Marinus A. Moerland

A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: Application to the prostate

PURPOSE This article presents a method of quantitative assessment of the degree of conformality and its designation by a single numerical value. METHODS AND MATERIALS A conformation number is introduced to evaluate objectively the degree of conformality. A comparison is made between the conformation number as found for external beam treatment plans and ultrasonically guided 125I seed implants for localized prostate cancer. RESULTS The conformation number in case of a planning target volume irradiated with two opposed open beams, three open beams, and three beams with customized blocks amounted to 0.17, 0.39, and 0.65, respectively. The conformation number as found for ultrasonically guided permanent prostate implants using 125I seeds averaged 0.72. CONCLUSIONS The conformation number is a convenient instrument for indicating the degree of conformality by a single numerical value. Treatments with a conformation number greater than 0.60 might be termed conformal radiotherapy.

Qantitative dose-volume response analysis of changes in parotid gland function after radiotheraphy in the head-and-neck region

Abstract Purpose: To study the radiation tolerance of the parotid glands as a function of dose and volume irradiated. Methods and Materials: One hundred eight patients treated with primary or postoperative radiotherapy for various malignancies in the head-and-neck region were prospectively evaluated. Stimulated parotid flow rate was measured before radiotherapy and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from CT-based treatment planning. The normal tissue complication probability model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow rate Results: The mean stimulated preradiotherapy flow rate of 174 parotid glands was 0.34 mL/min. The mean flow rate reduced to 0.12 mL/min 6 weeks postradiotherapy, but recovered to a mean flow rate of 0.20 mL/min at 1 year after radiotherapy. Reduction in postradiotherapy flow rate correlated significantly with mean parotid dose. No threshold dose was found. Increasing the irradiated volume of parotid glands from 0%–40% to 90–100% in patients with a mean parotid dose of 35–45 Gy resulted in a decrease in flow ratio from, respectively, approximately 100% to less than 10% 6 weeks after radiation. The flow ratio of the 90%–100% group partially recovered to 15% at 6 months and to 30% at 1 year after radiotherapy. The normal tissue complication probability model parameter TD 50 (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35, and 39 Gy at 6 weeks, 6 months, and 1 year postradiotherapy, respectively. The volume dependency parameter n was around 1, which means that the mean parotid dose correlates best with the observed complications. There was no steep dose-response curve ( m = 0.45 at 1 year postradiotherapy). Conclusions: This study on dose/volume/parotid gland function relationships revealed a linear correlation between postradiotherapy flow ratio and parotid gland dose and a strong volume dependency. No threshold dose was found. Recovery of parotid gland function was shown at 6 months and 1 year after radiotherapy. In radiation planning, attempts should be made to achieve a mean parotid gland dose at least below 39 Gy (leading to a complication probability of 50%).

Evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging

PURPOSE The aim of this study is the evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging (MRI). METHODS AND MATERIALS Twenty-one patients underwent radiography on the simulator and MRI within 3 days after implantation of the I-125 seeds. Isocentric radiographs were used for reconstruction of the seed distribution, after which registration with the seed-induced signal voids on MRI provided the seed positions in relation to the prostate. The prostate was contoured on the transversal magnetic resonance images, and dose-volume histograms were computed to evaluate the implants. The validity of the ellipsoidal prostate volume approximation, as applied in preimplant dose calculation, was assessed by comparison of ellipsoidal volumes given by prostate width, height, and length and prostate volumes obtained by a slice-by-slice contouring method, both on postimplant MRI. Prostate volume changes due to postimplant prostate swelling were assessed from radiographs taken at 3 days and 1 month after the implantation. RESULTS The seeds were readily identified on T1-weighted spin-echo images and matched with the seed distribution reconstructed from the isocentric radiographs. The matching error, averaged over 21 patients, amounted to 1.8 +/- 0.4 mm (mean +/- standard deviation). The fractions of the prostate volumes receiving the prescribed matched peripheral dose (MPD) ranged from 32 to 71% (mean +/- standard deviation: 60 +/- 10%). Prostate volumes, obtained by the contouring method on postimplant MRI, were a factor 1.5 +/- 0.3 larger than the ellipsoidal volumes given by the prostate dimensions on postimplant MRI. Prostate volumes 3 days after the implantation were a factor 1.3 +/- 0.2 larger than the prostate volumes 1 month after the implantation. Registration of the reconstructed seed distribution and the MR images showed inaccuracies in seed placement, for example, two or more seeds clustering together or seeds outside the prostate. CONCLUSIONS Registration of the reconstructed seed distribution and the MR images enabled evaluation of target coverage, which amounted to 60 +/- 10%. The discrepancy between prescribed dose and realized dose was caused by underestimation of the preimplant prostate volume due to the ellipsoidal approximation, postimplant prostate swelling at the time of evaluation, and inaccuracies in seed placement.

Long-term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy.

PURPOSE To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT). METHODS AND MATERIALS Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for <or=T2c Nx/0 Mx/0 prostate cancer were evaluated. All patients were treated with I-125 seeds (prescription dose 144 Gy). Eighty-five patients with a gland volume >or=50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4-186 months); mean age was 67 years. RESULTS Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival. CONCLUSIONS These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.

Parotid Gland Function after Radiotherapy: The Combined Michigan and Utrecht Experience

PURPOSE To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. PATIENTS AND METHODS A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. RESULTS A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD(50) (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. CONCLUSIONS A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD(50) was equal to 40 Gy.

Clinical outcome and dosimetric parameters of chemo-radiation including MRI guided adaptive brachytherapy with tandem-ovoid applicators for cervical cancer patients: A single institution experience

PURPOSE To evaluate dosimetric parameters and clinical outcome for cervical cancer patients treated with chemo-radiation and MR-image guided adaptive brachytherapy (MR-IGABT) using tandem-ovoid applicators for intracavitary or combined intracavitary/interstitial approaches. METHOD This retrospective analysis includes 46 patients treated between 2006 and 2008. Dose-volume parameters D90 HR-CTV (high-risk clinical target volume) and D(2cc) OARs (organs at risk) were determined and converted into biologically equivalent doses in 2 Gy fractions (EQD2). Clinical outcome parameters (local control (LC), progression free survival (PFS) and overall survival (OS)) were analysed actuarially and late morbidity crude rates were scored using CTCAEv3.0. RESULTS Mean D90 HR-CTV was 84 (SD9) Gy EQD2 for HR-CTV volumes of mean 57 (SD37) cm(3) at time of first brachytherapy (BT). Median follow-up was 41 (range, 4-67) months. Three year LC, PFS, and OS rates were 93, 71, and 65%, respectively. Node negative patients had significantly higher 3-year survival rates compared to node positive ones (PFS 85 versus 53% (p=0.013), OS 77 versus 50% (p=0.032), respectively) with an even larger difference for patients with FIGO stages IB-IIB (PFS 87 versus 42% (p=0.002), OS 83 versus 46% (p=0.007), respectively). Late grade 3-4 mainly gastrointestinal or vaginal morbidity was observed in 4 patients (9.5%). No correlations were seen between morbidity and D(2cc) OAR values. CONCLUSION (Chemo-) radiation and MR-IGABT with tandem-ovoid applicators result in high LC and promising survival rates with reasonable morbidity.

MRI-guided robotic system for transperineal prostate interventions: proof of principle

In this study, we demonstrate the proof of principle of the University Medical Center Utrecht (UMCU) robot dedicated to magnetic resonance imaging (MRI)-guided interventions in patients. The UMCU robot consists of polymers and non-ferromagnetic materials. For transperineal prostate interventions, it can be placed between the patients legs inside a closed bore 1.5T MR scanner. The robot can manually be translated and rotated resulting in five degrees of freedom. It contains a pneumatically driven tapping device to automatically insert a needle stepwise into the prostate using a controller unit outside the scanning room. To define the target positions and to verify the needle insertion point and the needle trajectory, a high-resolution 3D balanced steady state free precession (bSSFP) scan that provides a T2/T1-weighted contrast is acquired. During the needle insertion fast 2D bSSFP images are generated to track the needle on-line. When the target position is reached, the radiation oncologist manually places a fiducial gold marker (small seed) at this location. In total two needle trajectories are used to place all markers. Afterwards, a high-resolution 3D bSSFP scan is acquired to visualize the fiducial gold markers. Four fiducial gold markers were placed transperineally into the prostate of a patient with a clinical stage T3 prostate cancer. In the generated scans, it was possible to discriminate the patients anatomy, the needle and the markers. All markers were delivered inside the prostate. The procedure time was 1.5 h. This study proves that MRI-guided needle placement and seed delivery in the prostate with the UMCU robot are feasible.

MRI-guided treatment-planning optimisation in intracavitary or combined intracavitary/interstitial PDR brachytherapy using tandem ovoid applicators in locally advanced cervical cancer

PURPOSE To study the impact of MRI-guided treatment planning on dose/volume parameters in pulsed dose rate (PDR) brachytherapy (BT) for cervical cancer. Additionally, we investigated the potential benefit of an intracavitary/interstitial (IC/IS) modification of the classical tandem ovoid applicator. MATERIAL AND METHODS For 24 patients we compared Standard PDR BT plans, Scaled Standard plans and MRI-guided Optimised plans. The total EBRT/BT prescribed dose to Manchester point A or to 90% of the HR-CTV (D90 HR-CTV) expressed in EQD(2) was 80 Gy(alphabeta10) in 17 patients (Period I) and 84 Gy(alphabeta10) in 7 patients (Period II). The constraints to 2 cm(3) of the OAR were 90 Gy(alphabeta3) for bladder and 75 Gy(alphabeta3) for rectum, sigmoid and bowel. Most cases were treated with a traditional intracavitary tandem ovoid applicator. In 6 patients we used a newly designed combined IC/IS modification for the second PDR fraction and investigated the benefit of the interstitial part. RESULTS The average gain of MRI-guided optimisation expressed in D90 HR-CTV was 4+/-9 Gy(alphabeta10) (p<0.001) and 10+/-7 Gy(alphabeta10) (p=0.003) in the two periods. The dose to 2 cm(3) of the OAR met the constraints. In the group that was treated with the combined IC/IS approach, we could increase the D90 HR-CTV for the second PDR fraction with 5.4+/-4.2 Gy(alphabeta10) (p=0.005) and the D100 with 4.8+/-3.1 Gy(alphabeta10) (p=0.07). CONCLUSIONS Three-dimensional MRI-guided treatment planning and optimisation improves the DVH parameters compared to conventional planning strategies. Additional improvement can be achieved by using a combined IC/IS approach.

Analysis and correction of geometric distortions in 1.5 T magnetic resonance images for use in radiotherapy treatment planning

The aim of this study is to investigate and correct for machine- and object-related distortions in magnetic resonance images for use in radiotherapy treatment planning. Patients with brain tumours underwent magnetic resonance imaging (MRI) in the radiotherapy position with the head fixed by a plastic cast in a Perspex localization frame. The imaging experiments were performed on a 1.5 T whole body MRI scanner with 3 mT m-1 maximum gradient capability. Image distortions, caused by static magnetic field inhomogeneity, were studied by varying the direction of the read-out gradient. For purposes of accuracy assessment, external and internal landmarks were indicated. Tubes attached to the cast and in the localization frame served as external landmarks. In the midsagittal plane the brain-sinus sphenoidalis interface, the pituitary gland-sinus sphenoidalis interface, the sphenoid bone and the corpora of the cervical vertebra served as internal landmarks. Landmark displacements as observed in the reversed read-out gradient experiments were analysed with respect to the contributions of machine-related static magnetic field inhomogeneity and susceptibility and chemical shift artifacts. The machine-related static magnetic field inhomogeneity in the midsagittal plane was determined from measurements on a grid phantom. Distortions due to chemical shift effects were estimated for bone marrow containing structures such as the sphenoid bone and the corpora of the cervical vertebra using the values obtained from the literature. Susceptibility-induced magnetic field perturbations are caused by the patient and the localization frame. Magnetic field perturbations were calculated for a typical patient dataset.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal Salvage Guided by T2-Weighted and Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Prostate Cancer Recurrences

PURPOSE Salvage treatment of the entire prostate for local recurrent cancer after primary radiotherapy is associated with high toxicity rates. Our goal was to show that, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the visualization of a recurrence, focal salvage treatment can be performed, with, potentially, a reduction in toxicity. METHODS AND MATERIALS We performed MRI, including a DCE sequence, in 7 patients with biopsy-proven locally recurrent prostate cancer. The specific regions of interest suspect for containing tumor were delineated using DCE and T(2)-weighted MRI scans. Subsequently, focal salvage high-dose-rate brachytherapy plans were created to illustrate the principle of focal salvage. Total salvage treatment plans were also created for comparison. RESULTS The transfer constant (K(trans)) values from the DCE were 0.33-0.67 min(-1) for areas suspect for tumor and 0.07-0.25 min(-1) for normal tissue. In 4 cases, a focal salvage plan could be generated; 93-100% of the gross tumor volume was covered with the prescribed dose, with relative sparing of the bladder, rectum, and urethra. In the total salvage plans, 24-53% of the gross tumor volume was covered, and the organs at risk received high doses. In 3 cases, a focal salvage plan could not be created because of multifocal tumor, seminal vesicle extension, or capsular extension. CONCLUSION Focal salvage treatment plans can be created in patients with local recurrent prostate cancer after radiotherapy. DCE-MRI supports the localization of the target area. This could lead to less toxicity in patients with local recurrent prostate cancer.