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2.
J Med Imaging Radiat Oncol ; 65(6): 748-754, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34318603

RESUMO

INTRODUCTION: This study aims to investigate whether nodal metabolic tumour volume (nMTV) and nodal total lesion glycolysis (nTLG) on Fluorine-18 fluoro-deoxy-glucose positron emission tomography-computed tomography (18 F-FDG PET/CT) in inoperable node-positive stage II and III non-small cell lung cancer (NSCLC) are independent predictors of overall survival (OS) in patients undergoing curative-intent chemoradiotherapy/radiotherapy (CRT/RT). METHODS: Data from two prospective trials between 2004 and 2016 were analysed retrospectively. Primary, nodal and total metabolic tumour volume and total lesion glycolysis (pMTV, nMTV, tMTV, pTLG, nTLG and tTLG, respectively) were derived from baseline 18 F-FDG PET/CT. Cox regressions were used to model OS by 18 F-FDG PET/CT parameters adjusting for overall stage. RESULTS: 89 patients with stage II (8%) and stage III (92%) were included. The median age at diagnosis was 67 years; 62% were male. The median follow-up was 6.9 years; the median OS was 2.2 years (95% CI 1.7-3.1). The median pMTV, nMTV and tMTV were 14 mL (range 0-360), 8 mL (range 0-250) and 34 mL (range 3-384), respectively. In 3 patients, the primary lesion could not be delineated from the central hilar mass. There was no association between nMTV (adjusted HR 1.04, 95% CI 0.95-1.15, P-value 0.43), pMTV (adjusted HR 1.0, 95% CI 0.96-1.04, P-value 0.92), tMTV (adjusted HR 1.0, 95% CI 0.97-1.04, P-value 0.88), nTLG, pTLG or tTLG and OS. Consistent results were noted when patients with central hilar lesions were excluded from analysis. CONCLUSION: In node-positive stage II and III NSCLC patients who underwent 18 F-FDG PET/CT-guided target delineation curative-intent concurrent CRT/RT, metabolic parameters did not appear to provide independent prognostication.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Carga Tumoral
3.
J Nucl Med ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049983

RESUMO

To assess the efficacy and safety of 177Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET). Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with 177Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and 68Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of 177Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5. Results: Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment 68Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of 177Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available 68Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and 68Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on 68Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia. Conclusion: In patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.

5.
Eur J Nucl Med Mol Imaging ; 48(1): 204-216, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32572559

RESUMO

PURPOSE: This study aimed to analyse the molecular imaging (MI) phenotype of typical carcinoid (TC) and atypical carcinoid (AC) by 68Ga-DOTATATE (GaTATE) and 18F-FDG (FDG) PET/CT with the emphasis on its potential theranostic implications for peptide receptor radionuclide therapy (PRRT). METHODS: Retrospective review of patients with biopsy-proven TC or AC undergoing both GaTATE and FDG PET/CT at presentation. Based on correlative CT or MRI, positive lesions on either scan were defined by uptake above liver parenchyma. Per patient MI phenotypic pattern was classified as score 1, if all lesions were negative on both scans; score 2, if all were GaTATE positive/FDG negative; score 3, if all lesions were GaTATE positive but some or all were also FDG positive and score 4, if there were any GaTATE negative/FDG positive lesions. Scores 1 and 4 were deemed unsuitable for PRRT. RESULTS: Of 56 patients (median age 66.5 years, 32 female), 22 had TC, and 34 had AC. Distant metastases were seen in 32% of TC and 94% of AC. At a median follow-up of 37 months for TC and 38 months for AC, 100% and 63% were alive, respectively. Median OS for AC was 56 months (95% CI 43, not reached [NR]), and TC was NR. On inter-patient dual-tracer analysis, scores 1, 2, 3 and 4 were 23%, 18%, 36% and 23% in TC and 3%, 15%, 32% and 50% in AC, respectively. In 16 patients (score 2, N = 3; score 3, N = 12; score 4, N = 1) who were treated with PRRT, disease control rate at 3 months and OS were, 85% and 54.6 months (95% CI 44-70), respectively. CONCLUSIONS: TC and AC showed a wide inter-patient phenotypic heterogeneity on GaTATE and FDG with around half of patients (46% TC and 53% AC) having an unsuitable phenotype for PRRT. Dual-tracer MI phenotype can be used to select the most suitable patients for PRRT.


Assuntos
Tumor Carcinoide , Tumores Neuroendócrinos , Compostos Organometálicos , Idoso , Feminino , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Humanos , Imagem Molecular , Fenótipo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Medicina de Precisão , Estudos Retrospectivos
6.
Eur J Nucl Med Mol Imaging ; 47(12): 2776-2786, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32338306

RESUMO

PURPOSE: We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma. METHODS: We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) pre- and post-treatment FDG-PET/CT scans (pre-FDG-PET/CT and post-FDG-PET/CT) within 2 and 4 months of starting ICI, respectively; and (3) at least one lesion assessable by PET response criteria in solid tumors (PERCIST). Extracranial response was monitored by 3 monthly FDG-PET/CT. Whole-body metabolic tumor volume (wbMTV) was measured pre- and post-treatment and correlated with outcome. FDG-PET/CT manifestations of irAE were defined as new increased non-tumoral uptake on post-FDG-PET/CT and were correlated with clinical presentation. RESULTS: Thirty-one consecutive patients, median age 60 years (range, 30-78), were identified from 2016 to 2018. The median number of combination-ICI cycles to the first post-FDG-PET/CT response assessment was 3 (interquartile range (IQR), 2-4). The best-overall responses were complete metabolic response (CMR) in 25 (80%), partial metabolic response (PMR) in 3 (10%), and progressive metabolic disease (PMD) in 3 (10%) patients. Patients with PMD had significantly higher pre-treatment wbMTV (p = 0.009). At a median follow-up of 21.5 months, 26 (84%) patients were alive with median progression-free and overall survival not reached. Secondary progression occurred in 9/31 (29%) patients at a median of 8.2 months (IQR, 6.9-15.5), of those majority (78%) was detected by FDG-PET/CT. Of 36 findings on post-FDG-PET/CT suggestive of irAE, 29 (80%) had clinical confirmation. In 3 (7%), the FDG-PET/CT findings preceded clinical presentation. The most common FDG-PET/CT detectable irAEs were endocrinopathies (36%) and enterocolitis (35%). CONCLUSION: FDG-PET/CT response evaluation predicts the long-term outcome of patients treated with first-line combination-ICIs. Long-term treatment response monitoring for detection of extracranial secondary progression is feasible by FDG-PET/CT. Beyond response assessment, FDG-PET/CT frequently detects clinically relevant irAEs, which may involve multiple systems contemporaneously or at various time-points and may precede clinical diagnosis.


Assuntos
Melanoma , Nivolumabe , Fluordesoxiglucose F18 , Humanos , Imunidade , Ipilimumab/efeitos adversos , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Resultado do Tratamento
7.
Eur J Nucl Med Mol Imaging ; 47(10): 2322-2327, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32140802

RESUMO

PURPOSE: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial. METHODS: PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment. RESULTS: This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4-4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8-0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2-4.4), ALP (HR 1.1; 95% CI, 1-1.2) and LDH (HR 1.2; 95% CI, 1-1.5) as biomarkers prognostic of overall survival. CONCLUSIONS: In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Próstata Resistentes à Castração , Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Humanos , Lutécio , Masculino , Prognóstico , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Radioisótopos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
J Nucl Med ; 61(6): 857-865, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31732676

RESUMO

177Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted ß-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy. Methods: Fifty patients with PSMA-avid metastatic castration-resistant prostate cancer who had progressed after standard therapies received up to 4 cycles of 177Lu-PSMA every 6 wk. Endpoints included prostate-specific antigen (PSA) response (Prostate Cancer Working Group 2), toxicity (Common Terminology Criteria for Adverse Events, version 4.03), imaging response, patient-reported health-related quality of life, progression-free survival, and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including 177Lu-PSMA. Results: Seventy-five men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 mo) and extensive prior treatment, including prior docetaxel (84%), cabazitaxel (48%), and abiraterone or enzalutamide (92%). The mean administered radioactivity was 7.5 GBq/cycle. A PSA decline of at least 50% was achieved in 32 of 50 patients (64%; 95% confidence interval [CI], 50%-77%), including 22 patients (44%; 95% CI, 30%-59%) with at least an 80% decrease. Of 27 patients with measurable soft-tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to 177Lu-PSMA were self-limiting G1-G2 dry mouth (66%), transient G1-G2 nausea (48%), G3-G4 thrombocytopenia (10%), and G3 anemia (10%). Brief Pain Inventory severity and interference scores decreased at all time points, including at the 3-mo follow-up, with a decrease of -1.2 (95% CI, -0.5 to -1.9; P = 0.001) and -1.0 (95% CI, -0.2 to -0.18; P = 0.013), respectively. At a median follow-up of 31.4 mo, median overall survival was 13.3 mo (95% CI, 10.5-18.7 mo), with a significantly longer survival of 18.4 mo (95% CI, 13.8-23.8 mo) in patients achieving a PSA decline of at least 50%. At progression after prior response, further 177Lu-PSMA was administered to 15 (30%) patients (median of 2 cycles commencing 359 d from enrollment), with a PSA decline of at least 50% in 11 patients (73%). Four of 21 patients (19%) receiving other systemic therapies on progression experienced a PSA decline of at least 50%. There were no unexpected adverse events with 177Lu-PSMA retreatment. Conclusion: This expanded 50-patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity, and improved quality of life with 177Lu-PSMA radioligand therapy. On progression, rechallenge 177Lu-PSMA demonstrated higher response rates than other systemic therapies.


Assuntos
Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Nanomedicina Teranóstica , Idoso , Idoso de 80 Anos ou mais , Dipeptídeos/efeitos adversos , Seguimentos , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Lutécio , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/psicologia , Qualidade de Vida , Retratamento
9.
J Gastrointest Surg ; 24(4): 899-906, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31090036

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical presentation, with considerable morbidity and mortality if left untreated. In recent decades, there is growing acceptance for the use of cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC). The aim of this study was to report on our 10-year single-center experience on outcomes following CRS and HIPEC for PMP of appendiceal origin. METHODS: A retrospective analysis of a prospectively maintained database of all patients undergoing CRS and HIPEC for PMP of appendiceal origin over a 10-year period at a statewide referral center was conducted. RESULTS: One hundred and seventy-five cytoreductive procedures were undertaken in 140 patients. The mean patient age was 57.4 years, with a female preponderance (56%). The median PCI was 16, with 73.1% of cases having a complete cytoreduction. Grade III/IV complications occurred in 36 (20.6%) cases, with no mortalities. The median overall and disease-free survival was 100 months and 40 months, respectively, with a 71% 5-year survival. High-grade histology was the main factor identified as an independent predictor of worse overall survival. CONCLUSION: CRS and HIPEC are safe with acceptable rates of morbidity. It can provide very favorable survival in patients with PMP. High-grade histology is a key prognostic factor associated with a worse overall survival.


Assuntos
Neoplasias do Apêndice , Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Neoplasias do Apêndice/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Estudos Retrospectivos
10.
Contemp Clin Trials Commun ; 16: 100409, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650066

RESUMO

Background: MYB is a transcription factor that is overexpressed in colorectal cancer (CRC) and also a driver mutation in adenoid cystic carcinoma (AdCC). Therefore, the MYB protein is an ideal target to vaccinate against to aid recruitment of tumour infiltrating lymphocytes (TILs) against these tumours. The Peter MacCallum Cancer Centre (Melbourne, Australia) has engineered a DNA vaccine, TetMYB, based on the pVAX1 plasmid vector carrying a fusion construct consisting of the universal tetanus toxin T-cell epitopes flanking an inactivated MYB gene. Methods: This prospective first-in-human phase I single-arm multi-centre clinical trial involves patients with metastatic CRC or AdCC. Stage 1 will evaluate the safety profile of escalating doses of TetMYB vaccine, given sequentially and in combination with an anti-PD-1 inhibitory antibody, to determine the maximum tolerated dose (MTD). Stage 2 will assess the MTD in an expanded cohort. The calculated sample size is 32 patients: 12 in Stage 1 and 20 in Stage 2. The expected total duration of the trial is 3 years with 15 months of recruitment followed by a minimum of 18 months follow-up. Discussion: MYB transcription factor is aberrantly overexpressed in a range of epithelial cancers, not limited to the above tumour types. Based on promising pre-clinical data of vaccine-induced tumour clearance and establishment of anti-tumour memory, we are embarking on this first-in-human trial. If successful, the results from this trial will allow progression to a Phase II trial and validation of this breakthrough immunotherapeutic approach, not only in CRC and AdCC, but other MYB over-expressing cancers. Trial registration: ClinicalTrials.gov ID: NCT03287427. Registered: September 19, 2017.

11.
Thyroid ; 29(11): 1634-1645, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31637953

RESUMO

Background: Some patients with metastatic differentiated thyroid cancer (DTC) lack iodine avidity and are therefore unsuitable for radioactive iodine (RAI) therapy. Limited experience suggests that single-agent selective mitogen-activated protein kinase (MAPK) pathway inhibitors can restore expression of the sodium-iodide symporter rendering RAI refractory (RAIR) DTC patients amenable to RAI therapy. The aim of this study was to assess the feasibility of mutation-guided MAPK-pathway blockade combined with thyroid hormone withdrawal (THW) for redifferentiation. Methods: This is a retrospective review of metastatic RAIR DTC and driver mutation in MAPK pathway, treated on a redifferentiation protocol. All patients had metastatic disease that had never been RAI-avid and/or imaging and biochemical progression despite treatment with RAI within the past 12 months. Patients with tumors harboring an NRAS mutation were treated with an MEK inhibitor (trametinib), and tumors with a BRAFV600E mutation with combined BRAF and MEK inhibition (dabrafenib and trametinib; or vemurafenib and cobimetinib) for four weeks. Thyrotropin stimulation was performed by THW for four weeks. Restoration of RAI uptake was determined by 124I positron emission tomography/computed tomography imaging. The response was assessed at least three months post-RAI. Results: From 2015 to 2017, six patients (age 45-70, four females) received redifferentiation therapy. Three patients had an NRAS mutation; two with follicular thyroid carcinoma (FTC) and one with a poorly differentiated thyroid carcinoma (PDTC); and three patients had a BRAFV600E mutation and papillary thyroid carcinoma (PTC). One NRAS and all BRAFV600E mutation cases demonstrated restoration of RAI uptake and proceeded to RAI therapy with a median follow-up of 16.6 months (range 13.5-42.3 months). The patient with an NRAS mutation and two of three patients with a BRAFV600E demonstrated partial imaging response beyond a three-month follow-up. Grade 3 adverse events (acneiform rash) were observed in two patients with NRAS mutations. Conclusions: Mutation-guided MAPK pathway inhibition with MEK inhibitor or a combination of BRAF inhibitor and MEK inhibitor under concurrent THW is a feasible and a promising strategy to redifferentiate RAIR DTC, thereby rendering them suitable for RAI therapy with satisfactory retention following treatment.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Neoplasias da Glândula Tireoide/radioterapia , Idoso , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Piridonas/farmacologia , Pirimidinonas/farmacologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento
12.
Eur Urol Oncol ; 2(6): 670-676, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31412006

RESUMO

BACKGROUND: Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of 177Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies. OBJECTIVE: To determine outcomes for men screened for the trial but not treated because of low PSMA expression. DESIGN, SETTING, AND PARTICIPANTS: Patients screened with 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography in a prospective trial. Patients ineligible for enrolment with low PSMA expression or FDG-positive PSMA-negative (discordant FDG-avid) disease were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subsequent treatments received were recorded. Kaplan-Meier analysis was used to determine overall survival from date of screening. RESULTS AND LIMITATIONS: Sixteen patients (24%) had low PSMA expression (n=8) or discordant FDG-avid disease (n=8). The median prostate-specific antigen doubling-time was 2.1mo. Eleven patients had Gleason ≥8 disease. All patients had previously progressed after docetaxel, 44% after cabazitaxel, and 94% after abiraterone and/or enzalutamide. Nine patients had subsequent systemic antitumour treatment. Fifteen patients died, with median OS of 2.5mo (95% confidence interval 1.7-5.0). Study limitations include uncertainty for imaging thresholds that define low PSMA expression. It is also possible that theranostic therapy could have improved survival in this cohort. CONCLUSIONS: Low PSMA expression or discordant FDG-avid disease in patients with mCRPC who progress after conventional therapies identifies a group with poor prognosis and short survival. PATIENT SUMMARY: The 177Lu-PSMA-617 radioligand may be an effective therapy for patients with advanced prostate cancer who progress after standard therapies. In this report we looked at outcomes for patients who were not eligible for this novel therapy on the basis of low prostate-specific membrane antigen uptake on screening positron emission tomography scans. We found that their outcomes were poor, with short survival.


Assuntos
Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/biossíntese , Intervalo Livre de Doença , Glutamato Carboxipeptidase II/biossíntese , Humanos , Lutécio , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
13.
Eur J Nucl Med Mol Imaging ; 46(9): 1869-1877, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190177

RESUMO

PURPOSE: Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS). METHODS: Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1-5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural; B) diffuse (involving more than a segment); and C) peripheral (diffusely surrounding a photopenic region). RESULTS: Follow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days; interquartile range, 79-93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.6-2.5; p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7; 95% CI, 1.2-2.2; p < 0.001). CONCLUSION: PET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Fluordesoxiglucose F18 , Neoplasias Pulmonares/terapia , Pneumonia/diagnóstico por imagem , Pneumonia/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Eur J Nucl Med Mol Imaging ; 46(9): 1902-1910, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31187162

RESUMO

PURPOSE: Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN. METHODS: Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed. RESULTS: Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4-91). Twenty-two of 25 (88%) patients had grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 109/L, range 3-75) and 17 (68%) remained NEN progression-free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients with tumour protein 53 (TP53) mutation in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from first PRRT was 62 months (19-94), but from t-MN diagnosis was only 13 months (1-56), with death due primarily to haematological disease progression. CONCLUSIONS: The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia; unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN.


Assuntos
Quimiorradioterapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Receptores de Peptídeos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
15.
Cancer Imaging ; 19(1): 28, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142361

RESUMO

BACKGROUND: Testicular germ cell tumour is the commonest malignancy affecting males aged between 15 and 35, with an increased relative risk amongst those with a history of cryptorchidism. In patients presenting with locoregional metastatic disease, retroperitoneal and pelvic soft tissue masses are common findings on ultrasound and computed tomography, which has several differential diagnoses within this demographic cohort. On staging 18F-FDG-PET/CT, understanding the typical testicular lymphatic drainage pathway facilitates prompt recognition of the pathognomonic constellation of unilateral absence of testicular scrotal activity, and FDG-avid nodal masses along the drainage pathway. We describe the cases of three young males presenting with abdominopelvic masses, in whom FDG-PET/CT was helpful in formulating a unifying diagnosis of metastatic seminoma, retrospectively corroborated by a history of testicular maldescent. CASE PRESENTATIONS: In all three cases, the patients were males aged in their 30s and 40s who were brought to medical attention for back and lower abdominal pain of varying duration. Initial imaging evaluation with computed tomography and/or ultrasound revealed large abdominopelvic soft tissue masses, with lymphoproliferative disorders or soft tissue sarcomas being high on the list of differential diagnoses. As such, they were referred for staging FDG-PET/CT, all of whom demonstrated the pathognomonic constellation of, 1) unilateral absence of scrotal testicular activity, and 2) FDG-avid nodal masses along the typical testicular lymphatic drainage pathway. These characteristic patterns were corroborated by a targeted clinical history and examination which revealed a history of cryptorchidism, and elevated ß-hCG in two of three patients. All were subsequently confirmed as metastatic seminoma on biopsy and open resection. CONCLUSION: These cases highlight the importance of clinical history and examination for the clinician, as well as a sound knowledge of the typical testicular lymphatic drainage pathway for the PET physician, which would assist with prompt recognition of the characteristic imaging patterns on FDG-PET/CT. It further anecdotally supports the utility of FDG-PET/CT in evaluating undiagnosed abdominopelvic masses, as well as a potential role in the initial staging of germ cell tumours in appropriately selected patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Masculino , Compostos Radiofarmacêuticos
16.
J Clin Endocrinol Metab ; 104(11): 5091-5099, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30977831

RESUMO

PURPOSE: Germline succinate dehydrogenase (SDHx) mutation carriers, especially SDHB, are at increased risk for malignancy and require life-long surveillance. Current guidelines recommend periodic whole-body MRI imaging. We assessed the incremental value of 68Ga-DOTA-octreotate (GaTate) positron emission tomography (PET)/CT compared with conventional imaging in such patients. METHODS: SDHx mutation carriers who had GaTate PET/CT were retrospectively reviewed. Detection of lesions were compared with MRI or CT on a per-patient and per-lesion basis. Proof of lesions were based on histopathology or clinical/imaging follow-up. RESULTS: Twenty consecutive patients (median age, 46 years; 10 males) were reviewed. Fourteen patients had SDHB, four, SDHD, one SDHC, and one SDHA mutation. Fifteen had prior surgery and/or radiotherapy. Indications for PET/CT were as follows: 7 patients for surveillance for previously treated disease, 9 residual disease, 2 asymptomatic mutation carriers, and 2 for elevated catecholamines. Median time between modalities was 1.5 months.GaTate PET/CT had higher sensitivity and specificity than conventional imaging. On a per-patient basis: PET/CT sensitivity 100%, specificity 100%; MRI/CT 85% and 50%. Per-lesion basis: PET/CT sensitivity 100%, specificity 75%; MRI/CT 80% and 25%. PET/CT correctly identified additional small nodal and osseous lesions. MRI/CT had more false-positive findings. Change of management resulted in 40% (8/20 patients): 3 received localized treatment instead of observation, 1 changed to observation given extra disease detected, 4 with metastases had radionuclide therapy. CONCLUSIONS: GaTate PET/CT provided incremental diagnostic information with consequent management impact in SDHx-pheochromocytoma and paraganglioma. Incorporating this modality as part of a surveillance program seems prudent. Further research is needed to define the optimal surveillance strategy including use of MRI.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Compostos Organometálicos , Paraganglioma/diagnóstico por imagem , Feocromocitoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Adolescente , Adulto , Idoso , Catecolaminas/metabolismo , Reações Falso-Positivas , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Mutação , Metástase Neoplásica/diagnóstico por imagem , Paraganglioma/radioterapia , Paraganglioma/cirurgia , Feocromocitoma/radioterapia , Feocromocitoma/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
17.
J Nucl Med ; 60(3): 328-334, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30030343

RESUMO

The optimal methodology for defining response with 18F-FDG PET after curative-intent chemoradiation for non-small cell lung cancer (NSCLC) is unknown. We compared survival outcomes according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC), PERCIST 1.0, the Peter Mac metabolic visual criteria, and the Deauville criteria, respectively. Methods: Three prospective trials of chemoradiation for NSCLC, involving baseline and posttreatment 18F-FDG PET/CT imaging, were conducted between 2004 and 2016. Responses were categorized as complete metabolic response (CMR), partial metabolic response, stable metabolic disease, or progressive metabolic disease. Cox proportional-hazards models and log-rank tests assessed the impact of each response on overall survival (OS). Results: Eighty-seven patients underwent 18F-FDG PET/CT before and after radical chemoradiation for NSCLC. Follow-up 18F-FDG PET/CT scans were performed at a median of 89 d (interquartile range, 79-93 d) after radiotherapy. Median follow-up and OS after PET response imaging were 49 and 28 mo, respectively. Interobserver agreements for EORTC, PERCIST, Peter Mac, and Deauville had κ values of 0.76, 0.76, 0.87, and 0.84, respectively. All 4 response criteria were significantly associated with OS. Peter Mac and Deauville showed better fit than EORTC and PERCIST and distinguished better between CMR and non-CMR. Conclusion: All 4 response criteria were highly predictive of OS, but visual criteria showed greater interobserver agreement and stronger discrimination between CMR and non-CMR, highlighting the importance of visual assessment to recognize radiation pneumonitis, changes in lung configuration, and patterns of response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
18.
Intern Med J ; 49(8): 1001-1006, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30515932

RESUMO

BACKGROUND: Clinical audit may improve practice in cancer service provision. The UK National Lung Cancer Audit (NLCA) collects data for all new cases of thoracic cancers. AIM: To collect similar data for our Victorian patients from six hospitals within the Victorian Comprehensive Cancer Centre and associated Western and Central Melbourne Integrated Cancer Service. METHODS: We conducted a retrospective audit of all newly diagnosed patients with lung cancer and mesothelioma in 2013 across the six Victorian Comprehensive Cancer Centre/Western and Central Melbourne Integrated Cancer Service hospitals. The objectives were to adapt the NLCA data set for use in the Australian context, to analyse the findings using descriptive statistics and to determine feasibility of implementing a routine, ongoing audit similar to that in the UK. Individual data items were adapted from the NLCA by an expert steering committee. Data were collated from the Victorian Cancer Registry, Victorian Admitted Episodes Dataset and individual hospital databases. Individual medical records were audited for missing data. RESULTS: Eight hundred and forty-five patients were diagnosed across the sites in 2013. Most were aged 65-80 (55%) and were male (62%). Most had non-small-cell lung cancer (81%) with 9% diagnosed with small cell lung cancer and 2% with mesothelioma. Data completeness varied significantly between fields. For those with higher levels of completeness, headline indicators of clinical care were comparable with NLCA data. The Victorian population seem to lack access to specialist lung cancer nurse services. CONCLUSION: Lung cancer care at participating hospitals appeared to be comparable with the UK in 2013. In future, prospective data collection should be harmonised across sites and correlated with survival outcomes. One area of concern was a lack of documented access to specialist nursing services.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Auditoria Médica , Mesotelioma/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Bases de Dados Factuais , Feminino , Acesso aos Serviços de Saúde , Hospitais , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Registros Médicos , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Reino Unido
19.
J Nucl Med ; 60(4): 517-523, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30291192

RESUMO

177Lu-prostate-specific membrane antigen (PSMA)-617 enables targeted delivery of ß-particle radiation to prostate cancer. We determined its radiation dosimetry and relationships to pretherapeutic imaging and outcomes. Methods: Thirty patients with prostate cancer receiving 177Lu-PSMA-617 within a prospective clinical trial (ACTRN12615000912583) were studied. Screening 68Ga-PSMA-11 PET/CT demonstrated high PSMA expression in all patients. After therapy, patients underwent quantitative SPECT/CT at 4, 24, and 96 h. Pharmacokinetic uptake and clearance at a voxel level were calculated and translated into absorbed dose using voxel S values. Volumes of interest were drawn on normal tissues and tumor to assess radiation dose, and a whole-body tumor dose was defined. Correlations between PSMA PET/CT parameters, dosimetry, and biochemical and therapeutic response were analyzed to identify relationships between absorbed dose, tumor burden, and patient physiology. Results: Mean absorbed dose to kidneys, submandibular and parotid glands, liver, spleen, and bone marrow was 0.39, 0.44, 0.58, 0.1, 0.06, and 0.11 Gy/MBq, respectively. Median whole-body tumor-absorbed dose was 11.55 Gy and correlated with prostate-specific antigen (PSA) response at 12 wk. A median dose of 14.1 Gy was observed in patients achieving a PSA decline of at least 50%, versus 9.6 Gy for those achieving a PSA decline of less than 50% (P < 0.01). Of 11 patients receiving a tumor dose of less than 10 Gy, only one achieved a PSA response of at least 50%. On screening PSMA PET, whole-body tumor SUVmean correlated with mean absorbed dose (r = 0.62), and SUVmax of the parotids correlated with absorbed dose (r = 0.67). There was an inverse correlation between tumor volume and mean dose to the parotids (r = -0.41) and kidneys (r = -0.43). The mean parotid dose was also reduced with increasing body mass (r = -0.41) and body surface area (r = -0.37). Conclusion: 177Lu-PSMA-617 delivers high absorbed doses to tumor, with a significant correlation between whole-body tumor dose and PSA response. Patients receiving less than 10 Gy were unlikely to achieve a fall in PSA of at least 50%. Significant correlations between aspects of screening 68Ga-PET/CT and tumor and normal tissue dose were observed, providing a rationale for patient-specific dosing. Reduced salivary and kidney doses were observed in patients with a higher tumor burden. The parotid dose also reduced with increasing body mass and body surface area.


Assuntos
Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Lutécio , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Radioisótopos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Masculino , Metástase Neoplásica , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Radiometria , Resultado do Tratamento
20.
Eur J Nucl Med Mol Imaging ; 46(3): 718-727, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30343432

RESUMO

PURPOSE: Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres. METHODS: Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT. RESULTS: Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had 177Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia. CONCLUSION: Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.


Assuntos
Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Receptores de Somatostatina/metabolismo , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/metabolismo , Estudos Retrospectivos , Resultado do Tratamento
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