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BACKGROUND: The optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma (OGA) remains challenging. METHODS: Patients treated with trastuzumab (T) plus platinum salts and fluoropyrimidine (F) as first-line chemotherapy between 2010 and 2020 for HER2-positive advanced OGA at 17 academic care centers in France, Italy, and Austria were included. The primary objective was the comparison of F + T vs T alone as maintenance regimen in terms of progression-free survival (PFS) and overall survival (OS) after a platinum-based chemotherapy induction + T. As secondary objective, PFS and OS between patients treated with reintroduction of initial chemotherapy or standard second-line chemotherapy at progression were assessed. RESULTS: Among the 157 patients included, 86 (55%) received F + T and 71 (45%) T alone as a maintenance regimen after a median of 4 months of induction chemotherapy. Median PFS from start of maintenance therapy was 5.1 months in both groups (95% CI 4.2-7.7 for F + T and 95% CI 3.7-7.5 for T alone; p = 0.60) and median OS was 15.2 (95% CI 10.9-19.1) and 17.0 months (95% CI 15.5-21.6) for F + T and T alone, respectively (p = 0.40). Of 112/157 patients (71%) receiving systemic therapy after progression under maintenance, 26/112 (23%) were treated with a reintroduction of initial chemotherapy + T and 86/112 (77%) with a standard second-line regimen. Here, median OS was significantly longer with the reintroduction (13.8 (95% CI 12.1-19.9) vs 9.0 months (95% CI 7.1-11.9); p = 0.007) as confirmed by multivariate analysis (HR 0.49; 95% CI 0.28-0.85; p = 0.01). CONCLUSION: No additional benefit of adding F to T monotherapy as a maintenance treatment could be observed. Reintroduction of initial therapy at first progression may be a feasible approach to preserve later treatment lines.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Quimioterapia de Indução , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica , Trastuzumab/uso terapêuticoRESUMO
Tissue biopsy is essential for NSCLC diagnosis and treatment management. Over the past decades, liquid biopsy has proven to be a powerful tool in clinical oncology, isolating tumor-derived entities from the blood. Liquid biopsy permits several advantages over tissue biopsy: it is non-invasive, and it should provide a better view of tumor heterogeneity, gene alterations, and clonal evolution. Consequentially, liquid biopsy has gained attention as a cancer biomarker tool, with growing clinical applications in NSCLC. In the era of precision medicine based on molecular typing, non-invasive genotyping methods became increasingly important due to the great number of oncogene drivers and the small tissue specimen often available. In our work, we comprehensively reviewed established and emerging applications of liquid biopsy in NSCLC. We made an excursus on laboratory analysis methods and the applications of liquid biopsy either in early or metastatic NSCLC disease settings. We deeply reviewed current data and future perspectives regarding screening, minimal residual disease, micrometastasis detection, and their implication in adjuvant and neoadjuvant therapy management. Moreover, we reviewed liquid biopsy diagnostic utility in the absence of tissue biopsy and its role in monitoring treatment response and emerging resistance in metastatic NSCLC treated with target therapy and immuno-therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Biópsia Líquida/métodos , Biópsia , Medicina de Precisão/métodos , Biomarcadores Tumorais/genéticaRESUMO
BACKGROUND: Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). MATERIAL AND METHODS: This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR-LDH combined (group 1: MLR-LDH low; group 2: MLR or LDH high; group 3: MLR-LDH high). The second cohort was used to validate the model. RESULTS: At the median follow-up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39-4.04), high LDH (HR, 1.73; 95% C.I., 1.03-2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62-4.66), and group 3 (HR, 3.73; 95% C.I., 1.94-7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. CONCLUSION: MLR and LDH are circulating cost-effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC. IMPLICATIONS FOR PRACTICE: High monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels could be a sign of a tumor's recruitment of suppressive and inflammatory cells worsening prognosis of different types of cancer, including colorectal cancer (CRC). Currently, no data are available for metastatic CRC regarding a cutoff definition for MLR or the prognostic impact of MLR and MLR-LDH combined. The present study showed in the training cohort and confirmed in the validation and whole cohort that MLR is a reliable and independent laboratory biomarker, which is easy to use, to predict clinical outcomes in patients with mCRC. Moreover, MLR and composite MLR-LDH could potentially result in an incremental improvement in the prognostic value of these biomarkers, being used as stratification tools for patients with mCRC.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Colorretais/diagnóstico , Humanos , Lactato Desidrogenases , Linfócitos , Monócitos , Neutrófilos , Prognóstico , Estudos RetrospectivosRESUMO
Aim: A monitoring strategy for metastatic breast cancer patients (M-MBC) has been little studied. Materials & methods: This retrospective study analyzed a consecutive cohort of 382 MBC patients to analyze different M-MBC strategies to identify factors influencing intensive M-MBC. Results: Elevated baseline serum tumor markers (STM) was the strongest factor associated with increased use of STM tests. Having more frequent oncology office visits was associated with more intensive chemotherapy/magnetic resonance imaging (MRI) using. Increased use of imaging tests was associated with participation to clinical trial. Single and elderly patients were less likely to have frequent testing. Having clinically measurable disease was less likely to have more intensive M-MBC. Conclusion: STM testing and scans were frequently ordered in M-MBC. In the present study, strategies are little influenced by clinico-pathological characteristics.
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Neoplasias da Mama/diagnóstico , Diagnóstico por Imagem , Radiografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Tomada de Decisão Clínica , Comorbidade , Diagnóstico por Imagem/métodos , Gerenciamento Clínico , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Razão de Chances , Radiografia/métodos , Estudos Retrospectivos , Conduta ExpectanteRESUMO
Background: 'Drug holidays' (DH) for metastatic colorectal cancer (mCRC) were introduced to preserve quality of life. We studied factors associated to a DH offer in first line. Materials & methods: We retrospectively analyzed 754 consecutive patients treated with chemotherapy for mCRC in two Italian institutions between 2005 and 2017. Associations between baseline clinical-pathological factors and DH (56 or more days of treatment interruption) were investigated. Results: In 754 patients, previous metastasectomy, previous thermoablation and previous surgery of primary tumor were independently associated with DH. Excluding procedures or clinical trials: primary rectal cancer and resection of primary tumor were significantly associated to DH. Conclusions: DH was offered to patients with lower burden of disease, but further investigations are needed to safely guide a holiday strategy.
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Neoplasias Colorretais/epidemiologia , Tomada de Decisão Clínica , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Gerenciamento Clínico , Pesquisas sobre Atenção à Saúde , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
Prognostic characterization in the initial assessment of patients with advanced cancer disease is an essential step to plan the most appropriate therapeutic program. Since clinical prediction of survival (CPS) may be of limited value, some authors have tried to integrate specific prognostic factors into prognostic multidimensional scores. We carried out a prospective cohort study in two palliative care units to compare the accuracy of the Palliative Prognostic (PaP) Score, the Objective Prognostic Score (OPS), and the Palliative Prognostic Index (PPI). In addition, we compared the accuracy of the CPS independently estimated by different healthcare professionals and we tested the role of laboratory results, together with clinical and social factors in predicting survival. Clinical and laboratory data of 334 advanced cancer patients were prospectively collected from the time of in-hospital admission. PaP Score was the most accurate index of survival prediction, followed by PPI; CPS estimates' accuracy was similar among physicians and nurse. All healthcare professionals tended to underestimate the real survival. Integrating CPS with multidimensional indexes may further improve the patient's management. The degree of autonomy and the number of metastatic sites were independent prognostic factors for 30-days mortality and overall survival in multivariate analysis.
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Neoplasias/terapia , Cuidados Paliativos/métodos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Estudos ProspectivosRESUMO
Sarcopenia is a complex syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Malignancy is a major determinant of sarcopenia, and gastric cancer (GC) is among the most common causes of this phenomenon. As sarcopenia is a well-recognized poor prognostic feature in GC and has been associated with worse tolerance of surgical and medical treatments, members of the multidisciplinary team should be aware of the clinical relevance, pathogenic mechanisms, and potential treatments for this syndrome. The importance of sarcopenia is often underestimated in everyday practice and clinical trials, particularly among elderly or fragile patients. As treatment options are improving in all disease stages, deeper knowledge and greater attention to the metabolic balance in GC patients could further increase the benefit of novel therapeutic strategies and dramatically impact on quality of life. In this review, we describe the role of sarcopenia in different phases of GC progression. Our aim is to provide oncologists and surgeons dealing with GC patients with a useful tool for comprehensive assessment and timely management of this potentially life-threatening condition.
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Sarcopenia/etiologia , Neoplasias Gástricas/complicações , HumanosRESUMO
The CDH1 gene, coding for the E-cadherin protein, is linked to gastric cancer (GC) susceptibility and tumor invasion. The human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in a portion of GC. HER2 is an established therapeutic target in metastatic GC (mGC). Trastuzumab, in combination with various chemotherapeutic agents, is a standard treatment for these tumors leading to outcome improvement. Unfortunately, the survival benefit is limited to a fraction of patients. The aim of this study was to improve knowledge of the HER2 and the E-cadherin alterations in the context of GC to characterize subtypes of patients that could better benefit from targeted therapy. An association between the P7-CDH1 haplotype, including two polymorphisms (rs16260A-rs1801552T) and a subset of HER2-positive mGC with better prognosis was observed. Results indicated the potential evaluation of CDH1 haplotypes in mGC to stratify patients that will benefit from trastuzumab-based treatments. Moreover, data may have implications to understanding the HER2 and the E-cadherin interactions in vivo and in response to treatments.
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Caderinas/genética , Haplótipos/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Antígenos CD , Sequência de Bases , Feminino , Frequência do Gene/genética , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: Colorectal cancer is a worldwide leading cause of death accounting for high-rate mortality. Mutations in the epidermal growth factor receptor and RAS/MAPK pathways, as well as altered methylation genes profiles, have been described as molecular mechanisms promoting and sustaining tumour development and progression. Aberrant methylation is a well-known epigenetic mechanism involved in gene regulation; particularly several genes were reported as hypermethylated in CRC. Recently, it was shown that epigenetic alterations in genes such as neuropeptide y, proenkephalin and Wnt inhibitory factor 1 can be used as promising disease biomarkers. Almost all methods developed for the DNA methylation analysis combined next generation sequencing, conventional qRT-PCR or ddPCR with the prior DNA modification with sodium bisulfite. METHODS AND RESULTS: We implemented a ddPCR method to assess the methylation status of Wnt inhibitory factor 1 and neuropeptide y using the methylation sensitive restriction enzyme approach that does not impact on DNA quality and guarantees the discrimination of DNA methylation independent of bisulfite conversion. CONCLUSIONS: We showed that this method is robust and sensitive also allowing the monitoring of CRC disease progression when applied to circulating free DNA samples from liquid biopsies, proving to be a fast and easy to implement assay to be used for the monitoring of the methylation pattern of clinically relevant target genes.
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BACKGROUND: T-cell immune infiltrates are robust prognostic variables in localised colon cancer. Evaluation of prognosis using artificial intelligence is an emerging field. We evaluated whether machine learning analysis improved prediction of patient outcome in comparison with analysis of T cell infiltrate only or in association with clinical variables. METHODS: We used data from two phase III clinical trials (Prodige-13 and PETACC08) and one retrospective Italian cohort (HARMONY). Cohorts were split into training (N = 692), internal validation (N = 297) and external validation (N = 672) sets. Tumour slides were stained with CD3mAb. CD3 Machine Learning (CD3ML) score was computed using graphical parameters within the tumour tiles obtained from CD3 slides. CD3 infiltrates in tumour core and invasive margin were automatically detected. Associations of CD3 infiltrates and CD3ML with 5-year Disease-Free Survival (DFS) were examined using univariate and multivariable survival models by Cox regression. FINDINGS: CD3 density both in the invasive margin and the tumour core were significantly associated with DFS in the different sets. Similarly, CD3ML score was significantly associated with DFS in all sets. CD3 assessment did not provide added value on top of CD3ML assessment (Likelihood Ratio Test (LRT), p = 0.13). In contrast, CD3ML improved prediction of DFS when combined with a clinical risk stage (LRT, p = 0.001). Stratified by clinical risk score (High or Low), patients with low CD3ML score had better DFS. INTERPRETATION: In all tested sets, machine learning analysis of tumour cells improved prediction of prognosis compared to clinical parameters. Adding tumour-infiltrating lymphocytes assessment did not improve prognostic determination. FUNDING: This research received no external funding.
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Neoplasias do Colo , Linfócitos do Interstício Tumoral , Aprendizado de Máquina , Estadiamento de Neoplasias , Humanos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Despite contributions provided by the recent clinical trials, several issues and challenges still remain unsolved in adjuvant colon cancer (CC). Hence, further studies should be planned to better refine risk assessment as well as to establish the optimal treatment strategy in the adjuvant setting. However, it is necessary to request adequate, contemporary and relevant variables and report them homogeneously in order to bring maximal information when analyzing their prognostic value. MATERIAL AND METHODS: The project was devised to gain a consensus from experts engaged in the planning, accrual and analyses of stage II and III CC clinical trials, to identify mandatory and recommended baseline variables in order to i) harmonize future data collection worldwide in clinical trials dedicated to adjuvant treatment of CC; ii) propose guidance for Case Report Forms to be used for clinical trials in this setting. A total of 72 questions related to variables that should be reported and how to report them in adjuvant clinical trials were approved and then voted to reach a final consensus from panelists. RESULTS: Data items on patient-related factors, histopathological features, molecular profile, circulating biomarkers and blood analyses were analyzed and discussed by the whole expert panel. For each item, we report data supporting the acquired consensus and the relevant issues that were discussed. Nineteen items were deemed to be mandatory for resected stage III patients and 24 for resected stage II disease. In addition, 9 and 4 items were judged as recommended for stage III and II, respectively. CONCLUSION: In our opinion, these 28 variables should be used and uniformly reported in more comprehensive CRFs as research groups design future clinical trials in the field of adjuvant colon cancer.
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Neoplasias do Colo , Consenso , Humanos , Neoplasias do Colo/terapia , Neoplasias do Colo/patologia , Quimioterapia Adjuvante/normas , Coleta de Dados/normas , Ensaios Clínicos como Assunto/normasRESUMO
Gastric adenocarcinoma (GC) and gastroesophageal junction adenocarcinoma represent frequent and severe diseases whose management has radically changed over the last 10 years. With the advent of second- and third-line standard therapies for metastatic GC patients in the 2010s, the molecular dismemberment of the disease and positive trials with immunotherapy and targeted agents will mark the 2020s. New treatment options have emerged in the neoadjuvant, adjuvant, and metastatic setting. In addition to improved multimodal treatment in operable patients, new subgroups have emerged depending on molecular alterations (HER2, Microsatellite instability) or expression of specific proteins in the tumour (PDL1, Claudin 18.2) making immunohistochemistry central in profiling the tumour for an optimal individualised management. The aim of this review is to describe the current standards of management of early and late stage GC and the molecular markers needed today to optimally manage our patients together with future perspectives on this disease.
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Adenocarcinoma , Antineoplásicos , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/patologia , Terapia Combinada , Adenocarcinoma/tratamento farmacológico , Junção Esofagogástrica/patologiaRESUMO
The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice.
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Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM. In this study, 150 consecutive patients with MBM were retrospectively analyzed with the aim of evaluating independent prognostic factors for MBM patients, including LDH. Furthermore, we implemented a disease-specific prognostic score and estimated survival according to treatment modalities. On the basis of multivariable Cox regression analyses, six prognostic factors (age, BRAF status, number of MBM, number of extracranial metastatic sites, performance status, and LDH level) resulted statistically significant in terms of survival and were combined in a prognostic score to stratify patients in distinct prognostic groups ( P â <â 0.0001). Among treatment modalities, a multimodal approach with stereotactic radiosurgery or neurosurgery associated with systemic therapy showed the best outcome (median overall survival: 12.32â months, 95% confidence interval, 7.92-25.30). This is the first study to demonstrate that LDH has independent prognostic value for patients with MBM and might be used to improve prognostic stratification, albeit external validation is mandatory. Survival of patients with MBM is affected by both disease-specific risk factors and treatment modalities, with locoregional treatments associated with better outcomes.
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Neoplasias Encefálicas , Melanoma , Radiocirurgia , Neoplasias Cutâneas , Humanos , Prognóstico , Melanoma/patologia , Estudos Retrospectivos , L-Lactato Desidrogenase , Neoplasias Cutâneas/cirurgia , Neoplasias Encefálicas/secundárioRESUMO
BACKGROUND: High body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients. PATIENTS AND METHODS: Patients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses. RESULTS: Overall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m2 was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS. CONCLUSIONS: In our study, obesity with BMI > 30 kg/m2 was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.
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Neoplasias do Colo , Humanos , Índice de Massa Corporal , Quimioterapia Adjuvante/efeitos adversos , Estadiamento de Neoplasias , Obesidade/complicações , PrognósticoRESUMO
Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and occurs in15% of non-metastatic diseases and 5% in the metastatic setting. Nearly 30% of MSI CRCs occur in a context of constitutional mutation of the MMR system (Lynch syndrome). Others are sporadic cancers linked to a hypermethylation of the MLH-1 promoter. The pathogenic alterations of MMR genes lead to the accumulation of frequent somatic mutational events and these tumours arbour a high antigen burden and are highly infiltrated with cytotoxic T-cell lymphocytes. Microsatellite instability/DNA mismatch repair deficiency (MSI/dMMR) status has prognostic and predictive implications in non-metastatic and metastatic CRCs. The prognostic value of MSI status in non-metastatic CRCs has been studied extensively, yet the data are more limited for its predictive value in terms of adjuvant chemotherapy efficacy. In both cases (metastatic and non-metastatic settings) treatment with immune check-point inhibitors (ICIs) have shown a remarkable effectiveness in the context of MSI/dMMR status. Indeed, recent data from prospective cohorts and randomised trials have shown a dramatical improvement of survival with immunotherapy (programmed death-ligand 1 [PD-(L)1] cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] blockage) in metastatic or non-metastatic MSI/dMMR CRC. In this review we report and discuss how and for whom to test for the MSI/dMMR phenotype, as well as the prognostic value of this phenotype and the new treatment recommendations options for this unique CRC population. Despite their efficacy, primary and secondary resistance to immune checkpoint inhibitors (ICIs) are observed in more than 50% MSI-H/dMMR CRC patients and in the future how to identify these patients and to overcome resistance will be an important challenge.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Neoplasias Encefálicas , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Antígeno CTLA-4/genética , DNA , Reparo de Erro de Pareamento de DNA/genética , Inibidores de Checkpoint Imunológico , Instabilidade de Microssatélites , Repetições de Microssatélites , Síndromes Neoplásicas Hereditárias , Prognóstico , Estudos ProspectivosRESUMO
Colorectal cancer management has been dramatically impacted by molecular profiling these last years. Among these molecular subgroups, patients with microsatellite instability (MSI) are of particular interest, owing to the prognostic and predictive value of this tumor biomarker. This review article explains the molecular abnormalities underlying MSI phenotype and the consequences of such molecular abnormalities on carcinogenesis, genetic instability and immune infiltration. It details the diagnostic methods for identifying MSI colorectal cancer patients and describes how the prognostic and theranostic values of this marker are impacting treatment decision-making for these patients in 2022.
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Neoplasias Colorretais , Instabilidade de Microssatélites , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Prognóstico , Biomarcadores Tumorais/genéticaRESUMO
Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data.
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BACKGROUND: In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies. METHODS: This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment-related toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. RESULTS: 75 patients were treated with raltitrexed alone, TOMOX, or TOMIRI with or without bevacizumab. Grade 3-4 adverse events were seen in 31% of patients, without significant difference between the different treatment schedules. amongst the 36 patients with a history of fluoropyrimidine-induced cardiac toxicity, none developed cardiovascular events on raltitrexed. Median PFS and OS were 10.6 (95% CI 8.2 - 13.1) and 27.4 months (95% CI 24.1-38.1), respectively. Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone. CONCLUSIONS: In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile. PFS and OS were consistent with usual survival data in mCRC, and significantly better in patients treated with TOMOX, independently of associated targeted therapies.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Quinazolinas/efeitos adversos , Estudos Retrospectivos , TiofenosRESUMO
Background: A multidisciplinary team meeting (MDM) approach in breast cancer (BC) management is a standard of care. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early BC. The purpose of this study was to define whether there was an agreement between the planned program (i.e., MDMs-based decision) and that actually applied. In addition, the study explored factors associated with discordance. Methods: We conducted a retrospective study of a consecutive series of 291 patients with new diagnosis of early BC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. The association between clinico-biological factors and discordance between what was decided during the MDMs and what was consequently applied by the oncologist was explored through uni- and multivariate logistic regression analyses. Results: The median age was 62 years (range 27-88 years). Among invasive early BC patients, the most frequent phenotype was luminal A (38%), followed by luminal B (33%), HER2-positive (12%), and triple-negative (5%). In situ carcinoma (DCIS) represented 12% of cases. The median time from MDM discussion to first oncologic examination was 2 weeks. The rate of discordance between MDM-based decision and final choice, during a face-to-face consultation with the oncologist, was 15.8% (46/291). The most frequent reason for changing the MDM-based program was clinical decision (87%). Follow-up was preferred to the chemotherapy (CT) proposed within the MDMs in 15% of cases, and to the endocrine therapy (ET) in 39% of cases (among these, 44.5% had a diagnosis of DCIS). Therapeutic change from sequential CT-ET to ET alone was chosen in 16/46 pts (35%): among these patients, seven had a luminal B disease and six had an HER2-positive disease. On univariate analysis, factors associated with discordance were values of Ki-67 14%-30% (OR 3.91; 95% CI 1.19-12.9), age >70 years (OR 2.44, 95% CI 1.28-4.63), housewife/retired status (OR 2.35, 95% CI 1.14-4.85), polypharmacy (OR 1.95; 95% CI 1.02-3.72), postmenopausal status (OR 4.15; 95% CI 1.58-10.9), and high Charlson Comorbidity Index (OR 1.31; 95% CI 1.09-1.57). The association with marital status, educational level, alcohol and smoke habits, presence of a caregiver, parity, grading, histotype and phenotype, and stage was not statistically significant. On multivariate analysis, only Ki-67 value maintained its statistical significance. Conclusion: The results of our study could be useful for enhancing the role of MDMs in the clinical decision-making process in early BC.