title
stringlengths 1
1.19k
| keywords
stringlengths 0
668
| concept
stringlengths 0
909
| paragraph
stringlengths 0
61.8k
| PMID
stringlengths 10
11
|
|---|---|---|---|---|
Conflict of interest | The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC9531217 |
||
Ethical approval | Eligible participants (tertiary students) received detailed written information about the study and then provided their informed consent during each assessment session. To maintain the participants’ confidentiality, the research team de-identified and securely stored the collected data. This study has ethical approval from Curtin University’s Human Research Ethics Committee (Perth, Western Australia), a committee independent from the investigators (registration number: HRE2019-791), provided it is conducted following the standards of the institutional committee and the 1964 Helsinki declaration [ | PMC9531217 |
||
Consent to participate | EVENTS | Prior to study, all participants had provided their consent to take part in the study and have their de-identified data published, presented in public events and conferences. | PMC9531217 |
|
Consent for publication | EVENTS | Prior to study, all participants had provided their consent to have their de-identified data published, presented in public events and conferences. | PMC9531217 |
|
References | PMC9531217 |
|||
Background | tendinopathies, tendinopathy | DEGENERATIVE | The etiology of tendinopathy remains controversial and it is unknown whether degenerative structural changes in tendinopathies are reversible. | PMC10634075 |
Hypothesis | gluteal tendinopathy | There will be no structural change on magnetic resonance imaging (MRI) taken > 2-years after treatment for gluteal tendinopathy. | PMC10634075 |
|
Study Design | Extension of a single site, double-blind, prospective randomized-controlled trial to analyze the additional outcome measure; MRI changes. | PMC10634075 |
||
Methods | gluteal tendinopathy | University of Melbourne ethics approval number: 1852900, trial registration: ACTRN12613000677707. Participants with gluteal tendinopathy who had previously received a leukocyte-rich platelet-rich plasma injection (LR-PRP) or a corticosteroid injection (CSI) had a post treatment MRI between at least 2-years and up to 7 years following trial completion. A blinded, senior musculoskeletal radiologist graded all de-identified MRI scans using the Melbourne Hip Score (MHIP). The primary outcome measure was the change in overall pre- and post-treatment score. | PMC10634075 |
|
Results | Participants (n = 20) underwent MRI at mean time of 4.15 (SD 1.11; range 2–7) years after their initial treatment. There was no change in the overall mean MHIP score for the CSI group (Pre 4.3 (SD 2.3) Post 4.3 (SD 1.1), p = 1.00). Although there was an improvement in the LR-PRP group mean MHIP score (Pre 5.3 (SD 3.0) Post 4.77 (SD 2.5), p = 0.56) it was not statistically significant. However, in the LR-PRP intervention group, five out of nine of participants’ MHIP score improved, with four of these improving by 2–4 points. | PMC10634075 |
||
Conclusion | tendinopathy, gluteal tendinopathy | The hypothesis that there would be no improvement in MHIP scores following treatment of gluteal tendinopathy was supported. Findings of improvement in the LR-PRP group at 4 years would support further studies powered to look for structural improvement. These findings suggest that structural change following treatment for tendinopathy may be possible supporting the inclusion of MRI as a core outcome for future studies. | PMC10634075 |
|
Clinical relevance | DEGENERATIVE | The study suggests that degenerative structural changes in tendons may be reversible. | PMC10634075 |
|
Supplementary Information | The online version contains supplementary material available at 10.1186/s12880-023-01150-y. | PMC10634075 |
||
Significance | PMC10634075 |
|||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12880-023-01150-y. | PMC10634075 |
||
Keywords | PMC10634075 |
|||
Introduction | tendinopathic tendons, gluteal tendinopathy, tendinopathy, musculoskeletal diseases | PATHOPHYSIOLOGY, MUSCULOSKELETAL DISEASES | Accounting for up to 30% of all musculoskeletal consultations [Whilst tendinopathy was originally considered an ‘inflammatory’ condition, the pathophysiology of musculoskeletal diseases is being re-considered.Recent molecular evidence, has acknowledged the inflammatory nature of tendinopathy with key inflammatory processes occurring even before symptoms develop [A recent randomized controlled trial (RCT) study by Fitzpatrick et al. assessed the effectiveness of leukocyte-rich platelet-rich plasma (LR-PRP) injections in the management of gluteal tendinopathy [Limited studies to date have investigated if, and to what extent, structural change occurs on MRI in tendinopathic tendons following treatment [ | PMC10634075 |
Methods | PMC10634075 |
|||
Ethics approval | The study was conducted in accordance with the Declaration of Helsinki and Ethics approval was obtained from the University of Melbourne Human Research Ethics Committee (Ethics approval number: 1852900). The trial was registered with ACTRN12613000677707. All participants provided written informed consent to participate. | PMC10634075 |
||
Study design | This study is an extension of a single site (Melbourne), double-blind, prospective RCT to analyze the structural outcome measure of MRI changes at 2-years or more post treatment in addition to the previously reported clinical outcomes measures [ | PMC10634075 |
||
Participants | gluteal tendinopathy | Participants were drawn from the existing RCT comparing LR-PRP to corticosteroid injection (CSI) for gluteal tendinopathy [ | PMC10634075 |
|
Intervention | No treatment was given to the participants in this study although participants had previously received a single LR-PRP injection (group 1), a single CSI (group 2) or a single CSI followed by a LR-PRP injection (group 3) as described by the methodology and protocol of Fitzpatrick et al. [Where possible, scans were taken on the same machine. The MRI machine used a Skyra 3-T superconducting unit and Numaris/4 Syngo MR 11 software (Siemens), with a slew rate of 200 T/m/s, 45 mT/m gradient amplitude with a high-resolution 18-channel surface coil anteriorly and the 32-channel body coil posteriorly. Multiplanar sagittal, axial, and coronal proton density and fat saturated T2 weighted images were taken. Where it was not possible for participants to access this machine, scans were performed using standard protocols based on the European Society of Skeletal Radiology guidelines [ | PMC10634075 |
||
Outcome measure | bursitis, tendinopathy, fatty infiltration | BONE MARROW OEDEMA, BURSITIS, PATHOLOGY, FATTY INFILTRATION | A blinded, senior musculoskeletal radiologist graded all de-identified MRI scans using the Melbourne Hip Score (MHIP). The severity of soft tissue bursitis and direct gluteal tendon pathology has been shown to affect the adjacent structures, notably fatty infiltration of muscle and bone marrow oedema. Thus, the MHIP score was designed as a holistic score to fully represent the severity of tendinopathy by including both the direct measures of tendon pathology and the indirect measures in the adjacent muscle and bone [ | PMC10634075 |
Statistical analysis | Analysis was conducted using STATA version 13.1 (Stata Corp. 2016 Stata Statistical Software: Release 13.1. College station, TX: Stata Corp LP). Classical 2-sided paired student t-tests were performed to determine if there was a statistically significant difference in the change in pre-and post-treatment score within the trial groups. A sample size calculation performed using | PMC10634075 |
||
Results | PMC10634075 |
|||
Flow of patients | Demographic dataY | Of 76 participants who were eligible for this study, 36 were excluded as they did not have available baseline MRI scans and 8 did not consent to participate (Fig.
MHIP scores graphical representation. MHIP, Melbourne Hip MRI Score; LR-PRP, leukocyte-rich platelet-rich plasma; CSI, corticosteroid injection
Demographic dataY, years; N, number; SD, standard deviation; kg, kilograms, m, meters; mHHS, modified Harris Hip Score. | PMC10634075 |
|
Time to post-treatment MRI | Participants received post-treatment MRI at a mean time of 4.15 (SD 1.11; range 2–7) years after their initial treatment. | PMC10634075 |
||
Change in MHIP score overall | Table There was no change in the overall mean MHIP score for the CSI group (Pre 4.3 (SD 2.3) Post 4.3 (SD 1.2)) but there was an improvement in the LR-PRP group mean MHIP score (Pre 5.3 (SD 3.0) Post 4.8 (SD 2.5), p = 0.56) (supplementary tables S1 and S2).Figure
MHIP scores by treatment group comparisonMHIP, Melbourne Hip MRI Score; LR-PRP, leukocyte-rich platelet-rich plasma; CSI, corticosteroid injection.
MHIP scores graphical representation. MHIP, Melbourne Hip MRI Score; LR-PRP, leukocyte-rich platelet-rich plasma; CSI, corticosteroid injection
Pre- and post- MRI images from three participants who had improvement of more than 2 points in their MHIP scores. | PMC10634075 |
||
Change in MHIP score elements | TB, bone marrow oedema, gluteal tendinopathy, tendinopathy, fatty muscular atrophy | BONE MARROW OEDEMA, TROCHANTERIC BURSITIS, ATROPHIC | The MHIP score is calculated based on 5 elements although the total score reflects tendinopathy severity : gluteal tendinopathy rating (GT) and trochanteric bursitis (TB), cortical irregularity (CI) and bone marrow oedema (BO) and fatty muscular atrophy (FA) [Tendon related scores were similar between the CSI group and LR-PRP groups, with the CSI group showing a small reduction in GT scores (1.7 (SD 0.6) to 1.3 (SD 0.6)) but no change in TB scores and the LR-PRP group showing no change in GT scores but a small reduction in TB scores (2.0 (SD 1.0) to 1.6 (SD 1.1)) (supplementary tables S1 and S2).The bone related scores had the largest between group difference with CI increasing in the CSI group (0.3 (SD 0.6) to 0.6 (SD 0.6)) but decreasing in the LR-PRP group (0.6 (SD 0.7) to 0.4 (0.5)) and BO also reducing in the LR-PRP group (0.2 (SD 0.4) to 0 (SD 0)) (supplementary tables S1 and S2).Fatty atrophic muscular changes were the same in the CSI group pre- and post- treatment (0.6 SD 1.2) and similar in the LR-PRP group (0.5 (SD 0.9) to 0.6 (SD 0.9)) (supplementary tables S1 and S2). Figure 3 shows the pre and post MRI images from three participants who had improvement of more than 2 points in their MHIP scores. | PMC10634075 |
Discussion | tendinopathic achilles tendons, tendinopathy, gluteal tendinopathy | DISEASE PROGRESSION, DISEASE, NEOVASCULARIZATION | Our hypothesis was that there would be no improvement in MHIP MRI scores following treatment for gluteal tendinopathy at 2 years or more post-treatment. Overall, the results confirmed this. However, there was a reduction in the mean MHIP scores in the LR-PRP group from 5.3 (SD 3.0) to 4.77 (SD 2.5), p = 0.56) and in five out of nine participants the MHIP score improved. Four of these improved by 2–4 points whilst Our study is unique in that we analyzed MRI between at least two and up to seven years post-treatment (mean follow-up time; 4.15 ± 1.11 years). There are limited studies which look at structural change in tendinopathic tendons post biological injection treatment, and even fewer following patients in the longer-term. In their 2011 RCT, de Vos et al., showed that that there was no difference between the effect of PRP or placebo on structural changes and neovascularization in tendinopathic achilles tendons using ultrasound imaging [To date, tendon clinicians and researchers have a focused on measuring symptomatic rather than structural outcomes to determine improvement in tendinopathy. However, a recent consensus statement identified that almost 70% of tendinopathy researchers felt that structural analysis should be a core domain for tendinopathy assessment [It is possible that effectiveness of treatment in tendinopathy is grade or stage dependent. A recent review of 27 studies gluteal tendinopathy by Ladurner et al., identified good [Timing – both at imaging – and disease stage is likely to be important because time is required for tendons to undergo structural changes following treatment. This would corroborate patient-reported outcome measures from the original RCT by Fitzpatrick et al. which found that participants in the LR-PRP group continued to experience symptomatic improvement beyond 12 months and even further at final follow up at 24 months [Our study was strengthened by use of a reliable grading score for gluteal tendinopathy as a method of comparing disease progression before and after receiving treatment. The MHIP score enables researchers to compare radiological findings pre- and post-treatment, between patient cohorts and across multiple studies [Limitations of our study include that the study extension did not control for patients having subsequent interventions following completion of the trial. The sample size of the study was limited by the availability of baseline MRI scans from the RCT and thus is too small for ensuring significance and the results should be interpreted as hypothesis generating. | PMC10634075 |
Conclusion | tendinopathy, gluteal tendinopathy | The hypothesis that there would be no improvement in MHIP scores following treatment of gluteal tendinopathy was supported. Findings of improvement in the LR-PRP group at 4 years would support further studies powered to look for structural improvement. These findings suggest that structural change following treatment for tendinopathy may be possible supporting the inclusion of MRI as a core outcome for future studies. | PMC10634075 |
|
Acknowledgements | The authors would like to acknowledge Nathan Tso for his assistance in preparation of the data. Thanks also to Richard O’Sullivan for reading and grading MRI scans and Sally Boyd for her outstanding work as clinical trial coordinator. | PMC10634075 |
||
Authors’ contributions | J.F. contributed to the study design and both authors were involved in data collection, interpretation and analysis. G.C. wrote the first draft and J.F. made substantial contributions to critically revise subsequent drafts. Both authors gave final approval of the version published. The authors agree to be accountable for the accuracy and integrity of all aspects of this work. | PMC10634075 |
||
Funding | Funding for this project was received from Joint Health Institute Ltd. Australia. | PMC10634075 |
||
Data Availability | Data relating to this study has been published as a part of the article and the supplementary material. | PMC10634075 |
||
Declarations | PMC10634075 |
|||
Ethical approval and consent to participate | The study was conducted in accordance with the Declaration of Helsinki and Ethics approval was obtained from the University of Melbourne Human Research Ethics Committee (Ethics approval number: 1852900). The trial was registered with ACTRN12613000677707. All participants provided written informed consent to participate. | PMC10634075 |
||
Consent for publication | Not Applicable. | PMC10634075 |
||
Competing interests | The authors declare no competing interests. | PMC10634075 |
||
References | PMC10634075 |
|||
Background | hyperphosphatemia | HYPERPHOSPHATEMIA | This study aimed to investigate the effect of a family-centered empowerment program on hyperphosphatemia management. | PMC10476304 |
Method | hyperphosphatemia, coin toss | HYPERPHOSPHATEMIA | This experimental study was performed on 80 randomly selected eligible patients with hyperphosphatemia undergoing hemodialysis. Patients were assigned randomly to two groups of family-centered empowerment program (FCEPG) and control group (CG) by coin toss (40 people per group). Data collection tools were the researcher-made Phosphate Control Knowledge Scale, the researcher-made Adherence to Dietary Restriction of Phosphorus Intake Scale, the eight-item Morisky Medication Adherence Scale, and serum phosphorus measurements. Data were collected before the intervention, one month, and three months after the intervention. Patients in FCEPG participated in a family-centered empowerment program. The statistical significance level was considered to be 0.05. | PMC10476304 |
Results | Inter-group comparisons showed no significant difference between FCEPG and CG in terms of the mean score of knowledge of phosphate control, adherence to dietary restriction of phosphorus intake, adherence to medication, and the mean serum phosphorus level before the empowerment program, but showed significant differences between them in these respects at one month after the program and three months after the program ( | PMC10476304 |
||
Conclusion | The findings of this study can be used in various fields of healthcare in the hospital and community. | PMC10476304 |
||
Keywords | PMC10476304 |
|||
Introduction | hyperphosphatemia | END-STAGE RENAL DISEASE, HYPERPHOSPHATEMIA, COMPLICATION | Maintenance hemodialysis is a commonly used treatment for end-stage renal disease. In this condition, phosphate becomes easily retained in the body due to decreased renal function, leading to hyperphosphatemia, a common complication in these patients [Primary interventions for hyperphosphatemia management include the dietary restriction of phosphorus intake (DRPI) and the use of phosphate binders [There are a variety of strategies, including educational and behavioral interventions, to improve the phosphorus control of hemodialysis patients (HPs) by improving their adherence to treatment regimens and helping them engage in healthy behaviors [Considering the importance of empowering HPs with hyperphosphatemia and their FCGs in relation to adherence to dietary and medication regimens for the purpose of controlling serum phosphorus levels, this study investigated the effect of a family-centered empowerment program (FCEP) on hyperphosphatemia management and specifically the subjects’ knowledge of phosphate control, adherence to DRPI, adherence to medication, and serum phosphorus level. | PMC10476304 |
Literature review | hyperphosphatemia, ’ | HYPERPHOSPHATEMIA | The effects of education programs on knowledge, adherence to dietary and medication regimens, and serum phosphorus levels of HPs with hyperphosphatemia have been the subject of several studies. In a study by Yin et al., the results showed an improvement in the HPs’ phosphate control rate, their knowledge of phosphate control, and their adherence to phosphate binder regimens after the intervention [H1: FCEP affects patients’ knowledge of phosphate control.H2: FCEP affects patients’ adherence to DRPI.H3: FCEP affects patients’ adherence to medication.H4: FCEP affects patients’ serum phosphorus levels. | PMC10476304 |
Methods | PMC10476304 |
|||
Study design and setting | This study was experimental research conducted on two groups of HPs: 1- patients participating in an FCEP (hereafter refers to as FCEPG) and 2- patients in the control group (hereafter refers to as CG). All patients were recruited from the hemodialysis ward of Shahid Beheshti Hospital in Hamadan, Iran. This ward has 30 beds in three halls and provides hemodialysis to about 70 patients every day in morning and evening sessions.Designed as a single-blind experiment, the study was arranged such that patients remain unaware of the designated interventions so that their knowledge would not affect their behavior. | PMC10476304 |
||
Participants and recruitment | death, illness | All participants were HPs. The sample size was computed using the following formula based on the findings of Lim et al. [For sampling, the first researcher identified eligible HPs with the help of nurses. Participants of FCEPG were recruited exclusively from the morning shift and CG from the evening shift to prevent contamination. After assigning a number to each eligible HP, the numbered HPs in the morning shift were randomly assigned to FCEPG and in the evening shift to CG by casting lots. The selection of participants continued until the target sample size was reached. The two groups were matched in terms of age and gender. All participants were included in the study at the end of data collection.Inclusion criteria were: minimum age of 35 and maximum age of 70 years, serum phosphorus level of more than 5.5 mg/dl over the last six months, presence of a first- or second-degree family member (father, mother, sibling, spouse, child, son/daughter-in-law) as the constant FCG providing care for at least six months during the dialysis session and at home, no mental illness in HP or FCG based on their report, and HP or FCG not simultaneously participating in another educational program related to diet or medication. Exclusion criteria were: HP or FCG not wanting to continue participating in the study, HP or FCG not participating in education sessions after enrollment (absence in two sessions), and deterioration of the physical condition, hospitalization, or death of HP. | PMC10476304 |
|
Outcome measurements | PMC10476304 |
|||
Primary outcomes | The primary outcomes of the program were assumed to be a change in patients’ knowledge of phosphate control, adherence to DRPI, and adherence to medication, which were measured by the researcher-made Phosphate Control Knowledge Scale, researcher-made Dietary Restriction of Phosphorus Intake Scale (DRPI-S), and the eight-item Morisky Medication Adherence Scale (MMAS-8), respectively. | PMC10476304 |
||
Secondary outcomes | SECONDARY | The secondary outcome of the program was assumed to be a change in serum phosphorus level. | PMC10476304 |
|
Baseline | The first researcher collected data. Baseline measurements for FCEPG and CG were performed before interventions while HPs were undergoing hemodialysis. For illiterate HPs, the questions were read aloud and answers were recorded by the first researcher. | PMC10476304 |
||
Follow-ups | Follow-up measurements were performed once one month after FCEP (Follow-Up1) and another time three months after FCEP (Follow-Up2) at patients’ subsequent hemodialysis appointments before the start of hemodialysis. CONSORT flow chart of the study is illustrated in Fig. CONSORT flow chart of the study | PMC10476304 |
||
Measures | PMC10476304 |
|||
Sociodemographic and clinical data of participants and family caregivers | primary disease | Sociodemographic and clinical information questionnaire contained 11 questions about HPs (age, gender, education level, marital status, employment status, duration of undergoing hemodialysis, primary disease, dialysis frequency, receiving vitamin D, and calcimimetics, and smoking. This questionnaire also contained seven questions about FCGs (age, gender, education level, marital status, employment status, relation to the patient, and duration of providing care to the patient). | PMC10476304 |
|
Knowledge of phosphate control | Knowledge of phosphate control was measured by the Phosphate Control Knowledge Scale, which was a researcher-made tool. This questionnaire was developed by adapting the tools of similar studies and scientific recourses [This tool has 16 items with the answers “true” (1 point), “false” (0 points), and “I don’t know” (0 points). Items 1, 9, 10, and 13 were scored in reverse. The higher the score, the greater the Knowledge of phosphate control. This scale’s minimum and maximum scores are 0 and 16, respectively (Table Phosphate control knowledge scaleTo check the validity of the Phosphate Control Knowledge Scale, it was submitted for review to 10 faculty members of Shahid Beheshti University of Medical Sciences. During this process, in addition to qualitative content validity assessment, the necessity of the questions and their relevance to the research objectives were also evaluated based on Content Validity Ratio (CVR) and Content Validity Index (CVI), respectively [The reliability of this tool was established by test–retest and intra-class correlation calculation based on the responses of 10 participants who filled out the questionnaire two times with a 10-day interval. Using this method, the intra-class correlation coefficient was calculated to 0.75. The Cronbach’s alpha of the tool based on the responses of 20 HPs who were not included in the study was calculated to 0.88 that showed the instrument was reliable [ | PMC10476304 |
||
Adherence to dietary restriction of phosphorus intake | Adherence to DRPI was measured by the researcher-made Dietary Restriction of Phosphorus Intake Scale (DRPI-S), which was also developed by the researchers based on scientific sources [Dietary restriction of phosphorus intake scaleThe validity and reliability of this tool were established in the same way as described for the Phosphate Control Knowledge Scale. All items of this tool earned CVR and CVI scores of more than 0.62 and 0.96, respectively, which confirmed their necessity and relevance. The tool’s intra-class correlation coefficient and Cronbach’s alpha were determined to be 0.91 and 0.83, respectively, which confirmed the reliability of the tool [ | PMC10476304 |
||
Adherence to medication | Adherence to medication was measured using the version of eight-item Morisky Medication Adherence Scale (MMAS-8) | PMC10476304 |
||
Serum phosphorus measurement | hyperphosphatemia | HYPERPHOSPHATEMIA | At the dialysis ward, serum phosphorus level measurement was a routine procedure for all HPs with hyperphosphatemia while fasting. This procedure involved a nurse taking a blood sample, sending it to the hospital’s laboratory, and then recording the results in the HP’s medical file at 8 AM. The first researcher (responsible for implementing the interventions and collecting the data) extracted the participating HPs’ serum phosphorus level data from their medical files and recorded them in the data collection sheets.The blood samples of the CG participants undergoing evening hemodialysis sessions were also prepared in the morning. CG participants were asked to attend the hemodialysis department at 8 AM for the data collection sessions (baseline, follow-up 1, and follow-up 2) in a fasting state for blood sampling. The researcher went to their homes to take the blood sample for participants who did not want to go to the hemodialysis department in the morning. | PMC10476304 |
Data analysis | The collected data were processed using the software SPSS version 26. The data were analyzed by descriptive statistical methods such as computing numerical measures (mean and standard deviation) and inferential tests. The independent t-test and the chi-square test were used to compare FCEPG and CG in terms of demographic variables. The independent t-test was also used to compare FCEPG and CG in terms of knowledge of phosphate control, adherence to DRPI, adherence to medication, and serum phosphorus level. The GLM-repeated measures ANOVA was used to make intra-group comparisons between the three measurement stages: Baseline, Follow-Up1 (one month after FCEP), and Follow-Up2 (three months after FCEP). For all tests and analyses, the significance level was considered to be 0.05. | PMC10476304 |
||
Discussion | hyperphosphatemia, CKD | SECONDARY, HYPERPHOSPHATEMIA, ACUTE CORONARY SYNDROME | The goal of this study was to investigate the effect of an FCEP on hyperphosphatemia management in HPs. The results showed that FCEP could have a positive impact on the patients’ knowledge of phosphate control, adherence to DRPI, and adherence to medication as primary outcomes and on their serum phosphorus levels as the secondary outcome.Regarding the first research hypothesis, namely the effect of FCEP on knowledge of phosphate control, although we could not find any study on the effect of family-centered education on HPs’ knowledge, we found several studies showing that education and empowerment can improve the knowledge of patients with hyperphosphatemia. The study of Yin et al. for example showed that an intensive education program focused on phosphate control can improve HPs' phosphate control knowledge scores [In relation to the second hypothesis of this study, namely the effect of FCEP on adherence to DRPI, the literature contains several studies with findings similar to ours. In one of these studies, Montazami et al. reported that home visit-based FCEP can be an effective way to improve adherence to dietary and medication regimens in patients with acute coronary syndrome [Regarding the third hypothesis of the study, namely the effect of FCEP on adherence to medication, one study has shown that family-centered education is more effective than patient-centered education in improving HPs’ adherence to treatment and especially medication regimens [Concerning the fourth hypothesis of the study, namely the effect of FCEP on the secondary outcome, i.e. serum phosphorus level, the results of a study by Rabiei showed that FCEP could reduce the negative outcomes of CKD in patients [The present study is significant from these two perspectives. First, it focuses on the empowerment of not only HPs but also FCGs as people who play an essential role in the health promotion of these patients. Second, in addition to exploring the effect of FCEP on primary outcomes such as knowledge of phosphate control, adherence to DRPI, and adherence to medication, this study examines the effect of FCEP on the most important outcome for patients with hyperphosphatemia, i.e. serum phosphorus level. | PMC10476304 |
Acknowledgements | We would like to thank managers and patients at Shahid beheshti hospital in Hamedal for their assistance and cooperation. | PMC10476304 |
||
Authors’ contributions | Conceptualization and methodology: Parvaneh Vasli, and Noushin Bakhtiari; Formal analysis and investigation: Noushin Bakhtiari, Parvaneh Vasli, and Malihe Nasiri; Writing-original draft: Parvaneh Vasli; Writing– review and editing: Meimanat Hosseini. | PMC10476304 |
||
Funding | No funding or sponsorship was received for this study or publication of this article. | PMC10476304 |
||
Availability of data and materials | The data used to support the findings of this study are available from the corresponding author upon reasonable request. | PMC10476304 |
||
Declarations | PMC10476304 |
|||
Ethics approval and consent to participate | All the measures taken in this study were approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran (code no. IR.SBMU.PHNM.1400.104) in agreement with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all the participants or legal guardians of the illiterate participants for participation in the study. | PMC10476304 |
||
Consent for publication | Not applicable. | PMC10476304 |
||
Competing interests | The authors declare no competing interests. | PMC10476304 |
||
References | PMC10476304 |
|||
Background | tumor | TUMOR, SOLID TUMORS | Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors. | PMC10241827 |
Methods | SOLID TUMORS | ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors ( | PMC10241827 |
|
Results | asthenia, nausea, fatigue, PAD, toxicities | ADVERSE EVENTS, PAD | In Phase I, no dose-limiting toxicities were reported, the MTD was not reached; a PAD was not determined. ORR was 5.7%, with four partial responses. The most common treatment-related adverse events (AEs) were fatigue (42.9%) and nausea (42.9%). Twelve (17.1%) patients experienced ≥1 fatal AE, one of which (asthenia) was treatment-related. | PMC10241827 |
Conclusions | SOLID TUMORS | Although the azacitidine-epacadostat-pembrolizumab regimen was well tolerated, it was not associated with substantial clinical response in patients with advanced solid tumors previously exposed to immunotherapy. | PMC10241827 |
|
Subject terms | PMC10241827 |
|||
Introduction | NSCLC, tumor, T-cell apoptosis, Tumor | TUMOR, CANCER PROGRESSION, TUMOR, PROLIFERATION, DISEASE, NSCLC, IMMUNE TOLERANCE, TUMOR GROWTH | Tumor cells can evade host immune responses by exploiting immune checkpoint pathways [The mechanisms responsible for resistance to immune checkpoint inhibition are not fully defined, but treatment responsiveness has been associated with the presence of an inflamed tumor microenvironment [Immunotherapy strategies targeting indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme, may enhance the efficacy of immune checkpoint blockade. IDO1 contributes to tumor immune tolerance by inhibiting T-cell proliferation, inducing T-cell apoptosis, promoting the differentiation of naïve T cells into regulatory T cells, and regulating the pool of peptides available for antigen presentation [In preclinical studies, inhibition of both IDO1 and an immune checkpoint pathway provided greater control of tumor growth than immune checkpoint inhibition alone [Epigenetics refers to alterations in gene expression that occur independently of changes to inherited gene sequences. Epigenetic changes in malignant cells can lead to the upregulation of genes that promote cancer progression [Clinical data on the antitumor activity of combination treatment with an epigenetic modulator and an immune checkpoint inhibitor were limited at the time when the current study was designed. However, in a prior study, five patients with NSCLC previously treated with azacitidine and the histone deacetylase inhibitor entinostat exhibited durable (>6 months) disease control [ | PMC10241827 |
Methods | PMC10241827 |
|||
Study design and participants | NSCLC, colorectal cancer, tumor, CRC, PAD, Tumors | COLORECTAL CANCER, TUMOR, DISEASE, SOLID TUMORS, TUMORS, PAD, NSCLC | ECHO-206 (NCT02959437) was an international, open-label, Phase I/II study in which patients received an epigenetic priming regimen and an immunotherapy doublet consisting of epacadostat and pembrolizumab. The study was undertaken at 11 centers in the United States, United Kingdom, and Spain. Patients enrolled in Phase I had confirmed advanced or metastatic solid tumors and had failed prior standard treatment (no limit to the number of prior regimens). Phase II planned to enroll several refractory solid tumors and ultimately included NSCLC and microsatellite stable (MSS) colorectal cancer (CRC) cohorts. NSCLC patients with prior anti-PD(L)1 were selected because this tumor type is known to be responsive to anti-PD(L)1 therapy, and combination with an epigenetic modifier was hypothesized to improve or restore antitumor activity. MSS CRC does not have a high mutational burden, and the lack of immunogenicity makes this histology unlikely to respond to immunotherapy alone. MSS CRC became a tumor type of interest based on preclinical data suggesting that epigenetic reprogramming could increase the immunogenicity of the tumor and synergize with anti-PD(L1) immunotherapy to promote antitumor activity [Patients in both study phases were adults (≥18 years) with disease that was measurable per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [The Phase I study, which sought to determine the maximum tolerated dose (MTD) or pharmacologically active dose (PAD) of the triple-drug combination, employed a 3 + 3 + 3 study design. The Phase II study employed a Simon two-stage design and consisted of dose-expansion cohorts (to assess the safety and efficacy of the MTD or PAD) and treatment-sequencing, tumor-biopsy cohorts (to evaluate epigenetic changes, as well as changes in the tumor microenvironment). Patients in the dose-expansion cohorts had either NSCLC or MSS CRC and were required to undergo two biopsies, one before treatment and one prior to day 1 of cycle 3 (see Additional file 1: Supplementary Fig. | PMC10241827 |
Sample size considerations | toxicities, DLTs | PAD | Part 1 dose escalation used a 3 + 3 + 3 design, and the sample size was determined by the frequency of dose-limiting toxicities (DLTs) and final number of dose levels tested before the MTD or PAD was established.For Part 2 expansion, the sample size was based on the Simon 2-stage design. Based on a one-sided type I error of 0.05 and 80% power, a total of 27 patients with 8 subjects in Stage 1 would be required to demonstrate the desired response rate of 20% assuming the response rate for the historical control was 3%. | PMC10241827 |
Treatment | This study was originally designed to explore several epigenetic priming regimens, but azacitidine was the one tested due to the early study termination (discussed in the study conduct section).Treatment cycles were 21 days long. Dose escalation began with azacitidine 75 mg, pembrolizumab 200 mg IV Q3W, and oral epacadostat 100 mg BID. Five doses of azacitidine (75 or 100 mg per dose) were administered by intravenous infusion or subcutaneous injection over days 1–7 in cycles 1 and 2. Only the subcutaneous formulation of azacitidine was available to patients in the European Union. Dose reductions of azacitidine were permitted for the management of TEAEs, with a maximum of two dose reductions regardless of the initial starting dose. Epacadostat (100 or 300 mg) was administered orally BID without regard to food. Dose reductions of epacadostat were permitted for the management of TEAEs, with a maximum of two dose reductions regardless of the initial starting dose. Pembrolizumab 200 mg was administered as a 30-min, intravenous infusion every 3 weeks beginning on day 1 of cycle 1. Dose reductions of pembrolizumab were not permitted, but doses could be delayed to manage TEAEs. | PMC10241827 |
||
Study conduct | melanoma | MELANOMA | The study was initiated on February 27, 2017, and a strategic decision was made on April 11, 2018, to permanently stop enrollment. This decision was based on the results of the Phase III ECHO-301/ KEYNOTE-252 study, which compared epacadostat plus pembrolizumab with placebo plus pembrolizumab in patients with advanced melanoma [ECHO-206 was conducted in accordance with Good Clinical Practice guidelines, the provisions of the Declaration of Helsinki, and applicable national and local regulatory requirements. The study protocol was approved by the independent ethics committee/institutional review board at each participating site, and all patients provided written informed consent. | PMC10241827 |
Endpoints | tumor, death, Tumor, TILs, T-cell infiltration, Safety/tolerability | DISEASE PROGRESSION, TUMOR, ADVERSE EVENT, TUMOR, PAD, SECONDARY | In Phase I, the primary endpoints were safety/tolerability and identification of the MTD or PAD. The MTD was defined as the highest dose at which less than one-third of patients (out of a minimum of six patients) experienced a DLT (see Additional file 2: Supplementary Table SIn Phase II, investigator-assessed ORR per RECIST v1.1 was the primary endpoint, and safety/tolerability was a secondary endpoint. Tumor assessments were performed every 9 weeks or more frequently if clinically indicated. Either computed tomography or magnetic resonance imaging could have been used, but investigators were instructed to use the same imaging technique throughout the study. After 12 months of study treatment, tumor assessments could have been performed every 12 weeks. Imaging was performed until documented disease progression, the start of new anticancer treatment, withdrawal of consent, death, or the end of the study. Safety/tolerability was evaluated throughout the study. TEAEs were coded per Medical Dictionary for Regulatory Activities v19.1 and graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.Changes in T-cell infiltration in the tumor microenvironment was a secondary endpoint in both Phase I and Phase II. To determine expression of PD-L1 in the tumor microenvironment, chromogenic immunohistochemistry was performed at Indivumed (Hamburg, Germany) using the 22C3 pharmDx assay (Agilent/Dako; Santa Clara, California, USA). Membranous anti-PD-L1 staining was semi-quantitatively evaluated using the H-score and tumor proportion score (TPS) per the manufacturer’s instructions. Changes in T-cell infiltration were assessed using 5-color, multiplex immunohistochemistry and analyzed by Indivumed. To quantify T cells, tissue sections were stained with antibodies specific to CD3 (2GV6; Roche/Ventana, Cat # 05278422001), CD8 (SP16; DCS, Cat # CI008C002), and FoxP3 (SP97; Spring Biotech, Cat # M3970; LS Bio, Cat # LS-C210349; Thermo Fisher, Cat # MA5-16365). To identify tumor regions, sections were stained with antibodies specific to pan-cytokeratin (polyclonal; Agilent/Dako, Cat # Z0622) or PMEL (HMB45; Leica, Cat # NCL-L-HMB45). Nuclei were stained with 4′,6-diamidino-2-phenylindole. TILs positive for CD3, CD8, and FoxP3 were quantified by counting the number of cells present within the tumor, as assessed by co-localization with pan-cytokeratin. Cell densities (cells/mm | PMC10241827 |
Statistics | T-cell infiltration | The response-evaluable population, which was used for the efficacy analysis, comprised patients who received ≥1 dose of any study drug and completed a baseline scan. Patients in the response-evaluable population also had to have ≥1 post-baseline scan, been on study for ≥70 days, or discontinued study treatment. The safety population comprised patients who received ≥1 dose of any study drug. Efficacy and safety data collected during Phase I and Phase II were pooled and summarized using descriptive statistics (SAS v9.4 or later). No evaluation of the effect of treatment sequence was conducted. Changes in T-cell infiltration in pre- and on-treatment biopsies was compared using the Wilcoxon matched-pairs signed rank test in GraphPad Prism v7.02. The cutoff date for these analyses was February 15, 2019. | PMC10241827 |
|
Results | PMC10241827 |
|||
Changes in T-cell infiltration | tumor | TUMOR, EVALUABLE | Evaluable samples (defined as tumor content ≥10%) for paired pre- and on-treatment biopsies were available from seven patients who received concurrent administration of azacitidine, epacadostat, and pembrolizumab (dose escalation: | PMC10241827 |
Discussion | tumor, tumors, melanoma | TUMOR, TUMORS, SOLID TUMORS, MELANOMA | ECHO-206 represents the largest prospective study of combination treatment with an epigenetic modulator (azacitidine) and immunotherapy (epacadostat plus pembrolizumab) performed to date. Although this study established that azacitidine 100 mg could be safely combined with epacadostat and pembrolizumab, this regimen (with all agents administered concurrently or with a lead-in) was not associated with substantial clinical response in patients with immunotherapy-resistant solid tumors (predominately MSS CRC) or solid tumors that progressed following immunotherapy (predominately melanoma). Whether use of azacitidine could enhance immunotherapy response in the treatment naïve setting is unclear. Our findings contrast with preliminary results from the Phase I/II ENCORE-601 study, which evaluated combination treatment with the DNMT inhibitor entinostat and pembrolizumab in patients with anti-PD-1–refractory advanced tumors [The strategy of targeting the Trp–Kyn–AhR pathway through IDO1 inhibition experienced a setback following the negative results of the Phase III KEYNOTE-252/ECHO-301 study [Although preclinical findings strongly suggest an ability of epigenetic modulators to facilitate an influx of T cells into the tumor microenvironment [With the doses of pembrolizumab and azacitidine used in this study, we believe pharmacodynamic changes and/or any clinical benefit with combination treatment would have been observed. However, dosing of epacadostat may have been insufficient. A longitudinal analysis of plasma samples acquired from participants across multiple clinical studies revealed that epacadostat doses <600 mg BID were not sufficient to reduce plasma kynurenine levels when combined with PD-1 inhibition [It is apparent that many questions remain regarding the potential of epigenetic modifiers in enhancing the clinical activity of immunotherapy. Other epigenetic modifiers of clinical interest include agents targeting protein arginine methyltransferase 5, SET domain bifurcated, lysine demethylase 1, and cyclin-dependent kinase 9. These agents have all been demonstrated in the preclinical setting to induce viral mimicry responses, regulate type I and II IFN responses, and/or enhance the antitumor activity of PD-(L)1 inhibitors [In summary, we performed the largest prospective study to date combining epigenetic modulation (azacitidine) with IDO1 inhibition (epacadostat) and immune checkpoint blockade (pembrolizumab). We demonstrated that both epigenetic lead-in and concurrent therapy were moderately well-tolerated. However, overall efficacy was limited in our cohort of patients, the majority of whom had either prior experience with immunotherapy or had immunotherapy-refractory tumors. Although the DNMT inhibitor azacitidine suppressed influx of intratumoral regulatory T cells, no increase in the numbers of effector T cells was observed, suggesting that the ability of azacitidine to influence intratumoral CD8 | PMC10241827 |
Supplementary information | The online version contains supplementary material available at 10.1038/s41416-023-02267-1. | PMC10241827 |
||
Acknowledgements | Cancer | CANCER | Dr. Brana wishes to thank the Instituto de Salud Carlos III (Rio Hortega contract CM15/00255); the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), which was supported by the Banco Bilbao Vizcaya Argentaria Foundation (grant 89/2017); the La Caixa Foundation (LCF/PR/CEO7/50610001); and the Cellex Foundation, which provided research facilities and equipment. Editorial and medical writing support for this manuscript was provided by Tiffany DeSimone, PhD, and Jason Tuffree of Ashfield MedComms, an Inizio Company, and were funded by Incyte Corporation. | PMC10241827 |
Author contributions | JJL: conception and design of the study, acquisition of data, and analysis and interpretation of data. MF: acquisition of data and analysis and interpretation of data. CS: acquisition of data and analysis and interpretation of data. EGJ: acquisition of data and analysis and interpretation of data. JB: acquisition of data and analysis and interpretation of data. RKr: conception and design of the study, acquisition of data, and analysis and interpretation of data. RKu: Analysis and interpretation of data. SPB: acquisition of data and analysis and interpretation of data. IB: Acquisition of data and analysis or interpretation of data. LWG: acquisition of data. KOH: conception and design of the study, acquisition of data, and analysis and interpretation of data. RG: conception and design of the study and analysis and interpretation of data. MS: conception and design of the study, acquisition of data, and analysis and interpretation of data. FZ: conception and design of the study, analysis and interpretation of data. AN: conception and design of the study, acquisition of data, and analysis and interpretation of data. All authors contributed to the development and critical review of the manuscript and approved the final version. | PMC10241827 |
||
Funding | This study was sponsored by Incyte Corporation. | PMC10241827 |
||
Data availability | Access to individual patient-level data is not available for this study. | PMC10241827 |
||
Competing interests | TopAlliance, Cancer | EMD, DEFICIENCY, ONCOLOGY, EDWARDS, CANCER | JJL: DSMB (Abbvie and Immutep); scientific advisory board: ([no stock] 7 Hills, Fstar, Inzen, RefleXion, Xilio [stock] Actym, Alphamab Oncology, Arch Oncology, Kanaph, Mavu, Onc.AI, Pyxis, and Tempest); consultancy fees (Abbvie, Alnylam, Avillion, Bayer, Bristol-Myers Squibb, Checkmate, Codiak, Crown, Day One, Eisai, EMD Serono, Endeavor, Flame, Genentech, Gilead, HotSpot, Kadmon, KSQ, Janssen, Ikena, Immunocore, Incyte, Macrogenics, Merck, Mersana, Nektar, Novartis, Pfizer, Regeneron, Ribon, Rubius, Servier, Silicon, Synlogic, Synthekine, TRex, Werewolf, and Xencor); research support to institution (AbbVie, Agios, Astellas, Astrazeneca, Bristol-Myers Squibb, Corvus, Day One, EMD Serono, Fstar, Genmab, Ikena, Immatics, Incyte, Kadmon, KAHR, Macrogenics, Merck, Moderna, Nektar, Next Cure, Numab, Pfizer, Replimmune, Rubius, Scholar Rock, Synlogic, Takeda, Trishula, Tizona, and Xencor); provisional patents (Serial #15/612,657 [Cancer Immunotherapy], PCT/US18/36052 [Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof]). MF: Speaker Bureau (Amgen and Guardant360); advisory board (Array BioPharma, Bayer, BGB Group/GlaxoSmithKline, Mirati Therapeutics, Inc., Pfizer, Seattle Genetics, Taiho, and Zhuhai Yufan Biotechnology Co.); consulting/steering committee for study (Incyte Corp.); editorial board (Mirati Therapeutics, Inc.); research support to institution (Amgen, AstraZeneca, Novartis, Verastem, and Bristol Myers Squibb). CS has nothing to disclose. EGC: research funding (Boehringer-Ingelheim, BMS, Celgene, Clovis, Incyte, Lilly, MacroGenics, Roche, Stemline, Halozyme, Merck, Fibrogen, Rafael, Corcept, Lonza); scientific advisory boards/consultancy (AstraZeneca, Celgene, Eisai, Legend, Sobi, Pfizer, Noxxon, BioNTech, Ipsen, Bayer, Cardiff, Novartis, Merck). JB: research funding to institution (Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, EMD Serono, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Koltan,SynDevRex, Forty Seven, AbbVie, Array, Onyx, Sanofi, Takeda, Eisai, Celldex, Agios, Cytomx, Nektar, ARMO, Boston Biomedical, Ipsen, Merrimack, Tarveda, Tyrogenex, Oncogenex, Marshall Edwards, Pieris, Mersana, Calithera, Blueprint, Evelo, FORMA, Merus, Jacobio, Effector, Novocare, Arrys, Tracon, Sierra, Innate, Arch Oncology, Prelude Oncology, Unum Therapeutics, Vyriad, Harpoon, ADC, Amgen, Pfizer, Millennium, Imclone, Acerta Pharma, Rgenix, Bellicum, Gossamer Bio, Arcus Bio, Seattle Genetics, TempestTx, Shattuck Labs, Synthorx, Inc., Revolution Medicines, Inc., Bicycle Therapeutics, Zymeworks, Relay Therapeutics, Scholar Rock, NGM Biopharma, Stemcentrx, Beigene, CALGB, Cyteir Therapeutics, Foundation Bio, Innate Pharma, Morphotex, OncXerna, NuMab, AtlasMedx, Treadwell Therapeutics, IGM Biosciences, Mabspace, Hutchinson MediPharma, REPARE Therapeutics, NeoImmune Tech, Regeneron, PureTech Health); consulting/advisory role (Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Array, Sanofi. ARMO, Ipsen, Merrimack, Oncogenex, FORMA, Arch Oncology, Prelude Therapeutics, Phoenix Bio, Cyteir, Molecular Partners, Innate, Torque, Tizona, Janssen, Tolero, Amgen, Seattle Genetics, Moderna Therapeutics, Tanabe Research Laboratories, Beigene, Continuum Clinical, Agios, Bicycle Therapeutics, Relay Therapeutics, Evelo, Pfizer, Samsung Bioepios, Fusion Therapeutics); food/beverage/travel accommodations (Gilead, Genentech/Roche, BMS, Lilly, Merck, MedImmune, Celgene, Taiho, Novartis, OncoMed, BI, ARMO, Ipsen, Oncogenex, FORMA). RKr: advisory board/speaking role (Incyte). RKu: research funding (Biological Dynamics, Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance); consulting fees and/or speaker fees and/or advisory board (Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Biological Dynamics, EISAI, EOM Pharmaceuticals, Iylon, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, Roche, TD2/Volastra, Turning Point Therapeutics, and X-Biotech); equity interest (CureMatch Inc., CureMetrix, and IDbyDNA); board membership (CureMatch and CureMetrix); co-founder (CureMatch). SPB: research funding to conduct clinical trials (Nucana PLC, Sierra Oncology, Astex, Incyte, Tesaro, Redx, MSD, Roche, UCB); consulting (Ellipses, Amphista); director (RNA Guardian ltd). IB: research funding (Incyte, Merck Sharp & Dohme, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Gliknik, ISA Pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Nanobiotics, Novartis, Northern Biologics, Orion Pharma, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences); institutional grants (Cellex Foundation, La Caixa Foundation, Banco Bilbao Vizcaya Argentaria Foundation); consulting fees (Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme, Rakuten pharma); honoraria (Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme); meeting/travel accommodations (Merck Sharp & Dohme, Merck Serono). LWG: consulting or advisory role (Lilly, Eisai, Bayer/Onyx, Newlink Genetics, QED, AstraZeneca, Incyte, Genentech, and Merck); research funding (Astellas Pharma, Pfizer, Onyx, Sun Pharma, Lilly, Bristol-Myers Squibb, Agios, ArQule, H3 Biomedicine, Incyte, Leap Therapeutics, ASLAN Pharmaceuticals, BeiGene, and Basilea). KOH, RG, MS, and FZ are employees and stockholders of Incyte Corporation. AN: research funding (NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor/Millendo, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, PsiOxus, Arcus Biosciences, NeoImmuneTech, ImmuneOncia, and Surface Oncology); advisory board (CytomX Therapeutics, Novartis, Genome & Company, OncoSec KEYNOTE-695, Kymab, and STCube Pharmaceuticals); travel/accommodation expenses (ARMO BioSciences); research funding to spouse (Immune Deficiency Foundation, Jeffery Modell Foundation and chao physician-scientist, and Baxalta); advisory board participation by spouse (Takeda, CSL, Behring, and Horizon Pharma). | PMC10241827 |
Ethics approval and consent to participate | Cancer | CANCER | The study protocol was approved by the independent ethics committee/institutional review board at each institution (BSD/IRB, The University of Chicago Biological Sciences Division/University of Chicago Medical Center; Vanderbilt University Institutional Review Board; Western Institutional Review Board; UC San Diego Human Research Protections Program; The University of Texas MD Anderson Cancer Center Institutional Review Board Center; London – Surrey Boarders Research Ethics Committee; and CEIm de la Comunidad Foral de Navarra Departamento de Salud. Pabellón de Docencia). All patients provided written informed consent before initiating treatment. | PMC10241827 |
Consent for publication | Not applicable. | PMC10241827 |
||
References | PMC10241827 |
|||
Purpose | EVENTS, PRIMARY BRAIN TUMORS, LITTLE | Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT. | PMC10050019 |
|
Methods | medulloblastoma, ependymoma | DISEASE, MEDULLOBLASTOMA, EPENDYMOMA | Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan–Meier analysis. | PMC10050019 |
Results | medulloblastoma, ependymoma, radionecrosis | MEDULLOBLASTOMA, EPENDYMOMA | All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8–7.4), 6 patients remain alive with NED. | PMC10050019 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.