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1.
J Neuroendocrinol ; : e13412, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38754956

RESUMO

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

2.
Blood ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662991

RESUMO

In the phase-2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560mg and venetoclax 400mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term results. Treatment was initially continuous, with elective treatment interruption (ETI) allowed after protocol amendment for patients in MRD-negative CR. For R/R MCL, the estimated 7-year progression-free survival (PFS) was 30% [95%CI: 14-49] (median 28 months [95%CI: 13-82]) and overall survival was 43% [95%CI: 23-62] (median 32 months [95%CI: 15-NE]). Eight patients in MRD-negative CR entered ETI for a median of 58 months (95%CI, 37-79), with four experiencing disease recurrence. Two of 3 re-attained CR on retreatment. Time-to-treatment-failure (TTF), which excluded progression in ETI for those reattaining response, was 39% overall and 68% at 7-years for responders. Beyond 56 weeks Grade 3 and serious adverse events were uncommon. Newly emergent or increasing cardiovascular toxicity were not observed beyond 56 weeks. We demonstrate long-term durable responses and acceptable toxicity profile of venetoclax-ibrutinib in R/R MCL and show feasibility of treatment interruption while maintaining ongoing disease control. (NCT02471391).

3.
Artigo em Inglês | MEDLINE | ID: mdl-38528164

RESUMO

PURPOSE: To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). METHODS: This study was part of a phase I/II trial of [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. RESULTS: In all evaluated organs, maximum [177Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57-66% within 48 h following the first treatment cycle. At the first treatment cycle, [177Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [177Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles. CONCLUSION: [177Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. TRIAL REGISTRATION: NCT02592707. Registered October 30, 2015.

4.
PET Clin ; 19(2): 291-306, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38199917

RESUMO

Immunotherapy approaches have changed the treatment landscape in a variety of malignancies with a high anti-tumor response. Immunotherapy may be associated with novel response and progression patterns that pose a substantial challenge to the conventional criteria for assessing treatment response, including response evaluation criteria in solid tumors (RECIST) 1.1. In addition to the morphologic details provided by computed tomography (CT) and MRI, hybrid molecular imaging emerges as a comprehensive imaging modality with the capacity to interrogate pathophysiological mechanisms like glucose metabolism. This review highlights the current status of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in prognostication, response monitoring, and identifying immune-related adverse events. Furthermore, it investigates the potential role of novel immuno-PET tracers that could complement the utilization of 18F-FDG PET/CT by imaging the specific pathways involved in immunotherapeutic strategies.


Assuntos
Fluordesoxiglucose F18 , Neoplasias , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Tomografia por Emissão de Pósitrons , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imunoterapia
6.
J Neuroendocrinol ; 36(1): e13359, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38097193

RESUMO

Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.


Assuntos
Tumores Neuroendócrinos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Fluordesoxiglucose F18 , Consenso , Tomografia por Emissão de Pósitrons
7.
Nat Rev Endocrinol ; 20(3): 168-184, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38097671

RESUMO

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Adulto , Humanos , Criança , Feocromocitoma/genética , Feocromocitoma/terapia , Feocromocitoma/diagnóstico , Paraganglioma/genética , Paraganglioma/terapia , Mutação em Linhagem Germinativa/genética , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Succinato Desidrogenase/genética
8.
Biomed Phys Eng Express ; 10(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38100790

RESUMO

Utilisation of whole organ volumes to extract anatomical and functional information from computed tomography (CT) and positron emission tomography (PET) images may provide key information for the treatment and follow-up of cancer patients. However, manual organ segmentation, is laborious and time-consuming. In this study, a CT-based deep learning method and a multi-atlas method were evaluated for segmenting the liver and spleen on CT images to extract quantitative tracer information from Fluorine-18 fluorodeoxyglucose ([18F]FDG) PET images of 50 patients with advanced Hodgkin lymphoma (HL). Manual segmentation was used as the reference method. The two automatic methods were also compared with a manually defined volume of interest (VOI) within the organ, a technique commonly performed in clinical settings. Both automatic methods provided accurate CT segmentations, with the deep learning method outperforming the multi-atlas with a DICE coefficient of 0.93 ± 0.03 (mean ± standard deviation) in liver and 0.87 ± 0.17 in spleen compared to 0.87 ± 0.05 (liver) and 0.78 ± 0.11 (spleen) for the multi-atlas. Similarly, a mean relative error of -3.2% for the liver and -3.4% for the spleen across patients was found for the mean standardized uptake value (SUVmean) using the deep learning regions while the corresponding errors for the multi-atlas method were -4.7% and -9.2%, respectively. For the maximum SUV (SUVmax), both methods resulted in higher than 20% overestimation due to the extension of organ boundaries to include neighbouring, high-uptake regions. The conservative VOI method which did not extend into neighbouring tissues, provided a more accurate SUVmaxestimate. In conclusion, the automatic, and particularly the deep learning method could be used to rapidly extract information of the SUVmeanwithin the liver and spleen. However, activity from neighbouring organs and lesions can lead to high biases in SUVmaxand current practices of manually defining a volume of interest in the organ should be considered instead.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Fígado/diagnóstico por imagem
9.
Front Endocrinol (Lausanne) ; 14: 1295865, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38093958

RESUMO

Introduction: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. Methods: This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. Results: There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. Conclusion: Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.


Assuntos
Hipofisite , Neoplasias , Doenças da Hipófise , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Hipofisite/diagnóstico por imagem , Hipofisite/tratamento farmacológico
10.
Cancers (Basel) ; 15(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38136348

RESUMO

BACKGROUND: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. METHODS: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. RESULTS: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3-32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4-98.0), kappa 0.83. CONCLUSION: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.

11.
Cancer Imaging ; 23(1): 119, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102639

RESUMO

BACKGROUND: A recent randomised trial demonstrated [18F]fluorodeoxyglucose positron-emission tomography in combination with low-dose CT (FDG-PET/CT), compared to standard of care computed tomography (CT) imaging, positively impacted antimicrobial management and outcomes of acute leukaemia and haematopoietic stem cell transplant recipients with persistent and recurrent neutropenic fever. We conducted an economic evaluation from a healthcare perspective alongside the clinical trial. METHODS: Unit costs in Australian dollars were applied to all resources used (antimicrobials, diagnostic tests, ICU and hospital bed days). Effectiveness was measured as number of patients with antimicrobial rationalisation, 6-month mortality and quality-adjusted life years (QALYs) derived from patient-reported trial-based health-related quality-of-life. Generalised linear models were used to analyse costs and outcomes. Incremental cost-effectiveness ratios (ICERs) for all outcomes and net monetary benefit (NMB) for QALYs were calculated. We performed bootstrapping with 1000 replications using the recycled predictions method. RESULTS: The adjusted healthcare costs were lower for FDG-PET/CT (mean $49,563; 95%CI 36,867, 65,133) compared to CT (mean $57,574; 95% CI 44,837, 73,347). The difference in QALYs between the two groups was small (0.001; 95% CI -0.001, 0.004). When simulated 1000 times, FDG-PET/CT was the dominant strategy as it was cheaper with better outcomes than the standard CT group in 74% of simulations. The estimated NMBs at willingness-to-pay thresholds of $50,000 and $100,000 per QALY were positive, thus FDG-PET/CT remained cost-effective at these thresholds. CONCLUSIONS: FDG-PET/CT is cost effective when compared to CT for investigation of persistent/recurrent neutropenic fever in high-risk patients, providing further support for incorporation of FDG-PET/CT into clinical guidelines and funding. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT03429387.


Assuntos
Anti-Infecciosos , Hematologia , Humanos , Austrália , Análise Custo-Benefício , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
AORN J ; 118(6): 349-351, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38011066
14.
Theranostics ; 13(14): 4745-4761, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771787

RESUMO

Peptide receptor radionuclide therapy (PRRT) using 177Lutetium-DOTA-octreotate (LuTate) for neuroendocrine tumours (NET) is now an approved treatment available in many countries, though primary or secondary resistance continue to limit its effectiveness or durability. We hypothesised that a genome-wide CRISPR/Cas9 screen would identify key mediators of response to LuTate and gene targets that might offer opportunities for novel combination therapies for NET patients. Methods: We utilised a genome-wide CRISPR-Cas9 screen in LuTate-treated cells to identify genes that impact on the sensitivity or resistance of cells to LuTate. Hits were validated through single-gene knockout. LuTate-resistant cells were assessed to confirm LuTate uptake and retention, and persistence of somatostatin receptor 2 (SSTR2) expression. Gene knockouts conferring LuTate sensitivity were further characterised by pharmacological sensitisation using specific inhibitors and in vivo analysis of the efficacy of these inhibitors in combination with LuTate. Results: The CRISPR-Cas9 screen identified several potential targets for both resistance and sensitivity to PRRT. Two gene knockouts which conferred LuTate resistance in vitro, ARRB2 and MVP, have potential mechanisms related to LuTate binding and retention, and modulation of DNA-damage repair (DDR) pathways, respectively. The screen showed that sensitivity to LuTate treatment in vitro can be conferred by the loss of a variety of genes involved in DDR pathways, with loss of genes involved in Non-Homologous End-Joining (NHEJ) being the most lethal. Loss of the key NHEJ gene, PRKDC (DNA-PK), either by gene loss or inhibition by two different inhibitors, resulted in significantly reduced cell survival upon exposure of cells to LuTate. In SSTR2-positive xenograft-bearing mice, the combination of nedisertib (a DNA-PK specific inhibitor) and LuTate produced a more robust control of tumour growth and increased survival compared to LuTate alone. Conclusions: DDR pathways are critical for sensing and repairing radiation-induced DNA damage, and our study shows that regulation of DDR pathways may be involved in both resistance and sensitivity to PRRT. Additionally, the use of a DNA-PK inhibitor in combination with LuTate PRRT significantly improves the efficacy of the treatment in pre-clinical models, providing further evidence for the clinical efficacy of this combination.


Assuntos
Lutécio , Tumores Neuroendócrinos , Animais , Humanos , Camundongos , Sistemas CRISPR-Cas/genética , DNA , Lutécio/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/radioterapia , Octreotida/uso terapêutico , Radioisótopos/uso terapêutico
15.
Eur J Nucl Med Mol Imaging ; 51(1): 183-195, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37721581

RESUMO

PURPOSE: We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [177Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. METHODS: This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [177Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [177Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 µg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. RESULTS: Median cumulative administered activity of [177Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatment­related adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3-99.4), and overall response rate was 21.1% (95% CI: 9.6-37.3). CONCLUSION: [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02592707. Registered October 30, 2015.


Assuntos
Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/tratamento farmacológico , Receptores de Somatostatina , Octreotida/efeitos adversos , Seguimentos , Compostos Organometálicos/efeitos adversos
16.
BMJ Open ; 13(8): e071327, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37541751

RESUMO

INTRODUCTION: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication. METHODS AND ANALYSIS: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival. ETHICS AND DISSEMINATION: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12619001735145.


Assuntos
Neoplasias Encefálicas , Ficus , Glioblastoma , Adulto , Humanos , Adolescente , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tirosina , Estudos Prospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Austrália , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto
18.
Cancer Imaging ; 23(1): 57, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291656

RESUMO

BACKGROUND: The impact of molecular imaging (MI) on patient management after biochemical recurrence (BCR) following radical prostatectomy has been described in many studies. However, it is not known if MI-induced management changes are appropriate. This study aimed to determine if androgen deprivation therapy (ADT) management plan is improved by MI in patients who are candidates for salvage radiation therapy. METHODS: Data were analyzed from the multicenter prospective PROPS trial evaluating PSMA/Choline PET in patients being considered for salvage radiotherapy (sRT) with BCR after prostatectomy. We compared the pre- and post-MI ADT management plans for each patient and cancer outcomes as predicted by the MSKCC nomogram. A higher percentage of predicted BCR associated with ADT treatment intensification after MI was considered as an improvement in a patient's management. RESULTS: Seventy-three patients with a median PSA of 0.38 ng/mL were included. In bivariate analysis, a positive finding on MI (local or metastatic) was associated with decision to use ADT with an odds ratio of 3.67 (95% CI, 1.25 to 10.71; p = 0.02). No factor included in the nomogram was associated with decision to use ADT. Also, MI improved selection of patients to receive ADT based on predicted BCR after sRT : the predicted nomogram 5-year biochemical-free survivals were 52.5% and 43.3%, (mean difference, 9.2%; 95% CI 0.8 to 17.6; p = 0.03) for sRT alone and ADT±sRT subgroups, while there was no statistically significant difference between subgroups before MI. CONCLUSIONS: PSMA and/or Choline PET/CT before sRT can potentially improve patient ADT management by directing clinicians towards more appropriate intensification.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Seleção de Pacientes , Antígeno Prostático Específico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antagonistas de Androgênios/uso terapêutico , Estudos Prospectivos , Recidiva Local de Neoplasia/patologia , Prostatectomia/métodos , Colina , Estudos Retrospectivos
19.
J Am Assoc Nurse Pract ; 35(7): 400-401, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37390461

RESUMO

ABSTRACT: One of the overlooked professional networking tools is the elevator speech. Nurse practitioners (NPs) should consider the elevator speech as equally important as their current curriculum vitae and professional biosketch. With advanced planning and practice, NPs can convey the who, what, why, and findings in less than 150 words to expand their network.


Assuntos
Profissionais de Enfermagem , Fala , Humanos
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