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BACKGROUND: Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. METHODS: This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). FINDINGS: Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24-42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65-0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45-0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6-96·1) for BrECADD and 90·9% (88·7-93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7-99·5) and 98·2% (97·2-99·3), respectively. INTERPRETATION: BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma. FUNDING: Takeda Oncology.
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Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/efectos adversos , Brentuximab Vedotina/uso terapéutico , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Dacarbazina/uso terapéutico , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/mortalidad , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
PURPOSE: Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT). METHODS AND MATERIALS: In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET-positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT. RESULTS: A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival were 96.8% (95% CI, 91.6%-98.8%) in the IFRT group and 95.4% (95% CI, 89.9%-97.9%; HR, 1.40; 95% CI, 0.44-4.42) in the ISRT group. The pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P = .03). CONCLUSIONS: For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care.
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The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result.
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Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Seguimiento , Dacarbazina/efectos adversos , Vinblastina/efectos adversos , Bleomicina , Doxorrubicina , Estadificación de NeoplasiasRESUMEN
PURPOSE: Response-adapted treatment using early interim functional imaging with PET after two cycles of chemotherapy (PET-2) for advanced-stage Hodgkin's lymphoma (AS-HL) is the standard of care in several countries. However, the distribution of residual metabolic disease in PET-2 and the prognostic relevance of multiple involved regions have not been reported to date. METHODS: We retrospectively analyzed data from all PET-2-positive patients included in HD18. Residual tissue was visually compared with reference regions according to the Deauville score (DS). PET-2 positivity was defined as residual tissue with uptake above the liver (DS4). PFS was defined as the time from staging until progression, relapse, or death from any cause, or to the day when information was last received on the patient's disease status and analyzed using Kaplan-Meier and Cox regressions. Comparisons were made between patients with 1-2 and >2 positive regions in PET-2 as well as patients without PET-2-positive regions randomized into comparator arms of HD18. RESULTS: Between 2008 and 2014, 1964 patients with newly diagnosed AS-HL were recruited in HD18 and randomized following their PET-2 scan. Of these, 480 patients had a positive PET-2 and were eligible for this analysis. Upper and lower mediastinum in almost half of all patients: 230 (47.9%) and 195 (40.6%), respectively. 372 (77.5%) of patients have 1-2 positive regions in PET-2. 5y-PFS for patients with 1-2 regions was 91.7% (CI95: 88.7-94.6) vs. 81.8% (CI95: 74.2-90.1) for those with >2 regions with a corresponding hazard ratio (HR) of 2.2 (CI95: 1.2-4.0). Compared with patients without PET-2-positive disease receiving 6-8 cycles of chemotherapy, patients with 1-2 had a higher risk for a PFS event (HR 1.35; CI95 0.81-2.28), but it was not statistically significant (p=0.25). Patients with >2 PET-2-positive lesions had a significantly higher risk (HR 2.95; CI95: 1.62-5.37; p<0.001). CONCLUSION: PET-2-positive residuals of AS-HL are mostly located in the mediastinum, and a majority of patients have few affected regions. The risk of progression was twofold higher in patients with more than two positive regions in PET-2.
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Enfermedad de Hodgkin , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
RATIONALE AND OBJECTIVES: In oncological imaging, the use of metabolic tumor volume (MTV) for further prognostic differentiation and the development of risk adapted strategies appears promising. The aim of this analysis was to evaluate ultra-high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on different methods of MTV measurement. MATERIALS AND METHODS: We analyzed positron emission tomography combined with computed tomography (PET/CT) scans of 40 Hodgkin lymphoma patients before first-line treatment who had undergone fluorodeoxyglucose (FDG) PET/CT. The MTVs were determined taking an SUV of 4.0 (MTV4.0) as a fixed threshold or 41% of the single hottest voxel (MTV41%) as an adaptive threshold for automated lymphoma delineation in both UHD and OSEM reconstructions. We then compared the absolute and relative differences between MTV4.0 and MTV41% in UHD and OSEM reconstructions. The relative distribution of MTV4.0 and MTV41% in relation to the reconstruction method applied was recorded and respective differences were tested for statistical significance using the paired sample t-test. RESULTS: A comparison of MTV4.0 and MTV41% showed smaller relative and absolute differences in MTV between different reconstruction settings for the MTV4.0 method. Conversely, the absolute as well as the relative differences between MTVs obtained from different reconstructions settings were significantly greater when the MTV41% method was applied (p < 0001). CONCLUSION: MTV4.0 brings higher robustness between different reconstruction settings, while with MTV41% the deviation between volumes obtained with different reconstruction settings is greater. For clinical routine and for multicenter settings, the MTV4.0 therefore appears most promising.
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Fluorodesoxiglucosa F18 , Enfermedad de Hodgkin , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Carga Tumoral , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Masculino , Femenino , Persona de Mediana Edad , Fluorodesoxiglucosa F18/farmacocinética , Adulto , Radiofármacos/farmacocinética , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Anciano , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: In 2022, the American Food and Drug Administration and the European Medicines Agency approved [177Lu]Lu-PSMA-617 (PLUVICTO™, Novartis AG, Basel, Switzerland) for radionuclide therapy with prostate-specific membrane antigen (PSMA) ligands in metastatic prostate cancer. Theranostics require appropriate patients to be identified by positron emission tomography (PET) prior to radionuclide therapy, usually employing [68Ga]Ga-PSMA-11. Alternatively, several 18F-labelled PSMA-PET tracers are available and may increasingly replace 68Ga-labelled compounds, with respect to their image quality, availability and other practical advantages. However, alternative tracers may differ in uptake behaviour, and their comparability with regard to patient selection for [177Lu]Lu-PSMA therapy has not yet been established. Here, we analysed whether tumour-to-background ratios determined by PET using the 18F-labelled PSMA-specific radiopharmaceutical [18F]F-DCFPyL were comparable to those determined by PET using [68Ga]Ga-PSMA-11. RESULTS: No differences could be observed between [68Ga]Ga-PSMA-11-PET and [18F]F-DCFPyL-PET regarding tumour-to-liver ratios or tumour-to-mediastinum ratios (e. g. tumour-to-liver ratios using maximum SUV of the tumour lesion for ultra-high definition reconstructed PET images with a median of 2.5 (0.6-9.0) on [68Ga]Ga-PSMA-11-PET vs. 2,0 (0.6-11.4) on [18F]F-DCFPyL-PET). However, significant differences were observed in terms of contrast-to-noise ratios, thereby demonstrating the better image quality obtained with [18F]F-DCFPyL-PET. CONCLUSIONS: Our data showed that [18F]F-DCFPyl-PET and [68Ga]Ga-PSMA-11-PET provide comparable tumour-to-liver and tumour-to-mediastinum ratios. Therefore, a tumour uptake of [18F]F-DCFPyL above the liver background, like using [68Ga]Ga-PSMA-11, can be considered as equally suitable for defining PSMA-positivity by a semiquantitative assessment based on the liver background, e. g. prior to radioligand therapy with 177Lu-labelled PSMA ligands. In addition, our data suggest a tending advantage of [18F]F-DCFPyL in terms of lesion detectability.
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OBJECTIVES: The prognostic relevance of metabolic tumor volume (MTV) having recently been demonstrated in patients with early-stage favorable and advanced-stage Hodgkin lymphoma. The current study aimed to assess the potential prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in early-stage unfavorable Hodgkin lymphoma patients treated within the German Hodgkin Study Group HD17 trial. METHODS: 18 F-FDG PET/CT images were available for MTV analysis in 154 cases. We used three different threshold methods (SUV2.5 , SUV4.0 , and SUV41% ) to calculate MTV. Receiver-operating-characteristic analysis was performed to describe the value of these parameters in predicting an adequate therapy response. Therapy response was evaluated as PET negativity after 2 cycles of eBEACOPP followed by 2 cycles of ABVD. RESULTS: All three threshold methods analyzed for MTV showed a positive correlation with the PET response after chemotherapy. Areas under the curve (AUC) were 0.70 (95% CI 0.53-0.87) and 0.65 (0.50-0.80) using the fixed thresholds of SUV4.0 and SUV2.5 , respectively, for MTV- calculation. The calculation of MTV using a relative threshold of SUV41% showed an AUC of 0.63 (0.47-0.79). CONCLUSIONS: MTV does have predictive value after chemotherapy in early-stage unfavorable Hodgkin lymphoma, particularly when the fixed threshold of SUV4.0 is used for MTV calculation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01356680.
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Enfermedad de Hodgkin , Humanos , Pronóstico , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Carga Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/uso terapéutico , Vinblastina/uso terapéutico , Bleomicina/uso terapéutico , Dacarbazina/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Estudios RetrospectivosRESUMEN
The optimal first-line treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) diagnosed in early stages is largely undefined. We, therefore, analyzed 100 NLPHL patients treated in the randomized HD16 (early-stage favorable; n = 85) and HD17 (early-stage unfavorable; n = 15) studies. These studies investigated the omission of consolidation radiotherapy (RT) in patients with a negative interim positron emission tomography (iPET) (ie, Deauville score <3) after chemotherapy (HD16: 2× doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]; HD17: 2× escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP] plus 2× ABVD). Patients with NLPHL treated in the HD16 and HD17 studies had 5-year progression-free survival (PFS) rates of 90.3% and 92.9%, respectively. Thus, the 5-year PFS did not differ significantly from that of patients with classical Hodgkin lymphoma treated within the same studies (HD16: P = .88; HD17: P = .50). Patients with early-stage favorable NLPHL who had a negative iPET after 2× ABVD and did not undergo consolidation RT tended to have a worse 5-year PFS than patients with a negative iPET who received consolidation RT (83% vs 100%; P = .05). There were 10 cases of NLPHL recurrence. However, no NLPHL patient died during follow-up. Hence, the 5-year overall survival rate was 100%. Taken together, contemporary Hodgkin lymphoma-directed treatment approaches result in excellent outcomes for patients with newly diagnosed early-stage NLPHL and, thus, represent valid treatment options. In early-stage favorable NLPHL, consolidation RT appears necessary after 2× ABVD to achieve the optimal disease control irrespective of the iPET result.
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Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Bleomicina/efectos adversos , Doxorrubicina , Dacarbazina , Vinblastina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida , Vincristina/efectos adversos , Tomografía de Emisión de Positrones/métodos , PrednisonaRESUMEN
The preparation of 24 estrogens, their estrogen receptor (ER) affinity and studies of radioiodinated estrogen binding to ER-positive male bladder tumor cells (HTB9) are described. The estrogens with the highest affinity were selected using fluorescence anisotropy assays. A 2,2,2-trifluoroethyl group at the 11ß-position caused particularly promising affinity. (Radio)iodination was performed on the 17α-vinyl group. Binding studies on HTB9 cells revealed picomolar affinities of radioconjugates 19 and 31, indicating promising ability for targeting of urogenital tumors.
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Estradiol , Estrógenos , Masculino , Humanos , Receptores de Estrógenos/metabolismoRESUMEN
The introduction of chimeric antigen receptor (CAR) T-cell therapy has led to a fundamental shift in the management of relapsed and refractory large B-cell lymphoma. However, our understanding of risk factors associated with non-response is still insufficient and the search for predictive biomarkers continues. Some parameters measurable on 18F-fluorodeoxyglucose positron emission tomography (PET) may be of additional value in this context. A total of 47 individuals from three German university centers who underwent re-staging with PET prior to CAR T-cell therapy were enrolled into the present study. After multivariable analysis considering tumor characteristics and patient factors that might affect progression-free survival (PFS), we investigated whether metabolic tumor volume (MTV) or maximum standardized uptake value (SUVmax) further improve risk stratification. Their most suitable cut-offs were determined by Cox and logistic regression. Forward selection identified extra-nodal disease as the most predictive factor of those routinely available, and we found it to be associated with significantly inferior overall survival after CAR T-cell treatment (P = 0.012). Furthermore, patients with MTV and SUVmax higher than the optimal threshold of 11 mL and 16.7, respectively, experienced shorter PFS (P = 0.016 and 0.002, respectively). Hence, these risk factors might be useful for selection of individuals likely to benefit from CAR T-cell therapy and their management.
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The interdisciplinary possibilities inherent in nuclear medicine offer an opportunity for the patient-centered development of radioactive pharmaceuticals based on specific research questions. This approach provides radiopharmaceutical manufacturers with a robust scientific foundation on which to navigate the regulatory requirements for drug approval laid down by the law. A vivid illustration of this interdisciplinary cooperation has been the development of a Zr-89-labeled PSMA ligand where reliable results have been obtained across various domains, including chemistry, radiochemistry, biochemistry, and preclinical research. This comprehensive process extended to feasibility studies conducted with carefully selected patients from a single nuclear medicine clinic. The approach demonstrates how far close collaboration between different disciplines within nuclear medicine can further the move towards patient-oriented radiopharmaceutical treatments while simultaneously meeting regulatory demands. With such a strategy, innovative radiopharmaceutical solutions can be brought to the market more swiftly and efficiently, in line with the needs of patients.
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Medicina Nuclear , Humanos , Radioisótopos , Radiofármacos , CirconioRESUMEN
Currently, contrast-enhanced MRI is the method of choice for treatment planning and follow-up in patients with meningioma. However, positron emission tomography (PET) imaging of somatostatin receptor subtype 2 (SSTR2) expression using 68Ga-DOTATATE may provide a higher sensitivity for meningioma detection, especially in cases with complex anatomy or in the recurrent setting. Here, we report on a patient with a multilocal recurrent atypical meningioma, in which 68Ga-DOTATATE PET was considerably helpful for treatment guidance and decision-making.
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In patients with relapse of classical Hodgkin lymphoma (cHL) after autologous stem cell transplant, brentuximab vedotin and anti-PD1 treatment, the outcome is poor. To assess the efficacy of the bispecific anti-CD30/CD16A, NK-cell engaging antibody AFM13 and to select the optimal treatment schedule (arm A-C), we initiated a randomized two-stage phase II trial (NCT02321592). Due to slow recruitment, the trial was terminated after treatment of 25 patients. Treatment with AFM13 was well tolerated: only two treatment-associated serious adverse events (SAEs) were reported; all SAEs resolved completely. With an objective response rate (ORR) of 16.7% (1/5 in arm A, 1/11 in arm B, and 2/8 in arm C) and a 12-month progression-free survival (PFS) of 12.6% (95% CI 3.2-28.9), treatment efficacy of AFM13 monotherapy in all evaluable patients was modest. The continuous application schedule (arm C) might be more effective, but the visit schedule should be better aligned with patients' daily life.
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Antineoplásicos , Enfermedad de Hodgkin , Inmunoconjugados , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Brentuximab Vedotina , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Inmunoconjugados/uso terapéutico , Antígeno Ki-1 , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: 18F -fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the staging and response assessment of lymphoma patients. Our aim was to explore the predictive relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with early stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD16 trial. METHODS: 18F-FDG PET/CT images were available for MTV and TLG analysis in 107 cases from the HD16 trial. We calculated MTV and TLG using three different threshold methods (SUV4.0, SUV41% and SUV140%L), and then performed receiver-operating-characteristic analysis to assess the predictive impact of these parameters in predicting an adequate therapy response with PET negativity after 2 cycles of chemotherapy. RESULTS: All three threshold methods analyzed for MTV and TLG calculation showed a positive correlation with the PET response after 2 cycles chemotherapy. The largest area under the curve (AUC) was observed using the fixed threshold of SUV4.0 for MTV- calculation (AUC 0.69 [95% CI 0.55-0.83]) and for TLG-calculation (AUC 0.69 [0.55-0.82]). The calculations for MTV and TLG with a relative threshold showed a lower AUC: using SUV140%L AUCs of 0.66 [0.53-0.80] for MTV and 0.67 for TLG [0.54-0.81]) were observed, while with SUV41% an AUC of 0.61 [0.45-0.76] for MTV, and an AUC 0.64 [0.49-0.80]) for TLG were seen. CONCLUSIONS: MTV and TLG do have a predictive value after two cycles ABVD in early stage Hodgkin lymphoma, particularly when using the fixed threshold of SUV4.0 for MTV and TLG calculation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00736320 .
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Fluorodesoxiglucosa F18 , Enfermedad de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina , Dacarbazina , Doxorrubicina , Fluorodesoxiglucosa F18/metabolismo , Glucólisis , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios Prospectivos , Radiofármacos , Estudios Retrospectivos , Carga Tumoral , VinblastinaRESUMEN
AIM: The aim of our study was to address the prevalence of oligometastatic recurrent prostate cancer (PCa) on PSMA-PET and the associated practice of metastasis-directed therapy (MDT). Next, we aimed to determine a PSA threshold below which most patients had local and/or oligometastatic recurrence on PSMA-PET. METHODS: One hundred and ten consecutive patients with biochemical recurrence (BCR) after radical prostatectomy (RP) ± radiation were referred for 68Ga-PSMA-11 or 18F-DCFPyL PET/CT. We correlated the location and number of PSMA-positive lesions against the treatment choice after imaging. Detection rates were stratified by PSA levels at the time of PET/CT. The study design was monocentric retrospective. RESULTS: Thirty-four patients (30.9%) had a PSMA-negative scan, while 17 (15.5%) had local recurrence and 59 (53.6%) had metastatic recurrence on PSMA-PET. ROC analysis revealed a cut-off of ≤3 metastatic lesions on PSMA-PET for the steering of treatment decisions towards MDT rather than solely systemic therapy (AUC: 0.88). Defined as 3 or fewer metastatic lesions, oligometastatic recurrent PCa was found in up to 30% (33/110) of all patients. At PSA levels below 3.5 ng/ml, the rate of PSMA-positive disease that was locally confined or oligometastatic was 76% (45/59), dropping significantly to 29.4% (5/17) above this threshold (p<0.001) as polymetastatic findings became more frequent. CONCLUSION: The detection of ≤3 oligometastases on PSMA-PET encouraged the consecutive pursuit of MDT instead of systemic therapy alone. PSMA-PET predominantly captured patients at recurrence stages amenable to localized treatment when initiated at PSA levels below 3.5 ng/ml.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prevalencia , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
A consensus statement about indications for post-surgical radioiodine therapy (RIT) in differentiated thyroid cancer patients (DTC) was recently published by the European Thyroid Association (ETA) 1. This publication discusses indications for RIT on the basis of an individual risk assessment. Many of the conclusions of this consensus statement are well founded and accepted across the disciplines involved. However, especially from the perspective of nuclear medicine, as the discipline responsible for indicating and executing RIT, some of the recommendations may require further clarification with regard to their compatibility with established best practice and national standards of care. Assessment of the indications for RIT is strongly dependent on the weighing up of benefits and risks. On the basis of longstanding clinical experience in nuclear medicine, RIT represents a highly specific precision medicine procedure of proven efficacy with a favorable side-effect profile. This distinguishes RIT significantly from other adjuvant oncological therapies and has resulted in the establishment of this procedure as a usually well-tolerated, standard safety measure. With regard to its favorable risk/benefit ratio, this procedure should not be unnecessarily restricted, in the interest of offering reassurance to the patients. Both patients' interests and regional/national differences need to be taken into account. We would therefore like to comment on the recent consensus from the perspective of authors and to provide recommendations based on the respective published data.
Asunto(s)
Medicina Nuclear , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo/uso terapéutico , Cintigrafía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
BACKGROUND: Early and severe neuronal loss in the cholinergic basal forebrain is observed in Alzheimer's disease (AD). To date, cholinomimetics play a central role in the symptomatic treatment of AD dementia. Although basic research indicates that a cholinergic deficit is present in AD before dementia, the efficacy of cholinomimetics in mild cognitive impairment (MCI) remains controversial. Predictors of cholinergic impairment could guide individualized therapy. OBJECTIVE: To investigate if the extent of the cholinergic deficit, measured using positron emission tomography (PET) and the tracer 11C-N-methyl-4-piperidyl acetate (MP4A), could be predicted from the volume of cholinergic basal forebrain nuclei in non-demented AD patients. METHODS: Seventeen patients with a high likelihood of MCI due to AD and 18 age-matched cognitively healthy adults underwent MRI-scanning. Basal forebrain volume was assessed using voxel-based morphometry and a cytoarchitectonic atlas of cholinergic nuclei. Cortical acetylcholinesterase (AChE) activity was measured using MP4A-PET. RESULTS: Cortical AChE activity and nucleus basalis of Meynert (Ch4 area) volume were significantly decreased in MCI. The extent of the cholinergic deficit varied considerably across patients. Greater volumes of anterior basal forebrain nuclei (Ch1/2 area) and younger age (Spearman's rho (17) â=â-0.596, 95% -CI [-0.905, -0.119] and 0.593, 95% -CI [0.092, 0.863])) were associated with a greater cholinergic deficit. CONCLUSION: Data suggest that less atrophy of the Ch1/2 area and younger age are associated with a more significant cholinergic deficit in MCI due to AD. Further investigations are warranted to determine if the individual response to cholinomimetics can be inferred from these measures.