Parylene Membrane Research Articles

On reactive Ion Etching of Parylene-C with Simple Photoresist Mask for Fabrication of High Porosity Membranes to Capture Circulating and Exfoliated Tumor Cells.

A high porosity micropore arrayed parylene membrane is a promising device that is used to capture circulating and exfoliated tumor cells (CTCs and ETCs) for liquid biopsy applications. However, its fabrication still requires either expensive equipment or an expensive process. Here, we report on the fabrication of high porosity (>40%) micropore arrayed parylene membranes through a simple reactive ion etching (RIE) that uses photoresist as the etching mask. Vertical sidewalls were observed in etched parylene pores despite the sloped photoresist mask sidewalls, which was found to be due to the simultaneous high DC-bias RIE induced photoresist melting and substrate pedestal formation. A theoretical model has been derived to illustrate the dependence of the maximum membrane thickness on the final pore-to-pore spacing, and it is consistent with the experimental data. A simple, yet accurate, low number (<50) cell counting method was demonstrated through counting cells directly inside a pipette tip under phase-contrast microscope. Membranes as thin as 3 μm showed utility for low number tumor cell capture, with an efficiency of 87-92%.

MD-DFT Calculations on Dissociative Absorption Configurations of FOX-7 on (001)- and (101)-Oriented Crystalline Parylene Protective Membranes.

Crystalline poly-para-xylylene (parylene) has the potential for use as a protective membrane to delay the nucleation of explosives by separating the explosives and their decomposition products to decrease the explosive sensitivity. Here, molecular dynamics (MD) and density functional theory (DFT) techniques were used to calculate the dissociative adsorption configurations of 1,1-diamino-2,2-dinitroethylene (FOX-7) on (001)- and (101)-oriented crystalline parylene membranes. Based on the results of the calculations, this work demonstrates that the -NO2-π electrostatic interactions are the dominant passivation mechanism of FOX-7 on these oriented surfaces. FOX-7 can dissociatively adsorb on oriented parylene membranes due to the interactions between the LUMO of the toluene (or methyl) groups on parylene and the HOMO of the -NO2 (or -NH2) groups on FOX-7. The formation of a new intermolecular H-bond with the ONO group leads to FOX-7 decomposition via intramolecular C-NO2 bond fission and nitro-to-nitrite rearrangement. The most likely adsorption configurations are described in terms of the decomposition products, surface active groups of parylene, binding behaviors, and N charge transfer. Importantly, the (001)-oriented parylene AF8 membrane is promising for use as a protective membrane to passivate the high-energy -NO2 bonds during the dissociative adsorption of FOX-7. This study offers a new perspective on the development of protective membranes for explosives.

Needle‐type pressure sensor with silicone oil and parylene membrane inside for minimally invasive measurement

AbstractThis paper addresses a pressure sensor for body pressure measurement. Many pressure sensors have been developed for disease treatment in the medical field. However, these sensors require inserting electronic components and other sensor elements via surgical operations, so the measurement physically burdens patients. Hence, we proposed a needle‐type pressure sensor using MEMS (Micro Electro Mechanical Systems) cantilever. The sensor has a needle part with a thin membrane on the tip and is filled with incompressible fluid inside. The fractional resistance of the built‐in piezoresistive cantilever varies according to the pressure change applied to the needle tip. We can measure body fluid pressure with minimal surgery by inserting a simple needle into the target organ. Because the fabricated sensor responded to pseudo‐body pressure changes, it was suggested that the fabricated needle‐type pressure sensor could detect pressure inside the body.

Impact of Non-Accelerated Aging on the Properties of Parylene C

The polymer Parylene combines a variety of excellent properties and, hence, is an object of intensive research for packaging applications, such as the direct encapsulation of medical implants. Moreover, in the past years, an increasing interest for establishing new applications for Parylene is observed. These include the usage of Parylene as a flexible substrate, a dielectric, or a material for MEMS, e.g., a bonding adhesive. The increasing importance of Parylene raises questions regarding the long-term reliability and aging of Parylene as well as the impact of the aging on the Parylene properties. Within this paper, we present the first investigations on non-accelerated Parylene C aging for a period of about five years. Doing so, free-standing Parylene membranes were fabricated to investigate the barrier properties, the chemical stability, as well as the optical properties of Parylene in dependence on different post-treatments to the polymer. These properties were found to be excellent and with only a minor age-related impact. Additionally, the mechanical properties, i.e., the Young's modulus and the hardness, were investigated via nano-indentation over the same period of time. For both mechanical properties only, minor changes were observed. The results prove that Parylene C is a highly reliable polymer for applications that needs a high long-term stability.

Bio-Interface on Freestanding Nanosheet of Microelectromechanical System Optical Interferometric Immunosensor for Label-Free Attomolar Prostate Cancer Marker Detection.

Various biosensors that are based on microfabrication technology have been developed as point-of-care testing devices for disease screening. The Fabry–Pérot interferometric (FPI) surface-stress sensor was developed to improve detection sensitivity by performing label-free biomarker detection as a nanomechanical deflection of a freestanding membrane to adsorb the molecules. However, chemically functionalizing the freestanding nanosheet with excellent stress sensitivity for selective molecular detection may cause the surface chemical reaction to deteriorate the nanosheet quality. In this study, we developed a minimally invasive chemical functionalization technique to create a biosolid interface on the freestanding nanosheet of a microelectromechanical system optical interferometric surface-stress immunosensor. For receptor immobilization, glutaraldehyde cross-linking on the surface of the amino-functionalized parylene membrane reduced the shape variation of the freestanding nanosheet to 1/5–1/10 of the previous study and achieved a yield of 95%. In addition, the FPI surface-stress sensor demonstrated molecular selectivity and concentration dependence for prostate-specific antigen with a dynamic range of concentrations from 100 ag/mL to 1 µg/mL. In addition, the minimum limit of detection of the proposed sensor was 2,000,000 times lower than that of the conventional nanomechanical cantilevers.

Microengineered 3D Collagen Gels with Independently Tunable Fiber Anisotropy and Directionality.

Cellular processes, including differentiation, proliferation, and migration, have been linked to the alignment (anisotropy) and orientation (directionality) of collagen fibers in the native extracellular matrix (ECM). Given the critical role that biophysical cell-matrix interactions play in regulating biological functions, several microfluidic-based methods have been used to establish 3D collagen gels with defined fiber properties; these gels have helped to establish quantitative relationships between structural ECM cues and observed cell responses. Although existing microfluidic fabrication methods provide excellent definition over collagen fiber anisotropy, they have not demonstrated the independent control over fiber anisotropy and directionality necessary to replicate in vivo collagen architecture. Therefore, to advance collagen microengineering capabilities, we present a user-friendly technology platform that uses controlled fluid flows within a non-uniform microfluidic channel network to create collagen landscapes that can be tuned as a function of extensional strain rate. Herein, we demonstrate capabilities to i) control the degree of fiber anisotropy, ii) create spatial gradients in fiber anisotropy, iii) independently define fiber directionality, and iv) generate multi-material interfaces within a 3D environment. We then address the practical issue of integrating cells into microfluidic systems by using a peel-off template technique to provide direct access to microengineered collagen gels, and demonstrate that cells respond to the defined properties of the landscape. Finally, the platform's modular capability is highlighted by integrating a sub-micrometer thick porous parylene membrane onto the microengineered collagen as a method to define cell-substrate interactions.

Abstract B26: A new way of fabricating high-porosity parylene membranes for high-throughput capturing of viable circulating and exfoliated tumor cells from large-volume bodily fluids

Abstract Liquid biopsy is a critical component in cancer precision medicine. The ability to capture rare cancer cells from liquid samples, such as circulating tumor cells (CTCs) from peripheral blood as well as exfoliated tumor cells (ETCs) from other body fluids, has shown great promises in cancer detection and prognosis, as well as understanding of cancer biology at different stages. Different ways have been developed for rare cancer cell capture, including biomarker-based immunocapture and capture through other physical processes, such as size, mechanical or dielectric properties, hydrodynamic fluids, etc. However, the throughputs of these techniques are limited to 0.2-2 mL/min. Recently, a high-porosity parylene membrane has been shown to be able to process sample at a fluid rate of &amp;gt; 100 mL/min, which would greatly extend the capability of CTC and ETC-based liquid biopsy. The high porosity of the membrane can also dramatically reduce the shear stress the tumor cells encountered during capture, which has been shown to be critical to maintain cell viability. However, the current parylene membrane fabrication involves deep Si reactive ion etching, which is an expensive process and not widely available. The release of the parylene membrane can also be challenging. We report here a new method to fabricate the parylene membrane using simple photolithography and reactive ion etching techniques. The fabricated parylene membranes and their capability of processing large volume sample for viable cell capture will be presented. Citation Format: Jian Gu, Inad Rabadi, Frederic Zenhausern, David Carpentieri, Jue Wang. A new way of fabricating high-porosity parylene membranes for high-throughput capturing of viable circulating and exfoliated tumor cells from large-volume bodily fluids [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B26.

Vapor-phase synthesis of poly(p-xylylene) membranes for gas separations

We report a vapor-phase deposition of poly(p-xylylene) (parylene) membranes for gas separations. Three parylene membranes, poly[(2-chloro-p-xylylene)] (parylene C), poly[(4-amino-p-xylylene)-co-(p-xylylene)] (parylene A), and poly[(2-carboxylic acid N-hydroxysuccinimide ester)-co-(p-xylylene)] (parylene NHS ester), were evaluated. These membranes were deposited on a support of porous poly(vinylidene fluoride) with a dense layer of poly(vinyl alcohol) cast on its top surface. The as-synthesized parylene membranes were characterized by scanning electron microscopy, FT-IR spectroscopy, and the measurements of water contact angle. Single-gas permeation with hydrogen, nitrogen, methane, and carbon dioxide was performed on the parylene membranes for assessing their molecular transport properties. These parylene membranes showed gas permeability of up to hundreds of barrer. To further enhance the gas separation performance of the parylene membranes, polyethylenimine (PEI) was used for modifying the surface of the membranes composed of parylene NHS ester.

Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

Skin-Potential Variation Insensitive Dry Electrodes for ECG Recording.

A skin-potential variation (SPV) insensitive dry electrode is developed to remove the interference of SPV. Based on a conventional microneedles array-based electrode, a layer of Parylene membrane is coated at the root of microneedles to insulate the electrode from the corneum layer. Only tips of the needles are exposed to make it can contact with the stratum germinativum layer directly. As a result, skin potential will not be coupled into the recording electrode. Thus, SPV will not influence the biopotential recording in the dynamic state. The proposed electrode is potential for a device which is insensitive to the motion noise source from SPV. It paves the way for applications of the proposed dry electrode in the wearable technology which require strong anti-motion interference ability.

Wide-frequency-bandwidth whisker-inspired MEMS vector hydrophone encapsulated with parylene

In order to eliminate polyurethane hat resonance frequency intervention and reduce fluid influence, a whisker-inspired MEMS vector hydrophone (WIVH) encapsulated with parylene is proposed to broaden frequency bandwidth and improve sensitivity-frequency response performance, compared to the lateral line-inspired MEMS vector hydrophone (LLIVH). Parylene that is conformally deposited on the device surface replaces polyurethane encapsulating hat and silicone oil existing in current encapsulation technology. The main advantage of WIVH as demonstrated by modelling and characterization is the enhanced bandwidth response, which is the critical factor in hydrophone design. Acoustic pressure gradient properties of the WIVH and LLIVH are analyzed to demonstrate the influence of the polyurethane hat. The interactions of the parylene membrane with fluid and the influences on vibrating performance are also investigated. Resonance measurement and sensitivity-frequency response analysis demonstrate the frequency bandwidth of the WIVH could be extended twice compared to that of the LLIVH. Moreover, the WIVH is proved to act as a typical pressure gradient hydrophone with an increment of 6 dB per octave in the linear region.

In situ vapor-deposited parylene substrates for ultra-thin, lightweight organic solar cells

We fabricate the thinnest (1.3 μm) and lightest (3.6 g/m2) solar cells yet demonstrated, with weight-specific power exceeding 6 W/g, in order to illustrate the lower limits of substrate thickness and materials use achievable with a new processing paradigm. Our fabrication process uniquely starts with growth of an ultra-thin flexible polymer substrate in vacuum, followed by deposition of electrodes and photoactive layers in situ. With this process sequence, the entire cell—from transparent substrate to active layers to encapsulation—can be fabricated at room temperature without solvents and without breaking vacuum, avoiding exposure to dust and other contaminants, and minimizing damage risk associated with handling of thin substrates. We use in situ vapor-phase growth of smooth, transparent, and flexible parylene-C films to produce ultra-thin, lightweight molecular organic solar cells as thin as 2.3 μm including encapsulation with a second parylene-C film. These parylene-based devices exhibit power conversion efficiencies and fabrication yields comparable to glass-based cells. Flexible solar cells on parylene membranes can be seamlessly adhered to a variety of solid surfaces to provide additive solar power.

Fabrication of hemispherical liquid encapsulated structures based on droplet molding

We have developed and demonstrated a method for forming spherical structures of a thin polydimethylsiloxane (PDMS) membrane encapsulating a liquid. Liquid encapsulation can enhance the performance of microelectromechanical systems (MEMS) devices by providing deformability and improved dielectric properties. Parylene deposition and wafer bonding are applied to encapsulate liquid into a MEMS device. In parylene deposition, a parylene membrane is directly formed onto a liquid droplet. However, since the parylene membrane is stiff, the membrane is fragile. Although wafer bonding can encapsulate liquid between two substrates, the surface of the fabricated structure is normally flat. We propose a new liquid encapsulation method by dispensing liquid droplets. At first, a 20 μl PDMS droplet is dispensed on ethylene glycol. A 70 μl glycerin droplet is dispensed into a PDMS casting solution layer. The droplet forms a layer on heated ethylene glycol. Glycerin and ethylene glycol are chosen for their high boiling points. Additionally, a glycerin droplet is dispensed on the layer and surrounded by a thin PDMS casting solution film. The film is baked for 1 h at 75 °C. As the result, a structure encapsulating a liquid in a flexible PDMS membrane is obtained. We investigate the effects of the volume, surface tension, and guide thickness on the shape of the formed structures. We also evaluated the effect of the structure diameter on miniaturization. The structure can be adapted for various functions by changing the encapsulated liquid. We fabricated a stiffness-tunable structure by dispensing a magnetorheoligical fluid droplet with a stiffness that can be changed by an external magnetic field. We also confirmed that the proposed structure can produce stiffness differences that are distinguishable by humans.

“Lollipop-shaped” high-sensitivity Microelectromechanical Systems vector hydrophone based on Parylene encapsulation

This paper presents methods of promoting the sensitivity of Microelectromechanical Systems (MEMS) vector hydrophone by increasing the sensing area of cilium and perfect insulative Parylene membrane. First, a low-density sphere is integrated with the cilium to compose a “lollipop shape,” which can considerably increase the sensing area. A mathematic model on the sensitivity of the “lollipop-shaped” MEMS vector hydrophone is presented, and the influences of different structural parameters on the sensitivity are analyzed via simulation. Second, the MEMS vector hydrophone is encapsulated through the conformal deposition of insulative Parylene membrane, which enables underwater acoustic monitoring without any typed sound-transparent encapsulation. Finally, the characterization results demonstrate that the sensitivity reaches up to −183 dB (500 Hz 0dB at 1 V/μPa), which is increased by more than 10 dB, comparing with the previous cilium-shaped MEMS vector hydrophone. Besides, the frequency response takes on a sensitivity increment of 6 dB per octave. The working frequency band is 20–500 Hz and the concave point depth of 8-shaped directivity is beyond 30 dB, indicating that the hydrophone is promising in underwater acoustic application.

PerFlexMEA: a thin microporous microelectrode array for in vitro cardiac electrophysiological studies on hetero-cellular bilayers with controlled gap junction communication.

The new microelectrode array device presented is called PerFlexMEA and it enables controlled coupling between myocytes and nonmyocytes used in cardiovascular conduction studies. The device consists of an 8 μm thin parylene microporous membrane with a 4 × 5 microelectrode array patterned on one side. Myocytes and nonmyocytes can be plated on either side of the parylene membrane to create a tissue bilayer. The 3-3.5 μm diameter pores allow inter-layer dye and electrical coupling without transmembrane cell migration. Cell migration was found to vary with cell-type and micropore diameter. Pore density can be varied based on desired coupling ratio. The flexible parylene membrane is packaged between two rigid thermoplastic layers, such that the microelectrode array region is exposed, while the rest of the device remains insulated. The packaged PerFlexMEA fits in a 60 mm culture dish. Recording experiments are performed by simply plugging it into a commercially available multielectrode amplifier system. Recorded signals were processed and analysed using scripts generated in MATLAB. Our experimental results provide evidence of the reliability of this device, as conduction velocity was observed to decrease after inducing lateral hetero-cellular controlled coupling between myocytes and HeLa cells expressing connexin 43.

Microdevice-based cell therapy for age-related macular degeneration.

This chapter reports the application of a micromachined parylene-C device as an artificial Bruch's membrane for the stem cell-based therapy of age-related macular degeneration. The feasibility of parylene-C as a substitute substrate material is demonstrated by evaluating the permeability of membranes of submicron thicknesses. It has been found that parylene-C membranes thinner than 0.3 µm possess similar molecular weight exclusion limit and nutrient diffusion flux to that of the healthy human Bruch's membrane. This conclusion is further validated by the in vitro perfusion cell viability test. Since the submicron parylene-C itself is difficult to handle, we design a mesh-supported submicron parylene membrane (MSPM) to provide sufficient mechanical support. This MSPM can support the growth of retinal pigment epithelial (RPE) cells in a monolayer with well-polarized morphology. Human embryonic stem cell-derived H9-RPE cells are cultured in vitro on the MSPM for one month before the implantation of the MSPM into the rat's retina. To facilitate the surgical implantation, a parylene-C/SU-8 hybrid microfluidic device is designed as an inserter. Histological studies with hematoxylin-eosin staining and immunofluorescence staining show that the implanted RPE cells adhere well to the artificial Bruch's membrane and are able to maintain high viability and normal morphology in vivo.

Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

To evaluate cell survival and tumorigenicity of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects.

In Vivo Detection of hESC-RPE Cells via Confocal Near-Infrared Fundus Reflectance

To investigate whether the confocal near-infrared reflectance (NIR) imaging modality could detect the in vivo presence of retinal pigment epithelium cells derived from embryonic human stem cells (hESC-RPE) implanted into the subretinal space of the Royal College of Surgeons (RCS) rat. Monthly NIR images were obtained from RCS rats implanted with either hESC-RPE seeded on a parylene membrane (n = 14) or parylene membrane without cells (n = 14). Two independent, masked investigators graded the images. Histology and immunohistochemistry were performed at different time points (150, 210, and 270 postnatal days of age). NIR images revealed that an average of 20.53% of the parylene membrane area was covered by hESC-RPE. RPE-65 and TRA-1-85 confirmed the presence of human-specific RPE cells in those animals. No areas corresponding to cells were found in the group implanted with membrane only. Intergrader agreement was high (r = 0.89-0.92). The NIR mode was suitable to detect the presence of hESC-RPE seeded on a membrane and implanted into the subretinal space of the RCS rat.

Final results from a trial of a combination herbal supplement for biochemically recurrent prostate cancer.

e16020 Background: No standard exists for the treatment of bcrPC. Concern over deleterious effects of androgen deprivation (ADT) and lack of proven survival benefit in this setting makes initiation of ADT inappropriate for some patients. A non-hormonal, non-toxic agent to reduce PSA would be a welcome alternative to observation. We tested Prostate Health Cocktail (PHC), a supplement containing vitamin D &amp; E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could decrease PSA. Methods: Eligible men had a rising PSA with doubling time between 3 and 36 months, with no evidence of metastases on CT and bone scan. After IRB approval, 40 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after cycle 1, then every 2 cycles thereafter with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase above baseline/nadir AND absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: 60 men screened, 17 failed (28%). Median age was 67 (range 54-84) and baseline PSA 2.8 ng/mL (1.1-84.1). 23% had primary radiation only, 25% had prostatectomy, and 52% had both; 23% had Gleason 8-10. The median # of cycles was 8 (1-13). 15/40 men (37.5%) had a PSA decline (1.1%-55% maximum decrease). 43% stopped therapy for PSA progression, with median time to progression 10.2 months. Circulating tumor cells were detected in 5 of the first 23 subjects; complete CTC data will be presented. There was no significant change in testosterone or DHT during treatment. Toxicities possibly related to PHC included grade 1 or 2 liver enzyme elevations [transient], grade 1 or 2 gastrointestinal symptoms (9), grade 1 weakness/dizziness/pain (5), and grade 1 fatigue (2). 5 men continue on study, 3 lost to f/u, 16 have developed metastases, median time to mets 31.5 months from bcr. Conclusions: PHC induced PSA declines in 37% of patients with bcrPC, and was not associated with changes in serum androgens or significant toxicities. PHC is a potential alternative to observation in select patients with bcrPC. Clinical trial information: NCT00669656.

961 - Updated Analysis of a Combination Herbal Supplement Trial in Biochemically Recurrent Prostate Cancer

ABSTRACT Background After curative local therapy, thousands of men will experience rising PSA as an early indicator of recurrent prostate cancer. For these men no standard of care exists, and concern over serious side effects of androgen deprivation (ADT) makes delaying ADT common. We tested Prostate Health Cocktail (PHC), which contains vitamins D & E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could induce PSA declines. Methods Eligible men had a rising PSA with doubling time (DT) between 3 and 36 months, with no evidence of metastases on CT and bone scan. Treatment included PHC 3 capsules PO daily for 4 week cycles for a maximum of 1 year. PSA was repeated after 1 cycle and then every 2 cycles thereafter with imaging only as clinically indicated; the primary endpoint was PSA decline at 12 weeks. PSA progression was defined as 25% increase above baseline/nadir and absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results A total of 36 patients were enrolled as of January 31, 2012; 3 were retrospectively classified as ineligible and were excluded from all analyses except for toxicity. The median age was 67 (range 54-85) and baseline PSA was 2.9 ng/mL (1.1-53.2). The median number of cycles was 8 (1-13). Stable PSA was the best response for 25/27 men assessable at 12 weeks (93%) and 11/33 men (33%) had a PSA decline (1.1%-49.0% decrease). There was no significant change in testosterone or DHT during treatment. Circulating tumor cells were detected in some of the subjects. One patient had grade 3 transaminitis in the setting of alcohol consumption, otherwise the toxicities were limited to grade 1 or 2 and related to the gastrointestinal and metabolic/laboratory systems. Conclusion PHC demonstrated activity in men with biochemical recurrence, resulting in PSA declines in about a third of cases, and was not associated with changes in serum androgens or significant toxicities. For the first time, we are reporting that circulating tumor cells can be detected in men with biochemical recurrence using filter technology. Disclosure J. Pinski: I am a co-owner of OncoNatural Solutions Inc, the company which produces the Prostate Heath Coctail (PHC). All other authors have declared no conflicts of interest.