RESUMO
PURPOSE: The coronavirus pandemic is affecting global health systems, endangering daily patient care. Hemato-oncological patients are particularly vulnerable to infection, requiring decisive recommendations on treatment and triage. The aim of this survey amongst experts on radiation therapy (RT) for lymphoma and leukemia is to delineate typical clinical scenarios and to provide counsel for high-quality care. METHODS: A multi-item questionnaire containing multiple-choice and free-text questions was developed in a peer-reviewed process and sent to members of the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance. Answers were assessed online and analyzed centrally. RESULTS: Omission of RT was only considered in a minority of cases if alternative treatment options were available. Hypofractionated regimens and reduced dosages may be used for indolent lymphoma and fractures due to multiple myeloma. Overall, there was a tendency to shorten RT rather than to postpone or omit it. Even in case of critical resource shortage, panelists agreed to start emergency RT for typical indications (intracranial pressure, spinal compression, superior vena cava syndrome) within 24â¯h. Possible criteria to consider for patient triage are the availability of (systemic) options, the underlying disease dynamic, and the treatment rationale (curative/palliative). CONCLUSION: RT for hemato-oncological patients receives high-priority and should be maintained even in later stages of the pandemic. Hypofractionation and shortened treatment schedules are feasible options for well-defined constellations, but have to be discussed in the clinical context.
Assuntos
COVID-19/epidemiologia , Linfoma/radioterapia , Mieloma Múltiplo/radioterapia , Pandemias , Radioterapia (Especialidade)/normas , SARS-CoV-2/isolamento & purificação , Triagem/normas , Agendamento de Consultas , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste para COVID-19 , Infecção Hospitalar/prevenção & controle , Diagnóstico Diferencial , Fracionamento da Dose de Radiação , Humanos , Higiene/normas , Controle de Infecções/métodos , Controle de Infecções/normas , Linfoma/complicações , Linfoma/tratamento farmacológico , Mieloma Múltiplo/complicações , Osteólise/etiologia , Osteólise/radioterapia , Equipamento de Proteção Individual , Radioterapia (Especialidade)/métodos , Pneumonite por Radiação/diagnóstico , Síndrome da Veia Cava Superior/etiologia , Síndrome da Veia Cava Superior/radioterapia , Inquéritos e Questionários , Tempo para o Tratamento , Irradiação Corporal TotalRESUMO
BACKGROUND: Checkpoint blockade contributes to the immunosuppressive microenvironment in classical Hodgkin lymphoma (cHL) and in particular the interaction of Hodgkin cells and macrophages with Tcells and natural killer cells via programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1). OBJECTIVES: The aim of this article is the evaluation the role and potential of checkpoint blockade in cHL as compared with the results of standard chemo- and radiotherapy. METHODS: We analyzed preclinical and clinical data from phase I and phase II studies with checkpoint blockade in cHL. RESULTS AND DISCUSSION: In 60-70% of patients with chemotherapy-refractory cHL, PD1 blockade results in responses. Overall survival is excellent and a small number of patients achieve persistent response. Thus, the use of anti-PD1 monoclonal antibodies has become an important treatment approach in relapsed cHL in line with the label. The results of first-line therapy are still preliminary; initial phase II studies using nivolumab in combination with doxorubicin (=adriamycin), vinblastin and dacarbazin (AVD) in early unfavorable or advanced stages showed response rates of up to 90%. Thus, implementing immunomodulatory approaches using PD 1blockade have resulted in a significant reduction of chemotherapy. This might represent a paradigm shift in the therapy of cHL.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Imunoterapia/métodos , Recidiva Local de Neoplasia , Microambiente TumoralRESUMO
BACKGROUND: The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its treatment is thrombosis. Thrombotic events are regularly observed in HL patients but precise information on incidence and risk factors is lacking and the value of prophylactic anticoagulation unclear. PATIENTS AND METHODS: Thus, we comprehensively studied thrombotic events in 5773 patients from the German Hodgkin Study Group (GHSG) HD13-15 trials in early-favorable, intermediate and advanced HL. We estimated the incidence of and identified risk factors for thrombotic events. Additionally, we provide detailed data on the time course and characteristics of thrombotic events. RESULTS: A total of 193 thrombotic events occurred for an incidence of 3.3%. Out of these, 175 (90.7%) were venous thromboses, 3 (1.5%) newly emerging post-thrombotic syndromes and 15 (7.8%) arterial thromboses. There were 11 (0.7%) events in early-favorable, 27 (1.3%) in early-unfavorable and 155 (7.3%) in advanced patients, the latter incidence being significantly higher (P < 0.001). The most common locations were deep vein thrombosis of the arm (46.3%) and leg (24.6%). Most venous thrombotic events occurred during chemotherapy (78.9%). We observed 59 (30.6%) catheter-associated events and a descriptively increased risk of venous thrombotic events in patients with oral contraception use during treatment (6.8% versus 3.9%). In advanced HL, the incidence of venous thrombotic events was increased upon treatment with BEACOPP-14 (9.4%, P = 0.0079) compared with 5.1% with 6×BEACOPPesc and 5.7% with 8×BEACOPPesc. Among commonly applied risk factors, including the Khorana score, only age and smoking were prognostic. CONCLUSIONS: The incidence of thrombotic events in advanced stage HL is comparable to other high-risk cancer patients, especially if treated with dose-dense regimens. Additional risk factors are higher age and smoking. Selected HL patients could benefit from prophylactic anticoagulation, however, further interventional studies are needed before general recommendations can be made.
Assuntos
Anticoagulantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Trombose/epidemiologia , Administração Intravenosa/efeitos adversos , Administração Intravenosa/instrumentação , Administração Oral , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Catéteres/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Feminino , Alemanha/epidemiologia , Doença de Hodgkin/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Trombose/induzido quimicamente , Trombose/prevenção & controle , Adulto JovemRESUMO
Background: Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if 18F-fluorodeoxyglucose positron emission tomography (PET) scanning is carried out during staging. Patients and methods: Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not. Results: Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% [95% confidence interval (CI) 99.2% to 100%] with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% CI 75.1% to 99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy. Conclusions: When compared with BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol. Registered trials: The trials included in this analysis were registered at ClinicalTrials.gov: HD16-NCT00736320, HD17-NCT01356680, and HD18-NCT00515554.
Assuntos
Medula Óssea/patologia , Doença de Hodgkin/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso , Biópsia/normas , Medula Óssea/diagnóstico por imagem , Ensaios Clínicos Fase III como Assunto , Conjuntos de Dados como Assunto , Feminino , Fluordesoxiglucose F18/administração & dosagem , Alemanha , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrões de Referência , Adulto JovemRESUMO
BACKGROUND: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT. METHODS: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II). RESULTS: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [Assuntos
Transplante de Células-Tronco Hematopoéticas
, Doença de Hodgkin/terapia
, Análise de Sobrevida
, Adulto
, Idoso
, Feminino
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Prognóstico
, Modelos de Riscos Proporcionais
, Recidiva
, Fatores de Risco
RESUMO
In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.
Assuntos
Antineoplásicos/uso terapêutico , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons/normas , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X/normas , Antineoplásicos/efeitos adversos , Consenso , Meios de Contraste/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Fluordesoxiglucose F18/administração & dosagem , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. METHODS: Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. RESULTS: Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Quimiorradioterapia/tendências , Doença de Hodgkin/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Radioimunoterapia/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Quimiorradioterapia/métodos , Previsões , Alemanha , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/imunologia , Humanos , Terapia de Alvo Molecular/tendências , Radioterapia (Especialidade)/tendências , Radioimunoterapia/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved-site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin's lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). METHODS: In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. RESULTS: The expert panel developed guidelines and criteria to analyse "modern" field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). CONCLUSION: To develop a QAP of "modern RT", the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups.
Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/radioterapia , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Radioterapia (Especialidade)/normas , Radioterapia Conformacional/normas , Alemanha/epidemiologia , Fidelidade a Diretrizes/normas , Humanos , Prevalência , Radioterapia Conformacional/estatística & dados numéricos , Fatores de Risco , Integração de Sistemas , Resultado do TratamentoRESUMO
INTRODUCTION: As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings. METHODS: With the start of the fourth GHSG study generation (HD10-12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13-15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation. RESULTS: The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %). CONCLUSION: The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of "modern RT" in malignant lymphoma.
Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/radioterapia , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Radioterapia Conformacional/normas , Alemanha/epidemiologia , Fidelidade a Diretrizes/normas , Humanos , Prevalência , Radioterapia (Especialidade)/normas , Radioterapia Conformacional/estatística & dados numéricos , Fatores de Risco , Integração de Sistemas , Resultado do TratamentoRESUMO
BACKGROUND: Central collection of tissue blocks for pathological and translational research is particularly important in rare diseases. Transfer of tissue blocks from primary to central pathology is of crucial importance. OBJECTIVES: We aimed to answer the following questions: Has the transfer of tissue blocks sent for consultation or within clinical trials changed over the last 20 years? What are the reasons for reclaiming tissue blocks by the primary pathology and what actions would convince primary pathologists to leave the blocks in the reference pathology? MATERIAL AND METHODS: The first 100 biopsies of each year between 1995 and 2015 (n = 2100), as well as all tissue transfers within therapeutic studies (n = 1405, German Hodgkin Study Group, GHSG) between 1998 and 2015, were analyzed separately for block reclaims using the Department of Pathology database. A questionnaire evaluated the reasons for block reclaiming by the peripheral pathologists. RESULTS: There is a significant increase in block reclaims during the period analyzed among submissions for consultation as well as in clinical trials (linear regression, p = 0.0195 and p = 0.0107). The percentage of block reclaims does not differ between consultations and cases submitted upon request within clinical trials (p = 0.2404, t-test). A survey among pathologies that reclaim the block showed that their willingness to leave the block at the reference center would increase if the compatibility with accreditation guidelines (39.3%), a positive statement from professional associations (25%), or a formal confirmation of availability (53.6%) is provided. DISCUSSION: In particular, to improve research on rare diseases, it is desirable to point out the compatibility of central archiving in a designated center with accreditation guidelines.
Assuntos
Doença de Hodgkin/patologia , Linfonodos/patologia , Inclusão em Parafina , Alemanha , Humanos , Sistema de Registros , Inquéritos e QuestionáriosAssuntos
Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Humanos , Linfócitos , Tomografia por Emissão de Pósitrons , Prednisona/uso terapêutico , Procarbazina , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Health-related quality of life (HRQoL) comprises different domains of physical, mental, and social well-being. In this analysis, we focus on sexual quality of life in Hodgkin Lymphoma (HL) patients. METHODS: Four-thousand one-hundred and sixty patients enroled in the HD10-HD12 trials underwent HRQoL assessment. Instruments included the Quality of Life Questionnaire for survivors (QLQ-S), combining the European Organisation for Research and Treatment of Cancer QLQ-C30, Multidimensional fatigue (FA) inventory (MFI-20) and an additional sexual functioning (SX) scale. We describe SX up to 27 months after therapy and analyse relationship to stage, age, gender, FA, social functioning, and therapy. Statistical methods range from descriptive statistics to a classification of SX courses, and a longitudinal structural equations model with full information maximum likelihood estimation of missing data. In the analysis, a score below 50 was used to describe severe sexual dysfunction. RESULTS: Three-thousand two-hundred and eight patients provided data on SX. Patients in advanced stages reported lower SX than patients in early stages both, before and after the treatment. During follow-up, an improvement of SX compared with baseline was detected, except for those ≥50 years. Patients in early stages reached normal SX, whereas advanced-stage patients remained below the reference value for healthy controls. Sexual functioning during follow-up was significantly and strongly related to previous SX, other HRQoL measures, age, and stage, and to lesser degree with gender and chemotherapy. CONCLUSION: Overall, HL patients have a decreased sexual quality of life at baseline, which improves after therapy and normalises in early-stage patients. Importantly, long-term SX is more closely related to patient characteristics and SX at baseline than to the intensity of treatment.
Assuntos
Doença de Hodgkin/psicologia , Qualidade de Vida , Comportamento Sexual , Adulto , Fadiga/psicologia , Feminino , Doença de Hodgkin/fisiopatologia , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/terapia , Oncologia/normas , Recidiva Local de Neoplasia/terapia , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Biópsia , Quimiorradioterapia/métodos , Europa (Continente) , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Humanos , Assistência de Longa Duração/métodos , Assistência de Longa Duração/normas , Linfonodos/patologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Oncologia/métodos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/diagnóstico , Tomografia por Emissão de Pósitrons/normas , Prognóstico , Indução de Remissão/métodos , Sociedades Médicas/normas , Sobrevivência , Tomografia Computadorizada por Raios X/normas , Resultado do TratamentoRESUMO
BACKGROUND: In early-stage Hodgkin's lymphoma (HL), treatment according to the early favorable or unfavorable subgroup is guided by staging definitions, which differ between various study groups worldwide. We analyzed risk factors used in different international staging systems and their impact on the outcome of early-stage HL patients. PATIENTS AND METHODS: In 1173 early-stage HL patients treated homogenously within the German Hodgkin Study Group (GHSG) trials HD10 and HD11, the impact of three staging systems developed and used by the GHSG, the European Organization for Research and Treatment of Cancer (EORTC), and the National Comprehensive Cancer Network (NCCN) in discriminating risk groups for progression-free survival (PFS) and overall survival (OS) was assessed and the relevance of their single risk factors was investigated. RESULTS: All the three staging systems defined an unfavorable risk group out of early-stage patients of comparable size (56%, 55%, and 57%), having a significantly poorer PFS and OS as compared with the corresponding favorable group; 5-year differences between early favorable and early unfavorable in terms of PFS were 9.4% (HR 2.61, 95% CI 1.74-3.91), 6.7% (HR 2.10, 95% CI 1.41-3.13), and 8.6% (HR 2.14, 95% CI 1.45-3.16) with the GHSG, EORTC, and NCCN definition, respectively. Sensitivity was high for all systems (84%, 79%, and 83%); however, there was a low specificity with high rates of false-positive results (1-specificity 54%, 53%, and 55%, respectively). Models of high sensitivity included risk factors associated with large tumor burden and high tumor activity. Most risk factors for tumor-specific end points were also predictive of OS. CONCLUSIONS: Differentiating between a favorable and an unfavorable risk group has significant impact on PFS and OS in early-stage HL patients in the modern treatment era. Risk-adapted treatment strategies using new risk factors with higher specificity are needed.
Assuntos
Doença de Hodgkin/patologia , Adolescente , Adulto , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Pixantrone is an aza-anthracenedione with enhanced, preclinical antitumor activity and reduced cardiotoxicity compared with doxorubicin. PATIENTS AND METHODS: We compared the efficacy and toxic effect of CPOP-R (substituting pixantrone for doxorubicin) against CHOP-R in untreated, diffuse large B-cell lymphoma (DLBCL) patients. The primary objective was to demonstrate non-inferiority of CPOP-R by complete response/complete response unconfirmed (CR/CRu) rate. RESULTS: The CR/CRu rate for CPOP-R was 75% versus 84% for CHOP-R. Three-year overall survival was lower for CPOP-R (69% versus 85%) (P = 0.029). Median progression-free survival (PFS) was not reached for CPOP-R and was 40 months for CHOP-R [HR 95% confidence interval (CI) = 1.02 (0.60, 1.76), P = 0.934]. Fewer CPOP-R patients developed congestive heart failure (CHF) (0% versus 6%, P = 0.120), ≥ 20% declines in ejection fraction (2% versus 17%, P = 0.004), or elevations in troponin-T (P = 0.003). CONCLUSIONS: CPOP-R is an active regimen with modestly lower response rates than CHOP-R but similar PFS and event-free survival. This study demonstrates a substantially lower cardiotoxicity of pixantrone compared with doxorubicin when used as first-line therapy in DLBCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Isoquinolinas/efeitos adversos , Isoquinolinas/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab , Volume Sistólico/efeitos dos fármacos , Sobrevida , Taxa de Sobrevida , Inibidores da Topoisomerase II/efeitos adversos , Inibidores da Topoisomerase II/uso terapêutico , Resultado do Tratamento , Troponina T/metabolismo , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques. PATIENTS AND METHODS: Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses. RESULTS: With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). CONCLUSIONS: In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects. CLINICAL TRIALS: The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Bleomicina/uso terapêutico , Quimiorradioterapia , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Doença de Hodgkin/mortalidade , Humanos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Vimblastina/uso terapêuticoRESUMO
This report reviews aspects of the German evidence-based guidelines for Hodgkin's lymphoma relevant to radiation oncologists. Stage-adapted treatment is discussed with the focus on radiotherapy. Up-to-date literature citations provide an overview of current recommendations.