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P-164 Recent results of carbon ion radiotherapy for stage I non-small cell lung cancer
S132
Poster Session 1 /Radiotherapy Recent results of carbon ion radiotherapy for stage I non-small cell lung cancer
Tadaaki Mivamoto’, Masayuki Baba’, Toshiyuki Sugawara’, Naoyoshi YamamotoZ, Masashi Koto3, Hideki Nishimura4, Hirohiko Tujii’, Takahiko Fujisawa5. ’ National /nstitute of Radiological Sciences, Chiba, Japan; ’ Division of Thoracic Disease, Chiba Cancer Center, Chiba, Japan; 3 Department of Radiology Tohoku University of School of Medicine, Sendai, Japan; 4 Deparfment of Radiology Kobe University of School of Medicine, Kobe, Japan; 5Department of Thoracic Surgery, Chiba University of School of Medicine, Chiba, Japan Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effects on tumors. Using carbon beams, a phase l/l1 study was first conducted from 1994 to 1999 for the treatment of stage I non-small cell lung cancer (NSCLC) to determine the optimal dose. Irradiation was applied in 18 fractions over 6 weeks on 47 patients (48 lesions) and 9 fractions over 3 weeks on 34 patients. Dose escalation for the former was from 59.4 to g5.4GyE in 10% increments and for the latter from 68.4 to 79.2GyE in 5% increments, respectively. Grade Ill radiation pneumonitis occurred in 3 out of 81 patients (2.7%). Local control rates in the former and the latter fractionation Courses were 64% and 84%, respectively. There were 15 in-field and 4 marginal recurrences, with the total recurrence rate being 23.2% (19/82). In-field recurrence in the former shows a significant dose-dependence. The 5 year overall and cause-specific survival rate for the 47 patients of the first fractionation group was 40% and 60%, and that for the 34 patients of the second fractionation group was 50% and 63%, respectively. The following conclusions can be drawn from our study:, 1) Respiratory-gated irradiation and 4 portal irradiation excluding opposed ports proved successful in reducing the incidence of radiation pneumonitis, 2) the development of a copy paste irradiation technique helped prevent marginal recurrence, 3) 72GyE was determined as the optimal dose for the 9 fraction regimen, and 4) the early detection in the regular check-ups followed by elective nodal irradiation(ENl)with carbon beams prevented the survival rate from decreasing due to restricted regional node metastasis. As the next step, a phase II study using 72GyE spread into 9 fractions over 3 weeks was performed from April 1999 to December 2000 on 50 patients (51 lesions) were treated. There was no instance of Grade Ill radiation pneumonitis and the local control rate attained 98% (50/51). The 4 year overall and cause-specific survival rates were 74% (stagelA:83%, lB:57%) and 85% (stagelA:gO%, lB:81%), respectively. Carbon ion radiotherapy, which is an excellent new modality in QOL and ADL, is thus a valid alternative to surgery for stage I NSCLC especially for elderly and inoperable patients.
piiq
Robatic (da Vinci Robot) placement of I 125 seeds after wedge resection for lung cancer
Julianna Pisch, Mohamoud Gaildon, Robert Ashton, Scott Belsley, Karen McGinnis, Cliff Connery. Beth Israel Medical Center, New York, USA
Introduction: Limited wedge resection for lung cancer have been associated with an increased risk of local recurrence. In patients with limited pulmonary reserve or with medical illness precluding lobectomy external irradiation is seldom a treatment of choice because of resultant chronic fibrosis to a large lung volume. Thoracoscopic wedge resection and direct I - 125 seed suture implant cannot be effectively performed due to technical constraints with intracorporeal suturing. I- 215 seeds embedded in mesh were placed over the resected area by other investigators. Although this method is feasible via videoassisted surgery (VATS) techniques, a controlled accurate dose distribution is questionable due to displacement and/or folding of the mesh. To overcome the technical difficulties of direct intramural seed placement by VATS methods we used the da Vinci Robot with 3D visualization to place I- 125 seeds into the resection margin. Methods and Materials: Young well developed pigs with acceptable chest cavity size were used for this feasibility study. The protocol was approved by the Institutional Animal Care and Use Committee (IACUC).We performed the surgery and seed placement in the animal laboratory. General anesthesia with selective intubation was performed. The pig was positioned on his side. Appropriate, and usual preoperative skin preparation and draping was done. Sterile condition was maintained trough the surgery. Video camera recorded the procedure. As a first step VATS wedge resection was petformed.The da Vinci Robot was than positioned in the chest cavity. Under direct 3 D visualization I- 125 dummy seed in suture (Amersham Health, RAPID Strand) were sawn into the resection area. Two different technique were used - 1: the running longitudinal seed placement in three rows and the 2: looping technique. Seed numbers conformed to the length of resection. Orthogonal radiographs for dose calculation were taken in the operating room while the pig was under anesthesia. Results: Two pigs were sacrificed. Dosimetric calculations were done in two separate lobes. We aimed for finding the differences in dose distribution between the two different seed placement method. The number of seeds was tailored to the length of resection. Seed strength was equal for both technique.but
4 separate calculations were done with two hypothetical seed strength (0.5 mCi or 0.6 mCi)The looping technique used 10 seeds, (2.5 cm resection length) the running longitudinal technique used 16 seeds (4.4.cm resection length). The distance between seeds and sutures was kept to IO mm. For 3D calculations the Variseed 6.7 (Build 1312), for isodose display the Pinnacle V.5.2g software was used. Dose to volumes, seed strength: 0.5 mCi #I technique - Vi20 = 9.86 cc, V140 = 7.92 cc, #2 technique - Vi20 = 4.58 cc, V140 = 3.62 cc, seed strength: 0.6 mCi #I technique - V120 = 12.86 cc, VI40 = 10.28 cc, #2technique - V120 = 6.02 cc, V140 = 4.76 cc. Conclusion: This method gives excellent visualization and control of seed placement without undue risk to the patientsThe dose distribution between the 2 placement is comparable and both is acceptable. The seed strength should be tailored to the length of resection.On the average a volume of 8.3 cc is well covered with IO-17 seed with a strength of 0.5- 0.6 mCi and delivers 120-140. Gy to a volume of 8.3 cc.This technique avoids thoracotomy, saves hospital recovery time and may be utilizedin any Hospital with Robotic Surgery. Based on this study we are planning a feasibilityprotocol for lung cancer patients treated with VATS wedge resection.
I P 166
The significance of clinically staged bilateral mediastinal or supraclavicular adenopathy in patients with stage N3 non-small cell lung center
Sanq-Wook Lee’, Eun Kyung Cho?, Jong Hoon Kim*, Seung Do Ahr?, Jung Shin Lee3, Cheolwon Suh3, Sang We Kim3, Dong Soon Kim3, Woo Sung Kim3, Sang Do Lee3. ’ Departmenf of Radiation Onco/ogx Asan Medical Center, University of U/San, Seoul, Korea; ‘Departments of Radiation Oncology, Asan Medical Center, University of U/San, Seoul, Korea; 3 Departments of Infernal Medicine, Asan Medical Center, University of Wan, Seoul, Korea
Background: To evaluate the difference of the patterns of failure and treatment of outcome with concurrent chemoradiotherapy between clinical stage N2 and N3 in the locally advanced unresectable stage Ill non-small cell lung cancer (NSCLC). Methods: of 186 patients with gross mediastinal node positive non-small cell lung cancer received concurrent chemoradiation therapy at Asan Medical Center, University of Ulsan College of Medicine in Seoul, Korea between 1993 and 2000. Follow-up period was 1 to 65 month (median, 13 months). The patterns of failure and treatment of outcomes of N2 and N3 were retrospectively analyzed. Results: There were 170 men and 16 women, for a man-women ratio of IO to 1. The age of patients ranging from 37 to 76 years (median, 60 years). Number of patients with N2 and N3 were 91 and 95, respectively. Supraclavicular node metastasis showed in 35 patients. Distant metastasis free survival rate of N2 and N3 were 54% and 49% (p=O.6305). Overall survival rate of N2 and N3 were 21% and 14% (p=O.3236). There were no stastistically significant differences in distant metastasis free and overall survival rate by two group. Progression free survival rate were statistically significant differences in the supraclavicular fossae node positive or not (p=O.OOS). Locoregional failure within radiation fields was major patterns of failure. Conclusion: There were lack of differences of patterns of failure and treatment outcome with concurrent chemoradiation treatment. However, in this study, supraclavicular node metastasis patients were considered incurable disease. Therefore further investigation of treatment scheme were needed in this cases. ElP 167
p53 status and its in vitro relation to radiosensitivity lung cancer
in
Michael Berqqvist’, Daniel Brattstrom’, Patrik Hesselius’, Joachim Gullbo2, Gunnar Wagenius’ , Ola Brodin3. ’ Uppsala University Hospifal, Uppsala, Sweden; 2 Uppsala University Hospital, Sweden, Uppsala; 3 Huddinge Universitets Sjukhus, Uppsala, Sweden The following study was designed to investigate if mutations within the ~53 gene are associated with radiation responsiveness. Nine human lung cancer cell lines were examined (four SCLC and five NSCLC cell lines). CDNA-based sequencing of the entire ~53 gene was performed. Data from the clonogenic assay were studied to obtain information concerning radioresponsiveness.All cell lines expressed mutations, six were missence mutations and three were deletions. A statistical significant increased radiosensitivity was found for mutations in exon 7 (p=O.Oi 9), compared with the other mutations localised within different exons of ~53. We conclude that ~53 mutations in exon 7 were statistically associated with increased radiation sensitivity in these human lung cancer cell lines, when compared to other mutations within the ~53 gene.
Poster Session 1 /Radiotherapy Recent results of carbon ion radiotherapy for stage I non-small cell lung cancer
Tadaaki Mivamoto’, Masayuki Baba’, Toshiyuki Sugawara’, Naoyoshi YamamotoZ, Masashi Koto3, Hideki Nishimura4, Hirohiko Tujii’, Takahiko Fujisawa5. ’ National /nstitute of Radiological Sciences, Chiba, Japan; ’ Division of Thoracic Disease, Chiba Cancer Center, Chiba, Japan; 3 Department of Radiology Tohoku University of School of Medicine, Sendai, Japan; 4 Deparfment of Radiology Kobe University of School of Medicine, Kobe, Japan; 5Department of Thoracic Surgery, Chiba University of School of Medicine, Chiba, Japan Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effects on tumors. Using carbon beams, a phase l/l1 study was first conducted from 1994 to 1999 for the treatment of stage I non-small cell lung cancer (NSCLC) to determine the optimal dose. Irradiation was applied in 18 fractions over 6 weeks on 47 patients (48 lesions) and 9 fractions over 3 weeks on 34 patients. Dose escalation for the former was from 59.4 to g5.4GyE in 10% increments and for the latter from 68.4 to 79.2GyE in 5% increments, respectively. Grade Ill radiation pneumonitis occurred in 3 out of 81 patients (2.7%). Local control rates in the former and the latter fractionation Courses were 64% and 84%, respectively. There were 15 in-field and 4 marginal recurrences, with the total recurrence rate being 23.2% (19/82). In-field recurrence in the former shows a significant dose-dependence. The 5 year overall and cause-specific survival rate for the 47 patients of the first fractionation group was 40% and 60%, and that for the 34 patients of the second fractionation group was 50% and 63%, respectively. The following conclusions can be drawn from our study:, 1) Respiratory-gated irradiation and 4 portal irradiation excluding opposed ports proved successful in reducing the incidence of radiation pneumonitis, 2) the development of a copy paste irradiation technique helped prevent marginal recurrence, 3) 72GyE was determined as the optimal dose for the 9 fraction regimen, and 4) the early detection in the regular check-ups followed by elective nodal irradiation(ENl)with carbon beams prevented the survival rate from decreasing due to restricted regional node metastasis. As the next step, a phase II study using 72GyE spread into 9 fractions over 3 weeks was performed from April 1999 to December 2000 on 50 patients (51 lesions) were treated. There was no instance of Grade Ill radiation pneumonitis and the local control rate attained 98% (50/51). The 4 year overall and cause-specific survival rates were 74% (stagelA:83%, lB:57%) and 85% (stagelA:gO%, lB:81%), respectively. Carbon ion radiotherapy, which is an excellent new modality in QOL and ADL, is thus a valid alternative to surgery for stage I NSCLC especially for elderly and inoperable patients.
piiq
Robatic (da Vinci Robot) placement of I 125 seeds after wedge resection for lung cancer
Julianna Pisch, Mohamoud Gaildon, Robert Ashton, Scott Belsley, Karen McGinnis, Cliff Connery. Beth Israel Medical Center, New York, USA
Introduction: Limited wedge resection for lung cancer have been associated with an increased risk of local recurrence. In patients with limited pulmonary reserve or with medical illness precluding lobectomy external irradiation is seldom a treatment of choice because of resultant chronic fibrosis to a large lung volume. Thoracoscopic wedge resection and direct I - 125 seed suture implant cannot be effectively performed due to technical constraints with intracorporeal suturing. I- 215 seeds embedded in mesh were placed over the resected area by other investigators. Although this method is feasible via videoassisted surgery (VATS) techniques, a controlled accurate dose distribution is questionable due to displacement and/or folding of the mesh. To overcome the technical difficulties of direct intramural seed placement by VATS methods we used the da Vinci Robot with 3D visualization to place I- 125 seeds into the resection margin. Methods and Materials: Young well developed pigs with acceptable chest cavity size were used for this feasibility study. The protocol was approved by the Institutional Animal Care and Use Committee (IACUC).We performed the surgery and seed placement in the animal laboratory. General anesthesia with selective intubation was performed. The pig was positioned on his side. Appropriate, and usual preoperative skin preparation and draping was done. Sterile condition was maintained trough the surgery. Video camera recorded the procedure. As a first step VATS wedge resection was petformed.The da Vinci Robot was than positioned in the chest cavity. Under direct 3 D visualization I- 125 dummy seed in suture (Amersham Health, RAPID Strand) were sawn into the resection area. Two different technique were used - 1: the running longitudinal seed placement in three rows and the 2: looping technique. Seed numbers conformed to the length of resection. Orthogonal radiographs for dose calculation were taken in the operating room while the pig was under anesthesia. Results: Two pigs were sacrificed. Dosimetric calculations were done in two separate lobes. We aimed for finding the differences in dose distribution between the two different seed placement method. The number of seeds was tailored to the length of resection. Seed strength was equal for both technique.but
4 separate calculations were done with two hypothetical seed strength (0.5 mCi or 0.6 mCi)The looping technique used 10 seeds, (2.5 cm resection length) the running longitudinal technique used 16 seeds (4.4.cm resection length). The distance between seeds and sutures was kept to IO mm. For 3D calculations the Variseed 6.7 (Build 1312), for isodose display the Pinnacle V.5.2g software was used. Dose to volumes, seed strength: 0.5 mCi #I technique - Vi20 = 9.86 cc, V140 = 7.92 cc, #2 technique - Vi20 = 4.58 cc, V140 = 3.62 cc, seed strength: 0.6 mCi #I technique - V120 = 12.86 cc, VI40 = 10.28 cc, #2technique - V120 = 6.02 cc, V140 = 4.76 cc. Conclusion: This method gives excellent visualization and control of seed placement without undue risk to the patientsThe dose distribution between the 2 placement is comparable and both is acceptable. The seed strength should be tailored to the length of resection.On the average a volume of 8.3 cc is well covered with IO-17 seed with a strength of 0.5- 0.6 mCi and delivers 120-140. Gy to a volume of 8.3 cc.This technique avoids thoracotomy, saves hospital recovery time and may be utilizedin any Hospital with Robotic Surgery. Based on this study we are planning a feasibilityprotocol for lung cancer patients treated with VATS wedge resection.
I P 166
The significance of clinically staged bilateral mediastinal or supraclavicular adenopathy in patients with stage N3 non-small cell lung center
Sanq-Wook Lee’, Eun Kyung Cho?, Jong Hoon Kim*, Seung Do Ahr?, Jung Shin Lee3, Cheolwon Suh3, Sang We Kim3, Dong Soon Kim3, Woo Sung Kim3, Sang Do Lee3. ’ Departmenf of Radiation Onco/ogx Asan Medical Center, University of U/San, Seoul, Korea; ‘Departments of Radiation Oncology, Asan Medical Center, University of U/San, Seoul, Korea; 3 Departments of Infernal Medicine, Asan Medical Center, University of Wan, Seoul, Korea
Background: To evaluate the difference of the patterns of failure and treatment of outcome with concurrent chemoradiotherapy between clinical stage N2 and N3 in the locally advanced unresectable stage Ill non-small cell lung cancer (NSCLC). Methods: of 186 patients with gross mediastinal node positive non-small cell lung cancer received concurrent chemoradiation therapy at Asan Medical Center, University of Ulsan College of Medicine in Seoul, Korea between 1993 and 2000. Follow-up period was 1 to 65 month (median, 13 months). The patterns of failure and treatment of outcomes of N2 and N3 were retrospectively analyzed. Results: There were 170 men and 16 women, for a man-women ratio of IO to 1. The age of patients ranging from 37 to 76 years (median, 60 years). Number of patients with N2 and N3 were 91 and 95, respectively. Supraclavicular node metastasis showed in 35 patients. Distant metastasis free survival rate of N2 and N3 were 54% and 49% (p=O.6305). Overall survival rate of N2 and N3 were 21% and 14% (p=O.3236). There were no stastistically significant differences in distant metastasis free and overall survival rate by two group. Progression free survival rate were statistically significant differences in the supraclavicular fossae node positive or not (p=O.OOS). Locoregional failure within radiation fields was major patterns of failure. Conclusion: There were lack of differences of patterns of failure and treatment outcome with concurrent chemoradiation treatment. However, in this study, supraclavicular node metastasis patients were considered incurable disease. Therefore further investigation of treatment scheme were needed in this cases. ElP 167
p53 status and its in vitro relation to radiosensitivity lung cancer
in
Michael Berqqvist’, Daniel Brattstrom’, Patrik Hesselius’, Joachim Gullbo2, Gunnar Wagenius’ , Ola Brodin3. ’ Uppsala University Hospifal, Uppsala, Sweden; 2 Uppsala University Hospital, Sweden, Uppsala; 3 Huddinge Universitets Sjukhus, Uppsala, Sweden The following study was designed to investigate if mutations within the ~53 gene are associated with radiation responsiveness. Nine human lung cancer cell lines were examined (four SCLC and five NSCLC cell lines). CDNA-based sequencing of the entire ~53 gene was performed. Data from the clonogenic assay were studied to obtain information concerning radioresponsiveness.All cell lines expressed mutations, six were missence mutations and three were deletions. A statistical significant increased radiosensitivity was found for mutations in exon 7 (p=O.Oi 9), compared with the other mutations localised within different exons of ~53. We conclude that ~53 mutations in exon 7 were statistically associated with increased radiation sensitivity in these human lung cancer cell lines, when compared to other mutations within the ~53 gene.