RESUMO
BACKGROUND: The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date. MATERIALS AND METHODS: From 25 Italian centers, we recruited 1044 family members and germline sequenced 940 cutaneous melanoma index cases through a shared gene panel, which included the following genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, MITF and ATM. We assessed detection rate according to familial status, region of origin, number of melanomas and presence and type of non-melanoma tumors. RESULTS: The overall detection rate was 9.47% (5.53% analyzing CDKN2A alone), ranging from 5.14% in sporadic multiple melanoma cases (spoMPM) with two cutaneous melanomas to 13.9% in familial cases with at least three affected members. Three or more cutaneous melanomas in spoMPM cases, pancreatic cancer and region of origin predicted germline status [odds ratio (OR) = 3.23, 3.15, 2.43, P < 0.05]. Conversely, age > 60 years was a negative independent predictor (OR = 0.13, P = 0.008), and was the age category with the lowest detection rate, especially for CDKN2A. Detection rate was 19% when cutaneous melanoma and pancreatic cancer clustered together. CONCLUSIONS: Gene panel doubled the detection rate given by CDKN2A alone. National genetic testing criteria may need a revision, especially regarding age cut-off (60) in the absence of strong family history, pancreatic cancer and/or a high number of cutaneous melanomas.
Assuntos
Melanoma , Neoplasias Pancreáticas , Neoplasias Cutâneas , Inibidor p16 de Quinase Dependente de Ciclina , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Melanoma Maligno Cutâneo , Neoplasias PancreáticasRESUMO
PURPOSE: Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases. METHODS: We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan-Meier method, and comparisons were made using chi-square test. RESULTS: Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9 months (95% CI 14.1-17.9) versus 11.4 months (95% CI 9.4-13.4) for patients with BMs (p = 0.001). Eunatremic patients had a better outcome (mOS 16.3 months, 95% CI 14.6-18.0 vs 10.3 months, 95% I 7.6-12.8, p = 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1 months (95% CI 4.3-15.9), patients with hyponatremia without BMs 11.9 months (95% CI 11.4-12.4), while mOS was 13.1 months (95% CI 12.0-14.2) for eunatremic patients with BMs versus 17.1 months (95% CI 15.2-19.1) in eunatremic patients without BMs (p = 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76 months, p = 0.0187). CONCLUSIONS: Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.
Assuntos
Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Hiponatremia/diagnóstico , Hiponatremia/etiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Terapia Neoadjuvante , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: Hyponatremia is the most common electrolyte disorder in hospitalized patients, and it might be an indicator of poor prognosis and might have negative effects on hospitalization length and quality of life in non-malignant as well as in malignant diseases. The aim of this study is to determine the impact of hyponatremia on the length and on the cost of hospitalization as well as on outcome in cancer patients. METHODS: The present study includes 105 consecutive cancer patients hospitalized at our institution from June 2013 to December 2013. Data regarding age, sex, staging, histology, chemotherapy, and serum sodium levels at admission, during hospitalization, and at discharge were recorded and statistically analyzed. Impact of hyponatremia on length and cost of hospitalization and on outcome was evaluated. RESULTS: A significant difference in overall survival since the date of admission was observed between eunatremic and hyponatremic patients (p = 0.0255). A statistically significant correlation was also found between the length of stay and the detection of hyponatremia. At multivariate analysis, hyponatremia at admission, severity of hyponatremia, and stage of disease resulted independent prognostic factors. Furthermore, a patient with moderate or severe hyponatremia cost, in rate terms, 128 and 299 % more than a normonatremic patient, respectively. CONCLUSIONS: The occurrence of hyponatremia at the admission or during the hospitalization may represent a significant factor influencing the outcome and the length of hospitalization. Acting effective and timely on the normalization of sodium levels might have a positive effect on prognosis in this setting of patients, as well as on the length of stay in hospital, thus potentially resulting in savings.
Assuntos
Hiponatremia/sangue , Neoplasias/complicações , Neoplasias/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/sangue , Qualidade de Vida , Resultado do TratamentoRESUMO
PURPOSE: Hyponatraemia is one of the most common tumour-related electrolyte disorders. Several clinical, histological and serum factors have been found to influence prognosis, but, to date, there are no studies focusing on the prognostic role of hyponatraemia in mesothelioma. The aim of this study was to assess the prognostic role of hyponatraemia in malignant pleural mesothelioma. METHODS: We analysed 62 consecutive patients with histologically or cytologically proven advanced malignant pleural mesothelioma undergoing chemotherapy at our institution between January 2003 and September 2013. RESULTS: All patients received a first-line pemetrexed-based chemotherapy. A second-line chemotherapy was administered to 29 patients. The onset of hyponatraemia (serum sodium <135 mEq/L) during the treatment was significantly related to a worsened median overall survival (7.93 vs 13.48 months; p = 0.0069). The occurrence of hyponatraemia during first-line chemotherapy (cutoff 135 and 130 mEq/L) was significantly associated to a shorter median progression-free survival (p = 0.0214). Results were also similar in the subgroup receiving a second-line treatment. At the multivariate analysis, including haemoglobin and sodium level at the beginning of first-line chemotherapy, age, gender, smoking habit, job exposure and performance status, only hyponatraemia was found to be an independent factor (p = 0.029). Hyponatraemia was also found to be a predictive factor for both first-line chemotherapy, being related to poorer response to pemetrexed-based chemotherapy (p = 0.047) and second-line chemotherapy (p = 0.044). CONCLUSION: Our results show that hyponatraemia might be considered a negative prognostic parameter in malignant pleural mesothelioma patients. To our knowledge, this is the first study to evaluate the association of hyponatraemia with the outcome of malignant pleural mesothelioma patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hiponatremia/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/análogos & derivados , Humanos , Hiponatremia/induzido quimicamente , Hiponatremia/mortalidade , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/mortalidade , Mesotelioma Maligno , Pessoa de Meia-Idade , Análise Multivariada , Pemetrexede , Neoplasias Pleurais/mortalidade , Prognóstico , Análise de SobrevidaRESUMO
Fanconi anemia (FA) is an autosomal recessive disease characterized by pancitopenia, congenital malformations, predisposition to cancers and chromosomal instability. We report the clinical and molecular features of a patient initially identified as a potential FA case only because of chemotherapy toxicity during the treatment of a T-lineage acute lymphoblastic leukemia (ALL). Cells from this patient showed a moderate chromosomal instability, increasing sensitivity to DNA crosslinking agents but normal response to ionizing radiation. The analysis of FA proteins demonstrated a marked reduction of FANCD2 (>95%), but normal levels of FANCA or FANCG. Interestingly, this defect was associated with a homozygous missense mutation of FANCD2, resulting in a novel amino-acid substitution (Leu153Ser) at residue Leu153, which is highly conserved through evolution. The FANCD2(L153S) protein, whose reduced expression was not due to impaired transcription, was detected also in its monoubiquitinated form in the nucleus, suggesting that the mutation does not affect post-translation modifications or subcellular localization but rather the stability of FANCD2. Therefore, the hypomorphic Leu153Ser mutation represents the first example of a FANCD2 defect that might promote clonal progression of tumors, such as T-ALL, and severe chemotherapy toxicity in patients without any clinical manifestations typical of FA.