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1.
Medicine (Baltimore) ; 99(7): e19146, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049838

RESUMEN

The aim of this study was to test the hypothesis that computed tomography texture analysis (CTTA) is accurate for response assessment of Hodgkin lymphoma (HL).A total of 100 patients with HL were identified. CTTA in baseline and interim staging was performed generating volume of interests in lymphoma tissue from which CTTA features including 1st, 2nd, and higher order textural features were extracted. Baseline and interim 2-deoxy-fluor-glucose positron emission tomography results were used to determine therapy response and compared to CTTA in terms of patient outcome.At interim, 1st-order features yielded a significant drop (e.g., entropy of heterogeneity, P = .01) or a significant rise (deviation, P < .001), whereas 2nd and higher order features decreased (e.g., entropy of co-occurrence matrix, P < .001). Patients achieving complete remission at end of treatment had a significantly lower entropy of heterogeneity at baseline and interim compared to patients achieving partial remission (P < .05).CT textural features change in parallel to metabolic therapy response, and are therefore a feasible diagnostic tool for a more accurate response assessment of HL.


Asunto(s)
Fluorodesoxiglucosa F18 , Enfermedad de Hodgkin/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
3.
Ann Hematol ; 99(2): 293-299, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31897678

RESUMEN

The objective of this study is to investigate the prognostic value of the percentage change of maximum standardized uptake value (ΔSUVmax) assessed by PET/CT scan after 2 cycles of chemotherapy (iPET2) in patients with classic Hodgkin's lymphoma (CHL). ΔSUVmax was calculated as follows: the ratio of (SUVmax at baseline-SUVmax at iPET2)/SUVmax at baseline which was determined before initiation of ABVD chemotherapy. The median ΔSUVmax of 46 patients at iPET2 was 87.9% (range - 6.1-100.0%). The optimal ΔSUVmax cutoff value for progression-free survival (PFS) was 83.0% with the receiver operating characteristic curve. The area under the curve for PFS was 0.886 (95% CI 0.788-0.984, p < 0.001). The median PFS of 29 (63.0%) patients who achieved a SUVmax reduction of more than 83.0% was 34 months. The median PFS of 17 (37.0%) patients with ΔSUVmax < 83.0% was 9 months. This difference was significant (p < 0.001). Cohen's kappa coefficient of Deauville Score (DS)- and ΔSUVmax-judged positivity was 0.752 (95% CI 0.592-0.992, p < 0.001), suggesting a strong consistency. Multivariate analysis showed that ΔSUVmax at iPET2 less than 83.0% of SUVmax at diagnosis was an independent factor predicting PFS [HR = 11.339, 95% CI 2.485-51.742, p = 0.002]. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ΔSUVmax<83.0% was 84.6%, 81.8%, 67.7%, 93.1%, and 82.6%, which was similar to that of DS as 61.5%, 87.9%, 66.7%, 85.3%, and 80.4%, respectively. ΔSUVmax<83.0% of iPET2 effectively predicts prognosis of patients with CHL treated with ABVD.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adolescente , Adulto , Anciano , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Vinblastina/administración & dosificación
4.
Ann Hematol ; 99(2): 255-264, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31897676

RESUMEN

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin , Proteínas de Neoplasias/sangre , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Proteína C-Reactiva/metabolismo , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Recurrencia , Tasa de Supervivencia , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangre , Factor A de Crecimiento Endotelial Vascular/sangre
5.
Lancet Haematol ; 7(2): e146-e156, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31948928

RESUMEN

BACKGROUND: Several strategies are available for the initial treatment of advanced-stage Hodgkin lymphoma, but the optimal strategy in terms of cost-effectiveness is unclear. The aim of this study was to compare the quality-adjusted effectiveness and costs of five modern treatment options for transplantation-eligible patients with newly diagnosed advanced-stage Hodgkin lymphoma. METHODS: A Markov decision-analytic model was developed using a 20-year time horizon. Five of the most common treatment approaches were selected based on clinical experience and expert opinion: (1) six cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), including data from the HD2000 trial, Viviani and colleagues, and EORTC trial; (2) six cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP; from the HD15 trial or PET-adapted as in the HD18 trial, two initial cycles of BEACOPP followed by four additional cycles for patients with a positive PET and either two or four additional cycles of BEACOPP for patients with a negative PET); (3) PET-adapted escalation (as in the RATHL trial, two cycles of standard ABVD chemotherapy followed by an additional four cycles of ABVD or AVD in PET-negative patients and four cycles of BEACOPP in PET-positive patients); (4) six cycles of brentuximab vedotin, doxorubicin, vinblastine, dacarbazine (A-AVD) or ABVD as in the Echelon-1 trial; and (5) PET-adapted de-escalation (as in the AHL2011 trial, two cycles of BEACOPP followed by PET2 scan; PET-positive patients received two additional BEACOPP cycles and PET-negative patients received two cycles of ABVD; at PET4, PET-negative patients completed two further cycles of either ABVD or BEACOPP depending on what they received after PET2, and PET-positive patients received salvage therapy). Note that all uses of BEACOPP in these strategies were BEACOPPescalated. The randomised groups of interest from these studies comprised 4255 patients enrolled between April, 2000, and January, 2016. Baseline probability estimates and utilities were derived from the included trials in addition to a systematic review of published studies. A Canadian public health payer's perspective was considered (CAN$1=US$0·74) and adjusted for inflation for 2018. All costs and benefits were discounted by 1·5% per year because life-years now are more valuable than future potential life-years. FINDINGS: Probabilistic analyses (10 000 simulations) showed that, for a willingness-to-pay threshold of CAN$50 000, a PET-adapted de-escalation strategy based on AHL2011 was more cost-effective 87% of the time. This strategy had the highest number of life-years (14·6 years [95% CI 13·7-15·1]) and quality-adjusted life years (13·2 years [95% CI 10·2-14·4]), and the lowest direct costs ($53 129 [95% CI 31 914-94 446]) compared with the other treatment regimens. Sensitivity analyses showed that the model was robust to key variables, including probability of treatment-related mortality, relapse, frequency of secondary malignancy, death from secondary malignancy, and probability of infertility after BEACOPP. INTERPRETATION: Our results suggest that, when considering cost, effectiveness, and short and long-term toxicities, the preferred treatment strategy for patients with newly diagnosed advanced-stage Hodgkin lymphoma is the PET-adapted de-escalation regimen starting with BEACOPP and de-escalating to ABVD as appropriate. Although our findings do not provide an absolute best treatment approach for clinicians to follow for all patients, they can contribute to shared decision making between patients and treating physicians. FUNDING: None.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Bleomicina/administración & dosificación , Bleomicina/economía , Canadá , Análisis Costo-Beneficio , Ciclofosfamida/administración & dosificación , Ciclofosfamida/economía , Dacarbazina/administración & dosificación , Dacarbazina/economía , Doxorrubicina/administración & dosificación , Doxorrubicina/economía , Etopósido/administración & dosificación , Etopósido/economía , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/economía , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Prednisona/administración & dosificación , Prednisona/economía , Procarbazina/administración & dosificación , Procarbazina/economía , Vinblastina/administración & dosificación , Vinblastina/economía , Vincristina/administración & dosificación , Vincristina/economía
6.
Ann Hematol ; 99(2): 385-388, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31773213

Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/tratamiento farmacológico , Terapia Molecular Dirigida , Neoplasias Primarias Secundarias/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Aloinjertos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/etiología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/etiología , Humanos , Inmunosupresores/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/terapia , Masculino , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Protoporfiria Eritropoyética/terapia , Recurrencia , Inducción de Remisión , Activación Viral , Adulto Joven
7.
Cancer Treat Rev ; 82: 101931, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31756590

RESUMEN

Hodgkin lymphoma is a B cell derived malignancy characterized by a low number of tumor cells within an environment consisting of inflammatory cells. Recently, immune checkpoint blockade targeting the PD-1-PD-L1 axis has shown to be a great success in relapsed and refractory Hodgkin lymphoma patients. However, complete responses are scarce and median progression-free survival is limited to around 11-15 months. Efficiency of PD-1 blockade in HL might be dependent on CD4+ T cells, but also tumor associated macrophages (TAMs) and NK cells are implicated. The aim of this review is to highlight currently known prominent immune evasion strategies and discuss their possible contribution to primary or acquired resistance to immune checkpoint blockade in Hodgkin lymphoma. These include T cell dependent mechanisms such as shaping of the inflammatory infiltrate, lack of presentation of antigens and neoantigens and production of molecules involved in suppression of T cell functionality such as other immune checkpoints, indoleamine 2,3-dioxygenase and adenosine. Moreover, the role of NK cells and TAMs in efficient PD-1 blockade will be discussed. Targeting these mechanisms in parallel to PD-1 may potentially increase efficiency of PD-1 blockade therapy.


Asunto(s)
Enfermedad de Hodgkin , Terapia Molecular Dirigida , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Resistencia a Antineoplásicos/inmunología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/inmunología , Humanos , Terapia Molecular Dirigida/efectos adversos , Terapia Molecular Dirigida/métodos , Escape del Tumor/inmunología
9.
Lancet Haematol ; 6(11): e551-e561, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31564649

RESUMEN

BACKGROUND: Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS: We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS: Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION: Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING: European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico , Adulto , Antineoplásicos/uso terapéutico , Parto Obstétrico , Supervivencia sin Enfermedad , Femenino , Edad Gestacional , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/radioterapia , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Nacimiento Vivo , Embarazo , Atención Prenatal , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
10.
J Pak Med Assoc ; 69(9): 1266-1272, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31511710

RESUMEN

Purpose: Hodgkin lymphoma (HL) is one of the most curable paediatric cancers, with long-term survival rates now exceeding 90% after treatment with chemotherapy alone or combined with radiotherapy (RT). Treatment options for Hodgkin's Lymphoma differ among various study groups and there is still no consensus regarding the standard treatment for Hodgkin's lymphoma. Taking into account the impact of treatment-related mortality in low- and middle-income countries we propose to study the the clinical features and treatment outcomes by using different chemotherapy protocols in Hodgk in s' s Lymphoma children's at Shaukat khanam hospital Lahore.. METHODS: Clinical data from a large regional cancer center Pediatrics patients with Hodgkin's Lymphoma from January 2009 till December 2015 was retrospectively collected after Institutional Review Board (IRB) approval. RESULTS: A total of 748 patients were reviewed retrospectively. Mostly (45%) were in 6-10 years age group. Male showed predominance ,male to female ratio was 4:1. B symptoms were present in 51%, bulky disease in 44% and ESR was more than 30mm in 26% of patients. CD 30 was positive in 95%, Bone marrow involved in 13% of patients. Stage I in 8%, stage- II in 27%, stage -III in 39% and stage IV in 26% was seen. COPDAc/ABVD was given in 412 patients, CHLVPP/ABVD in 176 patients, OEPA/COPP in 57 patients, OEPA in 35 patients, OEPA/COPDAC in 33 Patients and remaining 33 received various chemotherapy protocol combination. XRT was given in 17% of patients. Of these 86% of patients were alive ,5% patients died , 3% patients abandoned, 6% patients relapsed ,3% patients progressed while on chemotherapy. Five years Overall survival was 94% and 5 Years Event free survival was 91%. Minimum haematological and other toxicity was seen in patients who had received COPDac/ABVD when compared to other regimen. CONCLUSIONS: Hodgkin's lymphoma patients had good outcome with different chemotherapy regimens, however our experience showed that the COPDac/ABVD regimen wass better tolerated with minimum toxicity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Bleomicina/uso terapéutico , Niño , Preescolar , Clorambucilo/uso terapéutico , Ciclofosfamida/uso terapéutico , Dacarbazina/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Enfermedad de Hodgkin/patología , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Estadificación de Neoplasias , Pakistán , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Procarbazina/uso terapéutico , Pronóstico , Radioterapia Ayuvante , Estudios Retrospectivos , Tasa de Supervivencia , Centros de Atención Terciaria , Resultado del Tratamiento , Vinblastina/uso terapéutico , Vincristina/uso terapéutico
11.
Cochrane Database Syst Rev ; 9: CD012643, 2019 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-31525824

RESUMEN

BACKGROUND: Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL. OBJECTIVES: To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov). SELECTION CRITERIA: We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results. DATA COLLECTION AND ANALYSIS: We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data. MAIN RESULTS: Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages).Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12).Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies.Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study.Overall survivalTwelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Nine studies were assessed as high risk, and three studies as moderate risk of bias for the domain study confounding. Eight studies were assessed as low risk, and four studies as high risk of bias for the domain statistical analysis and reporting.We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result.Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence).Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as high risk, nine studies as moderate risk and one study as low risk of bias for study confounding. Eight studies were assessed as high risk, three as moderate risk and nine as low risk of bias for statistical analysis and reporting.We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result.Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence).PET-associated adverse eventsNo study measured PET-associated AEs. AUTHORS' CONCLUSIONS: This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.


Asunto(s)
Quimioradioterapia/métodos , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto
12.
Medicine (Baltimore) ; 98(31): e16688, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31374054

RESUMEN

The objectives of this study were to analyze the clinical features of patients with bone involved lymphoma and identify the prognostic factors and to explore the optimized treatment strategy for bone involved lymphoma.A total of 1948 patients with lymphoma in our cancer center from September 2006 to October 2017 were retrospectively evaluated. Among these, 109 patients with skeletal involvement in lymphoma were enrolled. According to the pathologic subtypes, the patients were divided into 3 subgroups: classic Hodgkin lymphoma (cHL), B-cell non-Hodgkin lymphoma (B-NHL), and T-cell non-Hodgkin lymphoma (T-NHL). The clinical characteristics and overall survival (OS) of 3 groups of patients were reviewed, and the prognostic factors were analyzed.There were 9 (3 unifocal, 6 multifocal) patients with primary bone lymphoma. The 5-year OS of cHL, B-NHL, and T-NHL patients was 88.24%, 54.09%, and 61.58%, respectively. Advanced stage, elevated lactate dehydrogenase (LDH), age above 60, high International Prognostic Index score, and treatment without radiotherapy for the bone involved were significant poor prognostic factors for OS of all patients in univariate analysis. There was a trend toward better OS not only in limited-stage but also in advanced-stage patients with radiotherapy for the bone involved compared with the patients without radiotherapy. Elevated LDH level and age above 60 were the independent unfavorable prognostic factor in multivariate analysis.Elevated LDH level and age above 60 predict the poor prognosis of patients with bone involvement. The potential for long-term survival suggests that additional consolidative radiotherapy for the site of skeleton involvement may have a better chance of long-term success.


Asunto(s)
Neoplasias Óseas/radioterapia , Enfermedad de Hodgkin/radioterapia , Linfoma de Células B/radioterapia , Linfoma de Células T/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Estudios de Casos y Controles , Terapia Combinada , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/mortalidad , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Retrospectivos , Vincristina/uso terapéutico
13.
Blood ; 134(14): 1144-1153, 2019 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-31409671

RESUMEN

Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at www.clinicaltrials.gov as #NCT02453594.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
14.
Anticancer Res ; 39(8): 4333-4335, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31366526

RESUMEN

Secondary malignancies are relatively common and clinically important phenomena following both chemotherapy and radiotherapy. The majority of these cases are acute leukemias, the occurrence of which have been thoroughly documented and studied. More rarely, chronic myeloid leukemias (CML) may arise subsequent to treatment of a primary malignancy. Literature review on such developments following treatment of Hodgkin's Lymphoma (HL) is scant. Herein, the authors present three cases of CML diagnosed within five years of treatment initiation for Hodgkin's Lymphoma (HL); one of the three patients had CML with atypical variant carrying a rare mutation with BCR-JAK2 fusion.


Asunto(s)
Enfermedad de Hodgkin/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Neoplasias Primarias Secundarias/genética , Proteínas de Fusión bcr-abl/genética , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Primarias Secundarias/sangre , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/patología , Proteínas Proto-Oncogénicas c-bcr/genética
15.
Pediatr Blood Cancer ; 66(11): e27951, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31368255
17.
Acta Haematol ; 142(3): 171-175, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31454795

RESUMEN

AIM: Bleomycin is an antitumor antibiotic used successfully to treat a variety of malignancies, predominantly germ cell tumors and Hodgkin's lymphoma (HL). The major limitation of bleomycin therapy is the potential for life-threatening interstitial pulmonary fibrosis. Early identification of asymptomatic patients who may develop toxicity is important. We aimed to evaluate fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) findings to predict bleomycin toxicity (BT) early after chemotherapy with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy before clinical symptoms and radiological changes occur. MATERIALS AND METHODS: HL patients who were treated with ABVD were evaluated. SUVmax values of lung parenchyma were analyzed in FDG-PET/CT at diagnosis and after 4 cycles of chemotherapy in all patients. At the end of the chemotherapy cycles, lung parenchymal SUVmax values of patients with BT and without BT were compared statistically. RESULTS: Twenty (66.7%) male and 10 (33.3%) female patients with HL were included. Five (16.7%) HL patients developed BT. In 3 HL patients, BT was determined after 5 cycles and in 2 patients, BT was seen after 6 cycles. In all 5 of these patients with BT, FDG uptake in PET-CT was increased after 4 cycles of chemotherapy and BT was predicted before clinical and radiological findings by FDG-PET/CT. After 4 cycles of chemotherapy, lung parenchymal SUVmax of patients with BT (3.24 ± 0.76) was significantly higher than in patients without toxicity (1.84 ± 0.52) (p < 0.001). In patients with BT, a significant increase was established in lung parenchymal SUVmax after 4 cycles of chemotherapy when compared to the time of diagnosis (p = 0.043). CONCLUSION: BT can be fatal. Early detection of BT is essential in clinical practice. FDG-PET/CT can predict BT before clinical and radiological findings occur.


Asunto(s)
Bleomicina/efectos adversos , Enfermedad de Hodgkin , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fibrosis Pulmonar , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/diagnóstico por imagen , Vinblastina/administración & dosificación , Vinblastina/efectos adversos
18.
Cancer Radiother ; 23(8): 922-925, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31257097

RESUMEN

The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7Gy vs. 8.4Gy) and median dose (0.002Gy vs. 6.9Gy), heart mean dose (2.6Gy vs. 3.7Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4Gy vs. 4.4Gy) and left (1.9Gy vs. 4.6Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.


Asunto(s)
Enfermedad de Hodgkin/radioterapia , Neoplasias del Mediastino/radioterapia , Fotones/uso terapéutico , Terapia de Protones/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Corazón/diagnóstico por imagen , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Pulmón/diagnóstico por imagen , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/tratamiento farmacológico , Tratamientos Conservadores del Órgano/métodos , Órganos en Riesgo/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Guías de Práctica Clínica como Asunto , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Traumatismos por Radiación/prevención & control , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada , Vincristina/administración & dosificación , Adulto Joven
19.
Blood ; 134(15): 1238-1246, 2019 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-31331918

RESUMEN

Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)-adapted therapy on SWOG S0816. Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval [CI], 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2- and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2- patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Dacarbazina/administración & dosificación , Dacarbazina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Tomografía de Emisión de Positrones/métodos , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Procarbazina/administración & dosificación , Procarbazina/uso terapéutico , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Adulto Joven
20.
J Formos Med Assoc ; 118(10): 1466-1470, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31337522

RESUMEN

Hodgkin lymphoma (HL) is a highly curable hematologic malignancy. Relapsed/refractory (R/R) HL is an important clinical challenge, despite advances in treatment. Brentuximab vedotin (BV) is highly effective in R/R HL in the western world. However, there are no real-world data on the use of BV in the Asian population. Our study aimed to evaluate the efficacy and safety of BV as salvage therapy in R/R HL patients in Taiwan. We recruited 20 R/R HL patients who received BV at National Taiwan University Hospital. BV was administered at 1.8 mg/kg once every 3 weeks. The median number of systemic treatment received before BV was three. The overall response rate was 73.7% with a complete remission rate of 21.1% in R/R HL. Overall survival was not reached and progression-free survival was 6.8 months. BV could strengthen disease control before transplantation and improve post-transplant outcomes, even among those heavily pretreated patients, without significant overlapping toxicities with prior therapies. Our data suggest that BV is well tolerated and effective in the treatment of Asian patients with R/R HL. BV may offer long-term disease control in selected patients.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Recurrencia , Retratamiento , Terapia Recuperativa/efectos adversos , Tasa de Supervivencia , Taiwán , Adulto Joven
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