Surgically Resectable Non-Small Cell Lung Cancer: A Contemporary Approach.

New treatment paradigms for resectable non-small cell lung cancer (NSCLC), with an emphasis on personalized care and a multidisciplinary approach, have significantly improved patient outcomes. The incorporation of immune checkpoint inhibitors into neoadjuvant, perioperative and adjuvant treatment algorithms is reshaping the standard of care for resectable NSCLC. Adjuvant targeted therapy trials have also paved the way for a much-needed personalized approach for patients with actionable genomic alterations. Innovative surgical techniques and judicious use of post operative radiotherapy may mitigate the toxicity associated with a multimodality approach. Amidst many new treatment options, questions remain about the best approach to consider for each patient. Measurement of minimal residual disease and achievement of pathologic complete response are emerging biomarkers of interest to help further refine treatment selection. This review summarizes the current management of resectable NSCLC, focusing on ongoing and recent advances in surgical approaches, the role of postoperative radiotherapy, and the rapidly changing field of systemic therapies.

Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

OBJECTIVES: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading, Recommendation, Assessment, Development and Evaluation). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made. SHAREABLE ABSTRACT: This update of an ERS Task Force statement from 2015 provides a concise comprehensive update of the literature base. 24 evidence-based recommendations were made for management of pneumothorax, balancing clinical priorities and patient views.https://bit.ly/3TKGp9e.

Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

BACKGROUND: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.

Aerostasis to limit air leak following extended pleurectomy-decortication.

Extended pleurectomy-decortication is a cytoreductive surgical treatment for malignant pleural mesothelioma. Prolonged air leak remains a major postoperative challenge, lengthening hospital stay and increasing morbidity. In this video report, we present a stepwise approach for visceral decortication and introduce the concept of aerostasis by construction of an artificial neopleura. Our results suggest that improved aerostasis results in shortened air leak duration.

Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-centre analysis.

OBJECTIVES: Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema. METHODS: From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery. RESULTS: A total of 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy (EPP), of whom 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of the remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, EPP (odds ratio 2.8, 95% confidence interval 1.5-5.4, P = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months). CONCLUSIONS: Patients undergoing EPP had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter.

Triple-induction treatment for locally advanced non-small cell lung cancer: a case report of pathological complete response.

BACKGROUND: In patients with resectable stage III non-small cell lung cancer (NSCLC), induction chemoimmunotherapy followed by surgical resection has shown unprecedented rates of pathological response and event-free survival. However, a triple-induction including radiochemotherapy and immunotherapy followed by surgical resection has not been routinely established in clinical practice. CASE PRESENTATION: We report the case of a 47-year-old patient with stage IIIA NSCLC who was treated in a combined concept including induction concurrent radiochemotherapy, followed by 4 cycles of pembrolizumab and subsequent intrapericardial left-sided pneumonectomy. Histological analysis revealed a pathological complete response. CONCLUSIONS: The case demonstrates that the combination of neoadjuvant chemo-, radio- and immunotherapy in advanced NSCLC may lead to a relevant down-staging and may enable a R0-resection of a borderline resectable tumor. However, the combination of four different treatment modalities requires resilience and a good performance status. A triple induction treatment may be a promising option for selected patients with locally advanced NSCLC and good performance status.

Online Survey Evaluation of Three Years of European Society of Thoracic Surgeons Educational Webinars as Part of The E-learning Platform.

BACKGROUND: E-learning has become an important tool in surgical education in the last decade. The European Society of Thoracic Surgeons launched its e-learning platform in 2013 and started its educational webinars series in 2018. The aim of this paper is to discuss the introduction, evolution and impact of the educational webinars within this e-learning platform. METHODS: Twenty-four English spoken webinars discussing different subdomains in general thoracic surgery (21 expert talks, 2 pro-con debates and 1 multidisciplinary case discussion) were analyzed. An online questionnaire on timing, quality and technical aspects of the webinars was sent to 3012 registrants. RESULTS: The webinars reached 3128 unique registrants from 76 countries worldwide. The mean number of registrants was 355 with 171 live attendees (48%) and 155 replay watchers (36%). Hundred and twenty-six attendees (13.1% of people who registered for at least 4 webinars) completed the questionnaire. Timing and duration of the webinars were rated "very good" to "excellent" in 78%, and the quality of the webinar content and the expertise of the webinar presenters were rated "very good" to "excellent" in 88% and 90%, respectively. The impact on knowledge and clinical practice was scored with a weighted average of 7.27 out of 10 and 6.79 out of 10, respectively. CONCLUSIONS: The ESTS educational webinars were effective in delivering up-to-date knowledge to almost half of the countries around the globe. The impact of these events on knowledge and clinical practice were rated high. New e-learning tools should be added to the surgical educational curriculum.

Proposal for a new local recurrence score in patients with recurrent malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is associated with high rates of local recurrence (LR) up to 75%. Second line treatment should be applied tailored to relapse pattern. We aimed to establish a new score for LR pattern with prognostic impact in this observational study of retrospective nature. Methods: MPM patients with LR after surgery, verified by serial imaging during follow-up visits or biopsy were included in a retrospective analysis using a new local recurrence score (LRS). We divided the thoracic cavity into six sections and calculated the LRS according to the tumor burden. We assessed the impact on survival after recurrence using cox regression model. Results: From 2001 until 2017, 128 consecutive MPM patients with LR who underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy (EPP, n=61) or by (extended) pleurectomy/decortication [(E)PD, n=67], were included in the present analysis; 104 patients received second line therapy. Patients with chest wall (CW) recurrence had the shortest survival after recurrence (9 vs. 16 months, P=0.05) as well as patients with affected lymph nodes (LN) (9 vs. 17 months, P=0.02). In subgroup analysis, the (E)PD group had a significantly higher LRS (P≤0.001) despite a longer survival time after recurrence of 12.4 months (IQR, 6.45-20.32) compared to 9.3 months (IQR, 2.93-17.40, EPP group) (P=0.04). Patients with LRS ≤4 had a longer survival undergoing radiotherapy or local surgery for second line treatment whereas patients with LRS >4 only if they underwent chemotherapy. Conclusions: LRS might be a useful prognostic tool in MPM patients with LR after multimodality therapy to guide second line treatment allocation.

Acute on Chronic Thromboembolic Pulmonary Hypertension: Case Series and Review of Management.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of precapillary pulmonary hypertension classified as group 4 by the World Symposium on Pulmonary Hypertension (WSPH) and should be excluded during an episode of acute pulmonary embolism (PE). Patients presenting to emergency departments with sudden onset of signs and symptoms of acute PE may already have a pre-existing CTEPH condition decompensated by the new PE episode. Identifying an underlying and undiagnosed CTEPH during acute PE, while challenging, is an important consideration as it will alter the patients' acute and long-term management. Differential diagnosis and evaluation require an interdisciplinary expert team. Analysis of the clinical condition, the CT angiogram, and the hemodynamic situation are important considerations; patients with CTEPH usually have significantly higher sPAP at the time of index PE, which is unusual and unattainable in the context of acute PE and a naïve right ventricle. The imaging may reveal signs of chronic disease such as right ventricle hypertrophy bronchial collaterals and atypical morphology of the thrombus. There is no standard for the management of acute on chronic CTEPH. Herein, we provide a diagnostic and management algorithm informed by several case descriptions and a review of the literature.

Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients.

OBJECTIVES: Patient allocation to multimodality treatment in patients with malignant pleural mesothelioma remains a challenge. The aim of this study was to validate our previously established Multimodality Prognostic Score (MMPS) (tumour volume before chemotherapy, histological subtype, C-reactive protein before chemotherapy and tumour progression after chemotherapy) and to extend the score with additional blood parameters for better patient outcome. METHODS: Patients with histologically proven malignant pleural mesothelioma and curative intended therapy with clinical stage T1-T3 N0-N2 M0 were eligible. The existing MMPS was validated and further additional blood markers (erythrocytes, neutrophils, monocytes, albumin, gamma-glutamyl transferase and alkaline phosphatase) were evaluated for potential incorporation. RESULTS: For the validation of the existing MMPS, as the first part of this analysis, 117 patients treated as of September 2011 were included. A total of 88 patients were treated with macroscopic complete resection, whereas 29 patients were treated with palliative or no surgery. Patients treated with macroscopic complete resection and a high MMPS showed statistically significant lower overall survival. In the second part, the extension of the MMPS with additional blood parameters was analysed. Albumin, the only parameter showing evidence for having influence on overall survival, was further added to the extended MMPS. When comparing the performance measures Area under the curve (AUC) and Brier score, the extended score performed better (higher AUC, lower Brier score) than the original MMPS. CONCLUSIONS: The extended score with albumin showed improved performance in comparison to the original score. The extended MMPS also may help allocating patients to surgery.

Surgical management of lung cancer during the COVID-19 pandemic - a narrative review and single-centre report.

The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on oncological and thoracic surgical practice worldwide. In many hospitals, the care of COVID-19 patients required a reduction of elective surgery, to avoid viral transmission within the hospital, and to save and preserve personnel and material resources. Cancer patients are more susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and are at an increased risk of a severe course of disease. In many patients with lung cancer, this risk is further increased owing to comorbidities, older age and a pre-existing lung disease. Surgical resection is an important part of the treatment in patients with early stage or locally advanced non-small cell lung cancer, but the treatment of these patients during the COVID-19 pandemic becomes a challenging balance between the risk of patient exposure to SARS-CoV-2 and the need to provide timely and adequate cancer treatment despite limited hospital capacities. This manuscript aims to provide an overview of the surgical treatment of lung cancer patients during the COVID-19 pandemic including the triage and prioritisation as well as the surgical approach, and our own experience with cancer surgery during the first pandemic wave. We furthermore aim to highlight the risk and potential consequences of delayed lung cancer treatment due to the deferral of surgery, screening appointments and follow-up visits. With much attention being diverted to COVID-19, it is important to retain awareness of cancer patients, maintain oncological surgery and avoid treatment delay during the pandemic.

Sarcopenia, Precardial Adipose Tissue and High Tumor Volume as Outcome Predictors in Surgically Treated Pleural Mesothelioma.

BACKGROUND: We evaluated the prognostic value of Sarcopenia, low precardial adipose-tissue (PAT), and high tumor-volume in the outcome of surgically-treated pleural mesothelioma (PM). METHODS: From 2005 to 2020, consecutive surgically-treated PM-patients having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by CT-based parameters measured at the level of the fifth thoracic vertebra (TH5) by excluding fatty-infiltration based on CT-attenuation. The findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Additionally, tumor volume as well as PAT were measured. The findings were correlated with progression-free survival and long-term mortality. RESULTS: Two-hundred-seventy-eight PM-patients (252 male; 70.2 ± 9 years) were included. The mean progression-free survival was 18.6 ± 12.2 months, and the mean survival time was 23.3 ± 24 months. Progression was associated with chronic obstructive pulmonary disease (COPD) (p = <0.001), tumor-stage (p = 0.001), and type of surgery (p = 0.026). Three-year mortality was associated with higher patient age (p = 0.005), presence of COPD (p < 0.001), higher tumor-stage (p = 0.015), and higher tumor-volume (p < 0.001). Kaplan-Meier statistics showed that sarcopenic patients have a higher three-year mortality (p = 0.002). While there was a negative correlation of progression-free survival and mortality with tumor volume (r = 0.281, p = 0.001 and r = -0.240, p < 0.001; respectively), a correlation with PAT could only be shown for epithelioid PM (p = 0.040). CONCLUSIONS: Sarcopenia as well as tumor volume are associated with long-term mortality in surgically treated PM-patients. Further, while there was a negative correlation of progression-free survival and mortality with tumor volume, a correlation with PAT could only be shown for epithelioid PM.

The impact of gender bias in cardiothoracic surgery in Europe: a European Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery survey.

OBJECTIVES: The European Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery designed a questionnaire to assess the impact of gender bias on a cardiothoracic surgery career. METHODS: A 46-item survey investigating gender bias was designed using online survey software from December 2020 to January 2021. All European Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery members and non-members included in the mailing lists were invited to complete an electronic survey. Descriptive statistics and a comparison between gender groups were performed. RESULTS: Our overall response rate was 11.5% (1118/9764), of which 36.14% were women and 63.69% were men. Women were more likely to be younger than men (P < 0.0001). A total of 66% of the women reported having no children compared to only 19% of the men (P < 0.0001). Only 6% of women vs 22% of men were professors. More women (72%) also reported never having been a formal mentor themselves compared to men (38%, P < 0.0001). A total of 35% of female respondents considered leaving surgery because of episodes of discrimination compared to 13% of men; 67% of women said that they experienced being unfairly treated due to gender discrimination. Of the male surgeons, 31% reported that they were very satisfied with their career compared to only 17% of women (P < 0.0001). CONCLUSIONS: Women in cardiothoracic surgery reported significantly high rates of experiences with bias that may prevent qualified women from advancing to positions of leadership. Efforts to mitigate bias and support the professional development of women are at the centre of newly formed European committees.

Quality of Life Is Not Deteriorated After Extrapleural Pneumonectomy vs. (Extended) Pleurectomy/Decortication in Patients With Malignant Pleural Mesothelioma.

Background: Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) is highly abandoned due to high morbidity and mortality rates and impaired quality of life (QoL). However, there are still rare indications for this intervention. The aim of this longitudinal prospective study was to monitor QoL and lung function in patients undergoing EPP and compare the outcomes with extended pleurectomy/decortication [(E)PD]. Methods: Between June 2013 and June 2017, 42 patients underwent induction chemotherapy followed by either EPP (n = 7) or (E)PD (n = 35). All patients filled out the EORTC QLC-C15-PAL, -LC13, and SF-36 self-rating questionnaires pre-operatively, 6 weeks and 4 months after the operation. Additionally, lung function was measured pre-operatively and 4 months post-operatively. Results: We observed no significant differences in all QoL categories (general global health, pain, and dyspnea) between both surgical procedures, over the whole observation period. Moreover, a general tendency toward restoration of the pre-operative QoL status was documented at 4 months after the both operations. Forced expiratory volume in 1 s (FEV1) showed a significant decrease after surgery in both the groups [EPP group p = 0.06 and (E)PD group p < 0.001]; also, the forced volume vital capacity (FVC) significantly decreased (EPP group p = 0.046 P/D group <0.001). Diffusion capacity did not show significant changes. Conclusion: According to these results, QoL is no longer severely impaired after EPP compared with EPD, and therefore should not be used as an argument against EPP in principle. However, indication has to be carefully evaluated for each patient.

Implementing CT tumor volume and CT pleural thickness into future staging systems for malignant pleural mesothelioma.

OBJECTIVES: Tumor thickness and tumor volume measured by computed tomography (CT) were suggested as valuable prognosticator for patients' survival diagnosed with malignant pleural mesothelioma (MPM). The purpose was to assess the accuracy of CT scan based preoperatively measured tumor volume and thickness compared to actual tumor weight of resected MPM specimen and pathologically assessed tumor thickness, as well as an analysis of their impact on overall survival (OS). METHODS: Between 09/2013-08/2018, 74 patients were treated with induction chemotherapy followed by (extended) pleurectomy/decortication ((E)PD). In 53 patients, correlations were made between CT-measured volume and -tumor thickness (cTV and cTT) and actual tumor weight (pTW) based on the available values. Further cTV and pT/IMIG stage were correlated using Pearson correlation. Overall survival (OS) was calculated with Kaplan Meier analysis and tested with log rank test. For correlation with OS Kaplan-Meier curves were made and log rank test was performed for all measurements dichotomized at the median. RESULTS: Median pathological tumor volume (pTV) and pTW were 530 ml [130 ml - 1000 ml] and 485 mg [95 g - 982 g] respectively. Median (IQR) cTV was 77.2 ml (35.0-238.0), median cTT was 9.0 mm (6.2-13.7). Significant association was found between cTV and pTV (R = 0.47, p < 0.001) and between cTT and IMIG stage (p = 0,001) at univariate analysis. Multivariate regression analysis revealed, that only cTV correlates with pTV. Median follow-up time was 36.3 months with 30 patients dead at the time of the analysis. Median OS was 23.7 months. 1-year and 3-year survival were 90 and 26% respectively and only the cTV remained statistically associated with OS. CONCLUSION: Preoperatively assessed CT tumor volume and actual tumor volume showed a significant correlation. CT tumor volume may predict pathological tumor volume as a reflection of tumor burden, which supports the integration of CT tumor volume into future staging systems.

Perioperative Anaesthesiological Management of Malignant Pleural Mesothelioma Patients Undergoing Extrapleural Pneumonectomy (EPP) and Extended Pleurectomy/Decortication ((E)PD).

INTRODUCTION: Macroscopic complete resection (MCR) within a multimodality treatment concept offers currently the best survival for malignant pleural mesothelioma patients. The current standardised therapy is within a multimodality approach including (neo-)adjuvant chemotherapy followed by macroscopic complete resection (MCR). However, MCR in form of extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication ((E)PD) is correlated with significant morbidity and mortality if not performed in high volume centres as described previously according to the literature. In addition, there exist no standardised anaesthesiological protocol for this surgical approach according to the literature. METHODS: At our institution, diagnosed mesothelioma patients up to an International Mesothelioma Interest Group (IMIG) stage III receive induction chemotherapy followed by either EPP or (E)PD and in certain cases additional adjuvant therapy. In the period 1999-end 2019, 362 patients were intended to be treated and 303 underwent induction chemotherapy followed by MCR. MCR can be achieved either by EPP or (E)PD. Both procedures request a good teamwork between the surgeon and the anaesthesiologist. CONCLUSION: Although, there has been a shift lately from EPP towards lung sparing procedure (E)PD, both surgical approaches are still performed to date and is a challenging procedure for both, the surgeon as well as the anaesthesiologist. Herewith, we present our institutional perioperative standard operating procedures for the surgical and anaesthesiological management of EPP or (E)PD according to international terms of reference.

The Impact on Outcome by Adding Bevacizumab to Standard Induction Chemotherapy Prior to Mesothelioma Surgery: A Retrospective Single Center Analysis.

OBJECTIVES: Adding bevacizumab, an anti-Vascular Endothelial Growth Factor (VEGF), to platinum-based chemotherapy/pemetrexed in 1st line treatment of advanced malignant pleural mesothelioma (MPM), significantly improved overall survival. However, increased high grade bleeding after operation was reported in patients with colorectal cancer who previously received bevacizumab. In the present analysis, we assessed for the first time the impact of adding bevacizumab to induction chemotherapy prior to surgery for mesothelioma patients. METHODS: Two hundred twenty-seven MPM patients, intended to be treated with induction chemotherapy followed by surgery at the University Hospital of Zurich between 2002 and December 2018, were included in the present analysis. After propensity score matching for gender, histology and age (1:3 ratio), data from 88 patients were analyzed. Sixty-six patients underwent induction chemotherapy (with cis-/carboplatin and pemetrexed: control group) alone and 22 patients underwent induction chemotherapy with the addition of bevacizumab (bevacizumab group) prior macroscopic complete resection (MCR). Perioperative and long-term outcome variables were analyzed. RESULTS: Patients undergoing combination treatment with bevacizumab had a significantly better response than with chemotherapy alone as assessed by modified RECIST (p=0.046). Intraoperative complications in the bevacizumab group (one patient), or in the control group (three patients) were not related to intraoperative bleeding. Postoperative transfusion of blood products occurred in a larger amount in the control group than in the bevacizumab group (p=0.047). Overall survival was not statistically different between both groups. CONCLUSION: These initial data demonstrate that MCR can be performed safely after triple induction chemotherapy with bevacizumab without increased intra- and postoperative bleeding complications. Response rates were significantly improved by the addition of bevacizumab.

Aortobronchial fistula and Listeria endograft infection after repeated T/EVAR: a rare combination.

Here we present a rare combination of aortobronchial fistula and Listeria endograft infection after repeat endovascular aortic repair. Device retention, debridement and negative pressure wound therapy, in combination with suppressive antimicrobial therapy, led to satisfactory control of infection until the patient died due to another complication. The combination of an aortobronchial fistula and Listeria endograft infection has never been described before. This present case should encourage and show clinicians the importance of an interdisciplinary approach in highly difficult clinical courses.

Intracavitary cisplatin-fibrin chemotherapy after surgery for malignant pleural mesothelioma: A phase I trial.

OBJECTIVES: Intracavitary chemotherapy is a promising concept to improve local tumor control for malignant pleural mesothelioma with reported high morbidity rates. We have demonstrated that administration of cisplatin loaded to fibrin increased local drug concentration and reduced systemic toxicity in preclinical models. We present a phase I trial of intracavitary cisplatin-fibrin after surgical tumor resection. METHODS: A total of 12 patients (75% International Mesothelioma Interest Group stage III-IV) were treated with 4 dose levels of intracavitary cisplatin-fibrin (11-44 mg/m2 body surface area) in a dose-escalating design. Cisplatin-fibrin was sprayed on the resected surfaces after pleurectomy/decortication. Blood and tissue samples were taken to assess toxicity and pharmacokinetics. Patients were regularly followed up. RESULTS: No dose-limiting toxicity was observed. Major morbidity occurred in 4 patients (33%). The 30-day and 90-day mortality were both 0%. Of 80 adverse events, 9 were classified serious, but none of these were related to study treatment. Local cisplatin concentration in the chest wall tissue was high at all dose levels (median, 46.3 µg/g [12-133 µg/g]). In serum, median cisplatin area under the concentration time curve values were always below renal toxicity levels. The median overall survival with 95% confidence interval was 21 months (10-31 months). In 1 patient with epithelioid malignant pleural mesothelioma (International Mesothelioma Interest Group stage I), there was no sign of relapse 48 months after treatment (44 mg/m2 body surface area). CONCLUSIONS: The administration of intracavitary cisplatin-fibrin is safe with favorable pharmacokinetics. Although most patients had advanced disease, long-term outcomes are comparable to other multimodal concepts. A confirmation phase II trial is ongoing.

Stereotactic Body Radiation Therapy (SBRT) as Salvage Therapy for Oligorecurrent Pleural Mesothelioma After Multi-Modality Therapy.

Introduction: Therapy options for patients with oligoprogressive malignant pleural mesothelioma (MPM) are limited. Stereotactic Body Radiotherapy (SBRT) may be a promising therapeutic option, as it delivers a localized ablative dose of radiation and therefore balances efficacy and treatment related toxicities. The intent of this retrospective analysis was to evaluate the feasibility of SBRT for limited pleural recurrences. Methods and Materials: This retrospective single-institution study is based on the 21 consecutive patients treated with hypofractionated radiotherapy for oligoprogressive MPM. Clinical and radiological data was collected at regular follow-up visits including toxicity, local control and survival. Results: At primary diagnosis, 57% of the patients presented with stage III disease. Initial treatment of MPM consisted of induction chemotherapy (n = 12) prior to a macroscopic complete resection (n = 18). Three patients received additional intracavitary chemotherapy and another three patients were treated with chemotherapy alone without another treatment at the time of first diagnosis. A total of 50 lesions in recurrent MPM were treated with SBRT. The median number of radiotherapy fractions was 5 (range 3-20) with a median dose per fraction of 5 Gy (range 2.5-12.5 Gy). The median total treatment dose was 30 Gy (20-50 Gy) with a median prescription isodose line (IDL) of 65% (65-100%). Median follow-up of all patients from diagnosis was 28 months (range 7-152 months). Analyzing all lesions separately, the 12-months-local control from SBRT was 73.5%. The median progression free survival (PFS) after SBRT was 6 months (range 0-21 months) and the median OS from first first SBRT was 29 months (range 0-61 months). Only one patients experienced above Grade 3 toxicities. Conclusion: This analysis demonstrates the feasibility of a SBRT approach for oligorecurrent MPM. SBRT was well-tolerated even after multiple repetitions and local control was high with a promising median OS.