Major pathological response obtained after neoadjuvant chemotherapy combined with dual immunotherapy for malignant pleural mesothelioma: a case report
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Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking. Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment. Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.Keywords:
Extrapleural Pneumonectomy
Pleurectomy
Pemetrexed
Neoadjuvant Therapy
Extrapleural Pneumonectomy
Pleurectomy
Decortication
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Malignant pleural mesothelioma (MPM) is associated with a very poor prognosis. Unlike other solid tumors, any type of planned surgery for MPM would be cytoreductive rather than radical. There are two types of surgery for MPM. Extrapleural pneumonectomy (EPP) involves en bloc resection of the lung, pleura, pericardium, and diaphragm. Pleurectomy/decortication (P/D) is a lung-sparing surgery that removes only parietal/visceral pleura. In comparison with EPP, P/D is theoretically less radical but is associated with less perioperative mortality/morbidity and less postoperative deterioration of cardiopulmonary function. It still remains unclear which surgical technique is superior in terms of the risk/benefit ratio. In this context, selection between EPP and P/D has been a matter to debate.
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従来，わが国の胸膜中皮腫に対する外科分野の議論は主に安全且つ確実な胸膜外肺摘除術（extrapleural pneumonectomy, EPP）の術式を巡ってなされてきたが，今後は胸膜切除/剥皮術（Pleurectomy/decortication，P/D）との比較が重要になる．そこで今まで検討されることの少なかった下記の5項目ついて考察を加えた．I．EPPの成績と限界．Trimodalityによる集学的治療の成績と展望を述べた．II．Radical P/D（壁側および臓側胸膜の肉眼的全切除）の現況．自験65例（EPP 31例，P/D 34例，内Radical P/D 6例）の成績をまじえ，EPPに劣らない成績を示す本術式の適応について述べた．III．自動縫合器を用いたEPPの術後3日目に発症した肺障害に対する考察．原因としては1）臨床的に確認し難い極小断端瘻の先行とこれに起因する対側肺吸引，2）術中，術後のover-hydration，3）原因不明のARDS，が考えられる．1）2）であるならば外科医の責任においてこれを回避する必要がある．IV．EPPと胸内筋膜（EF）の関係．胸内筋膜は切除標本側にあるか，胸壁に残るか，明らかでない．代表的な教科書数冊の記載から判断するとEFを弾力線維の膜とするよりも疎なareolarな結合組織の層と考えるのが妥当である．外科医はこの層を剥離する．V．今後の課題．EPPにおけるmortalityを5％以下に抑え，早期例における病理診断の精度向上を計ることが今後の臨床研究の発展に不可欠である．
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Purpose: This study was performed to compare the outcome of pleurectomy/decortication (P/D) with that of extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma (MPM).
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Background: For patients with malignant pleural mesothelioma (MPM), a multimodality treatment concept including neoadjuvant chemotherapy and radical surgery offers improved overall survival.While the lung-sparing extended pleurectomy and decortication (EPD) has become the preferential surgical approach, the more aggressive extrapleural pneumonectomy (EPP) remains reserved for a selected group of patients.Based on our experience from the past two decades, we aim to discuss and assess today's role of EPP.Methods: Out of 523 MPM patients intended to be treated by induction chemotherapy followed by macroscopic complete resection between January 1999 and December 2019, we identified 151 consecutive patients who underwent EPP at our center.All patients were treated within a multimodality concept including neoadjuvant chemotherapy with platinum-based agents plus gemcitabine or pemetrexed.Clinical data were collected in an online database and analyzed retrospectively.Results: Of all patients, 57.6% were of IMIG stage IA or IB (n=87), 39.0% of all patients IMIG stage IIIA or IIIB (n=59).Mean tumor volume after induction chemotherapy was 294.6±315.0cm 3 .Most patients were operated in the first decade between 1999 and 2009 [112 patients (74.2%)].The overall 30-and 90-day mortality was 4.6% and 10.6%, respectively.The median overall survival was 18.5 months.Major postoperative morbidity was assessed as a composite outcome and occurred in 38.4% of all patients.Conclusions: Although EPD became the procedure of first choice, EPP is a reasonable approach in selected patients with high tumor burden and extensive involvement of the lung parenchyma, where parenchyma-sparing resection is technically not feasible or functionally not rational.All patients should be preoperatively assessed and informed about the eventuality of EPP, depending on intraoperative findings.
Extrapleural Pneumonectomy
Pleurectomy
Decortication
Neoadjuvant Therapy
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Pleurectomy
Extrapleural Pneumonectomy
Decortication
Debulking
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Pemetrexed
Antifolate
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Pemetrexed
Carboplatin
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Mesothelioma is a highly lethal tumor derived from mesothelial cells, and its global incidence is increasing because of widespread exposure of numerous individuals to asbestos in the last 50 years. Mesothelioma is largely untreatable with any of the therapeutic modalities. Recently, a novel multitargeted antifolate pemetrexed has shown promising activity against malignant pleural mesothelioma, producing response rates of up to 40% when used in combination with cisplatin. In a large phase III study, use of a combination of pemetrexed and cisplatin was associated with significantly improved survival time and with greater antitumor activity compared with cisplatin alone. This combination also gave a significant response rate of approximately 50% in patients with epithelioid malignant pleural mesothelioma. These clinical benefits of pemetrexed-cisplatin doublet have changed the perception of mesothelioma chemotherapy. Other combinations, including gemcitabine in combination with cisplatin, have also shown encouraging response rates. Prognosis depends on gender, clinical stage of the tumor, histological subtype, platelet count, leukocyte counts, and performance status. Radiotherapy can palliate mesothelioma patients with chest pain, and has been indicated to be of benefit for the prevention of malignant seeding along the tract of a chest tube or needle biopsy. Trimodality treatment using extrapleural pneumonectomy, radiation and chemotherapy has shown promising therapeutic value. The development of chemotherapeutic regimens and the favorable outcomes of trimodality have led to new combined modality trials. In Japan, multicenter national trials against mesothelioma will begin in the near future.
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Raltitrexed
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