RESUMO
Previous clinical trials indicate that 10%-25% of patients received genomically matched therapy after comprehensive genomic profiling (CGP) tests. However, the clinical utility of CGP tests has not been assessed in clinical practice. We assessed the clinical utility of CGP tests for advanced or metastatic solid tumor and determined the proportion of patients receiving genomically matched therapy among those with common and non-common cancers. From August 2019 to July 2020, a total of 418 patients had undergone CGP tests, and the results were discussed through the molecular tumor board at our site. The median age of patients was 57 (range: 3-86) years. Colorectal cancer was the most common, with 47 (11%) patients. Actionable genomic alterations (median 3, range: 1-17) were identified in 368 (88.0%) of 418 patients. Druggable genomic alterations were determined in 196 (46.9%) of 418 patients through the molecular tumor board. Genomically matched therapy was administered as the subsequent line of therapy in 51 (12.2%) patients, which is comparable to the proportion we previously reported in a clinical trial (13.4%) (p = 0.6919). The proportion of patients receiving genomically matched therapy was significantly higher among those with common cancers (16.2%) than non-common cancers (9.4%) (p = 0.0365). Genomically matched therapy after the CGP tests was administered to 12.2% of patients, which is similar to the proportion reported in the previous clinical trials. The clinical utility of CGP tests in patients with common cancers greatly exceeded that in patients with non-common cancers.
Assuntos
Segunda Neoplasia Primária , Neoplasias , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Genômica/métodos , Neoplasias/genética , Neoplasias/terapia , Biomarcadores Tumorais/genéticaRESUMO
This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.
Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Linfoma Folicular/mortalidade , Condicionamento Pré-Transplante/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Transplante HomólogoRESUMO
The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki-67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B-cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki-67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression-free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki-67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes.
Assuntos
Transformação Celular Neoplásica , Antígeno Ki-67/metabolismo , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Regras de Decisão Clínica , Feminino , Humanos , Linfoma Folicular/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
Neuroendocrine tumors (NET) are rare tumors for which somatostatin analogs (SSA) are used not only for symptom control due to a functioning tumor, but also for the disease control of unresectable NET. The efficacy of SSA for midgut NET has been verified by previous studies, but insufficient evidence exists for SSA treatment of NET in the foregut and hindgut (F/H-NET). The aim of this retrospective study was to evaluate the efficacy of SSA for unresectable F/H-NET. Patients with unresectable F/H-NET treated with SSA between February 2011 and August 2017 at our hospital were retrospectively reviewed. Parameters of efficacy were progression-free survival (PFS), overall survival, objective response rate (ORR), and adverse events. Twelve cases with unresectable F/H-NET were extracted from our database. With a median follow-up time of 25.9 months, the median PFS was 13.6 months. Two- and 3-year survival rates were 87.5 and 62.5%, respectively. The ORR was 8.3%, and the disease control rate was 75%. Serious adverse events were not observed. Subgroup analysis, including G1/G2, and hepatic tumor load, which is the volume of NET liver metastases, did not reveal a difference in PFS. The efficacy and safety of SSA for F/H-NET seemed similar to that found in the PROMID study, highlighting its relevance for the treatment of this disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Gastrointestinais/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Tumores Neuroendócrinos/mortalidade , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Feminino , Seguimentos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Peptídeos Cíclicos/administração & dosagem , Prognóstico , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/análogos & derivados , Taxa de SobrevidaAssuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Par 22 , Leucemia Megacarioblástica Aguda , Neoplasias Embrionárias de Células Germinativas , Segunda Neoplasia Primária , Proteínas de Fusão Oncogênica , Neoplasias Retroperitoneais , Translocação Genética , Adulto , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 1/metabolismo , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 22/metabolismo , Humanos , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/metabolismo , Leucemia Megacarioblástica Aguda/patologia , Masculino , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias Retroperitoneais/genética , Neoplasias Retroperitoneais/metabolismo , Neoplasias Retroperitoneais/patologiaRESUMO
Purpose: To determine a recommended dose of liposomal eribulin (E7389-LF) in combination with nivolumab in patients with advanced solid tumors, and to evaluate the safety, efficacy, pharmacokinetics, and biomarker impact of this regimen. Experimental Design: Japanese patients with advanced, nonresectable, or recurrent solid tumors and no existing alternative standard/effective therapy (except nivolumab monotherapy) were assigned to either E7389-LF 1.7 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 1.1 mg/m2 plus nivolumab 240 mg every 2 weeks, or E7389-LF 1.4 mg/m2 plus nivolumab 240 mg every 2 weeks. Primary objectives were to evaluate the safety/tolerability of each dose cohort and to determine the recommended phase II dose (RP2D). Secondary/exploratory objectives, including safety [dose-limiting toxicities (DLT) and adverse events (AE)], pharmacokinetics, efficacy [including objective response rate (ORR)], and biomarker results were used in determining the RP2D. Results: Twenty-five patients were enrolled to treatment [E7389-LF 1.7 mg/mg2 every 3 weeks (n = 6), E7389-LF 2.1 mg/m2 every 3 weeks (n = 6), E7389-LF 1.1 mg/m2 every 2 weeks (n = 7), E7389-LF 1.4 mg/m2 every 2 weeks (n = 6)]. Twenty-four patients were evaluated for DLTs, of whom 3 had DLTs (1 at E7389-LF 1.7 mg/m2 every 3 weeks, 1 at 1.1 mg/m2 every 2 weeks, and 1 at 1.4 mg/m2 every 2 weeks). All patients had ≥1 treatment-related treatment-emergent AE (TEAE); 68.0% had ≥1 grade 3-4 treatment-related TEAE. Changes in vasculature and IFN-related biomarkers were seen in each cohort. The overall ORR was 16%. Conclusions: E7389-LF plus nivolumab was tolerable overall; the recommended dose for future study was 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks. Significance: This phase Ib part of a phase Ib/II study assessed the tolerability and activity of a liposomal formulation of eribulin (E7389-LF) plus nivolumab in 25 patients with advanced solid tumors. The combination was tolerable overall; 4 patients had a partial response. Vasculature and immune-related biomarker levels increased, suggesting vascular remodeling.
Assuntos
Neoplasias , Alcaloides de Vinca , Humanos , Furanos/efeitos adversos , Cetonas/efeitos adversos , Lipossomos , Neoplasias/tratamento farmacológico , Nivolumabe/efeitos adversosRESUMO
Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low-tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow-up from the first progression was 79.8 months (range, 2.1-227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4-30.2), and 76.5% (95% CI, 68.0-84.1) of the patients subsequently underwent the second-line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6-94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4-38.8) (HR, 2.13; 95% CI, 1.48-3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first-line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7-NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0-25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes.
Assuntos
Linfoma Folicular , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Coortes , Humanos , Incidência , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Conduta ExpectanteRESUMO
Most patients with IgA deficiency are asymptomatic, but duodenal nodular lymphoid hyperplasia is one symptom known to be associated with common variable immunodeficiency (CVID), including selective IgA deficiency and agammaglobulinemia.
RESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common histological transformation (HT) of follicular lymphoma (FL). Other types of HT are very rare, and their incidence, histopathology, and patient outcomes have not been sufficiently described. Here, we assessed the clinicopathological characteristics of 19 cases of non-DLBCL HT of FL in a single institution in Japan to advance the understanding of the disease. Among 889 consecutive patients diagnosed with FL between 2000 and 2018, 191 suffered HT (21%). The median follow-up period was 94 months (range = 3-225). A total of 172 patients (90%) had DLBCL transformation, whereas the remaining 19 patients (10%) exhibited non-DLBCL transformation. In the latter cases, the following diagnoses were made based on morphology, immunohistochemistry, flow cytometry, and fluorescence in situ hybridization analyses: classic Hodgkin lymphoma (7 patients; 4%); high-grade B-cell lymphoma (HGBL) with MYC and BCL2 rearrangements (4 patients; 2%); HGBL, not otherwise specified (4 patients; 2%); B-cell lymphoblastic leukemia/lymphoma (2 patients; 1%); anaplastic large-cell lymphoma-like lymphoma (1 patient; 0.5%); and plasmablastic lymphoma (1 patient; 0.5%). Epstein-Barr virus-encoded RNA-1 did not associate with HT in any of the cases tested (n = 8). Patients with non-DLBCL transformation showed poor outcomes, with a median overall survival of 13 months (range = 2 days-107 months); 10 of the patients (53%) died of HT. In conclusions, non-DLBCL transformation was observed in 10% of patients with HT from FL. Our data show that timely, accurate, and comprehensive histopathological diagnosis is needed to ensure optimal treatment and improve the outcome of these patients.
Assuntos
Transformação Celular Neoplásica/patologia , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Adrenal insufficiency (AI) is an immune-related adverse event of immune checkpoint inhibitors and on occasion could be serious. There have been few reports of clinical information regarding AI associated with anti-programmed cell death protein-1 (anti-PD-1) antibody in non-small-cell lung cancer (NSCLC) patients. Patients with advanced NSCLC treated with anti-PD-1 antibodies between December 2015 and October 2017 were identified from the medical records of our institution. We investigated the frequency, symptoms, test results, and treatment outcomes of AI, and prognosis of patients who developed AI. In total, 282 NSCLC patients were treated with anti-PD-1 antibodies, and 4 patients (1.4%) were diagnosed as AI and 6 patients (2.1%) as suspicious of AI according to the laboratory data or clinical findings. The median follow-up period was 13.6 months. All patients with AI and suspicious of AI were treated with corticosteroid replacement, and performance status (PS) was improved in 50% of patients. Two of 10 patients were thought to have central AI. Six patients of 10 patients continued to receive anti-PD-1 antibodies with corticosteroid hormone replacement after diagnosis. The median progression-free survival and overall survival were 10.2 and 15.4 months, respectively. In conclusion, the incidence of AI among NSCLC patients treated with anti-PD-1 antibodies was similar to previous studies. Corticosteroid replacement improved PS, symptoms, and laboratory data of patients with AI and suspicious of AI. Corticosteroid replacement may contribute to continuation of anti-PD-1 antibodies and survival outcome was preferable in patients with AI and suspicious of AI receiving corticosteroid treatment.
Assuntos
Insuficiência Adrenal/induzido quimicamente , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/epidemiologia , Adulto , Idoso , Feminino , Glucocorticoides/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Although some patients with COVID-19 develop only mild symptoms, fatal complications have been observed among those with comorbidities. As patients with cancer are immunocompromised, they are thought to have a high risk of severe illness associated with COVID-19. We report a COVID-19 patient with adult T-cell leukemia-lymphoma (ATL) who was treated using favipiravir. A 69-year-old woman with lymphoma-type ATL was treated using cyclophosphamide, doxorubicin, vincristine, prednisolone and mogamulizumab (M-CHOP) with substantial efficacy. However, in cycle 4 of M-CHOP therapy, she developed fever with mild cough. The patient was admitted to the hospital and CT revealed bilateral ground-glass opacities. SARS-CoV-2 was detected by RT-PCR and the patient was diagnosed with COVID-19. Considering severe immunosuppression caused by ATL, we initiated favipiravir therapy. Subsequently, the fever improved without antipyretics and her C-reactive protein level decreased rapidly. SARS-CoV-2 PCR tests were negative on days 17 and 18 of favipiravir therapy, and the patient was discharged without residual disease on the final CT. This is the first documented case of COVID-19 in a patient with ATL. Although severe immunosuppression caused by ATL was present, severe COVID-19 pneumonia did not develop. The immunosuppressed condition caused by hematological malignancy may not always be a risk factor for severe illness associated with COVID-19. Further accumulation of data regarding COVID-19 in patients with hematological malignancies is warranted to clarify the risk factors for severe illness, the best-in-class antiviral agent, and the optimal treatment strategy in this population.
Assuntos
COVID-19/complicações , Leucemia-Linfoma de Células T do Adulto/virologia , Idoso , COVID-19/patologia , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/patologiaRESUMO
Cases with thrombi in multiple cardiac chambers are rare. We report an extremely rare case in which thrombi were formed in all four cardiac chambers at the same time. A 55-year-old man presented with biventricular failure and liver dysfunction. A 12-lead ECG and an echocardiogram revealed an old anteroseptal myocardial infarction with aneurysm formation and atrial flutter. A transesophageal echocardiogram and a CT of the chest revealed thrombi in the right and left atrial appendage, right ventricular apex and left ventricular aneurysm. Pulmonary emboli were also identified. Stasis of the blood due to ventricular dysfunction and atrial flutter was considered to be responsible. The patient died of multiorgan failure due to circulatory failure.