- Email: [email protected]
A Highly Sensitive Immunohistochemical Assay to Detect Braf V600E Mutations in Patients with Colorectal Cancer
Annals of Oncology 23 (Supplement 9): ix383–ix384, 2012 doi:10.1093/annonc/mds406
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A HIGHLY SENSITIVE IMMUNOHISTOCHEMICAL ASSAY TO DETECT BRAF V600E MUTATIONS IN PATIENTS WITH COLORECTAL CANCER
J. Desai1, F. Day2, A. Muranyi3, S. Singh3, K. Shanmugam3, T. Grogan3, P. Gibbs4, D. Williams2, O. Sieber2, P. Waring5 1 Medical Oncology, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Peter MacCallum Cancer Centre, Parkville, AUSTRALIA, 2LCCI, Ludwig Institute for Cancer Research, Parkville, AUSTRALIA, 3Ventana, Ventana Medical Systems, Tucson, AZ, UNITED STATES OF AMERICA, 4LCCI, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, VIC, AUSTRALIA, 5 Pathology, University of Melbourne, Parkville, AUSTRALIA
1174P
DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF THE ALTERNATIVELY SPLICED ACTN4 VARIANT IN HIGH-GRADE NEUROENDOCRINE PULMONARY TUMOURS
A. Miyanaga1, K. Honda1, K. Tsuta1, M. Masuda1, H. Tsuda2, H. Asamura3, A. Gemma4, T. Yamada1 1 Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, JAPAN, 2Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, JAPAN, 3Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, JAPAN, 4Internal Medicine, Nippon Medical School, Tokyo, JAPAN Background: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method of predicting their outcome has been established. Materials and methods: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4
1175P
CLINICAL FEASIBILITY STUDY OF A NOVEL CYTOMETRY-BASED SYSTEM FOR THE DETECTION OF CIRCULATING TUMOR CELLS IN PATIENTS WITH LUNG CANCER
Y. Koh1, M. Watanabe1, T. Sawada2, Y. Uehara2, Y. Fujimura3, T. Tamura4, F. Koizumi2 1 Division of Drug Discovery and Development, Shizuoka Cancer Center, Sunto-gun, JAPAN, 2Shien-Lab, National Cancer Center Hospital, Tokyo, JAPAN, 3R&D, On-Chip Biotechnologies Co., Ltd, Koganei, JAPAN, 4Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, JAPAN Background: The presence and number of circulating tumor cells (CTCs) in the peripheral blood of solid tumor patients are predictive of clinical outcome. To date the CellSearch system has been the only FDA-cleared CTCs enumeration system for advanced breast, prostate and colon cancers. However, low prevalence of CTCs and lack of capability as an application platform for molecular analysis have limited the use of CTCs in the clinic. To overcome these shortcomings, innovative and emerging technologies with easier access to further molecular analysis are under development worldwide. Methods: We have developed a flow cytometry-based CTCs detection system independent of EpCAM expression level of tumor cells with cytokeratin and vimentin-staining after the depletion of CD45-expressing cells. In a preclinical study, various cancer cell lines were spiked into blood from healthy donors and the sensitivity in detection was evaluated at two different sites (Shizuoka Cancer Center and National Cancer Center Tokyo). Then clinical feasibility study was conducted in patients with lung cancer. Results: Enumeration of the spiked cancer cells (10 to 1000 cells in 4 ml of blood) was linear, with a recovery rate of over 90%. A significantly higher recovery rate was observed with our system (90 to 102%) than that with CellSearch system (0%) particularly when EpCAM-negative PC-14 non-small lung cancer cells were spiked in, suggesting a superior sensitivity of our system in capturing EpCAM-negative tumor cells. In 22 blood samples from lung cancer patients, CTCs were detected with numbers ranging from 0 to 16 CTCs (median, 6.5) per 4 ml of blood with our system and in 72.7% (17/23) of the patients, 4 CTCs or more per 4 ml of blood were detected. On the other hand with CellSearch system, 2 CTCs or more per 7.5 ml of blood were detected in only 27% of the patients. Conclusions: The preclinical study and the results of the clinical feasibility study suggested superior sensitivity of our flow cytometry-based detection method than CellSearch system. Cell sorting device under development will be combined with this system for isolation and collection of CTCs for molecular analysis with next-generation sequencing. Disclosure: All authors have declared no conflicts of interest.
1176P
EBUS-TBNA GIVES ADEQUATE TISSUE INFORMATION ON CELL TYPE IN LUNG CANCER
M.K. Wong, M.S. Ip, D.C. Lam, J.C.M. Ho Medicine, Queen Mary Hospital, Hong Kong, HONG KONG Introduction: In formulating systemic treatment in patients with advanced stage lung cancer, it is now considered imperative to know the cell type such as squamous carcinoma, adenocarcinoma and large cell carcinoma as chemotherapeutic agents would be tailored to treat different cell type.
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
Downloaded from http://annonc.oxfordjournals.org/ by guest on April 2, 2016
Background: The BRAF V600E mutation is a well-validated negative prognostic biomarker in metastatic colorectal cancer (mCRC), and is a highly attractive drug target. Barriers to the development of agents targeting BRAF V600E in mCRC are the low rate of mutations (approximately 10%) and reliance on to sequencing-based technologies, which are not routinely available outside of large cancer centres. A simple immunohistochemistry (IHC) test, more suited to routine pathology practice, would provide much broader access to patient ( pt) identification, and would also enable studies of tumor heterogeneity. Aims: To validate an IHC-based method of detecting the BRAF V600E mutation in a large cohort of community-based CRC patients. Methods: Tissue microarrays, comprising matched normal and tumor paraffin embedded tissue samples obtained from colectomy specimens from a community cohort of 505 pts with stage I–IV CRC, were tested with 2 antibodies (Ab): pBR for total BRAF and VE1 for BRAF V600E, using the Ventana UltraView and OptiView kits, respectively. IHC was assessed independently by 2 blinded pathologists, and results compared to BRAF V600E status determined by Sanger sequencing (SS). pBR negative samples were considered non - evaluable. Nine discordant cases were re-tested with a BRAF V600E SNaPshot assay. Results: Demographic features were evenly matched. SS was evaluable in 504/505; IHC in 477/505; with both evaluable in 476/505 pts. 56/476 (11.8%) pts had V600E mutations detected by SS, 65/476 (13.7%) by IHC. The positive predictive value was 84.6% (55/65). 1 pt was negative by IHC and positive on SS and SNaPshot; resulting in a negative predictive value of 99.8% (410/411 cases). There was 100% concordance between SS and SNaPshot. Further validation is ongoing, and outcome data will be available at the time of presentation. Conclusions: We have conducted a comprehensive analytical and clinical validation and feasibility analysis of an IHC-based method to detect the BRAF V600E mutation in a large community-based population of pts with CRC. Shown to be highly sensitive, we are planning to adopt this approach as our initial screening step in an upcoming prospective combination trial targeting BRAF V600E in pts with mCRC. Disclosure: J. Desai: Research Support: Roche, Ventana Medical Systems, A. Muranyi: Employee: Ventana Medical Systems, K. Shanmugam: Employee and Shareholder, Ventana Medical Systems, T. Grogan: Shareholder and Chief Scientific Officer, Ventana Medical Systems, P. Gibbs: Research Support, Ventana Medical Systems, P. Waring: Research Support: Ventana Medical Systems, All other authors have declared no conflicts of interest.
immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. Results: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine lung cancers. Expression of variant actinin-4 was significantly associated with unfavorable overall survival in HGNT patients (P = 0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio, 2.18; P = 0.000714) after the presence of lymph node metastasis (hazard ratio, 2.30; P = 0.00012). Conclusions: Expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion. Disclosure: All authors have declared no conflicts of interest.
abstracts
new diagnostics
Annals of Oncology
Method: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA)was performed under local anaesthesia in patients presented with mediastinal abnormality suspected of or confirmed lung cancer for diagnosis and staging purpose. Once malignancy was confirmed from the pathological materials, exact cell type, origin of tumour, differentiation were recorded. In the later phase of the study period, molecular profiling was also deployed to confirm the EGFR mutation and ALK translocation status. Results: Over the study period of 4 years and 4 months, there were 269 EBUS-TBNA performed in 258 patients. Of the 209 patients confirmed having malignancy as their final diagnosis, EBUS-TBNA was able to detect extrathoracic malignancy in 23 (11.0%) and primary lung cancer in 133 (63.6%). Among those 133 patients confirmed having primary lung cancer, 116 (87.2%) had exact cell type delineated. For those 40 patients who had molecular profiling performed, patients with adequate tissue for EGFR mutation and/or ALK translocation were obtained in 38 (95.0%). Of the 157 patients confirmed to have malignancy by EBUS-TBNA, only 22 (14%) had revealed NSCLC without knowing the exact cell type, differentiation of the tumour, EGFR status or primary origin of the tumour. In the 220 patients with final diagnosis of malignancy, the sensitivity was 89.0% and negative predictive value was 65.0% Conclusion: EBUS-TBNA is effective in subtyping of tumour cells and molecular profiling in patients with lung cancer. Disclosure: All authors have declared no conflicts of interest.
1177P
F. Nakamura1, T. Higashi2, Y. Emori3, H. Nishimoto3 1 Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, JAPAN, 2Department of Public Health/Health Policy, The University of Tokyo Graduate School of Medicine, Tokyo, JAPAN, 3Cancer Surveillance Division, National Cancer Center, Tokyo, JAPAN Introduction: Previous studies showed that TNM stages that were clinically determined before surgery were not often concordant with pathological TNM stages. However, no previous studies have examined variations of discordance of the clinical TNM stage with the pathological TNM stage among hospitals. We aimed to examine the discordance of the clinical and pathological stages among Japanese designated cancer hospitals using compiled data from the hospital-based cancer registry submitted from 286 designated cancer care hospitals in Japan. Methods: The registry data had UICC TNM stages before and after surgery for stomach, colorectal, lung and breast cancer patients treated in these hospitals. We excluded patients who received adjuvant chemotherapy or radiotherapy, patients who received care from facilities with less than 10 patients, male breast cancer and patients whose stages were unknown from the analysis. We also calculated discordance of stages that could have theoretically resulted in changes in surgical procedures or treatment choice. Discordance was also calculated after excluding stage IV patients as sensitivity analysis. Results: In total, 145,726 patients (38,692 stomach, 47,304 colorectal, 19,643 lung and 40,096 breast cancer patients) were included in the analysis. Patients’ mean age and clinical TNM stage varied across hospitals. The facility-level discordance between clinical and pathological stages ranged from 4% to 52% in stomach cancer, 3% to
ix | Abstracts
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PROSPECTIVE EVALUATION OF PLANAR BONE SCINTIGRAPHY, SPECT/CT, 18F NAF PET/CT AND WHOLE BODY 1.5T MRI FOR DETECTION OF BONE METASTASES IN HIGH RISK BREAST AND PROSTATE CANCER PATIENTS
A.K. Kuisma1, I. Jambor2, R. Huovinen1, M. Sandell2 1 Oncology and Radiotherapy, University Hospital of Turku, Turku, FINLAND, 2 Radiology, University Hospital of Turku, Turku, FINLAND Purpose: The aim of the study was to compare the diagnostic accuracy of 99mTc methylene-diphosphonate planar bone scintigraphy (99mTc-MDP BS), 99mTc methylene-diphosphonate single photon emission tomography/computed tomography (99mTc-MDP SPECT/CT), 18F NaF positron emission tomography/ computed tomography (PET/CT) and whole body 1.5 Tesla magnetic resonance imaging (1.5T MRI) for the detection of bone metastases in high risk breast and prostate cancer patients. Materials and methods: Twenty breast cancer patients and eight prostate cancer patients at high risk of bone metastases prospectively underwent 99mTc-MDP BS, 99mTc-MDP SPECT/CT, 18F NaF PET/CT and whole body 1.5T MRI using spine and surface coils. Four independent reviewers interpreted each individual modality without the knowledge of other imaging findings. The final metastatic status was based on the consensus reading of all imaging modalities. The findings were compared on patient and region basis. In the region based analysis, the skeleton was divided into five regions. Results: Based on the consensus reading, 13 (46%) patients and 42 (30%) regions had presence of bone metastases while 15 patients and 98 regions were free of bone metastases. 99mTc-MDP BS was false negative in four patients. In the patient/region based analysis, the sensitivity for 99mTc-MDP BS, 99mTc-MDP SPECT/CT, 18F NaF PET/CT and whole body 1.5T MRI was 69%/44%, 77%/76%, 92%/90% and 77%/71%, respectively, while the accuracy was 86%/82%, 89%/92%, 96%/97% and 86%/91%, respectively. Conclusions: 99mTc-MDP SPECT/CT, 18F NaF PET/CT and whole body MRI including diffusion weighted imaging demonstrated higher sensitivity and accuracy in detection of bone metastasis compared to planar bone scintigraphy. Observed difference between imaging modalities might potentially affect the patient management. Clinical relevance statement: 99mTc-MDP SPECT/CT, 18F NaF PET/ CT and whole body MRI including diffusion weighted imaging showed higher sensitivity for detecting bone metastases in high risk breast and prostate cancer patients to planar bone scintigraphy. Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012
Downloaded from http://annonc.oxfordjournals.org/ by guest on April 2, 2016
VARIATIONS OF DISCORDANCE OF THE CLINICAL TNM STAGE WITH THE PATHOLOGICAL TNM STAGE BETWEEN JAPANESE DESIGNATED CANCER HOSPITALS
57% in colorectal cancer, 0% to 50% in lung cancer and 1% to 45% in breast cancer. TNM stages before surgery were lower than after surgery in more than half of the cases. The multi-level logistic regression model showed that variance in facilities existed after adjustment for age, sex and clinical TNM stage. Discordance of stages that could lead to changes in the surgical procedures or treatment choice ranged from 4% to 58% in stomach cancer, 4% to 63% in colorectal cancer, 0% to 5% in lung cancer, and 5% to 52% in breast cancer. Sensitivity analysis yielded similar results. Conclusion: We can confirm variations of discordance of TNM stages before and after surgery. Disclosure: All authors have declared no conflicts of interest.
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A HIGHLY SENSITIVE IMMUNOHISTOCHEMICAL ASSAY TO DETECT BRAF V600E MUTATIONS IN PATIENTS WITH COLORECTAL CANCER
J. Desai1, F. Day2, A. Muranyi3, S. Singh3, K. Shanmugam3, T. Grogan3, P. Gibbs4, D. Williams2, O. Sieber2, P. Waring5 1 Medical Oncology, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Peter MacCallum Cancer Centre, Parkville, AUSTRALIA, 2LCCI, Ludwig Institute for Cancer Research, Parkville, AUSTRALIA, 3Ventana, Ventana Medical Systems, Tucson, AZ, UNITED STATES OF AMERICA, 4LCCI, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, VIC, AUSTRALIA, 5 Pathology, University of Melbourne, Parkville, AUSTRALIA
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DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF THE ALTERNATIVELY SPLICED ACTN4 VARIANT IN HIGH-GRADE NEUROENDOCRINE PULMONARY TUMOURS
A. Miyanaga1, K. Honda1, K. Tsuta1, M. Masuda1, H. Tsuda2, H. Asamura3, A. Gemma4, T. Yamada1 1 Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, JAPAN, 2Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, JAPAN, 3Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, JAPAN, 4Internal Medicine, Nippon Medical School, Tokyo, JAPAN Background: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method of predicting their outcome has been established. Materials and methods: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4
1175P
CLINICAL FEASIBILITY STUDY OF A NOVEL CYTOMETRY-BASED SYSTEM FOR THE DETECTION OF CIRCULATING TUMOR CELLS IN PATIENTS WITH LUNG CANCER
Y. Koh1, M. Watanabe1, T. Sawada2, Y. Uehara2, Y. Fujimura3, T. Tamura4, F. Koizumi2 1 Division of Drug Discovery and Development, Shizuoka Cancer Center, Sunto-gun, JAPAN, 2Shien-Lab, National Cancer Center Hospital, Tokyo, JAPAN, 3R&D, On-Chip Biotechnologies Co., Ltd, Koganei, JAPAN, 4Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, JAPAN Background: The presence and number of circulating tumor cells (CTCs) in the peripheral blood of solid tumor patients are predictive of clinical outcome. To date the CellSearch system has been the only FDA-cleared CTCs enumeration system for advanced breast, prostate and colon cancers. However, low prevalence of CTCs and lack of capability as an application platform for molecular analysis have limited the use of CTCs in the clinic. To overcome these shortcomings, innovative and emerging technologies with easier access to further molecular analysis are under development worldwide. Methods: We have developed a flow cytometry-based CTCs detection system independent of EpCAM expression level of tumor cells with cytokeratin and vimentin-staining after the depletion of CD45-expressing cells. In a preclinical study, various cancer cell lines were spiked into blood from healthy donors and the sensitivity in detection was evaluated at two different sites (Shizuoka Cancer Center and National Cancer Center Tokyo). Then clinical feasibility study was conducted in patients with lung cancer. Results: Enumeration of the spiked cancer cells (10 to 1000 cells in 4 ml of blood) was linear, with a recovery rate of over 90%. A significantly higher recovery rate was observed with our system (90 to 102%) than that with CellSearch system (0%) particularly when EpCAM-negative PC-14 non-small lung cancer cells were spiked in, suggesting a superior sensitivity of our system in capturing EpCAM-negative tumor cells. In 22 blood samples from lung cancer patients, CTCs were detected with numbers ranging from 0 to 16 CTCs (median, 6.5) per 4 ml of blood with our system and in 72.7% (17/23) of the patients, 4 CTCs or more per 4 ml of blood were detected. On the other hand with CellSearch system, 2 CTCs or more per 7.5 ml of blood were detected in only 27% of the patients. Conclusions: The preclinical study and the results of the clinical feasibility study suggested superior sensitivity of our flow cytometry-based detection method than CellSearch system. Cell sorting device under development will be combined with this system for isolation and collection of CTCs for molecular analysis with next-generation sequencing. Disclosure: All authors have declared no conflicts of interest.
1176P
EBUS-TBNA GIVES ADEQUATE TISSUE INFORMATION ON CELL TYPE IN LUNG CANCER
M.K. Wong, M.S. Ip, D.C. Lam, J.C.M. Ho Medicine, Queen Mary Hospital, Hong Kong, HONG KONG Introduction: In formulating systemic treatment in patients with advanced stage lung cancer, it is now considered imperative to know the cell type such as squamous carcinoma, adenocarcinoma and large cell carcinoma as chemotherapeutic agents would be tailored to treat different cell type.
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
Downloaded from http://annonc.oxfordjournals.org/ by guest on April 2, 2016
Background: The BRAF V600E mutation is a well-validated negative prognostic biomarker in metastatic colorectal cancer (mCRC), and is a highly attractive drug target. Barriers to the development of agents targeting BRAF V600E in mCRC are the low rate of mutations (approximately 10%) and reliance on to sequencing-based technologies, which are not routinely available outside of large cancer centres. A simple immunohistochemistry (IHC) test, more suited to routine pathology practice, would provide much broader access to patient ( pt) identification, and would also enable studies of tumor heterogeneity. Aims: To validate an IHC-based method of detecting the BRAF V600E mutation in a large cohort of community-based CRC patients. Methods: Tissue microarrays, comprising matched normal and tumor paraffin embedded tissue samples obtained from colectomy specimens from a community cohort of 505 pts with stage I–IV CRC, were tested with 2 antibodies (Ab): pBR for total BRAF and VE1 for BRAF V600E, using the Ventana UltraView and OptiView kits, respectively. IHC was assessed independently by 2 blinded pathologists, and results compared to BRAF V600E status determined by Sanger sequencing (SS). pBR negative samples were considered non - evaluable. Nine discordant cases were re-tested with a BRAF V600E SNaPshot assay. Results: Demographic features were evenly matched. SS was evaluable in 504/505; IHC in 477/505; with both evaluable in 476/505 pts. 56/476 (11.8%) pts had V600E mutations detected by SS, 65/476 (13.7%) by IHC. The positive predictive value was 84.6% (55/65). 1 pt was negative by IHC and positive on SS and SNaPshot; resulting in a negative predictive value of 99.8% (410/411 cases). There was 100% concordance between SS and SNaPshot. Further validation is ongoing, and outcome data will be available at the time of presentation. Conclusions: We have conducted a comprehensive analytical and clinical validation and feasibility analysis of an IHC-based method to detect the BRAF V600E mutation in a large community-based population of pts with CRC. Shown to be highly sensitive, we are planning to adopt this approach as our initial screening step in an upcoming prospective combination trial targeting BRAF V600E in pts with mCRC. Disclosure: J. Desai: Research Support: Roche, Ventana Medical Systems, A. Muranyi: Employee: Ventana Medical Systems, K. Shanmugam: Employee and Shareholder, Ventana Medical Systems, T. Grogan: Shareholder and Chief Scientific Officer, Ventana Medical Systems, P. Gibbs: Research Support, Ventana Medical Systems, P. Waring: Research Support: Ventana Medical Systems, All other authors have declared no conflicts of interest.
immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. Results: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine lung cancers. Expression of variant actinin-4 was significantly associated with unfavorable overall survival in HGNT patients (P = 0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio, 2.18; P = 0.000714) after the presence of lymph node metastasis (hazard ratio, 2.30; P = 0.00012). Conclusions: Expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion. Disclosure: All authors have declared no conflicts of interest.
abstracts
new diagnostics
Annals of Oncology
Method: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA)was performed under local anaesthesia in patients presented with mediastinal abnormality suspected of or confirmed lung cancer for diagnosis and staging purpose. Once malignancy was confirmed from the pathological materials, exact cell type, origin of tumour, differentiation were recorded. In the later phase of the study period, molecular profiling was also deployed to confirm the EGFR mutation and ALK translocation status. Results: Over the study period of 4 years and 4 months, there were 269 EBUS-TBNA performed in 258 patients. Of the 209 patients confirmed having malignancy as their final diagnosis, EBUS-TBNA was able to detect extrathoracic malignancy in 23 (11.0%) and primary lung cancer in 133 (63.6%). Among those 133 patients confirmed having primary lung cancer, 116 (87.2%) had exact cell type delineated. For those 40 patients who had molecular profiling performed, patients with adequate tissue for EGFR mutation and/or ALK translocation were obtained in 38 (95.0%). Of the 157 patients confirmed to have malignancy by EBUS-TBNA, only 22 (14%) had revealed NSCLC without knowing the exact cell type, differentiation of the tumour, EGFR status or primary origin of the tumour. In the 220 patients with final diagnosis of malignancy, the sensitivity was 89.0% and negative predictive value was 65.0% Conclusion: EBUS-TBNA is effective in subtyping of tumour cells and molecular profiling in patients with lung cancer. Disclosure: All authors have declared no conflicts of interest.
1177P
F. Nakamura1, T. Higashi2, Y. Emori3, H. Nishimoto3 1 Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, JAPAN, 2Department of Public Health/Health Policy, The University of Tokyo Graduate School of Medicine, Tokyo, JAPAN, 3Cancer Surveillance Division, National Cancer Center, Tokyo, JAPAN Introduction: Previous studies showed that TNM stages that were clinically determined before surgery were not often concordant with pathological TNM stages. However, no previous studies have examined variations of discordance of the clinical TNM stage with the pathological TNM stage among hospitals. We aimed to examine the discordance of the clinical and pathological stages among Japanese designated cancer hospitals using compiled data from the hospital-based cancer registry submitted from 286 designated cancer care hospitals in Japan. Methods: The registry data had UICC TNM stages before and after surgery for stomach, colorectal, lung and breast cancer patients treated in these hospitals. We excluded patients who received adjuvant chemotherapy or radiotherapy, patients who received care from facilities with less than 10 patients, male breast cancer and patients whose stages were unknown from the analysis. We also calculated discordance of stages that could have theoretically resulted in changes in surgical procedures or treatment choice. Discordance was also calculated after excluding stage IV patients as sensitivity analysis. Results: In total, 145,726 patients (38,692 stomach, 47,304 colorectal, 19,643 lung and 40,096 breast cancer patients) were included in the analysis. Patients’ mean age and clinical TNM stage varied across hospitals. The facility-level discordance between clinical and pathological stages ranged from 4% to 52% in stomach cancer, 3% to
ix | Abstracts
1178TiP
PROSPECTIVE EVALUATION OF PLANAR BONE SCINTIGRAPHY, SPECT/CT, 18F NAF PET/CT AND WHOLE BODY 1.5T MRI FOR DETECTION OF BONE METASTASES IN HIGH RISK BREAST AND PROSTATE CANCER PATIENTS
A.K. Kuisma1, I. Jambor2, R. Huovinen1, M. Sandell2 1 Oncology and Radiotherapy, University Hospital of Turku, Turku, FINLAND, 2 Radiology, University Hospital of Turku, Turku, FINLAND Purpose: The aim of the study was to compare the diagnostic accuracy of 99mTc methylene-diphosphonate planar bone scintigraphy (99mTc-MDP BS), 99mTc methylene-diphosphonate single photon emission tomography/computed tomography (99mTc-MDP SPECT/CT), 18F NaF positron emission tomography/ computed tomography (PET/CT) and whole body 1.5 Tesla magnetic resonance imaging (1.5T MRI) for the detection of bone metastases in high risk breast and prostate cancer patients. Materials and methods: Twenty breast cancer patients and eight prostate cancer patients at high risk of bone metastases prospectively underwent 99mTc-MDP BS, 99mTc-MDP SPECT/CT, 18F NaF PET/CT and whole body 1.5T MRI using spine and surface coils. Four independent reviewers interpreted each individual modality without the knowledge of other imaging findings. The final metastatic status was based on the consensus reading of all imaging modalities. The findings were compared on patient and region basis. In the region based analysis, the skeleton was divided into five regions. Results: Based on the consensus reading, 13 (46%) patients and 42 (30%) regions had presence of bone metastases while 15 patients and 98 regions were free of bone metastases. 99mTc-MDP BS was false negative in four patients. In the patient/region based analysis, the sensitivity for 99mTc-MDP BS, 99mTc-MDP SPECT/CT, 18F NaF PET/CT and whole body 1.5T MRI was 69%/44%, 77%/76%, 92%/90% and 77%/71%, respectively, while the accuracy was 86%/82%, 89%/92%, 96%/97% and 86%/91%, respectively. Conclusions: 99mTc-MDP SPECT/CT, 18F NaF PET/CT and whole body MRI including diffusion weighted imaging demonstrated higher sensitivity and accuracy in detection of bone metastasis compared to planar bone scintigraphy. Observed difference between imaging modalities might potentially affect the patient management. Clinical relevance statement: 99mTc-MDP SPECT/CT, 18F NaF PET/ CT and whole body MRI including diffusion weighted imaging showed higher sensitivity for detecting bone metastases in high risk breast and prostate cancer patients to planar bone scintigraphy. Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012
Downloaded from http://annonc.oxfordjournals.org/ by guest on April 2, 2016
VARIATIONS OF DISCORDANCE OF THE CLINICAL TNM STAGE WITH THE PATHOLOGICAL TNM STAGE BETWEEN JAPANESE DESIGNATED CANCER HOSPITALS
57% in colorectal cancer, 0% to 50% in lung cancer and 1% to 45% in breast cancer. TNM stages before surgery were lower than after surgery in more than half of the cases. The multi-level logistic regression model showed that variance in facilities existed after adjustment for age, sex and clinical TNM stage. Discordance of stages that could lead to changes in the surgical procedures or treatment choice ranged from 4% to 58% in stomach cancer, 4% to 63% in colorectal cancer, 0% to 5% in lung cancer, and 5% to 52% in breast cancer. Sensitivity analysis yielded similar results. Conclusion: We can confirm variations of discordance of TNM stages before and after surgery. Disclosure: All authors have declared no conflicts of interest.