84 research outputs found
The enterprise in testudo formation: the protection zone of legal privilege in German and US penal law
No full textFor companies legal privilege represents an essential bulwark against the state. In the case of internal investigations legal privilege is of prime importance to the companies. At crucial points of intersection the legal situation in the US differs from that of Germany. In the US, confidentiality is regarded with the aura of a Holy Grail, applying to in-house counsel and external lawyers alike. However, in Germany those privileges do not apply to in-house counsels and neither are they intended to apply to the corporate lawyer (so-called Syndikus). This is explained by Criminal Law policy arguments, which according to the author\''s opinion are not tenable. This essay represents solutions de lege lata and de lege ferenda, in order to at least include in-house lawyers (so-called Syndikus) within the scope of legal privilege. For this purpose, the author argues in favor of a partial adoption of the American way
Outcome of hypofractionated biological optimized dose-painting radiotherapy for high-risk prostate cancer.
No full text 107 Background: Prostate dose-painting radiotherapy and hypo-fractionation both can improve biochemical contol in localised disease. We report toxicity and outcome for a cohort of high risk patients. Methods: We selected 28 patients with high-risk localised prostate cancer and 2 or 3 risk factors. Functional MRI’s were used to define boost volumes with a margin of 5 mm PTV. Neo-adjuvant hormone therapy was given for 3 months. Dose volume constraints, TCP and NTCP parameters were used for optimization of rotational IMRT treatment plans. We used fiducial markers, bowel and bladder preparation and daily IGRT. Results: Mean age was 66 years, mean PSA was 17.4 ng/ml (range 4.6-59.1), 20 patients had T3a and 10 had Gleason score ≥ 8. The mean dose to the prostate excluding the boost volume was 61.4 Gy (range 60.6-62.3) and the boost PTV 66.1 Gy (range 60.9-72.5). Mean NTCP for rectal bleeding was 4.7% (range 3.4-5.8), for faecal incontinence 3.5% (range 2.3-5) and mean TCP 75% (range 71-79) assuming a 71% biochemical control at 5 years for a standard plan. All patients completed radiotherapy, 16/28 patients had acute bladder toxicity grade 2 (RTOG score), but no grade 3 toxicity was observed. Worst acute bowel toxicity was grade 1 (4/28). Mean follow up was 15 months (range 8-25). For the 20 patients who had neo-adjuvant hormone therapy beyond 6months, the mean PSA was 0.33 ng/ml (range 0.2-0.8), 2 patients had relapsed at 12 month, 6 patients are still on hormone therapy. 4 patients had Grade 2 urinary late toxicities (CTCv4). Two patients developed grade 1 diarrhoea. Patient reported outcomes >6 month after completion of radiotherapy (EPIC QOL questionnaire) demonstrated similar scores to controls without prostate cancer for the bowel domains; reduction in the urinary domains was similar to other cohorts treated with external beam radiotherapy and hormone therapy. Conclusions: In this high risk group, dose escalation with hypo-fractionated dose painting radiotherapy achieved good biochemical control and urinary and bowel toxicity similar to standard dose radiotherapy during follow up. </jats:p
Forward and inverse-planned intensity-modulated radiotherapy (IMRT) in the CHHiP trial: A comparison of dosimetry and normal tissue toxicity.
No full text 37 Background: CHHiP (CRUK/06/016) is a multicentre randomised controlled trial investigating the use of hypofractionated radiotherapy dose schedules for treatment of localised prostate cancer. RT treatment employs a complex target volume treated with either a multi-segment “forward” plan or inverse-planned intensity-modulated radiotherapy (IMRT). This study compares dose-volume histogram (DVH) and toxicity data for rectum and bladder for the two planning techniques. Methods: Three hundred thirty seven patients (230 forward-planned [F]; 107 inverse-planned [I]) with prospectively collected 2 year toxicity and DVH data for rectum and bladder dose constraints were included. Patients were paired for comparison by matching on (1) rectum and prostate + seminal vesicle PTV volumes for the rectal dose comparison (53 matched pairs available); and (2) bladder and prostate-alone PTV volumes for bladder dose comparison (61 matched pairs). For the toxicity comparison patients were additionally matched on randomised dose schedule. Results: Forward-planned patients had significantly larger volumes of rectum irradiated to 50 to 70Gy and bladder at 50 to 60Gy. In contrast, inverse-planned patients had significantly larger volumes of bladder irradiated to 74 Gy. Acute bowel toxicity (G2+ toxicity within 18 weeks of start of RT) was significantly worse in forward-planned patients (27/53 [52%] F vs 11/53 [21%] I; Mann-Whitney p=0.0002). There were no significant differences in acute urinary symptoms. Late toxicity was rare in both planning groups with only two patients (0 F; 2 I) reporting RTOG G2+ bowel/bladder effects at 24 months. Considering LENTSOM data, there was a suggestion of less late bowel toxicity in the inverse group (G1+ at 18 months: 16/53 (30%) F vs. 6/53 (11%) I; p=0.008). Patient reported outcomes of bowel habits showed no consistent differences between planning methods, although there was a tendency for worse urinary function scores in the inverse group at 12 months. Conclusions: Both planning techniques were associated with low late toxicity. Significant differences were found between DVHs from forward and inverse plans. There were some associations between DVH differences and normal tissue effects; these resolved by 2 years. Clinical trial information: CRUK/06/016. </jats:p
10-Year efficacy and co-morbidity outcomes of a phase III randomised trial of conventional vs. hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CHHiP; CRUK/06/016)
No full textBackground: Five-year results from the CHHiP trial indicated that moderate hypofractionation of 60 Gray (Gy)/20 fractions (f) was non-inferior to 74Gy/37f (Lancet Oncology, 2016). Reporting of long-term efficacy and side effects is essential in a patient population that remain at risk of recurrence years after treatment. Here we report specific co-morbidity data collected at 10 years and an update of efficacy. Methods: Between October 2002 and June 2011, 3216 men with node negative T1b-T3a localised prostate cancer with risk of seminal vesical involvement ≤30% were randomised (1:1:1 ratio) to 74Gy/37f (control), 60Gy/20f or 57Gy/19f. Patients received 3-6 months of androgen deprivation prior to radiotherapy. The primary endpoint was time to biochemical failure (Phoenix consensus guidelines) or clinical failure (BCF). The non-inferiority design specified a critical hazard ratio (HR) of 1.208 for each hypofractionated schedule compared to control. Data on specific radiotherapy related co-morbidities were collected at 10-year follow-up and are presented as frequency and percentages. Analysis was by intention-to-treat; HRs quoted are unadjusted. Results: With a median follow up of 12.1 years, 10-year BCF-free rates (95% CI) were 74Gy: 76.0% (73.1%, 78.6%); 60Gy: 79.8% (77.1%, 82.3%) and 57Gy: 73.4% (70.5%, 76.1%). For 60Gy/20f, non-inferiority was confirmed: HR60=0.84 (90% CI 0.72, 0.97) with borderline significance for superiority (HR=0.84 (95% CI 0.70, 1.00). As in the primary analysis, for 57Gy/19f, non-inferiority could not be declared: HR57=1.13 (90% CI 0.98, 1.30). 10-year overall survival (95% CI) was 78.5% (75.9%, 81.0%), 82.9% (80.4%, 85.0%) and 79.9% (77.3%, 82.2%) in the 74Gy, 60Gy and 57Gy groups. Bone fractures were reported in 2% (15/700), 2% (19/771) and 3% (22/719) of patients in the 74Gy, 60Gy and 57Gy groups respectively at 10 years. The most common intervention reported was a sigmoidoscopy with 12% (79/681), 8% (60/739) and 9% (65/702) in the 74Gy, 60Gy and 57Gy groups respectively. Of those patients who underwent a sigmoidoscopy it was due to symptoms for 81% (63/78) 81% (48/59) and 85% (55/65) of patients in the 74Gy, 60Gy and 57Gy group respectively. Frequencies of all other pre-specified co-morbidities or related interventions (ureteric obstruction, bowel strictures, trans-urethral resection of prostate, urethrotomy, urethral dilatation or long term catheterisation or treatment of proctopathy with steroid, sucralfate, formalin, laser coagulation or rectal diversion) were <1% in all groups. Conclusions: With a median follow-up of 12 years, oncological outcomes following 60Gy/20f continue to be non-inferior to those with 74Gy/37f. Late co-morbidities were very low across all treatment groups. These data support the long-term safety of moderate hypofractionation. Clinical trial information: 97182923
Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)
No full textPurposeIn men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects.Methods and MaterialsThe UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires.ResultsIn the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade ≥2) was 1.55 (95% CI, 1.17–2.04); for diarrhea (LENT/SOM grade ≥2), the HR was 1.79 (95% CI, 1.10–2.94); and for proctitis (RTOG grade ≥2), the HR was 1.64 (95% CI, 1.20–2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively.ConclusionsThere is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up
EP-1333: Impact of 18 F-Choline PET scan acquisition time on delineation of GTV in Prostate cancer
No full textBackground: Dose painting radiotherapy requires accurate outlining of primary tumour volumes in the prostate. T2-Weighted (T2W) Magnetic Resonance Imaging (MRI) is the best imaging method for defining the gross tumour volume (GTV). Choline positron emission tomography (PET) is currently a controversial tracer. The image acquisition differs significantly in published studies. Many used early static imaging. One study found that 18F-choline PET/CT with late image acquisition has superior accuracy to T2W MR and functional MR alone1. We investigate whether increasing 18F-Choline PET scan acquisition time from 60 (PET-60) to 90 (PET-90) minutes improves GTV TVD.
Methods. Analysis was performed on 9 18F-Choline PET scans. Patients were injected with 370MBq of activity. Three clinicians (C1, C2 and C3) independently and without reference to each other contoured GTVs on each of the T2W-MRI, PET-60 and PET-90 scans at differing times. Scans were registered by a clinician using rigid co-registration. The treating clinicians MRI contour was used as a reference contour. The resulting PET and MRI GTVs were transferred to the PET-60 and PET-90 scans after image registration. The Dice Similarity Coefficient (DSC), Specificity (Sp) and Sensitivity (S) were calculated from contour mask voxel analysis.
Results. Table 1 shows the mean and range DSC, S and Sp scores on MRI, PET-60 and PET-90 for C1, C2 and C3 in comparison to the treating clinicians contour on MRI (C1). A 2 sampled T-test (P < 0.01) showed, no significant difference in the Sp, S and DSC between GTVs on PET-60 and PET-90 scans. Further to this, as shown in Figure 1, variability in GTV delineation is significant between observers in a singular case as well as across imaging modalities.
Conclusion. Compared to MRI delineated GTVs, 18F-Choline PET GTVs are significantly different. This study found however that increasing the PET scan acquisition time from 60 to 90 minutes did not improve the performance of GTV TVD in comparison to MRI delineated GTV
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