RESUMO
BACKGROUND: Nivolumab has shown a survival benefit compared with docetaxel as second-line treatment for patients with previously treated advanced squamous non-small cell lung cancer (NSCLC) in a randomized phase III trial. The experiences of patients and physicians in routine clinical practice are often different from those in a controlled clinical trial setting. We present data from the entire Italian cohort of patients with squamous NSCLC enrolled in a worldwide nivolumab NSCLC expanded access program. PATIENTS AND METHODS: Patients with pretreated advanced squamous NSCLC received nivolumab 3 mg/kg every 2 weeks for up to 24 months. Safety was monitored throughout; efficacy data collected included objective tumor response, date of progression, and survival information. RESULTS: The Italian cohort comprised 371 patients who received at least one dose of nivolumab. In the overall population, the objective response rate (ORR) was 18%, the disease control rate (DCR) was 47%, and median overall survival (OS) was 7.9 months (95% confidence interval 6.2-9.6). In subgroup analyses, ORR, DCR, and median OS were, respectively, 17%, 48%, and 9.1 months in patients previously treated with two or more lines of therapy (n = 209) and 8%, 40%, and 10.0 months in patients treated beyond disease progression (n = 65). In the overall population, the rate of any-grade and grade 3-4 adverse events was 29% and 6%, respectively. Treatment-related adverse events led to treatment discontinuation in 14 patients (5%). There were no treatment-related deaths. CONCLUSION: To date, this report represents the most extensive clinical experience with nivolumab in advanced squamous NSCLC in current practice outside the controlled clinical trial setting. These data suggest that the efficacy and safety profiles of nivolumab in a broad, real-world setting are consistent with those obtained in clinical trials. IMPLICATIONS FOR PRACTICE: Nivolumab is approved in the U.S. and Europe for the treatment of advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. In this cohort of Italian patients with previously treated, advanced squamous NSCLC treated in a real-world setting as part of the nivolumab expanded access program, the efficacy and safety of nivolumab was consistent with that previously reported in nivolumab clinical trials.
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Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Ensaios de Uso Compassivo , Esquema de Medicação , Feminino , Humanos , Imunoterapia , Itália , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Segurança , Resultado do TratamentoRESUMO
BACKGROUND: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. METHODS: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. DISCUSSION: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. TRIAL REGISTRATION: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).
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Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Junção Esofagogástrica/patologia , Paclitaxel/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Junção Esofagogástrica/metabolismo , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida/psicologia , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/psicologia , Resultado do Tratamento , RamucirumabRESUMO
Cytoreductive surgery and hyperthermic-intraoperative-intrapleural-chemotherapy (HITHOC) is a known approach for malignant pleural diseases (MPD). This study was started to clarify the role of cytoreductive surgery and HITHOC in MPD. Criteria of inclusion were early-stage disease in malignant pleural mesothelioma (MPM), young age, good condition and selected stage-M1a lung cancer. Six patients with MPM and two patients with lung cancer were enrolled. After surgical debulking, intrapleural cisplatin was administered for 60 min at 42.5°C. Wedge, rib resection and repaired diaphragm were added in three, one and one patient, respectively. Morbidity, toxicity and mortality was nil. Hospital stay was 8 days. Mean survival is 13.6 months. This experience confirms that cytoreductive surgery and HITHOC is a good option in the treatment of MPD. A randomized controlled trial is necessary.
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Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Idoso , Cisplatino/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma/cirurgia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/secundário , Neoplasias Pleurais/cirurgia , Estudos Prospectivos , Procedimentos Cirúrgicos Torácicos/métodosRESUMO
Cytoreductive surgery and hyperthermic intraoperative intrapleural chemotherapy (HITHOC) are a known option for malignant pleural mesothelioma (MPM). This prospective study was started to prove that pleurectomy/decortication and HITHOC could be successfully performed in a low volume center. Criteria of inclusion were a proven diagnosis of MPM, early-stage disease and good performance status. Six consecutive patients were enrolled. After pleurectomy/decortication, intrapleural cisplatin was administered for 60 min at 42.5 °C. Wedge resections and diaphragmatic reconstruction were added in two and one patient, respectively. Morbidity was 16.6%. Mortality was nil. Hospital stay was 7.8 days. Mean survival was 21.5 months (range: 6-30). This small experience confirms that pleurectomy/decortication and HITHOC are a good therapeutic option in the multimodality treatment of MPM. A randomized controlled trial is necessary.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Mesotelioma/tratamento farmacológico , Mesotelioma/cirurgia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/cirurgia , Idoso , Cisplatino/uso terapêutico , Terapia Combinada/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Estudos Prospectivos , Procedimentos Cirúrgicos Torácicos/métodosRESUMO
OBJECT: The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol. METHODS: A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered. RESULTS: All patients but 1 in Group A survived at least 18 months (range 18-101 months), and patients in Group B survived no more than 17 months (range 2-17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group. CONCLUSIONS: This study describes the longest experience so far reported with TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, who were treated using GTR. Statistically significant data confirm that median survival correlates with MGMT promoter methylation status as well as with the number of TMZ cycles administered. Long-term TMZ therapy appears feasible and safe.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Corticosteroides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Glioblastoma/diagnóstico , Glioblastoma/genética , Humanos , Avaliação de Estado de Karnofsky , Antígeno Ki-67/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sulfitos/uso terapêutico , Temozolomida , Fatores de Tempo , Proteínas Supressoras de Tumor/genéticaRESUMO
INTRODUCTION: The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC. METHODS: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response. RESULTS: Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively. CONCLUSION: Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Desoxicitidina , Gencitabina , Oxaliplatina , Paclitaxel , Humanos , Masculino , Feminino , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/mortalidade , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Adulto , Idoso de 80 Anos ou maisRESUMO
Immune checkpoint inhibitors (ICI) have become a cornerstone in medical oncology, with evolving therapeutic strategies and applications. These monoclonal antibodies, designed to enhance immune responses, have revealed a spectrum of immune-related adverse events (irAEs). While many irAEs exhibit favorable responses to corticosteroid or immunosuppressive therapy, most ICI-related endocrinopathies necessitate lifelong replacement therapy and pose significant clinical challenges. Adrenal insufficiency (AI), a noteworthy endocrine irAE, can manifest as primary AI (PAI) or secondary AI (SAI), resulting from adrenal or pituitary gland dysfunction, respectively. ICI-induced AI, albeit relatively infrequent, occurs in 1-2% of patients receiving single-agent anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) or Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) therapies and in a higher range of 4-9% when ICIs are used in combinations. Recognizing and addressing ICI-induced PAI is crucial, as it often presents with acute and potentially life-threatening symptoms, especially considering the expanding use of ICI therapy. This review provides an updated overview of ICI-induced PAI, exploring its clinical, diagnostic, and radiological aspects.
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Doença de Addison , Antineoplásicos Imunológicos , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/terapia , Doença de Addison/induzido quimicamente , Doença de Addison/tratamento farmacológico , Anticorpos Monoclonais/uso terapêuticoRESUMO
BACKGROUND: Bevacizumab significantly improves progression-free survival (PFS) and overall survival (OS) when added to chemotherapy for metastatic colorectal cancer (mCRC). The hypothesis that bevacizumab discontinuation could lead to an angiogenesis flare and eventually to an accelerated tumor progression has not been confirmed in a recent large pooled analysis. Therefore the optimal duration of bevacizumab still remains undefined. PATIENTS AND METHODS: PFS and OS were retrospectively analyzed in patients with previously untreated mCRC who received bevacizumab 5 mg/Kg and standard FOLFIRI regimen (leucovorin, infusional fluorouracil and irinotecan) up to a maximum of 12 cycles. RESULTS: Data from 209 patients were collected and analyzed. The median follow-up was 24 months. Fifty-five (26.3%) patients received at least 6 administrations and 114 (54.5%) received a maximum of 12 administrations of bevacizumab. Median exposure to bevacizumab was 148 days (4.9 months). Median PFS and OS were 10.7 months [95% confidence interval (CI) 9.2-12.2 months] and 31.6 months (95% CI 25.8-37.3 months), respectively. Overall objective response rate was 49.8% (95% CI 42.9-56.6) and the disease control rate 81.8%. Approximately 65% and 30% of patients received some form of second- and third-line therapy, respectively. The toxicity profile of bevacizumab was consistent with that documented in previous trials. CONCLUSIONS: In this retrospective analysis remarkably long PFS and OS were obtained with a first-line therapy duration limited to a maximum of 12 cycles. Our data does not support a decreased PFS or increased mortality after discontinuation of bevacizumab in mCRC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Estudos de Coortes , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/efeitos adversosRESUMO
Epidermal growth factor receptor (EGFR) exon 20 insertions occur rarely among different cancer types, with the highest frequency reported among non-small-cell lung cancer (NSCLC) patients, particularly adenocarcinomas (ADCs). Exon 20 insertions fall back in the tyrosine kinase domain, and can be clustered into two principal groups represented by in frame insertions and three to 21 bp (corresponding to 1-7 amino acids) duplications within amino acids 762 and 774. The identification of these alterations is key for an adequate management of NSCLC patients due to the possibility to treat these patients with specific targeted therapies. Next generation sequencing (NGS) technology, able to detect several hotspot gene mutations for different patients simultaneously, is the best detection approach due to its higher sensitivity and specificity compared to other techniques. Here we reviewed the principal biological characteristics, the main detection technologies and treatment options for NSCLC patients harbouring EGFR exon 20 insertions.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas QuinasesRESUMO
Rat sarcoma (RAS) oncogenes have intensively been investigated during the last decades. Taking into account all human tumours, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene is the most frequently mutated (about 22%) among the three isoforms, followed by Neuroblastoma RAS Viral Oncogene Homolog (NRAS) (8%) and Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS) (3%). In the last years, careful attention has been paid on KRAS and NRAS gene mutations in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients because of their prognostic and predictive roles. In particular, a large body of literature data has been generated investigating clinical outcomes of targeted treatments in NSCLC and CRC KRAS- and NRAS-mutated patients. The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mutação , Proteínas ras/genética , Neoplasias Colorretais/genética , Humanos , Neoplasias Pulmonares/genéticaRESUMO
PURPOSE: The availability of immune checkpoint inhibitors has deeply changed the therapeutic scenario of patients with advanced non-small cell lung cancer (NSCLC). Up until now, chemotherapy still represents the first-line treatment for patients with advanced NSCLC not harbouring genetic mutations or lacking high expression of programmed death ligand even if the addition of immunotherapy to first-line chemotherapy has recently been shown to improve clinical outcome. We carried out a multi-institutional retrospective analysis on third-line chemotherapy with metronomic oral vinorelbine (VNR) in a series of patients with metastatic NSCLC pre-treated with first-line chemotherapy and second-line immunotherapy. PATIENTS AND METHODS: Thirty patients with metastatic NSCLC with progressive disease after first-line chemotherapy and subsequent immunotherapy were treated with metronomic oral VNR continuously at the fixed dose of 30 mg three times per week. RESULTS: A partial response was achieved in 4 patients (13.3%), while 10 patients (33.3%) displayed disease stabilisation for an overall disease control rate of 46.7%. Median progression-free survival was 3.9 months (range 1-13 months) and median OS reached 8.1 months (range 4.0-24.0+ months) with a 12-month survival rate of 22%. CONCLUSION: Oral metronomic VNR appears to be active and safe in patients with metastatic NSCLC in progression after first-line chemotherapy and second-line immunotherapy. The results reported, although from a limited sample, may suggest its use for long-term stabilisation of the disease with good patient compliance.
RESUMO
BACKGROUND: This descriptive, unplanned investigation has been undertaken to report reactions, attitudes and countermeasures which have been put in place and implemented by medical oncology units facing the COVID-19 outbreak in Southern Italy. MATERIALS AND METHODS: Data have been retrospectively obtained from the time-related analysis of conversations via a WhatsApp messenger-based group chat between the medical directors belonging to the Italian College of Medical Oncology Directors. Overall number, intensity and time trend of conversations related to reactions during the 4 weeks of observation related to the crucial events which occurred between 24 February and 28 March, 2020 2020 are included. A sentiment analysis of conversations was also carried out. RESULTS: We report 956 conversations among 19 medical oncology units related to reactions to the crucial events, such as epidemic spread, Government ordinances and guidelines during the 4 weeks of observation. Data show significant awareness of problems linked to the COVID-19 spread among oncologists and rapid diffusion of countermeasures. Actions taken were correlated time wise to crucial events. A correlation between conversations and the volume of activity of oncology units was found. By analysing the sentiment analysis of raw data, positive emotions were reduced in percentage over the weeks. A significant increase in negative emotions was observed as the outbreak impacted on the healthcare system. CONCLUSION: In our experience, the WhatsApp instant-messaging system seems to be a useful tool to share news and reactions between medical oncologists to rapidly implement necessary health measures and answers to most cancer patients' needs and queries in the COVID-19 pandemic scenario.
RESUMO
BACKGROUND/AIM: Double diagnosis of lung cancer (LC) and ovarian cancer (OC) is rare. Here, we describe patients with synchronous/metachronous LC and OC to identify common clinical and pathological patterns. PATIENTS AND METHODS: Clinical, pathological and molecular data of patients diagnosed and treated at 30 European Institutions from 2008 to 2018 were retrieved and analysed. Whenever tissue was available, centralized pathology revision was performed. RESULTS: A total of 19 cases were found; one was excluded at pathology revision. Most LCs were adenocarcinomas (15/18) and most OCs were high-grade serous (15/18) carcinomas. Of the 9 patients analysed, 7 carried oncogene-addicted LC (4 EGFR, 1 B-RAF and 2 ALK) and five out of 7 carried BRCA mutations. One patient with a germline-BRCA1 mutation received olaparib, resulting in a durable response of both malignancies. Median overall survival was 33 months. CONCLUSION: In our series, most synchronous/metachronous LCs and OCs showed genetic alterations. Further analyses with wide NGS panel could shed light on the biological mechanisms driving their occurrence.
Assuntos
Neoplasias Pulmonares/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Proteína BRCA1/genética , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Mutação/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Estudos RetrospectivosAssuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Leiomiossarcoma/tratamento farmacológico , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/análise , Pirimidinas/uso terapêutico , Benzamidas , Humanos , Mesilato de Imatinib , Leiomiossarcoma/química , Leiomiossarcoma/secundário , Masculino , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
BACKGROUND: Three and 4-week cisplatin-gemcitabine schedules have shown similar dose-intensity (DI) and activity in non-small-cell lung cancer (NSCLC). The 3-week schedule is generally preferred because it enables better treatment compliance. To improve DI and compliance further, we delivered gemcitabine plus cisplatin over 4 days every 21 days. METHODS: Patients with any stage NSCLC or epithelial neoplasms and an ECOG PS < or = 2 were given gemcitabine 1000 mg/m(2) on days 1 and 4 plus cisplatin 70 mg/m(2) on day 2 of a 21-day cycle. Minimax design was used and a received DI for gemcitabine of > or = 580 mg/m(2)/wk was considered successful. RESULTS: Thirty-nine patients (34 NSCLC, 5 epithelial neoplasias) were enrolled. SWOG grade 3-4 neutropenia and thrombocytopenia were observed in 17.9% and 12.8% of patients, respectively. Nonhematological toxicity was minimal. Twenty-eight (18%) of 158 cycles required dose modifications and/or delays. Twenty-five patients received a gemcitabine dose intensity of > or = 580 mg/m(2)/wk. The received DIs were 601.8 mg/m(2)/wk for gemcitabine and 21.0 for cisplatin, with a relative DIs of 90.3% and 90.1%, respectively. The response rate of 27 evaluable patients with NSCLC was 44% (95% confidence interval [CI], 25.3 to 62.7%). CONCLUSIONS: The shorter schedule of gemcitabine on days 1 and 4 plus cisplatin on day 2 produces an effective DI and a toxicity profile comparable to that of weekly regimens.