Jan J. Battermann

ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer

INTRODUCTION The last few years has seen an enormous increase in interest in the role of new transrectal ultrasound and template guided techniques for brachytherapy in localised prostate cancer. In the USA there has been a dramatic rise in the number of implants performed in the last five years. A similar rapid expansion is expected in Europe and this guidance is intended to indicate to those embarking on brachytherapy the factors which may be related to successful outcomes.

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.

Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy

Induction chemotherapy of non-small-cell lung cancer (NSCLC) stage III with gemcitabine and cisplatin for downstaging of the tumour with the aim for further treatment with ionising radiation is one of the treatments for lung cancer patients. The purpose of this study was to investigate the influence of the waiting time for radiotherapy, that is, the interval between induction chemotherapy and radiotherapy, on the rate of tumour growth for patients with NSCLC. Interval times between the end of induction chemotherapy and date of diagnostic CT, planning CT and first day of radiotherapy were determined for 23 patients with NSCLC. Increase in gross tumour volume was measured for 18 patients by measuring the dimensions of the primary tumour and lymph node metastases on the diagnostic CT after induction chemotherapy and on the CT used for radiotherapy planning. For each patient, the volume doubling time was calculated from the time interval between the two CTs and ratio of the gross volumes on planning CT and diagnostic CT. The mean time interval between end of chemotherapy and day of diagnostic CT was 16 days, and till first day of radiotherapy 80.3 (range 29 – 141) days. In all, 41% of potentially curable patients became incurable in the waiting period. The ratio of gross tumour volumes of the two CTs ranged from 1.1 to 81.8 and the tumour doubling times ranged from 8.3 to 171 days, with a mean value of 46 days and median value of 29 days. This is far less than the mean doubling time of NSCLC in untreated patients found in the literature. This study shows that in the time interval between the end of induction chemotherapy and the start of radiotherapy rapid tumour progression occurs as a result of accelerated tumour cell proliferation: mean tumour doubling times are much shorter than those in not treated tumours. As a consequence, the gain obtained with induction chemotherapy with regard to volume reduction was lost in the waiting time for radiotherapy. We recommend diminishing the time interval between chemo- and radiotherapy to as short as possible.

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.

Radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate cancer: preliminary results

To report an interim clinical evaluation of combined external beam irradiation (EBRT) and interstitial or regional hyperthermia in the treatment of locally advanced prostate cancer.

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.

Prostate Brachytherapy and Second Primary Cancer Risk: A Competitive Risk Analysis

PURPOSE To assess the risk of second primary cancer (SPC) after [(125)I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population. PATIENTS AND METHODS In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison. RESULTS A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18). CONCLUSION Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.

Decline of dose coverage between intraoperative planning and post implant dosimetry for I-125 permanent prostate brachytherapy: Comparison between loose and stranded seed implants

BACKGROUND AND PURPOSE In permanent prostate brachytherapy the dose distributions 4 weeks post implant differ from the intraoperative dose distributions. The purpose of this study is to compare intraoperative planning and post implant dosimetry for loose and stranded seed implants. MATERIALS AND METHODS This study investigates prostate dose coverage in 389 patients with stage T1 or T2 prostate cancer treated in the years 2005, 2006 and 2007. The patients received either a loose seed or a stranded seed implant. All patients had US-based intraoperative planning and CT/MRI-based post implant dosimetry after 4 weeks. RESULTS Intraoperative and post implant D(90) values amounted 183+/-13 Gy (mean+/-standard deviation) and 161+/-30 Gy, respectively. Decline of D(90) values (mean and 95% confidence interval) between intraoperative planning and post implant dosimetry for RAPID strand (n=67), Intersource strand (n=136) and loose selectSeeds (n=186) implants amounted to -40 (-45 to -34) Gy, -25 (-28 to -21) Gy and -15 (-18 to -21) Gy, respectively. CONCLUSIONS The patients treated in the period 2005-2007 with stranded or loose seed implants had on average adequate D(90) values of 161+/-30 Gy. Post implant D(90) values were 22+/-27 Gy lower compared to intraoperative planning. Decline of dose coverage between intraoperative planning and post implant dosimetry was significantly larger for the stranded seed implants.