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BACKGROUND: Comprehensive genomic profiling (CGP) provides new opportunities for patients with advanced cancer to receive genome-matched therapies, but the availability rate of these remains low. We reviewed our CGP cases and suggested possible strategies to improve the current status from a clinical perspective. METHODS: Druggable genomic alterations and barriers to accessing genome-matched therapies were investigated in 653 patients with 30 various types of cancers who underwent CGP. RESULTS: While the availability rate of genome-matched therapies as a whole was 9.5%, CGP was useful in some cancer types. Patients with thyroid cancer and lung cancer harbored druggable genomic alterations at high rates, while sarcoma rarely harbored these alterations (100%, 76%, and 15.2%, respectively). In contrast, the availability rate of genome-matched therapies was highest in patients with sarcoma and head and neck cancer (HNC) (60% and 40%, respectively). One hundred thirteen patients (63.5%) had multiple barriers to accessing genome-matched therapy. Of 178 patients, 21 patients (11.8%) could not be considered for genome-matched therapies solely because of the deterioration of their performance status. CONCLUSION: This study demonstrated the usefulness of CGP for patients with sarcoma and HNC in addition to lung cancer in clinical practice. Performing CGP at the front line has the potential to improve the availability of genome-matched therapy.
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Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias/genética , Neoplasias/terapia , Adulto , Genômica/métodos , Medicina de Precisão , Idoso de 80 Anos ou mais , Sarcoma/genética , Sarcoma/terapiaRESUMO
Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent studies have expanded this spectrum to include other types of hereditary tumors, such as Lynch syndrome or familial adenomatous polyposis. Individuals harboring germline TP53 pathogenic variants that cause LFS have heterogeneous phenotypes depending on the respective variant type. As an example, R337H variant found in Brazilian is known as low penetrant. While 50-80% of pediatric ACC patients harbored a LFS, such a strong causal relationship is not observed in adult patients, which suggests different pathophysiologies between the two populations. As for PPGL, because multiple driver genes, such as succinate dehydrogenase (SDH)-related genes, RET, NF1, and VHL have been identified, universal multi-gene germline panel testing is warranted as a comprehensive and cost-effective approach. PPGL pathogenesis is divided into three molecular pathways (pseudohypoxia, Wnt signaling, and kinase signaling), and this classification is expected to result in personalized medicine based on genomic profiles. It remains unknown whether clinical characteristics differ between cases derived from genetic predisposition syndromes and sporadic cases, or whether the surveillance strategy should be changed depending on the genetic background or whether it should be uniform. Close cooperation among medical genomics experts, endocrinologists, oncologists, and early investigators is indispensable for improving the clinical management for multifaceted ACC and PPGL.
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INTRODUCTION: Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The evidence is limited regarding other diseases potentially associated with HTLV-1, such as HTLV-1-associated autoimmune diseases. AREA COVERED: We summarized the available information on complications associated with HTLV-1 infection. EXPERT OPINION: Previous studies showed that HTLV-1 carriers have an increased incidence of collagen diseases including Sjögren's syndrome, as well as dysthyroidism, diabetes mellitus, and atherosclerosis. Furthermore, cognitive deficits are observed in asymptomatic carriers and in symptomatic carriers who develop HAM/TSP. It is hypothesized that altered immunoregulation occurs as a result of persistent HTLV-1 infection. A systematic review and meta-analysis demonstrated that HTLV-1 infection itself has an adverse impact on overall survival. ATL alone cannot entirely explain the adverse impact of HTLV-1 infection on overall mortality, because the incidence is low, and therefore HTLV-1-associated diseases as a whole may contribute to the inferior clinical outcome. However, there are insufficient data to determine the causal relationship between HTLV-1 infection and each complication. While non-cancerous events linked to HTLV-1 infection are not fatal, they are likely to reduce quality of life. Large prospective studies should be conducted by international collaborators.
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Portador Sadio , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Humanos , Doenças Autoimunes/epidemiologia , Portador Sadio/virologia , Infecções por HTLV-I/complicações , Infecções por HTLV-I/epidemiologia , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/virologia , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/virologiaRESUMO
INTRODUCTION: Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While conventional antiviral agents such as ganciclovir can be used for CMV prophylaxis, toxicities such as myelosuppression are a major concern. AREA COVERED: This work aimed to summarize the latest information and practical issues regarding a new anti-CMV agent, letermovir (LET). EXPERT OPINION: LET inhibits CMV replication by binding to components of the DNA terminase complex. A phase 3 trial in allo-HSCT recipients showed a reduced incidence of clinically significant CMV infection in the LET group. In 2017, this agent was first approved for CMV prophylaxis in adult CMV-seropositive allo-HSCT recipients in the United States, and is now used worldwide. While LET has an excellent toxicity profile, there are issues to be aware of, such as interactions with other drug classes (e.g. immunosuppressants and antifungals) and reactivation of CMV infection following LET cessation. While LET is the current standard of care for CMV prophylaxis, there are no established protocols for preemptive treatment of asymptomatic CMV viremia or for treatment of developed CMV disease. Further research is needed to maximize the benefits of LET, including the discovery of biomarkers.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Quinazolinas , Adulto , Humanos , Acetatos/uso terapêutico , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Ensaios Clínicos Fase III como AssuntoRESUMO
INTRODUCTION: Cytarabine and anthracycline combination therapy (7 + 3 regimen) is the standard care for induction chemotherapy in adult patients with acute myeloid leukemia (AML). Although this intensive regimen achieves a high response rate, it is highly toxic, especially in elderly or frail patients. Hypomethylating agents approved initially for high-risk myelodysplastic syndrome had longer survival times than conventional care in elderly patients with newly diagnosed AML. AREAS COVERED: We summarize the latest information regarding induction therapy using hypomethylating agents (azacitidine and decitabine) for newly diagnosed AML. EXPERT OPINION: For untreated patients ineligible for an intensive regimen, a phase III trial exhibited the survival benefit of adding the highly selective BCL2 inhibitor venetoclax to azacitidine. The National Comprehensive Cancer Network guidelines recommend azacitidine or decitabine plus venetoclax as an option for patients with poor-risk AML, including those with TP53 mutations and AML with the cytogenetic features of myelodysplastic syndrome. Future studies should evaluate positioning this combination as an induction therapy for younger patients eligible for hematopoietic stem cell transplantation. Without randomized trials, propensity score matching analysis suggested a comparable prognosis between azacitidine combination and intensive chemotherapy. Considering the feasibility of a doublet regimen incorporating azacitidine, a triplet regimen should be examined.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Sulfonamidas , Adulto , Humanos , Idoso , Decitabina/uso terapêutico , Quimioterapia de Indução , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/tratamento farmacológicoRESUMO
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are widely used for multiple types of malignancies and are considered the fourth pillar in cancer treatment. Anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab are approved for relapsed/refractory classical Hodgkin lymphoma. Nonetheless, two phase 2 trials for T-cell lymphoma were terminated because of hyperprogression after a single dose in some patients. AREAS COVERED: In this review, we summarize available information on the rapid progression of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma (ATLL). EXPERT OPINION: In the abovementioned two trials, disease subtypes in patients who experienced hyperprogression were mostly ATLL or angioimmunoblastic T-cell lymphoma. Possible hyperprogression mechanisms induced by PD-1 blockade are the compensatory upregulation of the expression of other checkpoints, altered expression of lymphoma-promoting growth factors, functional blockade of stromal PD-ligand 1 acting as a tumor suppressor, and unique immune environment in indolent ATLL. The differentiation between hyperprogression and pseudoprogression is practically essential. There are no established methods to predict hyperprogression before administration of an ICI. In the future, the progress of novel diagnostic modalities such as positron emission tomography with computed tomography and circulating tumor DNA is expected to facilitate early cancer detection.
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Doença de Hodgkin , Leucemia-Linfoma de Células T do Adulto , Linfoma de Células T Periférico , Linfoma de Células T , Adulto , Humanos , Anticorpos Monoclonais/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Linfoma de Células T Periférico/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Receptor de Morte Celular Programada 1 , Doença de Hodgkin/tratamento farmacológico , Linfoma de Células T/tratamento farmacológicoRESUMO
INTRODUCTION: Concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. The Geriatric Nutritional Risk Index (GNRI) is a screening tool to predict the risk of morbidity and mortality in the older adult. Nutritional management is key during CCRT but the association between prognosis and initial nutritional status in older adults with LAHNC undergoing CCRT remains unknown. MATERIALS AND METHODS: Patients ≥65 years old with LAHNC who received definitive CCRT with cisplatin (80 mg/m2 or 100 mg/m2, every three weeks, three times) between 2012 and 2018 were included. Patients without completion of radiotherapy were excluded. Patients were stratified into two groups based on the GNRI (â¦98 or > 98). Overall survival (OS) and event-free survival (EFS) were analyzed by the Kaplan-Meier method and the log-rank test. The Cox proportional hazards model was adopted to identify prognostic factors. GNRI, sex, T and N categories were prespecified as variables for multivariable analysis. RESULTS: The median age of 111 patients (88 male, 79%) was 69 years (interquartile range: 67-71), among which 23 patients had low GNRI (20 male, 87%) and 88 patients had high GNRI (68 male, 77%). Baseline clinical characteristics were not statistically different between the two groups. OS was significantly worse in the low GNRI group than in the high GNRI group (p = 0.048). There was no statistical difference in EFS between the two groups (p = 0.12). Multivariable analysis revealed that low GNRI (hazard ratio [HR]: 3.17, 95% confidence interval [95%CI]: 1.12-8.96, p = 0.029) and higher N category (HR: 4.37, 95% CI: 1.58-12.06, p = 0.004) were associated with worse OS. For EFS, the higher N category was significantly associated with a worse outcome (HR: 2.54, 95% CI: 1.16-5.59, p = 0.02). DISCUSSION: Poorer nutritional status before initiation of CCRT was associated with worse OS in older adults with LAHNC in the definitive setting. The GNRI is a convenient tool for predicting OS in older adult patients with LAHNC treated with CCRT.
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Cisplatino , Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Idoso , Cisplatino/uso terapêutico , Prognóstico , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/terapia , Estado Nutricional , Quimiorradioterapia , Avaliação Nutricional , Avaliação Geriátrica , Fatores de RiscoRESUMO
BACKGROUND: E7130 is a novel anticancer agent created from a total synthetic study of norhalichondrin B. The authors report the E7130 dose-escalation part of a first-in-human study of patients with advanced solid tumors (NCT03444701). METHODS: Japanese patients ≥20 years of age were enrolled. E7130 was administered intravenously in two cycles: day 1 of a 21-day cycle (Q3W) or days 1 and 15 of a 28-day cycle (Q2W). Doses were escalated from 270 to 550 µg/m2 for the Q3W group or 25-400 µg/m2 for the Q2W group. The primary end point of the dose-escalation phase was safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs) and adverse events. Other end points included determination of the maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics. RESULTS: Forty-four patients were enrolled: 15 in the E7130 Q3W group and 29 in the Q2W group. Treatment-emergent adverse events (TEAEs) occurred in all patients; the most common TEAE overall was leukopenia (78.6%). Grade 3-4 TEAEs occurred in 93.3% of patients in the Q3W group and 86.2% of patients in the Q2W group. None had a TEAE resulting in study drug discontinuation, and no treatment-related deaths were reported. Per the DLT evaluation, the MTDs were determined as 480 µg/m2 Q3W and 300 µg/m2 Q2W. Significant changes in multiple plasma biomarkers, including vascular endothelial growth factor 3 and matrix metallopeptidase 9, were dose-dependent after initial doses of 350-480 µg/m2 . CONCLUSIONS: E7130 480 µg/m2 Q3W was chosen for the dose-expansion part over 300 µg/m2 Q2W primarily per dose-dependent biomarker results.
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Antineoplásicos , Neoplasias , Humanos , Fator A de Crescimento do Endotélio Vascular , Microambiente Tumoral , Neoplasias/patologia , Antineoplásicos/efeitos adversos , Biomarcadores , Microtúbulos/metabolismo , Microtúbulos/patologia , Dose Máxima TolerávelRESUMO
Trabectedin is a therapeutic option for patients with advanced sarcoma. While a randomized trial demonstrated its prolonged progression-free survival (PFS), the reported PFS was <6 months. Some patients can achieve long-term disease control with this treatment. However, the reference information is insufficient. Herein, we retrospectively reviewed 51 sarcoma patients who received trabectedin. We analyzed the clinicopathological features, trabectedin dose, administration schedule, and clinical outcomes, including the overall response rate (ORR) and PFS. Among them, we assessed the detailed data of patients who achieved long-term disease control (PFS >1 year). The ORR in the 49 evaluable patients was 8%, and the median PFS in 51 patients was 7.5 months. Six patients (12%) achieved PFS of >1 year. Five of the six patients had metastatic lesions at trabectedin initiation. The pathological subtypes were myxoid liposarcoma (n = 2), leiomyosarcoma (n = 2), synovial sarcoma (n = 1), and Ewing sarcoma (n = 1). The final administration dose was the minimum dose (0.8 mg/m2) in two patients who continued the treatment over 20 cycles. The best radiological response was partial response (PR) in two myxoid liposarcoma patients and stable disease in four. The durations from trabectedin initiation to the first response in the two PR cases were 163 and 176 days, respectively. Our results support the validity of continuing trabectedin at a sustainable dose and interval in patients who can tolerate it. These results may be useful when considering the clinical application of trabectedin.
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Leiomiossarcoma , Lipossarcoma Mixoide , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Adulto , Trabectedina , Estudos RetrospectivosRESUMO
Adult T-cell leukemia/lymphoma (ATLL) has aggressive clinical behaviors, and improving its prognosis is a great challenge. A disease progression model from asymptomatic human T-cell leukemia virus type 1 carrier to aggressive-type ATLL has been proposed, and indolent ATLL comprising a smoldering or favorable chronic type is located at the midpoint. Even the most favorable smoldering type has a 4-year overall survival rate of <60%. Although watchful waiting is pervasive in patients with indolent ATLL, early therapeutic intervention is discussed among hematologists. Indolent ATLL was once termed T-cell-derived chronic lymphocytic leukemia (CLL). Unlike indolent ATLL, several molecular-targeted agents at the initial treatment have dramatically improved CLL prognosis. Recent studies on CLL have revealed a similar progression model involving premalignant monoclonal B-cell lymphocytosis (MBL). In particular, individuals with high-count MBL have an increased lymphoma risk. Considering the unsatisfactory long-term prognosis of indolent ATLL, further treatment strategies, including precision medicine, are warranted.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Leucemia-Linfoma de Células T do Adulto , Adulto , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/etiologia , Leucemia-Linfoma de Células T do Adulto/terapia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Linfocítica Crônica de Células B/terapia , PrognósticoRESUMO
INTRODUCTION: Human T-cell leukemia virus type 1 (HTLV-I) associated bronchioloalveolar disorder (HABA) is a chronic and progressive bronchiolar/alveolar disorder related to HTLV-1 infection. Clinical knowledge and guidance are lacking for the diagnosis and management of this condition. AREAS COVERED: This work aimed to review the latest information and challenges regarding HABA diagnosis and treatment. EXPERT OPINION: HABA is an immune-mediated state induced by HTLV-1. For diagnosis of HABA, other infectious diseases and pulmonary infiltration of adult T-cell leukemia should be excluded by investigations such as computed tomography (CT), transbronchial biopsy, and bronchoalveolar lavage fluid (BALF) analysis. Typical CT findings in HABA include diffuse panbronchiolitis-like or bronchiectasis patterns, whereas cases with other abnormalities, including interstitial pneumonia, have also been reported. A high rate of polyclonal CD4+ and CD25+ lymphocytes is detected in BALF of patients with HABA, reflecting the infiltration of HTLV-1 infected T-cells in the lung. Current treatment options are not HABA specific, and include corticosteroids, macrolide antibiotics, and pirfenidone. Mitigation of the adverse effects of HTLV-1 infection requires the establishment of diagnostic criteria for the disease, screening programs for HABA in HTLV-1 infected individuals, and the development of effective disease treatment strategies.
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Bronquiolite , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Pneumopatias , Adulto , Humanos , Diagnóstico Diferencial , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/patologiaRESUMO
Performance status (PS) is widely used as an assessment of general condition in patients before performing comprehensive genomic profiling (CGP). However, PS scoring is dependent on each physician, and there is no objective and universal indicator to identify appropriate patients for CGP. Overall, 263 patients were scored using the modified Glasgow prognostic score (mGPS) from 0 to 2 based on the combination of serum albumin and c-reactive protein (CRP): 0, albumin ≥ 3.5 g/dl and CRP ≤ 0.5 mg/dl; 1, albumin < 3.5 g/dl or CRP > 0.5 mg/dl; and 2, albumin < 3.5 g/dl and CRP > 0.5 mg/dl. Overall survival was compared between mGPS 0-1 and mGPS 2 groups. The prognosis of patients with PS 0-1 and mGPS 2 was also evaluated. Thirty-nine patients (14.8%) were mGPS 2. Patients with mGPS 2 had significant shorter survival (14.7 months vs 4.6 months, p < 0.01). Twenty-eight patients were PS 0-1 and mGPS 2, and their survival was also short (5.6 months). Evaluation of mGPS is a simple and useful method for identifying patients with adequate prognosis using CGP.
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Without a current standard of care, patients with rare malignancy are subjected to precision oncology with next-generation sequencing to identify a course of treatment. We sought to establish the clinical relevance of comprehensive genomic profiling (CGP) among patients with rare malignancy. Rare malignancy was defined using the Rare Cancers in Europe definition (<6 cases per 100,000 individuals). We analyzed gene mutations, fusions, tumor mutational burden (TMB), and microsatellite instability (MSI) status. Level A gene alterations, categorized using Clinical Interpretations of Variants in Cancer and MD Anderson Knowledge Base for Precision Oncology, were considered druggable. Rare malignancy accounted for 149 (45%) cases, with female genital cancers (32%) most common. Among the rare malignancy cases, we identified a lower frequency of mutation in TP53 (41% vs. 60%, P<0.001), KRAS (13% vs. 43%, P<0.001) and APC (3% vs. 25%, P<0.001), and a higher frequency of ARID1A mutation (14% vs. 6%, P=0.03), as compared with common malignancies. TMB-high and MSI-high cases were found in 8% and 2% of cases, respectively. Druggable alterations were detected in 37 patients with rare malignancy; this percentage tended to be higher than that for patients with common malignancies (25% vs. 17%, P=0.08). Common druggable alterations were BRAF V600E, ERBB2 amplification, PIK3CA E542K, and BRCA1/2 variant. Five of the 37 patients with druggable alterations received genome-driven treatment. There was no significant difference in overall survival between the rare and common malignancy groups. Our results provide clues for future clinical development and treatment success among Japanese patients with rare cancers.
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Neoplasias , Biomarcadores Tumorais/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Humanos , Japão/epidemiologia , Instabilidade de Microssatélites , Mutação , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
BACKGROUND: Platinum-doublet chemotherapy has been conventionally used for patients with advanced gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) but evidence of chemotherapy is based on studies with small sample sizes and remains scarce. Thus, we conducted a systematic review and meta-analysis to elucidate the efficacy of platinum-doublet chemotherapy for advanced GEP-NEC. METHODS: We performed a database search in PubMed/MEDLINE and EMBASE. Eligible studies were prospective and retrospective studies documenting the efficacy of platinum plus etoposide (EP) and platinum plus irinotecan (IP) for advanced GEP-NEC. Overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were pooled and weighted using generic inverse variance in a random-effects meta-analysis model. RESULTS: Nineteen studies including 1157 patients were identified. The ORR of the platinum-doublet regimen, EP, and IP was 49.1% (95% confidence interval [CI], 41.8-56.5), 44.4% (95% CI: 35.9-53.0), and 59.4% (95% CI: 48.0-70.8). The pooled median OS of the platinum-doublet regimen, EP, and IP was 12.9 months (95% CI:10.9-15.3), 12.9 months (95% CI: 10.8-15.4), and 12.9 months (95% CI: 6.0-27.8), and the pooled median PFS of the platinum-doublet regimen, EP, and IP was 5.4 months (95% CI: 4.5-6.4), 5.4 months (95% CI 4.5-6.5), and 4.0 months (95% CI: 1.4-11.7), respectively. CONCLUSION: Considerable response rate and survival time of the platinum-doublet regimen for advanced GEP-NEC were observed. IP and EP regimens can be reasonably applicable and these results provide a reference for oncologists in deciding the suitable regimen for patients with advanced GEP-NEC.
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The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experienced a severe/repeated bacterial infection. The utility in hematopoietic stem-cell transplantation (HSCT) remains unknown. Although an early randomized trial demonstrated that IgRT decreased infection risk and transplant-related mortality after HSCT, subsequent clinical trials could not validate the benefit. Consequently, a meta-analysis did not show the benefit of IgRT in HSCT. Most of the available data derives from matched-related HSCT using myeloablative regimen, and the impact in haploidentical and cord blood transplantation, or reduced-intensity HSCT remains unknown. One crucial issue is that no studies exist for patients with only hypogammaglobulinemia after HSCT. Other challenges are heterogeneous patient characteristics, or immunoglobulin formulation, dosage, schedule, route and duration of IgRT. Without evidence in HSCT, it would be reasonable to follow the guidelines for other diseases with hypogammaglobulinemia.
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Agamaglobulinemia , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B , Agamaglobulinemia/terapia , Humanos , ImunoglobulinasRESUMO
BACKGROUND: Heart failure (HF) is one of the potential adverse events of pazopanib treatment for soft tissue sarcoma (STS), but detailed reports of such HF cases are scarce. This study determined the incidence and risk factors of HF following pazopanib treatment for STS at our Institute and the clinical outcomes.MethodsâandâResults:This study retrospectively analyzed the cases of STS patients treated with pazopanib (n=151) between 2012 and 2020. HF occurred in 6 patients (3.9%) at the median onset of 137 (range 14-468) days after the treatment initiation. When their HF was diagnosed, pazopanib was interrupted in all 6 patients. No patients experienced HF-related death, and HF development was not a significant factor for poor overall survival. The cumulative doses of anthracyclines (>225 mg/m2) before pazopanib initiation (83% vs. 37%, P=0.031), pazopanib initiation at age ≥60 years (83% vs. 35%, P=0.026), and the baseline B-type natriuretic peptide (BNP) concentration (≥50 pg/mL) before pazopanib (67% vs. 11%, P=0.002) initiation were predictive factors for post-pazopanib treatment HF. CONCLUSIONS: The study findings highlight the effect of past anthracycline exposure and baseline BNP for pazopanib-associated HF. Although the study patients' clinical outcomes were generally favorable, periodic monitoring of cardiac function using ultrasonic echocardiography or serum markers is essential to detect events early and begin therapeutic intervention appropriately under a cardiologist's instructions.
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INTRODUCTION: In the field of hematological malignancy, we often have the opportunity to use antibodies such as immune checkpoint inhibitors that can alter a patient's immune status before or after allo-HCT. The appropriate use of these novel agents is highly necessary to optimize disease control and reduce the risk of complications associated with adverse allo-immune reactions. AREAS COVERED: Clinical data on several monoclonal antibodies targeting programmed cell death 1 (PD-1) (nivolumab or pembrolizumab), C-C chemokine receptor 4 (CCR4) (mogamulizumab), CD30 (brentuximab vedotin), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (ipilimumab) are reviewed, with a focus on the incidence and severity of graft-versus-host disease (GVHD). EXPERT OPINION: While previous studies demonstrated a favorable prognosis in patients who received nivolumab prior to transplantation, the pretransplant use of nivolumab increases the incidence of GVHD, partly due to the expansion and activation of preexisting T cells. Mogamulizumab also has a significant impact on GVHD, caused by persistent depletion of regulatory T cells with CCR4 positivity. Regarding brentuximab vedotin, phase 1 trials have demonstrated considerable efficacy for steroid-refractory acute or chronic GVHD. In the future, sophisticated methods will be needed to determine the impact of each agent on immune status after allo-HCT.
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Antineoplásicos Imunológicos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Antineoplásicos Imunológicos/efeitos adversos , Brentuximab Vedotin , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , NivolumabeRESUMO
BACKGROUND: The clinical benefit of systemic chemotherapy for recurrent/metastatic retroperitoneal/intra-abdominal soft tissue sarcoma (STS) compared to its benefits for other primary lesions has not been known or sufficiently evaluated. METHODS AND PATIENTS: We retrospectively reviewed the cases of the STS patients who consulted a department of medical oncology in Tokyo between June 2011 and March 2018, and we extracted the cases of patients with primary sites at the retroperitoneum/intra-abdomen (cohort R) or extremities/trunk (cohort E) who received systemic chemotherapy in a recurrent/metastatic setting, comparing the cohorts' characteristics, chemotherapy details, and prognoses. RESULTS: Of all 337 STS patients, we enrolled 49 patients in cohort R and 75 patients in cohort E. Liposarcoma was more frequently observed in cohort R (51.0%) than cohort E (22.7%). The median chemotherapy treatment line was two lines (range: 1-6) in cohort R and three lines (range: 1-9) in cohort E. The doxorubicin usage rates differed in recurrent/metastatic settings (90.0% in cohort R and 55.0% in cohort E), due mainly to the higher rate of a perioperative chemotherapy treatment history in cohort E (52.0% vs. 6.1% in cohort R). The median overall survival from the start of salvage chemotherapy was 31.9 months (cohort R; 95% CI: 20.9-42.8) and 27.1 months (cohort E; 95% CI: 21.6-32.5) (p = 0.549). CONCLUSION: There were differences in the distributions of pathology and antitumor drugs used in a salvage setting between retroperitoneal/intra-abdominal and extremities/trunk STS patients in recurrent/metastatic settings, but the prognoses with salvage chemotherapy were similar in the two cohorts.
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Extremidades/patologia , Extremidades/cirurgia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologiaRESUMO
PURPOSE: The optimal timing for starting lenvatinib treatment in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) has long been controversial because of the relatively slow-growing nature of differentiated thyroid cancer. The aim of this study was to establish a scoring system using known clinical factors to simplify decision-making in when to start lenvatinib in RR-DTC patients. METHODS: We retrospectively analyzed RR-DTC patients treated with lenvatinib. We developed the clinical indication scoring algorithm on the basis of age, tumor-related symptoms, histology, metastatic sites, neutrophil-to-lymphocyte ratio, size of lung metastases, baseline sum of tumor diameters, and tumor-volume doubling time that was used to categorize patients into low-, intermediate-, and high-risk groups. RESULTS: A total of 59 patients were analyzed; 13 low-risk, 36 intermediate-risk, and 10 high-risk. The respective median progression-free survival from the initiation of lenvatinib was 93.7 months in the low-risk group, 20.3 months in the intermediate-risk group, and 6.2 months in the high-risk group (p < 0.02). Patients in the high-risk group had significantly worse overall survival compared with those in the low-risk (hazard ratio [HR] 6.59, 95% confidence interval [CI] 1.25-34.90, p < 0.03) or intermediate-risk (HR 2.99, 95% CI 1.03-8.63, p < 0.05) group. Using our proposed algorithm, patients in the intermediate-risk group showed treatment outcomes similar to that were observed in the pivotal trial of lenvatinib, and were the optimal patients to start lenvatinib. CONCLUSION: Our proposed scoring system can separate treatment outcomes and prognosis of RR-DTC patients treated with lenvatinib. This simple algorithm can be helpful for oncologists in deciding whether to start lenvatinib treatment in patients with RR-DTC.
Assuntos
Adenocarcinoma , Antineoplásicos , Quinolinas , Neoplasias da Glândula Tireoide , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
OBJECTIVE: The primary objective of this study was to identify novel genes that predispose people in the Japanese population to FPC. SUMMARY OF BACKGROUND DATA: Familial history of pancreatic cancer is an important risk factor but, to date, few genes predisposing individuals to increased risk of developing FPC have been identified. METHODS: We performed whole-exome sequencing of germline DNA from 81 Japanese FPC patients. We also investigated somatic gene alterations in 21 matched tumor tissues through whole-exome sequencing and copy number analysis. RESULTS: Our germline variants identified previously known FPC susceptibility genes such as ATM and BRCA2, and several novel tumor suppressor genes with potentially deleterious variants for FPC. Interestingly, somatic whole-exome analysis demonstrated that most tumor samples with suspicious loss of heterozygosity of candidate genes were KRAS wild-types, implying that these cases may not have required KRAS activation as a driver event for carcinogenesis. CONCLUSIONS: Our findings indicate that FPC patients harbor potentially deleterious causative germline variants in tumor suppressor genes, which are known to acquire somatic mutations in pancreatic cancer, and that somatic loss of heterozygosity of some FPC susceptibility genes may contribute to the development of FPC in the absence of somatic KRAS-activating mutation. Genetic testing for a wider variety of FPC-predisposition genes could provide better screening approach for high-risk groups of pancreatic cancer.