A comparison of side-effects and quality-of-life in patients operated on for prostate cancer with and without salvage radiation therapy.

PURPOSE: The extent of late side-effects in prostate cancer patients, after radical prostatectomy (RP = reference group) and salvage radiation therapy (SRT) in a self-reporting perspective (PROM) is still under-reported. We aimed to investigate the rate and severity of side-effects and quality-of-life (QoL) according to PROM. METHODS AND MATERIALS: A PROM survey was administered to a cohort of SRT patients matched to a reference group with median follow-up 10 years after surgery. In total, 740 patients were analyzed. To investigate the association between SRT versus reference group regarding side-effects and QoL, a Poisson regression analysis was conducted and presented as relative risk estimates (RR) together with 95% confidence intervals regarding questions related to urinary, rectal, sexual symptoms and QoL. RESULTS: RRs ranged from of 1.7-6.5 on rectal symptoms and 1.2-1.4 for urinary symptoms. In general health, QoL and sexual function all RRs were below 1.1. With increasing age, higher RRs were seen for urinary leakage and lowered sexual function whereas longer time following irradiation showed higher RRs for rectal symptoms and rectal leakage. Limitations of this study include the cross-sectional design and lack of baseline assessment. CONCLUSIONS: Adding SRT to RP does not seem to result in other than acceptable side-effects in the majority of men receiving SRT when taking a long follow-up time (median 10 years after surgery) into account. However, a subset of men develop severe side-effects where rectal bleeding dominates.

The value of a bladder-filling protocol for patients with prostate cancer who receive post-operative radiation: results from a prospective clinical trial.

BACKGROUND AND PURPOSE: This study compares two different strategies for maintaining a constant bladder volume during a course of postoperative radiotherapy in prostate cancer. In addition, we studied how changes in bladder filling affect the clinical target volume (CTV) and the coverage hereof. MATERIAL AND METHODS: Twenty-nine patients with PSA-relapse after radical prostatectomy were divided into two groups: voiding and drinking 300 ml 1 hour before treatment (Group 1); and maintained a comfortably filled bladder (Group 2). The bladder volumes were calculated based on the planning CT (pCT) and a weekly Cone Beam CT (CBCT) during the treatment period. Furthermore, the variability of bladder extension was analyzed and correlated to the volume of the bladder covered with the 95% of the dose (V95%,bladder). RESULTS: The estimated median bladder volumes were 120 ml (95% CI: (93, 154)) and 123 ml (95% CI: (98, 155)) in groups 1 and 2, respectively. The intra-individual variation in bladder volume, assessed as the standard deviation, was 64 ml (95% CI: (46, 105)) in Group 1 and 61 (95% CI: (45, 94)) ml in Group 2. Increasing the bladder volume extended the bladder cranially while the caudal extension was almost constant. The correlation between bladder volume and V95%,bladder was 3.5 ml per 100 ml in group 1 and 1.2 ml per 100 ml in group 2 with no significant difference. CONCLUSIONS: The intention to maintain a constant volume for the bladder is not fulfilled with either of the protocols in this study, and changes in bladder volumes does not seem to affect the position, or the coverage of the CTV.

Structure delineation in the presence of metal - A comparative phantom study using single and dual-energy computed tomography with and without metal artefact reduction.

BACKGROUND AND PURPOSE: Metal artefacts in computed tomography (CT) images impairs structure delineation. These artefacts can potentially be reduced with dual-energy CT (DECT) with or without using metal artefact reduction (MAR). The purpose was to investigate how structure delineation in DECT with or without MAR and single-energy CT (SECT) images were affected by metals. MATERIALS AND METHODS: A phantom with known irregular structures was developed. Reference structures were determined from a low-noise scan without metal. Bilateral hip prostheses were simulated with steel or titanium inserts. The phantom was scanned with SECT and fast-kV switching DECT with optional MAR. Four radiation oncologists delineated the structures in two phantom set-ups. Delineated structures were evaluated with Dice similarity coefficient (DSC) and Hausdorff distance relative to the reference structures. RESULTS: With titanium inserts, more structures were detected for non-MAR DECT compared to SECT while the same or less were detected with steel inserts. MAR improved delineation in DECT images. For steel inserts, three structures in the region of artefacts, were delineated by at least two oncologists with MAR-DECT compared to none with non-MAR DECT or SECT. The highest values of DSC for MAR-DECT were 0.69, 0.81 and 0.77 for those structures. CONCLUSIONS: Delineation was improved with non-MAR DECT compared to SECT, especially for titanium inserts. A larger improvement was seen with the use of MAR for both steel and titanium inserts. The improvement was dependent on the location of the structure relative to the inserts, and the structure contrast relative to the background.

Clinical feasibility and positional stability of an implanted wired transmitter in a novel electromagnetic positioning system for prostate cancer radiotherapy.

PURPOSE: Three aspects of the RayPilot real-time tracking system were investigated: (1) feasibility of the transmitter with respect to implantation and explantation procedures, (2) user and patients' experiences and (3) quantification of the transmitter positional stability in relation to fiducial markers. METHODS AND MATERIALS: Ten prostate cancer patients scheduled for radiotherapy received transmitter implantation in the prostate, concomitantly with fiducial markers. Transmitter and marker positions were assessed in 3D by orthogonal kV-imaging at daily treatment setup in eight patients. RESULTS: The transmitter was successfully implanted in all patients. Patients reported mild to moderate discomfort and impact on daily activities due to the implant but overall subjective tolerability was good. One patient had spontaneous explantation of the transmitter after four fractions. One patient had transmitter 3D shifts >9 mm, but also inter-marker shifts >6 mm. The mean inter-marker shift in the remaining patients was <1 mm. In four patients, maximum transmitter 3D shifts were 5-7 mm (mean >2 mm). In three patients, mean transmitter 3D shifts were <2 mm. CONCLUSIONS: Implantation and explantation of the transmitter is generally feasible and safe. Patient tolerability is good overall. However, due to interfractional transmitter positional instability in this cohort, use of the system for real-time tracking should be combined with other daily setup techniques.

Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and NIS mRNA expression in cultured thyroid cells.

UNLABELLED: Recent clinical and experimental data demonstrate that thyroid stunning is caused by previous irradiation and may influence the efficacy of (131)I radiation therapy of thyroid cancer and possibly hyperthyroidism. To avoid stunning, many clinics have exchanged (131)I for (123)I for pretherapeutic diagnostic imaging and dose planning. Furthermore, recent in vitro studies indicate that (131)I irradiation reduces iodide uptake by downregulating the expression of the sodium iodide symporter (NIS). The rationale for this study was therefore to study effects on iodide transport and NIS messenger RNA (mRNA) expression in thyrocytes exposed to both (123)I and (131)I in addition to some other potentially interesting radionuclides. METHODS: Thyrotropin-stimulated thyroid cell monolayers were exposed to 0.5 Gy of (123)I, (131)I, (99m)Tc, or (211)At, all being radionuclides transported via NIS, in the culture medium for 6 h, or to various absorbed doses of (123)I or (131)I for 48 h. NIS mRNA expression was analyzed using quantitative reverse-transcriptase polymerase chain reaction. RESULTS: Iodide transport and NIS mRNA expression were reduced by all radionuclides. At the same absorbed dose, iodide transport was reduced the most by (211)At, followed by (123)I and (99m)Tc (equally potent), whereas (131)I was least effective. The onset of NIS downregulation was rapid (<1 d after irradiation) in cells exposed to (123)I or (211)At and was delayed in cells irradiated with (131)I or (99m)Tc. Iodide transport and NIS expression were recovered only for (211)At. (123)I reduced the iodine transport and the NIS mRNA expression more efficiently than did (131)I at an equivalent absorbed dose, with a relative biological effectiveness of about 5. CONCLUSION: The stunning effect per unit absorbed dose is more severe for (123)I than for (131)I. Despite the lower absorbed dose per unit activity for (123)I than for (131)I, stunning by (123)I cannot be excluded in patients. The degree to which iodide transport capacity and NIS mRNA expression are reduced seems to be related to the biological effectiveness of the type of radiation delivering the absorbed dose to the target, with (211)At (which has the highest relative biological effectiveness) causing the highest degree of stunning per unit absorbed dose in the present study.

Transport of free 211At and 125I- in thyroid epithelial cells: effects of anion channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid on apical efflux and cellular retention.

INTRODUCTION: Astatine ((211)At; alpha-emitter; t(1/2)=7.21 h) shares several features with its halogen neighbour iodine. In the present study, we investigated whether 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) can be used to increase the cellular retention time of (211)At and radioiodide in thyroid epithelial cells. METHODS: The transepithelial transport and cellular uptake of (211)At and (125)I(-) were studied simultaneously in porcine thyrocytes cultured in bicameral chambers. The cells were prestimulated with thyroid-stimulating hormone (TSH) or epidermal growth factor (EGF) for 48 h. In addition, the acute effects of DIDS and forskolin were investigated. RESULTS: The transepithelial transport of both radionuclides was stimulated by TSH and down-regulated by EGF. DIDS rapidly reduced the efflux and increased the cellular content of (125)I(-) in control and TSH-stimulated cells, whereas DIDS had no effect on (125)I(-) transport in EGF-treated cells. DIDS blocked the (211)At efflux only in TSH-stimulated cells. Unexpectedly, DIDS caused an accelerated efflux of (211)At in both control and EGF-stimulated cells and, furthermore, reduced the cellular content of (211)At in the EGF-stimulated cultures. DIDS had no effect on the forskolin-induced efflux of the two radionuclides. CONCLUSIONS: The magnitude of thyroidal (211)At uptake and efflux is similar to that of (125)I(-), strongly dependent on the functional activity of the cells. However, (211)At efflux likely involves several permeating mechanisms with different sensitivity to DIDS, which are at least partly not shared by (125)I(-). The results suggest that anion channel blockage is potentially useful to increase the absorbed dose from both (211)At and radioiodine in NIS-expressing tumours.

Biodistribution of free 211At and 125I- in nude mice bearing tumors derived from anaplastic thyroid carcinoma cell lines.

UNLABELLED: Free 211At has been proposed for therapy of anaplastic thyroid carcinoma (ATC). However, no extensive biodistribution study comparing tumor-bearing and nontumor-bearing mice has previously been performed. The aim of this study was to perform a complete evaluation of the biodistribution of 211At, both for normal and ATC-bearing mice. For comparison, the biodistribution of 125I- was simultaneously studied. Dosimetric evaluations were performed to investigate if (211)At can be used for therapy of ATC. METHODS: Athymic nude mice were subcutaneously injected with either of two human ATC cell lines, HTh83 and KAT-4. Tumor-bearing and nontumor-bearing mice were injected intravenously with 0.3 MBq 211At and 0.3 MBq 125I- simultaneously. The mice were sacrificed 4-24 hours after injection, and the activity concentrations in tissues were determined. RESULTS: Except for the thyroid, the concentration of 211At was higher than that of 125I- in the tissues. The uptake of 211At was primarily high in NIS-expressing organs. Furthermore, the absorbed doses to these organs were higher than both tumor types. CONCLUSIONS: The biodistribution of 211At and 125I- differed in this animal model. The higher mean absorbed dose from 211At in several organs than in tumor tissue restricts the possibility of using free 211At for therapy of ATC.

Adsorption and volatility of free 211At and 125I-.

The present study was undertaken to extend our knowledge of the behaviour of 211At in the laboratory environment. An unexpectedly high volatility of free 211At was found, up to 85% during an hour. Free 211At also adsorbed more onto the plastic material studied than 125I-. The results of this study show that it is of great importance to pay careful attention to radiation protection procedures during the practical handling of free 211At.

Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial cells.

UNLABELLED: The existence of thyroid stunning (i.e., inhibited thyroidal iodide uptake after administration of diagnostic amounts of (131)I) is controversial and is currently a subject of debate. To our knowledge, the stunning phenomenon has not been investigated previously in vitro. METHODS: Growth-arrested porcine thyroid cells that formed a tight and polarized monolayer in a bicameral chamber were irradiated with 3-80 Gy (131)I present in the surrounding culture medium for 48 h. The iodide transport capacity after irradiation was evaluated 3 d later by measuring the transepithelial (basal to apical) flux of trace amounts of (125)I. RESULTS: The basal-to-apical (125)I transport decreased with increasing absorbed dose acquired from (131)I; a nearly 50% reduction was observed already at 3 Gy. Stable iodide at the same molarity as (131)I (10(-8) mol/L) had no effect on the (125)I transport. Cell number and epithelial integrity were not affected by irradiation. CONCLUSION: Stunning of iodide transport is detected after (131)I irradiation of cultured thyroid cells. The degree of inhibition of transport is dependent on the absorbed dose.