- Email: [email protected]
Does life add years to life? Clinical outcome in using autofluorescence bronchoscopy for occult cancers
Pulmona~ Imaging reverse tanscriptase polymerase chain reaction. We represented them as ratios to their overexpressing cell lines (K562/Adr and H69AR, respectively). Results: We found poor correlations between the RI and either Pgp (p = 0.19) or MRP (p = 0.07) mRNA expression levels. While we found that the group with the RI < 1.75 indicated significantly higher levels of MRP (p = 0.02) but not Pgp (p = 0.20) mRNA expression than the other and that the group with either or both kinds of mRNA expression levels that are higher than each median value showed significantly lower values of the RI than the other. Conclusion: Our results suggest that MIBI SPECT images is useful in reflecting either Pgp or MRP mRNA expression levels and that 1.75% of the RI is an appreciate cutoff value in reflecting MRP mRNA overexpression in clinical lung cancer.
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Does life add years to life? Clinical outcome in using autofluorescence bronchoscopy for occult cancers
H. Codriogton, P.E. Postmus, G. Sutedja. Free University Hospital
Amsterdam, The Netherlands Woolner et al. reported that only 68% of radiographically occult lung cancers a=e truly occult. The role of bronchoscopic therapy with curative intent and its long-term result in using LIFE (Laser Induced Fluorescence Endoscope) device and HRCT (high resolution CT) for the staging of patients with radiographically occult lung cancer have been analyzed. Twenty-four patients were referred to us with radiographically occult cancer, median age 63 years (range 48-74). Methods of staging with LIFE and HRCT have been reported before.* In 13 (54%) patients LIFE showed more extensive lesions > 1 cm2 surface area and/or invisible distal tumor margin. In four patients, HRCT showed that intraluminal cancers were not occult. The combination of LIFE and HRCT findings have changed the treatment policy, not to perform bronchoscopic therapy with curative intent (BT), in 17 patients (71%). BT resulted in a complete response status in 6/7 patients with true occult cancers after 37 months (SD 7.0) follow-up. Eleven of the seventeen patients with locally advanced cancer have died. Many patients with the so called "radiographically occult" cancer, do not have occult cancer if staged by LIFE and HRCT. Accurate selection and staging of patients suitable for BT is important and the recent role of bronchoscopic ultrasound should also be investigated. References [1] Venmans et al. J Bronchology 1998; 5:280 [2] Sutedja et al. Eur Resp J 1996; 9:1020-1023 stage bronchial • 7neoplasia -changes - (IEN)•ininearly Turanium h miners e in a intraepithelial one-year period with special reference to autofluorescence endoscopy (SAFE-1000) T.A. Horvath, J. Vomela, M. Horvathova, P. Pafko, B. Habanec, IR Benda, T. Svoboda, B. ~majer, E. Konecna, R. Talac, R. Vyzula, J. Zaloudik. Department of Surgery, University Hospital Bohunice,
University Oncology Center, Brno, Czech Republic Fifty-four symptom-free persons registered in the Autofluorescence Bronchoscopy Pilot Study for Czech Uranium Miners (n = 94) were examined by white light and again by autofluorescence bronchoscopy (SAFE-1000) in a one-year period. The biopsies stained by hematoxylin and eosin confirmed IEN in 18 areas in 12 persons. Approximately one year previously 21 early stage IEN lesions were found in 13 persons in the same group. Nothing the early lesions signs of IEN recurrence were found in three areas after simple excision by biopsy forceps of two protruding lesions and one with swollen and thickened mucosal folds. Eighteen lesions invisible on white light bronchoscopy or showing rednessed, granular or mixed appearance were diagnosed by SAFE-1000 and confirmed by histopathology. One lesion remained unchanged, three lesions emerged de novo, three
255
lesions disappeared spontaneously, eight lesions showed regression and six lesions showed progression. Let us use this approach to try to give new answers to the old question of early lung cancer diagnosis and management.
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VEGF measured in serum and its correlation to clinical parameters in patients with non-small cell lung cancer
F~ Hesselius, M. Bergqvist, D. Brattstrom, A. Larsson, O. Brodin, G. Wagenius. Department of Oncology, Akademiska Hospital,
Uppsala University, Uppsala; Department of Clinical Chemistry, Uppsala, Sweden Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors. In this study we investigate if elevated levels in serum of VEGF can be correlated to clinical parameters in patients with non-small cell lung cancer (NSCLC). To be included in the study, the patients must have had a histological verified diagnosis of NSCLC. All patients gave informed consent prior to collection of blood samples and the samples were stored at -70C until tested. Serum VEGF was measured using commercially available enzyme-linked immunosorbent assays (R&D Systems Inc., Minneapolis, MN, USA). Eighty-one patients fulfilled the inclusion criterion mention above. These patients donated, in a consecutively manner, 503 serum samples. The median survival time for the patients in this study was 389 days. Median survival time for the different TNM stages were, 3a: 389 days, 3b: 376 days and 4:388 days. The mean level of VEGF was 650 pg/ml, with a 95 percent confidence interval 600-701 pg/ml. The mean level of VEGF for the different TNM stages were: 3a: 8.5 pg/ml, 3b: 11.8 pg/ml and 4:12.0 pg/ml. The TNM-stages were not significantly correlated with VEGF levels (p-value = 0.50), correlation with reduced weight and the level of VEGF were also not statistically significant (p-value = 0.38). The remaining lifetime was constructed as the percentage remaining lifetime from diagnosis. The level of VEGF in a sera sample was plotted against the remaining lifetime. Using standard OLS estimation of the level of VEGF, gave the result that the smaller the percentage remaining lifetime is, the larger amount of VEGF was measured in the sera sample. The estimation of the VEGF level at diagnosis was 544 pg/ml and at the time of death the level was increased with 241 pg/ml to 785 pg/ml (p-level = 0.008). The level of platelets in the sera were highly correlated with the level of VEGF (p-value < 0.0001), with each rise of 1 x 109 in platelet count, S-VEFG rises 1.42 pg/ml Metastases had no significant correlation with the level of VEGF (p-level = 0.38). Toxicity showed no overall correlation with VEGF, but patients with oesophagitis had a lower mean level of VEGF (392 pg/ml, p-value < 0.05). We conclude that VEGF is a useful biological parameter and can be used to monitor patients with NSCLC.
~ - 8 ~ Comparison of unidimensional and bidimensional measurement for evaluating tumor response to chemotherapy in patients with non-small cell lung cancer (NSCLC) H. Watanabe, I. Sekine, M. Sawada, Y. Akiyama, H. Kusaba, N. Yamamoto, H. Kunitoh, Y. Ohe, T. Tamura, T. Kodama, N. Saijo.
National Cancer Center Hospital, Tokyo, Japan Background: Tumor response to chemotherapy is determined by bidimensional measurement in the standard WHO criteria. Theoretically, unidimensional measurement may correlate more linearly with biologic activity than bidimensional measurement (JNCI 1999; 91: 523). The aim of this study was to evaluate a response rate obtained by these two measurement methods in the same datasets. Methods: Eligible were: 1) histologically or cytologically proven NSCLC patients (pts) treated with cisplatin (CDDP)-based chemotherapy in clinical trials; 2) pts who had at least one measurable lesion; a n d 3) pts who underwent CT scanning periodically for evaluating tumor response. We calculated percentage changes in the length (the maximum diameter of a tumor), the area (the product of the length and the largest diameter perpendicular to this length) and the volume of
[•-•
Does life add years to life? Clinical outcome in using autofluorescence bronchoscopy for occult cancers
H. Codriogton, P.E. Postmus, G. Sutedja. Free University Hospital
Amsterdam, The Netherlands Woolner et al. reported that only 68% of radiographically occult lung cancers a=e truly occult. The role of bronchoscopic therapy with curative intent and its long-term result in using LIFE (Laser Induced Fluorescence Endoscope) device and HRCT (high resolution CT) for the staging of patients with radiographically occult lung cancer have been analyzed. Twenty-four patients were referred to us with radiographically occult cancer, median age 63 years (range 48-74). Methods of staging with LIFE and HRCT have been reported before.* In 13 (54%) patients LIFE showed more extensive lesions > 1 cm2 surface area and/or invisible distal tumor margin. In four patients, HRCT showed that intraluminal cancers were not occult. The combination of LIFE and HRCT findings have changed the treatment policy, not to perform bronchoscopic therapy with curative intent (BT), in 17 patients (71%). BT resulted in a complete response status in 6/7 patients with true occult cancers after 37 months (SD 7.0) follow-up. Eleven of the seventeen patients with locally advanced cancer have died. Many patients with the so called "radiographically occult" cancer, do not have occult cancer if staged by LIFE and HRCT. Accurate selection and staging of patients suitable for BT is important and the recent role of bronchoscopic ultrasound should also be investigated. References [1] Venmans et al. J Bronchology 1998; 5:280 [2] Sutedja et al. Eur Resp J 1996; 9:1020-1023 stage bronchial • 7neoplasia -changes - (IEN)•ininearly Turanium h miners e in a intraepithelial one-year period with special reference to autofluorescence endoscopy (SAFE-1000) T.A. Horvath, J. Vomela, M. Horvathova, P. Pafko, B. Habanec, IR Benda, T. Svoboda, B. ~majer, E. Konecna, R. Talac, R. Vyzula, J. Zaloudik. Department of Surgery, University Hospital Bohunice,
University Oncology Center, Brno, Czech Republic Fifty-four symptom-free persons registered in the Autofluorescence Bronchoscopy Pilot Study for Czech Uranium Miners (n = 94) were examined by white light and again by autofluorescence bronchoscopy (SAFE-1000) in a one-year period. The biopsies stained by hematoxylin and eosin confirmed IEN in 18 areas in 12 persons. Approximately one year previously 21 early stage IEN lesions were found in 13 persons in the same group. Nothing the early lesions signs of IEN recurrence were found in three areas after simple excision by biopsy forceps of two protruding lesions and one with swollen and thickened mucosal folds. Eighteen lesions invisible on white light bronchoscopy or showing rednessed, granular or mixed appearance were diagnosed by SAFE-1000 and confirmed by histopathology. One lesion remained unchanged, three lesions emerged de novo, three
255
lesions disappeared spontaneously, eight lesions showed regression and six lesions showed progression. Let us use this approach to try to give new answers to the old question of early lung cancer diagnosis and management.
•7-•
VEGF measured in serum and its correlation to clinical parameters in patients with non-small cell lung cancer
F~ Hesselius, M. Bergqvist, D. Brattstrom, A. Larsson, O. Brodin, G. Wagenius. Department of Oncology, Akademiska Hospital,
Uppsala University, Uppsala; Department of Clinical Chemistry, Uppsala, Sweden Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors. In this study we investigate if elevated levels in serum of VEGF can be correlated to clinical parameters in patients with non-small cell lung cancer (NSCLC). To be included in the study, the patients must have had a histological verified diagnosis of NSCLC. All patients gave informed consent prior to collection of blood samples and the samples were stored at -70C until tested. Serum VEGF was measured using commercially available enzyme-linked immunosorbent assays (R&D Systems Inc., Minneapolis, MN, USA). Eighty-one patients fulfilled the inclusion criterion mention above. These patients donated, in a consecutively manner, 503 serum samples. The median survival time for the patients in this study was 389 days. Median survival time for the different TNM stages were, 3a: 389 days, 3b: 376 days and 4:388 days. The mean level of VEGF was 650 pg/ml, with a 95 percent confidence interval 600-701 pg/ml. The mean level of VEGF for the different TNM stages were: 3a: 8.5 pg/ml, 3b: 11.8 pg/ml and 4:12.0 pg/ml. The TNM-stages were not significantly correlated with VEGF levels (p-value = 0.50), correlation with reduced weight and the level of VEGF were also not statistically significant (p-value = 0.38). The remaining lifetime was constructed as the percentage remaining lifetime from diagnosis. The level of VEGF in a sera sample was plotted against the remaining lifetime. Using standard OLS estimation of the level of VEGF, gave the result that the smaller the percentage remaining lifetime is, the larger amount of VEGF was measured in the sera sample. The estimation of the VEGF level at diagnosis was 544 pg/ml and at the time of death the level was increased with 241 pg/ml to 785 pg/ml (p-level = 0.008). The level of platelets in the sera were highly correlated with the level of VEGF (p-value < 0.0001), with each rise of 1 x 109 in platelet count, S-VEFG rises 1.42 pg/ml Metastases had no significant correlation with the level of VEGF (p-level = 0.38). Toxicity showed no overall correlation with VEGF, but patients with oesophagitis had a lower mean level of VEGF (392 pg/ml, p-value < 0.05). We conclude that VEGF is a useful biological parameter and can be used to monitor patients with NSCLC.
~ - 8 ~ Comparison of unidimensional and bidimensional measurement for evaluating tumor response to chemotherapy in patients with non-small cell lung cancer (NSCLC) H. Watanabe, I. Sekine, M. Sawada, Y. Akiyama, H. Kusaba, N. Yamamoto, H. Kunitoh, Y. Ohe, T. Tamura, T. Kodama, N. Saijo.
National Cancer Center Hospital, Tokyo, Japan Background: Tumor response to chemotherapy is determined by bidimensional measurement in the standard WHO criteria. Theoretically, unidimensional measurement may correlate more linearly with biologic activity than bidimensional measurement (JNCI 1999; 91: 523). The aim of this study was to evaluate a response rate obtained by these two measurement methods in the same datasets. Methods: Eligible were: 1) histologically or cytologically proven NSCLC patients (pts) treated with cisplatin (CDDP)-based chemotherapy in clinical trials; 2) pts who had at least one measurable lesion; a n d 3) pts who underwent CT scanning periodically for evaluating tumor response. We calculated percentage changes in the length (the maximum diameter of a tumor), the area (the product of the length and the largest diameter perpendicular to this length) and the volume of