Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
1.
Per Med ; 19(1): 51-66, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34873959

RESUMO

Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon (POLE), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.


Assuntos
Medicina de Precisão , Neoplasias da Próstata , Biomarcadores , Reparo de Erro de Pareamento de DNA , Humanos , Imunoterapia , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia
2.
Expert Rev Anticancer Ther ; 22(1): 115-121, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34738499

RESUMO

BACKGROUND: Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. RESULTS: We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48-0.92, p = 0.011). CONCLUSIONS: We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Anilidas/farmacologia , Anilidas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Piridinas , Estudos Retrospectivos
3.
Cancers (Basel) ; 13(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34359706

RESUMO

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

4.
Cancer Rep (Hoboken) ; 4(6): e1411, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34165246

RESUMO

BACKGROUND: Desmoid fibromatosis (DF) is a rare and locally infiltrative monoclonal fibroblastic proliferation arising from connective tissues, with lack of metastatic potential. About 10% of all DF cases are intra-abdominally sited. Complications in this site, due to the locally infiltrative nature of the disease, may be severe and potentially life threatening. However, data on incidence, management, and outcome of these complications are limited. AIM: Data of patients with sporadic or FAP-related intra-abdominal DF treated at Istituto Nazionale dei Tumori (INT) in Milano from 2005 to 2020 who developed a serious complication during the course of their disease were retrospectively collected and analyzed with a descriptive statistics. METHODS AND RESULTS: Out of 72 intra-abdominal DF, 8 cases were identified (M/F: 5/3, median age: 35 years, FAP-related/sporadic: 2/6): 3 with bowel obstruction, 5 with bowel perforation. In 4 cases the serious complication was the first evidence of disease; in the other 4 cases it occurred at a time interval from diagnosis in the range of 4-44 months (during an active surveillance program in one case and during chemotherapy in the other 3 cases). A surgical treatment was feasible and successful in 5 cases. In 3 surgically unmanageable patients, all progressing and experiencing acute complications while on chemotherapy, a non-surgical approach with intensive supportive treatment and with a prompt change of chemotherapy regimen was implemented, being successful in two, the other patient dying due to a concomitant progressive lymphoma thereafter. CONCLUSION: In this series of intra-abdominal DF, the incidence of serious complications was 11%. Most patients were successfully treated with surgery. When surgery was deemed to be unfeasible, a conservative management with intensive supportive care and a careful choice of chemotherapy was adopted, ensuring a favorable outcome in most.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Linfoma/tratamento farmacológico , Adulto , Gerenciamento Clínico , Feminino , Fibromatose Agressiva/complicações , Seguimentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Linfoma/etiologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
5.
Ther Adv Med Oncol ; 13: 17588359211006960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33948122

RESUMO

BACKGROUND: High body mass index (BMI) has been associated with worse clinical outcomes in patients with early-stage breast cancer (BC), and its negative effects could be mediated by hyperglycemia/diabetes. However, the prognostic impact of high BMI in early-stage HER2-positive (HER2+) BC patients remains controversial. METHODS: We conducted a retrospective study to investigate the impact of baseline BMI or glycemia on relapse-free survival (RFS) and overall survival (OS) in patients with surgically resected, stage I-III HER2+ BC treated with standard-of-care, trastuzumab-containing adjuvant biochemotherapy. The optimal BMI and glycemia cut-off values for RFS were identified through maximally selected rank statistics. Cox regression models were used to assess the impact of BMI, glycemia and other relevant variables on clinical outcomes. RESULTS: Among 505 patients included in the study, a BMI cut-off of 27.77 kg/m2 was identified as the best threshold to discriminate between patients with low BMI (n = 390; 77.2%) or high BMI (n = 115; 22.8%). At multivariable analysis, higher BMI was associated with significantly worse RFS [hazard ratio 2.26; 95% confidence interval (CI): 1.08-4.74, p = 0.031] and worse OS (hazard ratio 2.25, 95% CI 1.03-4.94, p = 0.043) in the whole patient population. The negative impact of high BMI was only observed in patients with hormone receptor (HR)-negative/HER2+ BC (hazard ratio 2.29; 95% CI: 1.01-5.20; p = 0.047), but not in patients with HR-positive (HR+)/HER2+ BC (hazard ratio 1.36; 95% CI: 0.61-3.07, p = 0.452). By contrast, hyperglycemia (⩾109 mg/dl) at baseline was associated with a trend toward significantly worse RFS at multivariable analysis only in patients with HR+/HER2+ BC (hazard ratio 2.52; 95% CI: 0.89-7.1; p = 0.080). CONCLUSIONS: High BMI is associated with worse clinical outcomes in early-stage HR-/HER2+ BC patients treated with trastuzumab-containing adjuvant biochemotherapy, while baseline hyperglycemia could be a predictor of worse RFS in HR+/HER2+ BC patients. Prospective studies are needed to investigate if modifying patient BMI/glycemia during treatment can improve clinical outcomes.

6.
Tumori ; : 3008916211007940, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849307

RESUMO

OBJECTIVE: To capture and monitor flu-like symptoms in relation to the clinical characteristics and the oncologic treatment of a large head and neck cancer (HNC) patient cohort during the Coronavirus disease 2019 (COVID-19) pandemic. METHODS: Patients were monitored through by 2 rounds of interviews. Clinical characteristics of patients with no symptoms (group 0) and of those reporting ⩾1 (group A), ⩾3 (group B), or ⩾5 symptoms (group C) were analyzed. Patients with ⩾1 symptom at both interviews were defined as group A2. RESULTS: Five hundred patients with HNC were analyzed. A higher frequency of patients with the following characteristics was observed in group A vs group 0: active treatment (40% vs 24%, p = 0.0002), gastrostomy (6% vs 2%, p = 0.027), recent active treatment (48% vs 29%, p < 0.0001), and higher number of concomitant medications (p = 0.01). A lower median age was observed in group B vs group no-B (patients with fewer than three symptoms) (59 vs 63.55 years, p = 0.016) and in group A2 vs group no-A2 (patients without at least one symptom at both interviews) (56 vs 63 years, p = 0.021); patients in group B received more recent active treatment than those in group no-B and in group A2 vs those in group no-A2 (p = 0.024 and 0.043, respectively); patients in group B had a lower body mass index than those in group no-B (22.4 vs 23.93 kg/m2, p = 0.0066). CONCLUSIONS: This work is based on patient-reported symptoms and signs independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. In the future, these results might serve as a a benchmark for clinicians triaging and managing patients with HNC during infectious outbreaks involving flu-like symptoms.

7.
Ther Adv Med Oncol ; 12: 1758835920970081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335565

RESUMO

BACKGROUND: Neoadjuvant anthracycline-taxane-based chemotherapy (ChT) is a standard of care treatment option for stage II-III breast cancer (BC) patients. However, the optimal duration of neoadjuvant ChT has been poorly investigated so far. MATERIAL AND METHODS: We retrospectively retrieved clinical data of patients with stage II-III human epidermal growth factor receptor 2-negative (HER2-) BC who were treated between October 2007 and January 2018 with neoadjuvant AT (doxorubicin-paclitaxel) for three cycles followed by CMF (cyclophosphamide-methotrexate-5-fluorouracil) for three cycles (cohort A) or with four AT cycles followed by four CMF cycles (cohort B). The aim of our study was to investigate the impact of neoadjuvant ChT duration (cohort A versus cohort B) on pathological complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS). RESULTS: Of 209 HER2- BC patients included, 62 had triple-negative breast cancer (TNBC) and 147 had hormone receptor-positive (HR+) BC. Median age was 48 years (range 30-74 years). A total of 111 patients belonged to cohort A and 98 patients belonged to cohort B. pCR was detected in 29 (13.9%) patients, 25 (40.3%) of whom had TNBC and four (2.7%) had HR+ HER2- BC. Patients achieving pCR had significantly longer DFS and OS, with statistical significance reached only in patients with TNBC. We found no differences between cohort A and cohort B in terms of pCR rates (15.3% versus 12.2%; p = 0.55), DFS (p = 0.49) or OS (p = 0.94). The incidence of grade 3/4 adverse events was similar in cohort A versus cohort B as well (22.5% versus 19.4%; p = 0.54). CONCLUSION: Shorter duration of neoadjuvant anthracycline-taxane ChT was not associated with worse clinical outcomes in patients with stage II-III BC. Prospective studies are needed to evaluate whether the duration of neoadjuvant anthracycline-taxane-based ChT can be reduced in specific patient subgroups without negatively affecting clinical outcomes.

8.
ESMO Open ; 5(Suppl 3)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33158968

RESUMO

BACKGROUND: In the midst of the COVID-19 pandemic, patients with cancer are regarded as a highly vulnerable population. Overall, those requiring hospital admission for treatment administration are potentially exposed to a higher risk of infection and worse outcome given the multiple in-hospital exposures and the treatment immunosuppressive effects. METHODS: COVINT is an observational study assessing COVID-19 incidence among patients receiving anticancer treatment in the outpatient clinic of the Istituto Nazionale dei Tumori di Milano. All consecutive patients with non-haematological malignancies treated with intravenous or subcutaneous/intramuscular anticancer therapy in the outpatient clinic were enrolled. The primary endpoint is the rate of occurrence of COVID-19. Secondary endpoints included the rate of COVID-19-related deaths and treatment interruptions. The association between clinical and biological characteristics and COVID-19 occurrence is also evaluated. COVID-19 diagnosis is defined as (1) certain if confirmed by reverse transcriptase PCR assay of nasopharyngeal swabs (NPS); (2) suspected in case of new symptoms or CT scan evidence of interstitial pneumonia with negative/not performed NPS; (3) negative in case of neither symptoms nor radiological evidence. RESULTS: In the first 2 months (16 February-10 April 2020) of observation, 1081 patients were included. Of these, 11 (1%) were confirmed and 73 (6.7%) suspected for COVID-19. No significant differences in terms of cancer and treatment type emerged between the three subgroups. Prophylactic use of myeloid growth factors was adopted in 5.3%, 2.7% and 0% of COVID-19-free, COVID-19-suspected and COVID-19-confirmed patients (p=0.003). Overall, 96 (8.9%) patients delayed treatment as a precaution for the pandemic. Among the 11 confirmed cases, 6 (55%) died of COVID-19 complications, and anticancer treatment was restarted in only one. CONCLUSIONS: During the pandemic peak, accurate protective measures successfully resulted in low rates of COVID-19 diagnosis, although with high lethality. Prospective patients' surveillance will continue with NPS and serology testing to provide a more comprehensive epidemiological picture, a biological insight on the impact of cytotoxic treatments on the immune response, and to protect patients and healthcare workers.


Assuntos
Antineoplásicos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Neoplasias/tratamento farmacológico , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Betacoronavirus , COVID-19 , Institutos de Câncer , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Estadiamento de Neoplasias , Neoplasias/epidemiologia , Neoplasias/patologia , Pandemias , Pneumonia Viral/mortalidade , SARS-CoV-2 , Tempo para o Tratamento , Adulto Jovem
9.
Radiol Med ; 123(2): 91-97, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28948442

RESUMO

PURPOSE: To investigate the correlation between enhancement parameters on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pathologic prognostic factors in invasive breast cancers (BCs). MATERIALS AND METHODS: A total of 25 invasive BCs were included: 22 invasive ductal, 2 invasive lobular and 1 invasive mucinous. The tumor volume was segmented using a semi-automatic software (Olea Sphere). The following voxel-wise enhancement parameters were extracted: (1) time to peak enhancement; (2) signal intensity at peak (SIP); (3) peak enhancement percentage (PEP); (4) post-initial enhancement percentage (PIEP). The following pathological prognostic factors were considered for potential correlation: tumor (pT) and nodal (pN) stage, grading, perivascular/perineural invasion, estrogen/progesterone receptor status, Ki-67 proliferation, and HER2 expression. Spearman and Pearson correlation coefficients were calculated according with type of variable and data distribution. RESULTS: Tumor volume was 2.8 ± 2.0 cm3 (mean ± standard deviation [SD]). Mean SIP correlated with pT (ρ = 0.424, p = 0.035); mean PEP correlated with HER2 overexpression (ϕ = 0.471, p = 0.017) and pT (ρ = 0.449, p = 0.024). The percentage of voxels with fast PEP directly correlated with pT (ρ = 0.482, p = 0.015) and pN (ρ = 0.446, p = 0.026), while the percentage of voxels with slow PEP inversely correlated with pT (ρ = -0.421, p = 0.039) and pN (ρ = -0.481, p = 0.015). Segmentation time was 14.6 ± 1.3 min (mean ± SD). CONCLUSION: In invasive BCs, DCE-MRI voxel-wise enhancement parameters correlated with HER2, pT, and pN.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Lobular/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adenocarcinoma Mucinoso/diagnóstico por imagem , Idoso , Algoritmos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Lobular/patologia , Meios de Contraste/farmacologia , Feminino , Humanos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...