Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.031
Filtrar
1.
J Hematol Oncol ; 14(1): 164, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641926

RESUMO

Peritoneal dissemination (PD) is a major type of gastric cancer (GC) recurrence and leads to rapid death. Current approaches cannot precisely determine which patients are at high risk of PD to provide early intervention. In this study, we developed a technology to detect minimal residual cancer cells in peritoneal lavage fluid (PLF) samples with a personalized assay profiling tumor-specific mutations. In a prospective cohort of 104 GC patients, the technology detected all the cases that developed PD with 100% sensitivity and 85% specificity. The minimal residual cancer cells in PLF were associated with a significantly increased risk of PD (HR = 145.13; 95% CI 20.20-18,435.79; p < 0.001), which was the strongest independent predictor over pathologic diagnosis and cytological diagnosis. In pathologically high-risk (pT4) patients, the PLF mutation profiling model exhibited a greater specificity of 91% and a positive predictive value of 88% while retaining a sensitivity of 100%. This approach may help in the postsurgical management of GC patients by detecting PD far before metastatic lesions grow to a significant size detectable by conventional methods such as MRI and CT scanning.


Assuntos
Neoplasia Residual/patologia , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Humanos , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/patologia , Neoplasia Residual/diagnóstico , Lavagem Peritoneal , Neoplasias Peritoneais/diagnóstico , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico
2.
BMC Cancer ; 21(1): 878, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332566

RESUMO

BACKGROUND: Patterns of failure after treatment of oral and squamous cell carcinomas (OSCC) are diversified, with recurrences being one of the common causes. A special group of patients are sometimes encountered in the outpatient clinic for improper or insufficient initial treatment with reports of positive margins, implying residual/persistent diseases. The question of whether these patients can be surgically salvaged remain unanswered. METHODS: A retrospective study was performed between January 2013 and December 2017 for patients with residual or rapid recurrent (within 3 months) OSCCs, who received salvage surgeries in our institution. The patients with residual/persistent OSCCs were those with microscopic or macroscopic positive surgical margins, while those with rapid recurrent OSCCs were those with close or negative margins, but unabated painful symptoms right after treatment. Both clinicopathological and prognostic variables were analyzed. The focus was also directed towards lessons for possible initial mistakes, resulting in these residual/persistent diseases. RESULTS: Of 103 patients, 68 (66%) were men, with mean age of 56.3 years. The overall survival reached 60.2%. Regarding the primary OSCC status, most of our patients (n = 75, 72.8%) were diagnosed with ycT2-3 stages. Besides, most patients were found with macroscopic residual diseases (52.4%) before our salvage surgery. The sizes of the residual/persistent OSCCs were generally under 4 cm (87.3%) with minimally residual in 21 (20.4%). Among all the variables, primary T stage (p = 0.003), and residual lesion size (p < 0.001) were significantly associated with the prognosis in multivariate analysis. Though the causes for the initial surgical failure were multifactorial, most were stemmed from poor planning and unstandardized execution. CONCLUSIONS: Cases with residual/persistent OSCCs were mostly due to mistakes which could have been avoided under well-round treatment plans and careful surgical practice. Salvage surgery for cases with smaller residual/persistent OSCCs is still feasible with acceptable outcomes.


Assuntos
Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Neoplasia Residual/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Encaminhamento e Consulta , Estudos Retrospectivos , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Falha de Tratamento , Resultado do Tratamento
3.
Sci Rep ; 11(1): 15840, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349149

RESUMO

B-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Células-Tronco Mesenquimais/patologia , Neoplasia Residual/patologia , Osteoblastos/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Transcriptoma , Técnicas de Cocultura , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/genética , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , RNA-Seq
4.
J Laryngol Otol ; 135(9): 785-790, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34238396

RESUMO

BACKGROUND: There is controversy regarding management of the neck at salvage laryngectomy. The aim of this study was to perform an analysis to determine the incidence of occult node positivity in this group and analyse factors affecting it. METHOD: A retrospective analysis of 171 patients who underwent salvage total laryngectomy between 2000 and 2015 for recurrent or residual disease following definitive non-surgical treatment and were clinico-radiologically node negative at the time salvage laryngectomy was carried out. RESULTS: A total of 171 patients with laryngeal or hypopharyngeal cancers underwent concurrent neck dissection at laryngectomy. There were 162 patients (94.7 per cent) who underwent bilateral neck dissection, and 9 patients (5.3 per cent) who underwent ipsilateral neck dissection. The occult lateral nodal metastasis rate was 10.5 per cent. Of various factors, initial node positive disease was the only factor predicting occult metastasis on univariable and multivariable analysis (p = 0.001). CONCLUSION: Risk of occult metastasis is high in patients who have node positive disease before starting radiotherapy. This group should be offered elective neck dissection.


Assuntos
Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Esvaziamento Cervical/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Laríngeas/patologia , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Pescoço/cirurgia , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento
5.
PLoS One ; 16(7): e0253998, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34283862

RESUMO

OBJECTIVE: This paper searches an ideal cone height for stage definition and safe treatment of cervical microinvasive squamous carcinoma stage IA1 (MIC IA1), avoiding excessive cervix resection, favoring a future pregnancy. METHODS: A retrospective study was performed involving 562 women with MIC IA1, from 1985 to 2013, evaluating cone margin involvement, depth of stromal invasion, lymph vascular invasion, conization height, and residual uterine disease (RD). High-grade squamous lesions or worse detection was considered recurrence. Univariate and multivariate regression analyses were performed, including age, conization technique (CKC, cold-knife, or ETZ, excision of transformation zone), and pathological results. Conization height to provide negative margins and the risk of residual disease were analyzed. RESULTS: Conization was indicated by biopsy CIN2/3 in 293 cases. Definitive treatments were hysterectomy (69.8%), CKC (20.5%), and ETZ (9.7%). Recurrence rate was 5.5%, more frequent in older women (p = 0.030), and less frequent in the hysterectomy group (p = 0.023). Age ≥40 years, ETZ and conization height are independent risk factors for margin involvement. For ages <40 years, 10 mm cone height was associated with 68.6% Negative Predictive Value (NPV) for positive margins, while for 15 mm and 25 mm, the NPV was 75.8% and 96.2%, respectively. With negative margins, the NPV for RD varied from 85.7-92.3% for up to 24 mm cone height and 100% from 25 mm. CONCLUSION: Conization 10 mm height for women <40 years provided adequate staging for almost 70%, with 10% of RD and few recurrences. A personalized cone height and staging associated with conservative treatment are recommended.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasia Intraepitelial Cervical/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Conização/métodos , Tratamento Conservador , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
6.
Taiwan J Obstet Gynecol ; 60(4): 718-722, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34247813

RESUMO

OBJECTIVE: To evaluate the efficacy and superiority of loop electrosurgical excision procedure (LEEP) in managing stage IA1 cervical microinvasive squamous cell carcinoma (MISCC) without lymph-vascular space invasion (LVSI). MATERIALS AND METHODS: The oncological and reproductive outcomes of a series of patients affected by stage IA1 MISCC without LVSI, initially treated by LEEP between February 2006 and December 2017, were retrospectively reviewed. RESULTS: Ultimately, 109 patients were included. The mean age at diagnosis was 35.4 years old, and 36 patients were nulliparous. Multifocal lesions were identified in 15 patients (13.8%). The mean cone depth was 17.4 mm. Resection margins were positive/unevaluable and negative in 26 (23.9%) and 83 (76.1%) cases, respectively. Among cases undergoing salvage treatments, the residual disease rate for patients with positive/unevaluable margins was significantly higher than those with negative margins (P = 0.003). During the follow-up period of 43.0 ± 28.9 months, no relapse was identified. Fifteen of 20 patients (75.0%) conceived successfully, with a full-term live birth rate of 93.3%. CONCLUSIONS: For stage IA1 MISCC without LVSI unexpectedly found in a loop excision, initial LEEP with clear margin is efficient and adequate. For cases with multifocal MISCC, or for those young patients who wish to become pregnant in the future, LEEP is the optimal choice.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Eletrocirurgia/métodos , Neoplasias do Colo do Útero/cirurgia , Adulto , Carcinoma de Células Escamosas/patologia , Feminino , Preservação da Fertilidade/métodos , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
7.
Leuk Res ; 108: 106605, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34090063

RESUMO

Some studies have elucidated that Minimal residual disease (MRD) in patient with Mantle Cell Lymphoma (MCL) was a significant prognostic factor, with potential value in assessing overall survival (OS) and progression-free survival (PFS). However, most studies were widely varied in included population, sample sources and MRD detection time points. Some studies even have conflicting results. In view of this, a meta-analysis was performed to evaluate association of MRD levels with clinical outcomes in patients with MCL. We identified 7 included articles, which were published in recent 20 years. Then, we extracted or calculated hazard ratios (HRs) and their 95 % confidence intervals (CIs). Our results reveal that patients with MRD negativity have improved OS (HR = 0.63; 95 % CI: 0.50-0.79) and PFS (HR = 0.40, 95 % CI: 0.21-0.76), comparing with patients with MRD positivity. There are also consistent results in subgroups based on sample sources and MRD detection time points. Our study also demonstrates that MRD level is a strong prognostic factor of clinical outcomes. Thus, MRD is expected to be an effective clinical indicator for assessing prognosis and guide treatment decisions in MCL patients.


Assuntos
Linfoma de Célula do Manto/mortalidade , Neoplasia Residual/mortalidade , Humanos , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Prognóstico , Resultado do Tratamento
8.
Sci Rep ; 11(1): 10112, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980938

RESUMO

This study aimed to evaluate the predictions of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prognosis of triple-negative breast cancer (TNBC), especially with residual disease (RD) after preoperative chemotherapy. This retrospective analysis included 74 TNBC patients who received preoperative chemotherapy. DCE-MRI findings from three timepoints were examined: at diagnosis (MRIpre), at midpoint (MRImid) and after chemotherapy (MRIpost). These findings included cancer lesion size, washout index (WI) as a kinetic parameter using the difference in signal intensity between early and delayed phases, and time-signal intensity curve types. Distant disease-free survival was analysed using the log-rank test to compare RD group with and without a fast-washout curve. The diagnostic performance of DCE-MRI findings, including positive predictive value (PPV) for pathological responses, was also calculated. RD without fast washout curve was a significantly better prognostic factor, both at MRImid and MRIpost (hazard ratio = 0.092, 0.098, p < 0.05). PPV for pathological complete remission at MRImid was 76.7% by the cut-off point at negative WI value or lesion size = 0, and 66.7% at lesion size = 0. WI and curve types derived from DCE-MRI at the midpoint of preoperative chemotherapy can help not only assess tumour response but also predict prognosis.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasia Residual/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Idoso , Antineoplásicos/uso terapêutico , Meios de Contraste/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Cinética , Imageamento por Ressonância Magnética/instrumentação , Pessoa de Meia-Idade , Neoplasia Residual/química , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
11.
Blood ; 138(1): 11-22, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-33827116

RESUMO

ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We report the phase 1 results. After fludarabine-cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2 × 106, 1 × 106, or 0.5 × 106 cells per kg. The rate of dose-limiting toxicities (DLTs) within 28 days after KTE-X19 infusion was the primary end point. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age, 46 years; range, 18-77 years). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 31% and 38% of patients, respectively. To optimize the risk-benefit ratio, revised adverse event (AE) management for CRS and NEs (earlier steroid use for NEs and tocilizumab only for CRS) was evaluated at 1 × 106 cells per kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NEs, with no grade 4 or 5 NEs. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1 × 106 cells per kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At a median follow-up of 22.1 months (range, 7.1-36.1 months), the median duration of remission was 17.6 months (95% confidence interval [CI], 5.8-17.6 months) in patients treated with 1 × 106 cells per kg and 14.5 months (95% CI, 5.8-18.1 months) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1 × 106 cells per kg with revised AE management. This trial is registered at www.clinicaltrials.gov as #NCT02614066.


Assuntos
Antígenos CD19/metabolismo , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Síndrome da Liberação de Citocina/induzido quimicamente , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Resultado do Tratamento , Adulto Jovem
12.
Sci Rep ; 11(1): 9056, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907236

RESUMO

For residual N1 nodal disease following neoadjuvant chemotherapy (NAC) for patients with breast cancer, the optimal local therapy for axilla is an evolving area. We analyzed the long-term results of these patients according to axillary surgical methods using propensity score matching (PSM) to clarify whether omission of axillary lymph node dissection (ALND) is oncologically safe. This was a single institution retrospective study of patients with ypN1 from Asan Medical Center (AMC). We included 324 patients who had undergone axillary surgery with either sentinel lymph node biopsy (SLNB) only or ALND. The patients received NAC at AMC between 2008 and 2013. General indications for ALND included prominent nodes detected clinically before NAC, evident macrometastasis on multiple nodes during SLNB. Patients who had either micrometastasis or macrometastasis in 1 or 2 node(s) were included. SLNB was performed for patients with good responders to NAC with limited nodal burden. Patients were matched for baseline characteristics. After matching, we included 98 patients in each SLNB only group and ALND group respectively. We compared axillary recurrence-free survival (ARFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-free survival (BCSS) according to the surgical method. The median follow-up period was 71 months. Univariate and multivariate analyses revealed no statistically significant differences between the two groups for ARFS, DMFS, OS, and BCSS. After the propensity score matching, no significant statistical differences were observed in 5-year ARFS, DMFS, OS, and BCSS between the SLNB only group and ALND group. SLNB might be a possible option for ALND in patients with breast cancer who have limited axillary node metastasis after NAC without compromising survival outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Excisão de Linfonodo/mortalidade , Linfonodos/cirurgia , Terapia Neoadjuvante/mortalidade , Neoplasia Residual/cirurgia , Biópsia de Linfonodo Sentinela/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Leuk Res ; 105: 106578, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33892341

RESUMO

BACKGROUND: Molecular response (MR) 4.0 or 4.3 remains an indicator of treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in countries that accept it as the criterion of undetectable minimal residual disease (UMRD) in clinical practice. We retrospectively analyzed the TFR outcomes to identify the clinical efficacy of MR4.0/4.3 as the UMRD criterion. PATIENTS AND METHODS: CML patients treated with tyrosine kinase inhibitors (TKIs) between March 2001 and May 2015 for >3 years and treatment cessation for over 6 months were included. TFR was analyzed using MR3.0 loss and UMRD loss as criteria. TFR failure-free survival was defined as the time from cessation of TKI therapy to MR loss or restarting TKI, and overall survival as the time from TKI cessation to death. The probability of regaining the MR was evaluated. RESULTS: In the 93 participants, the median duration of follow-up and TKI therapy were 17.3 (3.9-92.0) months and 7.4 (3.1-16.9) years, respectively. TFR at 5 years was 47.9 % and 44.4 %, for MR3.0 loss and UMRD loss, respectively. Among the 42 patients who restarted TKI, 41 regained MR3.0 (97.6 %). In multivariate analysis, the time to UMRD was ≤12 months, and the absence of prior TKI treatment (P = 0.018 and 0.044 in UMRD loss, respectively) was significantly correlated with TFR failure-free survival. CONCLUSION: Clinical outcomes were comparable to those of clinical trials. Our results suggest that the detection limit of MR4.3 can be used in clinical practice for TKI treatment cessation for TFR in CML patients.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Limite de Detecção , Neoplasia Residual/patologia , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Indução de Remissão , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Blood ; 138(2): 113-121, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33827114

RESUMO

Bortezomib, lenalidomide, and dexamethasone plus transplant is a standard of care for eligible patients with multiple myeloma. Because responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed. In this phase 2 study, patients received eight 28-day cycles of carfilzomib (K) 20/36 mg/m2 (days 1-2, 8-9, 15-16), lenalidomide (R) 25 mg (days 1-21), and dexamethasone (d) 20 mg (days 1-2, 8-9, 15-16, 22-23). All patients proceeded to transplant after 4 cycles and received 1 year of lenalidomide maintenance (10 mg, days 1-21). The primary objective was stringent complete response at the completion of consolidation. Overall, 48 patients were screened and 46 enrolled; 21% had adverse cytogenetics. Among 42 evaluable patients after consolidation, 26 were in stringent complete response (CR; 61.9%), 27 were at least in CR (64.3%): 92.6% had undetectable minimal residual disease according to flow cytometry (≥2.5 × 10-5) and 63.0% according to next-generation sequencing (10-6). Median time to CR was 10.6 months. According to multiparametric flow cytometry and next-generation sequencing, 69.0% and 66.7% of patients, respectively, had undetectable minimal residual disease at some point. With a median follow-up of 60.5 months, 21 patients progressed, and 10 died (7 of multiple myeloma). Median progression-free survival was 56.4 months. There were no KRd-related deaths. Four patients discontinued the program due to toxicities; 56 serious adverse events were reported in 31 patients, including 8 cardiovascular events (2 heart failures, 5 pulmonary embolisms or deep vein thrombosis). Common grade 3/4 adverse events were hematologic (74%) and infectious (22%). In summary, 8 cycles of KRd produce fast and deep responses in transplant-eligible patients with newly diagnosed multiple myeloma. The safety profile is acceptable, but cardiovascular adverse events should be closely monitored. This clinical trial is registered at www.clinicaltrials.gov as #NCT02405364.


Assuntos
Dexametasona/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Terapia Combinada , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Oligopeptídeos/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
15.
World Neurosurg ; 151: e466-e471, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33895370

RESUMO

BACKGROUND: Surgical strategy in vestibular schwannomas may require subtotal resection to preserve neurologic function. Residual tumor growth pattern and contrast enhancement in the immediate postresection period remain uncertain. We sought to evaluate changes in the enhancement pattern and volume of vestibular schwannomas after subtotal resection in the immediate postoperative period. METHODS: Volumetric analysis of tumor size and enhancement patterns of vestibular schwannomas were measured on magnetic resonance imaging (MRI) scans obtained within 3 days of surgery, 3 months after surgery, and 1 year after surgery. RESULTS: Nineteen patients were eligible for inclusion in the study (9 male and 10 female) with an average age of 47 years. Contrast enhancement was absent in 6 of 19 (32%) of cases on the immediate postresection MRI with return of expected enhancement on subsequent studies. Volumetric analysis identified that tumors decreased in size by an average of 35% in the first 3 months (P = 0.025) after resection and 46% in the first year after resection (P < 0.01). CONCLUSIONS: Vestibular schwannomas that undergo subtotal resection tend to decrease in size over the first 3 months after resection. Residual tumor volume may fail to enhance on the immediate postresection MRI. Both of these findings could lead surgeons to misinterpret degree of resection after surgery and have implications for clinical decision making and research reporting in the scientific literature for vestibular schwannomas after subtotal resection.


Assuntos
Neoplasia Residual/diagnóstico por imagem , Neoplasia Residual/patologia , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/patologia , Neuroma Acústico/cirurgia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
16.
J Korean Med Sci ; 36(16): e102, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33904259

RESUMO

BACKGROUND: Intended subtotal resection (STR) followed by adjuvant gamma knife radiosurgery (GKRS) has emerged as an effective treatment option for facial nerve (FN) preservation in vestibular schwannomas (VSs). This study aimed to identify the optimal cut-off volume of residual VS to predict favorable outcomes in terms of both tumor control and FN preservation. METHODS: This retrospective study assessed the patients who underwent adjuvant GKRS for residual VS after microsurgery. A total of 68 patients who had been followed up for ≥ 24 months after GKRS were included. Tumor progression was defined as an increase in tumor volume (TV) of ≥ 20%. House-Brackmann grades I and II were considered to indicate good FN function. RESULTS: The median residual TV was 2.5 cm³ (range: 0.3-27.4). The median follow-up period after the first adjuvant GKRS was 64 months (range: 25.7-152.4). Eight (12%) patients showed tumor progression. In multivariate analyses, residual TV was associated with tumor progression (P = 0.003; hazard ratio [HR], 1.229; 95% confidence interval [CI], 1.075-1.405). A residual TV of 6.4 cm³ was identified as the cut-off volume for showing the greatest difference in progression-free survival (PFS). The 5-year PFS rates in the group with residual TVs of < 6.4 cm³ (54 patients) and that with residual TVs of ≥ 6.4 cm³ (14 patients) were 93.3% and 69.3%, respectively (P = 0.014). A good FN outcome was achieved in 57 (84%) patients. Residual TV was not associated with good FN function during the immediate postoperative period (P = 0.695; odds ratio [OR], 1.024; 95% CI, 0.908-1.156) or at the last follow-up (P = 0.755; OR, 0.980; 95% CI, 0.866-1.110). CONCLUSION: In this study, residual TV was associated with tumor progression in VS after adjuvant GKRS following STR. As preservation of FN function is not correlated with the extent of resection, optimal volume reduction is imperative to achieve long-term tumor control. Our findings will help surgeons predict the prognosis of residual VS after FN-preserving surgery.


Assuntos
Doenças do Nervo Facial/epidemiologia , Nervo Facial/cirurgia , Neoplasia Residual/epidemiologia , Neuroma Acústico/cirurgia , Procedimentos Neurocirúrgicos/métodos , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Nervo Facial/patologia , Doenças do Nervo Facial/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Procedimentos Neurocirúrgicos/efeitos adversos , Tratamentos com Preservação do Órgão , Radiocirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Pediatr Blood Cancer ; 68(6): e28982, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33687135

RESUMO

In anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK+ ALCL), positive minimal residual disease (MRD+) after the first chemotherapy course was proven of strong prognostic significance. We aimed to validate these results in 138 French patients. Eighty-seven patients had a detectable minimal disseminated disease at diagnosis (MDD+). Early MRD assessment was performed in 33 of 87 patients and was positive in 18 and negative in 15 (MRD-). Three-year progression-free survival was significantly correlated with the MDD/MRD status: 81.1% in MDD-, 69.6% in MDD+/MRD-, and 15.2% in MDD+/MRD+ patients. In conclusion, we confirmed on an independent cohort that the MDD/MRD status has strong prognosis significance in ALK+ ALCL.


Assuntos
Quinase do Linfoma Anaplásico/metabolismo , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Neoplasia Residual/patologia , Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Humanos , Linfoma Anaplásico de Células Grandes/genética , Intervalo Livre de Progressão
18.
Expert Rev Anticancer Ther ; 21(4): 451-459, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33706635

RESUMO

Introduction: A systematic review was performed to assess the prognostic value of Measurable Residual Disease (MRD) during treatment, for relapse and overall survival in pediatric acute myeloid leukemia (AML).Areas covered: A systematic search of available literature was performed to identify original full-text articles concerning MRD as prognostic for relapse and survival in pediatric AML. Thirteen studies were included, and in all studies, MRD positivity during treatment was associated with worse clinical outcome. MRD positivity was significantly associated with a higher probability of relapse in eleven studies. However, MRD negativity does not exclude the possibility of relapse in pediatric AML, while positivity early during therapy does not exclude cure.Expert opinion: MRD positivity during treatment has emerged as the most powerful prognostic factor in pediatric AML concerning relapse and overall survival and is useful for risk-group adapted treatment. Future studies should identify the optimal time-point(s) for MRD measurements and the optimal technique, to further improve its prognostic significance.


Assuntos
Leucemia Mieloide Aguda/patologia , Neoplasia Residual/patologia , Criança , Humanos , Prognóstico , Recidiva , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
19.
Leukemia ; 35(6): 1529-1538, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33758317

RESUMO

Several methodologies that rely on the detection of immunophenotypic or molecular abnormalities of the neoplastic cells are now available to quantify measurable ("minimal") residual disease (MRD) in acute myeloid leukemia (AML). Although the perfect MRD test does not (yet) exist, the strong association between MRD and adverse patient outcomes has provided the impetus to use measures of MRD as biomarker in the routine care of AML patients and during clinical trials. MRD test results may inform the selection of postremission therapy in some patients but evidence supporting the use of MRD as predictive biomarker is still limited. Several retrospective studies have shown that conversion from undetectable to detectable MRD or increasing MRD over time is associated with overt disease recurrence, and MRD testing may therefore be valuable as a monitoring biomarker for early detection of relapse. Interpreting serial MRD data is complex, with open questions regarding the optimal timing and frequency of testing, as well as the identification of test-specific thresholds to define relapse. Importantly, it is unknown whether intervening at the time of MRD detection, rather than at overt disease recurrence, improves outcomes. Finally, using MRD as a surrogate efficacy-response biomarker to accelerate drug development/approval has already been accepted by regulatory authorities in other diseases and is of great interest as a potential strategy in AML. While the prognostic value of MRD in AML is well established, data from prospective clinical trials confirming that treatment effects on MRD directly relate to clinical outcomes are needed to further establish the role of MRD as a surrogate endpoint in AML.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Modelos Teóricos , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/patologia , Medição de Risco/métodos , Terapia Combinada , Humanos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia
20.
Medicine (Baltimore) ; 100(8): e24555, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663063

RESUMO

ABSTRACT: Some nasopharyngeal carcinoma (NPC) patients may present convincing radiological evidence mimicking residual or recurrent tumor after radiotherapy. However, by means of biopsies and long term follow-up, the radiologically diagnosed residuals/recurrences are not always what they appear to be. We report our experience on this "phantom tumor" phenomenon. This may help to avoid the unnecessary and devastating re-irradiation subsequent to the incorrect diagnosis.In this longitudinal cohort study, we collected 19 patients of image-based diagnosis of residual/recurrent NPC during the period from Feb, 2010 to Nov. 2016, and then observed them until June, 2019. They were subsequently confirmed to have no residual/recurrent lesions by histological or clinical measures. Image findings and pathological features were analyzed.Six patients showed residual tumors after completion of radiotherapy and 13 were radiologically diagnosed to have recurrences based on magnetic resonance imaging (MRI) criteria 6 to 206 months after radiotherapy. There were 3 types of image patterns: extensive recurrent skull base lesions (10/19); a persistent or residual primary lesion (3/19); lesions both in the nasopharynx and skull base (6/19). Fourteen patients had biopsy of the lesions. The histological diagnoses included necrosis/ inflammation in 10 (52.7%), granulation tissue with inflammation in 2, and reactive epithelial cell in 1. Five patients had no pathological proof and were judged to have no real recurrence/residual tumor based on the absence of detectable plasma EB virus DNA and subjective judgment. These 5 patients have remained well after an interval of 38-121 months without anti-cancer treatments.Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be unreliable. False positivity, the "phantom tumor phenomenon", is not uncommon in post-radiotherapy MRI. This is particularly true if the images show extensive skull base involvement at 5 years or more after completion of radiotherapy. MRI findings compatible with NPC features must be treated as a real threat until proved otherwise. However, the balance between under- and over-diagnosis must be carefully sought. Without a pathological confirmation, the diagnosis of residual or recurrent NPC must be made taking into account physical examination results, endoscopic findings and Epstein-Barr virus viral load. A subjective medical judgment is needed based on clinical and laboratory data and the unique anatomic complexities of the nasopharynx.


Assuntos
Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Herpesvirus Humano 4/genética , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...