- Email: [email protected]
Cytokeratin fragment 19 (CYFRA 21.1) and neuron specific enolase (NSE) as indicators of chemotherapy in lung cancer
Pulmonary Imaging
[8-•
The clinicopathologic significance of preoperative serumsoluble interleukin-2 receptor concentrations in operable non-small cell lung cancer patients
O. Kawashima, M. Kamiyoshihara, S. Sakata, Y. Otani 1 , Y. Morishita 1•
Department of Surgery, National Sanatorium Nishigunma Hospital, Shibukawa; I Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan Background: A soluble form of the interleukin-2 receptor (IL-2R), which can bind efficiently to IL-2, is released into the circulation by activated lymphocytes. Although circulating soluble IL-2R have been detected in healty individuals at low levels, abnormally high levels of soluble IL-2R have been detected in cancer patients. However, the importantce of this finding in patients with non-small cell lung cancer (NSCLC) has not been previously established. Patients and Methods: Preoperative serum-soluble IL-2R concentrations were determined in 65 consecutive patients with operable NSCLC. The correlation of preoperative serum-soluble IL-2R concentrations with various clinicopathologic features of this cancer was evaluated to clarify the clinical significance of this parameter. Results: Although serum-soluble IL-2R concentrations were not significantly higher in operable NSCLC patients than in normal controls (P = 0.1180), serum-soluble IL-2R concentrations were significantly higher in patients with pathological stage IIIB or IV disease than in normal controls (P = 0.0001). The presence of intrapulmonary metastasis (PM) was the only clinicopathologic feature that was significantly correlated to serum-soluble IL-2R concentrations (P = 0.0004). The sensitivity of serum-soluble IL-2R concentration in identifying the presence of PM was 87.5%; specificity was 33%. Conclusions: Elevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of PM. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in detecting the occurrence of PM preoperatively.
•8-•
Availability of markers of bone metabolism in the diagnosis of bone metastasis in primary lung cancer
H. Ryo, K. Toyama, M. Hiroi, T. Hojyo, K. Kimura, M. Nakata. First
Dept. of Internal Medicine, Toho University, Tokyo, Japan To examine the clinical value of serum Cross-linked carboxyterminal telopeptid of type I collagen (ICTP), Carboxyterminal propeptide of type I procollagen (PICP), Osteocalcin (BGP) and urinary Pyridinoline (Pyr), as well as Deoxypyridinoline (Dpyr) in the diagnosis and monitoring of bone metastasis in primary lung cancer patients. These were, at the same time, compared to the tumor markers measured. Bone metabolism markers were measured periodically in 80 patients with primary lung cancer (39 cases of bone metastasis, 41 cases of no bone metastasis). Bone metastasis was diagnosed generally based upon the results of a bone scintigram. When compared to the nonbone metastasis group, the bone metastasis patients displayed high levels of ICTP (8.4 + 3.9 vs 6.3 ± 2.8; p = 0.008), Pyr (52.1 ± 24.9 vs 36.6 ± 15.2; p = 0.001), Dpyr (8.5 ± 4.0 vs 6.2 ± 2.5; p = 0.003). However, a significant difference was not seen in PICP, BGP and tumor markers. Further, the sensitivity and specificity of the various markers was ICTP: 89/56%, PICP: 26/88%, BGP: 2/93%, Pyr: 89/40%, Dpyr: 69/56%. it can be seen that ICTP showed the greatest sensitivity and specificity. Of the 17 cases where periodic observation was possible, progression of bone metastasis was observed in 10 cases, and it was found that ICTP, Pyr and Dpyr were significantly elevated at the time of progression when compared to levels at the time of first diagnosis. Further, 5 of the 15 cases of nonbone metastasis showed expression of bone metastasis during observation, and the levels of ICTP, Pyr and Dpyr were significantly higher. ICTP, Pyr and Dpyr showed a high rate of false positive results, however, were found to be useful as a supplementary diagnostic tool. It has been suggested that these levels may be an important factor in the assessment and monitoring of the progress of bone metastasis.
~The
257
evolution of a lung cancer multidisciplinary team at a large teaching hospital in the United Kingdom
B.J. Hutchcroft. On Behalf of the Sheffield Lung Cancer Group, UK This paper describes the evolution of the Lung Cancer Multidisciplinary (MDT.), considered to be an essential element of a Lung cancer service, at the Northern General Hospital in Sheffield. Attendances at the meetings and the patients discussed have been recorded since August 1997. The specialty and number of Consultants attending the meetings and the numbers of patients discussed were assessed during the first 7 months of 1998 and the last 7 months of 1999. Between the two periods of study 2 time out meetings to review the lung cancer services were held which resulted in a review of MDT working; a new chest physician for lung cancer and a second lung cancer support nurse were appointed and the thoracic surgeon and a Histopathologist were replaced. During the first period of study 14 fortnightly meetings were held compared with 29 weekly meeting latterly. Attendance numbers changed significantly in surgery form a mean of 0.64 surgeons per meeting to 1.30, in histopathology from 0.79 to 1.57, in radiology from 0.42 to 1.43 and support nursing from 0.79 to 1.43. In 1998 139 patients were discussed, a mean of 9.9 per fortnightly meeting. In 1999 428 patients were discussed, a mean of 14.75 per weekly meeting. Setting up a structured MDT as part of a dedicated service makes a considerable impact on the way lung cancer care is delivered. A subsequent abstract will describe the impact on the care the patients received.
~ - - ~ Urine deoxypyridinoline leveL.An alternative to bone scan in lung cancer? I. Savas, O. Ural Gurkan, H. Savas, B.E. Gulbay, G. Ugur, N. Numan.
Chest Dept., Ankara, Turkey Bone metastasis is an important determinant of morbidity in cancer patients. Among all the cancers prostate, breast and lung cancers are well known as the ones in which bone metastasis seen most frequently. Accurate evaluation of metastasis is important in determining the therapeutic strategies therefore reliable methods to detect bone metastasis are needed. Specific laboratory markers to detect metastasis are being evaluated. Many bone resorption markers have been studied in prostate and breast cancer metastasis and the urinary DPD and the collagen crosslink associated N-telopeptide were considered to be the most specific ones In this study, the diagnostic validity of urine deoxypyridinoline, urinary calcium/creatinine ratio, serum calcium and serum total alkaline phosphatase in lung cancer patients has been evaluated. Thirty-two patients with lung cancer and 15 healthy controls were enrolled in the study. All the cancer patients were evaluated with bone scintigraphy The DPD levels in the urine were determined with an automated chemiluminescence system. When cancer patients without bone metastasis were compared to the patients with positive scans the DPD/creatinine ratio was statistically significant (p < 0.05). No statistically significant differences were observed with serum alkaline phosphatase, serum Ca and urine Ca/creatinine ratio. In conclusion, urine Dpd/creatinine ratio is a promising marker in prediction of bone metastasis of lung cancer.
~-~
Cytokeratin fragment 19 (CYFRA 21.1) and neuron specific enolase (NSE) as indicators of chemotherapy in lung cancer L. Stelmakh, T. Ses, S. Orlov, Y. Levashev. Research Institute of Pulmonology, St. Petersburgh 197089, Russia
The aim of the present study was to detect the diagnostic value of two tumor markers: NSE and CYFRA 21.1 in lung cancer. Serum samples were obtained from 17 patients with nonsmall cell lung cancer (NSCLC) and 12 patients with small cell lung cancer (SCLC) before (A) and after (B) the treatment by chemotherapy. Levels of NSE and CYFRA 21.1 were detected by ELISA method. We revealed significant
PulmonaryImaging
258
difference between levels of CYFRA 21.1 in patients with NSCLC before and after the treatment (A: 9.9 ± 0.9 ng/ml; B: 3.71 ± 0.9 ng/ml, p < 0.01). No differences between levels of NSE were found in patients with NSCLC before and after the treatment (A: 17.06 ± 1.06 ng/ml; B: 17.81 ± 1.68 ng/ml; p < 0.05). However, levels of NSE in patients with SCLC before the treatment were differed from levels of NSE after the treatment (A: 30.38 ± 1.53 ng/ml; B: 17.3 ± 1.15 ng/ml; p < 0.01), whereas no differences between levels of CYFRA 21.1 in patients with SCLC were found before and after the treatment (A: 3.96 ± 1.1 ng/ml; B: 3.33 + 0.4 ng/ml; p < 0.01). The data obtained suggest that CYFRA 21.1 and NSE might be useful as possible indicators of therapeutic effect of chemotherapy for lung cancer.
Survival of NSCLC patients with tumor greater then 9 •88--• centimeters and possibility of their shifting to stage IV B. Perin, T. Zikic, N. Secen, S. Jovanovic, N. Lalic, G. Balaban, V. Canak, E. Budisin, M. Antonic. University of Novi Sad, School of
Medicine, Institute of Lung Diseases, Sremska Kamenica, Yugoslavia Differences in survival of patients with non-small cell lung cancer (NSCLC) in certain TNM groups according to classification from 1986 were the main reason that new TNM revision was established in 1997. The new revision is an improvement of TNM system for lung cancer staging, but it seems that it does not fit all the criteria for an optimal classification. There are some evidences showing that tumor size should be involved in different manner in current TNM classification. The aim of the study was to analyze the survival of the NSCLC patients with measurable tumor greater then 9 cm and to evaluate the possibility of involving that cut-off point into current TNM grouping. Four hundred ninety eight patients with NSCLC. treated during 1991, in the Institute of Lung Diseases in Sremska Kamenica - Novi Sad, Yugoslavia, were analyzed. There were 229 (46%) with measurable tumor and 22 (9.6%) of them were with tumor greater then 9 cm in biggest perpendicular diameter. Among these patients with tumor greater then 9 cm. 5 (23%) were with MI disease. Survival of 17 patients without distant metastases and with tumor greater then 9 cm was compared to survival of 107 patients with MI disease (Log Rank and Breslow test). There were no survivors after 13 months among the patients with tumor greater then 9 cm. Mean survival time was 4 months. Seven of them were treated with antitumor therapy and they have mean survival time 5 months. Mean survival time of all MI patients was 5 months (7 months for those who were treated with antitumor therapy). There was no significant difference between survival curves of patients with tumor greater then 9 cm and patients with MI disease (Log Rank 0.8390, Breslow 0.5699) as well as between survival curves of the patients from both groups treated with some antitumor therapy (Log Rank 0.7052, Breslow 0.7710). The survival of the NSCLC patients with tumor greater then 9 cm is very poor. Because of similar prognosis there is possibility of shifting the NSCLC patients with tumor greater then 9 cm to stage IV.
~-~
Clinical features of lung cancer
B. Vanderschueren, F. Branle, M. Borges, V. Ninane, T. Bosschaerts, T. Berghmans, M. Paesmans, J.P. Sculler. Institut Jules Bordet,
Bruxelles, Belgium Despite the changes in epidemiology over the last decades, there are a few publications about the signs and symptoms (sas) at initial presentation with lung cancer. We conducted a retrospective study of the patients treated at the Jules Bordet Institute between 1985 and 1995. The purpose was to define if there were differences in the clinical presentation in relationship to histology, stage tumor, sex and smoking habits of the patient. Statistic tests performed were Student t and chi 2 tests. Over a total of 610 patients, we retained the 448 patients who presented with a new diagnosis of lung cancer without prior treatment. Nine % of these patients were free of symptoms and signs at clinical examination, the others had dyspnea (35.8%), cough (27.9%), thoracic pain (24.5%), hemoptysis (20.8%), asthenia (18.1%), anorexia
(17.4%), clubbing (8.5%) and superior vena cava syndrome (svcs (5.9%). There were no major significant differences in the clinical picture for histology (NSCLC versus SCLC: no difference detectable for each symptom except for svcs and hepatomegaly), sex ans smoking habits. Stage IV disease was found in 52.5% of the patients; signs and symptoms poorly predicted metastatic sites as shown by the following results: Metastatic sites
N patients
sas in favour of the site
Bone Liver Brain Adrenals
93 78 54 55
30 (32.3%) 16 (20.5%) 23 (42.6%) 4 (7.3%)
We concluded that the clinical presentation of lung cancer has not changed during last years and is not significantly different for sex, smoking and histopathology of the tumor, and does not allow to avoid additional work-up by imaging and other tests.
[•
Plasma telomerase activity predicts response and relapse in lung cancer
J.W. Strovel, J. Stamberg, W.E. Highsmith, D. Sotirescu, P. Hausner, M. Edelman, J. Sonett, M. Suntharalingam, M. Krasna, LA. Doyle.
Division of Human Genetics, Departments of Pathology, Medicine, Surgery and Radiation Oncology; Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical System, Baltimore, Maryland, USA Telomerase is a ribonucleoprotein enzyme associated with immortalization of cancer cells by repair of the ends of chromosomes shortened during DNA replication. Prior studies of this attractive tumor marker have used biopsied tumor tissue, but we have developed assays to measure plasma telomerase activity in lung cancer (Proc. ASCO, 18: 2372, 1999), as well as an assay which measures telomerase activity in circulating lung cancer cells precipitated by magnetic beads complexed with antibodies against epithelial antigens. We report on serial telomerase assays on 65 lung cancer patients, performed at diagnosis and with each restaging CT scan. There was an overall detection of telomerase activity in 88% of the lung cancer patients, including very intense activity in the 7 small cell lung cancer patients. No telomerase activity was noted in 20 healthy control samples. An initial low telomerase level in non-small cell lung cancer patients was associated with clinical response to treatment and improved survival. A decrease in plasma telomerase activity in the epithelial cell precipitation assay predicted radiographic response in 16 of 20 patients who achieved partial remission by CT. A decrease in plasma telomerase predicted CT responders in 18 of 29 patients, and of the 11 patients with increasing telomerase activity, 7 relapsed within 6 months. Increasing telomerase activity by the epithelial cell precipitation assay predicted radiographic recurrence in 18 of 21 patients, while increasing plasma telomerase activity preceded CT recurrence in 20 of 26 patients. Plasma telomerase activity was detectable in most patients with stage I and II non-small cell lung cancer, suggesting potential utility as a screening test for lung cancer. We conclude that assays of telomerase activity in plasma and circulating cancer cells are a sensitive and reproducible marker of response to therapy in lung cancer.
[8-•
The clinicopathologic significance of preoperative serumsoluble interleukin-2 receptor concentrations in operable non-small cell lung cancer patients
O. Kawashima, M. Kamiyoshihara, S. Sakata, Y. Otani 1 , Y. Morishita 1•
Department of Surgery, National Sanatorium Nishigunma Hospital, Shibukawa; I Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan Background: A soluble form of the interleukin-2 receptor (IL-2R), which can bind efficiently to IL-2, is released into the circulation by activated lymphocytes. Although circulating soluble IL-2R have been detected in healty individuals at low levels, abnormally high levels of soluble IL-2R have been detected in cancer patients. However, the importantce of this finding in patients with non-small cell lung cancer (NSCLC) has not been previously established. Patients and Methods: Preoperative serum-soluble IL-2R concentrations were determined in 65 consecutive patients with operable NSCLC. The correlation of preoperative serum-soluble IL-2R concentrations with various clinicopathologic features of this cancer was evaluated to clarify the clinical significance of this parameter. Results: Although serum-soluble IL-2R concentrations were not significantly higher in operable NSCLC patients than in normal controls (P = 0.1180), serum-soluble IL-2R concentrations were significantly higher in patients with pathological stage IIIB or IV disease than in normal controls (P = 0.0001). The presence of intrapulmonary metastasis (PM) was the only clinicopathologic feature that was significantly correlated to serum-soluble IL-2R concentrations (P = 0.0004). The sensitivity of serum-soluble IL-2R concentration in identifying the presence of PM was 87.5%; specificity was 33%. Conclusions: Elevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of PM. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in detecting the occurrence of PM preoperatively.
•8-•
Availability of markers of bone metabolism in the diagnosis of bone metastasis in primary lung cancer
H. Ryo, K. Toyama, M. Hiroi, T. Hojyo, K. Kimura, M. Nakata. First
Dept. of Internal Medicine, Toho University, Tokyo, Japan To examine the clinical value of serum Cross-linked carboxyterminal telopeptid of type I collagen (ICTP), Carboxyterminal propeptide of type I procollagen (PICP), Osteocalcin (BGP) and urinary Pyridinoline (Pyr), as well as Deoxypyridinoline (Dpyr) in the diagnosis and monitoring of bone metastasis in primary lung cancer patients. These were, at the same time, compared to the tumor markers measured. Bone metabolism markers were measured periodically in 80 patients with primary lung cancer (39 cases of bone metastasis, 41 cases of no bone metastasis). Bone metastasis was diagnosed generally based upon the results of a bone scintigram. When compared to the nonbone metastasis group, the bone metastasis patients displayed high levels of ICTP (8.4 + 3.9 vs 6.3 ± 2.8; p = 0.008), Pyr (52.1 ± 24.9 vs 36.6 ± 15.2; p = 0.001), Dpyr (8.5 ± 4.0 vs 6.2 ± 2.5; p = 0.003). However, a significant difference was not seen in PICP, BGP and tumor markers. Further, the sensitivity and specificity of the various markers was ICTP: 89/56%, PICP: 26/88%, BGP: 2/93%, Pyr: 89/40%, Dpyr: 69/56%. it can be seen that ICTP showed the greatest sensitivity and specificity. Of the 17 cases where periodic observation was possible, progression of bone metastasis was observed in 10 cases, and it was found that ICTP, Pyr and Dpyr were significantly elevated at the time of progression when compared to levels at the time of first diagnosis. Further, 5 of the 15 cases of nonbone metastasis showed expression of bone metastasis during observation, and the levels of ICTP, Pyr and Dpyr were significantly higher. ICTP, Pyr and Dpyr showed a high rate of false positive results, however, were found to be useful as a supplementary diagnostic tool. It has been suggested that these levels may be an important factor in the assessment and monitoring of the progress of bone metastasis.
~The
257
evolution of a lung cancer multidisciplinary team at a large teaching hospital in the United Kingdom
B.J. Hutchcroft. On Behalf of the Sheffield Lung Cancer Group, UK This paper describes the evolution of the Lung Cancer Multidisciplinary (MDT.), considered to be an essential element of a Lung cancer service, at the Northern General Hospital in Sheffield. Attendances at the meetings and the patients discussed have been recorded since August 1997. The specialty and number of Consultants attending the meetings and the numbers of patients discussed were assessed during the first 7 months of 1998 and the last 7 months of 1999. Between the two periods of study 2 time out meetings to review the lung cancer services were held which resulted in a review of MDT working; a new chest physician for lung cancer and a second lung cancer support nurse were appointed and the thoracic surgeon and a Histopathologist were replaced. During the first period of study 14 fortnightly meetings were held compared with 29 weekly meeting latterly. Attendance numbers changed significantly in surgery form a mean of 0.64 surgeons per meeting to 1.30, in histopathology from 0.79 to 1.57, in radiology from 0.42 to 1.43 and support nursing from 0.79 to 1.43. In 1998 139 patients were discussed, a mean of 9.9 per fortnightly meeting. In 1999 428 patients were discussed, a mean of 14.75 per weekly meeting. Setting up a structured MDT as part of a dedicated service makes a considerable impact on the way lung cancer care is delivered. A subsequent abstract will describe the impact on the care the patients received.
~ - - ~ Urine deoxypyridinoline leveL.An alternative to bone scan in lung cancer? I. Savas, O. Ural Gurkan, H. Savas, B.E. Gulbay, G. Ugur, N. Numan.
Chest Dept., Ankara, Turkey Bone metastasis is an important determinant of morbidity in cancer patients. Among all the cancers prostate, breast and lung cancers are well known as the ones in which bone metastasis seen most frequently. Accurate evaluation of metastasis is important in determining the therapeutic strategies therefore reliable methods to detect bone metastasis are needed. Specific laboratory markers to detect metastasis are being evaluated. Many bone resorption markers have been studied in prostate and breast cancer metastasis and the urinary DPD and the collagen crosslink associated N-telopeptide were considered to be the most specific ones In this study, the diagnostic validity of urine deoxypyridinoline, urinary calcium/creatinine ratio, serum calcium and serum total alkaline phosphatase in lung cancer patients has been evaluated. Thirty-two patients with lung cancer and 15 healthy controls were enrolled in the study. All the cancer patients were evaluated with bone scintigraphy The DPD levels in the urine were determined with an automated chemiluminescence system. When cancer patients without bone metastasis were compared to the patients with positive scans the DPD/creatinine ratio was statistically significant (p < 0.05). No statistically significant differences were observed with serum alkaline phosphatase, serum Ca and urine Ca/creatinine ratio. In conclusion, urine Dpd/creatinine ratio is a promising marker in prediction of bone metastasis of lung cancer.
~-~
Cytokeratin fragment 19 (CYFRA 21.1) and neuron specific enolase (NSE) as indicators of chemotherapy in lung cancer L. Stelmakh, T. Ses, S. Orlov, Y. Levashev. Research Institute of Pulmonology, St. Petersburgh 197089, Russia
The aim of the present study was to detect the diagnostic value of two tumor markers: NSE and CYFRA 21.1 in lung cancer. Serum samples were obtained from 17 patients with nonsmall cell lung cancer (NSCLC) and 12 patients with small cell lung cancer (SCLC) before (A) and after (B) the treatment by chemotherapy. Levels of NSE and CYFRA 21.1 were detected by ELISA method. We revealed significant
PulmonaryImaging
258
difference between levels of CYFRA 21.1 in patients with NSCLC before and after the treatment (A: 9.9 ± 0.9 ng/ml; B: 3.71 ± 0.9 ng/ml, p < 0.01). No differences between levels of NSE were found in patients with NSCLC before and after the treatment (A: 17.06 ± 1.06 ng/ml; B: 17.81 ± 1.68 ng/ml; p < 0.05). However, levels of NSE in patients with SCLC before the treatment were differed from levels of NSE after the treatment (A: 30.38 ± 1.53 ng/ml; B: 17.3 ± 1.15 ng/ml; p < 0.01), whereas no differences between levels of CYFRA 21.1 in patients with SCLC were found before and after the treatment (A: 3.96 ± 1.1 ng/ml; B: 3.33 + 0.4 ng/ml; p < 0.01). The data obtained suggest that CYFRA 21.1 and NSE might be useful as possible indicators of therapeutic effect of chemotherapy for lung cancer.
Survival of NSCLC patients with tumor greater then 9 •88--• centimeters and possibility of their shifting to stage IV B. Perin, T. Zikic, N. Secen, S. Jovanovic, N. Lalic, G. Balaban, V. Canak, E. Budisin, M. Antonic. University of Novi Sad, School of
Medicine, Institute of Lung Diseases, Sremska Kamenica, Yugoslavia Differences in survival of patients with non-small cell lung cancer (NSCLC) in certain TNM groups according to classification from 1986 were the main reason that new TNM revision was established in 1997. The new revision is an improvement of TNM system for lung cancer staging, but it seems that it does not fit all the criteria for an optimal classification. There are some evidences showing that tumor size should be involved in different manner in current TNM classification. The aim of the study was to analyze the survival of the NSCLC patients with measurable tumor greater then 9 cm and to evaluate the possibility of involving that cut-off point into current TNM grouping. Four hundred ninety eight patients with NSCLC. treated during 1991, in the Institute of Lung Diseases in Sremska Kamenica - Novi Sad, Yugoslavia, were analyzed. There were 229 (46%) with measurable tumor and 22 (9.6%) of them were with tumor greater then 9 cm in biggest perpendicular diameter. Among these patients with tumor greater then 9 cm. 5 (23%) were with MI disease. Survival of 17 patients without distant metastases and with tumor greater then 9 cm was compared to survival of 107 patients with MI disease (Log Rank and Breslow test). There were no survivors after 13 months among the patients with tumor greater then 9 cm. Mean survival time was 4 months. Seven of them were treated with antitumor therapy and they have mean survival time 5 months. Mean survival time of all MI patients was 5 months (7 months for those who were treated with antitumor therapy). There was no significant difference between survival curves of patients with tumor greater then 9 cm and patients with MI disease (Log Rank 0.8390, Breslow 0.5699) as well as between survival curves of the patients from both groups treated with some antitumor therapy (Log Rank 0.7052, Breslow 0.7710). The survival of the NSCLC patients with tumor greater then 9 cm is very poor. Because of similar prognosis there is possibility of shifting the NSCLC patients with tumor greater then 9 cm to stage IV.
~-~
Clinical features of lung cancer
B. Vanderschueren, F. Branle, M. Borges, V. Ninane, T. Bosschaerts, T. Berghmans, M. Paesmans, J.P. Sculler. Institut Jules Bordet,
Bruxelles, Belgium Despite the changes in epidemiology over the last decades, there are a few publications about the signs and symptoms (sas) at initial presentation with lung cancer. We conducted a retrospective study of the patients treated at the Jules Bordet Institute between 1985 and 1995. The purpose was to define if there were differences in the clinical presentation in relationship to histology, stage tumor, sex and smoking habits of the patient. Statistic tests performed were Student t and chi 2 tests. Over a total of 610 patients, we retained the 448 patients who presented with a new diagnosis of lung cancer without prior treatment. Nine % of these patients were free of symptoms and signs at clinical examination, the others had dyspnea (35.8%), cough (27.9%), thoracic pain (24.5%), hemoptysis (20.8%), asthenia (18.1%), anorexia
(17.4%), clubbing (8.5%) and superior vena cava syndrome (svcs (5.9%). There were no major significant differences in the clinical picture for histology (NSCLC versus SCLC: no difference detectable for each symptom except for svcs and hepatomegaly), sex ans smoking habits. Stage IV disease was found in 52.5% of the patients; signs and symptoms poorly predicted metastatic sites as shown by the following results: Metastatic sites
N patients
sas in favour of the site
Bone Liver Brain Adrenals
93 78 54 55
30 (32.3%) 16 (20.5%) 23 (42.6%) 4 (7.3%)
We concluded that the clinical presentation of lung cancer has not changed during last years and is not significantly different for sex, smoking and histopathology of the tumor, and does not allow to avoid additional work-up by imaging and other tests.
[•
Plasma telomerase activity predicts response and relapse in lung cancer
J.W. Strovel, J. Stamberg, W.E. Highsmith, D. Sotirescu, P. Hausner, M. Edelman, J. Sonett, M. Suntharalingam, M. Krasna, LA. Doyle.
Division of Human Genetics, Departments of Pathology, Medicine, Surgery and Radiation Oncology; Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical System, Baltimore, Maryland, USA Telomerase is a ribonucleoprotein enzyme associated with immortalization of cancer cells by repair of the ends of chromosomes shortened during DNA replication. Prior studies of this attractive tumor marker have used biopsied tumor tissue, but we have developed assays to measure plasma telomerase activity in lung cancer (Proc. ASCO, 18: 2372, 1999), as well as an assay which measures telomerase activity in circulating lung cancer cells precipitated by magnetic beads complexed with antibodies against epithelial antigens. We report on serial telomerase assays on 65 lung cancer patients, performed at diagnosis and with each restaging CT scan. There was an overall detection of telomerase activity in 88% of the lung cancer patients, including very intense activity in the 7 small cell lung cancer patients. No telomerase activity was noted in 20 healthy control samples. An initial low telomerase level in non-small cell lung cancer patients was associated with clinical response to treatment and improved survival. A decrease in plasma telomerase activity in the epithelial cell precipitation assay predicted radiographic response in 16 of 20 patients who achieved partial remission by CT. A decrease in plasma telomerase predicted CT responders in 18 of 29 patients, and of the 11 patients with increasing telomerase activity, 7 relapsed within 6 months. Increasing telomerase activity by the epithelial cell precipitation assay predicted radiographic recurrence in 18 of 21 patients, while increasing plasma telomerase activity preceded CT recurrence in 20 of 26 patients. Plasma telomerase activity was detectable in most patients with stage I and II non-small cell lung cancer, suggesting potential utility as a screening test for lung cancer. We conclude that assays of telomerase activity in plasma and circulating cancer cells are a sensitive and reproducible marker of response to therapy in lung cancer.