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53 oral Factors influencing recovery of nasopharyngeal carcinoma with cranial nerve paralysis after radiotherapy
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reporter gone or the p53 gone, and these were used to engineer two AE1/AE3 adenoviral vectors denoted as adv.oriPB-gal, or adv.oriPp53 respectively. Two NPC cell lines, the EBV-negative CNE-2Z, and EBVpositive C666-1, as well as the EBV-negative normal nasopharyngeal fibroblasts KS1, were evaluated. To prove that adv.oriP-mediated B-gal expression was mediated by EBNA1, CNE-2Z cells were stably transfected with EBNA1 cDNA. Western blotting was used to evaluate p53 protein production, and the MTT assay was conducted to determine cell viability after gone transfer. The non-selective adv.CMV.B-gal or adv.CMVp53 were used to determine the extent of EBV-targeted expression by the newly constructed adv.oriP vectors. Resultslnfection of parent CNE-2Z, EBNAl-transfected CNE-2Z, C666-1, and KSl fibroblasts with adv.CMV.B-gaidemonstrated significant expression in all cell lines. In contrast, infection with adv.oriPB-gal demonstrated no expression in the KSI fibroblasts, <1% in the parent CNE-2Z cells, but nearly 100% X-gal pesitivity in the EBNA1-transfected CN E-2Z and C6661 cells. Significant p53 expression was observed in the C666-1 cells 48 hours after infection with adv.oriPp53. Adv.CMVp53 (25 pfu/cell) infection of KS1 and parent CNE-2Z cells demonstrated 20% and 60% cytotoxicity respectively. In contrast, only 5% and 15% cytotoxicity were observed in the same cell lines after treatment with iso-effect doses of adv.oriPp53. Conclusion: We have successfully developed a novel adenoviral vector, that incorporates an EBNAl-responsive element, and provides for selective transcription of a therapeutic gene in EBV-positive NPC cells. This vector will be evaluated further, in combination with other cytotoxic modalities, in order to maximize therapeutic gain in cancer gene therapy. 53
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Factors influencing recovery of nasopharyngeal carcinoma with cranial nerve paralysis after radiotherapy S.F. Wang, A. Wang, R.S. Wang The First Affiliated Hospital, Guangxi Medical University, Nanning, China Purpose: to evaluate the factors influencing recovery of nasopharyngeal carcinoma (NPC) with cranial nerve paralysis after radiotherapy. Methods: from May 1980 through May 1990, 250 NPC patients with cranial nerve paralysis were treated by radiotherapy in our hospital, 52 patients had only one single nerve paralysis and the rest 198 patients had a total 219 nerves parNysis, Results: after radiotherapy, the overall response rate was 78.6%, the major factors influencing recovery were relevant to following items: A. the duration of involvement prior to radiotherapy, the shorter the duration of nerve paralysis, the better chance of recovery; 2. time of nitial recovery, the earlier the time of initial recovery, the more they will recover; 3. the speed of tumor disappearance, the quicker tumor disappearance, the bigger possibility of recovery; 4. anterior group of cranial nerve paralysis was easier to recover than that of posterior group of crania nerve paralysis, involvement of both anterior and posterior cranial nerves was difficult to recover. Conclusions: major factors influencing recovery of NPC with cranial nerve paralysis after radiotherapy were as following: 1. the duration of involvement prior to radiotherapy; 2. time of initial recovery; 3. the speed of tumor disappearance; and 4. anterior or posterior cranial nerves paralysis ? single or multiple nerves involvement ? involvement of both anterior and posterior cranial nerves had a poor prognosis. 54
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High dose re-irradiation by fractionated stereotactic radiation therapy for locally recurrent nasopharynx cancer. Y. Ahn 1, D. Kim 1, S. Huh 1, C. Back 2, D. Lim 1, J. Lee 1, Y. Noh 1 l Samsung Medical Center, Sungkyunkwan Universoty School of Medicine, Dept. of Radiation Oncology, Seoul, Korea 2Samsung Medical Center, Sungkyunkwan University School of Medicine, Dept. of Otorhinolaryngology and Head & Neck Surgery, Seoul, Korea Purpose: Re-irradiation has been accepted as the best policy for recurrent nasopharynx cancer. Delivery of high radiation dose by conventional 2dimensional radiotherapy (RT) techniques has usually been associated with significant complication risk. This is to retrospectively analyze and report the clinical experiences of high dose re-irradiation by fractionated stereotactic radiation therapy (FSRT) for locally recurrent nasopharynx
caRcer. Materials and methods: From May 1995 to June. 2000, FSRT was applied to 20 patients with locally recurrent nasopharynx cancer. Male to female ratio was 13:7 with the median age of 54 years. Histologic types were undifferentiated carcinoma in 10 patients, and squamous cell carcinoma in 10. FSRT was the 2nd RT in 15 patients while it was the 3rd RT in 5 patients. FSRT was applied with the curative intent in 14 patients with local recurrence only, while it served as the palliative measure for local symp-
Wednesday, 31 January 2001
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toms in 6 patients with local recurrence plus regional or distant metastases. Individualized RT planning was performed by XKnife-3 system. The median size of the collimator cone was 6 cm, the median number of the arcs was 4, and the median total arc angle was 120 degree. The treatment schedule was to give five daily fractions per week of 2.5 Gy or 3.0 Gy prescribed at 75%-100% of isocenter dose, and the median total FSRT dose was 54 (45-70) Gy over 3.5 to 5.5 weeks. Results: No unusual acute morbidity other than focal mucositis over the nasopharynx and the oropharynx was observed. After the median followup of 23 months, four local progressions within the FSRT volume and seven deaths were observed. Distant metastases were the main cause of death occurring in five patients. The local control and survival rates at 3 year in all patients were 76.0% and 50.2%, respectively, while those in patients with local recurrence only were 63.3% and 68.6%, respectively. Conclusions: High dose re-irradiation by FSRT for locally recurrent nasopharynx cancer resulted in satisfactory local tumor control, which not only enabled local symptom palliation but also cast a light on the chance of cure for those with isolated local recurrence. 55
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Design and fabrication of a stereotactic Iocaliser for extracranial head and neck radiotherapy C. Hombv 1, C. Shinopulos, 2 L. Finn2, L. Peters 2 1peter Maccallum Cancer Institute, Division of Radiation Oncology, Melbourne, Australia 2Radionics, Burlington, USA Purpose: To design and fabricate a Iocaliser for stereotactic radiotherapy of extra-cranial head and neck cancers Methods: Design criteria were developed for a device to attach to the couch mount of the standard BRW stereotactic head frame incorporating patient immobilisation and position verification features and fiducial markers for stereotactic Iocalisation of target volumes. Prototype devices were fabricated and tested in the clinical setting. After several iterations, the final product was manufactured Results: Patient set-up reproducibilty was specified as _+3mm. In practice, this has been achieved only for reference points at or above the level of the larynx. The system has the following features: A honeycomb carbon fibre baseplate with XYZ fine adjustments, a double sided bite-block mechanism with longitudinal vertical and rotational freedom of movement for fixation of the maxilla and mandible where necessary, a customised head mould support and shoulder restraints. All adjustable movements are calibrated for reproducibility. There are no metal parts restricting beam access to the face or upper neck. The stereotactic box Iocaliser incorporates depth probes to verify patient position relative to the stereotactic fiducials and translucent sheets to provide optical checks of beam position and shape. Conclusions: A clinically useful and practical system has been developed with excellent reproducibility of set-up from the skull base to the larynx. The system is currently in use with the Radionics Miniature Multileaf Collimator for small volume, boost, and re-treatment applications 56
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Risk of symptomatic temporal lobe necrosis following various fractionation schedules for nasopharyngeal carcinoma. A.W.M. Lee 1, S.Y. Tung2, D.L.W. Kwong 3, P.M.L. Tee4, T.W. Leung2, P.M. Wu3, S.F. Leung 4, R. Chappell5 J.F. Fowler 6, L.J. Peters 7 1pamela Youde Nethersole Eastern Hospital, Clinical Oncology, Hong Kong, China 2Tuen Mun Hospital, Clinical Oncology, Hong Kong, China 3Queen Mary Hospital, Clinical Oncology, Hong Kong, China 4prince of Wales Hospital, Clinical Oncology, Hong Kong, China 5University of Wisconsin, Statistics, Madison, USA 6Univ. of Wisconsin, Dept. Human Oncology, Madison, USA 7peter Mac Callum Cancer Ctr, Melbourne, Australia Purpose: To study the factors affecting the risk of symptomatic temporal lobe necrosis (STLN) following different fractionation schedules for nasopharyngeal carcinoma. Methods: A retrospective analysis was performed on 1032 patients who completed a course of radical radiotherapy for T1-2 primary tumors in Hong Kong 1990-1995. They were treated in four different centers with similar techniques but different fractionations. Forty-eight patients were irradiated twice daily (BID) with an interfractlon interval of 6 hours for part of the course, while the rest were irradiated once daily throughout (QD). The median total dose (D) was 62.5 (range 50.4-71.2) Gy, dose per fraction (d) was 2.5 (range 1.6-4.2) Gy, and overall treatment times (T) were
reporter gone or the p53 gone, and these were used to engineer two AE1/AE3 adenoviral vectors denoted as adv.oriPB-gal, or adv.oriPp53 respectively. Two NPC cell lines, the EBV-negative CNE-2Z, and EBVpositive C666-1, as well as the EBV-negative normal nasopharyngeal fibroblasts KS1, were evaluated. To prove that adv.oriP-mediated B-gal expression was mediated by EBNA1, CNE-2Z cells were stably transfected with EBNA1 cDNA. Western blotting was used to evaluate p53 protein production, and the MTT assay was conducted to determine cell viability after gone transfer. The non-selective adv.CMV.B-gal or adv.CMVp53 were used to determine the extent of EBV-targeted expression by the newly constructed adv.oriP vectors. Resultslnfection of parent CNE-2Z, EBNAl-transfected CNE-2Z, C666-1, and KSl fibroblasts with adv.CMV.B-gaidemonstrated significant expression in all cell lines. In contrast, infection with adv.oriPB-gal demonstrated no expression in the KSI fibroblasts, <1% in the parent CNE-2Z cells, but nearly 100% X-gal pesitivity in the EBNA1-transfected CN E-2Z and C6661 cells. Significant p53 expression was observed in the C666-1 cells 48 hours after infection with adv.oriPp53. Adv.CMVp53 (25 pfu/cell) infection of KS1 and parent CNE-2Z cells demonstrated 20% and 60% cytotoxicity respectively. In contrast, only 5% and 15% cytotoxicity were observed in the same cell lines after treatment with iso-effect doses of adv.oriPp53. Conclusion: We have successfully developed a novel adenoviral vector, that incorporates an EBNAl-responsive element, and provides for selective transcription of a therapeutic gene in EBV-positive NPC cells. This vector will be evaluated further, in combination with other cytotoxic modalities, in order to maximize therapeutic gain in cancer gene therapy. 53
oral
Factors influencing recovery of nasopharyngeal carcinoma with cranial nerve paralysis after radiotherapy S.F. Wang, A. Wang, R.S. Wang The First Affiliated Hospital, Guangxi Medical University, Nanning, China Purpose: to evaluate the factors influencing recovery of nasopharyngeal carcinoma (NPC) with cranial nerve paralysis after radiotherapy. Methods: from May 1980 through May 1990, 250 NPC patients with cranial nerve paralysis were treated by radiotherapy in our hospital, 52 patients had only one single nerve paralysis and the rest 198 patients had a total 219 nerves parNysis, Results: after radiotherapy, the overall response rate was 78.6%, the major factors influencing recovery were relevant to following items: A. the duration of involvement prior to radiotherapy, the shorter the duration of nerve paralysis, the better chance of recovery; 2. time of nitial recovery, the earlier the time of initial recovery, the more they will recover; 3. the speed of tumor disappearance, the quicker tumor disappearance, the bigger possibility of recovery; 4. anterior group of cranial nerve paralysis was easier to recover than that of posterior group of crania nerve paralysis, involvement of both anterior and posterior cranial nerves was difficult to recover. Conclusions: major factors influencing recovery of NPC with cranial nerve paralysis after radiotherapy were as following: 1. the duration of involvement prior to radiotherapy; 2. time of initial recovery; 3. the speed of tumor disappearance; and 4. anterior or posterior cranial nerves paralysis ? single or multiple nerves involvement ? involvement of both anterior and posterior cranial nerves had a poor prognosis. 54
oral
High dose re-irradiation by fractionated stereotactic radiation therapy for locally recurrent nasopharynx cancer. Y. Ahn 1, D. Kim 1, S. Huh 1, C. Back 2, D. Lim 1, J. Lee 1, Y. Noh 1 l Samsung Medical Center, Sungkyunkwan Universoty School of Medicine, Dept. of Radiation Oncology, Seoul, Korea 2Samsung Medical Center, Sungkyunkwan University School of Medicine, Dept. of Otorhinolaryngology and Head & Neck Surgery, Seoul, Korea Purpose: Re-irradiation has been accepted as the best policy for recurrent nasopharynx cancer. Delivery of high radiation dose by conventional 2dimensional radiotherapy (RT) techniques has usually been associated with significant complication risk. This is to retrospectively analyze and report the clinical experiences of high dose re-irradiation by fractionated stereotactic radiation therapy (FSRT) for locally recurrent nasopharynx
caRcer. Materials and methods: From May 1995 to June. 2000, FSRT was applied to 20 patients with locally recurrent nasopharynx cancer. Male to female ratio was 13:7 with the median age of 54 years. Histologic types were undifferentiated carcinoma in 10 patients, and squamous cell carcinoma in 10. FSRT was the 2nd RT in 15 patients while it was the 3rd RT in 5 patients. FSRT was applied with the curative intent in 14 patients with local recurrence only, while it served as the palliative measure for local symp-
Wednesday, 31 January 2001
St5
toms in 6 patients with local recurrence plus regional or distant metastases. Individualized RT planning was performed by XKnife-3 system. The median size of the collimator cone was 6 cm, the median number of the arcs was 4, and the median total arc angle was 120 degree. The treatment schedule was to give five daily fractions per week of 2.5 Gy or 3.0 Gy prescribed at 75%-100% of isocenter dose, and the median total FSRT dose was 54 (45-70) Gy over 3.5 to 5.5 weeks. Results: No unusual acute morbidity other than focal mucositis over the nasopharynx and the oropharynx was observed. After the median followup of 23 months, four local progressions within the FSRT volume and seven deaths were observed. Distant metastases were the main cause of death occurring in five patients. The local control and survival rates at 3 year in all patients were 76.0% and 50.2%, respectively, while those in patients with local recurrence only were 63.3% and 68.6%, respectively. Conclusions: High dose re-irradiation by FSRT for locally recurrent nasopharynx cancer resulted in satisfactory local tumor control, which not only enabled local symptom palliation but also cast a light on the chance of cure for those with isolated local recurrence. 55
oral
Design and fabrication of a stereotactic Iocaliser for extracranial head and neck radiotherapy C. Hombv 1, C. Shinopulos, 2 L. Finn2, L. Peters 2 1peter Maccallum Cancer Institute, Division of Radiation Oncology, Melbourne, Australia 2Radionics, Burlington, USA Purpose: To design and fabricate a Iocaliser for stereotactic radiotherapy of extra-cranial head and neck cancers Methods: Design criteria were developed for a device to attach to the couch mount of the standard BRW stereotactic head frame incorporating patient immobilisation and position verification features and fiducial markers for stereotactic Iocalisation of target volumes. Prototype devices were fabricated and tested in the clinical setting. After several iterations, the final product was manufactured Results: Patient set-up reproducibilty was specified as _+3mm. In practice, this has been achieved only for reference points at or above the level of the larynx. The system has the following features: A honeycomb carbon fibre baseplate with XYZ fine adjustments, a double sided bite-block mechanism with longitudinal vertical and rotational freedom of movement for fixation of the maxilla and mandible where necessary, a customised head mould support and shoulder restraints. All adjustable movements are calibrated for reproducibility. There are no metal parts restricting beam access to the face or upper neck. The stereotactic box Iocaliser incorporates depth probes to verify patient position relative to the stereotactic fiducials and translucent sheets to provide optical checks of beam position and shape. Conclusions: A clinically useful and practical system has been developed with excellent reproducibility of set-up from the skull base to the larynx. The system is currently in use with the Radionics Miniature Multileaf Collimator for small volume, boost, and re-treatment applications 56
oral
Risk of symptomatic temporal lobe necrosis following various fractionation schedules for nasopharyngeal carcinoma. A.W.M. Lee 1, S.Y. Tung2, D.L.W. Kwong 3, P.M.L. Tee4, T.W. Leung2, P.M. Wu3, S.F. Leung 4, R. Chappell5 J.F. Fowler 6, L.J. Peters 7 1pamela Youde Nethersole Eastern Hospital, Clinical Oncology, Hong Kong, China 2Tuen Mun Hospital, Clinical Oncology, Hong Kong, China 3Queen Mary Hospital, Clinical Oncology, Hong Kong, China 4prince of Wales Hospital, Clinical Oncology, Hong Kong, China 5University of Wisconsin, Statistics, Madison, USA 6Univ. of Wisconsin, Dept. Human Oncology, Madison, USA 7peter Mac Callum Cancer Ctr, Melbourne, Australia Purpose: To study the factors affecting the risk of symptomatic temporal lobe necrosis (STLN) following different fractionation schedules for nasopharyngeal carcinoma. Methods: A retrospective analysis was performed on 1032 patients who completed a course of radical radiotherapy for T1-2 primary tumors in Hong Kong 1990-1995. They were treated in four different centers with similar techniques but different fractionations. Forty-eight patients were irradiated twice daily (BID) with an interfractlon interval of 6 hours for part of the course, while the rest were irradiated once daily throughout (QD). The median total dose (D) was 62.5 (range 50.4-71.2) Gy, dose per fraction (d) was 2.5 (range 1.6-4.2) Gy, and overall treatment times (T) were