 2 plans. The proton SBRT plans reduced the CW doses at all dose levels measured. The median CW V₂₀ was 364.0 cm³ and 160.0 cm³ (p < 0.0001), V₃₀ was 144.6 cm³ vs 77.0 cm³ (p = 0.0012), V₃₅ was 93.9 cm³ vs 57.9 cm³ (p = 0.005), V₄₀ was 66.5 cm³ vs 45.4 cm³ (p = 0.0112), and mean lung dose was 5.9 Gy vs 3.8 Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures.     

Large prostate gland size is not a contraindication to low-dose-rate brachytherapy for prostate adenocarcinoma

PurposeProstate volume greater than 50 cc is traditionally a relative contraindication to prostate seed implantation (PSI), but there is little consensus regarding prostate size and clinical outcomes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size.Methods and MaterialsA total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by prostate volume into small, medium, and large subgroups. Differences were analyzed using the Mann–Whitney and Pearson's χ² tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes.ResultsPatient pretreatment factors were balanced between groups except for age (p = 0.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p = 0.47). In a multivariate analysis, plan type (hazard ratio [HR] = 0.25, p = 0.03), dose to 90% of the gland (D₉₀: HR = 0.98, p = 0.02), volume receiving 200 Gy (V₂₀₀: HR = 0.98, p = 0.026), and biologic effective dose (HR = 0.99, p = 0.045), but not prostate size (HR = 2.27, p = 0.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score.ConclusionIn men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size.