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Background: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H 2 O 2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations., Methods: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood., Results: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H 2 O 2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects., Conclusions: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells., (© 2024. The Author(s).)

Metal peroxide nanomaterials as efficient hydrogen peroxide (H 2 O 2 ) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H 2 O 2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO 2 /Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO 2 ) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO 2 /Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H 2 O 2 was released. Simultaneously, Pd NPs catalyze self-supplied H 2 O 2 to generate abundant hydroxyl radicals ( • OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant • OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO 2 /Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.

Early use of targeted radionuclide therapy (TRT) to eradicate disseminated tumor cells (DTCs) might offer cure. Selection of appropriate radionuclides is required. This work highlights the potential of 103 Pd (T 1/2 = 16.991 d) which decays to 103m Rh (T 1/2 = 56.12 min) then to stable 103 Rh with emission of Auger and conversion electrons. Methods: The Monte Carlo track structure code CELLDOSE was used to assess absorbed doses in single cells (14-μm diameter; 10-μm nucleus) and clusters of 19 cells. The radionuclide was distributed on the cell surface, within the cytoplasm, or in the nucleus. Absorbed doses from 103 Pd, 177 Lu and 161 Tb were compared after energy normalization. The impact of non-uniform cell targeting, and the potential benefit from dual-targeting was investigated. Additional results related to 103m Rh, if used directly, are provided. Results: In the single cell, and depending on radionuclide distribution, 103 Pd delivered 7- to 10-fold higher nuclear absorbed dose and 9- to 25-fold higher membrane dose than 177 Lu. In the 19-cell clusters, 103 Pd absorbed doses also largely exceeded 177 Lu. In both situations, 161 Tb stood in-between 103 Pd and 177 Lu. Non-uniform targeting, considering four unlabeled cells within the cluster, resulted in moderate-to-severe dose heterogeneity. For example, with intranuclear 103 Pd, unlabeled cells received only 14% of the expected nuclear dose. Targeting with two 103 Pd-labeled radiopharmaceuticals minimized dose heterogeneity. Conclusion: 103 Pd, a next-generation Auger emitter, can deliver substantially higher absorbed doses than 177 Lu to single tumor cells and cell clusters. This may open new horizons for the use of TRT in adjuvant or neoadjuvant settings, or for targeting minimal residual disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: To determine the incidence and type of strabismus in patients with uveal melanoma treated with plaque brachytherapy., Design: Multicenter, retrospective incidence estimation study., Methods: A total of 438 eyes of 438 patients with uveal melanoma treated with plaque brachytherapy between October 2011 and May 2021. Intervention was Iodine 125, and Palladium 103 plaque brachytherapy. The variables reviewed included incidence of nonresolving strabismus post-plaque brachytherapy, type of strabismus developed, extraocular muscles operated, and modality of treatment received., Results: A total of 438 patients underwent plaque brachytherapy treatment for uveal melanoma. Eleven patients developed strabismus post-plaque brachytherapy (2.5%, n = 11/438). Of these patients, 5 (1.1%, n = 5/438) developed strabismus immediately postoperation. Specifically, 2 patients (0.5%, n = 2/438) developed strabismus immediately postoperation due to slipped muscles, 2 patients (0.5%, n = 2/438) due to decompensated phorias, and 1 patient (0.5%, n = 1/438) due to a fibrotic muscle. Six patients (1.4%, n = 6/438) developed late-onset sensory strabismus. A total of 355 patients (81.1%, n = 355/438) had their extraocular muscles disinserted during surgery, with the lateral rectus being the most common, accounting for 45.4% (n = 161/355), followed by the superior rectus at 26.8% (n = 95/355). Strabismus surgery was the most common treatment modality, comprising 72.7% (n = 8/11) of patients., Conclusions: The incidence of strabismus after plaque brachytherapy treatment for uveal melanoma was low and primarily classified as late-onset sensory strabismus. Previous studies may underestimate the long-term incidence of strabismus after plaque brachytherapy by focusing primarily on strabismus present immediately postoperatively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Staphylococcus aureus leads to diverse infections, and their treatment relies on the use of antibiotics. Nevertheless, the rise of antibiotic resistance poses an escalating challenge and various mechanisms contribute to antibiotic resistance, including modifications to drug targets, enzymatic deactivation of drugs, and increased efflux of antibiotics. Hence, the quest for innovative antimicrobial solutions has intensified in the face of escalating antibiotic resistance and the looming threat of superbugs. The NorA protein of S. aureus , classified as an efflux pump within the major facilitator superfamily, when overexpressed, extrudes various substances, including fluoroquinolones (such as ciprofloxacin) and quaternary ammonium. Addressing this, the unexplored realm of inorganic and organometallic compounds in medicinal chemistry holds promise. Notably, the study focused on investigating two different series of palladium-based metal complexes consisting of QSL_P A and QSL_P B ligands to identify a potent NorA efflux pump inhibitor that can restore the susceptibility to fluoroquinolone antibiotics. QSL_Pd 5A was identified as a potent efflux pump inhibitor from the real-time efflux assay. QSL_Pd 5A also resensitized SA1199B to ciprofloxacin at a low concentration of 0.125 µg/mL without elucidating cytotoxicity on the NRK-62E cell line. The in vitro findings were substantiated by docking results, indicating favorable interactions between QSL_Pd 5A and the NorA efflux pump., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Shobana, Thahirunnisa, Sivaprakash, Amali, Solomon and Suresh.)

Objective: To investigate the potential of hybrid Pd/Fe-oxide magnetic nanoparticles designed for thermo-brachytherapy of breast cancer, considering their specific loss power ( SLP ) and clinical constraints in the applied magnetic field., Methods: Hybrid nanoparticles consisting of palladium-core and iron oxide shell of increasing thickness, were suspended in water and their SLPs were measured at varying magnetic fields (12-26 mT peak) and frequencies (50-730 kHz) with a commercial alternating magnetic field generator (magneTherm™ Digital, nanoTherics Ltd.)., Results: Validation of the heating device used in this study with commercial HyperMag-C nanoparticles showed a small deviation (±4%) over a period of 1 year, confirming the reliability of the method. The integration of dual thermometers, one in the center and one at the bottom of the sample vial, allowed monitoring of homogeneity of the sample suspensions. SLP s measurements on a series of nanoparticles of increasing sizes showed the highest heating for the diameter of 21 nm ( SLP  = 225 W/g) at the applied frequencies of 346 and 730 kHz. No heating was observed for the nanoparticles with the size <14 nm, confirming the importance of the size-parameter. The heating ability of the best performing Pd/Fe-oxide-21 was calculated to be sufficient to ablate tumors with a radius ±4 and 12 mm using 10 and 1 mg/mL nanoparticle concentration, respectively., Conclusions: Nanoparticles consisting of non-magnetic palladium-core and magnetic iron oxide shell are suitable for magnetic hyperthermia/thermal ablation under clinically safe conditions of 346 kHz and 19.1 mT, with minimal eddy current effects in combination with maximum SLP .

Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly involving the colon and rectum, which features recurrent mucosal inflammation. The excessive production of reactive oxygen species (ROS) is a trigger for pathological changes such as cell apoptosis and disordered immune microenvironments, which are crucial for the progression of UC and can be a promising therapeutic target. Nowadays, the development of targeted therapeutic strategies for UC is still in its infancy. Thus, developing effective therapies based on ROS scavenging and elucidating their molecular pathways are urgently needed. Herein, a biomimetic nanoformulation (Pd@M) with cubic palladium (Pd) as the core and macrophage-derived extracellular vesicles (MEVs) as the shell is synthesized for the treatment of UC. These Pd@M nanoformulations exhibit multienzyme-like activities for effective ROS scavenging, excellent targeting ability as well as good biocompatibility. It is verified that Pd@M can regulate the polarization state of macrophages by inhibiting glycolysis, and decrease neutrophil infiltration and recruitment. In this way, the colonic inflammatory and immune microenvironment is remodeled, and apoptosis is prevented, ultimately improving colonic mucosal barrier function and alleviating colitis in the mouse model. This finding provides a promising alternative option for the treatment of UC patients., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background and Purpose: Pd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer., Materials and Methods: We retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression., Results: Compared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971)., Conclusions: Pd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125., 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 © 2023. Published by Elsevier B.V.)

Introduction: Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7-20.2 per cent chance of receiving curative surgery after induction systemic chemotherapy. Intratumoral injection therapies have been studied as complementary treatment options for improved local tumour control. The aim of this systematic review was to provide an overview of intratumoral injection therapies, their safety, and oncological outcome in patients with locally advanced pancreatic cancer., Methods: A literature search was conducted in PubMed, Embase and the Cochrane Library for articles written in English up to 28 November 2022. All study designs involving at least five patients with locally advanced pancreatic cancer who were treated with an intratumoral injection therapy were included. Critical appraisal of the included studies was performed using the Newcastle-Ottawa scale., Results: After evaluation of the 1680 articles yielded by the systematic search, 52 studies treating 1843 patients were included. Included intratumoral injection treatment modalities comprised iodine-125 (125I) seed brachytherapy (32 studies, 1283 patients), phosphorus-32 (32P) microbrachytherapy (5 studies, 133 patients), palladium-103 (103Pd) seed brachytherapy (2 studies, 26 patients), immunotherapy (9 studies, 330 patients), and chemotherapy (4 studies, 71 patients). Overall survival ranged between 7.0 and 16.0 months for 125I, 5.2 and 15.5 months for 32P, 6.9 and 10.0 months for 103Pd, 5.8 and 13.8 months for immunotherapy, and 9.0 and 16.2 months for chemotherapy. Severe complication (greater than or equal to grade III complications using Clavien-Dindo classification) rates were 6.2 per cent for 125I, 49.2 per cent for 32P, 15 per cent for 103Pd, 57.9 per cent for immunotherapy, and 0 per cent for chemotherapy., Conclusion: Five intratumoral injection therapies are described and an overview is reported. Some intratumoral injection therapies for patients with locally advanced pancreatic cancer seem safe, although 32P microbrachytherapy and immunotherapy require additional evidence. Currently available data are insufficient to provide firm conclusions regarding the added value to survival. The potential advantage of intratumoral injection therapies complementary to conventional care should be studied in well designed RCTs., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Reactive oxygen species (ROS) have become an effective "weapon" for cancer therapy due to their strong oxidation and high anti-tumor activity. Photodynamic therapy (PDT) is one of the classical methods to induce reactive oxygen species. Therefore, an ultraminiature palladium ruthenium alloy (sPdRu) and Ru(II) were combined with thermally responsive phase change materials (PCMs). Polypyridyl-complex (RCE) co-encapsulation was performed to obtain thermally responsive nanoparticles (PdRu-RCE@PCMNPs) for multimodal synergistic anti-breast cancer therapy. On the one hand, the thermosensitive PCM protective layer can realize the slow release of sPdRu, and then catalyze the production of oxygen from tumor endogenous H 2 O 2 to perform RCE-mediated PDT. At the same time, sPdRu further increased ROS levels through peroxidase (POD) activity. On the other hand, sPdRu has high photothermal conversion efficiency and can be effectively used for photothermal therapy and photodynamic therapy. Importantly, PdRu-RCE@PCM NPs not only can effectively inhibit primary tumor growth, but also can inhibit tumor metastasis. In addition, due to the effective accumulation of sPdRu and RCE, PdRu-RCE@PCM NPs also show excellent fluorescence and photothermal imaging capabilities of tumors, which can be used for tumor tracing and evaluation of treatment. Accordingly, PdRu-RCE@PCM NPs are useful in treating primary tumors and inhibiting tumor metastasis.

Purpose/objective: To compare toxicity profiles of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT)., Materials/methods: 99 patients with intermediate-risk prostate cancer underwent an HDR (n = 59) or LDR (n = 40) boost combined with UH-EBRT (5 Gy x 5) . HDR (Ir-192) was delivered a single dose (15 Gy) and LDR (Pd-103) prescription dose was 100 Gy. Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3mos. Cumulative incidences were calculated for toxicity. Fisher exact tests were used to evaluate associations., Results: Overall incidence of grade 2 genitourinary toxicity for the entire cohort at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% vs 5.1% and 55% vs 11%; p<0.001). On MVA, only treatment regimen (LDR versus HDR) was associated with grade 2+ genitourinary toxicity (p<0.001). Two patients experienced grade 2 rectal toxicity in each cohort. No grade > 3 toxicities were observed., Conclusions: Both LDR and HDR brachytherapy combined with UH-EBRT had favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: PALLADIUM and IRIDIUM studies demonstrated efficacy and safety of indacaterol/mometasone (IND/MF) versus salmeterol/fluticasone (SAL/FLU). This post hoc analysis of pooled data from PALLADIUM and IRIDIUM studies evaluated efficacy and safety of IND/MF versus SAL/FLU in Asian patients with inadequately controlled asthma., Methods: Both studies were Phase III, 52-week, randomized, double-blind, active-controlled that included patients with predicted pre-bronchodilator FEV 1 (PALLADIUM, ≥50%-<85%; IRIDIUM, <80%), ACQ-7 score ≥1.5. Patients treated with IND/MF high- (150/320 μg) or medium-dose (150/160 μg) or SAL/FLU high-dose (50/500 μg) were included. Lung function, asthma control, and asthma exacerbations were evaluated., Results: In total, 323 patients (IND/MF high-dose, n  = 107; IND/MF medium-dose, n  = 106, SAL/FLU high-dose, n  = 110) were included. IND/MF high-dose showed improvement in trough FEV 1 versus SAL/FLU high-dose at Weeks 26 (Δ, 42 mL; 95% CI, -35 to 120 mL), and 52 (Δ, 41 mL; 95% CI, -37 to 120 mL). IND/MF high-dose exhibited numerically greater improvement in ACQ-7 score versus SAL/FLU high-dose at Weeks 26 (Δ, -0.215; 95% CI, -0.385 to -0.044) and 52 (Δ, -0.176; 95% CI, -0.348 to -0.005). Improvements in trough FEV 1 and ACQ-7 score were comparable between IND/MF medium-dose and SAL/FLU high-dose. IND/MF high- and medium-dose showed reductions in moderate or severe (45%; 30%), severe (39%; 41%), and all (9%; 25%) exacerbations, respectively, versus SAL/FLU high-dose over 52 weeks. All treatments were well tolerated., Conclusions: Once-daily, single-inhaler IND/MF high-dose improved lung function with better asthma control, reduced asthma exacerbations with comparable safety versus twice-daily SAL/FLU high-dose. IND/MF medium-dose showed comparable outcomes to SAL/FLU high-dose at a reduced steroid dose.

Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment., (© 2022. The Author(s).)

Background: Sonodynamic therapy (SDT) is a burgeoning modality for cancer therapy owing to its high tissue-penetrating capability, controllability and safety. Whereas, the undesirable reactive oxygen species (ROS) yield of sonosensitizers and tumor hypoxia are two vulnerable spots of SDT. Therefore, it is an advisable strategy to augment ROS level and simultaneously relieve hypoxia for SDT to arrive its full potential in cancer treatment., Results: In this work, the defected two-dimensional (2D) Pd/H-TiO 2 nanosheets (NSs) with triple antineoplastic properties were dexterously elaborated and engineered using a facile one-pot Pd-catalyzed hydrogenation tactic by loading a tiny amount of Pd and then inletting hydrogen flow at atmospheric pressure and temperature. The 2D black Pd/H-TiO 2 NSs with oxygen defects exerted eximious SDT effect based on the decreased bandgap that made it easier for the separation of electrons and holes when triggered by ultrasound as theoretically guided by density functional theory calculations. Additionally, Pd/H-TiO 2 NSs could serve as Fenton-like agents because of the presence of oxygen defects, facilitating the conversion of hydrogen peroxide into hydroxyl radicals for exerting the chemodynamic therapy (CDT). Simultaneously, the introduced tiny Pd component possessed catalase-like activity responsible for oxygen production to ameliorate hypoxic condition and thus contributed to improving SDT and CDT efficacies. Both in vitro and in vivo results provided compelling evidences of high ROS yield and aggrandized sono-chemodynamic effect of Pd/H-TiO 2 nanosonosensitizers with the detailed underlying mechanism investigation by RNA sequencing., Conclusion: This work delves the profound potential of Pd-catalyzed hydrogenated TiO 2 on oncotherapy, and the effective antineoplastic performance and ignorable therapeutic toxicity make it a powerful competitor among a cornucopia of nanosonosensitizers., (© 2022. The Author(s).)

Objective: Prostate cancer is one of the most common types of cancer found to occur in males and is ranked as the second-highest cause of cancer-associated deaths among male patients. In this study, we have shown the influence of a new palladium-based anticancer agent in contrast to the six distinct prostate cancer lines and the primary cultures., Methods: In this study, we have used six distinct prostate cell lines, that is, PNT2-C2, LNCaP, BPH-1, PC-3, PNT1A, and P4E6. The MTP and ATP assay were performed to evaluate the growth of the cell and the flow cytometry to investigate the status of the cell cycle. The antigrowth effect of the palladium complex was evaluated against different cell lines at three time zones 24 h, 48 h, and 72 h. [PdCl(terpy)] (capsule)-2H 2 O is synthesized by direct encapsulation of equimolar amounts of capsule ions into [Pd (terpy) Cl] Cl-2H 2 O., Results: A comparative analysis was done on 25 mM etoposide and 12 mM cisplatin, cytotoxic agents. The lowest IC50 value at 72 hours was 0.128 mM for BPH-1 cell lines with 0.139 mM, whereas PNT2-C2 cells were found to be most resistant with IC50 values of 0.829 mM. The antigrowth effect of palladium complex on cell lines was measured using the MTS assay at 24, 48, and 72 hours. BPH-1, PNT2-C2, and PNT1A either possess normal tissues or have benign prostatic hyperplasia tissues whereas P4E6, PC-3, and LNCaP cell lines possess malignant origin. The Pd complex exhibited significant cytotoxic action in stem cells when compared against etoposide. An antigrowth effect was reported for Pd complex at lower concentration, but it was more cytotoxic than etoposide with significant cytotoxicity ( P =0.001)., Conclusion: The palladium complex experienced a substantial antigrowth influence over most of the prostate tumor cell lines and the primary cultures, eventually, leading to the implementation of this Pd complex in the treating procedure of metastatic prostate cancer, which is tremendously resistant to the traditional treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Long Cheng et al.)

The treatment of borderline resectable (BR) pancreatic cancer is challenging and requires a multidisciplinary approach with chemotherapy, radiation and surgical resection. Despite using chemotherapy and radiotherapy in the neoadjuvant setting, achievement of negative surgical margins remains technically challenging. Positive margins are associated with increased local recurrences and worse overall survival and there are no standard options for treatment. The CivaSheet is an FDA-cleared implantable sheet with a matrix of unidirectional planar low-dose-rate (LDR) Palladium-103 (Pd-103) sources. The sources are shielded on one side with gold to spare radio-sensitive structures such as the bowel. The sheet can easily be customized and implanted at the time of surgery when there is concern for close or positive margins. The CivaSheet provides an interesting solution to target the region of close/positive margins after pancreatectomy. Here we discuss the physical properties, the dosimetry, clinical workflow and early patient outcomes with the CivaSheet in pancreatic cancer., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

In recent years, targeted therapies and immunotherapeutics, along with conventional chemo- and radiotherapy, have greatly improved cancer treatments. Unfortunately, in cancer patients, anemia, either as a complication of cancer progression or as the result of cancer treatment, undermines the expected therapeutic efficacy. Here, we developed a smart nanosystem based on the palladium nanoplates (PdPLs) to deliver tocilizumab (TCZ, a widely used IL-6R antibody) to the liver for specific blockade of IL-6/IL-6R signaling to correct anemia. With chemical modifications, this nanosystem delivered a large mass of TCZ and enhanced liver delivery, inducing a marked suppression of hepcidin expression as a result of diminished IL-6 signaling. Through this mechanism, significant suppression of tumor progression was realized (at least in part) because of the corrected anemia after treatment.

Introduction: Brachytherapy using permanently implantable collagen tiles containing cesium-131 (Cs-131) is indicated for treatment of malignant intracranial neoplasms. We quantified Cs-131 source migration and modeled the resulting dosimetric impact for Cs-131, iodine-125 (I-125), and palladium-103 (Pd-103). Methods and Materials: This was a retrospective analysis of a subgroup of patients enrolled in a prospective, single-center, nonrandomized, clinical trial (NCT03088579) of Cs-131 collagen tile brachytherapy. Postimplant Cs-131 plans and hypothetical I-125 and Pd-103 calculations were compared for 20 glioblastoma patients for a set seed geometry. Dosimetric impact of decay and seed migration was calculated for 2 hypothetical scenarios: Scenario 1, assuming seed positions on a given image set were unchanged until acquisition of the subsequent set; Scenario 2, assuming any change in seed positions occurred the day following acquisition of the prior images. Seed migration over time was quantified for a subset of 7 patients who underwent subsequent image-guided radiotherapy. Results: Mean seed migration was 1.7 mm (range: 0.7-3.1); maximum seed migration was 4.3 mm. Mean dose to the 60 Gy volume differed by 0.4 Gy (0.6%, range 0.1-1.0) and 0.9 Gy (1.5%, range 0.2-1.7) for Cs-131, 1.2 Gy (2.0%, range 0.1-2.1) and 1.6 Gy (2.6%, range 1.2-2.6) for I-125, and 0.8 Gy (1.3%, range 0.2-1.5) and 1.4 Gy (2.3%, range 0.3-1.9) for Pd-103, for Scenarios 1 and 2, respectively, compared with the postimplant plan. For a set seed geometry mean implant dose was higher for Pd-103 (1.3 times) and I-125 (1.1 times) versus Cs-131. Dose fall-off was steepest for Pd-103: gradient index 1.88 versus 2.23 (I-125) and 2.40 (Cs-131). Conclusions: Dose differences due to source migration were relatively small, suggesting robust prevention of seed migration from Cs-131-containing collagen tiles. Intratarget heterogeneity was greater with Pd-103 and I-125 than Cs-131. Dose fall-off was fastest with Pd-103 followed by I-125 and then Cs-131.

Multifunctional phototherapy nanoagents for imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) are highly desirable in the field of solid tumor therapy. Nevertheless, the tumor microenvironment (TME) inherently associated with hypoxia significantly hampers the photodynamic effect of these multifunctional nanoagents. Herein, Pd nanocubes coated with an ultrathin Pt shell were prepared and further conjugated with fluorescein labeled and thiol functionalized polyethylene glycol (FITC-PEG-SH) (denoted as Pd@Pt-PEG). The deposition of a Pt shell on Pd nanocubes not only enhances the photothermal performance, exhibiting excellent hyperthermia outcomes and impressive photothermal (PT) imaging quality, but also leads to the formation of singlet oxygen ( 1 O 2 ) induced by plasmonic excitation. In the meantime, the catalytic activity of the Pt layer is enhanced by electronic coupling and the plasmonic effect, which induces the decomposition of endogenous overexpressed hydrogen peroxide (H 2 O 2 ) in tumors to generate O 2 for conquering TME and augmenting 1 O 2 generation for efficacious tumor cell apoptosis. The modification of FITC-PEG-SH improves the biocompatibility and provides outstanding fluorescence (FL) imaging properties. Upon NIR laser irradiation, Pd@Pt-PEG allows in situ O 2 generation and dual-mode imaging-guided synergistic PTT/PDT that effectively kills hypoxic tumor cells, which makes it a promising nanotherapeutic agent for enhanced tumor therapy.

Background: Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H 2 S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H 2 S gas therapy is expected to achieve synergistic tumor treatment., Methods: Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H 2 S donor to be loaded into Pd nanocubes through in-depth coordination for construction of the Pd-Su nanomedicine for the first time to achieve photo-controlled H 2 S release, realizing the effective combination of photothermal therapy and H 2 S gas therapy., Results: The Pd-Su nanomedicine shows a high Su loading capacity (85 mg g -1 ), a high near-infrared (NIR) photothermal conversion efficiency (69.4%), and NIR-controlled H 2 S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H 2 S produces a strong synergetic effect by H 2 S-induced inhibition of heat shock response, thereby effectively inhibiting tumor growth. Moreover, high intratumoral accumulation of the Pd-Su nanomedicine after intravenous injection also enables photothermal/photoacoustic dual-mode imaging-guided tumor treatment., Conclusions: The proposed NIR-responsive heat/H 2 S release strategy provides a new approach for effective cancer therapy., (© 2021. The Author(s).)

In women globally, breast cancer is responsible for most cancer-related deaths and thus, new effective therapeutic strategies are required to treat this malignancy. Platinum-based compounds like cisplatin are widely used to treat breast cancer, however, they come with limitations such as poor solubility, adverse effects, and drug resistance. To overcome these limitations, complexes containing other platinum group metals such as palladium have been studied and some have already entered clinical trials. Here we investigated the anti-cancer activity of a palladium complex, BTC2, in MCF-7 oestrogen receptor positive (ER+) and MDA-MB-231 triple negative (TN) human breast cancer cells as well as in a human breast cancer xenograft chick embryo model. BTC2 exhibited an average IC 50 value of 0.54 μM, a desirable selectivity index of >2, inhibited the migration of ER+ and TN breast cancer cells, and displayed anti-cancer stem cell activity. We demonstrate that BTC2 induced DNA double strand breaks (increased levels of γ-H2AX) and activated the p-ATM/p-CHK2 and p-p38/MAPK pathways resulting in S- and G2/M-phase cell cycle arrests. Importantly, BTC2 sensitised breast cancer cells by triggering the intrinsic (cleaved caspase 9) and extrinsic (cleaved caspase 8) apoptotic as well as necroptotic (p-RIP3 and p-MLKL) cell death pathways and inhibiting autophagy and its pro-survival role. Furthermore, in the xenograft in vivo model, BTC2 displayed limited toxicity and arrested the tumour growth of breast cancer cells over a 9-day period in a manner comparable to that of the positive control drug, paclitaxel. BTC2 thus displayed promising anti-breast cancer activity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

1T-phase transition-metal dichalcogenides (TMDs) nanomaterials are one type of emerging and promising near-infrared II (NIR-II) photothermal agents (PTAs) derived from their distinct metallic electronic structure, but it is still challenging to synthesize these nanomaterials. Herein, PdTe 2 nanoparticles (PTNs) with a 1T crystal symmetry and around 50 nm in size are prepared by an electrochemical exfoliation method, and the corresponding photothermal performances irradiated under a NIR-II laser have been explored. The encapsulation of 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) endows PTNs with water solubility, enhanced photothermal stability, and high biocompatibility. Notably, PTN/DSPE-PEG displays a potent absorbance through the NIR-II zone and considerable photothermal conversion efficiency, which is up to 68% when irradiated with a 1060 nm laser. With these unique photothermal properties, excellent in vitro and in vivo tumor inhibition effects of PTN/DSPE-PEG have been achieved under the irradiation of a NIR-II (1060 nm) laser without visible toxicity to normal tissues, suggesting that it is an efficient NIR-II photothermal nanoagent.

Cutaneous leishmaniasis (CL) is a neglected tropical disease (NTD), endemic mainly in low-income countries that lack adequate basic health care. The emergence of resistant parasites to pentavalent antimonials has led to the search for new treatments for CL. Photodynamic therapy (PDT) is a promising non-invasive and less toxic alternative for the treatment of CL. The present work describes the synthesis, characterization and photodynamic effect against CL of a new metalloporphyrin Pd (II) meso-tetra[4-(2-(3-n-pentadecylphenoxy)ethoxy]phenylporphyrin (PdP) derived from the cashew nut shell liquid (CNSL). The PdP complex presented a singlet oxygen quantum yield of 0.49, favoring a type II photochemical reaction. The results of the photodynamic experiment carried out with PdP on the promastigote forms of Leishmania braziliensis indicated a mortality percentage of 70 % of the cells when compared to the control after exposure to blue light (λ = 420 nm). Besides this, the metalloporphyrin PdP did not show considerable toxicity to macrophages, indicating the cell viability of the compound. Therefore, this metalloporphyrin derived from biomass represents an interesting alternative as a potential therapeutic drug for the treatment of CL through PDT, especially for patients with intolerance to the chemotherapeutic drugs currently available., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Nanoparticles (NPs) with radioactive atoms incorporated within the structure of the NP or bound to its surface, functionalized with biomolecules are reported as an alternative to low-dose-rate seed-based brachytherapy. In this study, authors report a mathematical dosimetric study on low-dose rate brachytherapy using radioactive NPs., Method: Single-cell dosimetry was performed by calculating cellular S-values for spherical cell model using Au-198, Pd-103 and Sm-153 NPs. The cell survival and tumor volume versus time curves were calculated and compared to the experimental studies on radiotherapeutic efficiency of radioactive NPs published in the literature. Finally, the radiotherapeutic efficiency of Au-198, Pd-103 and Sm-153 NPs was tested for variable: administered radioactivity, tumor volume and tumor cell type., Result: At the cellular level Sm-153 presented the highest S-value, followed by Pd-103 and Au-198. The calculated cell survival and tumor volume curves match very well with the published experimental results. It was found that Au-198 and Sm-153 can effectively treat highly aggressive, large tumor volumes with low radioactivity., Conclusion: The accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumor repopulation rate is important for the calculation of cell survival curves. Self-absorption of emitted radiation and dose enhancement due to AuNPs must be considered in the calculations. Selection of radionuclide for radioactive NP must consider size of tumor, repopulation rate and radiosensitivity of tumor cells. Au-198 NPs functionalized with Mangiferin are a suitable choice for treating large, radioresistant and rapidly growing tumors.

Objective: Retinoblastoma is the most common cancer among children under 5 years of age. The common conventional methods for the treatment of retinoblastoma include chemotherapy and brachytherapy (BT). This study investigated the concurrent use of BT with 125 I and 103 Pd sources and chemotherapy with platinum-based chemotherapy drugs for retinoblastoma., Materials and Methods: The absorbed doses in different parts of the eye were measured with and without platinum. Platinum concentrations of 5, 7.5, 10, and 15 mg/g were evaluated, and the dose enhancement factors (DEFs) were calculated for different cases., Results: For the 125 I source, the DEFs at the tumor apex were 1.49, 1.67, 1.81, and 1.97 at concentrations of 5, 7.5, 10, and 15 mg/g, respectively. The DEF decreased dramatically beyond the apex at 0.85 cm from tumor base and was 0.87, 0.82, 0.76, and 0.63 for the abovementioned concentrations, respectively. For the 103 Pd source, the DEFs were 1.15, 1.24, 1.21, and 1.07, respectively, at the apex and 0.76, 0.65, 0.56, and 0.39, respectively, beyond the apex., Conclusions: Our results showed that the concurrent use of low-dose-rate plaque BT and platinum-based chemotherapy significantly increased the tumor-absorbed dose and decreased the absorbed dose in areas outside the tumor and the treatment time.

Purpose: To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer., Methods and Materials: This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months., Results: The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure., Conclusion: Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Brachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy., Methods and Materials: Of 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ 2 test with survival determined by the Kaplan-Meier method and Cox regression., Results: Men treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150-200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes., Conclusions: Brachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: MRI-assisted radiosurgery (MARS) is a modern technique for prostate brachytherapy that provides superior soft tissue contrast. The purpose of this analysis was to evaluate treatment planning factors associated with urinary toxicity, particularly damage to the membranous urethra (MUL) and external urethral sphincter (EUS), after MARS., Material and Methods: We retrospectively reviewed 227 patients treated with MARS. Comparisons were made between several factors including preimplantation length of the MUL and EUS dosimetric characteristics after implantation with longitudinal changes in American Urological Association (AUA) urinary symptom score., Results: Rates of grade 3 urinary incontinence and obstructive urinary symptoms were 4% and 2%. A piecewise mixed univariate model revealed that MUL and V 200 , V 150 , V 125 , and D 5 to the EUS were all associated with increased rates of urinary toxicity over time. On univariate logistic regression, MUL >14.2 mm (odds ratio [OR] 2.03 per cm 3 , 95% confidence interval [CI] 1.10-3.77, p = 0.025), V 125 to the EUS (OR 3.21 cm 3 , 95% CI 1.18-8.71, p = 0.022), and use of the I-125 isotope (OR 3.45, 95% CI 1.55-7.70, p = 0.001) were associated with subacute urinary toxicity (i.e., that occurring at 4-8 months). Optimal dose-constraint limits to the EUS were determined to be V 200  < 0.04 cm 3  (p = 0.002), V 150  < 0.12 cm 3  (p = 0.041), V 125  < 0.45 cm 3  (p = 0.033), D 30  < 160 Gy (p = 0.004), and D 5  < 218 Gy (p = 0.016)., Conclusions: MARS brachytherapy provides detailed anatomic information for treatment planning, implantation, and quality assurance. Overall rates of urinary toxicity are low; however, several dosimetric variables associated with the EUS were found to correlate with urinary toxicity., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Men with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT)., Methods and Materials: Three hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan-Meier method with associations determined by log rank and Cox regression., Results: Ten-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001)., Conclusions: Survival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Pd nanosheets (Pd NSs) have attracted extensive attention due to their promising application in photothermal therapy. However, their photodynamic properties have rarely been reported. Herein, holey Pd NSs (H-Pd NSs) with intrinsic photodynamic and hypoxia-resistant capacities are fabricated for the first time using an anisotropic oxidative etching strategy, which introduces one-dimensional nanoholes with active (100) facets on the hole walls. Gradual degradation of H-Pd NSs is observed in simulated physiological media due to the oxidative etching. In vitro and in vivo studies indicate that the single-component H-Pd NSs can act as a photothermal/photodynamic agent for imaging-guided hypoxic tumor therapy, with a high tumor inhibition rate of 99.7%. This work provides ideas for introducing active facets in metallic pore walls, broadening the application of Pd NSs and the design of biodegradable noble metal nanotheranostic agents for cancer therapy.

Background/aim: Melanoma represents a big challenge for clinical treatment. Besides being the most aggressive and the deadliest form of skin cancer, it is often refractory to commonly used anticancer drugs. Hence, developing new anti-cancer agents is crucial to improve refractory melanoma treatment. Studies using palladium(II) complexes have reported antitumor effects on cancer cells. In this study, we aimed to determine the cytotoxic effect of three novel synthesized Pd(II) complexes with Schiff bases derived from 4-aminoacetophenone on the MDA-MB-435 melanoma cell line., Materials and Methods: Cells were treated with ligand and Pd(II) complexes. Cell viability, morphology and death induction upon treatment were examined., Results: Novel synthesized Pd(II) complexes led to decreased viability of cells. They also induced morphological alterations and cell death, mainly in the C3 complex., Conclusion: The novel synthesized complexes have a significant cytotoxic effect on cell line MDA-MB-435, especially C3 and can be considered as an antitumor agent for further studies., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Chemical protein synthesis and biorthogonal modification chemistries allow production of unique proteins for a range of biological studies. Bond-forming reactions for site-selective protein labeling are commonly used in these endeavors. Selective bond-cleavage reactions, however, are much less explored and still pose a great challenge. In addition, most of studies with modified proteins prepared by either total synthesis or semisynthesis have been applied mainly for in vitro experiments with very limited extension to live cells. Reported here is an approach for studying uniquely modified proteins containing a traceless cell delivery unit and palladium-based cleavable element for chemical activation, and monitoring the effect of these proteins in live cells. This approach is demonstrated for the synthesis of a caged ubiquitin-aldehyde, which was decaged for the inhibition of deubiquitinases in live cells., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: The CivaSheet device uses multiple directionally shielded Pd-103 CivaDot sources to produce a directional planar dose distribution. In postplanning, manually digitizing the 3D source orientation is challenging because the 3D vector must be digitized by using 2D displayed images. The aim of this study is to develop an algorithm that will automatically determine the direction of each CivaDot source based on the location of sources adjacent to it., Methods and Materials: The algorithm determines the source direction by averaging the normal directions of multiple local planes established by the adjacent sources. The algorithm was tested on a manually constructed CivaSheet-like device that was CT scanned in known flat geometries and two known curved geometries. Algorithmically determined source directions were compared with the known directions. The algorithm was also used on a postplan for a gynecological pelvic sidewall tumor bed implant and compared against manual digitization of the source directions., Results: For the flat and curved test geometries, the average angular difference between the algorithm determined and known orientation was 1.2° ± 0.8° (flat geometry), 1.7° ± 2.1° (curve about vertical axis), and 2.3° ± 2.4° (curve about horizontal axis). For the patient case, results showed on average a 23.1° ± 10.8° difference between the manual digitized orientation and the algorithm's predicted orientation., Conclusions: The algorithm calculates the source orientation with accuracy better than 2.3° for the controlled experiments. In addition to its accuracy, the algorithm produces consistent results and lessens the difficult challenge of orienting the partially shielded sources., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy., Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined., Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = &lt;0.001., Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses.

Purpose: Adjuvant partial breast radiotherapy is the standard of care for early-stage favorable breast cancer. We report dosimetry, acute and late tolerance for 67 permanent breast seed implants., Materials and Methods: From July 2012 to October 2018, 67 postmenopausal women with unifocal pT1pN0 invasive ductal or ductal carcinoma in situ received partial breast radiotherapy using stranded Pd-103 seeds after breast-conserving surgery, delivering 90 Gy to the seroma + margin (1.25-1.5 cm), planned with computed tomography simulation and performed as an ultrasound-guided outpatient procedure. The planning and postimplant computed tomography images were fused for seroma delineation for postimplant dosimetry. Evaluations were performed at 1, 2, 6, and 12 months and then annually., Results: Although patient acceptance is high, only 40% met technical requirements of seroma volume, location, and visibility. For 67 patients, the median seroma volume was 6.6 cc, PTV 61 cc, and number of needles 18. In day 0 dosimetry, median seroma D90 dose was 132 Gy; seroma + 5 mm, 106 Gy; and seroma + 10 mm, 80 Gy. Peak reaction at 6 weeks is limited to the implant site: 51% grade 1 erythema and 12% focal desquamation. Late reactions (>2 years) are generally minimal: 35% no sequelae, 43% localized fibrosis, 20% mild telangiectasia (6% moderate but asymptomatic), 22% contour change. At minimum 6-month follow-up, 94% were "very or totally satisfied." Recurrences (median follow-up: 3.3 years) were one in breast (different quadrant) and 2 contralateral. Three patients have had biopsies of fibrosis, all negative for malignancy., Conclusions: Our experience with permanent breast seed implant is favorable with a high patient acceptance and satisfaction, excellent early efficacy, and very satisfactory cosmesis., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Treatment of triple-negative breast carcinoma (TNBC) remains an unmet medical need with no targeted therapy available to date. Accounting for 10-30% of all human breast cancer tumors, this mammary carcinoma subtype has a particularly poor prognosis owing to its high metastatic potential, aggressive biology and limited pharmacological treatment options. Platinum chemotherapeutics are the mainstay therapy in patients with TNBC but their clinical use is limited by severe toxicity and acquired resistance. Palladium-based complexes are appealing alternative metal-based drugs because of significant similarities regarding structure and coordination chemistry with the platinum agents. This review summarizes the knowledge gathered so far on 121 Pd(II) complexes, emphasizing their anticancer activity and putative pharmacological targets toward TNBC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The directional planar palladium-103 LDR device (CivaSheet TM ) may be used for intraoperative implantation at the interface between the tumor site and healthy tissue. Its dosimetric properties have been studied in the ideal case of application on a flat surface. The dosimetric impact of implanting this highly directional device on a curved surface that may be encountered in clinical treatments is analyzed., Methods: CivaSheet is designed as an array of directional palladium-103 sources (CivaDots). From the postoperative computed tomography (CT) scans of three patients, the shape of each implanted CivaSheet was reconstructed. In order to obtain a realistic estimate of the distribution of curvatures, the mean radius of curvature at the location of each CivaDot was calculated. A Monte Carlo simulation (FLUKA) of a single CivaDot was designed, based upon published geometry and material specifications. Both the radial dose function analog and the two-dimensional anisotropy function analog for the CivaDot were validated in comparison with film measurements and benchmarked to published Monte Carlo data. A value for the dose-rate constant Λ = 0.587(19) cGy/h/U for a CivaDot source in water was calculated as well. Knowledge of the dose distribution in the vicinity of each source allowed the dose at any point around CivaSheets of different curvatures and orientations to be calculated., Results: The local radius of curvature was found to be primarily between 2 and 8 cm in all three patient implants. On the unshielded side of an inward-facing curved CivaSheet implant of radius 2 cm, the calculated dose at 0.5 cm depth exceeded the prescribed dose by ∼20%, while on the shielded side the dose increased by a factor of two, thus compromising the shielding efficiency of the original design. On the unshielded side of an outward-facing curved implant, the dose at 0.5 cm depth decreased by ∼20%., Conclusions: When tumor bed curvature can be estimated from the preplanning CT scan, the results from this study provide quantitative guide for modifying the source strength to achieve the desired clinical results. In many intraoperative cases, however, accurate preplanning based on surface curvature may not be practical. In such situations, knowledge of the dosimetric impact of the surface curvature provides motivation for avoiding implantation geometries that can lead to either over/underdosing the target, or excess dose to healthy tissue., (© 2019 American Association of Physicists in Medicine.)

IGF1R and CD44 are overexpressed in most advanced melanomas so we designed chemotherapeutic nanoparticles to target those receptors. Tris(dibenzylideneacetone)dipalladium (Tris DBA-Pd) is a novel inhibitor of N-myristoyltransferase 1 (NMT-1) and has proven in vivo activity against melanoma. However, poor solubility impairs its effectiveness. To improve its therapeutic efficacy and overcome drug resistance in advanced melanomas, we synthesized Tris DBA-Pd hyaluronic acid nanoparticles (Tris DBA-Pd HANP) and evaluated them against in vivo xenografts of LM36R, an aggressive BRAF mutant human melanoma resistant to BRAF inhibitors. We treated xenografted mice in four arms: empty HANPs, free Tris DBA-Pd, Tris DBA-Pd HANPs, and Tris DBA-Pd HANPs with IGF1R antibody. The Tris DBA-Pd HANP group was the most responsive to treatment and showed the greatest depletion of CD44-positive cells on IHC. Surprisingly, the HANP containing IGF1R antibody was less effective than particles without antibody, possibly due to steric hindrance of IGF1R and CD44 binding. Tris DBA-Pd nanoparticles are an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.

Oxidative stress-induced mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease (AD). Hydrogen molecule, a special antioxidant, can selectively scavenge highly cytotoxic reactive oxygen species such as ·OH, exhibiting a potential to treat AD by reducing oxidative stress. However, there is no effective route to realize the continuous and efficient accumulation of administrated hydrogen in AD brain owing to its low solubility. Here, we develop the small-sized Pd hydride (PdH) nanoparticles for high payload of hydrogen and in situ sustained hydrogen release in AD brain. By virtue of the catalytic hydrogenation effect of Pd, the released hydrogen from PdH nanoparticles exhibits high bio-reductivity in favor of effectively scavenging cytotoxic ·OH in a self-catalysis way. Bio-reductive hydrogen is able to recover mitochondrial dysfunction, inhibit Aβ generation and aggregation, block synaptic and neuronal apoptosis and promote neuronal energy metabolism by eliminating oxidative stress and activating the anti-oxidative pathway, consequently ameliorating the cognitive impairment in AD mice. The proposed hydrogen-releasing nanomedicine strategy would open a new window for the treatment of AD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Episcleral eye plaques provide excellent local control of ocular melanoma, but vision sparing remains a significant problem with 30% or more of patients experiencing significant visual acuity degradation. The use of silicone oil shielding with Iodine-125 plaques has previously been reported to improve critical structure sparing. We hypothesized that the use of Palladium-103 would improve the shielding effectiveness of silicone oil due to the strong energy dependence of the photoelectric effect. This Monte Carlo simulation study reports a comparison of the shielding effects of silicone oil when used in conjunction with Pd-103 and with I-125 plaques., Materials and Methods: GEANT4 was used to simulate eye plaque treatments to an eye with either water-equivalent vitreous humor, or silicone oil in place of the vitreous humor. Two solid gold plaques, 15 and 23 mm, were simulated loaded with I-125 and with Pd-103 source seeds. Seed activity was normalized such that 85 Gy was delivered to the tumor apex in the water-equivalent cases. Tumor apex dose, central axis dose, and inner sclera dose reductions with silicone oil were evaluated., Results: Silicone oil resulted in an underdosing to the tumor apex of 6.1% and 7.5% in the 15 mm plaque for I-125 and Pd-103, respectively, and 3.4% and 4.3% in the 23 mm plaque for I-125 and Pd-103, respectively. When renormalized to 85 Gy to the tumor apex in all scenarios, silicone oil reduced the dose to the inner sclera 90° from the plaque by 19-32% for the 15 and 23 mm plaques using I-125, and by 33-65% for the 15 and 23 mm plaques using Pd-103., Conclusions: The combination of silicone oil and Pd-103 eye plaques offers the potential for greatly improved sparing to normal structures compared to Pd-103 plaques alone or I-125 plaques with or without silicone oil., (© 2018 American Association of Physicists in Medicine.)

Methotrexate (MTX) is a drug that is used for the clinical treatment of rheumatoid arthritis (RA), a stubborn disease caused by over-immunization. However, the toxicity that arises as a result of poor selectivity to inflammatory cells severely limits the application of MTX. Therefore, new therapeutic strategies are needed for treating RA. Here, we describe the design and synthesis of a nanotherapy agent, Pd-Cys@MTX@RGD, which can target inflammatory cells and control MTX release. The novel hexagonal palladium (Pd) nanosheets were used as a near-infrared (NIR) photothermal agent modified with arginine-glycineaspartic acid (RGD) peptides on the surface to enhance the ability of the nanosheet targeting of inflammatory cells. In subsequent experiments, the Pd-Cys@MTX@RGD nanosheets were observed to greatly reduce the toxicity of MTX, showing controlled MTX release under irradiation of 808 nm (0.3 W cm -2 ). Moreover, taking advantage of the fact that MTX can be combined with multiple therapeutic methods, the photothermal therapy (PTT) of Pd nanosheets provided a compensatory effect to enhance the therapeutic efficacy of MTX. Under combination therapy, Pd-Cys@MTX@RGD was shown to effectively inhibit the inflammatory response induced by vascular endothelial growth factor (VEGF) and IL-1β. And, in vivo, multifunctional Pd-Cys@MTX@RGD effectively inhibited the symptoms of RA by inhibiting the expression of pro-inflammatory cytokines (TNF-α,COX-2). We hope that the construction of nanomaterials can add potential value to the design of chemical drugs and therapeutic strategies for RA.

Purpose:: To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy., Methods:: Retrospective interventional case series including 170 consecutive patients treated with 103 Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology., Results:: The mean initial tumor thickness was 3.9 mm (median 2.8 mm; range 2-11.3 mm) that decreased to 1.7 mm (median 1.2 mm; range 0-7.1 mm) after plaque brachytherapy. On imaging, tumors were pigmented in 51% ( n = 86/170), amelanotic in 10% ( n = 17/170), and variably pigmented in 39% ( n = 67/170). Tumor pigmentation increased in 64% ( n = 106/166), decreased in 18% ( n = 30/166), and was unchanged in 18% ( n = 30/166). Of the 120 that demonstrated intrinsic vascularity, 10% ( n = 12/120) had decreased tumor-related vascularity and 90% ( n = 108/120) showed complete resolution. Subretinal fluid was present in 34% ( n = 58/170) of eyes at presentation. Of them, 15% (9; n = 9/58) had persistent SRF at last follow-up. On ultrasound imaging, 88% ( n = 149/170) tumors presented with low to moderate internal reflectivity of which 61% ( n = 91/149) showed increased reflectivity on regression. We noted a crescendo-decrescendo fluctuation in the presence of orange pigment lipofuscin along with complete resolution of drusenoid retinal pigment epithelial detachments. In the entire series of 170 patients, there was 0.5% (1) failure of local control, 2% (4) secondary enucleations, and 6% (10) patients developing metastasis., Conclusion:: Findings related to choroidal melanoma regression after 103 Pd plaque brachytherapy included decreased intrinsic tumor vascularity, decreased tumor-related subretinal fluid, increased pigmentation, specific changes in orange pigment lipofuscin and resolution of drusenoid retinal pigment epithelial detachments, as well as decreased tumor thickness with an increase in internal reflectivity on ultrasound.

Purpose: To present a unique approach to eye and vision sparing for a patient with squamous cell carcinoma invading through a penetrating keratoplasty (PK) wound., Methods: A 56-year-old functionally monocular man was found to have squamous cell carcinoma with intraocular invasion through a PK wound. Eye- and vision-salvaging palladium-103 plaque radiation was performed. An amniotic membrane graft was used to buffer and thus protect the cornea during the 7-day treatment. Leaded eye glasses were worn during the day to block emitted radiation and allow functional vision during irradiation., Results: At 3.5 years status posttreatment, the tumor has regressed, PK has become progressively hazy (within the irradiated zone), and his vision is stable at 20/320. The epicorneal tumor has disappeared, and the intraocular tumor nodules are more highly reflective, but persistent. There has been no intraocular tumor progression, worsening of his glaucoma, or evidence of intraocular radiation vasculopathy., Conclusions: Transcorneal intraocular tumor invasion was controlled using palladium-103 ophthalmic plaque radiation therapy applied through the natural and donor cornea. Definitive treatment resulted in local tumor control and preservation of vision.

Purpose: To provide a clinical description of a case of bilateral choroidal melanoma in a patient treated with palladium-103 ( 103 Pd) plaque brachytherapy., Methods: An 81-year-old man presented with choroidal melanoma in both eyes. In consideration of tumor sizes and locations, treatment involved insertion of 103 Pd radioactive plaque in the right eye followed by the left at an interval of 2 months., Results: At 1-year follow-up, bilateral local control has been associated with apical tumor height regression, and visual acuity has been preserved (20/20 in the right eye and 20/25 in the left). Exudative subretinal fluid has resolved. There has been no metastasis., Conclusion: Bilateral choroidal melanomas are rare, reported to be either simultaneous or sequential as well as treatable. In this case, we were able to achieve tumor regression and preserve visual acuity in both eyes after plaque brachytherapy.

Nowadays, Monte Carlo calculations are commonly used for the evaluation of dose distributions and dose volume histograms in eye brachytherapy. However, currently available eye models have simple geometries, and main substructures of the eye are either not defined in details or not distinguished at all. In this work absorbed doses of eye substructures have been estimated for eye plaque brachytherapy using the most realistic eye model available, and compared with absorbed doses obtained with other available eye models. For this, a medium-sized tumour on the left sides of the right eye was considered. Dosimetry calculations were performed for four different eye models developed based on a literature review, and using a 12 mm Collaborative Ocular Melanoma Study plaque containing 131 Cs, 103 Pd, and 125 I sources. Obtained results illustrate that the estimated doses received by different eye substructures strongly depend on the model used to represent the eye. It is shown here that using a non-realistic eye model leads to a wrong estimation of doses for some eye substructures. For example, dose differences of up to 35% were observed between the models proposed by Nogueira and co-workers and Yoriyaz and co-workers, while doses obtained by use of the models proposed by Lesperance and co-workers, and Behrens and co-workers differed up to 100 and 63% as compared to the situation when a realistic model was used, respectively. Moreover, comparing different radionuclides showed that the most uniform dose distribution in the considered tumour region was that from 131 Cs, with a coefficient of variation of 33%. In addition, considering the realistic eye model, it was found that the radiosensitive region of the lens received more than the threshold dose of cataract induction (0.5 Gy), for all investigated radionuclides.

The authors present a case of a pregnant woman with uveal melanoma treated with plaque brachytherapy. Her calculated fetal radiation dose was significantly below accepted levels. The use of the authors' novel, custom-made lead chin shield further diminished irradiation of the fetus. This patient had uncomplicated treatment course, delivered a healthy child full term, achieved local tumor control, and maintained 20/25 vision at 1-year follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:364-368.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To present our 12-year experience with low-energy-photon, slotted eye plaque radiation therapy., Design: Retrospective interventional case series., Methods: Setting: The New York Eye Cancer Center., Study Population: Fifty-two consecutive patients with uveal melanomas near, touching, or surrounding the optic disc., Intervention: Slotted eye plaque radiation therapy., Main Outcome Measures: Change in visual acuity, local tumor control, radiation side effects, eye salvage, and systemic metastases., Results: Tumors were peripapillary within 1.5 mm of the optic disc (n = 8, 15%), juxtapapillary touching ≤180 degrees (n = 23, 44%), or circumpapillary >180 degrees and encircling the disc (n = 21, 41%). Mean follow-up was 47 months (median 34 months, range 6-146 months). Radiation induced a mean 41.2% reduction in tumor thickness. Life table analysis showed that 69% of patients retained their visual acuities ≥ 20/40 and had a vision loss-free survival 84 months after treatment. Also, 90% of patients retained their visual acuity between 20/50 and 20/200 and had a vision loss-free survival 36 months after treatment. Slotted plaque brachytherapy was associated with 4% secondary cataract, 11% neovascular glaucoma, and no dry eye or eyelash loss. Local tumor control (no recurrence) was achieved in 98.1% of patients. Life table analysis showed an overall enucleation-free survival of 93% and metastasis-free survival of 94%., Conclusions: Slotted plaque radiation therapy provided a normalized plaque-tumor position, such that the entire choroidal melanoma plus a 2- to 3-mm free margin of normal-appearing tissue was included in the targeted zone. At 12 years, slotted plaque radiation therapy resulted in high rates of local tumor control and vision and eye retention., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gold nanoparticles (Au NPs) distributed in the vicinity of low-dose rate (LDR) brachytherapy seeds could multiply their efficacy thanks to the secondary emissions induced by the photoelectric effect. Injections of radioactive LDR gold nanoparticles (LDR Au NPs), instead of conventional millimeter-size radioactive seeds surrounded by Au NPs, could further enhance the dose by distributing the radioactivity more precisely and homogeneously in tumors. However, the potential of LDR Au NPs as an emerging strategy to treat cancer is strongly dependent on the macroscopic diffusion of the NPs in tumors, as well as on their microscopic internalization within the cells. Understanding the relationship between interstitial and intracellular distribution of NPs, and the outcomes of dose deposition in the cancer tissue is essential for considering future applications of radioactive Au NPs in oncology. Here, LDR Au NPs ( 103 Pd:Pd@Au-PEG NPs) were injected in prostate cancer tumors. The particles were visualized at time-points by computed tomography imaging ( in vivo), transmission electron microscopy ( ex vivo), and optical microscopy ( ex vivo). These data were used in a Monte Carlo-based dosimetric model to reveal the dose deposition produced by LDR Au NPs both at tumoral and cellular scales. 103 Pd:Pd@Au-PEG NPs injected in tumors produce a strong dose enhancement at the intracellular level. However, energy deposition is mainly confined around vesicles filled with NPs, and not necessarily close to the nuclei. This suggests that indirect damage caused by the production of reactive oxygen species might be the leading therapeutic mechanism of tumor growth control, over direct damage to the DNA.

Purpose: Interest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction., Methods and Materials: Patients treated with Pd-103 to either 125 Gy or 90-100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90-100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model., Results: One hundred ninety-one and 41 patients were treated with 125 Gy versus 90-100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS., Conclusion: Lower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes., Methods and Materials: Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs., Results: From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively., Conclusions: The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)