RESUMO
The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E's preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345).
Assuntos
Resistencia a Medicamentos Antineoplásicos , Mesotelioma Maligno , Neoplasias Pleurais , Vírus Sendai , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/patologia , Neoplasias Pleurais/tratamento farmacológico , Injeções Subcutâneas , Terapia Viral Oncolítica/métodos , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Injeções Intralesionais , Proteínas do Envelope ViralRESUMO
BACKGROUND: The aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30. METHODS: The study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure. RESULTS: Out of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery. CONCLUSION: Although there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.
Assuntos
Hipertermia Induzida , Mesotelioma , Neoplasias Pleurais , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Neoplasias Pleurais/terapia , Neoplasias Pleurais/cirurgia , Hipertermia Induzida/métodos , Mesotelioma/terapia , Mesotelioma/cirurgia , Seguimentos , Terapia Combinada , Glicemia/metabolismo , Glicemia/análise , Mesotelioma Maligno/terapia , Mesotelioma Maligno/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Período Pós-OperatórioRESUMO
BACKGROUND: Tenosynovial giant cell tumor is a rare soft tissue tumor of the synovium of joint, bursae, or tendon sheath. It is divided into localized or diffuse types on the basis of the growth pattern. Localized tenosynovial giant cell tumors are usually benign and treated successfully by excision. Diffuse tenosynovial giant cell tumors, in contrast to localized type, can destroy bone and cartilage and are associated with frequent local recurrences and distant metastasis. Localized type tenosynovial giant cell tumors rarely metastasize to distant organs. Here, we report a case of localized tenosynovial giant cell tumor presenting with lung metastases and systematically review literature. CASE PRESENTATION: A 55-year-old Asian male presented with a dry cough, right-sided chest pain and progressive dyspnea for 1 month. At 18 months before this presentation, he had undergone excision of a painless swelling on his right index finger. The swelling recurred within 3 months of excision, and a biopsy was then suggestive of a giant cell tumor. Given the suspicion of a giant cell tumor, a wide excision of the lesion was performed and the excisional biopsy was consistent with a diagnosis of tenosynovial giant cell tumor, localized type. At admission to our hospital, the patient had tachypnoea and absent breath sounds on the right side. A chest radiograph showed a right-sided pleural effusion with a homogenous opacity in the left mid-zone. A contrast-enhanced computed tomography of the chest and abdomen showed right massive pleural effusion and bilateral multiple lobulated heterogeneously enhancing pleural-based masses with areas of internal calcification. Pleural fluid analysis revealed an exudate with no malignant cells on cytology. A lung biopsy showed osteoclast-like giant cells and mononuclear spindle cells with areas of hemorrhage and necrosis, suggesting tenosynovial giant cell tumor metastasis. A final diagnosis of localized type tenosynovial giant cell tumor of the right index finger with metastases to the lungs and pleura was made. The patient passed away after receiving three cycles of denosumab injection owing to progressive disease. CONCLUSION: Lung metastasis is extremely rare in patients with localized tenosynovial giant cell tumor. The survival is usually poor in patients with lung metastasis. A close follow-up of patients with localized type tenosynovial giant cell tumor is necessary for early detection of pleuropulmonary complications.
Assuntos
Tumor de Células Gigantes de Bainha Tendinosa , Neoplasias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pleurais/secundário , Neoplasias Pleurais/patologia , Tomografia Computadorizada por Raios X , Evolução FatalRESUMO
Ranked high in worldwide growing health issues, pleural diseases affect approximately one million people globally per year and are often correlated with a poor prognosis. Among these pleural diseases, malignant pleural mesothelioma (PM), a neoplastic disease mainly due to asbestos exposure, still remains a diagnostic challenge. Timely diagnosis is imperative to define the most suitable therapeutic approach for the patient, but the choice of diagnostic modalities depends on operator experience and local facilities while bearing in mind the yield of each diagnostic procedure. Since the analysis of pleural fluid cytology is not sufficient in differentiating historical features in PM, histopathological and morphological features obtained via tissue biopsies are fundamental. The quality of biopsy samples is crucial and often requires highly qualified expertise. Since adequate tissue biopsy is essential, medical or video-assisted thoracoscopy (MT or VATS) is proposed as the most suitable approach, with the former being a physician-led procedure. Indeed, MT is the diagnostic gold standard for malignant pleural pathologies. Moreover, this medical or surgical approach can allow diagnostic and therapeutic procedures: it provides the possibility of video-assisted biopsies, the drainage of high volumes of pleural fluid and the administration of sterile calibrated talcum powder under visual control in order to achieve pleurodesis, placement of indwelling pleural catheters if required and in a near future potential intrapleural therapy. In this context, dedicated diagnostic pathways remain a crucial need, especially to quickly and properly diagnose PM. Lastly, the interdisciplinary approach and multidisciplinary collaboration should always be implemented in order to direct the patient to the best customised diagnostic and therapeutic pathway. At the present time, the diagnosis of PM remains an unsolved problem despite MDT (multidisciplinary team) meetings, mainly because of the lack of standardised diagnostic work-up. This review aims to provide an overview of diagnostic procedures in order to propose a clear strategy.
Assuntos
Mesotelioma Maligno , Neoplasias Pleurais , Humanos , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/terapia , Mesotelioma Maligno/patologia , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Biópsia/métodos , Cirurgia Torácica Vídeoassistida/métodosRESUMO
OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting.
Assuntos
Inibidores de Checkpoint Imunológico , Imunoterapia , Mesotelioma Maligno , Recidiva Local de Neoplasia , Neoplasias Pleurais , Humanos , Neoplasias Pleurais/terapia , Mesotelioma Maligno/terapia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Mesotelioma/terapia , Mesotelioma/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Salvação/métodosRESUMO
In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.
Assuntos
Inibidores de Checkpoint Imunológico , Mesotelioma Maligno , Neoplasias Pleurais , Humanos , Mesotelioma Maligno/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Japão , Neoplasias Pleurais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.
Assuntos
Capecitabina , Citidina Desaminase , Mesotelioma Maligno , Pemetrexede , Neoplasias Pleurais , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Capecitabina/farmacologia , Animais , Linhagem Celular Tumoral , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/patologia , Citidina Desaminase/metabolismo , Citidina Desaminase/genética , Camundongos , Pemetrexede/farmacologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Mesotelioma/tratamento farmacológico , Mesotelioma/metabolismo , Mesotelioma/patologia , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
PURPOSE: The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma. PATIENTS AND METHODS: A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network. Patients with pleural mesothelioma that expressed mesothelin and had previously received platinum-based therapy were eligible. RESULTS: In phase 1 (n = 12) only one dose limiting toxicity was observed and the rules for dose reduction were not met. In phase 2, there was no difference in the confirmed response rates between the combination group (n = 18, 2 partial responses [PR], 11 %) and the pembrolizumab group (n = 17, 1 PR, 6 %; z = -0.5523, p = 0.29116). The median PFS was 12.2 months (95 % CI 5.1-not evaluable [NE]) for the combination, and 3.9 months for pembrolizumab (95 % CI 2.1-NE)(HR=0.55, p = 0.20). Patients with high baseline levels of soluble mesothelin who received anetumab ravtansine had a median PFS of 5 months. CONCLUSIONS: The numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin.
Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Mesotelioma , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Idoso , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Mesotelioma/tratamento farmacológico , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelina , Maitansina/análogos & derivados , Maitansina/uso terapêutico , Maitansina/efeitos adversos , Idoso de 80 Anos ou mais , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Neoplasias Pleurais/mortalidade , Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , ImunoconjugadosAssuntos
Mesotelioma , Recidiva Local de Neoplasia , Neoplasias Peritoneais , Neoplasias Pleurais , Humanos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Neoplasias Pleurais/patologia , Neoplasias Pleurais/cirurgia , Prognóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Mesotelioma/patologia , Mesotelioma/cirurgia , Taxa de Sobrevida , Mesotelioma Maligno/patologia , Mesotelioma Maligno/cirurgia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologiaRESUMO
Four primary extraskeletal osteosarcomas of the pleura are presented. The patients were men between the ages of 63 and 78 years (average: 70.5 years) who presented with symptoms of chest pain, cough, and shortness of breath. Diagnostic imaging showed variably calcified, pleural-based masses and/or diffuse pleural thickening, clinically mimicking mesothelioma. Thoracoscopic surgical material was obtained for histopathological diagnosis. Histological findings showed the presence of a neoplastic spindle cell proliferation composed of fusiform cells with scant cytoplasm, elongated nuclei and inconspicuous nucleoli. Mitotic activity was easily identified. Additionally, all tumors showed extensive osseous differentiation in the form of osteoid matrix production; one tumor demonstrated additional chondrosarcomatous elements and another showed focal myxoid changes. Immunohistochemical analysis revealed that the tumor cells were uniformly negative for a wide variety of antibodies, including keratin AE1/AE3, keratin 5/6, D2-40, EMA, calretinin, WT-1, BerEP4, and HEG1; BAP1 was retained in all cases. In addition, fluorescence in situ hybridization for CDKN2A (p16) was negative for homozygous deletion in all tumors. Clinical follow-up showed that one patient had died 8 months after diagnosis and one had remained alive with short post-diagnostic follow-up. The tumors herein described highlight a challenging issue in the separation of mesothelioma with heterologous elements from true osteosarcomas of pleural origin. We propose that a diagnosis of extraskeletal osteosarcoma of the pleura is rendered for tumors with malignant osseous and/or cartilaginous differentiation in which comprehensive immunohistochemical studies and FISH analysis have failed to provide support for a diagnosis of mesothelioma with heterologous elements.
Assuntos
Biomarcadores Tumorais , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Osteossarcoma , Neoplasias Pleurais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Neoplasias Pleurais/genética , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Osteossarcoma/patologia , Osteossarcoma/genética , Osteossarcoma/química , Diagnóstico Diferencial , Evolução FatalRESUMO
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments. METHODS: This historical cohort study based on routinely collected Danish National Registry data included adults newly diagnosed with MPM between 01 January 2011 and 31 May 2018. Summary statistics were used to describe patient characteristics and initial treatment. OS was estimated using Kaplan-Meier methods; Cox regression was used to compare patient mortality against the (age/sex-matched) general population and to investigate mortality predictors. RESULTS: Overall, 880 patients were included; 44% had advanced MPM, 37% had non-advanced MPM, and 19% had unknown MPM stage. Median age at diagnosis was 71.9 years, and 82% of the patients were male. Within 180 days of diagnosis, no treatment was recorded for 215 patients (54%) with advanced MPM and 150 (46%) with non-advanced MPM. Median time-to-initial treatment (interquartile range) was 47 days (31-111) overall, 40 days (28-77) in patients with advanced MPM, and 53 days (35-121) with non-advanced MPM. Median OS was 13.7 months overall (non-advanced MPM: 18.0 months vs. advanced MPM: 10.0 months). Predictors of higher mortality were older age at diagnosis, histology, and advanced MPM stage. INTERPRETATION: These findings provide a baseline upon which to evaluate MPM epidemiology as newer treatments are adopted in routine practice.
Assuntos
Mesotelioma Maligno , Neoplasias Pleurais , Sistema de Registros , Humanos , Dinamarca/epidemiologia , Masculino , Idoso , Feminino , Mesotelioma Maligno/terapia , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/patologia , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Neoplasias Pleurais/patologia , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos de Coortes , Idoso de 80 Anos ou mais , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the efficiency of pemetrexed cisplatin in comparison with gemcitabine cisplatin and to validate the EORTC (European Organisation for Research and Treatment of Cancer) prognostic score in combination chemotherapy treatment for malignant pleural mesothelioma. STUDY DESIGN: An observational study. Place and Duration of the Study: Department of Oncology, Dicle University Hospital, Diyarbakir, Turkiye, from October 2000 to November 2017. METHODOLOGY: Malignant pleural mesothelioma (MPM) patients with EORTC score 0- were recruited. Factors affecting the prognosis of the disease and the effectiveness of first-line treatment were retrospectively analysed. EORTC prognostic score was calculated with a cut-off and survival analyses were used by the Kaplan-Meier method. Log-rank and univariable Cox regression tests were used to search for prognostic factors' impact on survival. RESULTS: Patients who received gemcitabine cisplatin treatment had a median progression-free survival (PFS) of 9 months, while those who received pemetrexed cisplatin therapy had a median PFS of 7 months. Median overall survival (OS) was 17 months in the gemcitabine cisplatin group and 18 months in the pemetrexed cisplatin group (p = 0.051). When the low-risk group was compared with the high-risk group, the median OS was found to be statistically significant (p = 0.009). CONCLUSION: The EORTC prognostic score, which is used for prognostic prediction in the period when pemetrexed is not utilised in the treatment of MPM, accurately predicts prognosis subsequent to the administration of pemetrexed in treatment. In the context of first-line treatment, cisplatin in combination with gemcitabine and cisplatin in combination with pemetrexed demonstrated comparable efficacy with respect to both overall survival and progression-free survival. KEY WORDS: Chemotherapy, Mesothelioma, Prognosis, Gemcitabine, Progression-free survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Desoxicitidina , Gencitabina , Mesotelioma Maligno , Pemetrexede , Neoplasias Pleurais , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pemetrexede/uso terapêutico , Pemetrexede/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Pessoa de Meia-Idade , Mesotelioma Maligno/tratamento farmacológico , Prognóstico , Idoso , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Adulto , Intervalo Livre de ProgressãoRESUMO
Malignant pleural mesothelioma (MPM) represents a significant clinical challenge due to limited therapeutic options and poor prognosis. Beyond mere survivorship, setting up an effective framework to improve functioning and quality of life is an urgent need in the comprehensive management of MPM patients. Therefore, this study aims to review the current understanding of MPM sequelae and the effectiveness of rehabilitative interventions in the holistic approach to MPM. A narrative review was conducted to summarize MPM sequelae and their impact on functioning, disability, and quality of life, focusing on rehabilitation interventions in MPM management and highlighting gaps in knowledge and areas for further investigation. Our findings showed that MPM patients experience debilitating symptoms, including fatigue, dyspnea, pain, and reduced exercise tolerance, decreasing quality of life. Supportive and rehabilitative interventions, including pulmonary rehabilitation, physical exercise improvement, psychological support, pain management, and nutritional supplementation, seem promising approaches in relieving symptoms and improving quality of life but require further research. These programs emphasize the pivotal synergy among patient-tailored plans, multidisciplinary team involvement, and disease-specific focus. Despite advancements in therapeutic management, MPM remains a challenging disease with limited effective interventions that should be adapted to disease progressions. Rehabilitative strategies are essential to mitigate symptoms and improve the quality of life in MPM patients. Further research is needed to establish evidence-based guidelines for rehabilitative interventions tailored to the unique needs of MPM patients.
Assuntos
Mesotelioma Maligno , Qualidade de Vida , Humanos , Mesotelioma Maligno/reabilitação , Neoplasias Pleurais/reabilitação , Neoplasias Pleurais/psicologiaRESUMO
This review delves into the intricate landscape of pleural mesothelioma (PM), emphasizing the need for nuanced therapeutic strategies. While platinum-based chemotherapy remains a cornerstone, the advent of immune checkpoint inhibitors (ICIs), notably through the Checkmate 743 trial, has reshaped treatment paradigms. Challenges persist due to patient heterogeneity and a lack of specific biomarkers. Targeting genotypic and phenotypic alterations emerges as a promising avenue, demanding precision oncology in this rare disease. CDKN2A loss, prevalent in PM, may respond to CDK4/6 inhibitors. Defects in MMR and HR suggest tailored approaches with ICI or PARP inhibitors, respectively. Ongoing trials explore novel inhibitors and promising targets like mesothelin. Implementing these strategies requires overcoming challenges in patient selection, combination therapies, biomarker identification, and cost considerations. Collaboration is crucial for transforming these insights into impactful clinical interventions, heralding the era of personalized and precision medicine for PM.
Assuntos
Mesotelioma , Terapia de Alvo Molecular , Neoplasias Pleurais , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Terapia de Alvo Molecular/métodos , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/patologia , Mesotelioma Maligno/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
Background: Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy. Method: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology. Results: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFß1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor. Conclusion: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.
Assuntos
Interleucina-6 , Derrame Pleural Maligno , Humanos , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/imunologia , Interleucina-6/metabolismo , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Neoplasias Pleurais/imunologia , Neoplasias Pleurais/secundário , Citocinas/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/imunologia , Feminino , Masculino , Idoso , Biomarcadores Tumorais/metabolismo , Quimiocinas/metabolismo , Transdução de Sinais , Microambiente Tumoral/imunologia , Pessoa de Meia-IdadeRESUMO
Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM is often diagnosed late, at a point where limited treatment options are available, but early intervention could improve the chances of successful treatment for MPM patients. Biomarkers to detect MPM in at-risk individuals are needed to implement early diagnosis technologies. Volatile organic compounds (VOCs) have previously shown diagnostic potential as biomarkers when analysed in MPM patient breath. In this study, chorioallantoic membrane (CAM) xenografts of MPM cell lines were used as models of MPM tumour development for VOC biomarker discovery with the aim of generating targets for investigation in breath, biopsies or other complex matrices. VOC headspace analysis of biphasic or epithelioid MPM CAM xenografts was performed using solid-phase microextraction and gas chromatography-mass spectrometry. We successfully demonstrated the capture, analysis and separation of VOC signatures from CAM xenografts and controls. A panel of VOCs was identified that showed discrimination between MPM xenografts generated from biphasic and epithelioid cells and CAM controls. This is the first application of the CAM xenograft model for the discovery of VOC biomarkers associated with MPM histological subtypes. These findings support the potential utility of non-invasive VOC profiling from breath or headspace analysis of tissues for detection and monitoring of MPM.
Assuntos
Membrana Corioalantoide , Cromatografia Gasosa-Espectrometria de Massas , Neoplasias Pulmonares , Mesotelioma Maligno , Neoplasias Pleurais , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Animais , Humanos , Mesotelioma Maligno/patologia , Neoplasias Pleurais/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/análise , Mesotelioma/patologia , Linhagem Celular Tumoral , Xenoenxertos , Testes Respiratórios/métodos , Microextração em Fase Sólida/métodosRESUMO
BACKGROUND: First- and second-generation anti-epithelial growth factor receptor tyrosine kinase inhibitors have shown great efficacy in the treatment of advanced adenocarcinoma with epithelial growth factor receptor mutations, but this efficacy is limited by certain resistance mechanisms, in particular the T790M mutation, which must be screened before second-line treatment with osimertinib is indicated. The search for this mutation is sometimes difficult, especially in cases of intracranial relapse, through this case report we attempt to discuss the possibility of initiating treatment with osimertinib despite an unknown T790M mutation in such situation. CASE REPORT: We present the case of a 70-year-old Moroccan male patient diagnosed with non-small cell lung carcinoma initially metastatic to the pleura with an epithelial growth factor receptor mutation who received gefitinib in first line with a complete response, he subsequently presented with cerebral oligo-progression with extra cranial stability. The patient was started on osimertinib with unknown T790M status, as it was impossible to perform a cerebral biopsy, the evolution was characterized by a partial response followed by stereotactic radiotherapy then a complete response for 2 years. CONCLUSION: We can discuss osimertinib as an option for patients with stage IV non-small cell lung cancer with brain oligo-progression on prior tyrosine kinase inhibitors and unknown T790M status, further studies are needed in this area.
Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Neoplasias Encefálicas , Receptores ErbB , Gefitinibe , Neoplasias Pulmonares , Mutação , Neoplasias Pleurais , Humanos , Masculino , Compostos de Anilina/uso terapêutico , Acrilamidas/uso terapêutico , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Gefitinibe/uso terapêutico , Receptores ErbB/genética , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Antineoplásicos/uso terapêutico , Neoplasias Pleurais/secundário , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Progressão da Doença , Resultado do Tratamento , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Indóis , PirimidinasRESUMO
Mesotheliomas are neoplasia developed from the mesothelium, a layer covering the viscera (visceral layer) and the cavity where the organs are (parietal layer). The best known, and the most frequently encountered is the pleural mesothelioma. This disease has a close link with exposure to asbestos, a mineral fibre now banned in several countries. However, other exposure factors have also been incriminated, including another one recognised as a certain carcinogenic agent for several years now : erionite. We present the case of a patient with pleural mesothelioma whose exposure to erionite could be demonstrated. The presentation of this clinical case will be complemented by a literature review on this less known and mostly environmental exposure, contrary to asbestos which is mostly professional.
Les mésothéliomes sont des néoplasies se développant à partir du mésothélium, feuillet recouvrant, d'une part, les viscères (feuillet viscéral) et, d'autre part, la cavité où se trouvent les organes (feuillet pariétal). Le plus connu, et le plus fréquemment rencontré, est le mésothéliome pleural. Cette maladie a un lien étroit avec l'exposition à l'amiante, fibre minérale maintenant interdite dans plusieurs pays. Cependant, d'autres facteurs expositionnels ont également été incriminés, dont un autre reconnu comme cancérogène certain depuis plusieurs années : l'érionite. Nous présentons le cas d'un patient atteint d'un mésothéliome pleural pour lequel une exposition à l'érionite a pu être étayée. La présentation du cas clinique sera complétée d'une revue de la littérature sur cette exposition particulière moins connue et majoritairement environnementale, contrairement à l'amiante dont l'exposition est majoritairement professionnelle.