Chris Dickhoff

Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy for locally advanced non-small cell lung cancer.

OBJECTIVES Curative intent treatment options for locoregional recurrence or persistent tumor after radical chemoradiotherapy for locally-advanced non-small cell lung cancer (NSCLC) are limited. In selected patients, surgery can be technically feasible, although it is widely believed to be hazardous. As data regarding the outcome of this approach is sparse, we evaluated our institutional experience with salvage surgery. MATERIALS AND METHODS Patients with a pulmonary resection for in-field locoregional recurrence or persistent tumor after high dose chemoradiotherapy (≥60 Gy) for the treatment of non-small cell lung cancer, were identified and retrospectively analyzed. RESULTS A total of 15 patients treated between January 2007 and August 2015 were eligible for evaluation. In 13 patients (87%), the indication for surgery was a locoregional recurrence, while 2 patients had persistent tumor. The prior median radiotherapy dose was 66 Gy (range 60-70). All patients underwent an anatomical resection, with 8 patients having a pneumonectomy, and all pathological specimens revealed the presence of viable tumor. The in-hospital morbidity rate was 40% (6 patients), and the 90-day mortality rate was 6.7% (1 patient). Median follow-up was 12.1 months. The estimated median overall and event-free survivals were 46 months and 43.6 months, respectively. CONCLUSION Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy, resulted in acceptable morbidity, mortality and promising outcome. It should be considered as a treatment option for selected patients.

Population-Based Patterns of Surgical Care for Stage IIIA NSCLC in the Netherlands between 2010 and 2013

Introduction: Current guidelines include both induction therapy plus an operation and chemoradiotherapy (CRT) as options for clinical stage IIIA (cIIIA) non–small cell lung cancer (NSCLC) after multidisciplinary evaluation. We explored the use of operations for cIIIA NSCLC in the Netherlands. Methods: Data about the primary treatment of patients with cIIIA NSCLC (according to the seventh edition of the Tumour, Node, and Metastasis Classification of Malignant Tumours) between 2010 and 2013 were extracted from the Netherlands Cancer Registry. Mortality information was obtained from the automated civil registry. Results: A total of 4816 patients with cIIIA NSCLC (stage cN2, 3240 [67%]; stage T4, 1252 [26%]) were identified. CRT was used in 45% of patients and an operation was a component of treatment in 15%, with 28% of the latter having induction therapy. The 4‐year survival rate was highest with induction therapy plus an operation (51%), followed by an operation plus adjuvant therapy (39%) and CRT (27%). Patients receiving induction therapy plus an operation were younger than those receiving CRT (median age 60 versus 66 years). The 30‐ and 90‐day postoperative mortality rates after induction therapy plus lobectomy were 0.6% and 3.7% compared with 4.2% and 12.5% after induction therapy plus bilobectomy or pneumonectomy. Factors associated with poorer survival after induction therapy plus an operation were age older than 69 years, histological findings of nonsquamous cell carcinoma, and bilobectomy or pneumonectomy. Pathological stage IIIA NSCLC was present in only 51% of patients with cIIIA NSCLC who underwent an operation with or without adjuvant therapy, and the disease was of a lower stage in most of the remaining patients. Conclusions: In the Netherlands between 2010 and 2013, 15% of patients with cIIIA NSCLC received an operation, with the minority of these patients receiving induction therapy. In those receiving induction therapy, 90‐day mortality after bilobectomy or pneumonectomy was more than three times higher than that for lobectomy. The discrepancy between clinical and pathological stage in patients receiving an upfront operation merits further investigation.

Metabolic activity measured by FDG PET predicts pathological response in locally advanced superior sulcus NSCLC

OBJECTIVES Pathological complete response and tumor regression to less than 10% vital tumor cells after induction chemoradiotherapy have been shown to be prognostically important in non-small cell lung cancer (NSCLC). Predictive imaging biomarkers could help treatment decision-making. The purpose of this study was to assess whether postinduction changes in tumor FDG uptake could predict pathological response and to evaluate the correlation between residual vital tumor cells and post-induction FDG uptake. METHODS NSCLC patients with sulcus superior tumor (SST), planned for trimodality therapy, routinely undergo FDG PET/CT scans before and after induction chemoradiotherapy in our institute. Metabolic end-points based on standardized uptake values (SUV) were calculated, including SUV(max) (maximum SUV), SUV(TTL) (tumor-to-liver ratio), SUV(peak) (SUV within 1 cc sphere with highest activity), and SUV(PTL) (peak-to-liver ratio). Pathology specimens were assessed for residual vital tumor cell percentages and scored as no (grade 3), <10% (grade 2b) and >10% vital tumor cells (grade 2a/1). RESULTS 19 and 23 patients were evaluated for (1) metabolic change and (2) postinduction PET-pathology correlation, respectively. Changes in all parameters were predictive for grade 2b/3 response. ΔSUV(TTL) and ΔSUV(PTL) were also predictive for grade 3 response. Remaining vital tumor cells correlated with post-induction SUV(peak) (R=0.55; P=0.007) and postinduction SUV(PTL) (R=0.59; P=0.004). Postinduction SUV(PTL) could predict both grades 3 and 2b/3 response. CONCLUSION In NSCLC patients treated with chemoradiotherapy, changes in SUV(max), SUV(TTL), SUV(peak), and SUV(PTL) were predictive for pathological response (grade 2b/3 and for SUV(TTL) and SUV(PTL) grade 3 as well). Postinduction SUV(PTL) correlated with residual tumor cells.

Trimodality therapy for stage IIIA non-small cell lung cancer: Benchmarking multi-disciplinary team decision-making and function

OBJECTIVES Although the standard treatment for patients with stage IIIA non-small cell lung cancer (NSCLC) is chemoradiotherapy, some patients are considered for trimodality therapy [TT]. We analyzed outcomes for stage IIIA NSCLC, treated with TT and compared them with concurrent chemoradiotherapy [con-CRT]. MATERIALS AND METHODS Patients treated between January 2007 and December 2011 were retrospectively analyzed. Not included were patients with sulcus superior tumors, unknown T/N-status, or recurrent disease after con-CRT followed by surgery. All patients were discussed at our multidisciplinary thoracic tumor board (MTB). RESULTS Mean Charlson Comorbidity Index was 2 for TT and con-CRT patients. TT patients were younger (median TT=56 years vs. con-CRT=62 years; p=0.001) and had less advanced cN-stage (TT cN2=41% vs. 83% for CRT; p<0.001). 44% of TT patients had T4-stage vs. 12% of con-CRT patients. Median RT dose was lower for TT (50 Gy vs. 66 Gy; p=0.001) and median RT planning target volume (PTV) in TT and con-CRT patients was 525 cm(3) and 655 cm(3) (p=0.010), respectively. The majority of TT patients had a lobectomy (23/32). Median follow-up was 30.3 months (95% CI=18.7-41.9) for TT and 51 months (95% CI=24.9-77.4) for con-CRT. Median overall survival was not reached for TT and was 18.6 months (95% CI=12.8-24.4) for con-CRT (p=0.001). For PTV</≥500 cm(3), median OS for TT was not reached/33.9 months and 29.1/17.1 months for con-CRT. TT patients with cN0/1 had better survival than those receiving con-CRT (p=0.015), but those with cN2 did not (p=0.158). The 90-day mortality from start of RT was 0% (0/32) for TT and 1.7% (1/58) for con-CRT. 90-day post-operative mortality for TT was 3.1% (1/32, event unrelated to TT). CONCLUSIONS Selected patients with IIIA NSCLC treated with TT had favorable long-term survival with acceptable short-term mortality. These outcomes support the decision-making and function of our MTB/treatment team. The role of TT in cN2 disease and large tumors merits further evaluation.

Saved from a fatal flight: A ruptured splenic artery aneurysm in a pregnant woman

Highlights • Although rupture of a splenic artery aneurysm is rare, its consequences can be devastating for both mother and child.• Early recognition and prompt multidisciplinary treatment might save the life of mother and child.• There is a difficulty in recognizing hemodynamic instability in pregnancy due to the increase in circulating volume.

Patterns of care and outcomes for stage IIIB non-small cell lung cancer in the TNM-7 era: Results from the Netherlands Cancer Registry

OBJECTIVES There is limited data on the pattern of care for locally advanced, clinical (c) IIIB non-small cell lung cancer (NSCLC) in the TNM-7 staging era. The primary aim of this study was to investigate national patterns of care and outcomes in the Netherlands, with a secondary focus on the use of surgery. MATERIAL AND METHODS Data from patients treated for TNM-7 cIIIB NSCLC between 2010 and 2014, was extracted from the Netherlands Cancer Registry (NCR). Survival data was obtained from the automated Civil Registry. RESULTS 43.762 patients with NSCLC were recorded in the NCR during this 5-year period, with cIIIB accounting for 10% (n=4.401). Clinical N2 (37%) and N3 (63%) nodal involvement was pathologically confirmed in 50.8%. The use of endobronchial ultrasound (EBUS) increased with time from 9% to 29% (p<0.001), while the rate of pathological confirmation of N2 or N3 nodes increased from 44% to 54% (p<0.001). 48% of patients received chemoradiotherapy (CRT), 19% chemotherapy (CT), RT in 10% and surgery in 2.2%. 22% received best supportive care (BSC). The percentage of patients treated with CRT decreased from 65% for patients aged <60 years to 13% for patients aged 80 years or older. Overall survival for surgery was 28 months, followed by CRT (19mths), CT (9mths), RT (8mths) and BSC (3mths). CONCLUSION In the Netherlands, CRT is the most frequent treatment for cIIIB NSCLC in the TNM-7 era. The use of surgery is limited. Accurate staging requires specific attention and the scarce use of radical treatment in elderly patients merits further evaluation.

Tumor size does not predict pathological complete response rates after pre-operative chemoradiotherapy for non-small cell lung cancer

Patients with locally advanced (LA) non-small cell lung carcinoma (NSCLC) and a large primary tumor are at risk of being considered to have incurable disease or excluded from radical-intent treatment [1,2]. We generally consider radical chemoradiotherapy in eligible patients so long as the risk of toxicity appears acceptable – absolute tumor size is not used to allocate treatment. We decided to test the hypothesis that even large tumors can respond well to chemoradiotherapy. We studied superior sulcus tumors (SST), considered a subgroup of NSCLC, because patients with operable SST receive induction chemoradiotherapy followed by resection. This allowed us to use pathological complete response (pCR), which has been correlated with survival, as an objective, clinically meaningful end-point of treatment response [3 – 6]. At the same time we also tested the hypothesis that large tumors could be sterilized with modest doses of radiotherapy (45 – 50 Gy).

Nintedanib improves cardiac fibrosis but leaves pulmonary vascular remodelling unaltered in experimental pulmonary hypertension

Aims Pulmonary arterial hypertension (PAH) is associated with increased levels of circulating growth factors and corresponding receptors such as platelet derived growth factor, fibroblast growth factor and vascular endothelial growth factor. Nintedanib, a tyrosine kinase inhibitor targeting primarily these receptors, is approved for the treatment of patients with idiopathic pulmonary fibrosis. Our objective was to examine the effect of nintedanib on proliferation of human pulmonary microvascular endothelial cells (MVEC) and assess its effects in rats with advanced experimental pulmonary hypertension (PH). Methods and results Proliferation was assessed in control and PAH MVEC exposed to nintedanib. PH was induced in rats by subcutaneous injection of Sugen (SU5416) and subsequent exposure to 10% hypoxia for 4 weeks (SuHx model). Four weeks after re-exposure to normoxia, nintedanib was administered once daily for 3 weeks. Effects of the treatment were assessed with echocardiography, right heart catheterization, and histological analysis of the heart and lungs. Changes in extracellular matrix production was assessed in human cardiac fibroblasts stimulated with nintedanib. Decreased proliferation with nintedanib was observed in control MVEC, but not in PAH patient derived MVEC. Nintedanib treatment did not affect right ventricular (RV) systolic pressure or total pulmonary resistance index in SuHx rats and had no effects on pulmonary vascular remodelling. However, despite unaltered pressure overload, the right ventricle showed less dilatation and decreased fibrosis, hypertrophy, and collagen type III with nintedanib treatment. This could be explained by less fibronectin production by cardiac fibroblasts exposed to nintedanib. Conclusion Nintedanib inhibits proliferation of pulmonary MVECs from controls, but not from PAH patients. While in rats with experimental PH nintedanib has no effects on the pulmonary vascular pathology, it has favourable effects on RV remodelling.

Feasibility of 3-dimensional video-assisted thoracic surgery (3D-VATS) for pulmonary resection

BackgroundTwo-dimensional video-assisted thoracic surgery (2D-VATS) has gained its position in daily practise. Although very useful, its two-dimensional view has its drawbacks when performing pulmonary resections. We report our first experience with 3-dimensional video-assisted surgery (3D-VATS). Advantages and differences with 2D-VATS and robotic surgery (RS) are discussed.MethodsTo evaluate feasibility, we scheduled patients for surgery by 3D-VATS who would normally be treated with 2D-VATS. The main difference of the equipment in 3D-VATS compared with former VATS equipment, is the flexible camera-tip (100-degrees) and the necessary 3D-glasses.ResultsFour patients were successfully operated for anatomic pulmonary resections. On-the-structure dissection was easily performed and with the flexible camera-tip, a perfect view can be obtained, with clear visualisation of important (hilar) structures. These features highly facilitate the surgeon in tissue preparation and recognition of the dissection planes.ConclusionIn our opinion, 3D-VATS is superior to 2D-VATS for performing anatomic pulmonary resection and we expect an improvement in terms of operation time and learning curve. Furthermore, it is a valuable alternative for RS at lower costs.

Pneumomediastinum and (bilateral) pneumothorax after high energy trauma: Indications for emergency bronchoscopy.

High energy trauma may cause injury to tracheobronchial structures. This is sometimes difficult to diagnose immediately. Pneumomediastinum and (bilateral) pneumothorax seen on a CT-scan of the thorax may suggest possible damage to central airways. Emergency bronchoscopy should be performed to detect and locate a possible tracheobronchial injury.