Phillippe Coucke - Academia.edu (original) (raw)
Papers by Phillippe Coucke
Radiotherapy and Oncology, 2015
Purpose/Objective: To compare half (H-arc)-vs. quarter-arc (Q-arc) VMAT simultaneously integrated... more Purpose/Objective: To compare half (H-arc)-vs. quarter-arc (Q-arc) VMAT simultaneously integrated boost (SIB) approach to further reduce normal breast tissue dose burden using hypofractionated whole breast irradiation. Materials and Methods: Fifty-eight patients were included in this study using Pinnacle 9.6 (Philips, Best, NL). For the breast (PTV1) irradiation two tangential field-in-field beams were used, while treating the boost (PTV2) volume a single VMAT was applied. SIB was optimized using inverse SmartARC technique taking into account the dose contribution of the initial breast tangents. For all cases a tangent-to-tangent 180° arc-(H-arc, single class solution) and a tumor bed location adapted 90-110° arcs (Q-arcs, two set of class solution) were created. Ipsilateral lung (IL), heart (H), contralateral breast (CB) were contoured as OARs. The following DVH parameters were used for comparison: V107 (107% of breast prescription dose) for PTV1 and PTV1-2 (PTV1 excluding the PTV2 volume), V95 (95% of boost prescription) for PTV1-2 and PTV2, and V107 for PTV2 (107% of the boost prescription). For the IL V18, for the H V15, Dmean, D2 and for the CB Dmean were compared using paired two tailed ttest with a significance level of p<0.05. Results: There were no statistical differences between H-arc vs. Q-arcs VMAT SIB techniques in terms of PTV2 coverage (V95: 96.7 vs. 96.3 %, p=0.55) and conformity (V95boost for PTV1-PTV2: 2.2 vs. 1.9 %, p=0.28). Q-arcs VMAT SIB significantly reduced normal breast tissue dose burden (V107breast for PTV1-PTV2: 24.7 vs 21.7 %, p= 0.029). No statistical differences were observed between the dosevolume parameters of the OARs (IL V18: 11.9 vs. 11.3 %,
Radiotherapy and Oncology, 2014
Introduction.-La dysplasie de trochlée est un des éléments majeurs de l'instabilité fémoropatella... more Introduction.-La dysplasie de trochlée est un des éléments majeurs de l'instabilité fémoropatellaire. Si sa correction par trochléoplastie apparaît logique, le résultat à long terme de cette intervention n'est pas connu et il persiste une incertitude sur l'évolution arthrosique. Aussi, nous avons mené une étude rétrospective d'une série de trochléoplasties de creusement au recul de 15 ans avec pour objectifs : (1) d'évaluer à long terme les résultats cliniques et le taux radiologique d'arthrose ; (2) de préciser les résultats en fonction du type d'instabilité et du grade de la dysplasie. Hypothèse.-La trochléoplastie de creusement est une intervention efficace sur la stabilisation de l'articulation fémoropatellaire sans augmenter le risque d'arthrose. Patients et méthodes.-Cette étude analyse rétrospectivement 34 trochléoplasties de creusement au moyen de scores cliniques (scores IKS, Lillois, Kujala et Oxford) et leurs résultats radiologiques (stade d'arthrose selon Iwano) au recul moyen de 15 ans (12-19 ans). Une plastie d'Insall était associée systématiquement et une transposition de la tubérosité tibiale antérieure dans 17 cas (7 transpositions préalables). Résultats.-Aucune récidive d'instabilité objective n'a été observée. Six genoux ont été repris par prothèse pour arthrose et un par transposition de la tubérosité tibiale pour douleur et dérobements au recul moyen de 7 ans (2-16). Les scores moyens Lillois, Kujala et IKS passaient respectivement de 53,3 (30-92), 55 (13-75) et 127 (54-184) en préopératoire à 61,5 (25-93), 76 (51-94) et 152,4 (66-200) au recul (p < 0,05) (reprises incluses). Les résultats fonctionnels étaient significativement meilleurs pour les dysplasies avec éperon (score IKS 168 [127-200] versus 153 [98-198] et Kujula 81,5 [51-98] versus 76 [51-94] [p < 0,05]). Les patients étaient satisfaits dans 65 % des cas et le score Oxford total moyen étaient de 24,1 points/60 (12-45 points). La douleur était occasionnelle ou nulle dans 53 % des cas. La saillie de la trochlée passait de 4,9 mm (3-9 mm) à −1,2 mm (−7-4 mm). L'arthrose fémoropatellaire, 10 cas en préopératoire mais aucune > Iwano 2, était présente dans 33/34 cas avec 20 cas > Iwano 2 (65 %) au recul. Discussion.-La trochléoplastie de creusement permet la stabilité fémoropatellaire même en cas de dysplasie sévère pour lesquelles elle donne de meilleurs résultats fonctionnels à long terme. En revanche, elle ne prévient pas l'arthrose fémoropatellaire. Elle doit être réservée aux dysplasies sévères avec éperon en l'associant à des gestes de réalignement de l'appareil extenseur. Niveau de preuve.-IV, étude rétrospective de cohorte.
Cancer/Radiothérapie, 1998
Journal of the American Society of Echocardiography, 2013
Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in l... more Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed.
International Journal of Radiation Oncology*Biology*Physics, 1998
Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from ... more Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (؊1.8) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (؊3.6). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.
Radiotherapy and Oncology, 2014
S37 ESTRO 33, 2014 (6.71±1.09%) was slightly worse than VMAT Full (5.37±1.33%) although could not... more S37 ESTRO 33, 2014 (6.71±1.09%) was slightly worse than VMAT Full (5.37±1.33%) although could not be shown statistically significant (p=0.054). All techniques achieved similar CN. Treatment delivery times for HT (332.7±87.6s, p<0.05), VMAT Full (158.7±2.2s, p<0.001) and VMAT Ltd (136.0±10.2s, p<0.001) are significantly shorter than IMRT (416.2±31.2s). Conclusions: Our results indicate that HT provides better sparing of spinal cord in treating thyroid cancers. No significant advantage of sparing larynx, oesophagus or oral cavity could be found in any of the treatment techniques. All treatment techniques have similar target homogeneity and conformity. Limiting the arc span from posterior neck in VMAT planning does not help in spinal cord sparing but scarifying target homogeneity slightly. OC-0090 Clinical introduction of an all-in class solution for prone breast hypofractionated SIB with multibeam IMRT
Revue médicale de Liège
Breast reconstruction is nowadays integral part of the treatment of breast cancer. When it is pro... more Breast reconstruction is nowadays integral part of the treatment of breast cancer. When it is proposed as an immediate reconstruction, the plastic surgeon has to deal with several constraints. The coverage of the patients that must benefit from a mastectomy is complicated by additional treatments of radiotherapy. We propose, in this work, a multidisciplinary splitting of the patients into specific subgroups. An immediate reconstruction will be proposed to certain patients considering the adjuvant radiotherapy. The choices of orientation are complex and a scarce literature on this subject does not allow us to guide in a systematic way all the patients. More studies, with a prospective design, are necessary to guide the patients wishing an immediate reconstruction associated with a radiotherapy after mastectomy.
International Journal of Radiation Oncology*Biology*Physics, 1998
Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from ... more Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (؊1.8 ) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (؊3.6 ). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.
Journal of the American Society of Echocardiography, 2013
Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in l... more Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed. (J Am Soc Echocardiogr 2013;26:1013-32.)
Journal of the American College of Cardiology, 2004
Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from ... more Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (؊1.8 ) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (؊3.6 ). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.
Radiotherapy and Oncology, 2015
Purpose/Objective: To compare half (H-arc)-vs. quarter-arc (Q-arc) VMAT simultaneously integrated... more Purpose/Objective: To compare half (H-arc)-vs. quarter-arc (Q-arc) VMAT simultaneously integrated boost (SIB) approach to further reduce normal breast tissue dose burden using hypofractionated whole breast irradiation. Materials and Methods: Fifty-eight patients were included in this study using Pinnacle 9.6 (Philips, Best, NL). For the breast (PTV1) irradiation two tangential field-in-field beams were used, while treating the boost (PTV2) volume a single VMAT was applied. SIB was optimized using inverse SmartARC technique taking into account the dose contribution of the initial breast tangents. For all cases a tangent-to-tangent 180° arc-(H-arc, single class solution) and a tumor bed location adapted 90-110° arcs (Q-arcs, two set of class solution) were created. Ipsilateral lung (IL), heart (H), contralateral breast (CB) were contoured as OARs. The following DVH parameters were used for comparison: V107 (107% of breast prescription dose) for PTV1 and PTV1-2 (PTV1 excluding the PTV2 volume), V95 (95% of boost prescription) for PTV1-2 and PTV2, and V107 for PTV2 (107% of the boost prescription). For the IL V18, for the H V15, Dmean, D2 and for the CB Dmean were compared using paired two tailed ttest with a significance level of p<0.05. Results: There were no statistical differences between H-arc vs. Q-arcs VMAT SIB techniques in terms of PTV2 coverage (V95: 96.7 vs. 96.3 %, p=0.55) and conformity (V95boost for PTV1-PTV2: 2.2 vs. 1.9 %, p=0.28). Q-arcs VMAT SIB significantly reduced normal breast tissue dose burden (V107breast for PTV1-PTV2: 24.7 vs 21.7 %, p= 0.029). No statistical differences were observed between the dosevolume parameters of the OARs (IL V18: 11.9 vs. 11.3 %,
Radiotherapy and Oncology, 2014
Introduction.-La dysplasie de trochlée est un des éléments majeurs de l'instabilité fémoropatella... more Introduction.-La dysplasie de trochlée est un des éléments majeurs de l'instabilité fémoropatellaire. Si sa correction par trochléoplastie apparaît logique, le résultat à long terme de cette intervention n'est pas connu et il persiste une incertitude sur l'évolution arthrosique. Aussi, nous avons mené une étude rétrospective d'une série de trochléoplasties de creusement au recul de 15 ans avec pour objectifs : (1) d'évaluer à long terme les résultats cliniques et le taux radiologique d'arthrose ; (2) de préciser les résultats en fonction du type d'instabilité et du grade de la dysplasie. Hypothèse.-La trochléoplastie de creusement est une intervention efficace sur la stabilisation de l'articulation fémoropatellaire sans augmenter le risque d'arthrose. Patients et méthodes.-Cette étude analyse rétrospectivement 34 trochléoplasties de creusement au moyen de scores cliniques (scores IKS, Lillois, Kujala et Oxford) et leurs résultats radiologiques (stade d'arthrose selon Iwano) au recul moyen de 15 ans (12-19 ans). Une plastie d'Insall était associée systématiquement et une transposition de la tubérosité tibiale antérieure dans 17 cas (7 transpositions préalables). Résultats.-Aucune récidive d'instabilité objective n'a été observée. Six genoux ont été repris par prothèse pour arthrose et un par transposition de la tubérosité tibiale pour douleur et dérobements au recul moyen de 7 ans (2-16). Les scores moyens Lillois, Kujala et IKS passaient respectivement de 53,3 (30-92), 55 (13-75) et 127 (54-184) en préopératoire à 61,5 (25-93), 76 (51-94) et 152,4 (66-200) au recul (p < 0,05) (reprises incluses). Les résultats fonctionnels étaient significativement meilleurs pour les dysplasies avec éperon (score IKS 168 [127-200] versus 153 [98-198] et Kujula 81,5 [51-98] versus 76 [51-94] [p < 0,05]). Les patients étaient satisfaits dans 65 % des cas et le score Oxford total moyen étaient de 24,1 points/60 (12-45 points). La douleur était occasionnelle ou nulle dans 53 % des cas. La saillie de la trochlée passait de 4,9 mm (3-9 mm) à −1,2 mm (−7-4 mm). L'arthrose fémoropatellaire, 10 cas en préopératoire mais aucune > Iwano 2, était présente dans 33/34 cas avec 20 cas > Iwano 2 (65 %) au recul. Discussion.-La trochléoplastie de creusement permet la stabilité fémoropatellaire même en cas de dysplasie sévère pour lesquelles elle donne de meilleurs résultats fonctionnels à long terme. En revanche, elle ne prévient pas l'arthrose fémoropatellaire. Elle doit être réservée aux dysplasies sévères avec éperon en l'associant à des gestes de réalignement de l'appareil extenseur. Niveau de preuve.-IV, étude rétrospective de cohorte.
Cancer/Radiothérapie, 1998
Journal of the American Society of Echocardiography, 2013
Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in l... more Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed.
International Journal of Radiation Oncology*Biology*Physics, 1998
Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from ... more Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (؊1.8) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (؊3.6). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.
Radiotherapy and Oncology, 2014
S37 ESTRO 33, 2014 (6.71±1.09%) was slightly worse than VMAT Full (5.37±1.33%) although could not... more S37 ESTRO 33, 2014 (6.71±1.09%) was slightly worse than VMAT Full (5.37±1.33%) although could not be shown statistically significant (p=0.054). All techniques achieved similar CN. Treatment delivery times for HT (332.7±87.6s, p<0.05), VMAT Full (158.7±2.2s, p<0.001) and VMAT Ltd (136.0±10.2s, p<0.001) are significantly shorter than IMRT (416.2±31.2s). Conclusions: Our results indicate that HT provides better sparing of spinal cord in treating thyroid cancers. No significant advantage of sparing larynx, oesophagus or oral cavity could be found in any of the treatment techniques. All treatment techniques have similar target homogeneity and conformity. Limiting the arc span from posterior neck in VMAT planning does not help in spinal cord sparing but scarifying target homogeneity slightly. OC-0090 Clinical introduction of an all-in class solution for prone breast hypofractionated SIB with multibeam IMRT
Revue médicale de Liège
Breast reconstruction is nowadays integral part of the treatment of breast cancer. When it is pro... more Breast reconstruction is nowadays integral part of the treatment of breast cancer. When it is proposed as an immediate reconstruction, the plastic surgeon has to deal with several constraints. The coverage of the patients that must benefit from a mastectomy is complicated by additional treatments of radiotherapy. We propose, in this work, a multidisciplinary splitting of the patients into specific subgroups. An immediate reconstruction will be proposed to certain patients considering the adjuvant radiotherapy. The choices of orientation are complex and a scarce literature on this subject does not allow us to guide in a systematic way all the patients. More studies, with a prospective design, are necessary to guide the patients wishing an immediate reconstruction associated with a radiotherapy after mastectomy.
International Journal of Radiation Oncology*Biology*Physics, 1998
Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from ... more Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (؊1.8 ) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (؊3.6 ). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.
Journal of the American Society of Echocardiography, 2013
Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in l... more Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed. (J Am Soc Echocardiogr 2013;26:1013-32.)
Journal of the American College of Cardiology, 2004
Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from ... more Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (؊1.8 ) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (؊3.6 ). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.