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100High dose rate brachytherapy in the treatment of endo-bronchial metastasis of extrapulmonary malignancies
Posters
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report the spatial and temporal distribution of dose to target volume, partial target structures and structures at risk. Acknowledgement: these recommendations are now part of the recommendations of the DGMP report 16: guideline for Medical Physical Aspects of Intrasvascular Srachytherapy (www.dgmp.de), those of the revision draft of the AAMP TG 60 Report (AAPM Subcommittee Intrasvascular Brachytherapy Physics) and of those recommendations of GEC-ESTRO (EVA). 97
poster
Novel optimisation of endovascular brachytherapy - targeted radioimmunotherapy. E.C. Sims 1, M.E.B. Powelt2, M.T. Rothman 1,3, T.D. Warner 1 1Depts. of Cardiac, Vascular & Inflammation Research, 2Clinical Oncology & 3Cardiology, Ban's & The London Queen Mary's School of Medicine & Dentistry, United Kingdom Introduction: coronary artery brachytherapy is the most exciting breakthrough in cardiology of the last decade. Currently used techniques necessitate irradiation immediately post angioplasty, which leaves little scope to investigate key radiobiological issues. These include defining the optimal dose and fractionation schedule, timing of radiation delivery and radioprotection. By inserting an antigen-coated stent at the time of angioplasty, we have developed a new technique enabling targeted radiotherapy to be delivered after angioplasty using radiolabelled antibody. This innovation allows the important issues of dose scheduling to be evaluated and minimizes radiation exposure to the medical team. Method: 15mm metal stents were incubated in biotin-BSA (expt. 1), digoxin-BSA (expt.2) or PBS as control to absorb antigen (Ag). Commercially available anti biotin antibody (Ab) and anti digoxin Fab fragments were labeled with 125-1 in an iodination suite (24-32 kBq/pg). Ag-coated stents were placed individually in the aortae of heparinised Wistar rats using an angioplasty balloon and the aortae were repaired. Return and maintenance of blood flow was confirmed by Doppler ultrasound of the lilac vessels. Radiolabelled Ab/Fab was then injected intravenously and the animals were sacrificed after 2 hrs. The stents were carefully dissected out and captured radioactivity was recorded in a gamma counter. Organ samples were counted simultaneously to assess potential toxicity of the treatment allowing antibody distribution and clearance to be estimated. Results: groups quoted as mean ± standard error. Uptake of radioantibody by antigen-coated stents was significantly greater than control with minimal uptake by uncoated stents. Clearance of radioantibody was related to molecular weight being quicker with smaller Fab fragments. Expt. Ag N= Counts/min kBq Ab bound ng/stent P value 1 biotin 3 27271 0.46 14.1±1.8 0.002 PBS 3 1071 0.02 0.6:~0.2 2 digoxin 4 42108 0.70 29±1 <10-4 2 PBS 4 1752 0.03 1.2±-0.4 Conclusion: this is the first study to demonstrate successful delivery of radiation to stents after the angioplasty procedure. Future aims are to maximize antigen loading on stents and to develop an antibody-antigen pair with optimised pharmacokinetics. This exciting technique promises immense therapeutic benefit in humans, not least because it suggests a means of fractionating therapy, thereby decreasing dose per fraction and the risk of late radiation effects.
LUNG TUMOURS 98
poster
Endobronchial high dose rate brachytherapy (HDR-BT) in the treatment of patients with lung cancer and with histology positive margins after sleeve Iobectomy (SL) or pneumonectomy (SP)o Results on 14 patients. R. Mazzarotto, O. Lora, L. Loreggian, F. Rea 1, M. Loy 1, F. Sartori 1, U. Fantoni2, G. Di Vittorio 2, A. Palamidse 2, G. Sotti 1Department of Radiotherapy, Thoracic Surgery and 2pneumology Azienda Ospedaliera di Padova and Padova University - Padova - Italy Introduction: the microscopic positivity of resection margins, at definitive histologic examination, is a rare event occurring in aproximately 1-2% of pts who undergo SL or SP for bronchial cancer. In these cases a further treatment is mandatory. HDR-BT, alone or associated with external radiotherapy (RTE), has been found to be effective in the treatment of bronchial cancer also with radical intent. Material and meethods: from March 1997 to September 2000 14 pts with histology positive margins after SL (11 pts) or SP (3 pts), underwent endobronchial HDR-BT alone (7 pts) or plus RTE (7 pts). Twelve pts were male
and 2 female, with a median age of 65 yrs (min 54 - max 71). Stage was pT1 in 3 pts, pT2 in 7 and pT3 in 4. Six pts were N0, 4 N1 and 4 N2. Seven pts (6 NO and 1 N1) received BT-HDR alone (30 Gy/6F in 5 and 34 Gy/7F in 2 pts) while 7 pts (3 N1 and 4 N2) received RTE (54 Gy/27F) plus BTHDR (15 Gy/3F). Results: after a medium follow-up of 23.5 mths (min 4 and max 46) no pt had relapsed at the site of BT treatment. One pt, previously treated with HDR-BT alone, developed a second cancer in the contra-lateral tung, was treated with RTE and died due to progressive disease 8 mths later. Another pt, previously treated with RTE and HDR-BT, developed a second cancer in the same lung, but distally to the previous one in a non irradiated bronchus, after 10 mths and was treated with HDR-BT alone (35 Gy/7F) obtaining a still lasting CR. No side effects related to HDR-BT treatment were reported. Conclusions: HDR-BT can successfully and safely treat residual persistent disease after SL or SP in pts with lung cancer. 99
poster
High-dose-rate brachytherapy for the treatment of airway tumors - use of special applicator for endotracheal tumors R.C. Fogarotil, G.C. Takayl, J.V. Salvajolil, R.N. Younesl, P.E.R.S. Novaes 1, A.C.A. Pellizzon 1, M.A.C. Maia I, R. Ferrigno 1, M.A. Miziara 2, S. Nakakubo2 1H.A.C. Camargo, Radiotherapy, Sao Paulo, Brazil 21.C.A.V. Carvalho, Radiotherapy, Sao Paulo, Brazil Introduction: this study evaluates efficacy and toxicity of iridium-192 highdose-rate (HDR) endobronchial brachytherapy (EBBT) for the palliation of symptoms caused by airway tumors. Methods: we reviewed the treatment outcomes between 1995 and 2000 in 29 patients (age: 37-75, median: 57) who underwent HDR-EBBTfor the treatment of airways tumors. Twenty-two patients received thoracic external beam irradiation associated with HDR-EBBT, with median dose of 45 Gy, and 8 patients received only HDR-EBBT. Most patients received 15 Gy HDR-EBBT delivered at a distance of 10 mm from the midsource divided into 3 fractions over 3 weeks.The mean treatment lenght was 6 cm (range: 4 to 10 cm). For endotracheal tumors we used a special applicator with four lateral "wings", to avoid the direct contact of the catether with the tracheal walls. The catether was attached to the Microselectron HDR remote afterloading unit with Iridium-192 radioactive (activity: 9-5 Ci). Subjective response was assessed by questionnaire at follow-up, and objective response was assessed by bronchoscopy and chest X-rays or CT scan. Results: Tumor histologic types was: squamous cell carcinoma: 24 (84%), adenocarcinoma: 3 (10%), small cell carcinoma: 1 (3%), metastatic osteosarcoma: 1 (3%). The clinical indications for the treatment was: treatment of lung metastatic tumors: 9 (30%); relapsed prymary lung tumor : 11 (38%); persistent primary lung tumors after first treatment: 5 (17%), palliative treatment for primary lung tumor: 4 (15%). Twenty-two patients (76%) had symptoms: hemoptysis: 14; dyspnea: 9; cough: 10. For these patients the symptomatic improvement rate (subjective response) was 77%. The overall objective response was 79%. All patients with exclusive endotracheal tumors (5 cases), treated with the special applicator showed objective response, with no significant complications. The median acturial survival for entire group was 10.1 months; the median survival was 10.5 months for the patients who had objective response and 3,5 months for patients with no objective response. Complications ocurred in five patients (17%): fistula: 1; massive hemoptysis: 1; and pneumonia: 3 cases. Conclusions: HDR- EBBT effectively palliates most symptoms caused by airway tumors. The objective response was stronger correlated with survival. The special applicator used for endotracheal tumors was efficient, however more studies are necessary for further evaluation of this method. 100 poster High d o s e rate b r a c h y t h e r a p y
in the treatment of endobronchial metastasis of extrapulmonary malignancies
M. Babelova, V. Chovanova, P. Bemat National Cancer Institute, Radiotherapy Department, Bratislava, Slovak Republic In the treatment of bronchial infiltrative stenosis and exophytic lesions remote afterloading HDR brachytherapy with Ir192 is used. During the period from May 1997 to March 2001, 93 patients with endobronchial metastasis were treated in National Cancer Institute in Bratislava. Out of all treated patients 28 had breast cancer as a primary diagnosis. Indications for brachytherapy were symptoms as dyspnea, pneumonitis due to obstruction of an airway, haemoptysis, intractable cough or previous Nd-YAG laser debulking of tumor. Total dose 22.5 Gy was delivered to 10 mm distance from the applicator axis in 3 fractions of 7.5 Gy during three
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report the spatial and temporal distribution of dose to target volume, partial target structures and structures at risk. Acknowledgement: these recommendations are now part of the recommendations of the DGMP report 16: guideline for Medical Physical Aspects of Intrasvascular Srachytherapy (www.dgmp.de), those of the revision draft of the AAMP TG 60 Report (AAPM Subcommittee Intrasvascular Brachytherapy Physics) and of those recommendations of GEC-ESTRO (EVA). 97
poster
Novel optimisation of endovascular brachytherapy - targeted radioimmunotherapy. E.C. Sims 1, M.E.B. Powelt2, M.T. Rothman 1,3, T.D. Warner 1 1Depts. of Cardiac, Vascular & Inflammation Research, 2Clinical Oncology & 3Cardiology, Ban's & The London Queen Mary's School of Medicine & Dentistry, United Kingdom Introduction: coronary artery brachytherapy is the most exciting breakthrough in cardiology of the last decade. Currently used techniques necessitate irradiation immediately post angioplasty, which leaves little scope to investigate key radiobiological issues. These include defining the optimal dose and fractionation schedule, timing of radiation delivery and radioprotection. By inserting an antigen-coated stent at the time of angioplasty, we have developed a new technique enabling targeted radiotherapy to be delivered after angioplasty using radiolabelled antibody. This innovation allows the important issues of dose scheduling to be evaluated and minimizes radiation exposure to the medical team. Method: 15mm metal stents were incubated in biotin-BSA (expt. 1), digoxin-BSA (expt.2) or PBS as control to absorb antigen (Ag). Commercially available anti biotin antibody (Ab) and anti digoxin Fab fragments were labeled with 125-1 in an iodination suite (24-32 kBq/pg). Ag-coated stents were placed individually in the aortae of heparinised Wistar rats using an angioplasty balloon and the aortae were repaired. Return and maintenance of blood flow was confirmed by Doppler ultrasound of the lilac vessels. Radiolabelled Ab/Fab was then injected intravenously and the animals were sacrificed after 2 hrs. The stents were carefully dissected out and captured radioactivity was recorded in a gamma counter. Organ samples were counted simultaneously to assess potential toxicity of the treatment allowing antibody distribution and clearance to be estimated. Results: groups quoted as mean ± standard error. Uptake of radioantibody by antigen-coated stents was significantly greater than control with minimal uptake by uncoated stents. Clearance of radioantibody was related to molecular weight being quicker with smaller Fab fragments. Expt. Ag N= Counts/min kBq Ab bound ng/stent P value 1 biotin 3 27271 0.46 14.1±1.8 0.002 PBS 3 1071 0.02 0.6:~0.2 2 digoxin 4 42108 0.70 29±1 <10-4 2 PBS 4 1752 0.03 1.2±-0.4 Conclusion: this is the first study to demonstrate successful delivery of radiation to stents after the angioplasty procedure. Future aims are to maximize antigen loading on stents and to develop an antibody-antigen pair with optimised pharmacokinetics. This exciting technique promises immense therapeutic benefit in humans, not least because it suggests a means of fractionating therapy, thereby decreasing dose per fraction and the risk of late radiation effects.
LUNG TUMOURS 98
poster
Endobronchial high dose rate brachytherapy (HDR-BT) in the treatment of patients with lung cancer and with histology positive margins after sleeve Iobectomy (SL) or pneumonectomy (SP)o Results on 14 patients. R. Mazzarotto, O. Lora, L. Loreggian, F. Rea 1, M. Loy 1, F. Sartori 1, U. Fantoni2, G. Di Vittorio 2, A. Palamidse 2, G. Sotti 1Department of Radiotherapy, Thoracic Surgery and 2pneumology Azienda Ospedaliera di Padova and Padova University - Padova - Italy Introduction: the microscopic positivity of resection margins, at definitive histologic examination, is a rare event occurring in aproximately 1-2% of pts who undergo SL or SP for bronchial cancer. In these cases a further treatment is mandatory. HDR-BT, alone or associated with external radiotherapy (RTE), has been found to be effective in the treatment of bronchial cancer also with radical intent. Material and meethods: from March 1997 to September 2000 14 pts with histology positive margins after SL (11 pts) or SP (3 pts), underwent endobronchial HDR-BT alone (7 pts) or plus RTE (7 pts). Twelve pts were male
and 2 female, with a median age of 65 yrs (min 54 - max 71). Stage was pT1 in 3 pts, pT2 in 7 and pT3 in 4. Six pts were N0, 4 N1 and 4 N2. Seven pts (6 NO and 1 N1) received BT-HDR alone (30 Gy/6F in 5 and 34 Gy/7F in 2 pts) while 7 pts (3 N1 and 4 N2) received RTE (54 Gy/27F) plus BTHDR (15 Gy/3F). Results: after a medium follow-up of 23.5 mths (min 4 and max 46) no pt had relapsed at the site of BT treatment. One pt, previously treated with HDR-BT alone, developed a second cancer in the contra-lateral tung, was treated with RTE and died due to progressive disease 8 mths later. Another pt, previously treated with RTE and HDR-BT, developed a second cancer in the same lung, but distally to the previous one in a non irradiated bronchus, after 10 mths and was treated with HDR-BT alone (35 Gy/7F) obtaining a still lasting CR. No side effects related to HDR-BT treatment were reported. Conclusions: HDR-BT can successfully and safely treat residual persistent disease after SL or SP in pts with lung cancer. 99
poster
High-dose-rate brachytherapy for the treatment of airway tumors - use of special applicator for endotracheal tumors R.C. Fogarotil, G.C. Takayl, J.V. Salvajolil, R.N. Younesl, P.E.R.S. Novaes 1, A.C.A. Pellizzon 1, M.A.C. Maia I, R. Ferrigno 1, M.A. Miziara 2, S. Nakakubo2 1H.A.C. Camargo, Radiotherapy, Sao Paulo, Brazil 21.C.A.V. Carvalho, Radiotherapy, Sao Paulo, Brazil Introduction: this study evaluates efficacy and toxicity of iridium-192 highdose-rate (HDR) endobronchial brachytherapy (EBBT) for the palliation of symptoms caused by airway tumors. Methods: we reviewed the treatment outcomes between 1995 and 2000 in 29 patients (age: 37-75, median: 57) who underwent HDR-EBBTfor the treatment of airways tumors. Twenty-two patients received thoracic external beam irradiation associated with HDR-EBBT, with median dose of 45 Gy, and 8 patients received only HDR-EBBT. Most patients received 15 Gy HDR-EBBT delivered at a distance of 10 mm from the midsource divided into 3 fractions over 3 weeks.The mean treatment lenght was 6 cm (range: 4 to 10 cm). For endotracheal tumors we used a special applicator with four lateral "wings", to avoid the direct contact of the catether with the tracheal walls. The catether was attached to the Microselectron HDR remote afterloading unit with Iridium-192 radioactive (activity: 9-5 Ci). Subjective response was assessed by questionnaire at follow-up, and objective response was assessed by bronchoscopy and chest X-rays or CT scan. Results: Tumor histologic types was: squamous cell carcinoma: 24 (84%), adenocarcinoma: 3 (10%), small cell carcinoma: 1 (3%), metastatic osteosarcoma: 1 (3%). The clinical indications for the treatment was: treatment of lung metastatic tumors: 9 (30%); relapsed prymary lung tumor : 11 (38%); persistent primary lung tumors after first treatment: 5 (17%), palliative treatment for primary lung tumor: 4 (15%). Twenty-two patients (76%) had symptoms: hemoptysis: 14; dyspnea: 9; cough: 10. For these patients the symptomatic improvement rate (subjective response) was 77%. The overall objective response was 79%. All patients with exclusive endotracheal tumors (5 cases), treated with the special applicator showed objective response, with no significant complications. The median acturial survival for entire group was 10.1 months; the median survival was 10.5 months for the patients who had objective response and 3,5 months for patients with no objective response. Complications ocurred in five patients (17%): fistula: 1; massive hemoptysis: 1; and pneumonia: 3 cases. Conclusions: HDR- EBBT effectively palliates most symptoms caused by airway tumors. The objective response was stronger correlated with survival. The special applicator used for endotracheal tumors was efficient, however more studies are necessary for further evaluation of this method. 100 poster High d o s e rate b r a c h y t h e r a p y
in the treatment of endobronchial metastasis of extrapulmonary malignancies
M. Babelova, V. Chovanova, P. Bemat National Cancer Institute, Radiotherapy Department, Bratislava, Slovak Republic In the treatment of bronchial infiltrative stenosis and exophytic lesions remote afterloading HDR brachytherapy with Ir192 is used. During the period from May 1997 to March 2001, 93 patients with endobronchial metastasis were treated in National Cancer Institute in Bratislava. Out of all treated patients 28 had breast cancer as a primary diagnosis. Indications for brachytherapy were symptoms as dyspnea, pneumonitis due to obstruction of an airway, haemoptysis, intractable cough or previous Nd-YAG laser debulking of tumor. Total dose 22.5 Gy was delivered to 10 mm distance from the applicator axis in 3 fractions of 7.5 Gy during three