共查询到20条相似文献，搜索用时 13 毫秒
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《Journal of thoracic oncology》2017,12(11):1704-1714
IntroductionControversy exists regarding the optimal surgical technique for malignant pleural mesothelioma (MPM). We evaluated national practice patterns and outcomes of MPM treated with extrapleural pneumonectomy (EPP) versus lung-sparing extended pleurectomy/decortication (P/D).MethodsThe National Cancer Database was queried for patients with newly diagnosed MPM undergoing EPP or P/D. Multivariable logistic regression ascertained clinical factors independently associated with P/D receipt. Kaplan-Meier analysis was used to evaluate overall survival (OS) between cohorts; multivariable Cox proportional hazards modeling was used to evaluate factors associated with OS. Survival was then evaluated between propensity-matched populations.ResultsOverall, 1307 patients (271 undergoing EPP [21%] and 1036 undergoing P/D [79%]) met the criteria. Patients receiving P/D were older (p = 0.028), whereas those undergoing EPP were more likely to live in a rural area (p = 0.044), live farther from the treating facility (p = 0.039), and receive treatment at an academic center (p = 0.050). There were no differences between cohorts in 30-day readmission or mortality (all p > 0.05). The median OS times in the EPP and P/D groups were 19 versus 16 months, respectively (p = 0.120); no differences were observed after propensity matching (p = 0.540).ConclusionsIn this largest analysis of its kind to date, findings from this contemporary cohort demonstrate that P/D comprised most surgical procedures for MPM. Procedure type was influenced by sociodemographic and geographical factors, without observed differences in survival or postoperative mortality and readmission rates between techniques. 相似文献
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Yannis Metaxas Gareth Rivalland Laetitia A. Mauti Dirk Klingbiel Steven Kao Sabine Schmid Anna K. Nowak Oliver Gautschi Tammo Bartnick Brett G. Hughes Hasna Bouchaab Sacha I. Rothschild Nick Pavlakis Sibylle Wolleb Ulf Petrausch Kenneth O&#x;Byrne Patrizia Froesch Melanie L?ffler-Baumann Thomas John 《Journal of thoracic oncology》2018,13(11):1784-1791
Introduction
There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1).Methods
Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%).Results
A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected.Conclusion
These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti–PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM. 相似文献8.
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Bryan M. Burt William G. Richards Hyun-Sung Lee Sylvia Bartel Marcelo C. Dasilva Ritu R. Gill Michael T. Jaklitsch Bruce E. Johnson Scott J. Swanson Raphael Bueno David J. Sugarbaker 《Journal of thoracic oncology》2018,13(9):1400-1409
Introduction
The primary objective of this single-institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma.Methods
The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators’ assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175–225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3-plus-3 design from 100 mg/m2 in 100-mg increments.Results
From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43–85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm3 (range 16–4285 cm3). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm3 (range 6–1107 cm3). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose-limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m2, in combination with 175 mg/m2 of cisplatin. The median overall and recurrence-free survival times in treated patients were 20.3 and 10.7 months, respectively.Conclusions
Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D. 相似文献10.
《Clinical lung cancer》2021,22(4):361-370.e3
IntroductionNew therapeutic approaches in unresectable malignant pleural mesothelioma (MPM) are eagerly awaited. Trabectedin is an antitumor agent with an effect on cancer cell proliferation and a modulating action on tumor microenvironment. The ATREUS study explored the activity and safety of trabectedin in patients with unresectable MPM.MethodsEpithelioid patients with MPM received trabectedin as second-line while biphasic/sarcomatoid patients with MPM as first- or second-line therapy. Treatment was given intravenously at an initially planned dose of 1.3 mg/m2 every 3 weeks, until progression or unacceptable toxicity. The primary endpoint was progression-free survival rate at 12 weeks (PFS12wks).ResultsOverall, 78 patients (54%) had epithelioid and 67 (46%) nonepithelioid MPM. PFS12wks in 62 evaluable patients with epithelioid MPM was 43.5% (80% confidence interval 34.9%-52.5%); median progression-free and overall survival were 2.4 and 9.0 months, respectively. PFS12wks in 52 evaluable patients with nonepithelioid MPM was 30.8% (90% confidence interval 20.3%-42.9%); median progression-free and overall survival were 1.7 and 5.4 months. Trabectedin starting dose was amended due to excess of liver toxicity. Eighty-four (64%) and 48 (36%) patients received 1.3 mg/m2 and 1.1. mg/m2, respectively. The most common grade 3-4 toxicities were hepatotoxicity, leukopenia/neutropenia, and fatigue. Grade 3-4 hepatotoxicity was reported in 59 (70%) patients treated at 1.3 mg/m2, and in 19 (40%) treated at 1.1 mg/m2.ConclusionsTrabectedin showed modest clinical activity, at the expense of relevant liver toxicity. Further development of this drug in MPM at full doses is not warranted. 相似文献
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Sherif G. Shaaban Vivek Verma J. Isabelle Choi Jacob Shabason Sonam Sharma Erica Glass Surbhi Grover Shahed N. Badiyan Charles B. Simone 《Clinical lung cancer》2018,19(5):e685-e692
Background
Although postoperative radiotherapy (RT) for malignant pleural mesothelioma (MPM) has historically been delivered using 3-dimensional conformal RT (3DCRT) techniques, multiple reports show noteworthy safety and efficacy of the more advanced intensity-modulated RT (IMRT). To our knowledge, this is the only known study to evaluate national practice patterns of IMRT utilization for MPM.Materials and Methods
The National Cancer Data Base was queried for newly-diagnosed MPM patients who underwent definitive surgery (extrapleural pneumonectomy [EPP] or extended pleurectomy/decortication [P/D]) followed by adjuvant RT. Patients with metastatic disease, non-EPP or P/D surgical techniques, and lack of RT receipt (or without specified RT technique) were excluded. Statistics included multivariable logistic regression, Kaplan–Meier overall survival (OS) analysis, and Cox proportional hazards modeling.Results
Overall, 286 patients met criteria (181 [63%] IMRT and 105 [37%] 3DCRT). Temporal trends revealed that although 3DCRT was more common at initial time periods, IMRT utilization rose from 2004 to 2007 and stayed as a relatively constant majority thereafter. This was also present when substratifying the cohort according to EPP versus P/D approaches. IMRT was more often delivered at academic centers, along with institutions in the Southern United States, whereas 3DCRT was more frequently utilized in community facilities and in the Northeast (P ≤ .05 for all). RT technique did not affect OS (P > .05 for all comparisons).Conclusion
In the United States, IMRT is now the most commonly utilized adjuvant RT technique for MPM. Facility and regional differences might associate with IMRT delivery. The findings of this investigation have implications for insurance coverage, clinical referral patterns, and ongoing and future prospective trial design. 相似文献15.
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Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma
Josine Quispel-Janssen Vincent van der Noort Jeltje F. de Vries Marion Zimmerman Ferry Lalezari Erik Thunnissen Kim Monkhorst Robert Schouten Laurel Schunselaar Maria Disselhorst Houke Klomp Koen Hartemink Sjaak Burgers Wieneke Buikhuisen Paul Baas 《Journal of thoracic oncology》2018,13(10):1569-1576
Introduction
Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM.Methods
In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response.Results
Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome.Conclusions
Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population. 相似文献17.
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