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1033 Elevated circulating transforming growth factor beta1 (TGFB1) levels decreased after radiotherapy in patients with lung cancer, cervical cancer and Hodgkin's disease: A possible tumor marker
Proceedings of the 37th Annual ASTRO Meeting
239
1 032 EVALUATION OF CYTOKINE LEVELS IN PROSTATE CANCER P A ' I I E N I S UNDERGOING RADIOTHERAPY Gridley, Dalla S , Slater, Jerry D , Yonemoto. Leslie T , Miller, Daniel W Rossi, Carl, Archambeau John O , Andres, Melba L , Oey, Ming, and Slater, James M Loma Linda University/Independent Order of foresters Cancer Research Laboratory, Deparlments of Microbiology & Molecular Genetics and Radiation Medicine, Loma Linda University and Medical Center, Loma Linda, ('A 92350, L I S A Purpose/Objeclive
The mechanisms responsible for damage to normal tissues following radiotherapy are largely unknown and currently there is no way to predict risk for developing complications It has been recently shown that ionizing radiation can actwate certain genes in mammalian cells, including some which code for cytokines Increased expression ofcytokines may be associated with morbidity The purpose of the present study was to evaluate the kinetics of several selected cytokines in prostate cancer patients receiving one of three possible radiation treatment regimens Materials and Methods:
The three radiation regimens consist~:l of a) photon irradiation alone (n-5), b) combination of proton and photon irradiation (n-8), and c) proton irradiation alone (n-7) All patients had adenocarcinoma of the prostate except for one with carcinosarcoma; the majority had stage B disease and a Gleason score of 5 or greater Standard fractionated doses of 180-200 cGy per day, 5 days a week, werc delivered until the total prescribed dose was achieved. Peripheral blood samples were collected in EDTA-containing tubes from each subject immediately before, during the first week, and immediately after the end of radiation treatment: the integral radiation dose delivered at each time of blood collection was calculated. Three healthy male volunteers provided control blood samples The plasma was aliquoted and stored at -70°C until testing Enzyme-linked immunosorbent assays were performed for quantitation of transforming growth factor-t31 (TGF-[31), basic fibroblast growth factor (bFGF}, tumor necrozis factor-c= (TNF-a), and interleukin 1~3 (IL-1 [3) Cytokine concentrations in the samples were obtained by extrapolation from the appropriate standard curves Acute morbidity scores were assigned using the Radiation Therapy Ontology G~oup (RTOG) scoring system of 0 to 5 Results:
The data show that a significantly lower (p<0 005) integral radiation dose was delivered with protons as compared to photon radiation Significant positive correlations (p<0 05) were obtained between bFGF, [L-I {3 and TNF-cx and the integral dose during the first week of treatment. Correlations approaching significance (p<0 1) were obtained with bFGF and acute morbidity scores No significance was obtained with any of the cytokines and pretreatment PSA levels, grade or stage of disease, or the integral dose by the end of radiation treatment Conclusion:
These results show that large changes occur in the plasma levels of certain cytokines early after initiation of radiotherapy and that larger treatment volumes are more likely to induce these changes Our data support further investigation of the role of cytokines during radiotherapy and long-term followup to determine if one or mare of the c~okines is predictive of risk for late radiation complications
1033 ELEVATED CIRCULATING TRANSFORMING GROWTH FACTOR BETA1 (TGFR1) LEVELS DECREASED AFTER RADIOTHERAPY IN PATIENTS WITH LUNG CANCER, CERVICAL CANCER AND HODGKIN'S DISEASE: A POSSIBLE TUMOR MARKER Fengming Kong, Mitchell S. Anseher, ZhiFang Xiong and Randy L.Jirtle Department of Radiation Oncology, Duke University Medical Center Purpose/Objective: It has been reported that patients with hepatocellular carcinoma and breast cancer had increased plasma TGFR levels which decreased significantly after surgical removal of the tumor. The purpose of this study was to investigate the potential role of TGFI~as a tumor marker in patients with lung cancer, cervical cancer and Hodgkin's disease. Material & Methods:
Plasma samples from patients before, during and after radiation therapy were analyzed TGF£1 was extracted from plasma using an acidethanol method. An enzyme linked immunosorbent assay was used to quantify the plasma l"GFIgl levels. Resulte: Baseline TGFB1 levels (mean.tSEMI in patients with newly diagosed lung cancer, cervical cancer and Hodgkin's disease were 20.5-~_.5, 30.6£11.0 and 28.3±12.6ng/ml respe~vely. All were signfficandy higher than normal controls (4.41_'0.2n g / m l , p<0.0S, plasma TGFgl level i'wo standard deviations above mean of normal controls was shown as horizontal line in F'/g_l and Fig.2)_ Elevated TGFgl levels were Found in 27/54 (50%) of lung carcinoma patients, 7/7 (100%) of cervical cancer patients, and 4/4 (100%) of Hodgkin's' disease patients. The increased pretreatment TGFI~I levels decreased gradually during fractionationed irradiation (Fig. 1). By the completion of treatment, the mean TGFgl levels dropped down m normal in patients with cecvical carcinoma, and Hodgkin's' disease but not in patients with lung cancer In patients with lung cancer, the last follow up plasma TGFIgl levels were associated with the disease status: patients w h o are alive with disease (AWD) had significantly higher TGF~I levels (11.8:L2.7ng/ml, n=13) than those w h o are alive with no evidence of disease (ANED) (6.3:t2.8 ng/ml, n=5, p-0.fl3 ) (Fig. 2). The median durations of follow up in AWl) and ANED groups were 6.5±1.8 and 11±4.9 months, respectively. C,ondua/oam These data suggest the possibility of using plasma TGFIgl level as a tumor marker in patients with lung ca~inoma, cervical cancer and Hodgkin's' disease.
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239
1 032 EVALUATION OF CYTOKINE LEVELS IN PROSTATE CANCER P A ' I I E N I S UNDERGOING RADIOTHERAPY Gridley, Dalla S , Slater, Jerry D , Yonemoto. Leslie T , Miller, Daniel W Rossi, Carl, Archambeau John O , Andres, Melba L , Oey, Ming, and Slater, James M Loma Linda University/Independent Order of foresters Cancer Research Laboratory, Deparlments of Microbiology & Molecular Genetics and Radiation Medicine, Loma Linda University and Medical Center, Loma Linda, ('A 92350, L I S A Purpose/Objeclive
The mechanisms responsible for damage to normal tissues following radiotherapy are largely unknown and currently there is no way to predict risk for developing complications It has been recently shown that ionizing radiation can actwate certain genes in mammalian cells, including some which code for cytokines Increased expression ofcytokines may be associated with morbidity The purpose of the present study was to evaluate the kinetics of several selected cytokines in prostate cancer patients receiving one of three possible radiation treatment regimens Materials and Methods:
The three radiation regimens consist~:l of a) photon irradiation alone (n-5), b) combination of proton and photon irradiation (n-8), and c) proton irradiation alone (n-7) All patients had adenocarcinoma of the prostate except for one with carcinosarcoma; the majority had stage B disease and a Gleason score of 5 or greater Standard fractionated doses of 180-200 cGy per day, 5 days a week, werc delivered until the total prescribed dose was achieved. Peripheral blood samples were collected in EDTA-containing tubes from each subject immediately before, during the first week, and immediately after the end of radiation treatment: the integral radiation dose delivered at each time of blood collection was calculated. Three healthy male volunteers provided control blood samples The plasma was aliquoted and stored at -70°C until testing Enzyme-linked immunosorbent assays were performed for quantitation of transforming growth factor-t31 (TGF-[31), basic fibroblast growth factor (bFGF}, tumor necrozis factor-c= (TNF-a), and interleukin 1~3 (IL-1 [3) Cytokine concentrations in the samples were obtained by extrapolation from the appropriate standard curves Acute morbidity scores were assigned using the Radiation Therapy Ontology G~oup (RTOG) scoring system of 0 to 5 Results:
The data show that a significantly lower (p<0 005) integral radiation dose was delivered with protons as compared to photon radiation Significant positive correlations (p<0 05) were obtained between bFGF, [L-I {3 and TNF-cx and the integral dose during the first week of treatment. Correlations approaching significance (p<0 1) were obtained with bFGF and acute morbidity scores No significance was obtained with any of the cytokines and pretreatment PSA levels, grade or stage of disease, or the integral dose by the end of radiation treatment Conclusion:
These results show that large changes occur in the plasma levels of certain cytokines early after initiation of radiotherapy and that larger treatment volumes are more likely to induce these changes Our data support further investigation of the role of cytokines during radiotherapy and long-term followup to determine if one or mare of the c~okines is predictive of risk for late radiation complications
1033 ELEVATED CIRCULATING TRANSFORMING GROWTH FACTOR BETA1 (TGFR1) LEVELS DECREASED AFTER RADIOTHERAPY IN PATIENTS WITH LUNG CANCER, CERVICAL CANCER AND HODGKIN'S DISEASE: A POSSIBLE TUMOR MARKER Fengming Kong, Mitchell S. Anseher, ZhiFang Xiong and Randy L.Jirtle Department of Radiation Oncology, Duke University Medical Center Purpose/Objective: It has been reported that patients with hepatocellular carcinoma and breast cancer had increased plasma TGFR levels which decreased significantly after surgical removal of the tumor. The purpose of this study was to investigate the potential role of TGFI~as a tumor marker in patients with lung cancer, cervical cancer and Hodgkin's disease. Material & Methods:
Plasma samples from patients before, during and after radiation therapy were analyzed TGF£1 was extracted from plasma using an acidethanol method. An enzyme linked immunosorbent assay was used to quantify the plasma l"GFIgl levels. Resulte: Baseline TGFB1 levels (mean.tSEMI in patients with newly diagosed lung cancer, cervical cancer and Hodgkin's disease were 20.5-~_.5, 30.6£11.0 and 28.3±12.6ng/ml respe~vely. All were signfficandy higher than normal controls (4.41_'0.2n g / m l , p<0.0S, plasma TGFgl level i'wo standard deviations above mean of normal controls was shown as horizontal line in F'/g_l and Fig.2)_ Elevated TGFgl levels were Found in 27/54 (50%) of lung carcinoma patients, 7/7 (100%) of cervical cancer patients, and 4/4 (100%) of Hodgkin's' disease patients. The increased pretreatment TGFI~I levels decreased gradually during fractionationed irradiation (Fig. 1). By the completion of treatment, the mean TGFgl levels dropped down m normal in patients with cecvical carcinoma, and Hodgkin's' disease but not in patients with lung cancer In patients with lung cancer, the last follow up plasma TGFIgl levels were associated with the disease status: patients w h o are alive with disease (AWD) had significantly higher TGF~I levels (11.8:L2.7ng/ml, n=13) than those w h o are alive with no evidence of disease (ANED) (6.3:t2.8 ng/ml, n=5, p-0.fl3 ) (Fig. 2). The median durations of follow up in AWl) and ANED groups were 6.5±1.8 and 11±4.9 months, respectively. C,ondua/oam These data suggest the possibility of using plasma TGFIgl level as a tumor marker in patients with lung ca~inoma, cervical cancer and Hodgkin's' disease.
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