Patient characteristics, treatment patterns, and survival outcomes for patients with malignant pleural mesothelioma in Denmark between 2011 and 2018: a nationwide population-based cohort study.

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.

Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma-Protocol of the Immuno-MESODEC study.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial's primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.

A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205.

BACKGROUND: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. METHODS: EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality. FINDINGS: 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. INTERPRETATION: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].

Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy.
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Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study.

BACKGROUND: Dendritic cell immunotherapy has proven to be safe and induces an immune response in humans. We aimed to establish the efficacy of dendritic cells loaded with allogeneic tumour cell lysate (MesoPher, Amphera BV, 's-Hertogenbosch, Netherlands) as maintenance therapy in patients with pleural mesothelioma. METHODS: In this open-label, randomised, phase 2/3 study, patients with histologically confirmed unresectable pleural mesothelioma, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status score of 0-1, and non-progressing disease after four to six cycles of standard chemotherapy (with pemetrexed 500 mg/m2 plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve of 5]) were recruited from four centres in Belgium, France, and The Netherlands. Participants were randomly assigned (1:1), using block randomisation (block size of 4), stratified by centre and histology (epithelioid vs other), to MesoPher treatment plus best supportive care or best supportive care alone. Patients received up to a maximum of five MesoPher infusions, with treatment administered on days 1, 15, and 29, and weeks 18 and 30. At each timepoint, participants received an injection of 25 × 106 dendritic cells (two-thirds of the dendritic cells were administered intravenously and a third were injected intradermally). Best supportive care was per local institutional standards. The primary endpoint was overall survival, assessed in all participants randomly assigned to treatment (full analysis set) and safety assessed in all randomly assigned participants, and who underwent leukapheresis if they were in the MesoPher group. This study is registered with ClinicalTrials.gov, NCT03610360, and is closed for accrual. FINDINGS: Between June 21, 2018, and June 10, 2021, 176 patients were screened and randomly assigned to the MesoPher group (n=88) or best supportive care alone group (n=88). One participant in the MesoPher group did not undergo leukapheresis. Mean age was 68 years (SD 8), 149 (85%) of 176 were male, 27 (15%) were female, 173 (98%) were White, two were Asian (1%), and one (1%) was other race. As of data cutoff (June 24, 2023), after a median follow up of 15·1 months (IQR 9·5-22·4), median overall survival was 16·8 months (95% CI 12·4-20·3; 61 [69%] of 88 died) in the MesoPher group and 18·3 months (14·3-21·9; 59 [67%] of 88 died) in the best supportive care group (hazard ratio 1·10 [95% CI 0·77-1·57]; log-rank p=0·62). The most common grade 3-4 treatment-emergent adverse events were chest pain (three [3%] of 87 in the MesoPher group vs two [2%] of 88 in the best supportive care group), dyspnoea (none vs two [2%]), anaemia (two [2%] vs none), nausea (none vs two [2%]), and pneumonia (none vs two [2%]). No deaths due to treatment-emergent adverse events were recorded. Treatment-related adverse events consisted of infusion-related reactions (fever, chills, and fatigue), which occurred in 64 (74%) of 87 patients in the MesoPher group, and injection-site reactions (itch, erythema, and induration), which occurred in 73 (84%) patients, and all were grade 1-2 in severity. No deaths were determined to be treatment related. INTERPRETATION: MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities. FUNDING: Amphera BV and EU HORIZON.

Malignant pleural mesothelioma: Description of pleural decortication and hyperthermic chemotherapy technique in multimodal therapy.

The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is laborious and detailed and must be followed step by step to achieve good results. We present the case of a patient with epithelioid mesothelioma meeting surgical criteria who underwent the mentioned technique, experiencing an adequate postoperative period and an early discharge. This experience demonstrates that the technique is safe when performed in centres with experience and the means to address this complex pathology.

Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study.

OBJECTIVES: Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent. DESIGN: A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period. SETTING: Secondary thoracic cancer care. RESULTS: Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment. CONCLUSIONS: With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible. TRIAL REGISTRATION NUMBER: ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.

Leveraging the pleural space for anticancer therapies in pleural mesothelioma.

Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Pediatric, Adolescent and Young Adult (AYA) Peritoneal and Pleural Mesothelioma: A National Cancer Database Review.

PURPOSE: Malignant peritoneal and pleural mesothelioma are rare in young patients, with a paucity of data regarding clinical characteristics and outcomes. We aimed to describe the clinical characteristics, treatment strategies, and outcomes for pediatric and adolescent/young adult (AYA) patients. METHODS: The National Cancer Database (NCDB) was queried for malignant peritoneal and pleural mesothelioma in pediatric and AYA patients (ages 0-39) from 2004 to 2019. Stratification was performed for pediatric (age 0-21) and young adult (age 22-39) patients. Chi-squared, multivariable cox regression, and Kaplan-Meier analyses were performed. RESULTS: We identified 570 total patients, 46 pediatric and 524 young adult, with mesothelioma (363 peritoneal and 207 pleural). There were significant differences in sex distribution as patients with peritoneal mesothelioma were more frequently female (63.1%). Patients with peritoneal mesothelioma were more likely to have radical surgery compared to pleural mesothelioma (56.7% v. 24.6%, respectively). A majority of patients with peritoneal and pleural mesothelioma received chemotherapy (66.4% and 61.4%, respectively). For peritoneal mesothelioma, surgical resection was associated with improved overall survival, whereas male sex, neoadjuvant chemotherapy, and radiation were associated with worse overall survival. For pleural mesothelioma, intraoperative chemotherapy was associated with improved overall survival, whereas Black race was associated with worse overall survival. Mean overall survival was greater for patients with peritoneal mesothelioma (125 months) compared to those with pleural mesothelioma (69 months), which remained significant after stratification of pediatric and young adult patients. CONCLUSION: By analyzing a large cohort of pediatric and AYA mesothelioma, this study highlights clinical, prognostic, and survival differences between peritoneal and pleural disease. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective.

Involvement of Palliative Care in Malignant Pleural Mesothelioma Patients and Associations with Survival and End-of-Life Outcomes.

Malignant pleural mesothelioma is a rare, aggressive, and incurable cancer with a poor prognosis and high symptom burden. For these patients, little is known about the impact of palliative care consultation on outcomes such as mortality, hospital admissions, or emergency department visits. The aim of this study is to determine if referral to supportive and palliative care in patients with malignant pleural mesothelioma is associated with survival and decreased hospital admissions and emergency department visits. This is a retrospective chart review. Study participants include all malignant pleural mesothelioma patients seen at The Ottawa Hospital-an acute care tertiary center-between January 2002 and March 2019. In total, 223 patients were included in the study. The mean age at diagnosis was 72.4 years and 82.5% were male. Of the patients diagnosed between 2002 and 2010, only 11 (9.6%) were referred to palliative care. By comparison, of those diagnosed between 2011 and 2019, 49 (45.4%) were referred to palliative care. Median time from diagnosis to referral was 4.1 months. There was no significant difference in the median survival of patients referred for palliative care compared to those who did not receive palliative care (p = 0.46). We found no association between receiving palliative care and the mean number of hospital admissions (1.04 vs. 0.91) from diagnosis to death, and an increase in mean number of emergency department visits in the palliative care group (2.30 vs. 1.18). Although there was increased utilization of palliative care services, more than half of the MPM patients did not receive palliative care despite their limited survival. There was an increase in emergency department visits in the palliative care group; this may represent an increase in the symptom burden (i.e., indication bias) in those referred to palliative care.

[Interdisciplinary diagnostics and therapy of malignant mesothelioma]. / Interdisziplinäre Diagnostik und Therapie von malignen Mesotheliomen.

The asbestos-related malignant mesothelioma (MM) is one of the common occupational cancers in Germany with approximately 1000 new cases per year. Provided that the appropriate diagnostic criteria are fulfilled, MM can be diagnosed with high specificity from both histological and cytological specimens. However, many MM are detected cyto-/histologically only at advanced stages. Clinical/radiological aspects complement each other and enable interdisciplinary assessment of tumor stage and individualized decisions on the best possible therapeutic options. Diagnostically, video-assisted thoracoscopy (VATS) has the highest priority. Therapy planning is based on the MM subtype, tumor spread and stage, and the patient's clinical condition. MM has generally a very unfavorable prognosis. Accordingly, the standard therapy aims at a macroscopic radical tumor resection in terms of cytoreduction within the framework of a suitable multimodal therapy concept (chemotherapy, radiotherapy, psychooncology). The aim of palliative measures should be primarily symptom control. Overall, interdisciplinary diagnosis and therapy of MM is crucial for the best possible care of MM patients.

Aspectos diagnósticos y terapéuticos en el mesotelioma pleural maligno / Diagnostic and therapeutic aspects in malignant pleural mesothelioma

Para el diagnóstico de mesotelioma se requiere distinguir entre afectación mesotelial benigna y maligna, y entre mesotelioma maligno y carcinoma metastásico. Para ello son necesarias técnicas inmuno-histoquímicas realizadas sobre biopsias amplias. La toracoscopia es la técnica de elección, aunque la biopsia con aguja usando técnicas de imagen en tiempo real puede ser muy útil si hay marcado engrosamiento nodular. Es improbable que la cirugía radical (pleuroneumonectomía) sea realmente curativa, por lo que está ganando adeptos la reducción de masa tumoral mediante pleurectomía/decorticación, con asociación de quimioterapia y radioterapia a la cirugía (terapia multimodal). Cuando la resección no es factible se plantea quimioterapia, con pleurodesis o colocación de un catéter pleural tunelizado si se requiere el control del derrame pleural y se reserva la radioterapia para tratar la infiltración de la pared torácica. También es esencial un completo control del dolor (que adquiere particular protagonismo en esta neoplasia) en unidades especializadas.

Diagnosis of malignant pleural mesothelioma requires making the distinction between benign mesothelial hiperplasia and true mesothelioma, and between malignant mesothelioma and metastatic pleural adenocarcinoma. This involves immunohisto-chemical techniques applied on large biopsy specimens, and thoracoscopy is the best choice for obtaining them. Real-time image-guided needle biopsy can also be very helpful in presence of marked nodular pleural thickening. Radical surgery (ie, extrapleural pneumonectomy) is unlikely to cure completely the patient, and cyto-reduction surgery with preservation of the underlying lung (pleurectomy/decortication), with addition of chemo and radiation therapy (muiltimodal treatment) is gaining adepts in the last few years. When surgery is not feasible at all, early chemotherapy -with pleurodesis or placement of a indwelling pleural catheter (to control the effusion if necessary)- is advisable. Radiation therapy should be reserved to treat chest wall infiltration in those cases, and complete control of pain in specialized units is also essential in those patients.

Tratamento quimioterápico do mesotelioma pleural maligno: uma revisão sistemática / Chemotherapy treatment of malignant pleural mesothelioma: a systematic review

Contexto - O mesotelioma pleural maligno é um tipo de câncer raro, agressivo e com uma expectativa de aumento na incidência até 2030. As melhores formas de diagnosticar,estadiar e tratar essa neoplasia continuam em debate. Objetivos - Estabelecer a evidência de eficácia e segurança dos diferentes esquemas quimioterápicos disponíveis para o tratamento do mesotelioma pleural maligno.Fontes de Dados - As bases bibliográficas utilizadas para a busca de artigos indexados foram Cochrane Controlled Trials Register, Lilacs, Medline (via Pubmed), Scopus e Webof Science. Além disso, foram buscados estudos na literatura cinzenta.Critérios de Elegibilidade – Participantes: pacientes com mesotelioma pleural maligno virgens de tratamento quimioterápico; Intervenção: tratamento quimioterápico; Controle:tratamento quimioterápico ou controle ativo de sintomas; Desfechos: Tempo de sobrevida,tempo livre de progressão, resposta tumoral e toxicidade; Estudos: ensaios clínicos randomizados de fase II ou III.Resultados - Um total de nove estudos envolvendo treze esquemas terapêuticos preencheram os critérios para inclusão nesta revisão. Em relação à eficácia, o único esquema quimioterápico que se apresenta superior ao seu comparador com significância estatística nos três desfechos é cisplatina mais pemetrexede. Os outros esquemas que demonstraram superioridade, mas sem a significância estatística foram: cisplatina mais raltitrexede, vinorelbina e carboplatina mais pemetrexede. Em relação à toxicidade, cisplatinamais pemetrexede, cisplatina mais raltitrexede se destacaram negativamente...

Background - Malignant pleural mesothelioma is a rare and aggressive cancer with anexpected increase in the incidence by 2030. The best ways to diagnose, staging and treat this disease still under discussion.Objectives - To establish the evidence of efficacy and safety of different chemotherapy regimens available for the treatment of malignant pleural mesothelioma. Data Sources - The bibliographic databases used for the search of indexed articles were Cochrane Controlled Trials Register, Lilacs, Medline (via Pubmed), Scopus and Web of Science. In addition, studies were sought in the gray literature. Study Eligibility Criteria - Participants: chemotherapy naïve patients with malignant pleural mesothelioma; Intervention: chemotherapy; Control: chemotherapy or active symptom control; Outcomes: survival time, progression-free time, tumor response and toxicity; Studies: phase II or III randomized clinical trials. Data Synthesis - A total of nine studies involving thirteen regimens met the criteria for inclusion in this review. Regarding efficacy, the only chemotherapy regimen that appears superior to their control group with statistical significance in the three outcomes is cisplatinplus pemetrexed. The other schemes that have shown superiority but without statistical significance were: cisplatin plus raltitrexed, vinorelbine and carboplatin plus pemetrexed. Regarding toxicity, cisplatin plus pemetrexed, cisplatin plus raltitrexed stood out negatively. Conclusions - The use of platinum more antifolate combination as first line chemotherapy ofmalignant pleural mesothelioma is in accordance with therapeutic guidelines and other systematic reviews published. Cisplatin and pemetrexed have preference over carboplatinand raltitrexed. Economic evaluations and a clinical study in Brazil are required to give foundation incorporating decision of antifolates in the routine treatment of this cancer...

Massive pleural effusion due to metastasis of prostate cancer / Efusión pleural masiva debido a metástasis de cáncer de próstata

We describe the case of a 72-year old male with pleural effusion associated with prostate cancer. There was a previous history of tobacco smoking (pack/year: 47) and of total prostatectomy followed by external beam radiation therapy seven years previously for prostate cancer. Furthermore, he was submitted to orchiectomy plus non-steroidal anti-androgen blockage, in addition to docetaxel-based chemotherapy and prednisone. After the beginning of chemotherapy, a progressive elevation in prostate specific antigen (PSA) levels was observed. On admission, he presented with fever, weight loss, and respiratory symptoms due to a massive right pleural effusion. Fluid samples obtained by needle aspiration showed haemorrhagic exudates without malignant cells. Pleural metastasis were detected by thorax imaging studies, and biopsy samples revealed prostate adenocarcinoma as the origin of his pleural effusion. Pleural fluid was drained and talc pleurodesis was performed. This report aims to describe the occurrence of massive pleural effusion due to metastasis of prostate cancer, and emphasizes the role of pleural biopsy with immunohistochemical studies to characterize this diagnosis.

Se describe un hombre de 72 años con efusión pleural asociada con cáncer de próstata. Había antecedentes de tabaquismo (47 paquetes por año) así como una historia de prostatectomía radical, seguida por terapia de radiación externa, siete años antes. Además, se le sometió a orquiectomía junto con bloqueo antiandrogénico no esteroideo, además de quimioterapia a base de docetaxel y prednisona. Después de iniciada la quimioterapia, se observó una elevación progresiva en los niveles de PSA. En el momento del ingreso, el paciente presentaba fiebre, pérdida de peso, y síntomas respiratorios debidos a una efusión pleural derecha voluminosa. Las muestras de fluido obtenidas mediante punción aspirativa con aguja fina, mostraron exudados hemorrágicos sin células malignas. Se detectaron implantes pleurales con los estudios imaginológicos del tórax, y las muestras de la biopsia revelaron que el origen de su efusión pleural, era un adenocarcinoma de la próstata. Se drenó el fluido pleural, y se procedió a practicar una pleurodesis con talco. Este reporte tiene por objetivo describir la ocurrencia de la efusión pleural masiva debido a la metástasis del cáncer de la próstata, y enfatiza el papel que desempeña la biopsia pleural junto a los estudios inmunohistoquímicos a la hora de caracterizar este diagnóstico.

Blastoma pleuropulmonar: reporte de caso y revisión de la literatura / Pleuropulmonary blastoma: case report and review of the literature

The pleuropulmonary blastoma is an aggressive primary lung tumor. Is most frequent in paediatric population, and there are a few cases reported worldwide. It consists of embrionary primitive mesenquimal tissue, and is different of the adult Pulmonary Blastoma. The clinical presentation can be missed by other prevalent diseases or may be an accidental diagnosis. The outcome following diagnosis is poor, overall for types ii and iii, with bad response to surgery and quimiotherapy, high rates or recurrence to more aggressive forms (eg. BPP type i to type ii o iii). This report describes the clinical picture of a two years old preschool child with aggressive BPP. We reviewed the actual literature about this topic.

El blastoma pleuropulmonar (BPP), es un tumor agresivo primario de pulmón. Afecta sobre todo en la edad pediátrica, habiendo sido reportado pocos casos a nivel mundial. El BPP consiste de tejido mesenquimal primitivo embrionario, de características diferentes al blastoma pulmonar del adulto. La presentación clínica suele confundirse con otras patologías frecuentes o puede ser incidental. La sobrevida luego del diagnóstico es pobre, sobre todo para los tipos ii y iii, con poca respuesta a la quimioterapia- cirugía, y alta frecuencia de recaídas a formas más agresivas. Se describe el caso de una pre-escolar de 2 años, con diagnóstico de BPP, que presentó una evolución clínica agresiva, se realizó la revisión de la literatura sobre los principales tópicos concernientes a esta patología.

Tumor fibroso solitario gigante de la pleura / Giant solitary fibrous tumor of the pleura

Introducción: El tumor fibroso solitario es el segundo tumor primario de la pleura y puede alcanzar hasta 39 cm de diámetro; para tener la denominación de “gigante” debe ocupar al menos 40 % del hemitórax afectado. Por lo general su comportamiento es benigno, pero existen criterios de malignidad. El objetivo de esta investigación fue efectuar una revisión de la evaluación inicial, diagnóstico, manejo quirúrgico, resultado del tratamiento y pronóstico. Material y métodos: Estudio descriptivo, observacional, longitudinal y retrospectivo, realizado de 2002 a 2006, en pacientes operados con diagnóstico de tumor fibroso solitario gigante de la pleura. Resultados: Se incluyeron seis pacientes, 83.3 % del sexo femenino, con edad promedio de 48 años; todos sintomáticos con predominio de disnea, tos y dolor; en 66.7 % se encontró del lado izquierdo; a 83.3 % se realizó angiografía y embolización preoperatorias, logrando resección completa en todos; predominó aporte arterial de la arteria mamaria interna. Se encontró una tasa de complicaciones transoperatorias de 17 %. En 66.7 % se identificó un pedículo ascular; el tumor mayor midió 40 cm de diámetro con peso de 4500 g; solo uno presentó actividad mitótica elevada. El seguimiento promedio fue de 14 meses. Conclusiones: La sintomatología encontrada fue acorde con informes previos, aunque en porcentajes mayores. El diagnóstico correcto es de vital importancia, ya que con la resección quirúrgica el tumor fibroso solitario es potencialmente curable, sin embargo, requiere seguimiento a largo plazo. Dado el tamaño de este tipo de tumores es aconsejable llevar a cabo embolización preoperatoria.

BACKGROUND: Solitary fibrous tumor is the second primary malignancy of the pleura and can reach up to 39 cm in diameter; however, to be referred to as 'giant' it must occupy at least 40% of the affected hemithorax. Although this tumor usually shows a benign behavior, malignancy criteria have been described. The aim of the study was to assess the initial evaluation, diagnostic procedures, surgical management, treatment outcome, and prognosis. METHODS: We performed a descriptive, observational, longitudinal, and retrospective study from 2002 to 2006 on patients who underwent surgery with a diagnosis of giant solitary fibrous tumor of the pleura. RESULTS: Six patients were included; 83.3% were females. Mean age was 48 years. All patients were symptomatic, mainly dyspnea, cough and chest pain; 66.7% were left-sided. Preoperative angiography and embolization were performed in 83.3% cases with successful surgical resection. The predominant blood supply was derived from the internal mammalian artery. Intraoperative complication rate was 17%. A vascular pedicle was found in 66.7%. The largest lesion was 40 cm in diameter and weighed 4500 g. Only one case showed high mitotic activity. Mean follow-up to date is 14 months. CONCLUSIONS: Symptomatology found was consistent with previous reports but in higher percentages. Accurate diagnosis is critical because surgical resection involves a potential cure; however, long-term follow-up is mandatory. Preoperative embolization is recommended due to tumor size.

Hemangioendotelioma epitelioide de pleura: presentación de un caso con hemotórax / Epithelioid hemangioendothelioma of the pleura: presentation of a case with hemotorax

Los hemangioendoteliomas son tumores vasculares que pueden afectar pulmón. Abarcan desde lesiones benignas o de baja malignidad hasta lesiones de malignidad intermedia, como el hemangioendotelioma epitelioide o el polimorfo. El hemangioendotelioma epitelioide es un tumor muy raro que afecta principalmente a mujeres menores de 40 años, ha sido asociado al uso de anticonceptivos orales y a la inhalación de cloruro de vinilo. Sólo se describen en la literatura unos cincuenta casos de hemangioendotelioma epitelioide pulmonar y muy pocos pleurales. Inmunomarcadores permiten caracterizar este tipo de neoplasias. El diagnóstico diferencial incluye tumores benignos y malignos y el pronóstico es poco predecible. No hay consenso en cuanto al tratamiento, el cual ha incluído cirugía, carboplatino más etopósido e interferón. Se presenta una paciente de 37 años, se discuten los hallazgos clínicos su tratamiento y evolución.

The hemangioendotheliomas are vascular tumors that may involve lungs. The malignancy of these tumours can be benign, low or intermediate, such as the epithelioid or the polymorph hemangioendothelioma. The epithelioid hemangioendothelioma is an unusual tumour that appears more frequently in females, younger than 40 years of age. It has been associated to the use of oral contraceptives and the inhalation of vinile chloride. Only some 50 cases of pulmonary epithelioid hemangioendothelioma and few of pleural origin have been described in the literature. Immunomarkers may help to characterize this kind of tumours. The differential diagnosis includes malignant and benign tumours and its prognosis is hard to predict. Its therapy remains controversial, surgery, chemotherapy with carboplatin plus etoposide and interferon were used. The case of a 37 year old female is presented; clinical findings, therapy and outcome are discussed.