Intensity-Modulated Radiotherapy (IMRT) of Localized Prostate Cancer

PURPOSE: The present status of intensity-modulated radiation therapy (IMRT) for treatment of localized prostate cancer is discussed. METHODS: The technological basis of IMRT and the rationale for the use in treatment of prostate cancer are described. Clinical results from the literature are presented and treatment strategies for further reduction of safety margins are outlined. RESULTS AND DISCUSSION: Multiple planning studies demonstrated the dosimetric advantage of IMRT compared to three-dimensional conformal radiotherapy. Though randomized studies are missing, retrospective studies indicate that improved dose distributions of IMRT transfer into improved rates of local control and/or lower rates of rectal toxicity. However, with standard safety margins the benefit of IMRT seems to be limited. Image guidance is considered to be essential to reduce errors of patient setup and internal motion of the prostate.     

Precision of Image-Guided Radiotherapy (IGRT) in Six Degrees of Freedom and Limitations in Clinical Practice

PURPOSE: To evaluate the precision of image-guided radiotherapy (IGRT) using cone-beam computed tomography (CB-CT) for volume imaging and a robotic couch for correcting setup errors in six degrees of freedom. PATIENTS AND METHODS: 47 consecutive patients with 372 fractions were classified according to whether a patient fixation device was used (pat(fix): n = 28) or not (pat(non-fix): n = 19). Prior to treatment a CB-CT was acquired and translational and rotational setup errors were corrected online without an action level using a robotic couch (HexaPOD). A second CB-CT was acquired after the correction process and after treatment in 134 and 238 fractions, respectively. RESULTS: In 17 fractions (4.6%) rotational errors > 3 degrees exceeded the motion range of the HexaPOD. Errors (3D vector) after the correction process were significantly smaller for pat(fix) compared to pat(non-fix) (p < 0.001): 0.9 mm +/- 0.5 mm and 1.6 mm +/- 0.8 mm, respectively. For pat(non-fix) the correction of rotational errors resulted in displacements of the patients on the angled couch of 0.6 mm/1 degree. Intrafractional motion further decreased precision in pat(non-fix) but not in pat(fix). CONCLUSION: Very high precision in cranial and extracranial treatment of immobilized patients was demonstrated. Without application of adequate immobilization the correction of rotational errors and intrafractional patient motion significantly decreased the accuracy of the online correction protocol.     

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

BACKGROUND AND PURPOSE: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). MATERIALS AND METHODS: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). RESULTS: A decrease of TC to <95% was found in 3/60 simulations (5%) of pulmonary and 7/58 simulations (12%) of hepatic targets. In two of 22 pulmonary targets (9%) and in four of 21 hepatic targets (19%) a TC of <95% occurred in at least one fraction. At risk for a decreased TC <95% were pulmonary targets with increased breathing mobility and hepatic targets with a CTV exceeding 100 cm(3). CONCLUSIONS: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV >or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.     

The effectiveness of diversion programmes for offenders using Class A drugs: a systematic review and meta-analysis

Aims: To review existing evidence on effectiveness of community-based diversion programmes for Class A drug-using offenders.

Methods: 31 databases were searched for studies published 1985–2012 (update search 2012–2016) involving community-based Criminal Justice System diversion of Class A drug users via voluntary or court-mandated treatment.

Findings: 16 studies were initially included (US, 10; UK, 4; Canada, 1; Australia, 1). There was evidence for a small impact of diversion to treatment on drug use reduction (primary Class A drug use: OR 1.68, CI 1.12–2.53; other drug use: OR 2.60, 1.70–3.98). Class A drug users were less likely to complete treatment (OR 0.90, 0.87–0.94) than users of other drugs. There was uncertainty surrounding results for offending, which were not pooled due to lack of outcome measure comparability and heterogeneity. Individual studies pointed to a minor effect of diversion on offending. Findings remained unchanged following an update review (evidence up to March 2016: US, 3; Australia, 1).

Conclusions: Treatment accessed via community-based diversion is effective at reducing drug use in Class A drug-using offenders. Evidence of a reduction in offending amongst this group as a result of diversion is uncertain. Poor methodological quality and data largely limited to US methamphetamine users limits available evidence.     

Does in vitro colony formation and chemosensitivity relate to DNA ploidy and S-phase fractions?

Summary In vitro colony formation and chemosensitivity were analyzed in 65 human solid tumors and compared to proliferation parameters simultaneously obtained by DNA flow cytometry of the same tumor specimens.Colony growth in the human tumor colony assay was enhanced in aneuploid tumors (39/65) in comparison to diploid tumors (26/65, P<0.05). In addition, there was a relationship between % S-phase and colony growth. The existence of polyploid sublines (23/65) improved in vitro growth even in tumors with a diploid main G_0/1-peak or with a low % S-phase. Metastases exhibited a higher proportion of aneuploidy and showed slightly better growth in vitro than primary tumors.Sensitivity testing in 34 of the 65 tumors showed no convincing relation between DNA parameters and the inhibition of colony formation by five standard anticancer agents with different mechanisms of action. This indicates additional factors other than the proliferative activity of the tumor to be responsible for drug sensitivity or resistance.     

Strahlentherapie des lokal fortgeschrittenen Lungenkarzinoms

Combined radio-chemotherapy treatment is suitable for patients in good general health with localised advanced non-small cell lung cancer from stage?IIIA3 onwards. The benefit of additional (consolidating or inductive) chemotherapy has not been conclusively determined. Results of recent phase?III studies, however, suggest caution. Similarly undefined to date is the benefit of novel targeted therapies in combination with radiotherapy. Procedures introduced into clinical routine in recent years, such as FDG-PET and EBUS, enable improved detection of metastases and their differentiation from normal tissue and thus new target volume concepts (PET-CT/involved-field radiotherapy). The ongoing development of technical options for the planning and implementation of this therapy (IMRT) allows dosage increases without harming organs at risk and provides hope of greater improvements in the treatment of a disease which generally still has an unfavourable course.     

Online health information seeking,health literacy,and human papillomavirus vaccination among transgender and gender-diverse people

ObjectiveThe purpose of this study is to describe online health information seeking among a sample of transgender and gender diverse (TGD) people compared with cisgender sexual minority people to explore associations with human papillomavirus (HPV) vaccination, and whether general health literacy and eHealth literacy moderate this relationship.Materials and MethodsWe performed a cross-sectional online survey of TGD and cisgender sexual minority participants from The PRIDE Study, a longitudinal, U.S.-based, national health study of sexual and gender minority people. We employed multivariable logistic regression to model the association of online health information seeking and HPV vaccination.ResultsThe online survey yielded 3258 responses. Compared with cisgender sexual minority participants, TGD had increased odds of reporting HPV vaccination (aOR, 1.5; 95% CI, 1.1-2.2) but decreased odds when they had looked for information about vaccines online (aOR, 0.7; 95% CI, 0.5-0.9). TGD participants had over twice the odds of reporting HPV vaccination if they visited a social networking site like Facebook (aOR, 2.4; 95% CI, 1.1-5.6). No moderating effects from general or eHealth literacy were observed.DiscussionDecreased reporting of HPV vaccination among TGD people after searching for vaccine information online suggests vaccine hesitancy, which may potentially be related to the quality of online content. Increased reporting of vaccination after using social media may be related to peer validation.ConclusionsFuture studies should investigate potential deterrents to HPV vaccination in online health information to enhance its effectiveness and further explore which aspects of social media might increase vaccine uptake among TGD people.     

Combined error of patient positioning variability and prostate motion uncertainty in 3D conformal radiotherapy of localized prostate cancer

: TO measure the patient positioning and prostate motion variability and to estimate its influence on the calculated 3D dose distribution in 3D conformal radiotherapy of patients with localized prostate carcinoma.

: Patient positioning variability was determined retrospectively by comparing weas determined by 107 computed tomography (CT) examinations with a CT simulator in 28 patients during radiotherapy.

: In each observed direction, the patient positioning variability and prostate motion showed a normal distribution. This observation enabled the calculation of a combined error of both components. The standard deviation (1 SD) of the patient positioning error in three directions ranged 3.1 to 5.4 mm; the prostate motion variability was significantly greater in the anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior-posterior direction 6.1 mm and in mediolateral direction 3.6 mm.

: The range of patient positioning variability and prostate motion statistically predictable under the patient setup cnditions used. Dose-volume histograms demonstrating the influence of the combined error of both components on the calculated dose distribution are presented.     

In vitro radiosensitivity measured in lymphocytes and fibroblasts by colony formation and comet assay: comparison with clinical acute reactions to radiotherapy in breast cancer patients

PURPOSE: To compare colony-forming and comet assays on fibroblasts and lymphocytes of 32 breast cancer patients irradiated after breast-conserving operations and to correlate the results with acute clinical radiation reactions in the skin. MATERIAL AND METHODS: Skin fibroblasts were isolated and cultivated before radiotherapy and lymphocytes were drawn prior to the first and directly after the final external irradiation. The colony-forming assay was performed with fibroblasts and the comet assay with lymphocytes and fibroblasts of breast cancer patients according to standard protocols. The clinical radiation reactions of the patients were graded according to the RTOG system. RESULTS: No significant correlation (p =0.09) was detected between clinical acute skin reactions and the in vitro clonogenic data in fibroblasts. Results of the comet assay in lymphocytes, however, showed a significant correlation (p <0.05) with the clinical data when patients were divided into two groups with average and elevated acute reactions. Apart from initial damage, fibroblasts did not show significant differences between the two patient groups. Repeated comet assays in lymphocytes of the same patient drawn before treatment and before and after external radiotherapy demonstrated good reproducibility of the test and no significant impact of preceding radiation treatment. There was a good correlation (r =0.65) between the comet assay results in fibroblasts and lymphocytes of the same individual. CONCLUSIONS: In this cohort of patients, a significant correlation between the in vitro results of the comet assay in lymphocytes and clinical acute reactions was detected. The results of the comet assay and of fibroblast colony formation did not correlate with in vitro radiosensitivity.     

Intraoperative and postoperative PTH secretion mode in patients with hyperparathyroidism

The development of a sensitive 2-site immunoradiometric assay which detects only intact human PTH (1–84) enabled us to study kinetics of PTH secretion intraoperatively. In a prospective study, we assessed the PTH (1–84) secretion mode intraoperatively in 54 patients with adenomas, in 14 patients with tertiary hyperparathyroidism (HPT), and in 2 patients with persistent HPT. After the removal of adenomatous or hyperplastic tissue, a significant drop of PTH (1–84) concentration was seen. A 50% decrease in the basal PTH concentration was reached significantly earlier for adenomas than for hyperplasias. In the 2 cases with unrevealing neck exploration, the PTH (1–84) concentrations showed hardly any change. The recovery of PTH secretion was studied in 23 patients, 20 of whom had a single adenoma; in 2 cases, a hyperplasia was present and 1 patient showed the clinical signs of a toxic HPT. We found an initial drop of PTH concentration 4 hours postoperatively below the limit of detection and a rapid recovery within 24 hours postoperatively. The PTH concentration values were well within the normal range after 48–72 hours.

---

Resumen El desarrollo de una muy sensible determinación inmunoradiométrica capaz de detectar exclusivamente la HPT (1–84) humana nos ha permitido realizar un estudio de la cinética de la secreción intraoperatoria de hormona paratiroidea (PTH). En un estudio prospectivo hemos hecho la determinación del modo de secreción de PTH (1–84) en 54 pacientes con adenomas, en 14 con hiperparatiroidismo terciario, y en 2 con hiperparatiroidismo persistente. Una vez resecado el tejido adenomatoso o hiperplásico, se observó un descenso significativo de la concentración sérica de PTH (1–84). Un descenso de 50% en el nivel de la concentración basal de PTH apareció, en forma significativa, más precozmente en los adenomas que en las hiperplasias. En los 2 casos con exploración cervical negativa, la concentración de PTH (1–84) prácticamente no exhibió modificación. La recuperación de la secreción de PTH fue estudiada en 23 pacientes, 20 de los cuales tenían adenoma único, 2 hiperplasia y 1 exhibía signos clínicos de hiperparatiroidismo tóxico. Encontramos un descenso inicial de la concentración de PTH a valores por debajo del nivel de detección a las 4 horas postoperatorias y una recuperación rápida dentro de las primeras 24 horas. Las concentraciones de PTH regresaron a valores normales a las 48–72 horas.

---

Résumé Le perfectionnement d'un dosage immunoradiométrique à 2 sites, sensible, qui ne détecte que la parathormone humaine intacte (PTH 1–84) a permis d'étudier les cinétiques de la sécrétion peropératoire de ia PTH. Dans une étude prospective, nous avons évalué la sécrétion peropératoire de PTH 1–84 chez 54 patients ayant un adénome, chez 14 patients ayant une hyperparathyroïdie tertiaire (HPT), et chez 2 patients ayant une HPT persistante. On a observé une chute significative de PTH 1–84 après l'ablation de tissus athéromateux ou hyperplasiques. La réduction de la sécrétion de base de PTH de 50% était atteinte plus tôt de façon significative pour les adénomes que pour les hyperplasies. Dans les 2 cas où l'exploration cervicale était négative, les concentrations en PTH 1–84 sont restées pratiquement inchangées. La reprise de la sécrétion en PTH a été étudiée chez 23 patients, dont 20 avaient un adénome solitaire; dans 2 cas, on a découvert une hyperplasie, et chez 1 patient, il y avait des signes cliniques de HPT toxique. La chute initiale de PTH 4 heures après l'opération n'était pas sensible et la reprise était rapide, moins de 24 heures après l'intervention. La PTH était dans les limites de la normale après 48–72 heures.

---

---

Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.