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BACKGROUND: Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients' (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN). METHODS: PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test. RESULTS: Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum-maximum 1-23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723. CONCLUSIONS: Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02864030.
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Neoplasias da Mama , Neutropenia , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Qualidade de Vida , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Resultado do Tratamento , Polimorfismo Genético , Metástase NeoplásicaRESUMO
Placement of traditional transvenous implantable cardioverter defibrillator (ICD) system in low-weight children is often difficult because of their vessel size, the elevated risk of lead malfunction and failure, children's growth and various anatomic constraints, creating the need for alternative solutions. Subcutaneous array leads combined with an abdominally placed ICD device can minimize the surgical approach. In this case series, we analyse the data behind indications for subcutaneous finger cardioverter defibrillator (SFCD) and discuss the preliminary clinical experience in low-weight children. We considered 4 consecutive children (mean age 3.9 years, range 3-5.5 years, mean body weight 17.6 Kg, range 14-23 Kg) who underwent SFCD implant from April 2016 to August 2020. All patients showed a good compliance to the device system with no complications (infections or skin erosions). No patients experienced in the observation period (mean time 44.5±21.5 months) sustained ventricular arrhythmias requiring shocks. No inappropriate shocks released by the device occurred. No significant changes were observed in LET (lowest energy tested) performed around 24 months of follow-up. All patients showed a good compliance and stable atrio-ventricular sensing and pacing thresholds. In smaller children in whom a transvenous approach is not feasible or not possible for anatomic reasons, the SFCD appears to be a safe method to prevent SCD with little surgical trauma and preservation of an intact vascular system, providing an adequate bridge to transvenous ICD or subcutaneous ICD implant late in the life.
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Desfibriladores Implantáveis , Cardioversão Elétrica , Humanos , Criança , Pré-Escolar , Cardioversão Elétrica/efeitos adversos , Arritmias Cardíacas , Desfibriladores Implantáveis/efeitos adversos , Eletrocardiografia , Fatores de Tempo , Resultado do Tratamento , Morte Súbita Cardíaca/prevenção & controleRESUMO
Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12-218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32-2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11-0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.
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Background: COVID-19 pandemic rendered the surgical approach as well as the surgical indication very complex due to the outstanding consumption of public health system' resources, especially in the intensive care subdivision. A multidisciplinary team-based strategy is necessary to adapt guidelines and medical practices to the actual situation. The aim of this study is to evaluate the changes in the therapeutic algorithm in a small group of patients with hepatocellular carcinoma (HCC) enlisted for surgery during the COVID-19 outbreak. Materials and Methods: A multidisciplinary strategy has been adopted to allocate HCC patients to a treatment that permitted to reduce the risk of complications and the hospital stay, thus preventing contamination by the virus. Nasopharyngeal swab and a chest radiograph were performed in all patients within 48 hours before the surgical procedure: in the suspected cases with negative COVID tests, we prudently postponed surgery and repeated the diagnostic tests after 15 days. Results: During the emergency state, 11 HCC patients were treated (8 laparoscopic ablations and 3 hepatic resections). We reported only 1 postoperative complication (hemothorax) and 1 death during the follow-up for COVID pneumonia. Comparing our performances with those in the same time frame in the past 4 years, we treated a similar number of HCC patients, obtaining a decrease in operative timing (P = .0409) and hospital stay (P = .0412) (Fig. 2b) with similar rates of immediate postoperative complications, without ICU admissions. Conclusions: An adapted algorithm for the treatment of HCC to COVID outbreak permitted to manage safely these patients by identifying those most at risk of evolution of the neoplastic disease.
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COVID-19/epidemiologia , Carcinoma Hepatocelular/cirurgia , Gerenciamento Clínico , Fidelidade a Diretrizes , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Comorbidade , Feminino , Humanos , Tempo de Internação , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pandemias , SARS-CoV-2RESUMO
The Coronavirus Disease-2019 (COVID-19) pandemic is spreading in Italy and Lombardy is one of the most affected region. Cancer patients are higher risk of complication from COVID-19 complications; therefore they should be protected from contagion while still ensuring access to cancer care. The aim of this article is to suggest a strategy to reorganize hospital spaces and Healthcare Professionals (HCPs) staff in order to avoid COVID-19 nosocomial infection in an Oncology ward. SARS-CoV-2 is primarily transmitted through respiratory droplets and by contact. We speculated that precautions against droplet and contact transmission should be the proper way to preserve ward from COVID-19. The essence of our protocol involves: triage outside of the ward, identification of risk zones, traffic control, surveillance of all the involved subjects. Whoever attends the ward must follow the general risk prevention and mitigation measures. The application of this practical strategy can contribute to breaking the cycle of community-hospital-community transmission.
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COVID-19 , Utopias , Humanos , Itália/epidemiologia , Pandemias , SARS-CoV-2RESUMO
INTRODUCTION: Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors. PATIENTS AND METHODS: COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS. RESULTS: A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years). CONCLUSIONS: The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.
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Neoplasias da Mama/mortalidade , Sobreviventes de Câncer/estatística & dados numéricos , Idoso , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: In patients with advanced lung adenocarcinoma, the impact of LKB1 mutations on cytotoxic chemotherapy efficacy remains poorly explored. Here, we aimed at investigating the potential impact of LKB1 mutational status on chemotherapy efficacy in advanced non-small-cell lung cancer (NSCLC) patients enrolled in the TArceva Italian Lung Optimisation tRial (TAILOR) trial. METHODS: The multicenter TAILOR trial randomised patients with EGFR-wild type (wt) advanced NSCLC progressing on/after previous platinum-based chemotherapy to receive docetaxel or erlotinib. Here, we evaluated the impact of LKB1 mutational status on progression-free survival (PFS) and overall survival (OS) in patients treated with second-line docetaxel/erlotinib or during prior platinum-based chemotherapy. RESULTS: Out of 222 patients randomised in the TAILOR trial, left-over tumour tissues were available for 188 patients, and 120 patients with evaluable LKB1 status were included. Of them, 17 (14.17%) patients had LKB1-mutated tumours, while 103 (85.83%) had LKB1-wt disease. During second-line treatment, PFS and OS were not statistically significantly different in patients with LKB1-mutated when compared with LKB1-wt NSCLC (adjusted HR (aHR)=1.29, 95% CI 0.75 to 2.21; p=0.364 and aHR=1.41, 95% CI 0.82 to 2.44; p=0.218, respectively). Similarly, we found no significant association between LKB1 mutations and patient PFS or OS during prior first-line platinum-based chemotherapy (aHR=1.04, 95% CI 0.55 to 1.97; p=0.910 and aHR=0.83, 95% CI 0.42 to 1.65; p=0.602, respectively). CONCLUSION: Among advanced NSCLC patients receiving two lines of systemic therapy, LKB1 mutations were not associated with PFS or OS during second-line docetaxel or prior first-line platinum-based chemotherapy. While larger prospective trials are needed to confirm our findings, cytotoxic chemotherapy remains the backbone of investigational combination strategies in this patient population.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinases Proteína-Quinases Ativadas por AMP , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Mutação , Estudos Prospectivos , Proteínas Serina-Treonina Quinases , Taxoides/uso terapêuticoRESUMO
PURPOSE: Adjuvant treatment decisions in early breast cancer (eBC) have traditionally been driven by risk stratification based on clinical and pathological risk factors. The 21-gene Oncotype DX® assay has been validated as a predictive test for benefit from adjuvant chemotherapy (CT), hence assessing its impact in clinical decisions is of high interest. The objective of this study was to estimate the rate of adjuvant treatment decision modification impacted by the Recurrence Score® result, and the consequent budget impact. METHODS: The study was a multicentre, prospective, real-life experience in Lombardy (Italy) including consecutive patients with T1-T3, N0-N1a, and ER+/HER2-eBC with clinical-pathologic "intermediate risk" of relapse. The change in treatment recommendations was assessed before and after availability of Recurrence Score result. A budget model evaluated the implications of 21-gene testing in the study population. RESULTS: The overall proportion of CT recommendations was reduced from 24.6% to 15.2% after 21-gene testing, with a major impact in patients initially considered for CT plus hormone therapy (CHT). In these patients, the total budget was reduced, leading to a net saving of -81,017. The greater the physician propensity to prescribe CHT, the higher the potential savings for the health system from sparing CT in most tested patients. CONCLUSIONS: Our real-life experience suggests that all intermediate-risk ER+/HER2-eBC patients who are initially deemed candidates for CHT should be tested with the 21-gene test. The potential to spare CT in at least half of them offers relevant advantages for patients and national health services.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Análise Custo-Benefício , Feminino , Perfilação da Expressão Gênica/economia , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Receptor ErbB-2 , Medição de RiscoRESUMO
Attitudes toward cancer-related malnutrition vary considerably among oncologists and nutritional support is often not handled according to the available guidelines. The Italian Association of Medical Oncology (AIOM), Italian Society of Artificial Nutrition and Metabolism (SINPE), Italian Federation of Volunteer-based Cancer Organizations (FAVO), and Fondazione AIOM Working Group conducted a national web-based survey addressed to all Italian Oncology Units referees and Italian Cancer Patients Associations. The aim was to investigate the current management of malnutrition and views on nutritional care among oncologists and patients. One hundred and seventy-one (51.6%) of the 331 registered Italian Oncology Units and 75 (38.5%) of the 195 FAVO local communities participated in the survey. Nutritional assessment and support were integrated into patient care from diagnosis for 35% of Oncology Unit referees and 15% of FAVO associates. According to 42% of oncologists, nutritional assessment was carried out only after patients requested it, while it was not performed at all for 45% of FAVO associates. Almost 60% of patient affiliates were not aware of clinical referrals for home artificial nutrition management. However, for almost all responders, the evaluation of nutritional status was considered crucial in predicting tolerance to anticancer treatment. Although malnutrition was considered a limiting factor in oncology treatments by both oncologists and patients, nutritional care practices still appear largely inappropriate. Attitudes differ between oncologists and patients, the latter reporting a more dissatisfied picture. Improving nutritional care in oncology remains a challenging task.
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Desnutrição/prevenção & controle , Neoplasias/fisiopatologia , Terapia Nutricional/métodos , Oncologistas/psicologia , Padrões de Prática Médica/estatística & dados numéricos , Atitude do Pessoal de Saúde , Humanos , Desnutrição/epidemiologia , Desnutrição/psicologia , Prognóstico , Inquéritos e QuestionáriosRESUMO
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Supressoras de Tumor/genética , Idoso , Bevacizumab/administração & dosagem , Biomarcadores Tumorais/metabolismo , Camptotecina/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Qualidade de Vida , Taxa de Sobrevida , Temozolomida/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Trabectedin, in addition to its antiproliferative effect, can modify the tumour microenvironment and this could be synergistic with bevacizumab. The efficacy and safety of trabectedin and bevacizumab ± carboplatin have never been investigated. METHODS: In this phase 2 study, women progressing between 6 and 12 months since their last platinum-based therapy were randomised to Arm BT: bevacizumab, trabectedin every 21 days, or Arm BT+C: bevacizumab, trabectedin and carboplatin every 28 days, from cycles 1 to 6, then trabectedin and bevacizumab as in Arm BT. Primary endpoints were progression-free survival rate (PFS-6) and severe toxicity rate (ST-6) at 6 months, assuming a PFS-6 ≤35% for BT and ≤40% for BT+C as not of therapeutic interest and, for both arms, a ST-6 ≥ 30% as unacceptable. RESULTS: BT+C (21 patients) did not meet the safety criteria for the second stage (ST-6 45%; 95%CI: 23%-69%) but PFS-6 was 85% (95%CI: 62%-97%). BT (50 patients) had 75% PFS-6 (95%CI: 60%-87%) and 16% ST-6 (95%CI 7%-30%). CONCLUSIONS: BT compared favourably with other platinum- and non-platinum-based regimens. The combination with carboplatin needs to be assessed further in a re-modulated safer schedule to confirm its apparent strong activity. CLINICAL TRIAL REGISTRATION: NCT01735071 (Clinicaltrials.gov).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Taxa de Sobrevida , Trabectedina/administração & dosagem , Trabectedina/efeitos adversosRESUMO
One of the challenges during chemotherapy and radiotherapy is to complete the planned cycles and doses without dose-limiting toxicity. Growing evidence clearly demonstrates the relationship between dose-limiting toxicity and low muscle mass. Moreover, malnutrition leads to low performance status, impaired quality of life, unplanned hospital admissions, and reduced survival. In the past, the lack of clear and authoritative recommendations and guidelines has meant that oncologists have not always fully appreciated the importance of nutritional therapy in patients receiving anticancer treatments. Therefore, collaboration between oncologists and clinical nutrition specialists needs to be urgently improved. Recent guidelines from scientific societies and practical recommendations by inter-society consensus documents can be summarized as follows: 1) timely nutritional therapy should be carefully considered if patients undergoing anticancer treatments are malnourished or at risk of malnutrition due to inadequate oral intake; 2) if oral intake is inadequate despite counseling and oral nutritional supplements, supplemental enteral nutrition or, if this is not sufficient or feasible, parenteral nutrition should be considered; 3) home artificial nutrition should be prescribed and regularly monitored using defined protocols developed between oncologists and clinical nutrition specialists; 4) appropriate nutritional management in the context of simultaneous care should become a guaranteed right for all patients with cancer. The purpose of this review is to provide oncologists with an overview of the aims and current evidence about nutrition in oncology, together with updated practical and concise recommendations on the application of nutritional therapy in cancer patients receiving chemoradiotherapy.
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Aim: This subgroup analysis of the RAINBOW study evaluated the efficacy and safety of ramucirumab in patients with gastric cancer/gastroesophageal junction adenocarcinoma who received prior trastuzumab therapy. Patients & methods: Of adult patients enrolled in the RAINBOW study, 39 had received prior trastuzumab therapy. Of these, 20 patients were treated with ramucirumab plus paclitaxel and 19 patients with placebo plus paclitaxel within the RAINBOW trial. Results: Overall survival was longer with ramucirumab plus paclitaxel (11.4 months; 95% CI: 7.0-17.9) versus placebo plus paclitaxel (7.0 months; 95% CI: 3.4-14.6), hazard ratio: 0.68 (0.33-1.41); p = 0.30. Longer progression-free survival, higher objective response were observed in ramucirumab combination group. Conclusion: Ramucirumab plus paclitaxel demonstrated efficacy benefits with manageable safety profile in a subgroup of patients pretreated with trastuzumab. Clinical trial registration number: NCT01170663.
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Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/uso terapêutico , Adenocarcinoma/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Neoplasias Gástricas/patologia , RamucirumabRESUMO
The efficacy of second-line treatment in patients with epidermal growth factor receptor (EGFR) wild-type tumours is still debatable. We assessed the efficacy of a standard second-line chemotherapy compared with erlotinib in an individual patient data approach for meta-analysis. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS). Both were compared by log-rank test. The 'restricted mean survival time' (RMST) was estimated in each study and the difference in mean survival time up to the last available time point was calculated. The Cox proportional hazards model was used on survival analyses to provide HRs, to adjust for confounding variables and to test possible interaction with selected factors. Three randomised trials comparing chemotherapy versus erlotinib were analysed, including 587 randomised patients. Overall, 74% of patients included in the original trials were considered. 464 deaths and 570 progressions or deaths were observed. Compared with erlotinib, chemotherapy was associated to a decreased risk of progression (29%; HR: 0.71, 95% CI: 0.60 to 0.84, p< 0.0001;) but with no statistical significant reduction in OS (HR: 0.89, 95% CI: 0.74 to 1.06; p<0.20). No heterogeneity was found in both analyses. Patients treated with chemotherapy gained an absolute 1.5 and 1.6 months, respectively, in PFS and lifetime (RMST 95% CI: PFS 0.49 to 2.44; OS 95% CI: -1.04 to 4.25). These results showed that patients without a constitutively activated EGFR had better PFS with chemotherapy rather than with erlotinib while no statistical difference was observed in OS.
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Although limited by severe side effects and development of resistance, platinum-based therapies still represent the most common first-line treatment for non-small cell lung cancer (NSCLC). However, a crucial need in the clinical management of NSCLC is represented by the identification of cases sensitive to DNA damage response (DDR)-targeting drugs, such as cisplatin or PARP inhibitors. Here, we provide a molecular rationale for the stratification of NSCLC patients potentially benefitting from platinum compounds based on the expression levels of RANBP9, a recently identified player of the cellular DDR. RANBP9 was found overexpressed by immunohistochemistry (IHC) in NSCLC compared to normal adjacent tissues (NATs) (n = 147). Moreover, a retrospective analysis of 132 platinum-treated patients from the multi-centric TAILOR trial showed that RANBP9 overexpression levels are associated with clinical response to platinum compounds [Progression Free Survival Hazard Ratio (RANBP9 high vs low) 1.73, 95% CI 1.15-2.59, p = 0.0084; Overall Survival HR (RANBP9 high vs low) 1.99, 95% CI 1.27-3.11, p = 0.003]. Accordingly, RANBP9 KO cells showed higher sensitivity to cisplatin in comparison with WT controls both in vitro and in vivo models. NSCLC RANBP9 KO cells were also more sensitive than control cells to the PARP inhibitor olaparib alone and in combination with cisplatin, due to defective ATM-dependent and hyper-activated PARP-dependent DDR. The current investigation paves the way to prospective studies to assess the clinical value of RANBP9 protein levels as prognostic and predictive biomarker of response to DDR-targeting drugs, leading to the development of new tools for the management of NSCLC patients.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas do Citoesqueleto/metabolismo , Dano ao DNA/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Pulmonares/patologia , Proteínas Nucleares/metabolismo , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cisplatino/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Fasting in disease prevention and treatment has recently become a popular topic, particularly in the context of oncology. Unfortunately, the growing attention paid by the media has created a background of speculations and ambiguous messages. The attitude towards the role of fasting in cancer patients should be very cautious, as the risk of malnutrition/sarcopenia and disinformation may be associated with this approach. Whether the results obtained by fasting in the cellular and animal models can be transferred to cancer patients is still to be ascertained. At the moment, more preclinical studies are required to determine in which cancers, at which stage, and in what combinations fasting, fasting-mimicking diets or caloric restriction mimetics may prove effective. So, despite the "rumors" of marketing and media, nowadays fasting and calorie restriction around CT represent only a promising intuition, which requires proper efforts and time to be validated by evidence-based clinical data.
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Jejum/metabolismo , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Restrição Calórica , Dieta , Metabolismo Energético/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/imunologia , Resultado do TratamentoRESUMO
BACKGROUND: The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. METHODS: The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. RESULTS: 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002). CONCLUSIONS: In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on biological features.
Assuntos
Neoplasias da Mama/patologia , Idoso , Neoplasias da Mama/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
One of the priorities of personalized medicine regards the role of early integration of palliative care with cancer-directed treatments, called simultaneous care. This article, written by the Italian Association of Medical Oncology (AIOM) Simultaneous and Continuous Care Task Force, represents the position of Italian medical oncologists about simultaneous care, and is the result of a 2-step project: a Web-based survey among medical oncologists and a consensus conference. We present the opinion of more than 600 oncologists who helped formulate these recommendations. This document covers 4 main aspects of simultaneous care: 1) ethical, cultural, and relational aspects of cancer and implications for patient communication; 2) training of medical oncologists in palliative medicine; 3) research on the integration between cancer treatments and palliative care; and 4) organizational and management models for the realization of simultaneous care. The resulting recommendations highlight the role of skills and competence in palliative care along with implementation of adequate organizational models to accomplish simultaneous care, which is considered a high priority of AIOM in order to grant the best quality of life for cancer patients and their families.
Assuntos
Oncologia , Cuidados Paliativos , Sociedades Médicas , Humanos , ItáliaRESUMO
BACKGROUND: Early integration of palliative care in oncology practice ("simultaneous care", SC) has been shown to provide better care resulting in improved quality-of-life and also survival. We evaluated the opinions of Italian Association of Medical Oncology (AIOM) members. PATIENTS AND METHODS: A 37-item questionnaire was delivered to 1119 AIOM members. Main areas covered were: social, ethical, relational aspects of disease and communication, training, research, organizational and management models in SC. Three open questions explored the definition of Quality of Life, Medical Oncologist and Palliative Care. RESULTS: Four hundred and forty-nine (40.1%) medical oncologists returned the questionnaires. Forty-nine percent stated they address non-curability when giving a diagnosis of metastatic tumor, and 43% give the information only to patients who clearly ask for it. Fifty-five percent say the main formative activity in palliative medicine came from attending meetings and 90% agree that specific palliative care training should be part of the core curriculum in oncology. Twenty-two percent stated they consulted guidelines for symptom management, 45% relied upon personal experience and 26% make a referral to a palliative care specialist. Seventy-four percent were in favor of more research in palliative medicine. An integration between Units of Oncology and Palliative Care Services early in the course of advanced disease was advocated by 86%. Diverse and multifaceted definitions were given for the concepts of Quality of Life, Palliative Care and Medical Oncologist. CONCLUSION: SC is felt as an important task, as well as training of medical oncologists in symptom management and research in this field.