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1.
Lancet Oncol ; 22(2): 223-234, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33539742

RESUMO

BACKGROUND: Combined-modality treatment consisting of chemotherapy and consolidation radiotherapy is standard of care for patients with early-stage unfavourable Hodgkin lymphoma. However, the use of radiotherapy can have long-term sequelae, which is of particular concern, as Hodgkin lymphoma is frequently diagnosed in young adults with a median age of approximately 30 years. In the German Hodgkin Study Group HD17 trial, we investigated whether radiotherapy can be omitted without loss of efficacy in patients who have a complete metabolic response after receiving two cycles of escalated doses of etoposide, cyclophosphamide, and doxorubicin, and regular doses of bleomycin, vincristine, procarbazine, and prednisone (eBEACOPP) plus two cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy (2 + 2). METHODS: In this multicentre, open-label, randomised, phase 3 trial, patients (aged 18-60 years) with newly diagnosed early-stage unfavourable Hodgkin lymphoma (all histologies) and an Eastern Cooperative Oncology Group performance status of 2 or less were enrolled at 224 hospitals and private practices in Germany, Switzerland, Austria, and the Netherlands. Patients were randomly assigned (1:1) to receive either standard combined-modality treatment, consisting of the 2 + 2 regimen (eBEACOPP consisted of 1250 mg/m2 intravenous cyclophosphamide on day 1, 35 mg/m2 intravenous doxorubicin on day 1, 200 mg/m2 intravenous etoposide on days 1-3, 100 mg/m2 oral procarbazine on days 1-7, 40 mg/m2 oral prednisone on days 1-14, 1·4 mg/m2 intravenous vincristine on day 8 [maximum dose of 2 mg per cycle], and 10 mg/m2 intravenous bleomycin on day 8; ABVD consisted of 25 mg/m2 intravenous doxorubicin, 10 mg/m2 intravenous bleomycin, 6 mg/m2 intravenous vinblastine, and 375 mg/m2 intravenous dacarbazine, all given on days 1 and 15) followed by 30 Gy involved-field radiotherapy (standard combined-modality treatment group) or PET4-guided treatment, consisting of the 2 + 2 regimen followed by 30 Gy of involved-node radiotherapy only in patients with positive PET at the end of four cycles of chemotherapy (PET4; PET4-guided treatment group). Randomisation was done centrally and used the minimisation method and seven stratification factors (centre, age, sex, clinical symptoms, disease localisation, albumin concentration, and bulky disease), and patients and investigators were masked to treatment allocation until central review of the PET4 examination had been completed. With the final analysis presented here, the primary objective was to show non-inferiority of the PET4-guided strategy in a per-protocol analysis of the primary endpoint of progression-free survival. We defined non-inferiority as an absolute difference of 8% in the 5-year progression-free survival estimates between the two groups. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01356680. FINDINGS: Between Jan 13, 2012, and March 21, 2017, we enrolled and randomly assigned 1100 patients to the standard combined-modality treatment group (n=548) or to the PET4-guided treatment group (n=552); two patients in each group were found ineligible after randomisation. At a median follow-up of 46·2 months (IQR 32·7-61·2), 5-year progression-free survival was 97·3% (95% CI 94·5-98·7) in the standard combined-modality treatment group and 95·1% (92·0-97·0) in the PET4-guided treatment group (hazard ratio 0·523 [95% CI 0·226-1·211]). The between-group difference was 2·2% (95% CI -0·9 to 5·3) and excluded the non-inferiority margin of 8%. The most common grade 3 or 4 acute haematological adverse events were leucopenia (436 [83%] of 528 patients in the standard combined-modality treatment group vs 443 [84%] of 529 patients in the PET4-guided treatment group) and thrombocytopenia (139 [26%] vs 176 [33%]), and the most frequent acute non-haematological toxic effects were infection (32 [6%] vs 40 [8%]) and nausea or vomiting (38 [7%] vs 29 [6%]). The most common acute radiotherapy-associated adverse events were dysphagia (26 [6%] in the standard combined-modality treatment group vs three [2%] in the PET4-guided treatment group) and mucositis (nine [2%] vs none). 229 serious adverse events were reported by 161 (29%) of 546 patients in the combined-modality treatment group, and 235 serious adverse events were reported by 164 (30%) of 550 patients in the PET4-guided treatment group. One suspected unexpected serious adverse reaction (infection) leading to death was reported in the PET4-guided treatment group. INTERPRETATION: PET4-negativity after treatment with 2 + 2 chemotherapy in patients with newly diagnosed early-stage unfavourable Hodgkin lymphoma allows omission of consolidation radiotherapy without a clinically relevant loss of efficacy. PET4-guided therapy could thereby reduce the proportion of patients at risk of the late effects of radiotherapy. FUNDING: Deutsche Krebshilfe.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
4.
Cancer Radiother ; 25(1): 32-38, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33402292

RESUMO

PURPOSE: To evaluate attenuation of the totally implantable vascular access device (TIVAD) and assess its clinical and dosimetric impact on radiotherapy (RT) of lymphoma patients. MATERIALS AND METHODS: The first part of the study consisted of an in vitro approach by irradiating the TIVAD with different electron and photon energies. The attenuation data measured were compared with data calculated by our treatment planning system. All patients treated by radiotherapy for Hodgkin's lymphoma with their TIVAD in the target volume were then reviewed to assess the clinical outcome and dosimetric comparison using different plan metrics. All patients were treated by 3D conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy delivered by Helical Tomotherapy (HT). RESULTS: Nineteen patients treated for stage I-III HL were studied. Seven patients were treated exclusively on the side of TIVAD and 12 were treated bilaterally. Median prescription dose was 30Gy. No significant clinical or dosimetric differences were observed between the side of the TIVAD and the contralateral side in patients treated bilaterally. HT resulted in a significantly higher conformity index (P<0.0022) and a significantly lower healthy tissue coverage (P=0.0008) than 3DCRT. The observed attenuation was 79% for 6 MeV, 59% for 9 MeV, and 46% for 12 MeV for electrons and 9% for 4 MV, 8% for 6 MV, 5% for 10 MV and 15 MV and 3% for 20 MV for X photons. CONCLUSION: TIVADs induce significant beam attenuation when using electrons, which can be overcome by using high-energy photons or by creating an exclusion zone in when HT is used.


Assuntos
Doença de Hodgkin/radioterapia , Radioterapia Conformacional/métodos , Dispositivos de Acesso Vascular , Adulto , Elétrons/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Terapia com Prótons , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Adulto Jovem
5.
BMJ Case Rep ; 13(12)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33372025

RESUMO

Cardiac disease after mediastinal radiotherapy can result in progressive valvular thickening and dystrophic calcification with ensuing leaflet restriction and dysfunction. This can ultimately manifest as valvular stenosis and/or regurgitation. We report a case of a 61-year-old woman with symptomatic severe aortic stenosis and severe mitral stenosis due to severe dystrophic calcification postmediastinal radiotherapy for lymphoma. She was deemed surgically inoperable due to dense, continuous calcification throughout the leaflets and annuli of both valves, aortomitral continuity, proximal coronary arteries and proximal porcelain aorta. She underwent simultaneous transcatheter aortic valve replacement and transcatheter mitral valve replacement with an excellent technical and clinical result at 7-month follow-up. We also describe the central role of multimodality three-dimensional transoesophageal echocardiography and multidetector cardiac CT imaging in assessing the severity of valve disease, characterising the nature of cardiac calcification and guiding decisions on surgical operability and transcatheter intervention.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Calcinose/complicações , Doenças das Valvas Cardíacas/complicações , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/cirurgia , Radioterapia/efeitos adversos , Estenose da Valva Aórtica/etiologia , Calcinose/etiologia , Ecocardiografia Transesofagiana , Feminino , Doenças das Valvas Cardíacas/etiologia , Implante de Prótese de Valva Cardíaca , Doença de Hodgkin/radioterapia , Humanos , Neoplasias do Mediastino/radioterapia , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Estenose da Valva Mitral/etiologia , Tomografia Computadorizada Multidetectores , Imagem Multimodal , Substituição da Valva Aórtica Transcateter
6.
Int Heart J ; 61(5): 1041-1043, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879262

RESUMO

The current treatment of radiation-induced coronary artery disease (RCAD) is comparable to that of generic coronary artery disease (CAD); however, the outcomes of these treatment measures have not been fully examined in RCAD. A 33-year-old woman, without conventional cardiovascular risk factors, presented with left main coronary artery (LMCA) lesions. At the age of 26, she received mediastinal radiation therapy (RT) to treat mixed cellularity Hodgkin lymphoma. One BiodivYsio 3.5 × 18 mm stent was implanted at the LMCA site. At the age of 38, the patient was treated by balloon dilatation because of approximately 50% in-stent stenosis. At the last follow-up in February 2018, when the patient was 51 years old, she no longer complained of chest pain. Coronary angiography showed no de novo or in-stenosis lesions, although optical coherence tomography showed mild neointimal proliferation, calcific plaque, small ruptured intima, and several uncovered struts. The experience of treating this case may shed some light on coronary stenting in coronary lesions caused by RCAD.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Doença de Hodgkin/radioterapia , Lesões por Radiação/terapia , Stents , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediastino , Pessoa de Meia-Idade , Neointima/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Tomografia de Coerência Óptica
9.
J Card Surg ; 35(3): 612-619, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31971292

RESUMO

BACKGROUND: Mediastinal radiation therapy (MRT) is a widely used therapy for thoracic malignancies. This therapy has the potential to cause cardiovascular injuries, which may require surgery. The primary aim of this study is to identify the perioperative outcomes of cardiac surgery in patients with a history of MRT. Second, potential predictors of mortality and adverse events were identified. METHODS: A retrospective study was conducted among 59 patients with prior MRT who underwent cardiac surgery between December 2009 and March 2015. Included surgeries consisted of procedures through median- and ministernotomy. Baseline, perioperative, and follow-up data were obtained and analyzed. RESULTS: The majority of patients had a history of breast cancer (n = 43), followed by Hodgkin lymphoma (n = 10) and non-Hodgkin lymphoma (n = 3). Preoperative estimated mortality with the Euroscore II was 3.4%. Overall 30-day mortality was 6.8% (n = 4), with a total in-hospital mortality of 10.2% (n = 6). Postoperatively, nine rethoracotomies (15.3%) had to be performed. During a mean follow-up of 53 months, an additional 10 patients (16.9%) died, of which 60% (n = 6) as a result of cancer-related events. Cox proportional modeling showed no differences in mortality between primary malignancies (P > .05). CONCLUSION: This study shows that cardiac surgery after mediastinal radiotherapy is associated with increased short- and long-term mortality when compared to preoperative mortality risks predicted by the Euroscore II. Surgery-related events caused all short-term mortality cases, while malignancy-related events were the main cause of death during the follow-up. Mortality was higher in patients with a previous stroke and a lower estimated glomerular filtration rate.


Assuntos
Neoplasias da Mama/radioterapia , Procedimentos Cirúrgicos Cardíacos , Doenças Cardiovasculares/cirurgia , Doença de Hodgkin/radioterapia , Linfoma não Hodgkin/radioterapia , Mediastino , Radioterapia/métodos , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Doença de Hodgkin/complicações , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/mortalidade , Masculino , Radioterapia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
10.
Radiat Oncol ; 15(1): 12, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931861

RESUMO

BACKGROUND: To investigate the role of intensity modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for advanced supradiaphragmatic Hodgkin's lymphoma (HL) in young female patients by assessing dosimetric features and modelling the risk of treatment related complications and radiation-induced secondary malignancies. METHODS: A group of 20 cases (planned according to the involved-site approach) were retrospectively investigated in a comparative planning study. Intensity modulated proton plans (IMPT) were compared to VMAT RapidArc plans (RA). Estimates of toxicity were derived from normal tissue complication probability (NTCP) calculations with either the Lyman or the Poisson models for a number of endpoints. Estimates of the risk of secondary cancer induction were determined for lungs, breasts, esophagus and thyroid. A simple model-based selection strategy was considered as a feasibility proof for the individualized selection of patients suitable for proton therapy. RESULTS: IMPT and VMAT plans resulted equivalent in terms of target dose distributions, both were capable to ensure high coverage and homogeneity. In terms of conformality, IMPT resulted ~ 10% better than RA plans. Concerning organs at risk, IMPT data presented a systematic improvement (highly significant) over RA for all organs, particularly in the dose range up to 20Gy. This lead to a composite average reduction of NTCP of 2.90 ± 2.24 and a reduction of 0.26 ± 0.22 in the relative risk of cardiac failures. The excess absolute risk per 10,000 patients-years of secondary cancer induction was reduced, with IMPT, of 9.1 ± 3.2, 7.2 ± 3.7 for breast and lung compared to RA. The gain in EAR for thyroid and esophagus was lower than 1. Depending on the arbitrary thresholds applied, the selection rate for proton treatment would have ranged from 5 to 75%. CONCLUSION: In relation to young female patients with advanced supradiaphragmatic HL, IMPT can in general offer improved dose-volume sparing of organs at risk leading to an anticipated lower risk of early or late treatment related toxicities. This would reflect also in significantly lower risk of secondary malignancies induction compared to advanced photon based techniques. Depending on the selection thresholds and with all the limits of a non-validated and very basic model, it can be anticipated that a significant fraction of patients might be suitable for proton treatments if all the risk factors would be accounted for.


Assuntos
Doença de Hodgkin/radioterapia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Feminino , Humanos , Órgãos em Risco , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Adulto Jovem
12.
J Natl Cancer Inst ; 112(1): 63-70, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31070751

RESUMO

BACKGROUND: Adolescent women treated for Hodgkin lymphoma (HL) are at increased risk of breast cancer (BC). We evaluate the cost-utility of eight high-risk BC surveillance strategies for this population, including the Children's Oncology Group guideline of same-day annual mammography and magnetic resonance imaging (MRI) beginning at age 25 years. METHODS: A discrete event simulation model was used to simulate the life histories of a cohort of 500 000 25-year-old women treated for HL at age 15 years. We estimated BC incidence and mortality, life expectancy, quality-adjusted life-years (QALYs), health-care costs, and the relative cost-utility (incremental cost-utility ratio [ICUR]) under the eight assessed surveillance strategies. One-way sensitivity analysis enabled modeling of uncertainty evaluation. A publicly funded health-care payer perspective was adopted. RESULTS: Costs across the eight screening strategies ranged from $32 643 to $43 739, whereas QALYs ranged from 24.419 to 24.480. In an incremental cost-effectiveness analysis, annual mammography beginning at age 25 years was associated with an ICUR of $43 000/QALY gained, annual MRI beginning at age 25 years with a switch to annual mammography at age 50 years had an ICUR of $148 000/QALY, and annual MRI beginning at age 25 years had an ICUR of $227 222/QALY. Among all assessed surveillance strategies, the differences in life expectancy were small. CONCLUSIONS: Current high-risk BC surveillance guidelines do not reflect the most cost-effective strategy in survivors of adolescent HL. The results suggest that groups at high risk of BC may require high-risk surveillance guidelines that reflect their specific risk profile.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Detecção Precoce de Câncer/economia , Doença de Hodgkin/epidemiologia , Radioterapia/efeitos adversos , Adolescente , Adulto , Tomada de Decisão Clínica , Análise Custo-Benefício , Árvores de Decisões , Feminino , Doença de Hodgkin/radioterapia , Humanos , Imagem por Ressonância Magnética/efeitos adversos , Mamografia/efeitos adversos , Modelos Teóricos , Vigilância em Saúde Pública , Anos de Vida Ajustados por Qualidade de Vida , Radioterapia/métodos
13.
Ital J Pediatr ; 45(1): 170, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881905

RESUMO

Radiation therapy represents an important approach in the therapeutic management of children and adolescents with malignant tumors and its application with modern techniques - including Proton Beam Therapy (PBT) - is of great interest. In particular, potential radiation-induced injuries and secondary malignancies - also associated to the prolonged life expectancy of patients - are still questions of concern that increase the debate on the usefulness of PBT in pediatric treatments. This paper presents a literary review of current applications of PBT in non-Central Nervous System pediatric tumors (such as retinoblastoma, Hodgkin Lymphoma, Wilms tumor, bone and soft tissues sarcomas). We specifically reported clinical results achieved with PBT and dosimetric comparisons between PBT and the most common photon-therapy techniques. The analysis emphasizes that PBT minimizes radiation doses to healthy growing organs, suggesting for reduced risks of late side-effects and radiation-induced secondary malignancies. Extended follow up and confirms by prospective clinical trials should support the effectiveness and long-term tolerance of PBT in the considered setting.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons , Neoplasias Ósseas/radioterapia , Doença de Hodgkin/radioterapia , Humanos , Órgãos em Risco , Doses de Radiação , Dosagem Radioterapêutica , Retinoblastoma/radioterapia , Sarcoma/radioterapia , Tumor de Wilms/radioterapia
16.
Lancet Haematol ; 6(11): e551-e561, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31564649

RESUMO

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.


Assuntos
Doença de Hodgkin/diagnóstico , Adulto , Antineoplásicos/uso terapêutico , Parto Obstétrico , Intervalo Livre de Doença , Feminino , Idade Gestacional , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Nascimento Vivo , Gravidez , Cuidado Pré-Natal , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
Radiat Oncol ; 14(1): 157, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477141

RESUMO

Radiotherapy is frequently used in the therapy of lymphoma. Since lymphoma, for example Hodgkin's disease, frequently affect rather young patients, the induction of secondary cancer or other long-term adverse effects after irradiation are important issues to deal with. Especially for mediastinal manifestations numerous organs and substructures at risk play a role. The heart, its coronary vessels and cardiac valves, the lungs, the thyroid and, for female patients, the breast tissue are only the most important organs at risk. In this study we investigated if proton-radiotherapy might reduce the dose delivered to the organs at risk and thus minimize the therapy-associated toxicity. METHODS: In this work we compared the dose delivered to the heart, its coronary vessels and valves, the lungs, the thyroid gland and the breast tissue by different volumetric photon plans and a proton plan, all calculated for a dose of 28.8 Gy (EURO-NET-PHL-C2). Target Volumes have been defined by F18-FDG PET-positive areas, following a modified involved node approach. Data from ten young female patients with mediastinal lymphoma have been evaluated. Three different modern volumetric IMRT (VMAT) photon plans have been benchmarked against each other and against proton-irradiation concepts. For plan-evaluation conformity- and homogeneity-indices have been calculated as suggested in ICRU 83. The target volume coverage as well as the dose to important organs at risk as the heart with its substructures, the lungs, the breast tissue, the thyroid and the spinal cord were calculated and compared. For statistical evaluation mean doses to organs at risk were evaluated by non- parametric Kruskal-Wallis calculations with pairwise comparisons. RESULTS: Proton-plans and three different volumetric photon-plans have been calculated. Proton irradiation results in significant lower doses delivered to organ at risk. The median doses and the mean doses could be decreased while PTV coverage is comparable. As well conformity as homogeneity are slightly better for proton plans. For several organs a risk reduction for secondary malignancies has been calculated using literature data as reference. According to the used data derived from literature especially the secondary breast cancer risk, the secondary lung cancer risk and the risk for ischemic cardiac insults can be reduced significantly by using protons for radiotherapy of mediastinal lymphomas. CONCLUSION: Irradiation with protons for mediastinal Hodgkin-lymphoma results in significant lower doses for almost all organs at risk and is suitable to reduce long term side effects for pediatric and adolescent patients.


Assuntos
Mama/efeitos da radiação , Coração/efeitos da radiação , Doença de Hodgkin/radioterapia , Pulmão/efeitos da radiação , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Glândula Tireoide/efeitos da radiação , Adolescente , Criança , Feminino , Humanos , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica
18.
Am J Hematol ; 94(11): 1208-1213, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31396979

RESUMO

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first-line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies. Among the 33 GHSG patients, 21 patients presented with a typical growth pattern at initial diagnosis, whereas 12 patients had a variant histology. The histopathological growth patterns at initial diagnosis and at relapse were consistent in 67% of cases. A variant histology at initial diagnosis was associated with a shorter median time to lymphoma recurrence (2.8 vs 5.2 years; P = .0219). A similar tendency towards a shorter median time to lymphoma recurrence was observed for patients presenting with a variant histology at relapse, irrespective of the growth pattern at initial diagnosis. Results obtained from the 41 NLPHL patients who had been treated outside GHSG studies were comparable (median time to lymphoma recurrence for variant histology vs typical growth pattern at initial diagnosis: 1.5 vs 7.0 years). In conclusion, the histopathological growth pattern remains consistent at relapse in the majority of NLPHL cases, and has major impact on the time of relapse.


Assuntos
Intervalo Livre de Doença , Doença de Hodgkin/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Terapia Combinada , Feminino , Seguimentos , Alemanha/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Recidiva , Rituximab/uso terapêutico , Transplante Autólogo
19.
Am J Case Rep ; 20: 1182-1188, 2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31401643

RESUMO

BACKGROUND Tumor disease has improved survival due to therapeutic advances and early diagnosis. However, anti-neoplastic treatment involves generating harmful side effects in the body, both in the short-term and in the long-term. One of the most important side effects is cardiovascular disease after radiotherapy, which in addition to being influenced by classic cardiovascular risk factors, can be also be influenced by anti-neoplastic therapy, and represents the main cause of death after a second cancer. We present a case that synthesizes the most relevant and determining aspects of radiotherapy-induced heart disease. CASE REPORT We present the case of a 48-year-old male with a personal history of mediastinal Hodgkin lymphoma who was treated with local radiotherapy 20 years ago, and who was admitted to hospital due to dyspnea and oppressive chest pain with efforts. He was diagnosed with severe aortic stenosis, and a coronary angiography confirmed the existence of coronary disease. Two years before, he had been admitted to hospital due to syncope and a pacemaker had been implanted. This patient experienced several cardiovascular complications that could be attributed to the radiotherapy treatment received in his past. CONCLUSIONS Radiotherapy shows multiple cardiological complications, especially when applied at the thoracic level. This fact is very relevant, and this report can help determine the aspects of radiotherapy-induced heart disease affecting the mortality and morbidity of these patients.


Assuntos
Estenose da Valva Aórtica/etiologia , Doença da Artéria Coronariana/etiologia , Coração/efeitos da radiação , Doença de Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Lesões por Radiação , Dor no Peito , Dispneia , Humanos , Masculino , Pessoa de Meia-Idade
20.
Medicine (Baltimore) ; 98(31): e16688, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374054

RESUMO

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.


Assuntos
Neoplasias Ósseas/radioterapia , Doença de Hodgkin/radioterapia , Linfoma de Células B/radioterapia , Linfoma de Células T/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Estudos de Casos e Controles , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Vincristina/uso terapêutico
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