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Nitroaromatic compounds (NACs) are key contaminants of anthropogenic origin and pose a severe threat to human and animal lives. Although the catalytic activities of Re nanostructures (NSs) are significantly higher than those of other heterogeneous catalysts containing NSs, few studies have been reported on the application of Re-based nanocatalysts for NAC hydrogenation. Accordingly, herein, catalytic reductions of nitrobenzene (NB), 4-nitrophenol (4-NP), 2-nitroaniline (2-NA), 4-nitroaniline (4-NA), and 2,4,6-trinitrophenol (2,4,6-TNP) over new Re-based heterogeneous catalysts were proposed. The catalytic materials were designed to enable effective syntheses and stabilisation of particularly small Re structures over them. Accordingly, catalytic hydrogenations of NACs under mild conditions were significantly enhanced by Re sub-nanostructures (Re-sub-NSs). The highest pseudo-first-order rate constants for NB, 4-NP, 2-NA, 4-NA, and 2,4,6-TNP reductions over the catalyst acquired by stabilising Re using bis(3-aminopropyl)amine (BAPA), which led to Re-sub-NSs with Re concentrations of 16.7 wt%, were 0.210, 0.130, 0.100, 0.180, and 0.090 min -1 , respectively., (© 2023. Springer Nature Limited.)

Background: Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT., Methods: In a cohort of 11,982 BC patients diagnosed in 1998-2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events., Results: Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94-1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98-1.01, P = .68)., Conclusions: Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany., Methods: A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account., Results: After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85-1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88-1.25)., Conclusions: Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy., (© 2021. The Author(s).)

Purpose: Cardiac effects after breast cancer radiation therapy potentially affect more patients as survival improves. The heart's heterogeneous radiation exposure and composition of functional structures call for establishing individual relationships between structure dose and specific late effects. However, valid dosimetry requires reliable contouring which is challenging for small volumes based on older, lower-quality computed tomography imaging. We developed a heart atlas for robust heart contouring in retrospective epidemiologic studies., Methods and Materials: The atlas defined the complete heart and geometric surrogate volumes for six cardiac structures: aortic valve, pulmonary valve, all deeper structures combined, myocardium, left anterior myocardium, and right anterior myocardium. We collected treatment planning records from 16 patients from 4 hospitals including dose calculations for 3D conformal tangential field radiation therapy for left-sided breast cancer. Six observers each contoured all patients. We assessed spatial contouring agreement and corresponding dosimetric variability., Results: Contouring agreement for the complete heart was high with a mean Jaccard similarity coefficient (JSC) of 89%, a volume coefficient of variation (CV) of 5.2%, and a mean dose CV of 4.2%. The left (right) anterior myocardium had acceptable agreement with 63% (58%) JSC, 9.8% (11.5%) volume CV, and 11.9% (8.0%) mean dose CV. Dosimetric agreement for the deep structures and aortic valve was good despite higher spatial variation. Low spatial agreement for the pulmonary valve translated to poor dosimetric agreement., Conclusions: For the purpose of retrospective dosimetry based on older imaging, geometric surrogate volumes for cardiac organs at risk can yield better contouring agreement than anatomical definitions, but retain limitations for small structures like the pulmonary valve., (© 2021. The Author(s).)

The present work presents a new nanocomposite catalyst with rhenium nanostructures (ReNSs) for the catalytic hydrogenation of 4-nitrophenol and 4-nitroaniline. The catalyst, based on an anion exchange resin with functionality derived from 1,1'-carboimidazole, was obtained in the process involving anion exchange of ReO 4 - ions followed by their reduction with NaBH 4 . The amino functionality present in the resin played a primary role in the stabilization of the resultant ReNSs, consisting of ≈1% ( w/w ) Re in the polymer mass. The synthesized and capped ReNSs were amorphous and had the average size of 3.45 ± 1.85 nm. Then, the obtained catalyst was used in a catalytic reduction of 4-nitrophenol (4-NP) and 4-nitroaniline (4-NA). Following the pseudo-first-order kinetics, 5 mg of the catalyst led to a 90% conversion of 4-NP with the mass-normalized rate constant (k m1 ) of 6.94 × 10 -3 min -1 mg -1 , while the corresponding value acquired for 4-NA was 7.2 × 10 -3 min -1 mg -1 , despite the trace amount of Re in the heterogenous catalyst. The obtained material was also conveniently reused.

Background and Purpose: Salvage radiotherapy (SRT) is the main potentially curative treatment option for prostate cancer patients with post-prostatectomy PSA progression. Improved diagnostics by positron emission tomography/computed tomography (PET/CT) can lead to adjustments in treatment procedures (e.g. target volume of radiotherapy, androgen deprivation therapy). We analyzed the impact of 68 Ga-PSMA-11-PET/CT on the target volume in early biochemical recurrence (PSA up to 0.5 ng/ml)., Patients and Methods: We retrospectively analyzed 76 patients with biochemical recurrence after radical prostatectomy in whom SRT was planned after 68 Ga-PSMA-11-PET/CT. All patients had a PSA ≤0.5 ng/ml. An experienced radiation oncologist determined the radiotherapy concept, first with consideration of the PET/CT, second hypothetically based on the clinical and pathological features excluding PET/CT results., Results: Without considering the PET/CT, all 76 patients would have been assigned to RT, 60 (79%) to the bed of the prostate and seminal vesicles alone, and 16 (21%) also to the pelvic lymph nodes because of histopathologic risk factors. Uptake indicative for tumor recurrence in 68 Ga-PSMA-11-PET/CT was found in 54% of the patients. The median pre-PET/CT PSA level was 0.245 ng/ml (range 0.07-0.5 ng/ml). The results of the PET/CT led to a change in the radiotherapeutic target volume in 21 patients (28%). There were major changes in the target volume including the additional irradiation of lymph nodes or the additional or exclusive irradiation of bone metastases in 13 patients (17%). Minor changes including the additional irradiation of original seminal vesicle (base) position resulted in eight patients (11%)., Conclusion: Using 68 Ga-PSMA-11-PET/CT for radiation planning, a change in the treatment concept was indicated in 28% of patients. With PET/CT, the actual extent of the tumor can be precisely determined even with PSA values of ≤0.5 ng/ml. Thus, the treatment concept can be improved and individualized. This may have a positive impact on progression free survival. Our results warrant further prospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bottke, Miksch, Thamm, Krohn, Bartkowiak, Beer, Bolenz, Beer, Prasad and Wiegel.)

Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell's c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0-8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44-11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. PATIENT SUMMARY: Clinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials., (Copyright © 2019 European Association of Urology. All rights reserved.)

Purpose: The optimal treatment for patients with low to early-intermediate risk prostate cancer (PCa) remains to be defined. The randomized PREFERE trial (DRKS00004405) aimed to assess noninferiority of active surveillance (AS), external-beam radiotherapy (EBRT), or brachytherapy by permanent seed implantation (PSI) vs. radical prostatectomy (RP) for these patients., Methods: PREFERE was planned to enroll 7600 patients. The primary endpoint was disease specific survival. Patients with PCa stage ≤ cT2a, cN0/X, M0, PSA ≤ 10 ng/ml and Gleason-Score ≤ 3 + 4 at reference pathology were eligible. Patients were allowed to exclude one or two of the four modalities, which yielded eleven combinations for randomization. Sixty-nine German study centers were engaged in PREFERE., Results: Of 2251 patients prescreened between 2012 and 2016, 459 agreed to participate in PREFERE. Due to this poor accrual, the trial was stopped. In 345 patients reference pathology confirmed inclusion criteria. Sixty-nine men were assigned to RP, 53 to EBRT, 93 to PSI, and 130 to AS. Forty patients changed treatment shortly after randomization, 21 to AS. Forty-eight AS patients with follow-up received radical treatment. Median follow-up was 19 months. Five patients died, none due to PCa; 8 had biochemical progression after radical therapy. Treatment-related acute grade 3 toxicity was reported in 3 RP patients and 2 PSI patients., Conclusions: In this prematurely closed trial, we observed an unexpected high rate of termination of AS and an increased toxicity related to PSI. Patients hesitated to be randomized in a multi-arm trial. The optimal treatment of low and early-intermediate risk PCa remains unclear.

Background: In prostate cancer (PCa) recurring after radical prostatectomy (RP), salvage radiotherapy (SRT) is recommended to be given at PSA <0.5 ng/ml. It has been speculated, that the advantage from early SRT is mainly caused by lead-time bias: Calculating from time of SRT, earlier treatment would per-se result in longer time to event/censoring compared with later treatment, but not extend the interval from RP to post-SRT failure., Methods: In 603 consecutive PCa patients receiving SRT between 1997 and 2017, we compared outcomes, calculating from time of irradiation vs. time of surgery., Results: In multivariable analysis, tumor stage pT3-4, pathological Gleason score GS ≤6 vs. GS 7 vs. GS ≥8, post-RP PSA persistence (nadir ≥0.1 ng/ml), and the pre-SRT PSA (continuous or with cutoff 0.4 ng/ml) were significant risk-factors for biochemical progression (BCR) and progression-free survival (PFS) post-SRT and post-RP. A pre-SRT PSA <0.4 ng/ml was a significant discriminator for Kaplan-Meier rates of BCR and PFS. The Cox model for overall survival (OS) included age at RP (continuous), pT2 vs. pT3-4, and pre-SRT PSA (continuous) as significant predictors. However, no significant cutoff for the pre-SRT PSA could be identified to differentiate Kaplan-Meier estimates of OS, possibly because there were too few events, as 88% of the patients were still alive at last follow-up., Conclusions: The pre-SRT PSA has a significant impact on BCR, PFS and potentially on OS, calculating either from RP or from SRT to event/censoring, respectively. This contradicts the hypothesis of lead-time bias falsifying the advantage from early SRT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: 68 Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an individualized radiotherapy concept. However, subtle findings especially concerning small local recurrences can still be challenging to interpret and are prone to variability between different readers. Thus, we analyzed interobserver variability, detection rate, and lesion patterns systematically in a homogeneous patient population with low-level biochemical recurrence., Methods: We analyzed 68 Ga-PSMA-11-PET/CTs in 116 patients with status post-prostatectomy and PSA levels up to 0.6 ng/ml. None of them received ADT or radiotherapy beforehand. Images were interpreted and blinded by two nuclear medicine physicians (R1 and R2). Findings were rated using a 5-point scale concerning local recurrence, lymph nodes, bone lesions, and other findings (1: definitely benign, 2: probably benign, 3: equivocal, 4: probably malignant, 5: definitely malignant). In findings with substantial discrepancies of 2 or more categories and/or potentially leading to differences in further patient management, a consensus reading was done with a third reader (R3). Interobserver agreement was measured by Cohens Kappa analysis after sub-categorizing our classification system to benign (1 + 2), equivocal (3), and malignant (4 + 5). Time course of PSA levels after salvage treatment of patients rated as positive (4 + 5) was analyzed., Results: The overall detection rate (categories 4 and 5) was 50% (R1/R2, 49%/51%) and in the PSA subgroups 0-0.2 ng/ml, 0.21-0.3 ng/ml, and 0.31-0.6 ng/ml 24%/27%, 57%/57%, and 65%/68%, respectively. Local recurrence was the most common lesion manifestation followed by lymphatic and bone metastases. The overall agreement in the Cohens Kappa analysis was 0.74 between R1 and R2. For local, lymphatic, and bone sites, the agreement was 0.76, 0.73, and 0.58, respectively. PSA levels of PSMA PET/CT-positive patients after salvage treatment decreased in 75% (27/36) and increased in 25% (9/36). A decrease of PSA, although more frequent in patients with imaging suggesting only local tumor recurrence (86%, 18/21), was also observed in 67% (10/15) of patients with findings of metastatic disease., Conclusions: In a highly homogeneous group of prostate cancer patients with early-stage biochemical recurrence after radical prostatectomy, we could show that 68 Ga-PSMA-11-PET/CT has a good detection rate of 50% which is in accordance with literature, with clinically relevant findings even in patients with PSA < 0.21 ng/ml. The interobserver variability is low, particularly concerning assessment of local recurrences and lymph nodes. Therefore, PSMA-PET/CT is a robust diagnostic modality in this patient group for therapy planning.

Because cold atmospheric pressure plasma (CAPP)-based technologies are very useful tools in nanomaterials synthesis, in this work we have connected two unique in their classes approaches-a CAPP-based protocol and a green synthesis method in order to obtain stable-in-time gold nanoparticles (AuNPs). To do so, we have used an aqueous Gingko biloba leave extract and an aqueous Panax ginseng root extract (untreated or treated by CAPP) to produce AuNPs, suitable for catalytical uses. Firstly, we have adjusted the optical properties of resulted AuNPs, applying UV/Vis absorption spectrophotometry (UV/Vis). To reveal the morphology of Au nanostructures, transmission electron microscopy (TEM) in addition to energy dispersive X-ray scattering (EDX) and selected area X-ray diffraction (SAED) was utilized. Moreover, optical emission spectrometry (OES) in addition to a colorimetric method was used to identify and determine the concentration of selected RONS occurring at the liquid-CAPP interface. Additionally, attenuated total reflectance Fourier transform-infrared spectroscopy (ATR FT-IR) was applied to reveal the active compounds, which might be responsible for the AuNPs surface functionalization and stabilization. Within the performed research it was found that the smallest in size AuNPs were synthesized using the aqueous P. ginseng root extract, which was activated by direct current atmospheric pressure glow discharge (dc-APGD), generated in contact with a flowing liquid cathode (FLC). On the contrary, taking into account the aqueous G. biloba leave extract, the smallest in size AuNPs were synthesized when the untreated by CAPP aqueous G. biloba leave extract was involved in the Au nanostructures synthesis. For catalytical studies we have chosen AuNPs produced using the aqueous P. ginseng root extract activated by FLC-dc-APGD as well as AuNPs synthesized using the aqueous G. biloba leave extract also activated by FLC-dc-APGD. Those NPs were successfully used as homogenous catalysts for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP).

Objective: To test whether salvage radiotherapy (SRT) in patients with lymph node negative (N0) prostate cancer is equally effective with persistent prostate-specific antigen (PSA) and PSA rising from the undetectable range (<0.1 ng/mL) after radical prostatectomy (RP)., Patients and Methods: We assessed post-SRT PSA progression-free survival (PFS) in 555 patients with prostate cancer. The entire cohort was compared with a risk-adjusted subgroup of 112 patient pairs with matching pre-RP PSA level (±10 ng/mL), Gleason score (≤6 vs 7 vs ≥8), and pre-SRT PSA level (±0.5 ng/mL)., Results: The median follow-up was 6.1 years. After RP, PSA was undetectable in 422 and persistent in 133 patients. PSA persistence and a pre-SRT PSA level of ≥0.5 ng/mL reduced Kaplan-Meier rates of PFS significantly. In multivariate analysis of the entire cohort and after risk adjustment, the pre-SRT PSA level but not post-RP PSA persistence was a significant parameter. In the matched cohort's subgroup with early SRT at a PSA level of <0.5 ng/mL, a trend towards a worse outcome with post-RP PSA persistence was observed. Delayed SRT with a PSA level ≥0.5 ng/mL led to a PFS of <30%, irrespective of the post-RP PSA level., Conclusion: In patients with N0 prostate cancer with post-RP PSA persistence, early SRT at a PSA level <0.5 ng/mL seems to be less effective than in recurrent patients with post-RP undetectable PSA. They might benefit from intensified therapy, but larger case numbers are required to substantiate this conclusion. In patients with a PSA level ≥0.5 ng/mL and higher-risk features associated with post-RP PSA persistence, SRT alone is unlikely to provide long-term freedom from further progression., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial., Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics., Design, Setting, and Participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician., Outcome Measurements and Statistical Analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2)., Results and Limitations: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration., Conclusions: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT., Patient Summary: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT., (Copyright © 2019 European Association of Urology. All rights reserved.)

Background: For patients with recurrent prostate cancer after radical prostatectomy (RP), salvage radiotherapy (SRT) offers a second chance of cure. European guidelines (EAU) recommend SRT at a PSA < 0.5 ng/ml. We analyze the efficacy of SRT given according to this recommendation and investigate the predictive power of the post-SRT PSA nadir., Methods: Between 1998 and 2013, 301 patients of two university hospitals received SRT at a PSA < 0.5 ng/ml (median 0.192 ng/ml, IQR 0.110-0.300). Patients, who previously received androgen deprivation therapy, were excluded. All patients had 3D-conformal RT or intensity-modulated radiotherapy (IMRT, n = 59) (median 66.6 Gy). The median follow-up was 5.9 years. Progression and overall survival were the endpoints., Results: After SRT, 252 patients re-achieved an undetectable PSA. In univariate analysis, pre-RP PSA ≥ 10 ng/ml, pT3-4, Gleason score (GS) 7-10 or 8-10, negative surgical margins, post-RP PSA ≥ 0.1 ng/ml, pre-SRT PSA ≥ 0.2 ng/ml and post-SRT PSA nadir ≥ 0.1 ng/ml correlated unfavorably with post-SRT progression. In a multivariable Cox model, pT3-4, GS 7-10, negative margins and a pre-SRT PSA ≥ 0.2 ng/ml were significant risk factors. If the post-SRT PSA was added to the analysis, it dominated the outcome (HR = 9.00). Of the patients with a pre-SRT PSA < 0.2 ng/ml, only 9% failed re-achieving an undetectable PSA. Overall survival in these patients was 98% after 5.9 years compared to 91% in patients with higher pre-SRT PSA (Logrank p = 0.004)., Conclusions: SRT at a PSA < 0.2 ng/ml correlates significantly with achieving a post-SRT undetectable PSA (<0.1 ng/ml) and subsequently with improved freedom from progression. Given these overall favorable outcomes, whether additional androgen deprivation therapy is required for these men requires further study.

Hypothesis: A new, facile in-situ method for synthesis of polymeric nanocomposites (NCs) with nanoparticles (NPs) of Au, Pt and Pd is proposed. The method involves reduction-coupled sorption of Au(III), Pt(VI), and Pd(II), which avoids diffusion limitations, allowing the precipitation and stabilization of the NPs directly in the polymeric matrix., Experiments: The obtained nanomaterials were characterized by transmission electron microscopy (TEM), and Fourier-transformation infrared spectroscopy (FT-IR). NPs loaded into polymers were also investigated using X-ray diffraction (XRD)., Findings: Based on the results, it was concluded that the amino functionalities simultaneously reduced noble metals ions and capped the NPs. The average diameter of the obtained AuNPs ranged from 25 to 109 nm, while reduction-coupled sorption was carried out in 1 and 3 mol L -1 HCl solutions, respectively. Applying a 0.1 mol L -1 HCl solution containing Au(III), Pd(II) and Pt(VI), a NC with AuNPs and cubic-like PdNPs was fabricated, while using a solution of the same composition, but in 3 mol L -1 HCl, resulted in formation of a NC with flower-like PtNPs. Ultimately, the selected NC based on a resin with functionalities derived from 1-(2-aminoethyl)piperazine and with bi-metallic active sites, i.e. AuNPs and PdNPs, revealed catalytic activity in the reduction of 4-nitrophenol., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Size-controlled gold nanoparticles (AuNPs) were synthesised with solutions of three types of Polish honeys (lime, multiflower, honeydew) and used in microwave-induced hyperthermia cancer treatment. Optical and structural properties of nanostructures were optimized in reference to measurements made by using UV/Vis absorption spectrophotometry (UV/Vis), transmission electron microscopy (TEM) supported by energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and attenuated total reflectance Fourier transformation infrared spectroscopy (ATR FT-IR). In addition, concentrations of reducing sugars and polyphenols of honeys applied were determined to reveal the role of these chemical compounds in green synthesis of AuNPs. It was found that the smallest AuNPs (20.6 ± 23.3 nm) were produced using a 20% ( w / v ) multiflower aqueous honey solution and 25 mg·L -1 of Au(III) ions. These AuNPs were then employed in microwave-induced hyperthermia in a system simulating metastatic tissues. This research illustrated that AuNPs, as produced with the aid of a multiflower honey solution, could be suitably used for microwave-induced heating of cancer. A fluid containing resultant Au nanostructures, as compared to water, revealed facilitated heating and the ability to maintain a temperature of 45 °C required for hyperthermia treatment.

Poly(vinylpyrrolidone)-stabilized Pt nanoparticles (PVP-PtNPs) were produced in a continuous-flow reaction-discharge system by application of direct current atmospheric pressure glow discharge (dc-APGD) operated between the surface of a flowing liquid anode (FLA) and a pin-type tungsten cathode. Synthesized PVP-PtNPs exhibited absorption across the entire UV/Vis region. The morphology and elemental composition of PVP-PtNPs were determined with transmission electron microscopy (TEM) and energy dispersive X-ray scattering (EDX), respectively. As assessed by TEM, PVP-PtNPs were approximately spherical in shape, with an average size of 2.9 ± 0.6 nm. EDX proved the presence of Pt, C, and O. Dynamic light scattering (DLS) and attenuated total reflectance Fourier transform-infrared spectroscopy (ATR FT-IR) confirmed PtNPs functionalization with PVP. As determined by DLS, the average size of PtNPs stabilized by PVP was 111.4 ± 22.6 nm. A fluid containing resultant PVP-PtNPs was used as a heat conductive layer for a spiral radiator managing heat generated by a simulated internal combustion chamber. As compared to water, the use of PVP-PtNPs enhanced efficiency of the system, increasing the rate of heat transfer by 80% and 30% during heating and cooling, respectively.

Up to 50% of patients recur after salvage radiation therapy (sRT) for prostate-specific antigen (PSA) rise following radical prostatectomy (RP). Notably, the importance of lymph node dissection (LND) at the time of RP with regard to recurrence risk following sRT has not been previously determined. Therefore, we evaluated the association between nodal yield at RP and recurrence after sRT. We performed a multi-institutional review of men with a rising PSA after RP treated with sRT. Clinicopathologic variables were abstracted, and the associations between lymph node yield and biochemical (BCR) as well as clinical recurrence (CR) after sRT were assessed using multivariable Cox proportional hazards regression models. In total, 728 patients were identified; of these, 221 and 116 were diagnosed with BCR and CR, respectively, during a median follow-up of 8.4 (interquartile range: 4.2-11.2) yr. On multivariable analysis, the risk of BCR after sRT was inversely associated with the number of nodes resected at RP (hazards ratio [HR]: 0.98; 95% confidence interval [CI]: 0.96-0.99; p=0.049). Increased extent of dissection was also independently associated with a decreased risk of CR after sRT (HR: 0.97; 95%CI: 0.94-0.99; p=0.042). These data support the importance of an extensive LND at surgery and may be used in prognosis assessment when sRT is being considered., Patient Summary: We found that patients who had increased number of lymph nodes resected at surgery had improved outcomes after the receipt of salvage radiation therapy. These findings support the use of the extended lymph node dissection at initial surgery and should serve to improve counseling among patients who require salvage radiation therapy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

A new method for the production of nanocomposites, composed of gold nanoparticles (AuNPs) and (vinylbenzyl)trimethylammonium chloride- co - N , N -methylene bisacrylamide (VBTAC- co -MBA) hydrogel, is described. Raw-AuNPs of defined optical and granulometric properties were synthesized using direct current atmospheric pressure glow discharge (dc-APGD) generated in contact with a solution of HAuCl₄. Different approaches to the polymerization-driven synthesis of Au/VBTAC- co -MBA nanocomposites were tested. It was established that homogenous dispersion of AuNPs in this new nanomaterial with was achieved in the presence of NaOH in the reaction mixture. The new nanocomposite was found to have excellent heat-transfer properties., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results.

Background: For patients with recurrent prostate cancer after radical prostatectomy (RP), salvage radiotherapy (SRT) is a second chance of cure. However, depending on risk factors, 40-70% of the patients experience further progression. With a focus on the pre- and post-SRT serum level of the prostate-specific antigen (PSA), we assessed the determinants of the long-term outcome after SRT., Patient and Methods: Between 1997 and 2011, 464 patients received 3D-conformal SRT with median 66.6 Gy. The median PSA level before SRT was 0.31 ng/ml. In our retrospective analysis, post-SRT progression was defined as either a rising PSA >0.2 ng/ml above the nadir, or the application of anti-androgens or clinical recurrence. A PSA <0.1 ng/ml was termed undetectable. We analyzed the data with the Kaplan-Meier method (Logrank test) and multivariable Cox regression., Results: The median follow-up was 5.9 years. Overall, 178 patients had recurrence, 13 developed distant metastases and 30 died. Univariate, a pre-RP PSA <10 ng/ml, pathological stage pT <3, Gleason score <8, positive surgical margins, a pre-SRT PSA <0.2 ng/ml and a post-SRT PSA nadir <0.1 ng/ml correlated with fewer and later second recurrences. In a multivariable Cox model, pT, Gleason score, margin status and pre-SRT PSA were significant covariates of progression. If the post-SRT PSA response was included in the regression analysis, then a nadir ≥0.1 ng/ml was the strongest risk factor. Initiating SRT at a PSA <0.2 ng/ml correlated with a post-SRT PSA <0.1 ng/ml. Men who achieved an undetectable post-SRT PSA nadir also had lower rates of metastases and a better overall survival. However, there were too few events for Cox regression analysis of these two endpoints., Conclusions: Early SRT at a PSA <0.2 ng/ml correlates with re-achieving an undetectable PSA, which predicts improved freedom from progression and metastases and better overall survival.

Background: The optimal prostate-specific antigen (PSA) level after radical prostatectomy (RP) for defining biochemical recurrence and initiating salvage radiation therapy (SRT) is still debatable. Whereas adjuvant or extremely early SRT irrespective of PSA progression might be overtreatment for some patients, SRT at PSA >0.2 ng/ml might be undertreatment for others. The current study addresses the optimal timing of radiation therapy after RP., Patients and Methods: Cohort 1 comprised 293 men with PSA 0.1-0.19 ng/ml after RP. Cohort 2 comprised 198 men with SRT. PSA progression and metastases were assessed in cohort 1. In cohort 2, we compared freedom from progression according to pre-SRT PSA (0.03-0.19 vs. 0.2-0.499 ng/ml). Multivariable Cox regression analyses predicted progression after SRT., Results: In cohort 1, 281 (95.9%) men had further PSA progression ≥0.2 ng/ml and 27 (9.2%) men developed metastases within a median follow-up of 74.3 months. In cohort 2, we recorded improved freedom from progression according to lower pre-SRT PSA (0.03-0.19 vs. 0.2-0.499 ng/ml: 69 vs. 53%; log-rank p = 0.051). Patients with higher pre-SRT PSA ≥0.2 ng/ml were at a higher risk of progression after SRT (hazard ratio: 1.8; p < 0.05)., Conclusion: The vast majority of patients with PSA ≥0.1 ng/ml after RP will progress to PSA ≥0.2 ng/ml. Additionally, early administration of SRT at post-RP PSA level <0.2 ng/ml might improve freedom from progression. Consequently, we suggest a PSA threshold of 0.1 ng/ml to define biochemical recurrence after RP.

Purpose: Improved survival after locoregional breast cancer has increased the concern about late adverse effects after therapy. In particular, radiotherapy was identified as a risk factor for major cardiac events in women treated until the 1990s. While modern radiotherapy with computerized planning based on 3D-imaging can help spare organs at risk, heart exposure may remain substantial. In a retrospective cohort study of women treated for locoregional breast cancer, we investigated whether current radiotherapy is associated with an elevated long-term cardiac morbidity risk., Methods: The study included 11,982 women diagnosed with breast cancer in Germany in 1998-2008. After an individual mortality follow-up, 9338 questionnaires on cardiac events before or after therapy and on associated risk factors were sent out in 2014. Based on 4434 questionnaires from women with radiotherapy, we used Cox regression to analyze the association between self-reported cardiac morbidity and breast cancer laterality as a surrogate measure of radiation exposure., Results: After a median follow-up of 8.3 years, there was no significant association of tumor laterality with cardiac morbidity in irradiated patients (458 events, hazard ratio for left-sided vs. right-sided tumors 1.07, 95% CI 0.89-1.29). Significant risk factors for any cardiac event included age at diagnosis, chemotherapy, hypertension, hypercholesteremia, and chronic kidney disease., Conclusions: For contemporary radiotherapy, we found no evidence for a significantly elevated cardiac morbidity risk in left-sided versus right-sided breast cancer. Possible reasons for failing to confirm earlier reports on increased risk include shorter follow-up, application of newer radiotherapy techniques, and improved health monitoring.

Background: Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT)., Objective: To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT., Design, Setting, and Participants: Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml., Intervention: We compared aRT versus observation followed by esRT., Outcome Measurements and Statistical Analysis: The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis)., Results and Limitations: Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population., Conclusions: At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT., Patient Summary: At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Cardiac late effects are a major health concern for long-term survivors after radiotherapy for breast cancer. Large cohort studies to better understand the exact dose-response relationship require individual estimates of radiation dose to the heart. To predict individual cardiac dose from information that is typically available for all members of a retrospective epidemiological cohort study, 774 female breast cancer patients treated with megavoltage tangential field radiotherapy in 1998-2008 were examined. All dose distributions were calculated using Eclipse with the anisotropic analytical algorithm (AAA) for photon fields and the electron Monte Carlo algorithm for electron boost fields. Based on individual dose volume histograms, the authors calculated absorbed dose in the complete heart as well as in six functional substructures. Statistical models were developed to predict absorbed dose using only covariate information from patients' clinical records on tumor location, patient anatomy and radiotherapy prescription. The out-of-sample prediction error for mean heart dose was 54% (coefficient of variation). The prediction error in functional substructures ranged from 49-68% for mean dose and from 52-86% for extreme dose. The authors conclude that based on a patient sample with exact heart dosimetry, it is possible to use clinical information alone to predict absorbed heart dose in the remaining cohort with a quantified error suitable for dose-response analyses of cardiac late effects.

Purpose: In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. In a retrospective cohort study, we investigated the long-term cardiac mortality risk of breast cancer survivors treated with modern RT in Germany., Methods: A total of 11,982 women were included who were treated for breast cancer between 1998 and 2008. A systematic mortality follow-up was conducted until December 2012. The effect of breast cancer laterality on cardiac mortality and on overall mortality was investigated as a surrogate measure of exposure. Using Cox regression, we analyzed survival time as the primary outcome measure, taking potential confounding factors into account., Results: We found no evidence for an effect of tumor laterality on mortality in irradiated patients (N = 9058). For cardiac mortality, the hazard ratio was 0.94 (95% CI 0.64-1.38) for left-sided versus right-sided tumors. For all causes of death, the hazard ratio was 0.95 (95% CI 0.85-1.05). A diagnosis of cardiac illness prior to breast cancer treatment increased both cardiac mortality risk and overall mortality risk., Conclusions: Contemporary RT seems not to be associated with an increased risk of cardiac mortality or overall mortality for left-sided breast cancer relative to right-sided RT. However, an extended follow-up period and exact dosimetry might be necessary to confirm this observation.

Background and Purpose: To analyze the distribution of individually-determined radiation dose to the heart and its functional sub-structures after radiotherapy in breast cancer patients treated in Germany during 1998-2008., Material and Methods: We obtained electronic treatment planning records for 769 female breast cancer patients treated with megavoltage tangential field radiotherapy. All dose distributions were re-calculated using Eclipse with the anisotropic analytical algorithm (AAA) for photon fields, and the electron Monte Carlo algorithm for electron boost fields. Based on individual dose volume histograms for the complete heart and several functional sub-structures, we estimated various dose measures in patient groups., Results: Mean heart dose spanned a range of 0.9-19.1Gy for left-sided radiotherapy and 0.3-11.6Gy for right-sided radiotherapy. Average (median) mean heart dose was 4.6Gy (3.7Gy) for left-sided radiotherapy, and 1.7Gy (1.4Gy) for right-sided RT. With left-sided radiotherapy, 66% of the patients had 2cm(3) of the complete heart exposed to at least 40Gy. Younger age, higher body mass index, tumor location in a medial quadrant, and presence of a parasternal field were also associated with higher heart dose., Conclusion: Tumor location and treatment choices influence cardiac dose with complex interactions. There is considerable variability in heart dose, with dose metrics of different cardiac sub-structures showing different patterns in their dependency on external influences. Dose-response analysis of late cardiac effects after radiotherapy requires detailed individual dosimetry., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options., Objectives: This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy., Results: The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery., Conclusion: There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

Background and Purpose: In a retrospective analysis, we examined factors influencing the outcome of prostate cancer (PCa) patients receiving salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy (RP)., Material and Methods: 306 patients received 3D-conformal SRT at a median pre-SRT PSA of 0.298 ng/ml. Post-SRT progression was defined as PSA ⩾0.2 ng/ml above nadir and rising further, or hormone treatment, or clinical recurrence. Data were analyzed with the Kaplan-Meier method and multivariable Cox regression., Results: Application of SRT at a PSA <0.2 ng/ml correlated significantly with achieving a post-SRT PSA nadir <0.1 ng/ml and with improved freedom from progression (median follow-up 7.2 years). The post-SRT nadir <0.1 ng/ml correlated significantly with less recurrences and with better overall survival. In multivariable Cox analysis restricted to pre-SRT parameters, a pre-SRT PSA ⩾0.2 ng/ml had the strongest impact (hazard ratio 2.4) on progression. If the post-SRT PSA nadir was included in the model, then failing the nadir was the most important risk factor (hazard ratio 8.1)., Conclusions: Early SRT at a PSA <0.2 ng/ml is a favorable treatment option for post-RP biochemical recurrence. It correlated with a post-SRT PSA-nadir <0.1 ng/ml which was associated with improved freedom from progression and overall survival., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C)., Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method., Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression., Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: After radical prostatectomy (RP) the pre-RP PSA value, Gleason Score, pT-stage, state of seminal vesicles and state of surgical margins are key indicators for the risk of biochemical or clinical recurrence. Depending on the tumour stage, 50-70% of the high-risk patients suffer biochemical progression. The treatment options in these circumstances are adjuvant radiotherapy (ART, for an undetectable PSA) or salvage radiotherapy (SRT, for persisting PSA or PSA re-rising above detection limits). Data from ongoing randomised trials that compare ART and SRT directly have not yet been published., Method: A search in PubMed for ART and SRT after RP for prostate cancer was undertaken to compare the results of the 2 treatment approaches., Results: 3 randomised phase-III studies have shown a nearly 20% advantage in terms of biochemical progression after ART (60-64 Gy) compared with a wait-and-see strategy. The largest effect was seen in patients with pT3 prostate cancer with positive surgical margins. According to the German S3-guidelines, SRT with at least 66 Gy can be offered to patients with a post-RP persisting PSA or a PSA re-rising above detection limits. 30-70% of these patients re-achieve an undetectable PSA. Thus, there is a second option for curative treatment. Due to the lower total dose, ART seems to be connected with fewer late complications than SRT. SRT, on the other hand, reduces the risk of potential interactions with post-RP complications and of overtreatment. There is a controversial discussion about the inclusion of the pelvic lymph nodes in the treatment volume, the additional application of anti-androgens and the total dose of both ART and SRT., Conclusions: The comparison of SRT after PSA progression with ART at a PSA below the detection limits cannot yet be judged conclusively. The indication for ART depends on the associated risk factors. However, regarding freedom from biochemical progression, it is backed up by high level evidence. If SRT is applied for biochemical progression, then it should be initiated early, i. e., at the lowest PSA possible., (© Georg Thieme Verlag KG Stuttgart · New York.)

In pursuit for new reactive materials designed for synthesis of functional resins, the novel core-shell type polymeric supports with accessible chloromethyl groups were synthesized. The commercial Amberlite XAD-4 adsorbent was impregnated with different mixtures of vinylbenzylchloride and divinylbenzene, that were further polymerized in the structure of the polymer carrier. The syntheses have been evaluated by recording FT-IR spectra, capturing SEM micrographs as well as analyzing the sorption and desorption of nitrogen at 77 K. The amount of the introduced functionalities has been estimated by chlorine content determination. Based on the obtained results, the reactive chloromethyl groups were successfully introduced into XAD-4 structure. Captured SEM micrographs revealed that VBC/DVB copolymer has covered initial polymeric matrix of XAD-4 adsorbent. Based on the results we have determined conditions of the synthesis that allow us to receive that effect.

Background: Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Three prospectively randomized trials demonstrated an advantage for adjuvant radiotherapy (ART) compared with a wait-and-see (WS) policy., Objective: To determine the efficiency of ART after a 10-yr follow-up in the ARO 96-02 study., Design, Setting, and Participants: After RP, 388 patients with pT3 pN0 prostate cancer (PCa) were randomized to WS or three-dimensional conformal ART with 60 Gy. The present analysis focuses on intent-to-treat patients who achieved an undetectable prostate-specific antigen after RP (ITT2 population)--that is, 159 WS plus 148 ART men., Outcome Measurements and Statistical Analysis: The primary end point of the study was progression-free survival (PFS) (events: biochemical recurrence, clinical recurrence, or death). Outcomes were compared by log-rank test. Cox regression analysis served to identify variables influencing the course of disease., Results and Limitations: The median follow-up was 111 mo for ART and 113 mo for WS. At 10 yr, PFS was 56% for ART and 35% for WS (p<0.0001). In pT3b and R1 patients, the rates for WS even dropped to 28% and 27%, respectively. Of all 307 ITT2 patients, 15 died from PCa, and 28 died for other or unknown reasons. Neither metastasis-free survival nor overall survival was significantly improved by ART. However, the study was underpowered for these end points. The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity. No grade 4 events occurred., Conclusions: Compared with WS, ART reduced the risk of (biochemical) progression with a hazard ratio of 0.51 in pT3 PCa. With only one grade 3 case of late toxicity, ART was safe., Patient Summary: Precautionary radiotherapy counteracts relapse after surgery for prostate cancer with specific risk factors., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The increment model has previously been used to describe the growth of plants in general. Here, we examine how the same logistics enables the development of different superstructures., Methods: Data from the literature are analyzed with the increment model. Increments are growth-invariant molecular clusters, treated as heuristic particles. This approach formulates the law of mass action for multi-component systems, describing the general properties of superstructures which are optimized via relaxation processes., Results: The daily growth patterns of hypocotyls can be reproduced implying predetermined growth invariant model parameters. In various species, the coordinated formation and death of fine roots are modeled successfully. Their biphasic annual growth follows distinct morphological programs but both use the same logistics. In tropical forests, distributions of the diameter in breast height of trees of different species adhere to the same pattern. Beyond structural fluctuations, competition and cooperation within and between the species may drive optimization., Conclusion: All superstructures of plants examined so far could be reproduced with our approach. With genetically encoded growth-invariant model parameters (interaction with the environment included) perfect morphological development runs embedded in the uniform logistics of the increment model., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose of Review: As the appropriate management of patients after prostatectomy is still controversial, the two major approaches, adjuvant radiotherapy (ART) vs. prostate-specific antigen-based surveillance and - upon biochemical recurrence - salvage radiotherapy (SRT) are discussed., Recent Findings: Three prospectively randomized clinical trials into ART with 5-12 years median follow-up and overall 1800 patients show a significant gain in freedom from biochemical recurrence after prostatectomy and adjuvant irradiation (hazard ratio ∼0.5). Only one study reported an improved overall survival (hazard ratio 0.72). Patients with pT3 and positive surgical margins are the most likely to profit from ART. Retrospective analyses of adjuvant vs. SRT suggest a similar oncological outcome if SRT is given early after recurrence, that is at a prostate-specific antigen of 0.5 ng/ml or less. Also, toxicity is similar with the two strategies. With positive lymph nodes, hormone therapy and optionally extended field radiotherapy can be recommended., Summary: The alternative ART or surveillance along with SRT after prostatectomy cannot yet be decided on conclusively. Compliance, physical side-effects, psychological aspects and life expectancy should be taken into account when discussing treatment options. Ongoing and planned trials will hopefully identify subgroups that profit most from one or the other strategy.

The choice of treatment options for prostate cancer patients who have undergone radical prostatectomy depends on their risk profile, which is determined by the tumor node metastasis (TNM) status, histopathologic findings, and the pre- and post-radical prostatectomy PSA characteristics. The results of large clinical studies with a 10-year follow-up or more are the backbone of predictive models for risk estimates that incorporate these criteria and also for guideline recommendations. For low-to-intermediate-risk prostate cancer patients and older patients, observation with--in case of biochemical recurrence--early salvage radiotherapy can be advised after R0 resection, thus, avoiding overtreatment. After R1 resection, adjuvant radiotherapy should be considered. Patients with two or more positive lymph nodes and/or with distant metastasis may benefit from adjuvant hormone deprivation therapy. Beyond this rough outline, detailed analysis of subgroups is still required (and ongoing) to enable individually optimized treatment.

Purpose: Salvage radiotherapy (SRT) is applied routinely in patients with a biochemical relapse after radical prostatectomy (RP). Although the detection threshold for relapse after RP has steadily been lowered, only about 30% of the SRT patients achieve a durable response. We have previously shown the association between a PSA decrease below detectable levels after SRT and biochemical progression-free survival (BPFS). After recalculating our data according to a more recent definition of biochemical failure after SRT, we now show the significance of the post-RP PSA nadir., Materials and Methods: Among 159 prostate cancer patients without hormonal treatment after RP, SRT was given to 72 patients with persistently detectable PSA after RP and to 87 whose PSA increased out of an undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to the prostate bed., Results: The overall median follow-up time was 41.7 months. The probability for BPFS after this period was 52.8% in 72 patients with persistently detectable PSA after RP and 65.4% in 87 patients who had a post-RP PSA nadir below detection limit. Univariate and multivariate analyses showed no significant difference in BPFS of both patient groups (p > 0.05)., Conclusion: Our findings suggest that SRT is a viable treatment option for patients with persistently detectable PSA, giving similar results as in patients whose PSA increases out of an undetectable range after RP.

Background: Biochemical recurrence after radical prostatectomy (RP) is associated with risk indicators, including Gleason score, preoperative PSA level, tumor stage, seminal vesicle invasion, and positive surgical margins. The 5-year biochemical progression rate among predisposed patients is as high as 50-70%. Post-RP treatment options include adjuvant radiotherapy (ART, for men with undetectable PSA) or salvage radiotherapy (SRT, for PSA persisting or re-rising above detection threshold). Presently, there are no published randomized trials evaluating ART vs. SRT directly., Methods: Published data on ART and SRT were reviewed to allow a comparison of the two treatment approaches., Results: Three randomized phase III trials demonstrated an almost 20% absolute benefit for biochemical progression-free survival after ART (60-64 Gy) compared to a "wait and see" policy. The greatest benefit was achieved in patients with positive margins and pT3 tumors. SRT can be offered to patients with elevated PSA after RP. In 30-70% of SRT patients, PSA will decrease to an undetectable level, thus giving a second curative chance. The rate of side effects for both treatments is comparably low. The role of irradiation of pelvic lymph nodes and the additional use of hormone therapy and radiation dose are discussed., Conclusion: It remains unclear whether early SRT initiated after PSA failure is equivalent to ART. Where SRT is indicated, it should be started as early as possible.

Background and Purpose: Today, there is growing concern about radiotherapy induced secondary malignancies. We analysed the incidence and dose dependence of second cancer., Material and Methods: The study includes 12,000 one-year survivors of radiotherapy, treated between 1981 and 2007. For risk estimates a public databank on cancer in Germany served as reference. Contralateral second breast cancer, second oesophageal and colorectal cancer were analysed with retrospective dosimetry. GI-tract data were used for risk modelling., Results: The incidence rate of second cancers (493 cases) was ~1% per year. Contralateral breast cancer was the most frequent entity (relative risk RR=2.8). The scatter-dose gradient (2-3 Gy) across the contralateral breast did not cause a detectable risk gradient. There was an increased risk for second head and neck cancer (RR=5.1) and for male oesophageal cancer (RR=5.8). For both entities, dose response modelling with case-control data predicted maximum curves with peak induction at 1-5 Gy and positive excess absolute risk values at high doses., Conclusions: A survey of second cancer after radiotherapy requires follow-up over decades. Preliminary dose response modelling albeit with low case numbers suggests an increased risk from multiportal techniques. To improve risk assessment, prospective out-of-field dosimetry and long-term multicentre data collection are recommended., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Salvage radiotherapy (SRT) is applied routinely in patients with biochemical relapse after radical prostatectomy (RP). However, only ∼30% of these patients achieve a durable response after 10 years. As a standard, 66 Gy are given, ideally with a PSA below 0.5 ng/ml. We tried to determine more precisely the optimal PSA for starting SRT., Material and Methods: In 301 prostate cancer patients without hormonal treatment, we analysed the impact on the biochemical response (bNED) to SRT of two pre-SRT PSA levels, namely below or above the median of 0.28 ng/ml., Results: The median follow-up time for the entire group was 30 months. In 151 patients, SRT commenced at a PSA ≤ 0.28 ng/ml, in 150 at > 0.28 ng/ml. Eighty-two patients (27%) developed biochemical progression during follow up. The calculated two-year bNED was 74% for the entire group, 78% versus 61% for a PSA ≤ or > 0.28 ng/ml, respectively. In multivariate analysis, pT(3b), resection status, pre-SRT PSA dichotomized at median, PSA post-SRT undetectable, and PSA doubling time were statistically significant independent predictors of progression after SRT., Conclusions: Our findings suggest that a PSA of ≤ 0.28 ng/ml improves bNED compared with a PSA before SRT of > 0.28 ng/ml., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The optimal dose for salvage radiotherapy (SRT) after radical prostatectomy (RP) is still not defined. It should be at least 66 Gy. In the present study, the suitability of PSA regression as a selection criterion for an SRT dose escalation to 70.2 Gy was examined., Patients and Methods: Between 1997 and 2007, 301 prostate cancer patients received SRT after RP at the Charité - University Medicine Berlin, Campus Benjamin Franklin. None of the patients had antihormone therapy prior to SRT. A total of 234 patients received 66.6 Gy. From 2002 on, 67 patients with a PSA decrease during SRT were irradiated with 70.2 Gy. The influence of this selection and dose escalation on freedom from biochemical progression (bNED) was analyzed., Results: The median follow-up of the whole group was 30 months, the median pre-SRT PSA was 0.28 ng/ml. Of the patients, 27% (82/301) developed biochemical progression, 31% from the 66.6 Gy cohort (73/292) and 13% from the 70.2 Gy cohort (9/67) (p = 0.01). The calculated 2-years bNED was 74% for the whole group, 88% vs. 71% after 70.2 Gy and 66.6 Gy, respectively (p = 0.01). In a multivariate analysis, the total dose (p = 0.017), the re-achievement of an undetectable PSA after SRT (p = 0.005), and the infiltration of the seminal vesicles (p = 0.049) were independent parameters of bNED., Conclusion: Our analysis suggests that patient selection during SRT for a dose escalation to 70.2 Gy can improve the freedom from biochemical progression in patients with SRT after RP.

Vinylbenzyl chloride/divinylbenzene gel copolymer beads have been modified using piperidine, hexamethyleneimine, piperazine, 1-(2-aminoethyl)piperazine, and N-cyclohexyl-1,3-propanediamine. These resins were then tested for the sorption of noble metal ions, namely, Re(VII), Pd(II), Pt(IV), and Au(III), from a 0.1 M HCl solution. The effect of these resins on the sorption of other coexisting ions, such as Cu, Ni and Fe, was also studied. Of the resins tested, resin 4 [1-(2-aminoethyl)piperazine groups] showed the highest sorption capacity for Pt(IV) and Re(VII) from single and multicomponent solutions, with the sorption of Pt(IV) from the multicomponent solution (Re, Au, Pd, Pt, Cu, Ni Fe) in 0.1 M HCl reaching 68 mg Pt/g.

If growing cells in plants are considered to be composed of increments (ICs) an extended version of the law of mass action can be formulated. It evidences that growth of plants runs optimal if the reaction-entropy term (entropy times the absolute temperature) matches the contact energy of ICs. Since these energies are small, thermal molecular movements facilitate via relaxation the removal of structure disturbances. Stem diameter distributions exhibit extra fluctuations likely to be caused by permanent constraints. Since the signal-response system enables in principle perfect optimization only within finite-sized cell ensembles, plants comprising relatively large cell numbers form a network of size-limited subsystems. The maximal number of these constituents depends both on genetic and environmental factors. Accounting for logistical structure-dynamics interrelations, equations can be formulated to describe the bimodal growth curves of very different plants. The reproduction of the S-bended growth curves verifies that the relaxation modes with a broad structure-controlled distribution freeze successively until finally growth is fully blocked thus bringing about "continuous solidification".

Purpose: To characterize second tumors that developed in or near the high-dose areas of a previous radiotherapy, regarding their frequency, entities, latency, and dose dependence., Patients and Methods: 9,995/15,449 tumor patients of the Radiation Oncology Department in Ulm, Germany, treated between 1981 and 2003, survived at least 1 year after radiotherapy. By long-term follow-up and review of treatment documentation, 100 of them were identified who developed an independent second cancer in or near the irradiated first tumor site., Results: Major primary malignancies were breast cancer (27%), lymphoma (24%), and pelvic gynecologic tumors (17%). Main second tumors were carcinomas of the upper (18%) and lower (12%) gastrointestinal tract, head and neck tumors (10%), lymphoma (10%), breast cancer (9%), sarcoma (9%), and lung cancer (8%). Overall median second tumor latency was 7.4 years (1-42 years). For colorectal cancer it was 3.5 and for leukemia 4.3 years, but for sarcoma 11.7 and for breast cancer 17.1 years. The relatively frequent second tumors of the upper gastrointestinal tract were associated with median radiation doses of 24 Gy. By contrast, second colorectal cancer and sarcoma developed after median doses of 50 Gy., Conclusion: The 5- and 15-year probability to develop a histopathologically independent second tumor in or near the irradiated first tumor site, i.e., after intermediate or high radiation doses, was 0.5% and 2.2%, respectively. To identify potentially radiogenic second malignancies, a follow-up far beyond 5 years is mandatory. The incidence and potential dose-response relationship intermediate will be analyzed by a case-case and a case-control study of the Ulm data.

Background and Purpose: Radiation can induce multidrug resistance (MDR) and thus interfere with simultaneous or subsequent chemotherapy. In SW620 colon carcinoma cells, the interrelation of various biological endpoints of MDR was analyzed and the potential of fractionated irradiation and chemoselection to evoke MDR was compared., Material and Methods: To induce/select an MDR phenotype, SW620 were exposed to either 27 Gy in 1.8-Gy daily fractions or to 50% inhibiting concentrations of doxorubicin or cisplatin, given over 6-15 weeks. Expression of genes involved in MDR, including glutathione metabolism, was determined by semiquantitative RT-PCR (reverse transcription-polymerase chain reaction). Efflux was analyzed by flow cytometry after staining with rhodamine-123 or 5-chloromethyl fluorescein diacetate. Apoptosis was monitored after pulse exposure to doxorubicin or cisplatin. Colony-forming assays were performed under continuous drug exposure., Results: A pronounced gene induction was found in MRP2 after cisplatin selection and up to 3 weeks after radiation. LRP was activated only shortly after radiation. Radiation enhanced rhodamine-123 efflux to a similar extent as short-term chemoselection but not as much as long-term drug exposure. Drug-induced apoptosis was slightly delayed in preirradiated cells. Clonogenic growth in the progeny of irradiated cells was less sensitive to cisplatin but not to doxorubicin., Conclusion: Fractionated radiation can induce an MDR phenotype in SW620. However, long-term drug exposure establishes a more efficient selection. Various endpoints are not fully concordant regarding the extent of MDR. Posttranscriptional modifications, pleiotropic regulation, and alternative pathways may cause these discrepancies.