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Frontiers in Oncology 2024Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global...
BACKGROUND
Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT.
METHODS
A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan-Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores.
RESULTS
We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity ( < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 μg/L subgroups.
CONCLUSION
HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.
PubMed: 38434681
DOI: 10.3389/fonc.2024.1344798 -
The Cochrane Database of Systematic... Jul 2018Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality... (Review)
Review
BACKGROUND
Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality of life (QoL) and function. The underlying pathophysiological mechanism remains unclear for this condition, which makes establishing effective treatments challenging.
OBJECTIVES
To assess the effectiveness of interventions used for the treatment of brain radionecrosis in adults over 18 years old.
SEARCH METHODS
In October 2017, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for eligible studies. We also searched unpublished data through Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials for ongoing trials and handsearched relevant conference material.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any intervention directed to treat brain radionecrosis in adults over 18 years old previously treated with radiation therapy to the brain. We anticipated a limited number of RCTs, so we also planned to include all comparative prospective intervention trials and quasi-randomised trials of interventions for brain radionecrosis in adults as long as these studies had a comparison group that reflects the standard of care (i.e. placebo or corticosteroids). Selection bias was likely to be an issue in all the included non-randomised studies therefore results are interpreted with caution.
DATA COLLECTION AND ANALYSIS
Two review authors (CC, PB) independently extracted data from selected studies and completed a 'Risk of bias' assessment. For dichotomous outcomes, the odds ratio (OR) for the outcome of interest was reported. For continuous outcomes, treatment effect was reported as mean difference (MD) between treatment arms with 95% confidence intervals (CIs).
MAIN RESULTS
Two RCTs and one prospective non-randomised study evaluating pharmacological interventions met the inclusion criteria for this review. As each study evaluated a different drug or intervention using different endpoints, a meta-analysis was not possible. There were no trials of non-pharmacological interventions that met the inclusion criteria.A very small randomised, double-blind, placebo-controlled trial of bevacizumab versus placebo reported that 100% (7/7) of participants on bevacizumab had reduction in brain oedema by at least 25% and reduction in post-gadolinium enhancement, whereas all those receiving placebo had clinical or radiological worsening or both. This was an encouraging finding but due to the small sample size we did not report a relative effect. The authors also failed to provide adequate details regarding the randomisation and blinding procedures Therefore, the certainty of this evidence is low and a larger RCT adhering to reporting standards is needed.An open-label RCT demonstrated a greater reduction in brain oedema (T2 hyperintensity) in the edaravone plus corticosteroid group than in the corticosteroid alone group (MD was 3.03 (95% CI 0.14 to 5.92; low-certainty evidence due to high risk of bias and imprecision); although the result approached borderline significance, there was no evidence of any important difference in the reduction in post-gadolinium enhancement between arms (MD = 0.47, 95% CI - 0.80 to 1.74; low-certainty evidence due to high risk of bias and imprecision).In the RCT of bevacizumab versus placebo, all seven participants receiving bevacizumab were reported to have neurological improvement, whereas five of seven participants on placebo had neurological worsening (very low-certainty evidence due to small sample size and concerns over validity of analyses). While no adverse events were noted with placebo, three severe adverse events were noted with bevacizumab, which included aspiration pneumonia, pulmonary embolus and superior sagittal sinus thrombosis. In the RCT of corticosteroids with or without edaravone, the participants who received the combination treatment were noted to have significantly greater clinical improvement than corticosteroids alone based on LENT/SOMA scale (OR = 2.51, 95% CI 1.26 to 5.01; low-certainty evidence due to open-label design). No differences in treatment toxicities were observed between arms.One included prospective non-randomised study of alpha-tocopherol (vitamin E) versus no active treatment was found but it did not include any radiological assessment. As only one included study was a double-blinded randomised controlled trial, the other studies were prone to selection and detection biases.None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements.A limited number of prospective studies were identified but subsequently excluded as these studies had a limited number of participants evaluating different pharmacological interventions using variable endpoints.
AUTHORS' CONCLUSIONS
There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.
Topics: Adrenal Cortex Hormones; Adult; Antipyrine; Bevacizumab; Brain; Brain Edema; Drug Therapy, Combination; Edaravone; Gadolinium; Humans; Non-Randomized Controlled Trials as Topic; Radiation Injuries; Radiosurgery; Radiotherapy; Randomized Controlled Trials as Topic
PubMed: 29987845
DOI: 10.1002/14651858.CD011492.pub2 -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474 -
Cureus Jun 2024Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One... (Review)
Review
Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX). This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC. This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases. Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group. In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.
PubMed: 38835557
DOI: 10.7759/cureus.61547 -
Applied Radiation and Isotopes :... Apr 2016The present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond (89)Sr and (153)Sm. In addition,... (Review)
Review
PURPOSE
The present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond (89)Sr and (153)Sm. In addition, it aims to review and summarize the clinical outcomes associated with the palliative treatment of bone metastases using different radiopharmaceuticals.
MATERIALS AND METHODS
A literature search was conducted on Science Direct and PubMed databases (1990 - 2015). The following search terms were combined in order to obtain relevant results: "bone", "metastases", "palliative", "care", "therapy", "treatment", "radiotherapy", "review", "radiopharmaceutical", "phosphorus-32", "strontium-89", "yttrium-90", "tin-117m", "samarium-153", "holmium-166", "thulium-170", "lutetium-177", "rhenium-186", "rhenium-188" and "radium-223". Studies were included if they provided information regarding the clinical outcomes.
RESULTS AND CONCLUSIONS
A comparative analysis of the measured therapeutic response of different radiopharmaceuticals, based on previously published data, suggests that there is a lack of substantial differences in palliative efficacy among radiopharmaceuticals. However, when the comparative analysis adds factors such as patient's life expectancy, radionuclides' physical characteristics (e.g. tissue penetration range and half-life) and health economics to guide the rational selection of a radiopharmaceutical for palliative treatment of bone metastases, (177)Lu and (188)Re-labeled radiopharmaceuticals appear to be the most suitable radiopharmaceuticals for treatment of small and medium/large size bone lesions, respectively.
Topics: Bone Neoplasms; Female; Humans; Male; Pain Management; Palliative Care; Radioisotopes; Radiopharmaceuticals; Samarium; Strontium Radioisotopes
PubMed: 26773820
DOI: 10.1016/j.apradiso.2016.01.003 -
The British Journal of Radiology Jan 2019Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater...
Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Four randomised trials testing fraction sizes in the range 2.7-3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week.
Topics: Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Mastectomy; Mastectomy, Segmental; Middle Aged; Neoplasm Recurrence, Local; Radiation Dose Hypofractionation; Radiotherapy, Adjuvant
PubMed: 29345152
DOI: 10.1259/bjr.20170849 -
SAGE Open Medicine 2020In this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed... (Review)
Review
INTRODUCTION
In this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed tomography.
METHODS
We conducted review of the current literature at PubMed/MEDLINE until February 2020. The search language was English.
RESULTS
The most widely used radiopharmaceuticals are the following:Experimental/pre-clinical approaches: (18)F-Misonidazole (18F-MISO) under clinical development, D(18)F-Fluoro-Methyl-Tyrosine (18F-FMT), 18F-FAMT (L-[3-18F] (18)F-Fluorothymidine (18F-FLT)), (18)F-Fluoro-Azomycin-Arabinoside (18F-FAZA), (68)Ga-Neomannosylated-Human-Serum-Albumin (68Ga-MSA) (23), (68)Ga-Tetraazacyclododecane (68Ga-DOTA) (as theranostic agent), (11)C-Methionine (11C-MET), 18F-FPDOPA, αβ integrin, Ga-RGD, Cu-DOTA-RGD, F-Alfatide, Folate Radio tracers, and immuno-positron emission tomography radiopharmaceutical agents.Clinically approved procedures/radiopharmaceuticals agents: (18)F-Fluoro-Deoxy-Glucose (18F-FDG), (18)F-sodium fluoride (18F-NaF) (bone metastases), and (68)Ga-Tetraazacyclododecane (68Ga-DOTA). The quantitative determination and the change in radiopharmaceutical uptake parameters such as standard uptake value, metabolic tumor volume, total lesion glycolysis, FAZA tumor to muscle ratio, standard uptake value tumor to liver ratio, standard uptake value tumor to spleen ratio, standard uptake value maximum ratio, and the degree of hypoxia have prognostic and predictive (concerning the therapeutic outcome) value. They have been associated with the assessment of overall survival and disease free survival. With the positron emission tomography/computed tomography radiopharmaceuticals, the sensitivity and the specificity of the method have increased.
CONCLUSION
In terms of lung cancer, positron emission tomography/computed tomography may have clinical application and utility (a) in personalizing treatment, (b) as a biomarker for the estimation of overall survival, disease free survival, and (c) apply a cost-effective patient approach because it reveals focuses of the disease, which are not found with the other imaging methods.
PubMed: 33062275
DOI: 10.1177/2050312120961594 -
World Journal of Urology Nov 2023Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy...
PURPOSE
Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity.
METHOD
A systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: "urethra-steering" SBRT (restriction of hotspots to the urethra) and "urethra dose-reduction" SBRT (dose reduction to urethra below the prescribed dose).
RESULTS
By limiting the urethra D to 90GyEQD2 (α/β = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years.
CONCLUSION
US-SBRT techniques limiting maximum doses to urethra below a 90Gy (α/β = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.
Topics: Male; Humans; Urethra; Radiosurgery; Neoplasm Recurrence, Local; Prostatic Neoplasms; Urogenital System
PubMed: 37668718
DOI: 10.1007/s00345-023-04579-6 -
International Journal of Radiation... Dec 2018The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms...
PURPOSE
The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms after external beam radiation therapy (EBRT) alone and treatments involving brachytherapy (BT) for prostate cancer after Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and ultimately to perform quantitative syntheses of identified dose/volume tolerances represented by dose-volume histogram (DVH) thresholds, that is, statistically significant (P ≤ .05) cutoff points between symptomatic and asymptomatic patients in a certain study.
METHODS AND MATERIALS
PubMed was scrutinized for full-text articles in English after QUANTEC (January 1, 2010). The inclusion criteria were randomized controlled trials, case-control studies, or cohort studies with tolerance doses for late distinct symptoms ≥3 months after primary radiation therapy for prostate cancer (N > 30). All DVH thresholds were converted into equivalent doses in 2-Gy fractions (EQD2) and were fitted with a linear or linear-quadratic function (goodness of fit, R). The review was registered on PROSPERO (CRD42016042464).
RESULTS
From 33 identified studies, which included 36 to 746 patients per symptom domain, the majority of dose/volume tolerances were derived for GI toxicity after EBRT alone (GI, 97 thresholds; GU, 8 thresholds; SD, 1 threshold). For 5 symptoms (defecation urgency, diarrhea, fecal incontinence, proctitis, and rectal bleeding), relationships between dose/volume tolerances across studies (R = 0.93 [0.82-1.00]), and across symptoms, leading to a curve for overall GI toxicity (R = 0.98), could be determined. For these symptoms, mainly rectal thresholds were found throughout low and high doses (10 Gy ≤ equivalent dose in 2-Gy fractions using α/β = 3Gy (EQD2) ≤ 50 Gy and 55 Gy ≤ EQD2 ≤ 78 Gy, respectively). For BT with or without EBRT, dose/volume tolerances were also mainly identified for GI toxicity (GI, 14 thresholds; GU, 4 thresholds; SD, 2 thresholds) with the largest number of DVH thresholds concerning rectal bleeding (5 thresholds).
CONCLUSIONS
Updated dose/volume tolerances after QUANTEC were found for 17 GI, GU, or SD symptoms. A DVH curve described the relationship between dose/volume tolerances across 5 GI symptoms after EBRT alone. Restricting treatments for EBRT alone using the lower boundaries of this curve is likely to limit overall GI toxicity, but this should be explored prospectively. Dose/volume tolerances for GU and SD toxicity after EBRT alone and after BT with or without EBRT were scarce and support further research including data-sharing initiatives to untangle the dose/volume relationships for these symptoms.
Topics: Humans; Male; Prostatic Neoplasms; Radiation Dosage; Radiotherapy; Radiotherapy Dosage; Safety
PubMed: 30125635
DOI: 10.1016/j.ijrobp.2018.08.015 -
Clinical Orthopaedics and Related... Nov 2016Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range... (Review)
Review
BACKGROUND
Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range of orthopaedic applications. In bulk form, PEEK composites are generally accepted as biocompatible. In particulate form, however, the biologic response relevant to joint replacement devices remains unclear. The biologic response to wear particles affects the longevity of total joint arthroplasties. Particles in the phagocytozable size range of 0.1 µm to 10 µm are considered the most biologically reactive, particularly particles with a mean size of < 1 µm. This systematic review aimed to identify the current evidence for the biologic response to PEEK-based wear debris from total joint arthroplasties.
QUESTIONS/PURPOSES
(1) What are the quantitative characteristics of PEEK-based wear particles produced by total joint arthroplasties? (2) Do PEEK wear particles cause an adverse biologic response when compared with UHMWPE or a similar negative control biomaterial? (3) Is the biologic response affected by particle characteristics?
METHODS
Embase and Ovid Medline databases were searched for studies that quantified PEEK-based particle characteristics and/or investigated the biologic response to PEEK-based particles relevant to total joint arthroplasties. The keyword search included brands of PEEK (eg, MITCH, MOTIS) or variations of PEEK types and nomenclature (eg, PAEK, CFR-PEEK) in combination with types of joint (eg, hip, knee) and synonyms for wear debris or immunologic response (eg, particles, cytotoxicity). Peer-reviewed studies, published in English, investigating total joint arthroplasty devices and cytotoxic effects of PEEK particulates were included. Studies investigating devices without articulating bearings (eg, spinal instrumentation devices) and bulk material or contact cytotoxicity were excluded. Of 129 studies, 15 were selected for analysis and interpretation. No studies were found that isolated and characterized PEEK wear particles from retrieved periprosthetic human tissue samples.
RESULTS
In the four studies that quantified PEEK-based particles produced using hip, knee, and spinal joint replacement simulators, the mean particle size was 0.23 µm to 2.0 µm. The absolute range reported was approximately 0.01 µm to 50 µm. Rod-like carbon particulates and granular-shaped PEEK particles were identified in human tissue by histologic analysis. Ten studies, including six animal models (rat, mouse, and rabbit), three cell line experiments, and two human tissue retreival studies, investigated the biologic response to PEEK-based particles. Qualitative histologic assessments showed immunologic cell infiltration to be similar for PEEK particles when compared with UHMWPE particles in all six of the animal studies identified. However, increased inflammatory cytokine release (such as tumor necrosis factor-α) was identified in only one in vitro study, but without substantial suppression in macrophage viability. Only one study tested the effects of particle size on cytotoxicity and found the largest unfilled PEEK particles (approximately 13 µm) to have a toxic effect; UHMWPE particles in the same size range showed a similar cytotoxic effect.
CONCLUSIONS
Wear particles produced by PEEK-based bearings were, in almost all cases, in the phagocytozable size range (0.1-10 µm). The studies that evaluated the biologic response to PEEK-based particles generally found cytotoxicity to be within acceptable limits relative to the UHMWPE control, but inconsistent when inflammatory cytokine release was considered.
CLINICAL RELEVANCE
To translate new and advanced materials into clinical use more quickly, the clinical relevance and validity of preclinical tests need to be improved. To achieve this for PEEK-based devices, human tissue retrieval studies including subsequent particle isolation and characterization analyses are required. In vitro cell studies using isolated wear particles from tissue or validated joint replacement simulators, instead of manufactured particles, are also required.
Topics: Animals; Arthroplasty, Replacement; Benzophenones; Cytokines; Foreign-Body Reaction; Humans; Inflammation Mediators; Joint Prosthesis; Ketones; Particle Size; Phagocytosis; Polyethylene Glycols; Polyethylenes; Polymers; Prosthesis Design; Prosthesis Failure; Risk Factors; Stress, Mechanical; Treatment Outcome
PubMed: 27432420
DOI: 10.1007/s11999-016-4976-z