RESUMO
As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.
Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos , Rituximab/administração & dosagem , Vincristina/administração & dosagem , Adulto JovemRESUMO
This retrospective analysis of the phase III GOYA study investigated the prognostic value of baseline metabolic tumor volume parameters and maximum standardized uptake values for overall and progression-free survival (PFS) in treatment-naïve diffuse large B-cell lymphoma. Baseline total metabolic tumor volume (determined for tumors >1 mL using a threshold of 1.5 times the mean liver standardized uptake value +2 standard deviations), total lesion glycolysis, and maximum standardized uptake value positron emission tomography data were dichotomized based on receiver operating characteristic analysis and divided into quartiles by baseline population distribution. Of 1,418 enrolled patients, 1,305 had a baseline positron emission tomography scan with detectable lesions. Optimal cut-offs were 366 cm3 for total metabolic tumor volume and 3,004 g for total lesion glycolysis. High total metabolic tumor volume and total lesion glycolysis predicted poorer PFS, with associations retained after adjustment for baseline and disease characteristics (high total metabolic tumor volume hazard ratio: 1.71, 95% confidence interval [CI]: 1.35- 2.18; total lesion glycolysis hazard ratio: 1.46; 95% CI: 1.15-1.86). Total metabolic tumor volume was prognostic for PFS in subgroups with International Prognostic Index scores 0-2 and 3-5, and those with different cell-of-origin subtypes. Maximum standardized uptake value had no prognostic value in this setting. High total metabolic tumor volume associated with high International Prognostic Index or non-germinal center B-cell classification identified the highest-risk cohort for unfavorable prognosis. In conclusion, baseline total metabolic tumor volume and total lesion glycolysis are independent predictors of PFS in patients with diffuse large B-cell lymphoma after first-line immunochemotherapy.
Assuntos
Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Glicólise , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga TumoralRESUMO
Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [18F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI.
Assuntos
Encefalopatia Traumática Crônica , Tauopatias , Animais , Biomarcadores , Encéfalo , Humanos , Ratos , SíndromeRESUMO
A negative interim positron emission tomography/computerized tomography (PET/CT) after 1 to 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with newly diagnosed, nonbulky stage I or II Hodgkin lymphoma (HL) predicts a low relapse rate. This phase 2 trial was designed to determine if a population of patients with early-stage disease can be treated with short-course ABVD without radiation therapy (RT) on the basis of a negative interim PET/CT, thereby limiting the risks of treatment. Between 15 May 2010 and 21 February 2013, 164 previously untreated patients with nonbulky stage I/II HL were enrolled, and 149 were included in the final analysis. Patients received 2 cycles of ABVD followed by PET. Deauville scores 1 to 3 were negative (≤ liver uptake) based on central review. PET- patients received 2 more cycles of ABVD, and PET+ patients received 2 cycles of dose-intense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus 3060-cGy involved-field RT. The primary objective was to determine 3-year progression-free survival (PFS) for the PET- group. One hundred thirty-five patients (91%) were interim PET-, and 14 patients (9%) were PET+ With median follow-up time of 3.8 years, the estimated 3-year PFS was 91% for the PET- group and 66% for the PET+ group (hazard ratio, 3.84; 95% confidence interval, 1.50-9.84; P = .011). There was 1 death as a result of suicide. Four cycles of ABVD resulted in durable remissions for a majority of patients with early-stage nonbulky HL and a negative interim PET. This trial was registered at www.clinicaltrials.gov as #NCT01132807.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
PURPOSE: The prospective, multicenter LOCATE (F Fluciclovine [FACBC] PET/CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent. MATERIALS AND METHODS: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other. RESULTS: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%). CONCLUSIONS: F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.
Assuntos
Ácidos Carboxílicos/administração & dosagem , Ciclobutanos/administração & dosagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Seleção de Pacientes , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapiaRESUMO
Interim positron emission tomography (PET)/CT has shown encouraging results when used as a prognostic tool early in the course of treatment of advanced Hodgkin lymphoma, allowing for a reduction in treatment for patients with favorable characteristics, while suggesting a benefit from changing therapy for those with a positive scan. For patients with limited disease, a negative scan allows for a decrease in treatment; however, the benefits for those patients whose scans are positive are less certain. Here we critically analyze the role of PET/CT in the early assessment of Hodgkin lymphoma. In Part 2, we will review the role of interim PET/CT in diffuse large B-cell lymphoma (DLBCL), and also explore the question of whether new approaches to quantitative assessment improve the prognostic value of interim PET scans in both Hodgkin lymphoma and DLBCL.
Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Vimblastina/uso terapêutico , Vincristina/uso terapêuticoRESUMO
In Part 1, we reviewed the role of interim positron emission tomography (PET)/CT scans in Hodgkin lymphoma. In advanced Hodgkin lymphoma, interim PET is a useful prognostic tool that can be used to implement risk-adapted therapy with potential benefits for both patients who have negative interim scans and those whose scans are positive. Interim PET/CT has not shown as encouraging results in diffuse large B-cell lymphoma (DLBCL), with the exception of germinal center B-cell DLBCL. Thus, quantitative methods of interpreting interim PET scans have been pursued in an effort to improve their predictive value. Early results using the change in maximal standardized uptake value between baseline and interim PET (ΔSUVmax) to quantitatively interpret interim PET scans in DLBCL patients showed promise, but later results were contradictory. Thus, there is not firm evidence of a prognostic value for interim PET interpreted using either visual or ΔSUVmax-based analysis in patients with DLBCL. Nor are there data to support altering treatment in DLBCL on the basis of an interim PET scan. More sophisticated methods of quantitative interpretation of interim PET, using metabolic tumor volume and tumor lesion glycolysis measurements, have been investigated in both Hodgkin lymphoma and DLBCL. Although to date studies of these approaches have been small and heterogeneous, they do provide some support for the potential of a PET-derived volumetric approach to discriminate between risk groups better than ΔSUVmax; this remains to be proven in well-designed large-scale studies.
Assuntos
Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Carga TumoralRESUMO
Given the excellent survival rates for early-stage Hodgkin lymphoma (HL), the young age of many patients, and concerns regarding acute and late treatment-related toxicities, there is a desire to have a predictive tool that enables therapy to be tailored toward the individual patient. Early (or interim) (18)F-fluorodeoxyglucose positron emission tomography with computerized tomography (FDG-PET/CT), as a test of tumor sensitivity to ongoing/planned therapy, has been shown to be prognostic for survival in HL. Based on results of interim FDG-PET/CT, therapy may be subsequently modified through minimization or via intensification for low- and high-risk patient populations, respectively (ie, response-adapted therapy). Important data have been generated to standardize the interpretability and reproducibility of interim FDG-PET/CT (eg, the Deauville 5-point system), and observational and noncontrolled prospective studies have produced evidence supporting the hypothesis that response-adapted therapy may potentially serve as a predictive tool. Furthermore, results from noninferiority phase 3 clinical trials randomizing early-stage HL patients with negative interim FDG-PET/CT to combined modality therapy versus chemotherapy alone have been reported. The current collective findings from these randomized early-stage HL studies have shown that acute relapse rates are lower with combined modality therapy, even in patients with negative interim FDG-PET/CT. Additional randomized response-adapted studies are ongoing and novel FDG-PET/CT applications involving quantitative techniques and innovative imaging modalities are being investigated to identify more robust imaging biomarkers. Treatment of early-stage HL remains a clinical management choice for physicians and patients to make with consideration of acute and long-term outcomes.
Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Ensaios Clínicos Fase II como Assunto , Diagnóstico Precoce , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Pheochromocytomas are complex tumors that require a comprehensive and systematic management plan orchestrated by a multidisciplinary team. METHODS: To achieve these ends, The Mount Sinai Adrenal Center hosted an interdisciplinary retreat where experts in adrenal disorders assembled with the aim of developing a clinical pathway for the management of pheochromocytomas. RESULTS: The result was a consensus for the diagnosis, perioperative management, and postoperative management of pheochromocytomas, with specific recommendations from our team of adrenal experts, as well as a review of the current literature. CONCLUSION: Our clinical pathway can be applied by other institutions directly or may serve as a guide for institution-specific management.
Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Procedimentos Clínicos , Feocromocitoma/terapia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Humanos , Feocromocitoma/diagnósticoRESUMO
Despite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria. A final remark on the appropriate use of interim PET is also provided.
Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Tomografia por Emissão de Pósitrons/normas , PrognósticoRESUMO
A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of 'interim' positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2-110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen's kappa 0.69-0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study.
Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Seguimentos , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto JovemRESUMO
The management approach in Hodgkin's (HL) and high-grade non-Hodgkin's lymphomas (NHL) has shifted towards reducing the toxicity and long-term adverse effects associated with treatment while maintaining favorable outcomes in low-risk patients. The success of an individualized treatment strategy depends largely on accurate diagnostic tests both at staging and during therapy. In this regard, positron emission tomography (PET) using fluorodeoxyglucose (FDG) with computed tomography (CT) has proved effective as a metabolic imaging tool with compelling evidence supporting its superiority over conventional modalities, particularly in staging and early evaluation of response. Eventually, this modality was integrated into the routine staging and restaging algorithm of lymphomas. This review will summarize the data on the proven and potential utility of PET/CT imaging for staging, response assessment, and restaging, describing current limitations of this imaging modality.
Assuntos
Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , HumanosRESUMO
A significant amount of data has been published over the past decade regarding the clinical utility of F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and management of Hodgkin lymphoma (HL). This includes studies examining interim FDG-PET, which has been shown to be a strong tool for predicting relapse and survival, especially in advanced- stage HL. Despite progress, a number of questions remain regard- ing the precise role and value of FDG-PET in the diagnosis, risk stratification, and management of HL. These questions include the need for concomitant contrast enhanced computed tomography with FDG-PET, reproducibility and interpretability of FDG-PET, optimal imaging for the treatment surveillance of HL following definitive treatment, and the use of FDG-PET for patients with relapsed/refractory disease, including stem cell transplantation. In this review, these issues are critically examined and the study designs and results of observational and prospective FDG-PET response-adaptive clinical trials in HL are described in detail. In addition, novel techniques and future applications of FDG- PET, such as metabolic tumor volume, tumor proliferation via 3'-deoxy-3'-18F-fluorothymidine, and integrated PET/magnetic resonance imaging are discussed.
Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Prognóstico , Reprodutibilidade dos TestesRESUMO
PURPOSE: Artificial intelligence can reduce the time used by physicians on radiological assessments. For 18F-fluorodeoxyglucose-avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic. METHODS: Here, we present a deep learning-based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification. The proposed four-stage method, trained on a multicountry clinical trial (ClinicalTrials.gov identifier: NCT01287741) and tested in three independent multicenter and multicountry test sets on different non-Hodgkin lymphoma subtypes and different lines of treatment (ClinicalTrials.gov identifiers NCT02257567, NCT02500407; 20% holdout in ClinicalTrials.gov identifier NCT01287741), outputs the detected lesions at baseline and follow-up to enable focused radiologist review. RESULTS: The method's response assessment achieved high agreement with the adjudicated radiologic responses (eg, agreement for overall response assessment of 93%, 87%, and 85% in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, respectively) similar to inter-radiologist agreement and was strongly prognostic of outcomes with a trend toward higher accuracy for death risk than adjudicated radiologic responses (hazard ratio for end of treatment by-model CMR of 0.123, 0.054, and 0.205 in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, compared with, respectively, 0.226, 0.292, and 0.272 for CMR by the adjudicated responses). Furthermore, a radiologist review of the algorithm's assessments was conducted. The radiologist median review time was 1.38 minutes/assessment, and no statistically significant differences were observed in the level of agreement of the radiologist with the model's response compared with the level of agreement of the radiologist with the adjudicated responses. CONCLUSION: These results suggest that the proposed method can be incorporated into radiologic response assessment workflows in cancer imaging for significant time savings and with performance similar to trained medical experts.
Assuntos
Aprendizado Profundo , Fluordesoxiglucose F18 , Linfoma não Hodgkin , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Feminino , MasculinoRESUMO
BACKGROUND: Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL. METHODS: Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for 4 induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by computed tomography was correlated with clinical risk factors, [18F]fluorodeoxyglucose positron emission tomography findings at week 3, Fcγ polymorphisms, immunohistochemical markers, and statin use. RESULTS: Therapy was well-tolerated, with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (42.4%) and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (P = .022). CONCLUSIONS: The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemoimmunotherapies and further support the development of biologic, nonchemotherapeutic approaches for these patients.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Murinos/administração & dosagem , Imunoterapia/métodos , Linfoma Folicular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Imunoterapia/efeitos adversos , Linfoma Folicular/metabolismo , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Indução de Remissão , Rituximab , Resultado do TratamentoRESUMO
OBJECTIVE: The objective of this study was to compare the efficacy of surveillance high-resolution computed tomography (HRCT) and physical examination/endoscopy (PE/E) with the efficacy of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/HRCT for the detection of relapse in head and neck squamous cell carcinoma (HNSCC) after primary treatment. METHODS: This is a retrospective analysis of contemporaneously performed FDG-PET/HRCT, neck HRCT, and PE/E in 99 curatively treated patients with HNSCC during post-therapy surveillance to compare performance test characteristics in the detection of early recurrence or second primary cancer. RESULTS: Relapse occurred in 19 of 99 patients (20%) during a median follow-up of 21 months (range: 9-52 months). Median time to first PET/HRCT was 3.5 months. The median time to radiological recurrence was 6 months (range: 2.3-32 months). FDG-PET/HRCT detected more disease recurrences or second primary cancers and did so earlier than HRCT or PE/E. The sensitivity, specificity, and positive and negative predictive values for detecting locoregional and distant recurrence or second primary cancer were 100%, 87.3%, 56.5%, and 100%, respectively, for PET/HRCT versus 61.5%, 94.9%, 66.7%, and 93.8%, respectively, for HRCT versus 23.1%, 98.7%, 75%, and 88.6%, respectively, for PE/E. In 19 patients with true positive PET/HRCT findings, a significant change in the management of disease occurred, prompting either salvage or systemic therapy. Of the 14 curatively treated patients, 11 were alive with without disease at a median follow-up of 31.5 months. CONCLUSION: FDG-PET/HRCT has a high sensitivity in the early detection of relapse or second primary cancer in patients with HNSCC, with significant management implications. Given improvements in therapy and changes in HNSCC biology, appropriate modifications in current post-therapy surveillance may be required to determine effective salvage or definitive therapies.
Assuntos
Diagnóstico Precoce , Neoplasias de Cabeça e Pescoço/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias de Células Escamosas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia , Feminino , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias de Células Escamosas/diagnóstico por imagem , Neoplasias de Células Escamosas/patologia , Tomografia por Emissão de Pósitrons/métodos , Radiografia , Análise de SobrevidaRESUMO
To reduce doxorubicin, bleomycin, vinblastine and dacarbazine toxicity, the Cancer and Leukemia Group B conducted a phase 2 trial of doxorubicin, vinblastine, and gemcitabine for newly diagnosed, nonbulky stages I and II Hodgkin lymphoma. Ninety-nine assessable patients received 6 cycles of doxorubicin 25 mg/m(2), vinblastine 6 mg/m(2), and gemcitabine 800 mg/m(2) (1000 mg/m(2) in first 6) on days 1 and 15 every 28 days. Computed tomography (CT) and positron emission tomography (PET) were performed before and after 2 and 6 cycles. Complete remission (CR)/CR unconfirmed was achieved in 72 of 99 patients (72.7%) and partial remission in 24 of 99 patients (24.2%). The CR rate was 81% when using PET criteria. Two patients have died of Hodgkin lymphoma progression. Median follow-up for nonprogressing patients is 3.3 years. The progression-free survival (PFS) at 3 years was 77% (95% confidence interval, 68%-84%). The relapse rate was less than 10% for patients with favorable prognostic factors. The 2-year PFS for cycle 2 PET-negative and -positive patients was 88% and 54%, respectively (P = .0009), compared with 89% and 27% for cycle 6 PET-negative and -positive patients (P = .0001). Although the CR rate and PFS were lower than anticipated, patients with favorable prognostic features had a low rate of relapse. Cycle 2 PET and cycle 6 PET were predictive of PFS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Doença de Hodgkin/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Indução de Remissão , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Adulto Jovem , GencitabinaRESUMO
The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed. Landmark analyses of progression-free survival (PFS) and overall survival (OS) by end of treatment (EOT) and end of induction (EOI) response status according to RECIL 2017 and Lugano 2014 criteria, and prognostic value of response at EOT/EOI were also compared. Overall, 1333 patients were included from GOYA and 502 from GALLIUM. Complete response (CR) status according to RECIL 2017 criteria showed high concordance with complete metabolic response (CMR) status by Lugano 2014 criteria in both GOYA (92.5%) and GALLIUM (92.4%). EOT and EOI CR/CMR status by both criteria was highly prognostic for PFS in GOYA (RECIL 2017 [CR]: hazard ratio [HR], 0.35 [95% confidence interval [CI] 0.26-0.46]; Lugano 2014 [CMR]: HR, 0.35 [95% CI 0.26-0.48]; both p < .0001) and GALLIUM (RECIL 2017 [CR]: HR, 0.35 [95% CI 0.23-0.53]; Lugano 2014 [CMR]: HR, 0.21 [95% CI 0.14-0.31]; both p < .0001). In conclusion, response categorization by RECIL 2017 is similar to that by Lugano 2014 criteria, with high concordance observed. Both were prognostic for PFS and OS.
RESUMO
PURPOSE: Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease. METHODS: Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation. RESULTS: Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04). CONCLUSION: Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.
Assuntos
Doença de Hodgkin , Humanos , Feminino , Adulto , Masculino , Doença de Hodgkin/tratamento farmacológico , Vimblastina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina , Bleomicina , Dacarbazina , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Vincristina , PrednisonaRESUMO
INTRODUCTION: A good response to initial therapy is key to maximizing survival in patients with diffuse large B-cell lymphoma (DLBCL), but patients with chemorefractory disease and early progression have poor outcomes. PATIENTS AND METHODS: Data from the GOYA study in patients with DLBCL who received first-line rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were analyzed. Positron emission tomography/computed tomography (PET/CT)-derived characteristics associated with total metabolic tumor volume (TMTV) and clinical risk factors for primary chemorefractory disease and disease progression within 12 months (POD12) were explored. RESULTS: Of those patients fulfilling the criteria for analysis, 108/1126 (10%) were primary chemorefractory and 147/1106 (13%) had POD12. Primary chemorefractory and POD12 status were strongly associated with reduced overall survival. After multivariable analysis of clinical and imaging-based risk factors by backward elimination, only very high TMTV (quartile [Q] 1 vs. Q4 odds ratio [OR]: 0.45; Pâ¯=â¯.006) and serum albumin levels (low vs. normal OR of 1.86; Pâ¯=â¯.004) were associated with primary chemorefractoriness. After additionally accounting for BCL2/MYC translocation in a subset of patients, TMTV and BCL2/MYC double-hit status remained as significant predictors of primary chemorefractoriness (Q1 vs. Q4 OR: 0.32, Pâ¯=â¯.01 and double-hit vs. no-hit OR of 4.47, Pâ¯=â¯.02, respectively). Risk factors including very high TMTV, high sum of the product of the longest diameters (SPD), geographic region (Asia), short time since diagnosis, extranodal involvement and low serum albumin were retained for POD12. CONCLUSION: PET-derived TMTV has prognostic value in identifying patients at risk of early treatment failure.