Whole-pelvic irradiation with boost to involved nodes and prostate in node-positive prostate cancer-long-term data from the prospective PLATIN-2 trial.

PURPOSE: Node-positive prostate cancer is a potentially curable disease. Definitive radiotherapy to the prostate and lymphatic drainage is an effective treatment option but prospective long-term outcome data are scarce. Thus, the current study aimed to evaluate the toxicity and efficacy of definitive radiation therapy for men with prostate cancer and nodal metastases using modern irradiation techniques. METHODS: A total of 40 treatment-naïve men with node-positive prostate cancer were allocated to the trial. All patients received definitive radiation therapy at two German university hospitals between 2009 and 2018. Radiation was delivered as intensity-modulated radiation therapy (IMRT) with 51 Gy to the lymphatic drainage with simultaneous integrated boost (SIB) up to 61.2 Gy to involved nodes and 76.5 Gy to the prostate in 34 fractions. Feasibility and safety, overall and progression-free survival, toxicity, and quality of life measurements were analyzed. RESULTS: During a median follow-up of 79 months, median overall survival was 107 months and progression-free survival was 78 months. Based on imaging follow-up, no infield relapse was reported during the first 24 months of follow-up. There were 3 (8%) potentially treatment-related grade 3 toxicities. Common iliac node involvement was associated with a higher risk of progression (HR 15.8; 95% CI 2.1-119.8; p = 0.007). CONCLUSION: Definitive radiation to the lymphatic drainage with SIB to the involved nodes and prostate is a safe and effective treatment approach for patients with treatment-naïve, node-positive prostate cancer with excellent infield tumor control rates and tolerable toxicity. Location rather than number of involved nodes is a major risk factor for progression.

Primary immunosuppressive TNI-based conditioning regimens in pediatric patients treated with haploidentical hematopoietic cell transplantation.

PURPOSE: This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. MATERIALS AND METHODS: Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors. RESULTS: Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8-138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5-138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure (< 10th percentile) occurred in 2/5 patients (height) and 1/5 patient (weight). No secondary malignancies were reported. CONCLUSION: In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Precision of T2 TSE MRI-CT-image fusions based on gold fiducials and repetitive T2 TSE MRI-MRI-fusions for adaptive IGRT of prostate cancer by using phantom and patient data.

INTRODUCTION: To increase precision of radiation treatment (RT) delivery in prostate cancer, MRI-based RT as well as the use of fiducials like gold markers (GMs) have shown promising results. Their combined use is currently under investigation in clinical trials. Here, we aimed to evaluate a workflow of image registration based on GMs between CT and MRI as well as weekly MRI-MRI adaption based on T2 TSE sequence. MATERIAL AND METHODS: A gel-phantom with two inserted GMs was scanned with CT and three different MR-scanners of 1.5 and 3 T (T2 TSE and T1 VIBE-Dixon, isotropic, voxel size 2 × 2 × 2 mm). After image fusion, deviations for fiducial and gel match were measured and artifacts were evaluated. Additionally, CT-MRI-match deviations and MRI-MRI-match deviations of 10 Patients from the M-basePro study using GMs were assessed. RESULTS: GMs were visible in all imaging modalities. The outer gel contours were matched with <1 mm deviation, contour volumes varied between 0 and 1%. The deviations of the GMs were less than 2 mm in any direction of MRI/CT. Shifts of peripherally or centrally located GMs were randomly distributed. The average MRI-CT-match precision of 10 patients with GMs was 1.9 mm (range 1.1-3.1 mm). CONCLUSIONS: Match inaccuracies for GMs between reference CT and voxel-isotropic T2-TSE sequences are small. Spatial deviations of CT- and MR-contoured fiducials were less than 2 mm, i.e., below SLT of the applied modalities. In patients, the average CT-MRI-match precision for GMs was 1.9 mm supporting their use in MR-guided high precision RT.

p-Medicine: From data sharing and integration via VPH models to personalized medicine.

The Worldwide innovative Networking in personalized cancer medicine (WIN) initiated by the Institute Gustave Roussy (France) and The University of Texas MD Anderson Cancer Center (USA) has dedicated its 3rd symposium (Paris, 6-8 July 2011) to discussion on gateways to increase the efficacy of cancer diagnostics and therapeutics (http://www.winconsortium.org/symposium.html).Speakers ranged from clinical oncologist to researchers, industrial partners, and tools developers; a famous patient was present: Janelle Hail, a 30-year breast cancer survivor, founder and CEO of the National Breast Cancer Foundation, Inc. (NBCF).The p-medicine consortium found this venue a perfect occasion to present a poster about its activities that are in accordance with the take home message of the symposium.In this communication, we summarize what we presented with particular attention to the interaction between the symposium's topic and content and our project.

The influence of guiding equipment and stents on the beta dose distribution in the brachytherapy of in-stent restenosis.

BACKGROUND: Intracoronary devices such as stents or guide wires may disturb the dose distribution of beta sources in cardiovascular brachytherapy. As clinical observations indicate that underdosage increases the risk of restenosis, accurate measurements are mandatory to investigate these effects. METHODS AND RESULTS: Dose perturbation effects of different interventional equipment were systematically determined. Dose distributions of 90Sr-beta line sources were measured by means of a special set-up employing plastic scintillator dosimeters in a water phantom. Shielding effects were found to be 2-5% for single stents and 5-10% for graft stents, stent-in-stent geometries, and guiding catheters. Guide wires close to the source reduced the dose by 25-30%. CONCLUSIONS: Beta dose perturbation effects of typical stent types are almost negligible and can be corrected by an increased source dwell time if necessary. Guide wires produce effects which are clinically much more important and should therefore be retracted from the irradiation area.

A high-precision, high-resolution and fast dosimetry system for beta sources applied in cardiovascular brachytherapy.

A fast dosimetry system based on plastic scintillator detectors has been developed which allows three-dimensional measurement of the radiation field in water of beta-sources appropriate for application in cardiovascular brachytherapy. This system fulfills the AAPM Task Group 60 recommendations for dosimetry of cardiovascular brachytherapy sources. To demonstrate the use of the system, measurements have been performed with an 90Y-wire source. The dose distribution was determined with a spatial resolution of better than 0.2 mm, with only a few minutes needed per scan. The scintillator dosemeter was absolutely calibrated in terms of absorbed dose to water with a precision of +/-7.5%. The relative precision achievable is +/-2.5%. The response of the system is linear within +/-2% for dose rates from 0.5 mGy s(-1) to 500 mGy s(-1).

Fluorescence 125I eye applicator.

A new approach to optimize curative eye plaque brachytherapy is presented. The application of ophthalmic plaques is a common therapy modality for small and medium sized intraocular tumors. At Essen University Hospital eye applicators with photon emitting 125I seeds are used for the treatment of tumors with a thickness from 5 to 10 mm. Our clinical experiences indicate that the dose distributions of these applicators-used so far worldwide-are not optimal. A steeper dose falloff would meet the radiobiological requirements better, to provide the eradication of all tumor cells as well as sufficient occlusion of tumor supplying blood vessels. Our investigations for eye plaque optimization are based both on measurements and Monte Carlo simulation. For fast dosimetric measurements we have built a computer controlled device which allows reading out, directly and simultaneously, 16 1 mm3 scintillators. For the numerical simulations of the dose distribution of 125I eye plaques we have adapted a Monte Carlo program originally developed to calculate the synchrotron radiation in particle physics. We have investigated the influence of geometrical as well as physical eye plaque parameters on the dose distribution: Shielding of the primary radiation, penumbra modification, and energy conversion by exploiting fluorescence x-radiation have been considered. New types of fluorescence eye applicators have been designed which are more suitable for the prevention of radiopathic effects on structures at risk.

Characterization of two class II chitinase genes from peanut and expression studies in transgenic tobacco plants.

Two different genes encoding class II chitinases from peanut (Arachis hypogaea L. cv. NC4), A.h.Chi2;1 and A.h.Chi2;2, have been cloned. In peanut cell suspension cultures, mRNA levels of A.h.Chi2;2 increased after ethylene or salicylate treatment and in the presence of conidia from Botrytis cinerea. The second gene, A.h.Chi2;1, was only expressed after treatment with the fungal spores. Transgenic tobacco plants containing the complete peanut A.h.Chi2;1 gene exhibited essentially the same expression pattern in leaves as observed in peanut cell cultures. Expression characteristics of transgenic tobacco carrying a promoter-GUS fusion of A.h.Chi2;1 are described.

Expression of a reporter gene is reduced by a ribozyme in transgenic plants.

A chimeric gene encoding a ribozyme under the control of the cauliflower mosaic virus (CaMV) 35S promoter was introduced into transgenic tobacco plants. In vivo activity of this ribozyme, which was designed to cleave npt mRNA, was previously demonstrated by transient expression assays in plant protoplasts. The ribozyme gene was transferred into transgenic tobacco plants expressing an rbcS-npt chimeric gene as an indicator. Five double transformants out of sixteen exhibited a reduction in the amount of active NPT enzyme. To measure the amount of ribozyme produced, in the absence of its target, the ribozyme and target genes were separated by genetic segregation. The steady-state concentrations of ribozyme and target RNA were shown to be similar in the resulting single transformants. Direct evidence for a correlation between reduced npt gene expression and ribozyme expression was provided by crossing a plant containing only the ribozyme gene with a transgenic plant expressing the npt gene under control of the 35S promoter, i.e. the same promoter used to direct ribozyme expression. The expression of npt was reduced in all progeny containing both transgenes. Both steady-state levels of npt mRNA and amounts of active NPT enzyme are decreased. In addition, our data indicate that, at least in stable transformants, a large excess of ribozyme over target is not a prerequisite for achieving a significant reduction in target gene expression.