Treatment Of Malignant Pleural Mesothelioma Research Articles

Treatment for Malignant Pleural Mesothelioma

Treatment for Malignant Pleural Mesothelioma

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma

BackgroundNivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM.MethodsThis study included patients treated with nivolumab at Tokushima University Hospital from February 2009 to September 2021. We retrospectively reviewed the medical records to evaluate the several clinical factors, such as the presence or absence of irAEs, their severities, progression-free survival (PFS), overall survival (OS) or objective response to the treatment.ResultsEleven patients received treatment with nivolumab. Objective response rate was 18.2% and the disease control rate was 90.9%. Median PFS was 6.8 months (95% confidence interval, 1.3 to 11.9 months) and median OS was 15.2 months (95% confidence interval, 8.9 to 21.5 months). IrAEs occurred in eight patients (72.7%), and grade ≥ 2 irAEs occurred in six patients (54.5%). PFS and OS were significantly longer in the grade ≥ 2 irAEs group than in grade < 2 irAEs group (median PFS 13.6 vs. 3.8 months, p = 0.0093; median OS not reached vs. 8.6 months, p = 0.0108).ConclusionsThis is the first study to report the correlation between irAEs and therapeutic effects in patients with MPM. Because the presence of irAEs may be associated with a favorable clinical outcome, early detection and appropriate management of irAEs will increase the therapeutic benefits to patients.

The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.

Impact of Tumor Treating Fields (TTFields) on DNA Damage Repair in Mesothelioma

Tumor Treating Fields (TTFields) are low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields delivered to solid tumors noninvasively and locoregionally. TTFields have demonstrated a promising median overall survival in patients with malignant pleural mesothelioma (MPM), an aggressive thoracic cancer with poor prognosis, without increases in systemic toxicity (STELLAR clinical trial). Consequently, TTFields therapy combined with pemetrexed and a platinum-based chemotherapy agent are approved as first line treatment for unresectable MPM in the US and Europe. While efficacy of TTFields for MPM treatment is well-established, the underlying mechanism of action needs further elucidation. This study investigated the TTFields effect on DNA damage and repair in MPM and tested the combination of TTFields with DNA damaging agents such as cisplatin and pemetrexed, in vitro and in vivo.TTFields frequencies ranging from 100-400 kHz were applied to human MPM cell lines (NCI-H2052 and MSTO-211H) to identify the most effective frequency. To detect DNA double strand breaks (DSB), the effect of optimal TTFields frequency on the formation of ɣH2AX foci was examined by fluorescent microscopy. Levels of DNA damage repair related proteins were evaluated via immunoblotting of cell lysates. The combined cytotoxic effect of TTFields with cisplatin or pemetrexed was tested in vitro. Efficacy of TTFields concomitant with both cisplatin and pemetrexed was examined in C57BL/6 mice inoculated subcutaneously with RN-5 cells by measuring tumor volume and DNA damage within the tumor.The optimal TTFields frequency was identified as 150 kHz in both MPM cell lines, displaying significant cytotoxicity and formation of DNA DSB. These effects were accompanied by increased expression of p21 and p27, proteins involved in DNA damage-induced cell cycle arrest, and reduced expression of proteins from the Fanconi Anemia (FA) DNA repair pathway - FANCA, FANCD2, FANCJ, and BRCA1. Co-treatment of TTFields with cisplatin or pemetrexed augmented efficacy versus each treatment alone, with the TTFields-pemetrexed combination displaying an additive effect, and the co-administration of TTFields with cisplatin demonstrating synergistic interaction. In vivo, tumor volume fold change was significantly decreased for the combination of TTFields with chemotherapy (cisplatin + pemetrexed) versus control, while levels of DNA damage within the tumor were increased.Efficacy of TTFields for the treatment of MPM is associated with increased DNA damage, elevated levels of DNA-damage related cell cycle arrest proteins, and reduced expression of FA pathway proteins. This latter effect may account for the synergistic interaction displayed for the TTFields-cisplatin combination, as cisplatin is known to cause DNA damage that requires the FA pathway for repair.

Segmentation of the Upper Torso for Lung Cancer TTFields Treatment Planning

<h3>Purpose/Objective(s)</h3> Tumor Treating Fields (TTFields) is an FDA-approved treatment for glioblastoma multiforme (GBM) and malignant pleural mesothelioma (MPM). Moreover, TTFields therapy is currently investigated in a phase III clinical trial for the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Recent studies have shown that larger TTFields dose was associated with longer patients' survival. Therefore, personalized simulations to estimate the dose are performed as part of the patient treatment planning. For MPM and NSCLC treatment, these simulations require the segmentation of all upper torso tissues. A manual segmentation of the torso requires a few dozens of hours per patient and is impractical. Therefore, we have developed a computational method for semi-automatic segmentation of all upper torso tissues that are relevant to TTFields treatment planning. <h3>Materials/Methods</h3> We have incorporated a dataset of 40 CT images of NSCLC patients that underwent TTFields treatment in the lungs for this study. We have utilized threshold-based methods combined with morphological operations, region growing methods and known anatomical spatial relations to automatically identify and segment the lungs, bones, skin, muscle, fat, spinal cavity, costal cartilage, trachea and bronchi. Other structures such as the heart, blood vessels, liver, stomach, spleen, esophagus, diaphragm and intervertebral discs were semi-automatically segmented by using a few reference points that were provided by a human rater. Since there is no gold standard segmentation of the whole torso, an experienced radiation oncologist that is highly familiar with TTFields treatment inspected the results of the algorithm on top of the original CT images. <h3>Results</h3> The radiation oncologist has confirmed that the semi-automatic segmentation of the torso provides an adequate quality result for TTFields treatment planning for all cases. The segmentation time was reduced to one hour on a typical patient, compared to 20 hours that is the estimated time required for a fully manual segmentation. <h3>Conclusion</h3> We have presented a method for adequate quality segmentation of the upper torso in a reasonable time to facilitate TTFields treatment planning. In addition, this method facilitates the creation of a dataset for the development of state-of-the-art segmentation methods that utilize deep learning methods.

Multivariate Model for Predicting Overall Survival in Malignant Pleural Mesothelioma After Adjuvant Radiotherapy

<h3>Purpose/Objective(s)</h3> Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer arising from the cells of the thoracic pleura. Its anatomic complexity, large surface area, and unique location pose challenges for target coverage while sparing adjacent organs at risk (OARs) during treatment planning for adjuvant radiotherapy after pleurectomy and decortication. We aimed to investigate the associations between patient/target characteristics and achievable dosimetric plan quality with overall survival. <h3>Materials/Methods</h3> Sixty patients with MPM patients who were treated on a tomotherapy unit between 2013-2018 at a single institution were included. All patients received helical IMRT with 45 Gy/25 fractions. Dosimetric quantities for the lungs, heart, and liver were systematically examined for 37 right-sided (RSM) and 23 left-sided mesothelioma (LSM) patients. Patient characteristics and/or planning dosimetric metrics were input into machine learning algorithms, e.g., LASSO regression, support vector machine (SVM), and multiple layer perceptron (MLP), in order to construct predictive models for overall survival. The performance of predictive models was evaluated with area under the curve (AUC) using 3-fold cross validation. Normal tissue complication probabilities (NTCP) for selected OARs were estimated using the Lyman-Kutcher-Burman model based on individual dose volume histograms. <h3>Results</h3> The achieved dosimetric endpoints were significantly different (<b>P</b> < 0.05) between LSM vs. RSM patients, respectively: ipsilateral lung V20_Gy of 91.2 ± 6.7 vs. 85.3 ± 6.5%, ipsilateral mean lung doses of 39.1 ± 3.8 vs. 36.9 ± 2.5 Gy, heart mean doses of 25.2 ± 3.6 vs. 18.8 ± 3.7 Gy, and liver mean doses of 10.6 ± 2.7 vs. 23.4 ± 4.2 Gy. There was no significant difference in total lung – planning target volume (PTV) mean dose, 13.4 ± 2.0 vs. 14.4 ± 1.5 Gy, nor expected lung pneumonitis for the LSM vs. RSM. No differences were observed between PTV coverage of 94.2 ± 1.2 vs. 93.4 ± 2.4%, and average survival intervals were 16.8 ± 14.4 months and 18.0 ± 18.0 months after RT between LSM vs. RSM. The MLP model achieved AUCs of 0.65, 0.67 and 0.71 using patient characteristics, dosimetric features, and combined features. The identified predictors most associated with overall survival were age, PTV volume, ipsilateral lung volume/V20_Gy, and ipsilateral lung – PTV V20_Gy <h3>Conclusion</h3> We demonstrated correlations between patient specific characteristics and achieved planning dosimetric parameters for left- and right-sided MPM treatment planning endpoints. Combining patient characteristics and dosimetric endpoints, the multivariate predictive model achieved decent performance in predicting overall survival. The predictive model may guide treatment planning to achieve optimal planning dosimetry, and to improve clinical outcome via personalized treatment for MPM.

MA04.06 MicroRNAs Contribute to the Chemotherapy Response of Malignant Pleural Mesothelioma

Although platinum-pemetrexed chemotherapy remains the gold-standard for treatment of malignant pleural mesothelioma (MPM), to date we are still lacking true predictive biomarkers able to identify those patients who truly respond to chemotherapy. Aiming to overcome this problem, we previously performed microRNA expression profiling in tumour tissue of responders and non-responders to induction chemotherapy, which identified candidate predictive microRNAs. Candidates from this profiling are now investigated in vitro for their potential to alter the response of MPM cell lines to cisplatin and pemetrexed.

Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma.

There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell modelsevaluated. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest, thereby increasing cell senescence and increased the expression of interferon signalling pathway and tumour antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumour growth and prolonged overall survival using distinct xenograft models of MPM implanted in athymic mice. Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.

Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are limited biomarkers available in the clinic to effectively diagnose MPM, an invasive biopsy procedure is usually required to provide a definitive diagnosis. Due to the long latency period associated with MPM disease presentation, the cancer is usually at an advanced stage at the time of diagnosis where treatment options are largely ineffective at controlling disease progression. Previous MPM-based pre-clinical studies have made significant strides in determining the exact molecular mechanisms associated with asbestos carcinogenesis. Exploring less invasive blood-based biomarkers and treatment strategies involving targeted therapy, immunotherapy, and virotherapy is particularly important. Research in these areas is of crucial importance in relation to improving the rate of novel diagnostic biomarkers and treatment strategies progressing through to clinical trials and ultimately into the clinical setting. This review comprehensively summarises both previous and current pre-clinical research developments that have specifically contributed to an improved understanding of MPM disease biology, and the development of novel diagnostic biomarkers and treatment strategies.

New Updates of the Imaging Role in Diagnosis, Staging, and Response Treatment of Malignant Pleural Mesothelioma.

Simple SummaryComputed tomography plays a pivotal role in malignant pleural mesothelioma imaging management, ranging from diagnosis, differential diagnosis and staging to assessment of therapy response. Indeed, CT still presents some intrinsic limitations such as a poor contrast resolution between tumor and contiguous soft tissues, resulting in a challenging assessment of locoregional staging. Moreover, the current response evaluation criteria are based on unidimensional criteria, while malignant pleural mesothelioma has a complex tridimensional pattern of growth. To overcome these limits, the recent efforts in literature focused on computer-based methods, such as radiomics or automated segmentation, and magnetic resonance imaging. This review aims to describe their potential role in diagnosis, staging and assessment of therapy response in malignant pleural mesothelioma. Malignant pleural mesothelioma is a rare neoplasm with poor prognosis. CT is the first imaging technique used for diagnosis, staging, and assessment of therapy response. Although, CT has intrinsic limitations due to low soft tissue contrast and the current staging system as well as criteria for evaluating response, it does not consider the complex growth pattern of this tumor. Computer-based methods have proven their potentiality in diagnosis, staging, prognosis, and assessment of therapy response; moreover, computer-based methods can make feasible tasks like segmentation that would otherwise be impracticable. MRI, thanks to its high soft tissue contrast evaluation of contrast enhancement and through diffusion-weighted-images, could replace CT in many clinical settings.

Nivolumab In Combination With Ipilimumab (Opdivo-Yervoy)

&#x0D; CADTH recommends that Opdivo in combination with Yervoy (nivolumab plus ipilimumab) should be reimbursed by public drug plans for the treatment of malignant pleural mesothelioma (MPM) if certain conditions are met.&#x0D; Opdivo plus Yervoy should only be reimbursed if prescribed by clinicians with experience in immuno-oncology and treating MPM and if the cost of Opdivo plus Yervoy is reduced.&#x0D; Opdivo plus Yervoy should only be covered to treat patients who have not received prior systemic treatment for MPM and who have good performance status at the start of treatment.&#x0D;

V-178 Diode-Pumped Laser for Lung-Sparing Surgical Treatment of Malignant Pleural Mesothelioma – Single-Surgeon Experience

V-178 Diode-Pumped Laser for Lung-Sparing Surgical Treatment of Malignant Pleural Mesothelioma – Single-Surgeon Experience

Mesothelioma - Diagnosis and treatment

Malignant pleural mesothelioma (MPM) is a highly aggressive type of cancer more prevalent in males, although its most common etiology is exposure to asbestos fibers. Improvements in the prognosis of the disease are prevented due to the late manifestation of the disease, difficulties in diagnosis, and inadequate conventional treatments. In recent years, anti-cancer immunotherapy and treatments consisting of single or combined checkpoint inhibitors have been tested. Although programmed death-1 receptor, programmed death-ligand 1, and cytotoxic T-lymphocyte- associated protein 4 immunosuppressant checkpoint agents are promising for future developments, the studies showed that these approaches are currently inadequate due to toxicity problems and poor results. Despite the better understanding of carcinogenesis with new therapeutic approaches, further therapeutic research is needed for the treatment of MPM. A better understanding of multidisciplinary approaches is required to improve the prognosis of the disease and patient survival. Thus, it will be possible to develop more effective treatment strategies.

Advances in Immunotherapy of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) represents the uncommon cancer originating from pleural mesothelial cells, which is associated with dismal prognostic outcome. According to CheckMate-743 results, nivolumab plus ipilimumab has been approved to treat the unresectable MPM in treatment-naive patients as a first-line therapy by the FDA in October 2020. Immunotherapy is expected to be the best choice for MPM treatment. In the following article, the past treatment plan and the progress of immunotherapy for MPM will be reviewed.

Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.

Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.

Abstract 1186: Efficacy of Tumor Treating Fields (TTFields) in mesothelioma is associated with reduced capacity for DNA damage repair

Abstract Introduction: Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer with a poor prognosis and limited treatment options. Tumor Treating Fields (TTFields) are a noninvasive, locoregionally, antineoplastic treatment, delivering low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields, that has demonstrated a promising median overall survival in patients with MPM without increases in systemic toxicity (STELLAR clinical trial). Accordingly, TTFields with pemetrexed and a platinum-based chemotherapy agent received FDA-approval as first line therapy for MPM. While efficacy of TTFields for MPM treatment is well-established, the underlying mechanism of action needs further elucidation. Methods: Human MPM cell lines (NCI-H2052 and MSTO-211H) were treated using various TTFields frequencies to assess the most effective frequency. The effect of optimal frequency TTFields on levels of DNA double strand breaks (DSB) was examined by fluorescent microscopy detection of γH2AX foci, and the levels of DNA damage repair proteins was evaluated by immunoblotting. The combined cytotoxic effect of TTFields with cisplatin or pemetrexed was tested in vitro, and efficacy of TTFields in combination with both chemotherapeutic agents was examined in C57BL/6 mice injected subcutaneously with RN-5 cells, by measuring tumor volume and through detection for DNA damage within the tumor. Results: The optimal TTFields frequency in both MPM cell lines was 150 kHz, demonstrating significant cytotoxicity and increases in formation of DNA DSB. These effects were associated with reduced expression of proteins from the Fanconi Anemia (FA) repair pathway for DNA repair - FANCA, FANCD2, FANCJ, and BRCA1. Co-treatment of TTFields with cisplatin or pemetrexed significantly increased treatment efficacy versus each treatment alone, with an additive effect shown by the TTFields-pemetrexed combination, and a tendency towards synergism displayed for TTFields-cisplatin co-administration. In animal models, tumor volume fold increase was significantly decreased for co-treatment with TTFields and chemotherapy (cisplatin + pemetrexed) versus the control, showing also increased DNA damage within the tumor bed in comparison to control or chemotherapy alone. Conclusions: The results presented here demonstrate that the efficacy of TTFields for treatment of MPM is associated with reduced expression of FA pathway proteins and increased DNA DSB. This effect may account for the synergistic effect seen for TTFields-cisplatin co-treatment, as cisplatin is known to cause DNA damage that requires the FA pathway for repair. This research provides further insights on the mechanism of action of TTFields in MPM, a treatment already approved against this malignancy. Citation Format: Helena Mumblat, Antonia Martinez, Ori Braten, Mijal Munster, Eyal Dor-On, Rosa S. Schneiderman, Yaara Porat, Tali Voloshin, Shiri Davidi, Roni Blatt, Anna Shteingauz, Catherine Tempel-Brami, Einav Zeevi, Carolina Lajterer, Yuval Shmueli, Shiri Danilov, Adi Haber, Moshe Giladi, Adrian Kinzel, Uri Weinberg, Yoram Palti. Efficacy of Tumor Treating Fields (TTFields) in mesothelioma is associated with reduced capacity for DNA damage repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1186.

Abstract 1064: Antiproliferative effects of Tumor Treating Fields in human mesothelioma cell lines

Abstract Despite the increasing knowledge of the biology of malignant pleural mesothelioma (MPM), patients with this diagnosis still have a poor prognosis with a 5-year survival rate of lower than 10%. The effectiveness demonstrated by Tumor Treating Fields (TTFields) in combination with chemotherapy in preclinical experiments and in MPM patients (NCT02397928) affirms TTFields as a promising therapeutic tool. Knowledge of the mechanism of action of TTFields and its interaction with chemotherapeutic agents may contribute to the design of more effective clinical trials for MPM patients. A panel of primary MPM cells was isolated from pleural effusion and/or lavages of patients' thoracic cavity, before administration of therapeutic treatment, obtaining six cell lines from the 3 types of MPM cells: epithelioid CD473 and CD484, sarcomatoid CD60 and CD432, and biphasic CD487 and CD491. RNAseq analysis revealed that the transcriptional profiles of CD473 and CD60 cells were comparable with those derived from patient biopsies of the same histotype, representing clinically relevant MPM models. Antiproliferative effects induced by TTFields alone (1.12 V/cm; 150 KHz; for 96h duration) were studied in these MPM cell lines. Cell survival and cell cycle perturbations analyses during and after treatment were performed. Consistent with clinical observations, epithelioid MPM cells demonstrated greater sensitivity to TTFields than biphasic and sarcomatoid MPM cells. Cell cycle analysis revealed that the former cell type was blocked in G2M phase and was followed by formation of polyploid cells; while the latter cell types were only slightly affected by TTFields with a general delay in all cell cycle phases. Apoptotic cells were present in all treated samples, but while epithelioid and biphasic cell death was already observed during the first 24h of treatment, sarcomatoid cells needed to be treated for at least 24h before starting apoptotic pathways. The antiproliferative effect observed in epithelioid cells was persistent even after treatment cessation, whereas biphasic and sarcomatoid cells were able to reinitiate growth upon TTFields cessation. RNAseq experiments were performed in CD473 and CD60 cells at different times during TTFields application to explore transcriptional modifications that may explicate these varied MPM cell responses. Preliminary data suggested that TTFields induced a transcriptional response already detectable at earlier time points of treatment (8h; maximum effect at 24h). The number of differentially expressed genes was higher in CD473 relative to CD60 cells (1951 in CD473 and 336 in CD60 at 24h), involving several pathways, that need to be further investigated. These data demonstrate that TTFields induce specific effects on cell proliferation in varied subsets of mesothelioma cells and provide a mechanistic rationale for future therapies and combinations with other anticancer drugs for MPM treatment. Citation Format: Monica Lupi, Federica Mirimao, Nicolò Panini, Greta Piazza, Lara Paracchini, Laura Mannarino, Sergio Marchini, Federica Grosso, Serena Penpa, Antonio Maconi, Giovanni L. Ceresoli, Maurizio D'Incalci. Antiproliferative effects of Tumor Treating Fields in human mesothelioma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1064.

The minimum standard of care for managing malignant pleural mesothelioma in developing nations within the Asia-Pacific Region.

Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis. The relationship between asbestos exposure and MPM incidence is well-established. The incidence rate of MPM in Australia and New Zealand is among the highest globally. Matching the experience of other nations with legal restrictions on asbestos, incidence is expected to fall. In contrast, the incidence of MPM is rising in the developing nations of the Asia-Pacific as consumption and mining (albeit to a lesser extent) of asbestos continues. The incidence of MPM in these nations is currently low or unknown, reflecting insufficient latency periods since industrial use of asbestos, deficient resources for accurate diagnosis, and lack of occupational disease or cancer registries. The landscape of treatment for MPM is rapidly changing with combination immunotherapy now demonstrating improved survival in the first-line setting. Considering vast global inequity in access to anticancer treatments, establishing minimum standard of care for MPM in developing nations is of greater significance. Here, we review the evidence that form the basis of our minimum-standard recommendations for diagnosis, systemic treatment, management of recurrent pleural effusions, and symptom management. We also briefly review evidence-based treatment that may be considered for those with access.

Research Progress of Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma

恶性胸膜间皮瘤（malignant pleural mesothelioma, MPM）是一种侵袭性强、生存率低且缺乏有效治疗选择的恶性肿瘤。培美曲塞联合顺铂作为晚期MPM唯一的一线治疗方案长达20年之久。长期以来，免疫疗法被认为是MPM的一种潜在治疗方法，主要包括免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）、免疫毒素治疗、抗癌疫苗、过继性细胞治疗等。本篇综述重点总结了MPM中ICIs的研究进展，初步分析了MPM肿瘤异质性对ICIs治疗的影响，描述了以生物标志物为导向的免疫治疗是实现MPM个体化治疗的新愿景。