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1.
Radiol Med ; 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606609

RESUMO

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.

2.
Hum Vaccin Immunother ; : 1-10, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258435

RESUMO

Metastatic uveal melanoma (UM) is a poor prognosis malignancy. Immunotherapy is commonly employed, despite the low activity, considering the lack of other effective systemic treatments. In this study, the prognostic and predictive role of soluble immune checkpoints and inflammatory cytokines/chemokines in 22 metastatic UM patients was evaluated. Baseline levels of these molecules were assessed, as well as their changes during anti-PD-1 therapy. The correlation between soluble immune checkpoints/cytokines/chemokines and survival was analyzed. A comparison between circulating immune profile of metastatic cutaneous melanoma (CM), for which immunotherapy is a mainstay of treatment, and UM during anti-PD-1 therapy was also performed. Three immune molecules resulted significantly higher in metastatic UM patients with survival <6 months versus patients with survival ≥6 months: IL-8, HVEM and IDO activity. Considering these three molecules, we obtained a baseline score able to predict patients' survival. The same three molecules, together with soluble(s) CD137, sGITR and sCD27, resulted significantly lower in patients with survival >30 months. We also observed an increase of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 during anti-PD-1 treatment, as well as IDO activity, IP-10 and CCL2. Several of these molecules were significantly higher in UM compared to CM patients during anti-PD-1 therapy. The analysis of circulating immune molecules allows to identify patients with poor prognosis despite immunotherapy and patients with long survival treated with an anti-PD-1 agent. The different serum concentration of these molecules during anti-PD-1 therapy between UM and CM reflects the different efficacy of immune checkpoint inhibitors.

3.
Anticancer Res ; 42(3): 1487-1493, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220243

RESUMO

BACKGROUND/AIM: Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin. The aim of this study was to investigate the safety and activity of metformin combined with nivolumab in diabetic cancer patients. PATIENTS AND METHODS: Patients with advanced melanoma, renal cell carcinoma or lung cancer receiving nivolumab with concurrent diabetes treated with metformin were retrospectively collected. The primary endpoint was the safety of nivolumab plus metformin combination. RESULTS: We collected 40 patients with solid tumors who received metformin for concomitant diabetes and nivolumab as anticancer therapy in four Italian Hospitals. The concomitant use of nivolumab and metformin was well tolerated; adverse events (AEs) of any grade occurred in 75% of patients (mainly fatigue, pruritus, rash, and asthenia). Grade 3 AEs occurred only in 20% of cases; no grade 4 AEs were observed. A statistically significant correlation was found between higher doses of metformin (>1,000 mg daily) and longer progression-free survival (p=0.021), overall survival (p=0.037) and higher overall response rate. CONCLUSION: The combination of nivolumab and metformin was safe and might have an antitumor activity, supporting further investigations on the synergistic antitumor effect of this combination.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Metformina/uso terapêutico , Neoplasias/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Itália , Masculino , Metformina/efeitos adversos , Neoplasias/diagnóstico , Neoplasias/imunologia , Neoplasias/mortalidade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo
4.
Clin Cancer Res ; 28(5): 1027-1037, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34980602

RESUMO

PURPOSE: CD137 molecule is expressed by activated lymphocytes, and in patients with cancer identifies the tumor-reactive T cells. In solid tumors, high levels of circulating CD137+ T cells are associated with the clinical response and the disease-free status. Here, we examined the role of the CD137+ T cells in the improvement of patients' selection for immunotherapy treatment. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells derived from 109 patients with metastatic cancer (66 patients for the identification cohort and 43 for the validation cohort) were analyzed for the expression of CD3, CD4, CD8, CD137, and PD1 molecules before the beginning of anti-PD1 therapy. Twenty healthy donors were used as control. The soluble form of CD137 (sCD137) was also analyzed. The CD137+ T cell subsets and the sCD137 were correlated with the clinicopathologic characteristics. The distribution of CD137+ T cells was also examined in different tumor settings. RESULTS: The percentage of CD137+ T cells was higher in healthy donors and in those patients with a better clinical status (performance status = 0-1, n°metastasis≤2) and these high levels were ascribed to the CD8+CD137+ T cell population. The high frequency of CD137+ and CD8+CD137+ T cells resulted as a prognostic factor of overall survival (OS) and progression-free survival (PFS), respectively, and were confirmed in the validation cohort. High levels of CD3+CD137+PD1+ lymphocytes were associated with a low number of metastasis and longer survival. Instead, the high concentration of the immunosuppressive sCD137 in the serum is associated with a lower PFS and OS. In tumor bed, patients with a complete response showed a high percentage of CD137+ and CD8+ T cells. CONCLUSIONS: We propose the CD137+ T subset as an immune biomarker to define the wellness status of the immune system for successful anticancer immunotherapy.


Assuntos
Leucócitos Mononucleares , Neoplasias , Linfócitos T CD8-Positivos , Humanos , Imunoterapia , Leucócitos Mononucleares/metabolismo , Contagem de Linfócitos , Neoplasias/terapia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
5.
J Clin Apher ; 37(1): 65-69, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34822725

RESUMO

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.


Assuntos
Benzilaminas/uso terapêutico , Ciclamos/uso terapêutico , Recidiva Local de Neoplasia/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Benzilaminas/farmacologia , Remoção de Componentes Sanguíneos , Ciclamos/farmacologia , Feminino , Mobilização de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
6.
Urol Oncol ; 40(3): 108.e19-108.e25, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34903453

RESUMO

BACKGROUND: The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection of a bladder tumor consists of adjuvant intravesical therapy and strict and long surveillance with urine cytology and cystoscopy. The Bladder EpiCheck test (Nucleix Ltd) (BE) is a newly developed urinary markers based on DNA methylation changes in a panel of 15 genomic biomarkers, with a promising performance in term of non-invasive NMIBC detection. METHODS: In this study we prospectively enrolled 151 consecutive patients with high grade NMIBC, treated with intravesical BCG and mitomycin C therapy and evaluated during the follow-up by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. The Bladder EpiCheck test was performed at the same time of urine cytology in voided specimen. In all cases with positive cytology the diagnosis was confirmed by histology and a diagnosis was made according to the 2017 tumor, node, metastasis (TNM) classification and graded using both the 1973 and the 2004 World Health Organization (WHO) classifications. RESULTS: At three months of follow-up, we reported similar overall specificity rates for BE and urine cytology (85,1% vs 86,3%). In the group of patients with carcinoma in situ (CIS), we found the same specificity for BE and urine cytology (81,4%), while in the groups of patients with papillary high grade NMIBC, the specificity of BE was higher compared to cytology (96,3% vs 90,4%). The sensitivity of BE was always higher compared to cytology during all the follow-up both for papillary NMIBC and CIS. CONCLUSION: In the early follow-up of NMIBC the EpiCheck test might replace urinary cytology.


Assuntos
Carcinoma in Situ , Neoplasias da Bexiga Urinária , Carcinoma in Situ/patologia , Cistoscopia , Feminino , Seguimentos , Humanos , Masculino , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
7.
Dermatol Ther ; 35(3): e15276, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34923731

RESUMO

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.


Assuntos
Braquiterapia , COVID-19 , Neoplasias Cutâneas , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Neoplasias Cutâneas/terapia
8.
Immunotherapy ; 14(1): 65-75, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34751039

RESUMO

Kidney transplantation leads to an increased risk of cancer. Melanoma is one of the most frequent neoplasms in kidney transplant recipients. Transplanted patients were excluded from trials with checkpoint inhibitors in melanoma. The authors performed a systematic review regarding the use of anti-PD1 and anti-CTLA4 agents in renal transplanted patients with melanoma. Thirty-four cases were included (24 progressive disease, eight partial responses and one stable disease) but no complete response were reported. Fourteen graft rejections were observed, especially with anti-PD1 agent. The median time from the start of immune-checkpoint inhibitor and rejection was 21 days. Response rate was similar between patients with rejection and patients without rejection. The benefit of immune-checkpoint inhibitors versus the risk of allograft rejection should be carefully weighted for each patient. A multidisciplinary approach should be considered to discuss the most appropriate treatment for every case, given the aggressiveness of melanoma in these subsets of patients.


Assuntos
Rejeição de Enxerto/prevenção & controle , Inibidores de Checkpoint Imunológico/uso terapêutico , Transplante de Rim , Melanoma/tratamento farmacológico , Transplantados/estatística & dados numéricos , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Melanoma/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/uso terapêutico
9.
Cancers (Basel) ; 13(22)2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34830841

RESUMO

Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovative therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as the YAP/TAZ pathway. At present, there are no drugs that target the latter and this likely explains the failure of mitogen activated kinase kinase inhibitors. Immune checkpoint blockers, despite the game changing effect in cutaneous melanoma (CM), show only limited effects in UM probably because of the low mutational burden of 0.5 per megabase and the unavailability of antibodies targeting the main immune checkpoint active in UM. The highly pro-tumorigenic microenvironment of UM also contributes to therapy resistance. However, T-cell redirection by a soluble T-cell receptor that is fused to an anti-CD3 single-chain variable fragment, local, liver specific therapy, new immune checkpoint blockers, and YAP/TAZ specific drugs give new hope to repeating the success of innovative therapy obtained for CM.

10.
Curr Oncol Rep ; 23(12): 147, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748099

RESUMO

PURPOSE OF REVIEW: Therapeutic alternatives to treat metastatic renal cell carcinoma (mRCC) are increasing, and combination therapies, including antiangiogenic agents and tyrosine kinase/mTOR/immune checkpoint inhibitors, are identified as the gold standard driven by the results of recent clinical studies. Nevertheless, the real-world RCC population is very heterogeneous, with categories of patients not represented in the enrolled trial population who may not benefit more from these treatments. The purpose of this expert review is to assess the rationale on which tyrosine kinase alone may still be a viable first-line treatment option for some subgroups of patients with mRCC. RECENT FINDINGS: The first-line treatment with tyrosine kinase inhibitor monotherapy can still be considered an effective tool for addressing selected mRCCs, as highlighted by the successful outcome in a range of subjects such as favorable-risk patients, the ones suffering from autoimmune diseases, those with pancreatic or lung metastases, or previously undergoing organ transplantation and elderly subjects. Some selected categories of patients may still benefit from monotherapy with TKI, and smart sequential therapies can also be considered instead of a combination strategy. Tyrosine kinase inhibitors can also act as immune modulator agents, boosting the immune response to facilitate and potentiate the therapeutic effectiveness of subsequent immunotherapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Células Renais/mortalidade , Humanos , Proteínas Tirosina Quinases/antagonistas & inibidores , Análise de Sobrevida
11.
Immunotherapy ; 13(18): 1457-1463, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34664999

RESUMO

Determining the most appropriate management strategy for patients with large tumor masses is a very challenging issue. Unconventional radiotherapy modalities, such as spatially fractionated radiation therapy (SFRT), are associated with dramatic responses. Recent studies have suggested that systemic immune activation may be triggered by SFRT delivery to primary tumor lesion. This report describes the case of a patient treated with a novel form of immune-sparing partially ablative irradiation (ISPART) for a bulky peritoneal metastasis from renal cell cancer, refractory to anti-PD-1 therapy (nivolumab) as third-line therapy after sequential therapy with sunitinib and cabozantinib. The observed response suggests that there may be a synergistic effect between ISPART and immunotherapy. This case report supports the inclusion of ISPART in patients presenting with bulky lesions treated with checkpoint inhibitors .


Lay abstract Managing large tumor masses is a very challenging issue. In recent years, radiotherapy methods have been linked with good responses, which may be due to the activation of immune mechanisms. We describe the case of a patient with a large tumor mass from renal cell cancer. The patient had already been treated with anti-PD-1 therapy, after treatment with sunitinib and cabozantinib, along with radiotherapy. The results suggest that radiotherapy together with immunotherapy is very effective in enhancing immune response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais , Fracionamento da Dose de Radiação , Imunoterapia , Neoplasias Renais , Neoplasias Peritoneais , Anilidas/administração & dosagem , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/administração & dosagem , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Piridinas/administração & dosagem , Sunitinibe/administração & dosagem
12.
Hum Pathol ; 118: 42-48, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34582934

RESUMO

Numerous studies showed that bladder urothelial carcinoma and upper urothelial tract carcinoma (UTUC) display clinical and genomic similarities. In order to analyze that the same panel of biomarkers used in the diagnosis of bladder urothelial carcinoma could be suitable for early detection of UTUC, we performed a retrospective study in which we analyzed Bladder EpiCheck scores in the urinary samples obtained by selective ureteral catheterization in a high-grade UTUC cohort, correlating the results with urinary cytology and diagnostic urethral biopsies. The present study represents a retrospective analysis of 82 patients with clinically localized high-grade UTUC (60 renal pelvis UTUC, 22 ureter UTUC) who had undergone a radical nephroureterectomy (RNU) at our Urology department from June 2018 to November 2020. Before any surgical procedure, one sample of urine, obtained by selective ureteral catheterization, was collected for each patient for cytological examination, and the remaining material was stored for the Bladder EpiCheck test. Our results showed that the sensitivity of the methylation test for high-grade UTUC was about 97.4%, significantly higher than the sensitivity of urinary cytology either considering the HGUC cytological diagnosis or including in the positive cases the SHGUC cytological diagnosis (97.4% versus 59% or 70.5%). The methylation analysis of urinary samples may represent a valid tool in the diagnostic process of patients with suspected UTUC. In cases with a difficult clinical decision after upper urinary tract biopsy and cytology, the methylation test could assist in the clinical management of UTUC patients.


Assuntos
Carcinoma de Células de Transição/urina , Citodiagnóstico/métodos , Metilação de DNA , Neoplasias Urológicas/urina , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Urológicas/diagnóstico
13.
Cancers (Basel) ; 13(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209819

RESUMO

In this paper we aimed to address the role of pulmonary metastasectomy (PM) in patients affected by Lung Metastases (LM) from Renal Cell Carcinoma (RCC) and to analyse prognostic factors affecting overall survival (OS), disease-free interval (DFI) between primary RCC and first LM, and disease-free survival (DFS) after PM and before lung recurrence. Medical records of 210 patients who underwent PM from RCC in 4 Italian Thoracic Centres, from January 2000 to September 2019, were collected and analysed. All patients underwent RCC resection before lung surgery. The main RCC histology was clear cells (188, 89.5%). The 5- and 10-year OS from the first lung operation were 60% and 34%, respectively. LM synchronous with RCC (p = 0.01) and (Karnofsky Performance Status Scale) KPSS < 80% (p < 0.001) negatively influenced OS. Five- and 10-year DFI were 54% and 28%, respectively. The main factors negatively influencing DFI were: male gender (p = 0.039), KPSS < 80% (p = 0.009) and lactate dehydrogenase > 1.5 times 140 U/L (p = 0.001). Five- and 10-year disease-free survival were 54% and 28%, respectively; multiple LM (p = 0.036), KPSS < 80% (p = 0.001) and histology of RCC other than clear cells negatively influenced disease-free survival. Conclusions: patients with KPSS > 80%, single metachronous LM with a long DFI from RCC diagnosis, and clear cell histology, benefit from pulmonary metastasectomy.

14.
Transplant Rev (Orlando) ; 35(3): 100636, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34237586

RESUMO

INTRODUCTION: Cancer is the second most common cause of mortality and morbidity in Kidney Transplant Recipients (KTRs). Immunosuppression can influence the efficacy of cancer treatment and modification of the immunosuppressive regimen may restore anti-neoplastic immune responses improving oncologic prognosis. However, patients and transplant physicians are usually reluctant to modify immunosuppression, fearing rejection and potential graft loss. Due to the lack of extensive and recognised data supporting how to manage the immunosuppressive therapy in KTRs, in the context of immunotherapy, chemotherapy, radiotherapy and loco-regional treatments, a Consensus Conference was organised under the auspices of the European Society of Organ Transplantation and the Italian Society of Organ Transplantation. The conference involved a multidisciplinary group of transplant experts in the field across Europe. METHODS: The overall process included a) the formulation of 12 specific questions based on the PICO methodology, b) systematic literature review and summary for experts for each question, c) a two-day conference celebration and the collection of experts' agreements. The conference was articulated in three sessions: "Immunosuppressive therapy and immunotherapy", "Systemic therapy", "Integrated Therapy", while the final experts' agreement was collected with a televoting procedure and defined according to the majority criterion. RESULTS: Twenty-six European experts attended the conference and expressed their vote. A total of 14 statements were finally elaborated and voted. Strong agreement was found for ten statements, moderate agreement for two, moderate disagreement for one and uncertainty for the last one. CONCLUSIONS: The consensus statements provide guidance to transplant physicians caring for kidney transplant recipients with cancer and indicate key aspects that need to be addressed by future clinical research.


Assuntos
Transplante de Rim , Neoplasias , Transplante de Órgãos , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Neoplasias/terapia
15.
J Immunother Cancer ; 9(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34016723

RESUMO

BACKGROUND: Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs). METHODS: The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety. RESULTS: The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1-2). CONCLUSION: The INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Neoplasias/tratamento farmacológico , Vacinação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Incidência , Vacinas contra Influenza/efeitos adversos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/imunologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vacinação/efeitos adversos , Adulto Jovem
16.
Cancers (Basel) ; 13(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922803

RESUMO

Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.

17.
PLoS One ; 16(3): e0249210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765045

RESUMO

INTRODUCTION AND PURPOSE: Choroidal metastases (CM) are the most common intraocular malignancies. With longer survival rates for cancer patients, CM will be increasingly encountered. We evaluated clinical and ultrasonographic (US) characteristics of CM in order to identify diagnostic biomarkers that correlate with the primary tumor site. METHODS: The medical records of all patients with CM evaluated at the Ocular Oncology Unit between February 2010 and March 2020 were analyzed. RESULTS: 82 eyes of 70 patients were included. The primary cancer site was lung in 26 patients (37%), breast in 23 (33%), kidney in 9 (13%), gastrointestinal in 5 (7%), thyroid in 5 (7%), parathyroids and prostate respectively in 2 (3%). Fifty-five patients (78%) had other systemic metastases at the time of ocular diagnosis. Ten (14%) patients had no history of primary cancer. Bilateral CM were found in 20 patients (29%); fifty-six eyes (68%) had a single CM. The epicenter of CM was predominantly macula (43 eyes, 52%). The mean thickness was 4,1 mm (range 1,8-12,3). US structure was inhomogeneous in 67 eyes (82%). Reflectivity was mainly medium (39%) and medium-low (39%). In particular, CM from lung cancer showed lower reflectivity than those from the breast (p = 0,02). CM deriving from lung cancer were typically dome-shaped, whereas CM originating from breast were characteristically plateau shaped (p = 0,02). Seventy-four (91%) eyes presented fluid on optical coherence tomography. CONCLUSION: We significatively found that CM from lung cancer generally appear dome-shaped with medium-low internal reflectivity, whereas those from breast cancer typically present a plateau appearance and higher internal reflectivity. Though it is hard to identify the site of the primary tumor relying exclusively on clinical and US aspects, morphology and internal reflectivity can be considered as diagnostic biomarkers. Thus, the origin of the primary tumor can be suspected by integrating a constellation of findings.


Assuntos
Neoplasias da Coroide/patologia , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Corioide/diagnóstico por imagem , Corioide/patologia , Neoplasias da Coroide/diagnóstico por imagem , Neoplasias da Coroide/secundário , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Pulmonares/patologia , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica
18.
Hum Vaccin Immunother ; 17(1): 4-13, 2021 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32663057

RESUMO

Immunotherapy can be used for cutaneous, mucosal, uveal and conjunctival melanoma. Nevertheless, we cannot expect the same benefit from checkpoint inhibitors for all the types of melanoma. The different biological features can explain the variable efficacy. The main results obtained with immune checkpoint inhibitors in the various types of melanoma were reviewed.


Assuntos
Neoplasias da Túnica Conjuntiva , Melanoma , Neoplasias Uveais , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Melanoma/tratamento farmacológico , Neoplasias Uveais/tratamento farmacológico
19.
J Am Acad Dermatol ; 84(5): 1310-1320, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33279646

RESUMO

BACKGROUND: Immune checkpoint inhibitor (ICI)-mediated psoriasis poses significant diagnostic and therapeutic challenges. OBJECTIVE: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. METHODS: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. RESULTS: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P = .03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P < .001). Guttate psoriasis and grade 2 or 3 disease were significant positive predictors for antitumor response of ICI, whereas pruritus was a negative predictor. LIMITATIONS: Retrospective design. CONCLUSION: Acitretin, apremilast, and methotrexate are safe and effective modalities for ICI-mediated psoriasis. In most cases, ICI can be completed unhindered. A therapeutic algorithm is proposed.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Psoríase/tratamento farmacológico , Acitretina/uso terapêutico , Idoso , Produtos Biológicos/uso terapêutico , Quimioterapia Combinada/métodos , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasias/imunologia , Psoríase/induzido quimicamente , Psoríase/diagnóstico , Psoríase/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Resultado do Tratamento
20.
Recenti Prog Med ; 111(12): 48e-53e, 2020 12.
Artigo em Italiano | MEDLINE | ID: mdl-33362182

RESUMO

The treatment of cutaneous melanoma harboring BRAF mutation has been greatly enriched. BRAF/MEK inhibitors can improve the outcome of patients with this disease. On the other hand, immunotherapy can also be effective. A focus on the role of immune checkpoint inhibitors in advanced melanoma with BRAF mutation has been performed.


Assuntos
Imunoterapia , Melanoma , Neoplasias Cutâneas , Humanos , Fatores Imunológicos , Melanoma/genética , Melanoma/terapia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia
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