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1.
Cancer Radiother ; 24(4): 335-339, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32444284

RESUMO

Hodgkin lymphoma (HL) is a disease characterized by a high curability rate, and the treatment benefit-risk balance must be carefully addressed to achieve complete disease control with low risk of long-term toxicities. Most patients are treated with a combination of chemotherapy and radiotherapy, after disease staging and response to treatment evaluated by FDG PET/CT. We report the case of a 28-year-old patient concomitantly diagnosed of a Hodgkin lymphoma and active tuberculosis. Initial staging was difficult due to pulmonary and abdominal tuberculosis localization that induced FDG PET/CT hypermetabolism. Anti-tuberculosis treatment was first started, allowing secondary an early accurate Hodgkin lymphoma staging by FDG PET/CT. The patient was then treated by chemotherapy and radiotherapy. Helical TomoTherapy® was used with involved site (IS) irradiation volume was performed to decrease the high doses to organs-at-risk (OAR), especially lungs in this context of tuberculosis.


Assuntos
Doenças do Colo/tratamento farmacológico , Doença de Hodgkin/terapia , Tuberculose Gastrointestinal/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antituberculosos/uso terapêutico , Bleomicina/administração & dosagem , Doenças do Colo/complicações , Doenças do Colo/diagnóstico por imagem , Doenças do Colo/metabolismo , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Humanos , Pulmão , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Masculino , Órgãos em Risco , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radioterapia de Intensidade Modulada , Medição de Risco , Tomografia Computadorizada por Raios X , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/diagnóstico por imagem , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagem , Vimblastina/administração & dosagem
2.
Br J Haematol ; 190(1): e1-e3, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32379903
3.
J Cancer Res Ther ; 16(1): 1-6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362601

RESUMO

Background: Hodgkin's lymphoma (HL) can be treated with combined modality treatment (CMT) to limit long-term toxicities in the early favorable stage. Early unfavorable and advanced stage HL is mainly treated with chemotherapy followed by radiation to the bulky site. This study examines the impact of CMT in early as well as advanced stage HL. Materials and Methods: From 2001 to 2011, 125 patients with Stage I to IV HL were analyzed. Median age of the patients was 25 years (range 12-68 years). CMT, chemotherapy, and radiation alone were given to 51, 64, and 10 patients, respectively. Chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was given to 100 patients, 6 patients received ABVD-like regimen, and 9 patients received cyclophosphamide, vincristine, procarbazine, and prednisone regimen. Radiotherapy (RT) was given to 61 (49%) patients, involved field RT to 55 (90%), and extended-field RT to 6 (10%) patients, respectively. Median radiation dose was 30 Gy (18-40 Gy). Results: All 25 patients with early-stage achieved complete response (CR) with CMT. At a median follow-up of 70 months (range 12-230 months), relapse was seen in two patients (1 local and 1 distant). Of 26 patients with advanced stage, 25 achieved a CR and 1 had stable disease with CMT. Relapse occurred in one patient (distant). In patients with early-stage treated with chemotherapy only ( n = 30, 24%), 9 patients had relapse (4 local and 5 distant) while in those with RT only ( n = 10, 8%), 4 developed distant relapse. In patients with advanced stage treated with chemotherapy only ( n = 34, 27%), 8 relapsed (5 local and distant, 3 distant only). Patients with relapse were salvaged with CMT ( n = 6), chemotherapy ( n = 15), or RT ( n = 3). Two patients have died. Five years' disease-free survival (DFS) in patients with early favorable stage, early unfavorable stage, and advanced stage was 91%, 82%, and 73%, respectively ( P = 0.026). DFS was significantly better with CMT than chemotherapy or radiation alone. Five years' overall survival (OS) was 93%, 92%, and 84%, respectively ( P = 0.139). Second malignancy occurred in 3 (2.4%) patients; carcinoma of the tongue, pseudomyxoma peritonei, and non-HL each, respectively. None of these patients had received prior radiation. Conclusion: CMT improved DFS in patients with HL. OS was similar in all patients irrespective of treatment combinations. The incidence of second malignancy was 2.4%.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Radioterapia/mortalidade , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Criança , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
4.
Eur J Cancer ; 132: 85-97, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32334339

RESUMO

BACKGROUND: The clinical impact of the positivity of the Deauville scale (DS) of positron emission tomography (PET) performed at the end of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in patients with advanced Hodgkin lymphoma (HL), in terms of providing rationale to shift poor responders onto a more intensive regimen, remain to be validated by histopathology. PATIENTS AND METHODS: This prospective trial involved patients with stage IIB/IV HL who after six ABVD cycles underwent PET (PET6) and core-needle cutting biopsy (CNCB) of 2-deoxy-2[F-18] fluoro-d-glucose (FDG)-avid lymph nodes. Patients received high-dose chemotherapy/autologous haematopoietic stem cell rescue (HDCT/AHSCR) if CNCB was positive for HL, alternatively, if CNCB or PET was negative, received observation or consolidation radiotherapy (cRT) on residual nodal masses, as initially planned. The end-point was 5-year progression-free survival (PFS). RESULTS: In all, 43 of the 169 (25%) evaluable patients were PET6 positive (DS 4, 32; DS 5, 11). Among them, histology showed malignancy (HL) in 100% of DS 5 scores and in 12.5% of DS 4 scores. Fifteen patients with positive biopsy received HDCT/AHSCR, whereas 28 patients with negative biopsy, as well as 126 patients with negative PET6, continued the original plan (cRT, 78 patients; observation, 76 patients). The 5-year PFS in the negative PET6 group, negative biopsy group and positive biopsy group was 95.4%, 100% and 52.5%, respectively. CONCLUSION: DS positivity of end-of-ABVD PET in advanced HL carried a certain number of CNCB-proven non-malignant FDG-uptakes. The DS 4 scores which were found to have negative histology appeared to benefit from continuing the original non-intensive therapeutic plane as indicated by the successful outcome in more than 95% of them by obtaining similar 5-year PFS to the PET6-negative group. By contrast, the DS 5 score had consistently positive histology and was associated with unsuccessful conventional therapy, promptly requiring treatment intensification or innovative therapeutic approaches.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluordesoxiglucose F18/metabolismo , Glucose/metabolismo , Doença de Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Gerenciamento Clínico , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos/metabolismo , Taxa de Sobrevida , Vimblastina/administração & dosagem , Adulto Jovem
5.
Cancer Radiother ; 24(3): 206-214, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32171674

RESUMO

PURPOSE: The aim of this study was to extensively describe the epidemiological, clinical and therapeutic outcomes of adolescents and young adults (AYA) population with classical Hodgkin Lymphoma (cHL). Then, a comparison between AYAs and adults and between the subgroups of AYAs treated with the same adult protocol was accomplished to further inform on optimal therapy approach of choice for adolescent patients. MATERIAL AND METHODS: In this mono-centric, retrospective study, we reviewed the medical records. We analyzed 112 consecutive North Tunisian patients, including 66 AYAs (15 to 39 years) and 46 adults (≥40years) affected by cHL treated from 2000 to 2015 at Salah Azaiez Institute. Then, we performed a comparative analysis between AYA and 46 adult patients and a subgroup analysis between adolescents and young adults. All patients were treated according to the national protocol for HL, edited by the Tunisian Society of Hematology. The treatment included chemotherapy and involved-field radiotherapy (RT) at a dose of 20 or 30 Grays (Gy) for responders and 36Gy for non-responders. RESULTS: AYA patients presented with adverse features with nodular sclerosis subtype (p=3.88×10-02) and mediastinal mass involvement (p=9.40×10-04). At a median follow-up of 51 and 32 months for AYAs and adults, respectively, no statistical difference in terms of 3 and 5-years overall survival (OS) and event-free survival (EFS) was shown. Using the Kaplan-Meier method, in AYAs, the ABVD regimen has an impact on 3-years EFS (p=4.63×10-02). The 36Gy RT was associated with the best 3-years EFS (p=9.24×10-03). Besides, AYA patients with advanced-stage had the worst 3-years OS (76%) (p=2.41×10-02). Although the adolescents and young adults shared similar clinical presentation, we noted that the adolescent group had the worst 3-years EFS (48%), but the best 3-years OS (91%). We identified 15% of primary refractory patients and a rate of toxicity of 5.3% in AYA. CONCLUSION: The treatment approach used is well tolerated by adult patients. However, the AYA patients and particularly adolescent subgroup had more advanced disease at diagnosis and should be treated more intensively in dedicated units. RT dose<36Gy and ABVD chemotherapy were associated with lower EFS in this population.


Assuntos
Doença de Hodgkin/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Mecloretamina/administração & dosagem , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Dosagem Radioterapêutica , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Tunísia/epidemiologia , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
7.
Crit Rev Oncol Hematol ; 148: 102897, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32109715

RESUMO

Advanced classical Hodgkin lymphoma (cHL) is a rare lymphoid disease characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells. Each year, cHL accounts for 0.5% of all new cancer diagnoses and about 80% are diagnosed with advanced stage disease. Given the significant improvement in cure rates, the focus of treatment has shifted towards minimization of acute and long-term toxicities. PET-adapted strategies have largely been adopted as standard of care in the United States in an attempt to balance toxicities with adequate lymphoma control. However, the appropriate upfront chemotherapy regimen (ABVD versus eBEACOPP) remains controversial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem
8.
Blood ; 135(10): 735-742, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31945149

RESUMO

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival (PFS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2-) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2- patients aged <60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+ patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.gov as #NCT01712490 (EudraCT no. 2011-005450-60).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico
9.
Ann Hematol ; 99(2): 293-299, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897678

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Vimblastina/administração & dosagem
11.
Lancet Haematol ; 7(2): e146-e156, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31948928

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Bleomicina/administração & dosagem , Bleomicina/economia , Canadá , Análise Custo-Benefício , Ciclofosfamida/administração & dosagem , Ciclofosfamida/economia , Dacarbazina/administração & dosagem , Dacarbazina/economia , Doxorrubicina/administração & dosagem , Doxorrubicina/economia , Etoposídeo/administração & dosagem , Etoposídeo/economia , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/economia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prednisona/administração & dosagem , Prednisona/economia , Procarbazina/administração & dosagem , Procarbazina/economia , Vimblastina/administração & dosagem , Vimblastina/economia , Vincristina/administração & dosagem , Vincristina/economia
12.
Pediatr Blood Cancer ; 67(4): e28186, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31981415

RESUMO

OBJECTIVE: To describe characteristics and outcome of pediatric ovarian immature teratomas (IT) to better define the place of chemotherapy. METHODS: Children with ovarian IT enrolled in TGM95 and TGM2013 studies were analyzed. Norris grading and International Federation of Gynecology and Obstetrics staging system were used. RESULTS: Thirty-six cases were identified with a median age of 11 years (range = 1-18): 35 of 36 stage I (17 stage IA, 13 stage IC, and 5 stage IX), including seven patients with gliomatosis peritonei (GP), and 1 stage IIIB (IT peritoneal implants). Centrally reviewed Norris grading was performed in 31 cases: 14 grade I and 17 grade II/III tumors. All patients underwent upfront surgery: 19 unilateral oophorectomy, 14 unilateral adnexectomy, 2 unilateral cystectomy, and 1 bilateral cystectomy. No extensive GP surgery was performed. Six patients received adjuvant vinblastin, bleomycin, and cisplatinum because of tumor rupture (n = 5, including two patients with GP) or stage III (n = 1). After a median follow-up of 39.5 months (range = 6-238), two events occurred 10 and 11 months after diagnosis: one bilateralization (initial stage IX, grade I) and one IT peritoneal relapse (initial stage IA, grade II), respectively. Both were successfully rescued by platinum-based chemotherapy and delayed surgery. No stage IC patients treated without adjuvant chemotherapy relapsed (four grade I and three grade III). None of the seven patients with GP progressed. Five-year event-free survival and overall survival were 94% (95% CI = 81-98%) and 100%. CONCLUSIONS: The current series confirms the excellent prognosis of pediatric ovarian IT, arguing for conservative surgical approach in GP and against systematic adjuvant chemotherapy, even in ruptured tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ovarianas , Ovariectomia , Teratoma , Adolescente , Bleomicina/administração & dosagem , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , França , Humanos , Lactente , Gradação de Tumores , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Taxa de Sobrevida , Teratoma/mortalidade , Teratoma/terapia , Vimblastina/administração & dosagem
13.
Int J Clin Oncol ; 25(1): 165-174, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729625

RESUMO

BACKGROUND: The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. PATIENTS AND METHODS: Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. RESULTS: Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44-1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32-1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95-3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3-5 events, occurred less frequently with pembrolizumab. CONCLUSIONS: Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Docetaxel/administração & dosagem , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados
15.
Jpn J Clin Oncol ; 50(4): 419-424, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-31845730

RESUMO

OBJECTIVE: The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. This systematic review aims to evaluate the efficacy of low-dose chemotherapy with methotrexate and vinblastine for patients with extra-abdominal desmoid-type fibromatosis. METHODS: We searched the pertinent literature from January 1990 to August 2017. Two reviewers evaluated and screened the literature independently for eligibility and extracted data. We evaluated the quality of body of evidence and made a recommendation according to the Grading of Recommendations Development and Evaluation methodology. RESULTS: The search yielded 40 studies, 9 of which were included after the first and second screenings. There were three prospective case series but no randomized controlled trials among the nine studies. There was no case-control report (vs. no treatment). According to Response Evaluation Criteria in Solid Tumors criteria, the mean response rate (complete remission or partial response) was 36% (11-57%). Including stable disease, namely, clinical benefit was consistently as high as 85% (69-100%). Mean adverse event rate of G3 or G4 according to CTCAE was 31%. One study reported improvement of pain (87.5%) because of this chemotherapy. CONCLUSION: The efficacy of this chemotherapy was convincing. However, the overall evidence was weak, and this chemotherapy is not covered by insurance in Japan; we only weakly recommend low-dose chemotherapy with methotrexate and vinblastine in patients with extra-abdominal desmoid-type fibromatosis.


Assuntos
Abdome/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Metotrexato/uso terapêutico , Vimblastina/uso terapêutico , Adulto , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento , Vimblastina/administração & dosagem
16.
Ann Hematol ; 99(2): 277-282, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872362

RESUMO

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Transplante de Células-Tronco , Adulto , Autoenxertos , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Taxa de Sobrevida , Vimblastina/administração & dosagem
17.
Ann Hematol ; 99(2): 283-291, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872361

RESUMO

FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18-4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fluordesoxiglucose F18/administração & dosagem , Doença de Hodgkin , Tomografia por Emissão de Pósitrons , Transplante de Células-Tronco , Adulto , Autoenxertos , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Estudos Prospectivos , Taxa de Sobrevida , Vimblastina/administração & dosagem
18.
No Shinkei Geka ; 47(9): 977-984, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31564659

RESUMO

It is reported that vinblastine monotherapy has promising activity in patients with pediatric optic pathway/hypothalamic glioma(OPHG)who experienced treatment failure after initial treatment with standard chemotherapy. However, there have been no reports on vinblastine monotherapy against OPHG in Japan. Since vinblastine is an unauthorized drug under the Ministry of Health and Welfare, we used it after completing an in-hospital institutional review board application for each case. In the first case, a 6-year-old boy with recurrent OPHG with hydrocephalus was referred to our hospital. Weekly vinblastine was started at a dose of 6mg/m2 and was then reduced to 5mg/m2 and 4mg/m2 sequentially due to hematotoxicity. After 11 cycles of vinblastine, improvement in hydrocephalus was observed. After 22 cycles of vinblastine, the best response was observed, and we continued treatment up to 35 cycles. Progression of the disease was observed after 47 cycles and then we changed treatment to another regimen after 48 cycles of vinblastine. In the second case, a 6-year-old boy with chemotherapy-naïve recurrent OPHG underwent chemotherapy with vincristine and carboplatin. After 9 treatment cycles with carboplatin, hypersensitivity was observed. Subsequently, he was treated using weekly vinblastine as per the same protocol as that in our first case. A moderate response was observed after 18 cycles of vinblastine. After 48 cycles of vinblastine, the best response was observed, and we completed treatment. In both cases, severe adverse events were not observed and the treatment was well-tolerated. Vinblastine administered once per week is well-tolerated and maintains quality of life in children with OPHG.


Assuntos
Antineoplásicos Fitogênicos , Glioma , Neoplasias Hipotalâmicas , Vimblastina , Antineoplásicos Fitogênicos/administração & dosagem , Criança , Glioma/tratamento farmacológico , Humanos , Neoplasias Hipotalâmicas/tratamento farmacológico , Japão , Masculino , Qualidade de Vida , Resultado do Tratamento , Vimblastina/administração & dosagem
20.
Acta Haematol ; 142(3): 171-175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31454795

RESUMO

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.


Assuntos
Bleomicina/efeitos adversos , Doença de Hodgkin , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Fibrose Pulmonar , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Fluordesoxiglucose F18/administração & dosagem , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/diagnóstico por imagem , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos
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