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1.
J Endocrinol Invest ; 47(9): 2279-2294, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38402360

RESUMEN

PURPOSE: The aim of this study is to describe the clinical management of an Italian series of patients with advanced gastro-entero-pancreatic (GEP) MiNENs treated in clinical practice. METHODS: Clinical records of patients from four Italian referral Centers were retrospectively analyzed to correlate clinical/biological data with clinical outcomes. All the surgical specimens were centrally reviewed. RESULTS: Clinical data and surgical samples of 51 patients during 1995-2015 were analyzed. Sites of origin were: 32 colorectal, 14 gastro-esophageal, and 5 pancreatobiliary. Twenty-one out of fifty-one (42.2%) developed metachronous distant metastases. Only 5/51 (9.8%) patients received peri-operative therapy, and 23/51 (45.1%) first-line chemotherapy, mostly fluoropyrimidines/oxaliplatin. The NEN component was poorly differentiated in the whole population. Patients with Ki67 index < 55% in the NEC component had a significantly longer median overall survival (OS) (35.3 months; 95% CI 27.1-41.0) than those with Ki67 ≥ 55% (11.9 months; 95% CI 9.1-14.0) P = 0.0005. The median OS was 14 months (95% CI 10.1-19.1) in the whole cohort, with 11.4 months (95% CI 6.2-20.2) in patients who received a first-line therapy. CONCLUSION: This study confirms that GEP-MiNENs represent a complex disease and that over the past years the clinical management has been predominantly guided by the subjective judgment of the clinicians. Although, in this series, the NEC component appeared mostly responsible for the systemic spread and prognosis on the whole neoplasm, the lack of strong prognostic and predictive factors universally recognized seems to condition their management so far. Future prospective clinical and biomolecular studies could help clinicians to improve clinical management of GEP-MiNENs.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Italia/epidemiología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Anciano , Estudios Retrospectivos , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Adulto , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/patología , Neoplasias Intestinales/mortalidad , Anciano de 80 o más Años , Estudios de Seguimiento , Tasa de Supervivencia
2.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338777

RESUMEN

We investigated whether we could identify a panel of miRNAs associated with response to treatment in tumor tissues of patients with Hormone Receptor-positive/HER2-negative metastatic breast cancer treated with endocrine therapy (ET) and the CDK4/6 inhibitor (CDK4/6i)i palbociclib. In total, 52 patients were evaluated, with 41 receiving treatment as the first line. The overall median PFS was 20.8 months (range 2.5-66.6). In total, 23% of patients experienced early progression (<6 months). Seven miRNAs (miR-378e, miR-1233, miR-99b-5p, miR-1260b, miR-448, -miR-1252-5p, miR-324-3p, miR-1233-3p) showed a statistically significant negative association with PFS. When we considered PFS < 6 months, miR-378e, miR-99b-5p, miR-877-5p, miR-1297, miR-455-5p, and miR-4536-5p were statistically associated with a poor outcome. In the multivariate analysis, the first three miRNAs confirmed a significant and independent impact on PFS. The literature data and bioinformatic tools provide an underlying molecular rationale for most of these miRNAs, mainly involving the PI3K/AKT/mTOR pathway and cell-cycle machinery as cyclin D1, CDKN1B, and protein p27Kip1 and autophagy. Our findings propose a novel panel of miRNAs associated with a higher likelihood of early progression in patients treated with ET and Palbociclib and may contribute to shed some light on the mechanisms of de novo resistance to CDK4/6i, but this should be considered exploratory and evaluated in larger cohorts.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Piridinas , Humanos , Femenino , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Piperazinas/farmacología , Piperazinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Receptor ErbB-2/metabolismo , Quinasa 4 Dependiente de la Ciclina/genética
3.
Cancer ; 127(15): 2674-2682, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33857327

RESUMEN

BACKGROUND: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors such as everolimus. This post hoc pooled analysis assessed the potential impact of these events on the efficacy of everolimus. METHODS: Patients with advanced, low- or intermediate-grade pancreatic, gastrointestinal, or lung neuroendocrine tumors received either oral everolimus at 10 mg/d or a placebo in the RAD001 in Advanced Neuroendocrine Tumors 3 (RADIANT-3) and RAD001 in Advanced Neuroendocrine Tumors 4 (RADIANT-4) trials. A landmark progression-free survival (PFS) analysis by central review was performed for patients treated for at least 16 weeks (n = 308) and according to the occurrence of any-grade adverse events (AEs) within this treatment period. RESULTS: The overall PFS with everolimus from the pooled analysis was 11.4 months (95% confidence interval, 11.01-13.93 months), which was consistent with the findings of RADIANT-3 and RADIANT-4. Overall, 19.1% and 9.8% of patients in RADIANT-3 and 11.9% and 6.4% of patients in RADIANT-4 developed any-grade hyperglycemia and hypercholesterolemia, respectively (regardless of the study drug). The duration of everolimus exposure was longer in patients who developed these AEs versus patients without these AEs. Overall, 308 patients were exposed to treatment for at least 16 weeks (hyperglycemia, 39 of 269 patients; hypercholesterolemia, 20 of 288 patients). No association was observed between the development of these AEs and PFS (18.8 and 14.1 months with and without hyperglycemia, respectively, and 14.1 and 14.8 months with and without hypercholesterolemia, respectively). CONCLUSIONS: Although limitations apply because of the small number of AEs observed, there was no significant impact of these AEs on PFS; this suggests similar efficacy in the presence or absence of these events.


Asunto(s)
Antineoplásicos , Everolimus , Tumores Neuroendocrinos , Antineoplásicos/toxicidad , Ensayos Clínicos Fase III como Asunto , Everolimus/toxicidad , Humanos , Tumores Neuroendocrinos/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
4.
J Transl Med ; 19(1): 70, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588870

RESUMEN

BACKGROUND: The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP. METHODS: Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician's discretion. RESULTS: Between April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5-41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]). CONCLUSIONS: Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.


Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Cutáneas , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Carcinoma de Células de Merkel/tratamiento farmacológico , Humanos , Italia , Neoplasias Cutáneas/tratamiento farmacológico
5.
Gastroenterology ; 155(2): 479-489.e7, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29655834

RESUMEN

BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.


Asunto(s)
Antineoplásicos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Everolimus/uso terapéutico , Metformina/uso terapéutico , Tumores Neuroendocrinos/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Somatostatina/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Diabetes Mellitus Tipo 2/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
6.
Dig Dis ; 37(4): 325-333, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30897588

RESUMEN

BACKGROUND: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. OBJECTIVES: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. METHODS: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. RESULTS: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. CONCLUSION: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.


Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Organización Mundial de la Salud , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/diagnóstico , Estudios Retrospectivos
7.
Eur J Cancer Care (Engl) ; 28(3): e13007, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30740807

RESUMEN

INTRODUCTION: The well-being and quality of life (QoL) of long-term cancer survivors may be affected, both positively and negatively, by psychosocial factors related to the experience of being a cancer patient. We investigated whether, in long-term cancer survivors, the psychosocial impacts of cancer associate with socio-demographic-clinical variables; whether, within the positive and negative dimensions taken separately, some impacts are more intense than others; and whether these impacts explain QoL. METHODS: Italian long-term cancer survivors (n = 500) completed the Impact of Cancer (IOC-V2) and Short Form 36 Health Survey (SF-36) questionnaires. RESULTS: The IOC-V2 negative impact score associated with gender, education, occupational status and health issues, whereas no association was found between the positive impact score and socio-demographic-clinical variables. Of the positive impacts, Altruism/Empathy was the highest (p < 0.001); Positive self-evaluation was higher than Health awareness (p = 0.001); and Meaning of cancer was the lowest (p < 0.001). Among the negative impacts, Worry was the highest (p < 0.001), whereas Body changes concerns was higher than both Appearance concerns (p < 0.001) and Life Interferences (p < 0.001). The assessed impacts explained more than 25% of the variance of both physical and mental functioning scores. CONCLUSIONS: The provided data document psychosocial factors affecting QoL in Italian long-term cancer survivors.


Asunto(s)
Supervivientes de Cáncer/psicología , Calidad de Vida/psicología , Adulto , Anciano , Anciano de 80 o más Años , Altruismo , Imagen Corporal , Costo de Enfermedad , Escolaridad , Empatía , Empleo , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Italia , Masculino , Persona de Mediana Edad , Rendimiento Físico Funcional , Autoevaluación (Psicología) , Factores Sexuales
8.
Ann Surg Oncol ; 25(6): 1676-1685, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29488188

RESUMEN

BACKGROUND: Not all patients with resectable colorectal liver metastases (CLM) benefit from liver resection (LR); only patients with disease progression during chemotherapy are excluded from surgery. OBJECTIVE: This study was performed to determine whether tumor behavior (stable disease/progression) from the end of chemotherapy to LR impacts prognosis. METHODS: Patients undergoing LR after tumor response or stabilization during chemotherapy were considered. Overall, 128 patients who underwent examination by two imaging modalities (computed tomography/magnetic resonance imaging) after chemotherapy with a > 3-week interval between the two imaging modalities were analyzed. Any variation in CLM size was registered. Tumor progression was defined according to the response evaluation criteria in solid tumors (RECIST) criteria. RESULTS: Among 128 patients with stable disease or partial response to preoperative chemotherapy, 32 (25%) developed disease progression in the chemotherapy to LR interval, with a disease progression rate of 17% when this interval was < 8 weeks. Survival was lower among patients with progression than those with stable disease [3-year overall survival (OS) 23.0 vs. 52.4%, and recurrence-free survival (RFS) 6.3% vs. 21.6%; p < 0.001]. Survival was extremely poor in patients with early progression (< 8 weeks) (0.0% 2-year OS, 12.5% 6-month RFS). Disease progression in the chemotherapy to LR interval was an independent negative prognostic factor for OS and RFS [hazard ratio 3.144 and 2.350, respectively; p < 0.001]. CONCLUSIONS: Early disease progression in the chemotherapy to LR interval occurred in approximately 15% of patients and was associated with extremely poor survival. Even if these data require validation, the risk for early disease progression after chemotherapy should be considered, and, if progression is evident, the indication for surgery should be cautiously evaluated.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Neoplasias Hepáticas/terapia , Adulto , Anciano , Bevacizumab/administración & dosificación , Contraindicaciones de los Procedimientos , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Hepatectomía , Humanos , Irinotecán/administración & dosificación , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Criterios de Evaluación de Respuesta en Tumores Sólidos , Factores de Riesgo , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Carga Tumoral
9.
Pancreatology ; 18(2): 198-203, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29361429

RESUMEN

INTRODUCTION: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. AIM: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. PATIENTS AND METHODS: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th-75th IQR). RESULTS: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received ≥ 3 vs ≤ 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1-2 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. CONCLUSIONS: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases.


Asunto(s)
Antineoplásicos/uso terapéutico , Indoles/uso terapéutico , Tumores Neuroendocrinos/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Pirroles/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Humanos , Indoles/efectos adversos , Italia/epidemiología , Persona de Mediana Edad , Tumores Neuroendocrinos/epidemiología , Neoplasias Pancreáticas/epidemiología , Pirroles/efectos adversos , Estudios Retrospectivos , Sunitinib , Resultado del Tratamiento
10.
Neuroendocrinology ; 106(3): 211-220, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28554173

RESUMEN

PURPOSE: The RADIANT-4 randomized phase 3 study demonstrated significant prolongation of median progression-free survival (PFS) with everolimus compared to placebo (11.0 [95% CI 9.2-13.3] vs. 3.9 [95% CI 3.6-7.4] months) in patients with advanced, progressive, nonfunctional gastrointestinal (GI) and lung neuroendocrine tumors (NET). This analysis specifically evaluated NET patients with GI and unknown primary origin. METHODS: Patients in the RADIANT-4 trial were randomized 2:1 to everolimus 10 mg/day or placebo. The effect of everolimus on PFS was evaluated in patients with NET of the GI tract or unknown primary site. RESULTS: Of the 302 patients enrolled, 175 had GI NET (everolimus, 118; placebo, 57) and 36 had unknown primary (everolimus, 23; placebo, 13). In the GI subset, the median PFS by central review was 13.1 months (95% CI 9.2-17.3) in the everolimus arm versus 5.4 months (95% CI 3.6-9.3) in the placebo arm; the hazard ratio (HR) was 0.56 (95% CI 0.37-0.84). In the unknown primary patients, the median PFS was 13.6 months (95% CI 4.1-not evaluable) for everolimus versus 7.5 months (95% CI 1.9-18.5) for placebo; the HR was 0.60 (95% CI 0.24-1.51). Everolimus efficacy was also demonstrated in both midgut and non-midgut populations; a 40-46% reduction in the risk of progression or death was reported for patients in the combined GI and unknown primary subgroup. Everolimus had a benefit regardless of prior somatostatin analog therapy. CONCLUSIONS: Everolimus showed a clinically meaningful PFS benefit in patients with advanced progressive nonfunctional NET of GI and unknown primary, consistent with the overall RADIANT-4 results, providing an effective new standard treatment option in this patient population and filling an unmet treatment need for these patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Everolimus/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Tumores Neuroendocrinos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Método Doble Ciego , Everolimus/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
11.
Support Care Cancer ; 26(2): 651-656, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28918552

RESUMEN

PURPOSE: Understanding the quality of life (QoL) of cancer survivors is relevant to both clinical practice and health care policy. The current study compared the QoL profile in this specific population with that of a normative sample for the general population, as well as with those of both healthy and oncological patients normative sub-samples. In addition, associations between the obtained QoL profile and the main socio-demographic and clinical characteristics of the sample were examined. METHODS: Three hundred and ninety-two adult long-term cancer survivors (i.e., people 5 + years from their cancer diagnosis who were free from it and its treatments) were enrolled during follow-up visits and compiled the Short Form 36 Health Survey. RESULTS: In comparison with the normative data for the adult general population, the present sample showed lower scores in Physical functioning, Role-physical limitation, and Role-emotional limitations (all differences were both statistically and clinically significant); the difference in Vitality was only statistically significant. In all eight SF-36 scales, scores of the present sample were clinically and statistically lower than those of the normative healthy subsample, whereas they were statistically and clinically higher than those of normative subsample which had experienced cancer, except for Role-physical limitation. The QoL profile was associated with gender (p = 0.002), age (p = 0.001), education (p < 0.001), occupational status (p < 0.001), and the presence of other health issues (p < 0.001). CONCLUSION: These data support the utility of rehabilitative programs which integrate both healthcare and social interventions. In addition, they encourage the monitoring of the health status of this specific population, within a broad frame which simultaneously takes into consideration health and QoL.


Asunto(s)
Supervivientes de Cáncer/psicología , Oncología Médica/métodos , Calidad de Vida/psicología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
World J Surg ; 42(8): 2651-2659, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29423737

RESUMEN

BACKGROUND: Liver resection (LR) of colorectal metastases is associated with high recurrence risk. Aggressive local retreatment is advocated, but further recurrences may occur. Poor is known about presentation, treatment, and outcome of iterative recurrences. METHODS: A series of 323 consecutive patients undergoing first LR in the period 2004-2013 was reviewed. Patients with recurrence were included. Any local treatment (surgery, radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT)) was analyzed. If first recurrence (1st Rec) was treated, further recurrences and treatments were considered. RESULTS: Overall, 206 (63.8%) patients had 1st Rec; 105 (51.0%) were treated (72 surgery, 19 RFA, 14 SBRT). Among treated patients, 78.1% had 2nd Rec, 74.4% 3rd Rec, 72.2% 4th Rec. Liver involvement progressively decreased (from 81.6 to 30.8%), and pulmonary one increased (from 23.3 to 53.8%). The proportion of treated patients remained stable (1st Rec = 51%, 2nd Rec = 55%, 3rd Rec = 56.3%, 4th Rec = 69.2%): surgery and RFA decreased (from 35.4 to 23.1%; from 9.2 to 0%) and SBRT increased (from 6.8 to 46.2%). Overall, 105 patients received 205 treatments (133 operations in 80 patients). Surgery had the best local disease control: at 2 years 93.4% versus RFA 56.4% (p = 0.0008) and SBRT 74.0% (p = 0.051). In comparison with chemotherapy, recurrence treatment improved survival after 1st Rec (3-year survival 62.9 vs. 13.4%, p < 0.0001), 2nd Rec (61.3 vs. 22.5%, p < 0.0001), and 3rd Rec (2-year survival 88.9 vs. 30.8%, p = 0.005). CONCLUSIONS: Aggressive local treatment of recurrent metastases may improve survival, even in the case of iterative recurrences and extrahepatic lesions. Surgery is the standard, but a multidisciplinary approach should be adopted to enlarge the pool of treatable patients.


Asunto(s)
Ablación por Catéter , Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Radiocirugia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
13.
Lancet Oncol ; 18(10): 1411-1422, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28838862

RESUMEN

BACKGROUND: In the phase 3 RADIANT-4 trial, everolimus increased progression-free survival compared with placebo in patients with advanced, progressive, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (NETs). We now report the health-related quality of life (HRQOL) secondary endpoint. METHODS: RADIANT-4 is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 97 centres in 25 countries worldwide. Adults (aged ≥18 years) were eligible for the study if they had pathologically confirmed, advanced (unresectable or metastatic), non-functional, well-differentiated (grade 1 or 2) NETs of lung or gastrointestinal origin. Patients were randomly allocated (2:1) using block randomisation (block size of three) by an interactive voice response system to receive oral everolimus (10 mg per day) or placebo, both with best supportive care, with stratification by tumour origin, WHO performance status, and previous somatostatin analogue treatment. HRQOL was assessed with the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline (visit 2, day 1), every 8 weeks (±â€ˆ1 week) during the study for the first 12 months after randomisation, and every 12 weeks thereafter until study drug discontinuation. The primary endpoint, reported previously, was progression-free survival assessed by central review; HRQOL was a prespecified secondary endpoint. The prespecified secondary outcome measure was time to definitive deterioration (≥7 points) in FACT-G total score. Analyses were done on the full analysis set, consisting of all randomised patients, by intention to treat. Only data obtained while receiving the randomly allocated treatment were included in this analysis. Enrolment for RADIANT-4 was completed on Aug 23, 2013, but the trial is ongoing pending final analysis of the key secondary endpoint of overall survival. This trial is registered with ClinicalTrials.gov, number NCT01524783. FINDINGS: Between April 3, 2012, and Aug 23, 2013, 302 patients were enrolled; 205 were randomly allocated everolimus and 97 were assigned placebo. At baseline, 193 (94%) of 205 patients assigned everolimus and 95 (98%) of 97 allocated placebo had completed either fully or partly the FACT-G questionnaire; at week 48, 70 (83%) of 84 patients assigned everolimus and 22 (85%) of 26 allocated placebo completed FACT-G. Median time to definitive deterioration in FACT-G total score was 11·27 months (95% CI 9·27-19·35) with everolimus and 9·23 months (5·52-not estimable) with placebo (adjusted hazard ratio 0·81, 95% CI 0·55-1·21; log-rank p=0·31). INTERPRETATION: HRQOL was maintained for patients with advanced, non-functional, gastrointestinal or lung NETs, with no relevant differences noted between the everolimus and placebo groups. In view of the previous RADIANT-4 findings of longer progression-free survival with everolimus, our findings suggest that everolimus delays disease progression while preserving overall HRQOL, even with the usual toxic effects related to active targeted drug treatment for cancer. FUNDING: Novartis Pharmaceuticals.


Asunto(s)
Everolimus/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Tumores Neuroendocrinos/tratamiento farmacológico , Calidad de Vida , Adulto , Anciano , Supervivencia sin Enfermedad , Método Doble Ciego , Everolimus/efectos adversos , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/psicología , Humanos , Internacionalidad , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/psicología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/psicología , Placebos/uso terapéutico , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
14.
Lancet ; 387(10022): 968-977, 2016 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-26703889

RESUMEN

BACKGROUND: Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population. METHODS: In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783. FINDINGS: Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p<0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 [95% CI 0·40-1·05], one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 [9%] of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 [7%] vs 2 [2%]), infections (14 [7%] vs 0), anaemia (8 [4%] vs 1 [1%]), fatigue (7 [3%] vs 1 [1%]), and hyperglycaemia (7 [3%] vs 0). INTERPRETATION: Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract. FUNDING: Novartis Pharmaceuticals Corporation.


Asunto(s)
Antineoplásicos/uso terapéutico , Everolimus/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Neoplasias Gastrointestinales/mortalidad , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
15.
Oncologist ; 20(6): 586-92, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25948676

RESUMEN

BACKGROUND: Due to its rarity, male breast cancer (mBC) remains an inadequately characterized disease, and current evidence for treatment derives from female breast cancer (FBC). METHODS: We retrospectively analyzed the clinicopathological characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to 2013. RESULTS: From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed. Median age was 65 years (range: 25-87 years). Estrogen receptors were positive in 88 patients (96.7%), and progesterone receptors were positive in 84 patients (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was 51.5 months (range: 0.5-219.3 months). Five-year progression-free survival (PFS) was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2 presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5-year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%) experienced recurrent disease and 16 of 91 patients (17.6%) developed a second neoplasia. CONCLUSION: Male breast cancer shows different biological patterns compared with FBC, with higher positive hormone-receptor status and lower HER-2 overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS. IMPLICATIONS FOR PRACTICE: There is little evidence that prognostic features established in female breast cancer, such as grading and Ki-67 labeling index, could be applied to male breast cancer as well. This study found that grade 3 was associated with shorter overall survival and a trend for Ki-67 >20%; this could help in choosing the best treatment option in the adjuvant setting. Many questions remain regarding the impact of HER-2 positivity on survival and treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast cancer, the results suggest that common regimens of chemo-, endocrine and immunotherapy used in female breast cancer are safe and effective for men. Male breast cancer patients show a higher incidence of second primary tumors, especially prostate and colon cancers and should therefore be carefully monitored.


Asunto(s)
Neoplasias de la Mama Masculina/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Neoplasias Primarias Secundarias/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama Masculina/clasificación , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama Masculina/genética , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal no Infiltrante/tratamiento farmacológico , Carcinoma Intraductal no Infiltrante/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/genética , Pronóstico , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Estudios Retrospectivos
16.
Liver Int ; 35(3): 1077-86, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25040368

RESUMEN

BACKGROUND & AIMS: Sorafenib is the standard of care in advanced hepatocellular carcinoma (HCC), however no criteria have been established to select patients likely to benefit from this therapy. In this study, we evaluated the predictive role of microRNAs (miRNAs) in this setting of patients. METHODS: We profiled 522 miRNA in a series of 26 HCC patients treated with sorafenib (training set) and validated the results in an independent series of 58 patients (validation set). Formalin-fixed paraffin-embedded tumour and cirrhotic liver biopsies were used for RNA extraction and miRNAs profiling with TaqMan Arrays technology. Statistical analyses were used to correlate miRNA levels with clinical outcome, including time to progression (TTP), progression free (PFS), and overall survival. Cell viability and cell motility of HuH-7 or HepG2 HCC cells were tested in vitro after transfection with specific miRNA precursor, inhibitor or controls and sorafenib treatment. RESULTS: Six miRNAs were significantly associated with clinical variables in the training set and only miR-425-3p could be further validated. Higher levels of miR-425-3p were associated with longer TTP and PFS (P = 0.0008; HR = 0.4; 95% CI = 0.2-0.7 and P = 0.007; HR = 0.5; 95% CI = 0.3-0.9 respectively). Multivariate analysis confirmed the predictive significance of miR-425-3p. Furthermore, an association between increased miR-425-3p, cell death and reduced cell motility was defined in vitro in HCC cell lines treated with sorafenib. CONCLUSIONS: Assessment of miR-425-3p levels in liver biopsies could help in stratifying patients with advanced HCC for sorafenib treatment. These promising results need to be confirmed in a large prospective study.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , MicroARNs/metabolismo , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Estudios de Casos y Controles , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Niacinamida/uso terapéutico , Sorafenib
17.
World J Clin Cases ; 12(18): 3291-3294, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983428

RESUMEN

Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease. In addition to pathology, molecular analysis is pivotal in differential diagnosis, especially with malignant melanoma. A key aspect in identifying clear cell sarcoma is specific genetic alterations, notably the translocation of t(12;22) (q13;q13), a diagnostic hallmark of this sarcoma subtype, which is absent in malignant melanoma. Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.

18.
Endocr Pathol ; 35(3): 256-266, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38848012

RESUMEN

Ileal (I) and pancreatic (Pan) neuroendocrine tumors (NETs) are among the most common digestive neuroendocrine neoplasms (NENs). Coexisting NETs at both sites are rare, and establishing the primary or metastatic nature of the two lesions may be crucial for the appropriate treatment. We reviewed all the clinical reports of patients with INETs or PanNETs, diagnosed and treated in our ENETS Center of Excellence between 2012 and 2022. We selected patients with a history of synchronous or metachronous neuroendocrine (NE) lesions at the ileum and pancreas. For those with available histological samples from both sites, an immunohistochemistry (IHC) analysis for CDX2, Islet1, and serotonin has been performed. We found seven patients with NET in both the ileum and pancreas. F to M ratio was 4:3, and the median age at first diagnosis was 54 years (42-79). Five cases had synchronous lesions; in 2 cases, PanNETs were diagnosed respectively 8 and 56 months, after INETs. In four patients, with available histological samples from both the sites, a pathologic review and the IHC analysis have been performed, identifying three different scenarios: (i) primary INET metastatic to the pancreas, (ii) primary PanNET metastatic to the ileum, and (iii) synchronous primary PanNET and INET. In our experience, coexisting ileal and pancreatic NENs are rare occurrences. A multidisciplinary evaluation case-by-case and, whenever feasible, a comprehensive histopathological examination are needed to distinguish between metastatic and primary disease, in order to properly treat the patient.


Asunto(s)
Neoplasias del Íleon , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Neoplasias del Íleon/patología , Neoplasias del Íleon/complicaciones , Persona de Mediana Edad , Masculino , Anciano , Femenino , Adulto , Neoplasias Primarias Múltiples/patología
19.
Anticancer Res ; 44(8): 3507-3514, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39060087

RESUMEN

BACKGROUND/AIM: Surgical resection with a minimally invasive approach is the standard for diagnosing and treating solitary pulmonary nodules. A computed tomography (CT)-guided technetium99m-macroaggregated albumin (99mTc-MAA) injection-based procedure has been employed for small and non-palpable lung nodule radio-guided preoperative localization (ROLL). This procedure is usually followed by video-assisted thoracoscopic surgery (VATS). This study retrospectively evaluated the feasibility, clinicopathologic outcomes, and complications of this localization radio-guided procedure followed by uniportal VATS. PATIENTS AND METHODS: This retrospective study included 63 patients with suspicious lung nodules who underwent 99mTc-MAA CT-guided localization before uniportal VATS. The analysis examined the imaging and procedure characteristics, procedural risks, successful intra-operative localization, wedge resection, conversion from VATS to open thoracotomy, the reason, and histological diagnosis for each nodule. Also, it was evaluated how nodule and procedure features affected successful intra-operative localization. RESULTS: All patients were diagnosed using a CT scan, and 90.4% had a PET scan at basal staging. A round-glass morphology was present in 9.6% of cases, whereas most had a solid appearance. The mean nodule size was 9.78 mm (maximal tumoral diameter) with a 1-23 mm range. The mean distance from the pleural surface was 15.6 mm (range=1-117 mm). The detection rate of the 99mTc-MAA CT-guided localization procedure was 100%. Surgical procedures were uniportal VATS and transpleural thoracoscopy in 52 (82.5%) and 11 (17.5%) patients, respectively. The intraoperative localization rate was 98.4%. Pneumothorax represented the most frequent complication (6.3%), with one case clinically significant and three only with minimal radiological evidence. Pathology confirmed radical excision in all cases. CONCLUSION: Lung nodule localization with CT-guided 99mTc-MAA followed by uniportal VATS is feasible with a high success rate and low complication rate.


Asunto(s)
Neoplasias Pulmonares , Nódulo Pulmonar Solitario , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Cirugía Torácica Asistida por Video , Tomografía Computarizada por Rayos X , Humanos , Cirugía Torácica Asistida por Video/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Nódulo Pulmonar Solitario/cirugía , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología , Tomografía Computarizada por Rayos X/métodos , Adulto , Radiofármacos/administración & dosificación , Anciano de 80 o más Años
20.
Tumori ; 110(3): 203-208, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38326240

RESUMEN

INTRODUCTION: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials. This national initiative, here presented, aims to address the following knowledge gap: a) how much does histological diversity translate into clinical manifestation variety? b) are those chemotherapy regimens, recommended for conventional biliary tract cancers, potentially active in rare variants?Therefore, epidemiological, pathological, and clinical characterization of series of rare biliary histotypes/variants, for which therapeutic and follow-up data are available, will be collected. METHODS: An Italian task force on rare tumors of the biliary tract (IRaBiCa) has been created, whose initiative is a multicenter retrospective study involving 34 Italian cancer centers.Clinical data from approximately 100 patients will be collected and analyzed. Continuous variables will be presented as median ± standard deviation, while categorical variables will be expressed in terms of frequency. Kaplan-Maier analyses will be used to compare disease free, progression free and overall survival, according to the different histotypes. CONCLUSIONS: We expect to gather novel data on rare histotypes of biliary tract cancer that will be useful to support their molecular and immunological characterization.


Asunto(s)
Neoplasias del Sistema Biliar , Colangiocarcinoma , Humanos , Italia/epidemiología , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/terapia , Neoplasias del Sistema Biliar/tratamiento farmacológico , Estudios Retrospectivos , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Femenino , Masculino , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Persona de Mediana Edad , Anciano
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