Emma Mclean

Pleurectomy/Decortication is Superior to Extrapleural Pneumonectomy in the Multimodality Management of Patients with Malignant Pleural Mesothelioma

Introduction: To compare the outcomes of two different multimodality regimens involving neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant radiotherapy versus pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, and adjuvant chemotherapy in patients with malignant pleural mesothelioma. Methods: Nonrandomized prospective study of patients treated by multimodality therapy and operated on between January 2004 and June 2011. Second-line treatments were administered when appropriate. Survival and prognostic factors were analyzed by the Kaplan Meier method, log rank test, and Cox regression analysis. Results: Twenty-five consecutive patients received neoadjuvant chemotherapy, 22 underwent EPP, and 17 received adjuvant radiotherapy. Over the same period, 54 consecutive patients underwent P/D and hyperthermic pleural lavage and received prophylactic radiotherapy and adjuvant chemotherapy. The 30-day mortality rate was 4.5%in the EPP group and nil in the P/D group. Fifteen patients (68%) in the EPP group and 15 (27.7%) in the P/D group experienced complications. There were no differences between the EPP and P/D groups for age, sex, histology, pathologic stage, and nodal status. Trimodality therapy was completed by 68%of the patients in the EPP group and 100%in the P/D group. Survival was significantly better in the P/D group: median survival was 23 months versus 12.8 months, 2-year survival was 49%versus 18.2 %, and 5-year survival was 30.1%versus 9%, respectively (p = 0.004). At multivariate analysis, epithelioid histology, P/D, and completeness of resection were independent prognostic factors. Conclusions: In our experience, P/D, hyperthermic pleural lavage with povidone-iodine, and adjuvant chemotherapy were superior to neoadjuvant chemotherapy, EPP, and adjuvant radiotherapy.

Screening for EGFR and KRAS mutations in endobronchial ultrasound derived transbronchial needle aspirates in non-small cell lung cancer using COLD-PCR.

EGFR mutations correlate with improved clinical outcome whereas KRAS mutations are associated with lack of response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA) is being increasingly used in the management of NSCLC. Co-amplification at lower denaturation temperature (COLD)–polymerase chain reaction (PCR) (COLD-PCR) is a sensitive assay for the detection of genetic mutations in solid tumours. This study assessed the feasibility of using COLD-PCR to screen for EGFR and KRAS mutations in cytology samples obtained by EBUS-TBNA in routine clinical practice. Samples obtained from NSCLC patients undergoing EBUS-TBNA were evaluated according to our standard clinical protocols. DNA extracted from these samples was subjected to COLD-PCR to amplify exons 18–21 of EGFR and exons two and three of KRAS followed by direct sequencing. Mutation analysis was performed in 131 of 132 (99.3%) NSCLC patients (70F/62M) with confirmed lymph node metastases (94/132 (71.2%) adenocarcinoma; 17/132 (12.8%) squamous cell; 2/132 (0.15%) large cell neuroendocrine; 1/132 (0.07%) large cell carcinoma; 18/132 (13.6%) NSCL-not otherwise specified (NOS)). Molecular analysis of all EGFR and KRAS target sequences was achieved in 126 of 132 (95.5%) and 130 of 132 (98.4%) of cases respectively. EGFR mutations were identified in 13 (10.5%) of fully evaluated cases (11 in adenocarcinoma and two in NSCLC-NOS) including two novel mutations. KRAS mutations were identified in 23 (17.5%) of fully analysed patient samples (18 adenocarcinoma and five NSCLC-NOS). We conclude that EBUS-TBNA of lymph nodes infiltrated by NSCLC can provide sufficient tumour material for EGFR and KRAS mutation analysis in most patients, and that COLD-PCR and sequencing is a robust screening assay for EGFR and KRAS mutation analysis in this clinical context.

ALK rearrangements in EBUS-derived transbronchial needle aspiration cytology in lung cancer.

Patients with non‐small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib. ALK copy‐number abnormalities have also been described. In this study, we evaluated the suitability of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine ALK status in endobronchial ultrasound (EBUS)‐derived cytology samples.

Imaging Heterogeneity in Lung Cancer: Techniques, Applications, and Challenges.

OBJECTIVE Texture analysis involves the mathematic processing of medical images to derive sets of numeric quantities that measure heterogeneity. Studies on lung cancer have shown that texture analysis may have a role in characterizing tumors and predicting patient outcome. This article outlines the mathematic basis of and the most recent literature on texture analysis in lung cancer imaging. We also describe the challenges facing the clinical implementation of texture analysis. CONCLUSION Texture analysis of lung cancer images has been applied successfully to FDG PET and CT scans. Different texture parameters have been shown to be predictive of the nature of disease and of patient outcome. In general, it appears that more heterogeneous tumors on imaging tend to be more aggressive and to be associated with poorer outcomes and that tumor heterogeneity on imaging decreases with treatment. Despite these promising results, there is a large variation in the reported data and strengths of association.

Invasive cervical cancer audit: why cancers developed in a high-risk population with an organised screening programme.

Please cite this paper as: Herbert A, Anshu, Culora G, Dunsmore H, Gupta S, Holdsworth G, Kubba A, McLean E, Sim J, Raju K. Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme. BJOG 2010;

Gene expression profiling of endobronchial ultrasound (EBUS)-derived cytological fine needle aspirates from hilar and mediastinal lymph nodes in non-small cell lung cancer.

R. Lee, D. J. Cousins, E. Ortiz‐Zapater, R. Breen, E. McLean and G. Santis 
Gene expression profiling of endobronchial ultrasound (EBUS)‐derived cytological fine needle aspirates from hilar and mediastinal lymph nodes in non‐small cell lung cancer

Invasive cervical cancer audit: why cancers developed in a high-risk population with an organised screening programme: Audit of invasive cervical cancer

Please cite this paper as: Herbert A, Anshu, Culora G, Dunsmore H, Gupta S, Holdsworth G, Kubba A, McLean E, Sim J, Raju K. Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme. BJOG 2010;

Invasive cervical cancer audit

Please cite this paper as: Herbert A, Anshu, Culora G, Dunsmore H, Gupta S, Holdsworth G, Kubba A, McLean E, Sim J, Raju K. Invasive cervical cancer audit: why cancers developed in a high‐risk population with an organised screening programme. BJOG 2010;

Can N2 disease be predicted by FDG uptake in the primary lung tumour or hilar lymphadenopathy: preliminary results

The aim of this study was to assess the correlation between SUV values on 18F‐FDG PET/CT studies with histophatological findings as polymorphonuclear (PMN) in patients with suspected non‐small cell lung cancer (NSCLC). Material and methods: 58 patients with suspected NSCLC (43 male) were studied. All had complete surgical resection and were diagnosed based on the WHO classification of NSCLC. PET imaging was performed with hybrid PET/CT scanner 60 min after 370 Mbq 18F‐FDG administrations. Tumour lesions were identified as areas of focally increased uptake in the lungs. For semi‐quantitative analysis, the maximum standardized uptake value (SUV) was calculated. Histopathological findings as polymorphonuclear, tumour infiltrating lymphocites, necrosis and vascular invasion were examinated in a section of surgically resected lung lesion. We compared SUV with these histophatological findings with two subgroups defined as the presence or not of every of these findings. Results: PET/CT showed focal uptake in primary tumour in all cases. Vascular invasion were observed in 21 patients (36,2%), PMN in 14 (24,1 %), infiltrating lymphocites in 51 (88 %) and necrosis in 34 (58,6 %). Non significant correlation was observed with 18F‐FDG PET SUV value with tumour infiltrating lymphocites, necrosis or vascular invasion. On the other hand, significant correlation was observed between SUV values with polymorphonuclear analysis (p < 0,001). PMN subgroup showed a higher SUV values (mean 14, standard error 6,3) than the non PMN subgroup (mean 9, standard error 6,7). Conclusion: We observed significant differences between SUV values on 18F‐FDG PET with the presence of PMN in NSCLC. Surgically resected lung lesion with PMN showed higher SUV in all the cases studied. PW067 Correlation of SUV on 18F-FDG PET Uptake with Ki-67/MIB-1 index in Non-small Cell Lung Cancer A. Mestre-Fusco, M. Simo, L. Pijoan, T. Baro, B. Casado, S. Mojal, A. Rodriguez; CRC Mar, Barcelona, SPAIN, Hospital del Mar. Pathology Department, IMIM, Barcelona, SPAIN, Hospital del Mar. Pathology Department, IMIM, Barcelona, SPAIN, Hospital del Mar. Pathology Department, IMIM, Barcelona, SPAIN, Hospital del Mar. AMIB, Barcelona, SPAIN, Hospital del Mar. Surgery department., Barcelona, SPAIN. Introduction: The aim of this study was to assess the correlation between SUV values on 18F‐FDG PET/CT studies with proliferative activity by the Ki‐67/MIB‐1 index in patients with suspected non‐small cell lung cancer (NSCLC). Material and methods: 58 patients with suspected NSCLC (43 male) were studied. All had complete surgical resection and were diagnosed based on the WHO classification of NSCLC ( adenocarcinomas n=29, bronchioloalveolar carcinomas n=2, squamous cell carcinomas n=16, large cell carcinomas n=7, carcinoid n=3 and mucoepidermoid carcinoma n=1). PET imaging was performed with hybrid PET/CT scanner 60 min after 370 Mbq 18F‐FDG administrations. Tumour lesions were identified as areas of focally increased uptake in the lungs. For semi‐quantitative analysis, the maximum standardized uptake value (SUV) was calculated. Proliferating cell activity as indicated by the Ki‐67 index was estimated in a section of surgically resected lung lesion. We compared SUV with their corresponding Ki‐67 using linear regression analysis, in the total group and in small subgroups: With tumour lesions size at least 2 cm, in squamous carcinoma and adenocarcinoma subgroups. Results: PET/CT showed focal uptake in primary tumour in all cases. A low correlation was observed between SUV and Ki‐67 (r=0,6; p=0.001) in the total group. A high correlation coefficient was observed in the tumour size at least 2 cm (n=35, r=0,73; p=0.001), similar to previous reports. In patients with benign pathology Ki‐67 was < 1% and SUV <2.5 showing perfect correlation. Large cell carcinomas showed high SUV and high Ki67. No correlation was observed in adenocarcinomas subgroup (n=29; r=0,30) and low correlation in squamous subgroup (r= 0,58, p=0,01). Conclusion: The results of this prospective study demonstrated significant correlation between degree of semi‐ quantitative uptake by SUV on 18F‐FDG PET with proliferative activity by the Ki‐67/MIB‐1 index in the primary tumour only in the subgroup of patients with tumour size above 2 cm in diameter. PW068 Inmunohistochemical expression of the epidermal growth factor receptor (EGFR) in patients with non-small cell lung carcinomas. Correlation with other biological parameters and the values SUV-18F-FDG-PET A. Sanchez-Salmon, M. Garrido, M. Pombo, I. Abdulkader, F. Gude, L. Leon, A. Ruibal; Hospital Clinico Santiago, Santiago de Compostela, SPAIN. The EGFR is a tyrosinekinase transmembrane receptor involved in the physiopathology of the non‐small cell lung carcinomas (NSCLC). In order to study its behaviour, we have analyzed EGFRs expression in 98 NSCLC patients (59 squamous cell type and 39 adenocarcinoma) by means of tissue‐arrays (Kit phamDX (K‐1494) of DAKO (Denmark) prediluted) and have compared it to the expression of HIF‐1alfa, p16 and p53. EGFRs expression (> 10 % positive cells) was observed in 19 adenocarcinomas and 39 squamous carcinomas (p 0,087) and there was no differences in relation to the clinical stage (I‐II: 28/46 vs III‐IV: 30/52). EGFRs expression was correlated positively (p: <0,000) with that of HIF1alfa and negatively with that of p16 (p:0,027). After multivariant analysis, the clinical stage was an outcome prediction factor (I‐II vs III‐IV; RR 2,3), but EGFRs expression was not. In 42 patients we compared EGFRs expression with the values SUV in the 18F‐FDG‐PET. These were of 9,4 +/‐5,4 in 6 cases negative EGFR; 13,9 +/‐6,3 in 11 EGFR +, 16,5 +/‐3,9 in 8 EGFR ++ and 19,6 +/‐9,7 in 17 EGFR +++, existing statistically significant differences (p:0,034). This direct correlation between both parameters could be explained by the functional relationship between the EGFR and the Na/glucose transporter (Engelman JA et to. Cancer Cell 2008; 13:375‐6) and by the relation with the HIF1a, which associates also to SUVs higher value (Ruibal A, et al. Eur J Nucl Med Mol Imaging 2008; (Suppl 2): S221). The previous results induce us to the following considerations: 1) the expression of EGFR is higher in the squamous cell carcinomas that in the adenocarcinoma and does not correlate with the clinical stage, but it does positively with the HIF1alfa and negatively with p16; 2) in the squamous cell carcinomas, EGFRs expression is correlated positively with the SUV values; 3) EGFRs expression was not a prognostic factor, but it was the clinical stage. PW069 Two-phase F-FDG PET study does not improve diagnostic accuracy in the differentiation of malignant from benign solitary pulmonary nodules T. K. Au-Yong, M. O. Kong, C. M. Tong; Nuclear Medicine Unit and PDY Clinical PET Centre, Queen Elizabeth Hospital, Kowloon, HONG KONG. Aim: To evaluate whether two‐phase FDG PET imaging improves the diagnostic accuracy in differentiating malignant from benign solitary pulmonary nodules (SPN) comparing with 1‐hour imaging. Methods: a retrospective study on patients who were referred to us for the evaluation of SPN. FDG PET studies were performed using a hybrid PET/CT scanner. Imaging was taken at 1 hour with or without delayed imaging at 3.5 hours after injection of the tracer. The maximum SUV pixel value (SUVmax) of the lung lesion in 1‐hour and delayed imaging was designated as SUVe and SUVd respectively. SUVe > 2.5 and an interval increase in SUV value (i.e. SUVd‐SUVe > 0) were considered as positive findings. Results were correlated with final diagnoses, either histologically or clinically. Results: 81 patients (46 male, 35 female, mean age 64 years) were recruited. 41 patients had two‐phase study performed. All were followed up with mean duration of 38.4 months (range 12‐72 months). 53 patients were diagnosed to have malignant SPN and 28 patients had benign nodules. The malignant nodules had significantly higher SUVe (mean 6.5 + 4.1 vs. 3.2 + 2.9; median 5.5 vs. 2.1; Mann‐Whitney test, p = 0.000). 42/53 patients with malignant SPN and 11/28 patients with benign nodules had SUVe > 2.5. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy was 79.2 %, 60.7 %, 79.2 %, 60.7 % and 72.8 % respectively. 13/22 of patients with malignant nodules and 6/19 patients with benign nodules had delayed increase in SUVmax. These gave sensitivity, specificity, PPV, NPV and accuracy of 59.1 %, 68.4 %, 68.4 %, 59.1 % and 63.4 % respectively. If combining SUVmax > 2.5 AND change in SUVmax of > 0 as positive finding, the sensitivity was decreased to 50 %, while the specificity was increased to 77.3 %. The PPV, NPV and accuracy became 68.8 %, 60.7 % and 63.0 % respectively. If the diagnostic criteria of either SUVe > 2.5 OR change of SUVmax > 0 was used, the sensitivity, specificity, PPV, NPV and accuracy was 72.7 %, 62.5 %, 64 %, 62.5 % and 63.4 % respectively. Conclusions: SUVmax value at 1 hour post‐injection gives the highest sensitivity and accuracy in the diagnosis of malignant SPN. Two‐phase FDG PET provides little value in the selection of patients with SPN for further evaluation. PW070 The value of dual-phase F-FDG PET/CT in the assessment of single pulmonary nodules with an initial standard uptake value≥2.5. Z. Wu, Y. Zhang, Q. Jia, X. Sun; The PET Center of Union Hospital,Tongji Medical College,Huazhong University of Science&Technology, Wuhan, CHINA. [Aim] A cutoff standard uptake value (SUV) of 2.5 has been commonly adopted for F‐FDG PET to evaluate single pulmonary lesions(SPN),