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Everolimus and peptide receptor radionuclide therapy (PRRT, 177Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 mo (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 mo (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations.
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Background: 177Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy. Methods: Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT. Results: Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year (p < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level (p < 0.05) for patients with progressive disease. Conclusion: We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients.
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Neoplasias Intestinais , MicroRNAs , Tumores Neuroendócrinos , RNA Mensageiro , Humanos , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/patologia , Masculino , Feminino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Intestinais/sangue , Neoplasias Intestinais/patologia , Neoplasias Intestinais/genética , Neoplasias Intestinais/tratamento farmacológico , RNA Mensageiro/genética , RNA Mensageiro/sangue , Idoso , Seguimentos , Adulto , Prognóstico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Receptores de Peptídeos/genética , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/administração & dosagem , Lutécio , RadioisótoposRESUMO
BACKGROUND: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is a recognized option for treating neuroendocrine tumors and has few toxicities, except for the kidneys and bone marrow. The bone marrow dose is generally derived from a SPECT/CT image-based method with four timepoints or from a blood-based method with up to 9 timepoints, but there is still no reference method. This retrospective single-center study on the same cohort of patients compared the calculated bone marrow dose administered with both methods using mono, bi- or tri-exponential models. For the image-based method, the dose was estimated using Planetdose© software. Pearson correlation coefficients were calculated. We also studied the impact of late timepoints for both methods. RESULTS: The bone marrow dose was calculated for 131 treatments with the blood-based method and for 17 with the image-based method. In the former, the median absorbed dose was 15.3, 20.5 and 28.3 mGy/GBq with the mono-, bi- and tri-exponential model, respectively. With the image-based method, the median absorbed dose was 63.9, 41.9 and 60.8 with the mono-, bi- and tri-exponential model, respectively. Blood samples after 24h post-injection did not evidence any change in the absorbed bone marrow dose with the bi-exponential model. On the contrary, the 6-day post-injection timepoint was more informative with the image-based model. CONCLUSION: This study confirms that the estimated bone marrow dose is significantly lower with the blood-based method than with the image-based method. The blood-based method with a bi-exponential model proved particularly useful, without the need for blood samples after 24h post-injection. Nevertheless, this blood-based method is based on an assumption that needs to be more validated. The important difference between the two methods does not allow to determine the optimal one to estimate the true absorbed dose and further studies are necessary to compare with biological effects.
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BACKGROUND: Performance assessment of positron emission tomography (PET) scanners is crucial to guide clinical practice with efficiency. We have already introduced and experimentally evaluated a simulation method allowing the creation of a controlled ground truth for system performance assessment. In the current study, the goal was to validate the method using patient data and demonstrate its relevance to assess PET performances accuracy in clinical conditions. METHODS: Twenty-four patients were recruited and sorted into two groups according to their body mass index (BMI). They were administered with a single dose of 2 MBq/kg 18F-FDG and scanned using clinical protocols consecutively on two PET systems: the Discovery-IQ (DIQ) and the Discovery-MI (DMI). For each BMI group, sixty synthetic lesions were dispatched in three subgroups and inserted at relevant anatomical locations. Insertion of synthetic lesions (ISL) was performed at the same location into the two consecutive exams. Two nuclear medicine physicians evaluated individually and blindly the images by qualitatively and semi-quantitatively reporting each detected lesion and agreed on a consensus. We assessed the inter-system detection rates of synthetic lesions and compared it to an initial estimate of at least 1.7 more targets detected on the DMI and the detection rates of natural lesions. We determined the inter-reader variability, evaluated according to the inter-observer agreement (IOA). Adequate inter-reader variability was found for IOA above 80%. Differences in standardized uptake value (SUV) metrics were also studied. RESULTS: In the BMI ≤ 25 group, the relative true positive rate (RTPR) for synthetic and natural lesions was 1.79 and 1.83, respectively. In the BMI > 25 group, the RTPR for synthetic and natural lesions was 2.03 and 2.27, respectively. For each BMI group, the detection rate using ISL was consistent to our estimate and with the detection rate measured on natural lesions. IOA above 80% was verified for any scenario. SUV metrics showed a good agreement between synthetic and natural lesions. CONCLUSIONS: ISL proved relevant to evaluate performance differences between PET scanners. Using these synthetically modified clinical images, we can produce a controlled ground truth in a realistic anatomical model and exploit the potential of PET scanner for clinical purposes.
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In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data.
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PURPOSE: NETTER-R aimed to determine the efficacy, safety and tolerability of 177Lu-DOTATATE in patients with progressive, advanced pancreatic neuroendocrine tumours (panNETs) using retrospective real-world data from multiple sites. METHODS: This international study retrospectively included patients with panNETs treated with 177Lu-DOTATATE. The primary endpoint was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included overall survival (OS), safety and tumour response. RESULTS: In total, 110 patients with panNETs were studied; 65.5% received a cumulative dose of 177Lu-DOTATATE 29.6 GBq ± 10% (median: 7.4 GBq). In 62 patients with available RECIST v1.1 tumour response, the median PFS was 24.8 months (95% confidence interval [CI]: 17.5-34.5), and the objective response rate was 40.3% (95% CI: 28.1-53.6); all responses were partial. With a median follow up of 24.5 months (range: 2.0-123.4 months) after the first cycle of 177Lu-DOTATATE, the median OS in the full analysis set (n = 110) was 41.4 months (95% CI: 28.6-50.2). PFS (hazard ratio [HR]: 3.672; p = 0.0009) and OS (HR: 3.360; p < 0.0001) were longer in patients who received no chemotherapy prior to 177Lu-DOTATATE than those who did. No treatment-emergent adverse events (TEAEs) led to treatment discontinuation. Grade 3 anaemia, lymphopenia and thrombocytopenia occurred in 0.9%, 5.4% and 0.9% of patients, respectively. No acute leukaemia or myelodysplastic syndrome was reported. Six patients (5.5%) had renal TEAEs. All renal grade ≥ 3 events were transient and did not lead to treatment modification. CONCLUSIONS: These results reinforce the role of 177Lu-DOTATATE for the treatment of patients with advanced, somatostatin receptor-positive panNETs.
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Tumores Neuroendócrinos , Compostos Organometálicos , Neoplasias Pancreáticas , Compostos Radiofarmacêuticos , Humanos , Tumores Neuroendócrinos/radioterapia , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/radioterapia , Tomografia por Emissão de Pósitrons , Cintilografia , Compostos Radiofarmacêuticos/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: 177Lu-Dotatate is used in the treatment of somatostatin-receptor-positive inoperable progressive gastroenteropancreatic neuroendocrine tumors. A co-infusion of amino acids (AAs) is administered to prevent renal toxicity. OBJECTIVE: This study aimed to quantify the impact of two types of AA cocktails on the pharmacokinetics and toxicity of 177Lu-Dotatate. METHODS: Four injections of 7400 MBq 177Lu-Dotatate were given per patient with administration of either Primene® 10% (containing a cocktail of 20 AAs with 22g of Lysine and 16.8 g of Arginine) or Lysakare® (containing 25 g of Lysine and 25 g of Arginine). Nine blood samples were collected at each cycle. Radioactivity-time data were analyzed according to a population-based model using NONMEM (version 7.4.1). Renal and hematological toxicity was evaluated after each cycle. RESULTS: 1,678 177Lu-Dotatate plasma concentrations versus time were analyzed from 83 consecutive patients with Primene® (n= 45 pts) or Lysakare® (n= 36 pts). Population pharmacokinetic analysis showed that Primene® significantly increased the elimination rate constant of 177Lu-Dotatate as opposed to Lysakare®. Primene® also significantly lowered Lutathera® plasma exposure (AUC) by 34%, whereas Lysakare® increased AUC by 7%. There was no renal toxicity in either case. Lymphopenia significantly correlated with AUC (p=0.021) with a trend towards higher toxicity with Lysakare®. CONCLUSION: Unlike Primene®, Lysakare® does not increase 177Lu-Dotatate elimination. This difference is associated with a significant impact on AUC. The latter parameter has a high interpatient variability but a low intrapatient variability, which could have important clinical implications for treatment tailoring.
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Tumores Neuroendócrinos , Compostos Organometálicos , Arginina/uso terapêutico , Humanos , Neoplasias Intestinais , Lisina/uso terapêutico , Tumores Neuroendócrinos/radioterapia , Octreotida/farmacologia , Neoplasias Pancreáticas , Tomografia por Emissão de Pósitrons , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias GástricasRESUMO
Peptide receptor radionuclide therapy (PRRT) is a well-established treatment in somatostatin receptor-expressing neuroendocrine tumours (NETs). The safety and efficacy of PRRT in >79 years old patients (EP) have not been systematically investigated. All patients with inoperable/metastatic/progressive G1/G2 NET, >79 years (EP), treated with PRRT at the University Hospital of Basel between 2006 and 2018, were enrolled in this retrospective matched cohort study. Each patient was manually matched with ≥1 younger patient (YP = 60-70 years). The primary endpoint was toxicity. Toxicity (subacute, long-term) was graded according to the criteria for adverse events (CTCAE) v5.0. All toxicity grades ≥ 3, or whose delta (Δ) to baseline were ≥2, were considered significant. The odds ratio (OR) for developing toxicity was tested for non-inferiority of EP vs. YP. Clinical response to PRRT and overall survival (OS) were assessed as secondary outcome measures. Forty-eight EP and 68 YP were enrolled. Both cohorts were balanced regarding median time since diagnosis, tumour location, grading, treatment scheme, and baseline biochemical parameters, except for eGFR (EP: 61 ± 16 vs. YP: 78 ± 19; mL/min/1.73 m2). Twenty-two grade ≥ 3 or Δ ≥ 2 subacute hematotoxicities occurred in 10 EP (10.3% of cycles) and 37 in 19 YP (11.6% of cycles; p = NS). Long-term grade ≥ 3 renal toxicity occurred in 7 EP and 2 YP (p = NS). The median OS was 3.4 years (EP) vs. 6.0 years (YP), HR: 1.50 [0.75, 2.98], p = NS. PRRT is a valid therapeutic option in elderly NET patients with similar toxicity and non-inferior survival compared to matched younger patients.
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PURPOSE: Medical imaging plays a central and decisive role in guiding the management of patients with pancreatic neuroendocrine tumors (PNETs). Our aim was to synthesize all recent literature of PNETs, enabling a comparison of all imaging practices. METHODS: based on a systematic review and meta-analysis approach, we collected; using MEDLINE, EMBASE, and Cochrane Library databases; all recent imaging-based studies, published from December 2014 to December 2019. Study quality assessment was performed by QUADAS-2 and MINORS tools. RESULTS: 161 studies consisting of 19852 patients were included. There were 63 'imaging' studies evaluating the accuracy of medical imaging, and 98 'clinical' studies using medical imaging as a tool for response assessment. A wide heterogeneity of practices was demonstrated: imaging modalities were: CT (57.1%, n=92), MR (42.9%, n=69), PET/CT (13.3%, n=31), and SPECT/CT (9.3%, n=15). International imaging guidelines were mentioned in 2.5% (n=4/161) of studies. In clinical studies, imaging protocol was not mentioned in 30.6% (n=30/98) of cases and only mentioned imaging modality without further information in 63.3% (n=62/98), as compared to imaging studies (1.6% (n=1/63) of (p<0.001)). QUADAS-2 and MINORS tools deciphered existing biases in the current literature. CONCLUSION: We provide an overview of the updated current trends in use of medical imaging for diagnosis and response assessment in PNETs. The most commonly used imaging modalities are anatomical (CT and MRI), followed by PET/CT and SPECT/CT. Therefore, standardization and homogenization of PNETs imaging practices is needed to aggregate data and leverage a big data approach for Artificial Intelligence purposes.
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Lu-DOTATATE is an effective treatment for inoperable metastatic well-differentiated pancreatic neuroendocrine tumors. There are no guidelines for patients with terminal renal failure. We present the case of a 74-year-old woman who received different lines of treatment: analogs of somatostatin, chemotherapy, a first series of peptide receptor radionuclide therapy (PRRT), and finally chemoembolization. Because of persistent hepatic progression, a safe and successful administration of 4 cycles of a second series of PRRT under hemodialysis was administered. Patient was in scintigraphic complete remission at 12 months with normal hematological parameters at 12 and 30 months after PRRT.
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Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/uso terapêutico , Progressão da Doença , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Neoplasias Pancreáticas/radioterapia , Diálise Renal , Segurança , Idoso , Embolização Terapêutica , Feminino , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Neoplasias Pancreáticas/patologia , Resultado do TratamentoRESUMO
The majority of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are diagnosed at a non-resectable stage due to non-specific clinical syndromes, late manifestations from mass effects, or incidental detection of a clinically silent disease. Management strategies include curative or cytoreduction surgery, imaging-guided intervention, chemotherapy, immunotherapy, and radionuclide therapies. In this step-by-step review, we provide a structured approach for standardized reading and reporting of medical imaging studies covering content and terminology. This review explains which imaging studies should be used for different NETs and what should be reported when interpreting these studies. This standardized data collection guide should enable precision medicine for the management of patients with GEP-NETs of neuroectodermal origin: gastrointestinal-NETs (giNETs) and pancreatic NETs (pNETs). To improve outcomes from GEP-NETs, it contains a comprehensive evaluation of imaging aids for determining surgical non-resectability, and serves as a surrogate measure for tumor differentiation and proliferation, assessing the spatial and temporal heterogeneity of the tumor sites with prognostic and therapeutic implications.
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Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Intestinais/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Medicina de Precisão/métodos , Neoplasias Gástricas/cirurgia , Humanos , Neoplasias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , Prognóstico , Neoplasias Gástricas/terapiaRESUMO
Neuroendocrine tumors (NET) represent a heterogeneous group of tumors originating from cells of neuroendocrine origin, which express somatostatin receptors (SSTR). This property allowed the successful development of radionuclides for diagnostic and peptide radionuclide radiation therapy (PRRT). This is the paradigm for the theragnostic concept in NET personalized medicine. The only phase III study to date (NETTER-1) clearly demonstrated the ability of 177Lutetium-based PRRT to improve progression-free survival in advanced intestinal NETs. In clinical practice, the indications are limited to G1-G2 well-differentiated NETs with high expression of SSTR. NETs with a low tumor burden and slow progression are probably the optimal indication. This treatment is now available in France. However, its precise position in the treatment algorithm remains to be explored. We provide an overview of receptor radionuclide utilization and mechanism in diagnostic and pretherapeutic imaging and we focus on PRRT for endocrine tumors.
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Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Receptores de Somatostatina/análise , Ensaios Clínicos Fase III como Assunto , França , Humanos , Lutécio/uso terapêutico , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Medicina de Precisão/métodos , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos , Radioterapia/métodos , Receptores de Somatostatina/antagonistas & inibidoresRESUMO
A 58-year-old woman with 5-year history of grade 1 progressive metastatic intestinal neuroendocrine tumor with metachronous liver metastases initially treated by surgery and liver embolization underwent Ga-DOTANOC PET/CT before Lu-DOTATATE therapy. Ga-DOTANOC PET/CT revealed increased uptake in several liver metastases and right iliac lymph nodes, consistent with radiopeptide therapy, including a hypodense isthmic thyroid nodule. Fine needle ultrasound-guided biopsy of the thyroid nodule was realized. Immunohistochemistry was positive for CD56, chromogranin, and synaptophysin and negative for calcitonin, confirming neuroendocrine tumor intrathyroid metastasis. Lu-DOTATATE SPECT/CT showed therapeutic uptake on the thyroid metastasis.
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Neoplasias Intestinais/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Feminino , Humanos , Neoplasias Intestinais/patologia , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Octreotida/análogos & derivados , Compostos Organometálicos , Compostos Radiofarmacêuticos , Neoplasias da Glândula Tireoide/secundárioRESUMO
BACKGROUND: 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays an important part in the oncological evaluation of the abdomen and pelvis, but the interpretation and quantification is often hampered by intense physiological urinary activity. We evaluate 2 different diuretic imaging protocols by comparing intensity of urinary activity and we look at the impact of multiple variables on the final urinary activity. METHODS: Comparative analysis of 102 patients (median age: 64) having intrapelvic carcinoma. After full body acquisition, 58 patients were administered 20 mg of furosemide 90 min post injection of FDG (P90). For 44 patients, 20 mg of furosemide was administered 30 min post injection of FDG (P30). Comparisons between groups were performed using the Mann-Whitney Test and χ2. The BMI, creatinine, clearance, age, injected activity, diuretic protocol, gender and glycemia were evaluated with multivariate analysis for their impact on the final urinary activity. RESULTS: Concerning the comparison of the urinary activity we observe a significant difference (P=0.0029) between P90 and P30 for the SUVmax (median 4.3 [range 1.6: 17.7] vs. 6.0 [range 2.9: 15.1]), and for the SUVmean (P<0.001) (median 2.4 [range 1.1; 9.9] vs. 3.8 [range 2.0; 10.1]). For 2 patients of P30, the acquisition was interrupted because the patient needed to void. Multivariate analysis shows that creatinine and creatinine clearance do not have a significant independent impact on the final bladder activity. CONCLUSIONS: By comparing the 2 diuretic imaging protocols, we found a significant lower urinary activity for the P90 protocol and the regression decision tree shows that the P90 protocol is mostly superior. The P30 protocol, which seems to be less well tolerated, is adequate in the group of patients with an injected activity of less than 240 MBq and older than 65 years, if P90 is not feasible. For most patients with injected activity ≥240 MBq or BMI of ≥25 and a glycemia >120 mg/dL, a significant amount of residual urinary activity remains for both protocols.
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Diuréticos/farmacologia , Fluordesoxiglucose F18 , Neoplasias Pélvicas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Furosemida/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: 177Lu-Dotatate is a radio-labeled analog of somatostatin used in the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. In order to prevent nephrotoxic effects of 177Lu-Dotatate a co-infusion of amino acids (AA) is administered, resulting in a decrease in tubular renal reabsorption of 177Lu-Dotatate. This study aimed to quantify the impact of AA co-infusion on the pharmacokinetics of 177Lu-Dotatate in cancer patients and to evaluate its relationship with toxicity during the first treatment cycle (C1). METHODS: 7.4 GBq of 177Lu-Dotatate was administered to 42 patients over a 30-min intravenous infusion. Infusion of AA started 2 h before and continued for 6 h after the infusion of 177Lu-Dotatate. Radioactivity-time data (n = 346) were analyzed using NONMEM® (version 7.2.0). RESULTS: 177Lu-Dotatate pharmacokinetics was best described by a three-compartment model with first-order elimination. AA co-infusion had a significant effect ('fixed effect') on 177Lu-Dotatate pharmacokinetics, with a mean value of 1.5-fold (95% confidence interval 1.03-1.97) increase in the elimination rate constant (k10) from 0.204 to 0.306 h-1, but this AA co-infusion effect was associated with a large inter-individual variability (IIV) of 104%. The individual k10 values increased during concomitant AA infusion by a factor ranging from 1.01 to 21.3 for 27 patients, whereas the opposite effect was observed in 15 patients (range 0.36-0.99) of whom seven had a k10 value lower than 0.85. This variability in AA effect contributed to the variability in 177Lu-Dotatate plasma exposure (area under the concentration-time curve from time zero to Day 15 for C1 [AUCDay15]) that correlated with lymphopenia observed at Day 15 (p = 0.004). CONCLUSIONS: A substantial effect of AA co-infusion on 177Lu-Dotatate pharmacokinetics was shown but was associated with high IIV, contributing to IIV in hematological toxicity.
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Aminoácidos/administração & dosagem , Antineoplásicos/farmacocinética , Neoplasias Intestinais/metabolismo , Modelos Biológicos , Tumores Neuroendócrinos/metabolismo , Octreotida/análogos & derivados , Compostos Organometálicos/farmacocinética , Neoplasias Pancreáticas/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Feminino , Humanos , Infusões Intravenosas , Rim/efeitos dos fármacos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Octreotida/efeitos adversos , Octreotida/sangue , Octreotida/farmacocinética , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/sangueRESUMO
Mucormycosis is a life-threatening infection with most commonly rhino-orbital-cerebral and pulmonary syndromes that mostly occurs in immunocompromised patients. FDG-PET/CT emerged as a sensitive non-invasive tool to identify systemic mucormycosis. We present a 59-year-old woman for whom a PET/CT with 18F-FDG was performed in search of a primary location of mucormycosis with non-contributive conventional workup. A large left abdominal mass was seen, compatible with a fungus ball, with intense parietal uptake and without any central uptake. The localization of the infection provided a target for surgery and permitted to adapt the therapeutic strategy. After resection, the final diagnosis was consistent with mucormycosis. To our knowledge, this is the first report of a PET/CT image with FDG showing an intestinal fungus ball. PET/CT with 18F-FDG may contribute to the management of patients with fungal infections of unknown origin.
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PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. RESULTS: MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. CONCLUSION: Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization.
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Sangue/efeitos da radiação , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Colina/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Próstata Resistentes à Castração/patologia , Rádio (Elemento)/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Rádio (Elemento)/uso terapêuticoRESUMO
INTRODUCTION: Because of our previous preclinical results, we conducted a phase I study associating the specific αvß3/αvß5 integrin inhibitor cilengitide, given as a continuous infusion, with exclusive chemoradiotherapy for patients with stage III non-small-cell lung cancer. PATIENTS AND METHODS: A standard 3+3 dose escalation design was used. Cilengitide was given as a continuous infusion (dose levels of 12, 18, 27, and 40 mg/h), starting 2 weeks before and continuing for the whole course of chemoradiotherapy (66 Gy combined with platinum/vinorelbine), and then at a dose of 2000 mg twice weekly in association with chemotherapy. 2-Deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography (PET) and computed tomography scans were performed before and after the first 2 weeks of cilengitide administration and then every 3 months. RESULTS: Of the 14 patients included, 11 were evaluable for evaluation of the dose-limiting toxicities (DLTs). One DLT, a tracheobronchial fistula, was reported with the 40 mg/h dose. No relevant adverse events related to cilengitide were observed overall. At the PET evaluation 2 months after chemoradiotherapy, 4 of 9 patients had a complete response and 4 had a partial response. The median progression-free and overall survival was 14.4 months (95% confidence interval [CI], 8.4 to not reached) and 29.4 months (95% CI, 11.73 to not reached), respectively. CONCLUSION: Cilengitide, given continuously with chemoradiotherapy, showed acceptable toxicity and gave encouraging clinical results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Venenos de Serpentes/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/radioterapia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Vitronectina/antagonistas & inibidores , Venenos de Serpentes/efeitos adversos , Vinorelbina/administração & dosagemRESUMO
PURPOSE: The aim of this study was to evaluate the impact of using the Bayesian penalized likelihood (BPL) algorithm on a bismuth germanium oxide positron emission tomography (PET)/computed tomography (CT) system for F-FDG PET/CT exams in case of low injected activity and scan duration. MATERIALS AND METHODS: F-FDG respiratory gated PET/CT performed on 102 cancer patients, injected with â¼2 MBq/kg of F-FDG, were reconstructed using two algorithms: ordered subset expectation maximization (OSEM) and BPL. The signal-to-noise ratio (SNR) was calculated as the ratio of mean standard uptake value (SUV) over the standard deviation in a reference volume defined automatically in the liver. The peak SUV and volumes were also measured in lesions larger than 2 cm thanks to the automated segmentation method. RESULTS: On 85 respiratory gated patients, the median SNR was significantly higher with BPL (P<0.0001) and it is even better when the BMI of the patient increases (odds ratio=1.26).For the 55 lesions, BPL significantly increased the SUVpeak [difference: (-0.5; 1.4), median=0.4, P<0.0001] compared with OSEM in 83.6% of the cases. With BPL, the volume was lower in 61.8% of the cases compared with OSEM, but this was not statistically significant. CONCLUSION: The BPL algorithm improves the image quality and lesion contrast and appears to be particularly appropriate for patients with a high BMI as it improves the SNR. However, it will be important for patient follow-up or multicenter studies to use the same algorithm and preferably BPL.