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391 poster Radioresistant proliferating clonogen in the avascular cell aggregate of a tumor could induce accelerated repopulation in fractionated radiotherapy
Posters
389
S 103
poster
Analysis of acute morbidity after respiratory gating stereotactic radiosurgery for lung tumors. T. Aruqa 1, J. Itami2, R. Hara2, K. Nakajima2 K. Shibata2 H. /to 1 1Chiba University Hospital, Radiology, Chiba, Japan 2International Medical Center of Japan, Radiation Therapy and Oncology, Tokyo, Japan Purpose: To investigate the acute radiation morbidity after respiratory gating stereotactic radiosurgery (gating SRS) for lung tumors. Materials and methods: Twenty six tumors of 20 patients who had less than 3 lung tumors, two for primary lung cancer and 18 for metastatic lung cancer, were treated by gating SRS. Patients were irradiated using 3050ram circular 6MV X-ray beam and average of 17 fixed ports. Reference dose was defined by the minimum dose of gross tumor volume and ranged from 20 to 30 Gy. Follow up time ranged from 24 to 463 days, averaged 163 days. Results: Radiation pneumonitis occurred in 3 patients which did not accompany clinical symptoms but was indicated only chest X-rays. In one patient who was previously suffering from lung fiborsis, fibrosis turned for worse temporarily which did not correspond to the radiation fields. Two patients had grade 3 radiation dermatitis. There were no other severe complications related to gating SRS. Conclusion: Still there is not enough follow up time, gating SRS of 30Gy to lung tumor is thought to be tolerable and acceptable treatment. 390
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Combined chemotherapy of cisplatin and etoposide and twice daily thoracic radiotherapy for limited stage small cell lung cancer: a preliminary report of clinical phase 1/11trial G. Chen, L. Wang, G. Jianq, X. Fu, H. Qian, H. Yang, Z. Zhang, C. Flu, S. Zhao Cancer Hosp.,Shanghai Med. Univ., Radiation Oncology, Shanghai, China Purpose: To investigate the feasibility, toxicity and the efficacy of combined chemotherapy of cisplatin/etoposide and twice daily thoracic radiotherapy for limited stage small cell lung cancer (LSCLC). Methods: Patient eligibility: pathologically proved SCLC; LSCLC; KPS>60; 18-70 yr. old; weight loss <5% within 6months prior to the diagnosis. Treatment: Chemotherapy: One to three cycles of EP (cisplatin 2530mg/m 2 days1-3, etoposide 50-70mg/m 2 days1-3) were given before irradiation, and another three to five cycles followed after irradiation. Radiotherapy: Two fractions daily (1.4Gy, bid, with interval of _>6 hours), 5 days a week were delivered to a total dose ef 56Gy/40fx,4wks. The radiation fields just covered clinical tumors, which were demonstrated by thoracic CT with 1.5 margins. Irradiation commenced right after the complement of one to three cycles of chemotherapy. Results: From June 1997 to March 2000, 50 patients with LSCLC had been enrolled for this study. There were 45 males and 5 females with median age of 58 years (25-70). All patients were available for evaluation of sideeffects, toxicity and the response. Acute radiation esophagitis developed in 38% of patients with Grade I-II (RTOG), and 8% with Grade III. Acute radiation pneumonitis occurred in 30% of patients with Grade I-II (RTOG). Neutropenia was found in 66% of patients with Grade I-II (RTOG), 22% with Grade III, and 2% with Grade IV. Twenty-eight patients (56%) achieved complete response, 16 (32%), partial response, 5 (10%), stable disease and 1 (2%), progression disease. The overall response rate (CR+PR) was 88%. Conclusions: Combined chemotherapy of cisplatin and etoposide and twice daily thoracic radiotherapy could be tolerated by most of LSCLC patients. The immediate response was encouraging. 391
Results: The dynamics of clonogen in a tumor and its morphology after single irradiation were characterized by 1) the rapid recovery from initial cell killing within 24hr, implying PLDR and then 2) the active cell division observed in the avascular aggregates in which cells showed radioresistance as the cells in a hypoxic gas chamber, followed by the rapid propagation, and then 3) the clonogen in the tumor less increased but formed the vascular-rich tumor grown as at the same rate of the control tumor. Conclusions: The experimental results indicated that clonogen in a tumor after the recovery from cell killing by irradiation(PLDR) regained to proliferate and propagate themselves rapidly, which showed redioresistance in the hypoxic cell aggregate. Such colonogen are thought to cause accelelated repopulation in fractionated radiotherapy and grew up to form the vascular-rich tumor with increasing population. 392
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Escalated hyperfractionated accelerated radiation therapy combined with chemotherapy for non-small cell lung cancer: a preliminary report of clinical phase G. Chen, L. Wang, G. Jianq, X. Fu, H. Qian, S. Zhao, H. Yang, Z. Zhang, C. Hu Cancer Hosp., Shanghai Medical Univ., Radiation Oncology, Shanghai, China Purpose: To investigate the feasibility, toxicity and the efficacy of a combined modality treatment using escalated hyperfractionated accelerated radiation therapy (EHART) and chemotherapy for non-small cell lung cancer (NSCLC). Methods: Patient eligibility: histologically or cytologically proved; stage IIIb NSCLC (AJCC 1992) (T1-4N3M0 or T4N0-3M0, except malignant pleural effusion); KPS>60; 18-70 yr. old; weight loss <5% within 6months prior to the diagnosis. EHART was delivered by hyperfractionated irradiation with twice fractions daily with _>6-hour interval and five treatment days per week. In the first and second weeks, 1.2Gy/fraction, bid, was given, and then 1.3Gy/fraction, bid, in the 3rd week; 1.4Gy/fraction, bid, in the 4th week; 1.5Gy/fraction, bid, in the 5th week, respectively. The total tumor dose was 66Gy/50fx/5wks. Radiation fields covered just clinical tumors, which were determined by thoracic CT or MRI with 1.5 cm margins. One cycle of chemotherapy was administered right before irradiation, and 3 to 5 cycles more, every 4 weeks, after irradiation. Chemotherapy regimen were cisplatin 25-30mg/m 2 and etoposide 60-70mg/m 2 on day 1-3 for squamous cell carcinoma or large cell carcinoma or unclassified, and Mitomycin C 56mg/m 2on day 1, Vindesine 4mg on day 1, 8, and cisplatin 25-30mg/m 2on day 1-3 for adenocarcinoma. Results: From Feb. 1997 to Feb. 1999, 73 patients had been enrolled in this trial. The clinical characteristics were: male 59, female 14; median age: 58 yr. (33-70); T1-3N3M0 47, T4N0-2 M0 18, T4N3 M0 8; squamous cell carcinoma 27, adnocarcinoma 36, large cell carcinoma and unclassified 10; KPS=60 13, KPS70 60. Twelve patients did not completed EHART and were withdrawn from the trial for the following reasons: intolerance due to acute complications (esophagitis RTOG III, 3 cases; pneumonitis RTOG III, 1 case), distant metastases occurring during irradiation (6 cases), and intercurrent diseases (2 cases). Therefore, 61 cases remained was further analyzed to evaluate acute complications and immediate responses. Acute radiation esophagitis occurred in 71% of patients with Grade I-II (RTOG), and 8% with Grade III. Acute radiation pneumonitis developed in 32% of patients with Grade l-II (RTOG), and 7% with Grade III. The overall response rate (CR+PR) was 79% (48/61) for pulmonary tumors, and 97% (34/35) for metastatic supraclavicular nodes. The median survival time was 18 months and the 1-year survival rate was 59%. Conclusions: EHART combined with chemotherapy could be tolerated by most of the patients with stage IIIb NSCLC. The median survival time and 1-year survival were encouraging.
poster
Radioresistant proliferating clonogen in the avascular cell aggregate of a tumor could induce accelerated repopulation in fractionated radiotherapy T. Mivamoto, S. Ishi NIRS, Radiat medi, Chiba, Japan Purpose: To clarify the dynamics of clonogenic cells (clonogen) in a tumor after irradiation and to identify and characterize the clonogen leading to recurrence. Methods: A human lung cancer cell line grown in culture and in nude mice as a solid tumor was used. The clonogenicity of the cells was assayed by using colony- forming method. The hypoxic conditions in a tumor were measured by assaying cell survival compared to the survival of the irradiated cells in a chamber gassed with known concentrations of N2 . The tumors were stained with Ki-67 immunioantibody and AgNO3 to observe the cell division and vascularization.
393
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The effect of whole brain irradiation on metastatic brain tumor of lung cancer K. Kimbara Yokohama citizen Medical center,, Radiology, Yokohama, Japan Purpose: The lung cancer is prone to metastasize to the brain and patients' condition is marginal even after the treatment. The objective of this study is to analyze and evaluate treatment results and prognostic factors of whole brain irradiation on metastatic brain tumor from lung cancer. Materials and Methods: There were 64 cases of whole brain irradiation in order to cure brain tumors metastasized from lung cancer at Kanagawa Cardiovascular Resp. Ctr. during the period between July 1996 and December 1999. Seven of cases were detected at their brains and there were no treatment applied to their lung cancer. Their mean age was 64
389
S 103
poster
Analysis of acute morbidity after respiratory gating stereotactic radiosurgery for lung tumors. T. Aruqa 1, J. Itami2, R. Hara2, K. Nakajima2 K. Shibata2 H. /to 1 1Chiba University Hospital, Radiology, Chiba, Japan 2International Medical Center of Japan, Radiation Therapy and Oncology, Tokyo, Japan Purpose: To investigate the acute radiation morbidity after respiratory gating stereotactic radiosurgery (gating SRS) for lung tumors. Materials and methods: Twenty six tumors of 20 patients who had less than 3 lung tumors, two for primary lung cancer and 18 for metastatic lung cancer, were treated by gating SRS. Patients were irradiated using 3050ram circular 6MV X-ray beam and average of 17 fixed ports. Reference dose was defined by the minimum dose of gross tumor volume and ranged from 20 to 30 Gy. Follow up time ranged from 24 to 463 days, averaged 163 days. Results: Radiation pneumonitis occurred in 3 patients which did not accompany clinical symptoms but was indicated only chest X-rays. In one patient who was previously suffering from lung fiborsis, fibrosis turned for worse temporarily which did not correspond to the radiation fields. Two patients had grade 3 radiation dermatitis. There were no other severe complications related to gating SRS. Conclusion: Still there is not enough follow up time, gating SRS of 30Gy to lung tumor is thought to be tolerable and acceptable treatment. 390
poster
Combined chemotherapy of cisplatin and etoposide and twice daily thoracic radiotherapy for limited stage small cell lung cancer: a preliminary report of clinical phase 1/11trial G. Chen, L. Wang, G. Jianq, X. Fu, H. Qian, H. Yang, Z. Zhang, C. Flu, S. Zhao Cancer Hosp.,Shanghai Med. Univ., Radiation Oncology, Shanghai, China Purpose: To investigate the feasibility, toxicity and the efficacy of combined chemotherapy of cisplatin/etoposide and twice daily thoracic radiotherapy for limited stage small cell lung cancer (LSCLC). Methods: Patient eligibility: pathologically proved SCLC; LSCLC; KPS>60; 18-70 yr. old; weight loss <5% within 6months prior to the diagnosis. Treatment: Chemotherapy: One to three cycles of EP (cisplatin 2530mg/m 2 days1-3, etoposide 50-70mg/m 2 days1-3) were given before irradiation, and another three to five cycles followed after irradiation. Radiotherapy: Two fractions daily (1.4Gy, bid, with interval of _>6 hours), 5 days a week were delivered to a total dose ef 56Gy/40fx,4wks. The radiation fields just covered clinical tumors, which were demonstrated by thoracic CT with 1.5 margins. Irradiation commenced right after the complement of one to three cycles of chemotherapy. Results: From June 1997 to March 2000, 50 patients with LSCLC had been enrolled for this study. There were 45 males and 5 females with median age of 58 years (25-70). All patients were available for evaluation of sideeffects, toxicity and the response. Acute radiation esophagitis developed in 38% of patients with Grade I-II (RTOG), and 8% with Grade III. Acute radiation pneumonitis occurred in 30% of patients with Grade I-II (RTOG). Neutropenia was found in 66% of patients with Grade I-II (RTOG), 22% with Grade III, and 2% with Grade IV. Twenty-eight patients (56%) achieved complete response, 16 (32%), partial response, 5 (10%), stable disease and 1 (2%), progression disease. The overall response rate (CR+PR) was 88%. Conclusions: Combined chemotherapy of cisplatin and etoposide and twice daily thoracic radiotherapy could be tolerated by most of LSCLC patients. The immediate response was encouraging. 391
Results: The dynamics of clonogen in a tumor and its morphology after single irradiation were characterized by 1) the rapid recovery from initial cell killing within 24hr, implying PLDR and then 2) the active cell division observed in the avascular aggregates in which cells showed radioresistance as the cells in a hypoxic gas chamber, followed by the rapid propagation, and then 3) the clonogen in the tumor less increased but formed the vascular-rich tumor grown as at the same rate of the control tumor. Conclusions: The experimental results indicated that clonogen in a tumor after the recovery from cell killing by irradiation(PLDR) regained to proliferate and propagate themselves rapidly, which showed redioresistance in the hypoxic cell aggregate. Such colonogen are thought to cause accelelated repopulation in fractionated radiotherapy and grew up to form the vascular-rich tumor with increasing population. 392
poster
Escalated hyperfractionated accelerated radiation therapy combined with chemotherapy for non-small cell lung cancer: a preliminary report of clinical phase G. Chen, L. Wang, G. Jianq, X. Fu, H. Qian, S. Zhao, H. Yang, Z. Zhang, C. Hu Cancer Hosp., Shanghai Medical Univ., Radiation Oncology, Shanghai, China Purpose: To investigate the feasibility, toxicity and the efficacy of a combined modality treatment using escalated hyperfractionated accelerated radiation therapy (EHART) and chemotherapy for non-small cell lung cancer (NSCLC). Methods: Patient eligibility: histologically or cytologically proved; stage IIIb NSCLC (AJCC 1992) (T1-4N3M0 or T4N0-3M0, except malignant pleural effusion); KPS>60; 18-70 yr. old; weight loss <5% within 6months prior to the diagnosis. EHART was delivered by hyperfractionated irradiation with twice fractions daily with _>6-hour interval and five treatment days per week. In the first and second weeks, 1.2Gy/fraction, bid, was given, and then 1.3Gy/fraction, bid, in the 3rd week; 1.4Gy/fraction, bid, in the 4th week; 1.5Gy/fraction, bid, in the 5th week, respectively. The total tumor dose was 66Gy/50fx/5wks. Radiation fields covered just clinical tumors, which were determined by thoracic CT or MRI with 1.5 cm margins. One cycle of chemotherapy was administered right before irradiation, and 3 to 5 cycles more, every 4 weeks, after irradiation. Chemotherapy regimen were cisplatin 25-30mg/m 2 and etoposide 60-70mg/m 2 on day 1-3 for squamous cell carcinoma or large cell carcinoma or unclassified, and Mitomycin C 56mg/m 2on day 1, Vindesine 4mg on day 1, 8, and cisplatin 25-30mg/m 2on day 1-3 for adenocarcinoma. Results: From Feb. 1997 to Feb. 1999, 73 patients had been enrolled in this trial. The clinical characteristics were: male 59, female 14; median age: 58 yr. (33-70); T1-3N3M0 47, T4N0-2 M0 18, T4N3 M0 8; squamous cell carcinoma 27, adnocarcinoma 36, large cell carcinoma and unclassified 10; KPS=60 13, KPS70 60. Twelve patients did not completed EHART and were withdrawn from the trial for the following reasons: intolerance due to acute complications (esophagitis RTOG III, 3 cases; pneumonitis RTOG III, 1 case), distant metastases occurring during irradiation (6 cases), and intercurrent diseases (2 cases). Therefore, 61 cases remained was further analyzed to evaluate acute complications and immediate responses. Acute radiation esophagitis occurred in 71% of patients with Grade I-II (RTOG), and 8% with Grade III. Acute radiation pneumonitis developed in 32% of patients with Grade l-II (RTOG), and 7% with Grade III. The overall response rate (CR+PR) was 79% (48/61) for pulmonary tumors, and 97% (34/35) for metastatic supraclavicular nodes. The median survival time was 18 months and the 1-year survival rate was 59%. Conclusions: EHART combined with chemotherapy could be tolerated by most of the patients with stage IIIb NSCLC. The median survival time and 1-year survival were encouraging.
poster
Radioresistant proliferating clonogen in the avascular cell aggregate of a tumor could induce accelerated repopulation in fractionated radiotherapy T. Mivamoto, S. Ishi NIRS, Radiat medi, Chiba, Japan Purpose: To clarify the dynamics of clonogenic cells (clonogen) in a tumor after irradiation and to identify and characterize the clonogen leading to recurrence. Methods: A human lung cancer cell line grown in culture and in nude mice as a solid tumor was used. The clonogenicity of the cells was assayed by using colony- forming method. The hypoxic conditions in a tumor were measured by assaying cell survival compared to the survival of the irradiated cells in a chamber gassed with known concentrations of N2 . The tumors were stained with Ki-67 immunioantibody and AgNO3 to observe the cell division and vascularization.
393
poster
The effect of whole brain irradiation on metastatic brain tumor of lung cancer K. Kimbara Yokohama citizen Medical center,, Radiology, Yokohama, Japan Purpose: The lung cancer is prone to metastasize to the brain and patients' condition is marginal even after the treatment. The objective of this study is to analyze and evaluate treatment results and prognostic factors of whole brain irradiation on metastatic brain tumor from lung cancer. Materials and Methods: There were 64 cases of whole brain irradiation in order to cure brain tumors metastasized from lung cancer at Kanagawa Cardiovascular Resp. Ctr. during the period between July 1996 and December 1999. Seven of cases were detected at their brains and there were no treatment applied to their lung cancer. Their mean age was 64