RESUMO
BACKGROUND: Since the incidence of cancer increases with age, in older cancer patients important information may be missed without a Comprehensive Geriatric Assessment (CGA). On the other side, CGA is a time-consuming and complex instrument, so that Geriatric 8 (G8) has been proposed as a more feasible screening tool to identify patients who could benefit from a CGA evaluation. G8 consists of 8 questions (patient age + 7 items derived from the Mini Nutritional Assessment questionnaire). A G8 score ≤ 14 is considered associated with frailty and risk of malnutrition. Another screening test is Bioelectrical Impedance Analysis (Bioimpedentiometry, BIA), which enables to evaluate the nutritional status through a specific parameter known as Phase angle (PhA). This study is aimed at assessing the ability of G8 alone or in combination with PhA to detect elderly cancer patients at higher risk for malnutrition who cannot undergo immediate anticancer treatments. METHODS: A total of 289 cancer patients (168 men and 121 women) aged ≥ 70 years old were enrolled and performed both G8 test, body mass index (BMI) and BIA assessments. A concurrent G8 score ≤ 14 and PhA < 5 defined subjects most exposed to the risk of malnutrition. RESULTS: An association between BMI and G8 (p < 0.001, OR 1.54) and a clinically significant relationship between G8 and PhA (p = 0.013) were observed. CONCLUSION: G8 can be used to identify patients at risk for malnutrition who would benefit from comprehensive CGA. The concurrent use of G8 and BIA presents a higher power in discriminating subjects at higher risk of malnutrition than a single test. This study suggests the need for routine assessment of nutritional status in cancer patients using combinations of methods, in order to implement strategies for individually-tailored care before starting any treatment.
Assuntos
Fragilidade , Desnutrição , Neoplasias , Idoso , Masculino , Humanos , Feminino , Fragilidade/diagnóstico , Desnutrição/diagnóstico , Neoplasias/complicações , Neoplasias/terapia , Estado Nutricional , Avaliação Nutricional , Avaliação Geriátrica/métodosRESUMO
BACKGROUND: Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy. METHODS: In the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. A cut-off was determined using the maximally selected rank statistics method. Generalised boosted regression (GBR), the Kaplan-Meier method and Cox hazards regression models were used for survival analyses. RESULTS: A total of 438 patients were included. Overall, 208 patients (47%) had a low-baseline PIV and 230 (53%) had a high-baseline PIV. Patients with high PIV experienced a worse PFS (HR, 1.66; 95% CI, 1.36-2.03, P < 0.001) and worse OS (HR, 2.01; 95% CI, 1.57-2.57; P < 0.001) compared to patients with low PIV. PIV outperformed the other IIBs in the GBR model and in the multivariable models. CONCLUSION: PIV is a strong predictor of survival outcomes with better performance than other well-known IIBs in patients with mCRC treated with first-line therapy. PIV should be prospectively validated to better stratify mCRC patients undergoing first-line therapy.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/imunologia , Neoplasias Colorretais/tratamento farmacológico , Neutrófilos/imunologia , Idoso , Ensaios Clínicos como Assunto , Neoplasias Colorretais/imunologia , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Contagem de Plaquetas , Prognóstico , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Epstein-Barr virus (EBV)-positive gastric cancers (GCs) have been recently identified as a molecular subgroup showing excellent outcomes after surgery for early-stage disease and responsiveness to immune checkpoint inhibitors (ICIs) for metastatic stage. No data are available on the prevalence, clinical characteristics, and prognosis of this subgroup of GCs in the metastatic setting. MATERIALS AND METHODS: In this cohort study, we assessed the impact of EBV status in patients with metastatic GC treated with chemotherapy at two Italian institutions. RESULTS: Among the 175 cases analyzed, only 7 (4%) were EBV positive and all showed long-lasting and even complete responses to first-line chemotherapy with fluorouracil and platinum and a significantly better survival compared with EBV-negative patients (3-year overall survival: 80% vs. 20.1%; hazard ratio: 0.12). CONCLUSION: If confirmed in larger data sets, our results may give a strong rationale for investigating the addition of ICIs to chemotherapy, in order to maximize the chance of achieving durable and complete responses in this uncommon subtype of GC. IMPLICATIONS FOR PRACTICE: To date, no data are available on the prevalence and clinical characteristics of patients with Epstein-Barr virus (EBV)-positive metastatic gastric cancer (GC), a specific subtype of GC showing excellent outcomes after radical surgery in early-stage disease and responsiveness to immune checkpoint inhibitors (ICIs). This cohort study showed that patients with EBV-positive GC who did not receive ICIs had exceptional, long-lasting, and even complete responses to first-line chemotherapy with fluorouracil and platinum and a significantly better survival compared with EBV-negative patients. If confirmed in larger series, these results may give a strong rationale for investigating the combination of chemotherapy and ICIs to achieve durable and potentially complete response in this uncommon subtype of GC.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Estudos de Coortes , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Humanos , Prognóstico , Neoplasias Gástricas/tratamento farmacológicoRESUMO
BACKGROUND: Few real-world series on the efficacy and safety of anti-programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)-based therapy are available in molecularly unselected patients with poor performance status (PS) and specific types of advanced cancers, because such populations are typically excluded from clinical trials due to poor life expectancy and risk of toxicity. MATERIALS AND METHODS: This multicenter retrospective case series included patients with microsatellite instability (MSI)-high metastatic cancers with Eastern Cooperative Oncology Group (ECOG) PS of 2 or 3 not related to comorbidities receiving anti-PD-1 with or without anti-CTLA-4 therapy after failure of at least one prior treatment line. RESULTS: We included 27 patients with six diverse tumor types: colorectal (n = 18), gastric (n = 5), biliary tract, pancreatic, small bowel, and endometrial cancers (n = 1 each). Baseline ECOG PS was 2 (74%) or 3 (26%). Overall response rate was 33%, with six partial and three complete responses. Median time to response was 3.1, months and median duration of response was 16.9 months. Median progression-free survival was 3.4 months (95% CI: 2.3 to not evaluable), and 18-month overall survival was 50.8% (95% confidence interval, 32.7-78.8). Baseline variables were not associated with survival outcomes. ECOG PS 1 was reached by 52% of patients in a median time of 6 weeks, and ECOG PS 0 was reached by 30% of patients in a median time of 10 weeks. CONCLUSION: In a high proportion of patients with MSI-high cancers and poor performance status related to end-stage disease, salvage immunotherapy can induce potentially long-lasting "Lazarus responses". Immunotherapy decisions near the end-of-life should be carefully integrated with predictive biomarkers and with palliative care measures in the real-world setting. IMPLICATIONS FOR PRACTICE: In this retrospective cohort study of 27 pretreated patients with microsatellite instability (MSI)-high cancers and Eastern Cooperative Oncology Group performance status of 2 or 3 not related to comorbidities, PD-1/PD-L1-based therapy induced a RECIST response in 33% of patients, with a median duration of 16.9 months, and an improvement of performance status in 52% of patients. MSI-high status can be used in clinical practice as a tumor-agnostic predictive biomarker to select critically ill patients with end-stage cancers for salvage immunotherapy.
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Instabilidade de Microssatélites , Neoplasias , Efeitos Psicossociais da Doença , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Estudos RetrospectivosRESUMO
The treatment scenario of metastatic colorectal cancer (mCRC) has been rapidly enriched with new chemotherapy combinations and biological agents that lead to a remarkable improvement in patients' outcome. Kinase gene fusions account for less than 1% of mCRC overall but are enriched in patients with high microsatellite instability, RAS/BRAF wild-type colorectal cancer. mCRC patients harboring such alterations show a poor prognosis with standard treatments that could be reversed by adopting novel therapeutic strategies. Moving forward to a positive selection of mCRC patients suitable for targeted therapy in the era of personalized medicine, actionable gene fusions, although rare, represent a peculiar opportunity to disrupt a tumor alteration to achieve therapeutic goal. Here we summarize the current knowledge on potentially actionable gene fusions in colorectal cancer available from retrospective experiences and promising preliminary results of new basket trials.
Assuntos
Neoplasias Colorretais , Fusão Gênica , Instabilidade de Microssatélites , Proteínas de Fusão Oncogênica , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Metástase Neoplásica , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismoRESUMO
Human epidermal growth factor receptor 2 (HER2) positive cancers account for 15-20% of all breast tumors. Several drugs have been approved in the metastatic setting, including monoclonal antibodies, tyrosine kinase inhibitors (TKI) and, more recently, antibody-drug conjugates. Neratinib is a pan-HER, irreversible TKI with potent preclinical activity against trastuzumab-resistant breast cancer models. Based on Phase I and II clinical trials, the combination of neratinib plus capecitabine was compared to lapatinib and capecitabine, an established regimen for trastuzumab-resistant disease, in the randomized, Phase III NALA trial. In this trial, neratinib yielded increased progression-free survival, response duration and a benefit in time to intervention for CNS progression. However, there was no overall survival benefit, no increase in overall response rate and no improvement in QoL. The most frequent adverse event in the neratinib arm was diarrhea, which was manageable with prophylactic treatment with loperamide. Conclusion: Neratinib is a valuable addition to the therapeutic armamentarium to treat metastatic, HER2-positive breast cancer. The current positioning of the combination of neratinib and capecitabine based on the results of the NALA trial needs to consider the rapidly evolving scenario due to the recent introduction of new drugs, like the pure-HER2 TKI tucatinib and the antibody drug-conjugate trastuzumab-deruxtecan.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Feminino , Humanos , Qualidade de Vida , Quinolinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To determine whether second-line therapy with capecitabine and temozolomide was superior to irinotecan, leucovorin, and fluorouracil (FOLFIRI) in patients with RAS-mutated, methyl-guanine methyltransferase (MGMT)-methylated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In this randomized, phase II trial, we enrolled patients with RAS-mutated, MGMT-methylated mCRC after failure of oxaliplatin-based regimen. Patients with centrally confirmed MGMT methylation were stratified by first-line progression-free survival (PFS) and prior bevacizumab and randomized to either capecitabine plus temozolomide (arm A, CAPTEM) or FOLFIRI (arm B). The primary endpoint was PFS analyzed on intention-to-treat basis, with 90% power and one-sided significance level of 0.05 to detect an increase of median time from 2 months in arm B to 4 months in arm A. RESULTS: Between November 2014 and May 2019, 86 patients were randomly assigned to arm A (n = 43) or arm B (n = 43). After a median follow-up of 30.5 months (interquartile range, 12.2-36.3), 79 disease progression or death events occurred. Superiority of arm A was not demonstrated (one-sided P = 0.223). Progression-free survival and overall survival were 3.5 (2.0-5.0) and 9.5 (8.2-25.8) in arm A versus 3.5 (2.3-6.1) and 10.6 (8.5-20.8) in arm B [HR = 1.19 (0.82-1.72) and HR = 0.97 (0.58-1.61)], respectively. Grade ≥3 treatment-related adverse events had higher incidence in arm B versus A (47.6% vs 16.3%), and quality of life was significantly worse in arm B. Patients with positive MGMT expression by IHC did not benefit from CAPTEM. CONCLUSIONS: Temozolomide-based therapy warrants further investigation in molecularly hyperselected subgroups.