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1.
Dermatology ; 240(4): 523-530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38631324

RESUMEN

BACKGROUND: Novel oncologic therapies, including epidermal growth factor receptor inhibitors (EGFR-Is) and immune checkpoint inhibitors (ICIs), are associated with a new spectrum of adverse reactions, with prominent cutaneous toxicities. The impact of cutaneous adverse events (cAEs) on patients' quality of life (QoL) represents an unmet clinical need. OBJECTIVES: The aims of this study were (1) to assess whether cutaneous toxicities directed therapies are effective in reducing the QoL burden via the submission of 2 patient reported outcome measures (PROMs); (2) to investigate whether class of oncologic therapy, type of cAE and toxicity severity differently impact on patients' QoL. METHODS: A prospective observational study was conducted at the Dermatology department of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, from October 2018 to October 2019. Patients aged ≥18 years, under therapy with EGFR-Is or ICIs and experiencing a treatment-related cAE were eligible for the study. Dermatology Life Quality Index (DLQI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 version 3.0 (EORTC QLQ-C30) were administered to patients at first clinical visit (T0), at 1-month (T1), and at 3-month (T2) dermatological follow-up. RESULTS: Sixty cAEs of 51 patients have been recorded. A significant difference in the mean score for both DLQI and EORTC QLQ-C30 was found along the 3-months dermatological follow-up (p < 0.0001). A similar QoL improvement was reported for PROMs stratified by class of therapy and toxicity severity (p < 0.0001). No difference was reported for patients with pyogenic granuloma-like lesions and psoriasiform eruption as per DLQI. Class of therapy and toxicity severity did not differently impact on patients' QoL at selected timepoints; we reported a higher EORTC QLQ-C30 score at T2 for patients developing psoriasiform eruption compared to other types of cAEs. CONCLUSIONS: Early patients' referral to dermatologists and tailored management could result in better QoL.


Asunto(s)
Erupciones por Medicamentos , Receptores ErbB , Inhibidores de Puntos de Control Inmunológico , Calidad de Vida , Humanos , Femenino , Receptores ErbB/antagonistas & inhibidores , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Erupciones por Medicamentos/etiología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Adulto , Medición de Resultados Informados por el Paciente , Anciano de 80 o más Años , Antineoplásicos/efectos adversos
2.
Cancer Immunol Immunother ; 72(7): 2217-2231, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36869232

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. METHODS: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography-tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile. RESULTS: Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity. CONCLUSIONS: A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage.


Asunto(s)
Antineoplásicos Inmunológicos , Neoplasias , Humanos , Estudios Prospectivos , Espectrometría de Masas en Tándem , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Citocinas , Estudios Retrospectivos
3.
Pancreatology ; 23(5): 543-549, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37236853

RESUMEN

BACKGROUND/OBJECTIVES: Insulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a recent technique that has emerged as a minimally invasive therapeutic option for patients with pancreatic lesions not eligible for surgery. In this study, we aimed to describe a series of patients with unresectable pancreatic insulinoma treated with EUS-RFA. METHODS: This is a single-center, retrospective study including all consecutive patients with functioning pancreatic insulinoma undergoing EUS-RFA for surgical unfitness or surgery refusal, between March 2017 and September 2021. Technical success (i.e., complete mass ablation), adverse event rate and severity, clinical and radiologic outcomes (i.e., symptom remission with a normal concentration of blood glucose, and the presence of intralesional necrosis), and post-procedural follow-up were assessed. RESULTS: A total of 10 patients (mean age: 67.1 ± 10.1years; F:M 7:3) were included. The mean size of insulinoma was 11.9 ± 3.3 mm. Technical success and clinical remission were achieved in 100% of patients. Only one (10%) patient was successfully treated with two RFA sessions. Two procedure-related early adverse events occurred, including two (20%) cases of mild abdominal pain. No major complications were observed. The complete radiologic response within 3 months after EUS-RFA was observed in all patients (100%). After a median follow-up of 19.5 (range12-59) months, symptom remission and persistent euglycemia were assessed in all the patients. CONCLUSIONS: Data from this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for pancreatic insulinomas in patients unwilling or unable to undergo surgery with medium-term efficacy.


Asunto(s)
Insulinoma , Neoplasias Pancreáticas , Ablación por Radiofrecuencia , Humanos , Persona de Mediana Edad , Anciano , Insulinoma/diagnóstico por imagen , Insulinoma/cirugía , Insulinoma/patología , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Ablación por Radiofrecuencia/métodos , Endosonografía/métodos , Ultrasonografía Intervencional
4.
Int J Mol Sci ; 24(21)2023 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-37958702

RESUMEN

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Animales , Humanos , Neoplasias Hipofisarias/patología , Hipófisis/metabolismo , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/metabolismo , Agresión , Microambiente Tumoral/genética
5.
Dermatol Ther ; 35(3): e15276, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34923731

RESUMEN

In the context of the SARS-CoV-2 pandemic, it is important to ensure the quality of cancer treatment as well as patients and health professionals' safety. Individual-based treatment options should be considered in patients with advanced epithelial skin cancer, who are typically elderly and frail. Aim of this study was to assess feasibility and safety of Contact Skin Radiation Therapy (CSRT) to treat basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) during SARS-CoV-2 pandemic. Patients with advanced and difficult-to-treat BCC or SCC were discussed at skin multidisciplinary tumor board (S-MDTB) from February the 21st to May the 4th (phase 1 Italian Pandemic) and retrospectively analyzed. Patient's triage following internal recommendations was daily performed. CSRT was delivered in 8 fractions of 5 Gy each, twice a day. Beyond the clinical outcomes, treatment success indicators, such as the completion of CSRT without SARS-CoV-2 occurrence, were identified to evaluate the feasibility of CSRT during pandemic. A post-treatment psychological assessment regarding patient's safety perception was performed. Six male patients (median age 80 years; range 62-92) with histologically confirmed BCC or SCC were treated with CSRT. Complete clinical remission was achieved in 5/6 patients (83.4%). No high-grade acute toxicities occurred during treatment. No patients or healthcare personnel developed SARS-CoV-2 infection. All the treatment success indicators were achieved. CSRT represents a safe, and feasible treatment option even during the pandemic emergency period. Hypofractionation could be an option to reduce total number of fractions and, consequently, infective risk exposition.


Asunto(s)
Braquiterapia , COVID-19 , Neoplasias Cutáneas , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Neoplasias Cutáneas/terapia
6.
BMC Ophthalmol ; 22(1): 497, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36536312

RESUMEN

PURPOSE: The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. METHODS: A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant 'Core team' or - when required - by a broader 'Extended team'. RESULTS: During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). CONCLUSIONS: Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.


Asunto(s)
Neoplasias , Grupo de Atención al Paciente , Humanos , Centros de Atención Terciaria , Estudios Retrospectivos , Neoplasias/terapia , Oncología Médica
7.
J Clin Apher ; 37(1): 65-69, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34822725

RESUMEN

BACKGROUND: Germ cell tumors represent, among solid cancers, a potentially curable disease even if up to 20% to 30% of patients (pts) relapse after first-line treatment especially considering intermediate and poor prognosis groups. In this scenario, patients are candidates for high-dose chemotherapy and autologous stem-cells transplantation as second-line treatment even though stem-cells mobilization potential can be affected by several cycles and regimens of chemotherapy. To date, plerixafor is authorized in poor mobilizer adult pts diagnosed with lymphoma or multiple myeloma and in pediatric solid tumors or lymphoma. Therefore, the use of plerixafor in adult pts with relapsing/refractory GCT is still off label. MATERIALS AND METHODS: In our study, we describe mobilization and collection of peripheral blood stem cells for 10 pts with germ cell tumors. Six patients underwent plerixafor administration since classified as poor mobilizers based on WBC count (>5.000/µL) and CD34+ cell count (<15/µL) the day before apheresis procedure. RESULTS: On the first day of apheresis, plerixafor administration in poor mobilizers made possible a remarkable boost of CD34+ cells in such a way to overlap that of good mobilizers' (32/µL vs 35/µL, respectively, P > .05). CONCLUSION: Therefore, in our experience, plerixafor made a good fraction of poor mobilizer patients eligible for mobilization and collection and able to undergo the predicted autologous stem-cells transplantation; thus, the lack of access to the use of plerixafor in this setting of patients risks jeopardizing an effective treatment, especially in case of poor prognosis.


Asunto(s)
Bencilaminas/uso terapéutico , Ciclamas/uso terapéutico , Recurrencia Local de Neoplasia/terapia , Neoplasias de Células Germinales y Embrionarias/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Bencilaminas/farmacología , Eliminación de Componentes Sanguíneos , Ciclamas/farmacología , Femenino , Movilización de Célula Madre Hematopoyética , Humanos , Masculino , Persona de Mediana Edad , Células Madre de Sangre Periférica/efectos de los fármacos , Estudios Retrospectivos , Trasplante Autólogo , Adulto Joven
8.
Radiol Med ; 127(7): 773-783, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35606609

RESUMEN

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low ≥ G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team.


Asunto(s)
Neoplasias Encefálicas , Melanoma , Radiocirugia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Melanoma/terapia , Radiocirugia/métodos , Estudios Retrospectivos
9.
Cancer Immunol Immunother ; 68(7): 1179-1185, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31175402

RESUMEN

BACKGROUND: No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease. PATIENTS AND METHODS: In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed. RESULTS: Seventeen patients were enrolled. A median of 8 cycles were administered (range 2-28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869-0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3-4 side effects. CONCLUSIONS: The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Melanoma/tratamiento farmacológico , Neoplasias de la Úvea/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Estudios Prospectivos , Neoplasias de la Úvea/inmunología , Neoplasias de la Úvea/mortalidad
10.
Future Oncol ; 15(20): 2349-2360, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28440086

RESUMEN

Aim: This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases. Patients & methods: Forty patients with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m2 twice-daily on days 1-14 every 3 weeks. Results: Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients. Conclusion: DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Capecitabina/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Irinotecán/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Esquema de Medicación , Sistemas de Liberación de Medicamentos/métodos , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Microesferas , Persona de Mediana Edad , Supervivencia sin Progresión
11.
Curr Treat Options Oncol ; 20(3): 23, 2019 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-30790063

RESUMEN

OPINION STATEMENT: Unresectable or relapsed malignant pleural mesothelioma (MPM) has dismal prognosis. First-line combination therapy with pemetrexed and a platinum analog allows a modest survival benefit, while no clear therapeutic options exist for the second-line therapy. In this setting, pemetrexed seems to be the most active drug; however, the inclusion in front-line treatment limits its use in further lines. Nevertheless, rechallenge with one or both drugs used in first-line remains a feasible strategy for responder patients. Alternatively, only few cytotoxic drugs have demonstrated a mild activity in refractory MPM. Among other options, targeted therapy has unfortunately produced disappointing results as salvage treatment probably due to the lack of a clear understanding of the tumor biology. In contrast, recent data suggest moderate efficacy and mild toxicity of immunotherapy also for the treatment of MPM. The combination of checkpoint inhibitors with chemotherapy or other immunological agents seems promising and could really "raise the bar" in this setting.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Terapia Molecular Dirigida , Neoplasias Pleurales/tratamiento farmacológico , Antineoplásicos , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mesotelioma/mortalidad , Mesotelioma/patología , Mesotelioma Maligno , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Pronóstico , Resultado del Tratamiento
12.
Eur J Cancer Care (Engl) ; 28(5): e13112, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31148330

RESUMEN

OBJECTIVE: Painful bone metastases cause reduced quality of life (QoL) in patients with castration-resistant prostate cancer (CRPC). Alpha-emitter 223Radium is associated with a clear survival benefit and significant bone pain palliation in CRPC patients with symptomatic bone metastases. The aim of this study was to evaluate the association between pain relief and psychological distress during the time course of therapy in patients treated with 223Radium. METHODS: A total of 63 patients with mCRPC undergoing 223Radium treatment in our Nuclear Medicine Unit, carefully instructed on the possibility of improving the pain and increasing the survival by the treatment, were retrospectively evaluated. Pain response during treatment was assessed with the Brief Pain Inventory Numeric Rating Scale. Psychological distress was evaluated through the analysis of specific items from EORTC QoL questionnaires C30 and BM22, submitted to patients at baseline and after each 223Radium cycle. RESULTS: Pain intensity showed a significant decrease after first 223Radium administration (-1.03 points, p = 0.0032), with a subsequent stability through the course of treatment (-1.30 points, p = <0.001). Psychological status did not show significant variations during 223Radium treatment, and no association was found between psychological status and pain relief in our population. CONCLUSIONS: In our experience, bone pain palliation provided by 223Radium do not correlate with an improved psychological status in patients with advanced PC. This observation emphasises the role of the psychological aspect in the evaluation of the QoL and the necessity of a multidisciplinary approach in which the emotional aspect of the patient is carefully evaluated.


Asunto(s)
Neoplasias Óseas/radioterapia , Dolor en Cáncer/psicología , Neoplasias de la Próstata Resistentes a la Castración/patología , Distrés Psicológico , Radio (Elemento)/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/complicaciones , Neoplasias Óseas/psicología , Neoplasias Óseas/secundario , Dolor en Cáncer/etiología , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Calidad de Vida , Estudios Retrospectivos
13.
Int J Mol Sci ; 20(3)2019 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-30682772

RESUMEN

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is then able to enhance inflammation and to influence gene expression. At the same time, there is an intense cross-talk between the microbiota and the immunological niche in the intestinal mucosa. These interactions may pave the way to the development, growth and spreading of cancer, especially in the gastro-intestinal system. Here, we review the changes in microbiota composition, how they relate to the immunological imbalance, influencing the onset of different types of cancer and the impact of these mechanisms on the efficacy of traditional and upcoming cancer treatments.


Asunto(s)
Microbioma Gastrointestinal/inmunología , Neoplasias Gastrointestinales/microbiología , Animales , Neoplasias Gastrointestinales/inmunología , Humanos , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología
14.
Int J Mol Sci ; 20(21)2019 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-31683701

RESUMEN

Conjunctival melanoma (CjM) is a rare, primary cancer of the ocular region. Genetic and epigenetic characteristics of conjunctival melanoma have not been completely elucidated yet. Conjunctival melanoma presents similarities with cutaneous melanoma, with substantial differences in the biological behavior. We reviewed the genetic and epigenetic insights of CjM involved in invasion and metastatic spread. CjM is commonly characterized by mutations of v-raf murine sarcoma viral oncogene homolog B1 (BRAF), neurofibromin 1 (NF1) and telomerase reverse transcriptase (TERT), high expression of mammalian target of rapamycin (mTOR) and heat shock protein 90 (HSP90), frequent phosphatase and tensin homolog (PTEN) loss and upregulation of specific miRNAs. These features should identify CjM as a distinct subset of melanoma with its own profile, which is more similar to cutaneous melanoma than mucosal melanoma and remarkably different from uveal melanoma.


Asunto(s)
Neoplasias de la Conjuntiva/genética , Epigénesis Genética/genética , Predisposición Genética a la Enfermedad/genética , Melanoma/genética , Mutación , Humanos , Neurofibromina 1/genética , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas B-raf/genética , Telomerasa/genética
15.
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
16.
Neuroendocrinology ; 107(4): 375-386, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30300897

RESUMEN

BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.


Asunto(s)
Oncología Médica , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Guías de Práctica Clínica como Asunto , Adulto , Anciano , Estudios de Cohortes , Femenino , Historia del Siglo XXI , Humanos , Internacionalidad , Masculino , Oncología Médica/organización & administración , Oncología Médica/normas , Oncología Médica/tendencias , Persona de Mediana Edad , Clasificación del Tumor/métodos , Clasificación del Tumor/normas , Clasificación del Tumor/tendencias , Tumores Neuroendocrinos/epidemiología , Neoplasias Pancreáticas/epidemiología , Guías de Práctica Clínica como Asunto/normas , Estudios Retrospectivos , Sociedades Médicas/organización & administración , Sociedades Médicas/normas , Organización Mundial de la Salud
17.
Future Oncol ; 14(10): 919-926, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29528255

RESUMEN

AIM: To evaluate gefitinib outcomes in EGFR-mutated non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, according to their sarcopenia status. PATIENTS & METHODS: We retrospectively evaluated 33 patients with advanced NSCLC and EGFR mutations (exon 19 or 21), dividing them into sarcopenic patients, with low skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men, and nonsarcopenic patients. RESULTS: Sarcopenia does not affect response to gefitinib treatment in EGFR mutated NSCLC patients, even if it is a bad prognostic indicator for overall survival (p = 0.035). CONCLUSION: Early recognition of sarcopenia is beneficial for prevention of cancer cachexia and detection of patients at potential risk of serious adverse events. Gefitinib dosage should be reduced and modulated in sarcopenic patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Quinazolinas/uso terapéutico , Sarcopenia/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Caquexia/prevención & control , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Relación Dosis-Respuesta a Droga , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Estudios Retrospectivos , Sarcopenia/tratamiento farmacológico , Sarcopenia/mortalidad , Análisis de Supervivencia , Resultado del Tratamiento
18.
Curr Treat Options Oncol ; 17(12): 59, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27766545

RESUMEN

OPINION STATEMENT: New treatments-as immunotherapies and new antiangiogenic agents-are now available in second-line setting for patients affected by EGFR wild-type and ALK-negative non-small-cell lung cancer (NSCLC). Nintedanib, ramucirumab, nivolumab and pembrolizumab have to be included in the therapeutic sequences for patients affected by NSCLC, but no clear selection criteria are to date offered, except for patients with PD-L1 expression ≥50 %. Performance status, smoking habits and comorbidities should be considered as clinical criteria in order to select the appropriate treatment, but also tumour characteristics as histotype, platinum resistance and rapid progression after a first-line therapy should be taken into account. The aim of the present paper is to identify subgroups of patients eligible for different therapy sequences.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Animales , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Terapia Combinada , Humanos , Inmunoterapia , Terapia Molecular Dirigida , Estadificación de Neoplasias , Retratamiento , Resultado del Tratamiento
19.
Future Oncol ; 12(10): 1299-307, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26996100

RESUMEN

Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine therapy and in hormone-negative disease. Optimal duration, efficacy and safety of a maintenance endocrine therapy or chemotherapy after an induction treatment are still a matter of debate. We performed a literature review to identify studies regarding maintenance hormonal and chemotherapy treatments in metastatic breast cancer. We analyzed data relating to efficacy (improvement of progression-free survival and overall survival) and safety (symptoms relief and quality of life [QoL]). Maintenance endocrine therapy could prolong progression-free survival with a better control of symptoms and improving QoL. Maintenance chemotherapy prolong the response to a previous treatment, worsening the QoL, except for metronomic capecitabine.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia de Mantención/métodos , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Calidad de Vida
20.
Clin Nucl Med ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38914099

RESUMEN

ABSTRACT: A 61-year-old man underwent splenopancreasectomy for a 3-cm neuroendocrine tumor of the body of the pancreas (G2, pT1 pN0, Ki67 3%). Five months after surgery 68Ga-DOTATOC PET/CT showed increased radiotracer uptake in a solid tissue of the splenic fossa, possibly referring to a splenosis nodule. After 19 months, a further 68Ga-DOTATOC PET/CT showed a significant functional and dimensional increase of the previously detected tissue and the appearance of a new finding in the left lateral abdominal wall. In the suspicion of neuroendocrine tumor relapse, the patient underwent surgical excision of the documented lesions. Histology showed splenosis in both nodules.

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