RESUMO
Nodal peripheral T-cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL-TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. Patient diagnosis was centrally reviewed, and patients were reclassified according to the World Health Organization (WHO) 2016 criteria: 21 patients as PTCL-NOS, 55 as AITL and 23 as PTCL-TFH. Median follow-up was 56.07 months (95% CI 38.7-73.4). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL-TFH than in those with PTCL-NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001). Histological diagnosis maintained an independent influence on both PFS (hazard ratio [HR] 4.1 vs. PTCL-NOS, p = 0.008; HR 2.6 vs. AITL, p = 0.047) and OS (HR 5.7 vs. PTCL-NOS, p = 0.004; HR 2.6 vs. AITL, p = 0.096), regardless of the International Prognostic Index. These results suggest that PTCL-TFH could have more favourable features and prognosis than the other PTCL subtypes, although larger series are needed to corroborate these findings.
Assuntos
Linfadenopatia Imunoblástica , Linfoma de Células T Periférico , Humanos , Linfadenopatia Imunoblástica/genética , Prognóstico , Fenótipo , Estudos RetrospectivosRESUMO
In pretreatment tumor samples of EGFR-mutated non-small cell lung cancer (NSCLC) patients, EGFR-Thr790Met mutation has been detected in a variable prevalence by different ultrasensitive assays with controversial prognostic value. Furthermore, its detection in liquid biopsy (LB) samples remains challenging, being hampered by the shortage of circulating tumor DNA (ctDNA). Here, we describe the technical validation and clinical implications of a real-time PCR with peptide nucleic acid (PNA-Clamp) and digital droplet PCR (ddPCR) for EGFR-Thr790Met detection in diagnosis FFPE samples and in LB. Limit of blank (LOB) and limit of detection (LOD) were established by analyzing negative and low variant allele frequency (VAF) FFPE and LB specimens. In a cohort of 78 FFPE samples, both techniques showed an overall agreement (OA) of 94.20%. EGFR-Thr790Met was detected in 26.47% of cases and was associated with better progression-free survival (PFS) (16.83 ± 7.76 vs. 11.47 ± 1.83 months; p = 0.047). In LB, ddPCR was implemented in routine diagnostics under UNE-EN ISO 15189:2013 accreditation, increasing the detection rate of 32.43% by conventional methods up to 45.95%. During follow-up, ddPCR detected EGFR-Thr790Met up to 7 months before radiological progression. Extensively validated ultrasensitive assays might decipher the utility of pretreatment EGFR-Thr790Met and improve its detection rate in LB studies, even anticipating radiological progression.
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Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Receptores ErbB/genética , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Reação em Cadeia da Polimerase em Tempo RealRESUMO
We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.
Assuntos
Linfoma de Células T Periférico/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Antígeno Ki-1/análise , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Espanha/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
The purpose of this report is to provide long-term follow-up of 38 patients diagnosed of post-transplant lymphoproliferative disease (PTLD) included in a phase 2 clinical trial of first line therapy with rituximab and to evaluate the same therapy in a real world cohort of 21 consecutive patients treated once the trial was closed. Eligible patients were ≥ 18 years of age with a biopsy-proven CD20 positive B cell PTLD and treatment naive except for reduction of immunosuppression. Treatment consisted in four weekly infusions of rituximab at the standard dose of 375 mg/m2. Patients in complete remission (CR) were followed without further treatment, and those in partial remission (PR) were treated with another four cycles of weekly rituximab. Median follow-up in the clinical trial was 13.0 years. Disease-specific survival (DSS) at 10 years was 64.7% [95% confidence interval (CI) 48.2-81.2%]. For those patients who achieved CR (61%), DSS at 5 and 10 years was 94.4% (95% CI 83.8-100%) and 88.1% (95% CI 72.6-100%), respectively, and only 1 patient progressed beyond 5 years. The median follow-up of the real world patients was 6.5 years. DSS at 5 years was 75.2% (95% CI 56.4-94.0%). DSS at 5 years of patients who achieved CR (38%) was 87.5% (95% CI 64.6-100%). In conclusion, PTLD patients in CR after rituximab have an excellent long-term outcome. These results not only apply in the clinical trial setting but are also reproducible in the real world. However, those patients who do not respond represent an unmet clinical need and should be included in prospective clinical trials.
Assuntos
Antineoplásicos/uso terapêutico , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Linfócitos B/patologia , Progressão da Doença , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Estudos Prospectivos , Indução de Remissão , Rituximab/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish registry. Sixty-four HTs were recorded based on clinical criteria (55%) or histological confirmation (45%). The cumulative incidence rate of transformation at 5 years is 7.3%. The 5-year overall survival (OS) without HT was 85% (95% confidence interval [CI], 70%-90%) vs 66% (95% CI, 51%-76%; P = 0.0012) with HT. Factors associated with HT were elevated lactate dehydrogenase (LDH) (odds ratio [OR] 1.83), intermediate-high Follicular lymphoma international prognostic index (FLIPI) (OR 2.16-OR 3.21), B symptoms (OR 2.46), or Eastern Cooperative Oncology Group (ECOG) 1 (OR 2.35). Treatment options related to HT were "watch and wait" or no rituximab or anthracyclines initially. A 5-year OS for patients treated with chemotherapy before HT was 55% (95% CI, 38%-69%) versus 81% (95% CI, 53%-93%; P = 0.009) for those who had not received it. The HT rate has decreased after the introduction of rituximab, as has been previously described. The timing of this treatment had an impact on the survival of these patients.
Assuntos
Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Sistema de Registros , Rituximab/administração & dosagem , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Relatively few studies have analyzed the mortality of follicular lymphoma (FL) patients in comparison with a sex- and age-matched general population. This study analyzed the overall survival (OS) of patients with FL and compared their survival with the expected survival of a general population. METHODS: Patients diagnosed with FL were prospectively enrolled from 1980 to 2013. Standardized mortality ratios (SMRs) were obtained from yearly sex- and age-specific mortality rates in Spain, and OS was compared with age- and sex-matched general population data. RESULTS: A total of 1074 patients with newly diagnosed FL were enrolled. The median OS was 231 months (95% confidence interval [CI], 195-267 months). Event-free survival at 12 months (EFS12) and event-free survival at 24 months (EFS24) were associated with an increased probability of early death, with an SMR of 10.27 (95% CI, 8.26-12.77) for EFS12. The overall SMR, including all causes of death, was 2.55 (95% CI, 2.23-2.92), and it was higher for women (SMR, 3.02; 95% CI, 2.48-3.67) and young adults (SMR, 6.01; 95% CI, 3.13-11.55). More than 10 years after the diagnosis, mortality rates for FL patients were lower than those for the general population (SMR, 0.47; 95% CI, 0.28-0.78). When FL was excluded as a cause of death, the overall SMR was 1.35 (95% CI, 1.11-1.65) without a statistically significant mortality increase in the >60-year-old group in comparison with age- and sex-matched general population data. More than 15% of the patients included in the study (n = 158) had more than 10 years of follow-up. CONCLUSIONS: EFS12 and EFS24 predict an early increase in mortality. The long-term SMR, over the course of 10 years of follow-up, shows that patients with FL have a risk of dying similar to that of a sex- and age-matched general population. Cancer 2017;123:3709-3716. © 2017 American Cancer Society.
Assuntos
Linfoma Folicular/mortalidade , Rituximab/uso terapêutico , Adulto , Fatores Etários , Antineoplásicos/uso terapêutico , Estudos de Casos e Controles , Causas de Morte , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores Sexuais , Espanha/epidemiologia , Fatores de TempoRESUMO
Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.
Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Células Matadoras Naturais/patologia , Lenalidomida/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Resposta Patológica CompletaRESUMO
BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.
Assuntos
Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18/uso terapêutico , Prognóstico , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/tratamento farmacológico , Estudos RetrospectivosRESUMO
Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.
RESUMO
Next-generation sequencing (NGS) is a molecular approach able to provide a comprehensive molecular profile of non-small cell lung cancer (NSCLC). The broad spectrum of biomarker-guided therapies has positioned molecular diagnostic laboratories as a central component of patient clinical management. Here, we show the results of an UNE-EN ISO 15189:2022 NGS-accredited assay in a cohort of 350 patients. TP53 (51.0%), KRAS (26.6%) and EGFR (12.9%) were the most frequently mutated genes. Furthermore, we detected co-occurring and mutually exclusive alterations, as well as distinct molecular profiles according to sex and smoking habits. Actionable genetic alterations were significantly more frequent in female patients (80.5%, p < 0.001) and in never-smoker patients (87.7%, p < 0.001). When NGS was established as the main molecular testing strategy, 36.4% of patients received at least one line of targeted treatment. Among 200 patients with stage IV NSCLC, first-line treatment with targeted therapies was associated with a longer progression-free survival (PFS) (13.4 months (95% CI, 10.2-16.6) (p = 0.001)). Similarly, the overall survival (OS) of patients receiving at least one targeted drug was significantly longer (26.2 months (95% CI, 11.8-40.5) (p < 0.001)). Our results show that the implementation of NGS in the public healthcare system has provided a broader application of precision medicine.
RESUMO
Diffuse large B-cell lymphoma is the most frequent histological subtype of NHL and the paradigm for the management of aggressive lymphoma. An excisional or incisional lymph node biopsy evaluated by an experienced hemopathologist is recommended to establish the diagnosis. Twenty years following its introduction, R-CHOP remains the standard first-line treatment. No modification of this scheme (increased chemotherapy dose intensity, new monoclonal antibodies, or the addition of immunomodulators or anti-target agents) has significatively improved the clinical outcomes, whereas therapy for recurrence or progression is evolving rapidly. The irruption of CART cells, polatuzumab vedotin, tafasitamab, and CD20/CD3 bispecific antibodies are changing the natural history of relapsed patients and will challenge R-CHOP as the benchmark for newly diagnosed patients.
Assuntos
Anticorpos Biespecíficos , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adjuvantes Imunológicos , Benchmarking , BiópsiaRESUMO
PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.
Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Humanos , Lenalidomida/efeitos adversos , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coronavirus has generated a pandemic, in which there are population groups at higher risk and who are potentially fatal victims of the disease. Cancer patients have been considered a group with special susceptibility, particularly patients with lung tumour involvement and haematological neoplasms. The Spanish Lymphoma Oncology Group (GOTEL) carried out a multicenter study of SARS-CoV-2 seroprevalence in patients with lymphoma. Results: A total of 150 patients were included between 22 May and 11 June 2020. The mean age was 65 years (range 17-89), 70 women (46.5%) and 80 men (53, 5%). At the time of diagnosis of lymphoma, 13 cases were stage I (9%), 27 (18%) stage II, 37 (24.5%) stage III, and 73 (48.5%) stage IV, while 6.6% had a primary extranodal origin. A total of 10 cases with positive serology for SARS-CoV-2 were identified, which is a prevalence of 6% in this population. None of the patients required intensive care unit management and all fully recovered from the infection. Conclusion: IgG antibody seroprevalence in lymphoma patients appears similar to that of the general population and does not show greater aggressiveness.
Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Linfoma/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulina G/sangue , Linfoma/sangue , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/imunologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Células Supressoras Mieloides/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Análise de Sobrevida , Linfócitos T Reguladores/efeitos dos fármacos , Resultado do TratamentoRESUMO
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.
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Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Mutação , Adulto , Idoso , Antígenos CD79/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/classificação , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Receptor Notch1/genética , Reprodutibilidade dos Testes , Rituximab/administração & dosagemRESUMO
A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients <70 years and sixty-four >70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Progressão da Doença , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The establishment of precision medicine in cancer patients requires the study of several biomarkers. Single-gene testing approaches are limited by sample availability and turnaround time. Next generation sequencing (NGS) provides an alternative for detecting genetic alterations in several genes with low sample requirements. Here we show the implementation to routine diagnostics of a NGS assay under International Organization for Standardization (UNE-EN ISO 15189:2013) accreditation. For this purpose, 106 non-small cell lung cancer (NSCLC) and 102 metastatic colorectal cancer (mCRC) specimens were selected for NGS analysis with Oncomine Solid Tumor (ThermoFisher). In NSCLC the most prevalently mutated gene was TP53 (49%), followed by KRAS (31%) and EGFR (13%); in mCRC, TP53 (50%), KRAS (48%) and PIK3CA (16%) were the most frequently mutated genes. Moreover, NGS identified actionable genetic alterations in 58% of NSCLC patients, and 49% of mCRC patients did not harbor primary resistance mechanisms to anti-EGFR treatment. Validation with conventional approaches showed an overall agreement >90%. Turnaround time and cost analysis revealed that NGS implementation is feasible in the public healthcare context. Therefore, NGS is a multiplexed molecular diagnostic tool able to overcome the limitations of current molecular diagnosis in advanced cancer, allowing an improved and economically sustainable molecular profiling.
RESUMO
Post-transplant lymphoproliferative disorders (PTLD) are a rare complication after both solid organ (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single center retrospective study, we compared clinical, biological, and histological features, and outcomes of PTLD after both types of transplant. We identified 82 PTLD (61 after SOT and 21 after allo-HSCT). The presence of B symptoms, Waldeyer ring, spleen, central nervous system, and liver involvement, and advanced Ann-Arbor stage were more frequent in allo-HSCT recipients. PTLD had an earlier onset in allo-HSCT than in SOT cohort (4 vs. 64 months, p < .0001). PTLD was EBV-positive in 100% of allo-HSCT, in contrast to 47% of SOT (p = .0002). Four years after PTLD diagnosis, median overall survival was 32% (95% CI, 22-48) and 10% (95% CI, 2-49) in SOT and allo-HSCT recipients, respectively (p = .002). In conclusion, the clinical presentation and the outcome of PTLD varies greatly depending on the type of transplant.
Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/epidemiologia , Transplante de Órgãos/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/fisiologia , Humanos , Linfonodos/patologia , Linfonodos/virologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Ativação Viral/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVES: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC). The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting. MATERIAL AND METHODS: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomized1:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on days 1 and 8 in 4-week cycles; 2 cycles in concomitance). Both groups received concomitant radiotherapy 2 Gy/day (66 Gy). The primary endpoint was progression free survival (PFS). RESULTS: One hundred and forty patients were enrolled. Sixty-nine patients received OVP and 71 received EP. Globally adverse events grade 3/4 per cycle were fewer in the vinorelbine arm (19.4%) than in the etoposide arm (62.6%) (p < 0.001). One patient (1.5%) in the OVP arm and 12 pts (17.6%) in the EP arm presented esophagitis grade 3/4 (p = 0.002). Median PFS was similar in both groups (10.8 [95% CI 7.7-13.8] and 9.6 months [95% CI 4.4-14.8]; p = 0.457, respectively). Preliminary median overall survival was 30 months in the OVP arm and 31.9 months in the EP arm (p = 0.688). CONCLUSIONS: Our findings show that OVP could be considered a standard combination with similar efficacy and better safety profile for the treatment of LA-NSCLC patients.