To investigate the impact of treatment modality and radiation technique on oncologic outcomes and... more To investigate the impact of treatment modality and radiation technique on oncologic outcomes and toxicity of patients with locally advanced oropharyngeal cancer (OPC). Retrospective analysis of outcomes and toxicity. Between 2000 and 2011, 204 consecutive patients with locally advanced OPC were treated with definitive (chemo)radiotherapy using 3-dimensional conformal (3DCRT) or intensity-modulated radiotherapy (IMRT). Endpoints were local control (LC), regional control (RC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), and toxicity. After a median follow-up of 44 months (range 4-134), the 5-year Kaplan-Meier estimates of LC, RC, DFS, CSS, and OS were 78%, 92%, 60%, 64%, and 48%, respectively. Grade 3 mucositis and dysphagia (feeding-tube dependency) were reported in 75% and 65%, respectively. The overall incidence of grade ≥ 2 and grade 3 late toxicities were 44% and 16%, respectively. Dysphagia and xerostomia were the most frequently reported late toxicity. Chemotherapy was significantly predictive for improved outcomes and increased toxicity. IMRT was significantly correlated with reduced toxicity. Compared to radiation alone, chemoradiotherapy significantly improved oncologic outcomes, but with significantly increased toxicity. Compared to 3DCRT, the introduction of IMRT resulted in a significant reduction of acute and late toxicity with slightly better, or at least comparable, outcomes. Despite the improvements achieved by the implementation of chemo-IMRT, different new strategies to further improve outcome and reduce toxicity need to be thoroughly investigated in prospective, preferably, randomized trials.
International Journal of Radiation Oncology*Biology*Physics, 2012
Purpose/Objective(s): In locally advanced HNSCC, treatment of bilateral RPN to the skull base has... more Purpose/Objective(s): In locally advanced HNSCC, treatment of bilateral RPN to the skull base has been advocated to prevent failure in the contralateral RPN region. In addition, this is a historical practice as it was only possible to treat bilaterally prior to the IMRT era. In view of the relationship between pharyngeal constrictor muscles and swallowing function, we modified our treatment policy in 2007. Thereafter, we eliminated contralateral high level II and contralateral RPN coverage for selected patients (without N2c disease). We retrospectively analyzed the patterns of failure for these patients. Materials/Methods: From 1997 to 2010, 697 previously untreated patients with locally advanced HNSCC received definitive or postoperative IMRT +/chemotherapy. Sites included oropharynx, hypopharynx, larynx, oral cavity, and unknown primary. Two hundred sixty-five patients were treated with definitive IMRT, and 432 with postoperative IMRT. Three hundred seventyfour patients received chemotherapy. Overall, 443 patients were treated before, and 254 after this policy change. In addition to the policy change described above, for patients with N0 disease involving the oral cavity or larynx, BL RTP nodes and high level II nodes were spared. Specifically, high level II nodal coverage in the N0 side of the neck was contoured only up to the level were the posterior belly of the digastric crosses the internal jugular vein, and RTP nodes in the N0 side of the neck were excluded. CTV1 was defined as the tumor bed plus any node positive region of the neck, and received 70 Gy (definitive) and 60 to 66 Gy (postoperative), all at 2.0 Gy/ fraction. CTV2 was defined as the N0 neck, and received 52 to 54 Gy (postoperative) and 56 Gy (definitive), at 1.6 to 1.73 Gy/fraction. Results: Mean follow-up for living patients treated after the policy change was 24 months. Among the 254 patients treated after the policy change 46 (18%) had loco-regional recurrence (LRR) and 38 developed distant metastases. There were 44 in-field failures, 1 marginal failure and 1 out of field failure. To date there have been no failures in the spared high contralateral neck or retropharyngeal lymph node regions. Conclusions: For patients with locally advanced HNSCC exclusive of N2c neck disease, eliminating coverage of the high contralateral level II neck and contralateral RPN is associated with minimal risk of failure in these regions.
Background. To investigate the impact of up-front neck dissection on the outcome of patients with... more Background. To investigate the impact of up-front neck dissection on the outcome of patients with node-positive hypopharyngeal cancer (HPC) treated with (chemo)radiation. Methods. Of 135 consecutive patients with node-positive HPC, 32 patients underwent up-front neck dissection followed by (chemo)radiation (group 1), and 103 patients received definitive (chemo)radiation (group 2). Results. The 3-year regional, local and distant control for groups 1 and 2 were 92% versus 87% (p ¼ .37), 84% versus 72% (p ¼ .15), and 80% versus 62% (p ¼ .08), respectively. High T classification was the only significant predictor for poor overall survival on multivariate analysis (OR ¼ 3.0, p ¼ .02). Acute and late toxicities and the prospectively assessed quality of life were comparable in both groups. Conclusion. Upfront neck dissection followed by (chemo)radiation did not negatively impact on oncologic outcomes, toxicity, or quality of life and therefore is to be regarded as a safe and effective treatment option for small HPC with bulky nodal disease, especially in busy radiation departments with unacceptably long waiting time for definitive (chemo)radiation.
Intracoronary brachytherapy has recently emerged as a new therapy to prevent restenosis. Initial ... more Intracoronary brachytherapy has recently emerged as a new therapy to prevent restenosis. Initial experimental work was achieved in animal models and the results were assessed by histomorphometry. Initial clinical trials used angiography to guide dosimetry and to assess efficacy. Intravascular ultrasound (IVUS) permits tomographic examination of the vessel wall, elucidating the true morphology of the lumen and transmural components, which cannot be investigated on the lumenogram obtained by angiography. This paper reviews the use of IVUS in the clinical studies of brachytherapy conducted to date. IVUS allows clinicians to make a thorough assessment of the remodeling of the vessel and appears to have a major role to play in facilitating understanding of the underlying mechanisms of action in this emerging field. The authors propose that state-of-the-art IVUS techniques should be employed to further knowledge of the mechanisms of action of brachytherapy in atherosclerotic human coronary arteries.
This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response... more This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease.
Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed... more Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in 1H MR spectra of contrast-enhancing tumor at 5-10 min after Gd-contrast administration [Magn. Reson. Med. 37:222-225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0-5, 5-10, and/or 10-15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 +/- 3, 12 +/- 2, and 14 +/- 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.
Investigative Radiology a Journal of Clinical and Laboratory Research, Dec 1, 1995
The anatomic and metabolic changes in human brain tumors treated by radiation therapy were compar... more The anatomic and metabolic changes in human brain tumors treated by radiation therapy were compared using gadolinium-enhanced magnetic resonance imaging and hydrogen (1H) magnetic resonance spectroscopy. The study was intended to assess the potential of 1H magnetic resonance spectroscopy in monitoring response to therapy. Thirteen cases of brain cancer treated by radiation therapy were examined by 1H magnetic resonance spectroscopy and gadolinium-enhanced T1-weighted magnetic resonance imaging and reexamined at 2-month intervals. Follow-up after radiation therapy showed changes in post-gadolinium magnetic resonance imaging contrast that are inversely correlated with the changes in choline level (r = -0.69, P < 0.00001) and in tumor volume (r = -0.35, P < 0.05). The choline loss in tumors gaining post-gadolinium magnetic resonance imaging contrast after therapy is unexpected in view of previously reported correlation between the two in untreated metastatic brain tumors. Indicated is the use of 1H magnetic resonance spectroscopy to discriminate enhancing brain tumors with a high content of vital tumor cells (high choline) from tumors, combining decreased cell density with increased interstitial space (low choline).
International Journal of Radiation Oncology Biology Physics, Oct 1, 2005
The median volumes of respectively. The treatment plans showed that the D95 and V95 of GTV were 6... more The median volumes of respectively. The treatment plans showed that the D95 and V95 of GTV were 66.9Gy and 98.3%, respectively. The minimum, maximum and mean dose to GTV was 54.8Gy, 77.1Gy and 69.8Gy. The mean fractional dose was 2.32Gy (1.99 -2.91Gy). The average doses of the surrounding critical structures were much lower than the tolerance thresholds. Median follow-up was 12 months (range, 2-47 months). The 1-, 2-and 3-year local progression-free and overall survival rates were 96.4%, 88.4%, 85.3%, and 65.9%, 49.6%, 41.6%, respectively. Eleven patients (8.3%) developed distant metastases. On univariate analysis, T stage (pϭ0.009), maximum reirradiation dose to GTV (pϭ0.006), fractional dose to GTV (pϭ0.02), the volume of GTV and CTV (pϭ0.003 & 0.004), were significant prognostic factors for overall survival. On multivariate analysis by Cox proportional hazard model, only fractional dose (pϭ 0.029) and the volume of GTV and CTV (pϭ0.000) remained significant for overall survival. Conclusions: Reirradiation using IMRT may improve the local control of the local recurrence and prolong survival of these patients. The fractional dose was delivered to GTV and the volume of GTV and CTV were independent prognostic factors for overall survival.
We investigated the influence of tensile stress on plaque growth after balloon angioplasty with a... more We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy.
Aims We sought to compare the effect of intracoronary -radiation on the vessel dimensions in de n... more Aims We sought to compare the effect of intracoronary -radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting.
Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used ... more Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used for measurement of the volume through which the stents traversed during the cardiac cycle. This volume, less than 0.8% of the whole heart volume in all patients, represents a target volume for high-precision radiotherapy to treat coronary artery in-stent restenosis. q
This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response... more This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease.
After treatment with intracoronary brachytherapy, enlargement of lumen (negative late loss) at fo... more After treatment with intracoronary brachytherapy, enlargement of lumen (negative late loss) at follow-up has been demonstrated. The aim of the study is to analyze the sensitivity and specificity of quantitative coronary angiography (QCA) parameters to detect a positive vessel remodeling after intracoronary -radiation as compared to intravascular ultrasound (IVUS). Twenty-seven patients (27 vessels) treated with balloon angioplasty followed by catheter-based intracoronary -radiation with a (90)Strontium/(90)Yttrium source were assessed by both QCA and three-dimensional IVUS with electrocardiogram-gated pullback. Irradiated segments were analyzed over the total treatment length and in subsegment lengths of 5 mm. Change in minimum luminal diameter (MLD) was not a predictor for the positive remodeling in either total irradiated segments or 5 mm subsegments, with a 54.3% ROC curve area [95% confidence interval (CI), 30-79%], sensitivity of 39% and specificity of 44% (p = not significant) in the total irradiated segments and a 55.9% ROC curve area (95% CI, 46-66%), sensitivity of 55% and specificity of 54% (p = not significant) in the 5 mm subsegments. Changes in mean and maximal lumen diameter were not significant parameters to detect positive vessel remodeling. When only central subsegments were analyzed, change in MLD was a significant predictor, with a 63.3% ROC curve area (95% CI, 52-75%), sensitivity of 55% and specificity of 64% (p = 0.029). Lumen enlargement detected by QCA does not reliably indicate a positive vessel remodeling after intracoronary radiation. IVUS analysis may be necessary to investigate the mechanism of restenosis after balloon angioplasty followed by catheter-based radiation.
Advances in image guidance and dose delivery techniques, and increased use of hypofractionation, ... more Advances in image guidance and dose delivery techniques, and increased use of hypofractionation, have led to prolonged radiotherapy fraction duration. This is also the case with robotic radiosurgery, as extensive on-line image guidance procedures, many beams, and usually high fraction doses are used for tumor irradiation. At this institution, early stage non-small-cell lung cancer patients are treated with image guided tumor tracking for respiratory motion compensation. Approximately 130 circular beams and up to approximately 39 000 monitor units (MUs) are used for delivery of a total treatment dose of 60 Gy. The large number of MUs leads to long treatment times and the radiation leakage increases with the number of MUs. Generally, per patient, a single (small) cone is used. To substantially reduce the number of MUs, the authors have developed a new planning strategy for combined use of a small and a large cone. The large cone aims at dose delivery around the PTV center, while the small cone shapes the dose around the (irregular) PTV edges. The authors systematically investigated relationships between the number of MUs, the plan quality, the selected cone diameters, and the beam-direction setup. Plan quality was assessed with the conformity index, mean lung dose (MLD), V20 of the lungs, and by visual inspection. The reduction in MUs was determined by comparing two-cone plans with corresponding one-cone plans that yielded equal MLD, i.e., equal predicted lung toxicity. With the proposed two-cone approach, the required number of MUs reduced by on average 31% (range 4%-56%). The beam-on time per treatment fraction reduced by on average 8 min (range 1-15.2 min). All plans obeyed the clinically applied constraints and were considered clinically acceptable by an involved physician.
Http Dx Doi Org 10 1089 Ten 2006 12 3395, Dec 18, 2006
Oral mucositis is a major side effect of radiation therapy. Development of strategies for reducti... more Oral mucositis is a major side effect of radiation therapy. Development of strategies for reduction of this problem calls for quantitative models. The goal of the present study was to test the feasibility of detecting double-strand breaks (DSBs) and DSB repair proteins upon radiation of mucosa in a 3-dimensional culture system using morphology and immunohistochemistry. Human oral keratinocytes and fibroblasts were seeded onto and into an acellular dermal carrier to produce a cultured mucosal substitute (CMS). CMSs were gamma-irradiated with 0, 2, and 12 Gy. One group received 4 Gy through 2 Gy fractions with a 24-h interval. Radiation-induced damage was quantified using hematoxylin and eosin (H&E). DSBs and DSB repair proteins were visualized and quantified using antibodies against P53 binding protein 1 (53BP1), MRE11, and RAD51. As in cell culture, CMSs showed intranuclear loci of damage and repair, mostly in the proliferative basal cell layers. Maximum percentages of damaged basal layer keratinocytes were 54.8% using H&E (12 Gy) up to 78.9% (12 Gy) for 53BP1. This study shows the feasibility of DNA repair markers to quantify radiation damage. This is an important step forward in the study of mucositis and the development of treatment and prevention strategies, proving once more the power and clinical importance of tissue engineering.
To investigate the impact of treatment modality and radiation technique on oncologic outcomes and... more To investigate the impact of treatment modality and radiation technique on oncologic outcomes and toxicity of patients with locally advanced oropharyngeal cancer (OPC). Retrospective analysis of outcomes and toxicity. Between 2000 and 2011, 204 consecutive patients with locally advanced OPC were treated with definitive (chemo)radiotherapy using 3-dimensional conformal (3DCRT) or intensity-modulated radiotherapy (IMRT). Endpoints were local control (LC), regional control (RC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), and toxicity. After a median follow-up of 44 months (range 4-134), the 5-year Kaplan-Meier estimates of LC, RC, DFS, CSS, and OS were 78%, 92%, 60%, 64%, and 48%, respectively. Grade 3 mucositis and dysphagia (feeding-tube dependency) were reported in 75% and 65%, respectively. The overall incidence of grade ≥ 2 and grade 3 late toxicities were 44% and 16%, respectively. Dysphagia and xerostomia were the most frequently reported late toxicity. Chemotherapy was significantly predictive for improved outcomes and increased toxicity. IMRT was significantly correlated with reduced toxicity. Compared to radiation alone, chemoradiotherapy significantly improved oncologic outcomes, but with significantly increased toxicity. Compared to 3DCRT, the introduction of IMRT resulted in a significant reduction of acute and late toxicity with slightly better, or at least comparable, outcomes. Despite the improvements achieved by the implementation of chemo-IMRT, different new strategies to further improve outcome and reduce toxicity need to be thoroughly investigated in prospective, preferably, randomized trials.
International Journal of Radiation Oncology*Biology*Physics, 2012
Purpose/Objective(s): In locally advanced HNSCC, treatment of bilateral RPN to the skull base has... more Purpose/Objective(s): In locally advanced HNSCC, treatment of bilateral RPN to the skull base has been advocated to prevent failure in the contralateral RPN region. In addition, this is a historical practice as it was only possible to treat bilaterally prior to the IMRT era. In view of the relationship between pharyngeal constrictor muscles and swallowing function, we modified our treatment policy in 2007. Thereafter, we eliminated contralateral high level II and contralateral RPN coverage for selected patients (without N2c disease). We retrospectively analyzed the patterns of failure for these patients. Materials/Methods: From 1997 to 2010, 697 previously untreated patients with locally advanced HNSCC received definitive or postoperative IMRT +/chemotherapy. Sites included oropharynx, hypopharynx, larynx, oral cavity, and unknown primary. Two hundred sixty-five patients were treated with definitive IMRT, and 432 with postoperative IMRT. Three hundred seventyfour patients received chemotherapy. Overall, 443 patients were treated before, and 254 after this policy change. In addition to the policy change described above, for patients with N0 disease involving the oral cavity or larynx, BL RTP nodes and high level II nodes were spared. Specifically, high level II nodal coverage in the N0 side of the neck was contoured only up to the level were the posterior belly of the digastric crosses the internal jugular vein, and RTP nodes in the N0 side of the neck were excluded. CTV1 was defined as the tumor bed plus any node positive region of the neck, and received 70 Gy (definitive) and 60 to 66 Gy (postoperative), all at 2.0 Gy/ fraction. CTV2 was defined as the N0 neck, and received 52 to 54 Gy (postoperative) and 56 Gy (definitive), at 1.6 to 1.73 Gy/fraction. Results: Mean follow-up for living patients treated after the policy change was 24 months. Among the 254 patients treated after the policy change 46 (18%) had loco-regional recurrence (LRR) and 38 developed distant metastases. There were 44 in-field failures, 1 marginal failure and 1 out of field failure. To date there have been no failures in the spared high contralateral neck or retropharyngeal lymph node regions. Conclusions: For patients with locally advanced HNSCC exclusive of N2c neck disease, eliminating coverage of the high contralateral level II neck and contralateral RPN is associated with minimal risk of failure in these regions.
Background. To investigate the impact of up-front neck dissection on the outcome of patients with... more Background. To investigate the impact of up-front neck dissection on the outcome of patients with node-positive hypopharyngeal cancer (HPC) treated with (chemo)radiation. Methods. Of 135 consecutive patients with node-positive HPC, 32 patients underwent up-front neck dissection followed by (chemo)radiation (group 1), and 103 patients received definitive (chemo)radiation (group 2). Results. The 3-year regional, local and distant control for groups 1 and 2 were 92% versus 87% (p ¼ .37), 84% versus 72% (p ¼ .15), and 80% versus 62% (p ¼ .08), respectively. High T classification was the only significant predictor for poor overall survival on multivariate analysis (OR ¼ 3.0, p ¼ .02). Acute and late toxicities and the prospectively assessed quality of life were comparable in both groups. Conclusion. Upfront neck dissection followed by (chemo)radiation did not negatively impact on oncologic outcomes, toxicity, or quality of life and therefore is to be regarded as a safe and effective treatment option for small HPC with bulky nodal disease, especially in busy radiation departments with unacceptably long waiting time for definitive (chemo)radiation.
Intracoronary brachytherapy has recently emerged as a new therapy to prevent restenosis. Initial ... more Intracoronary brachytherapy has recently emerged as a new therapy to prevent restenosis. Initial experimental work was achieved in animal models and the results were assessed by histomorphometry. Initial clinical trials used angiography to guide dosimetry and to assess efficacy. Intravascular ultrasound (IVUS) permits tomographic examination of the vessel wall, elucidating the true morphology of the lumen and transmural components, which cannot be investigated on the lumenogram obtained by angiography. This paper reviews the use of IVUS in the clinical studies of brachytherapy conducted to date. IVUS allows clinicians to make a thorough assessment of the remodeling of the vessel and appears to have a major role to play in facilitating understanding of the underlying mechanisms of action in this emerging field. The authors propose that state-of-the-art IVUS techniques should be employed to further knowledge of the mechanisms of action of brachytherapy in atherosclerotic human coronary arteries.
This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response... more This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease.
Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed... more Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in 1H MR spectra of contrast-enhancing tumor at 5-10 min after Gd-contrast administration [Magn. Reson. Med. 37:222-225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0-5, 5-10, and/or 10-15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 +/- 3, 12 +/- 2, and 14 +/- 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.
Investigative Radiology a Journal of Clinical and Laboratory Research, Dec 1, 1995
The anatomic and metabolic changes in human brain tumors treated by radiation therapy were compar... more The anatomic and metabolic changes in human brain tumors treated by radiation therapy were compared using gadolinium-enhanced magnetic resonance imaging and hydrogen (1H) magnetic resonance spectroscopy. The study was intended to assess the potential of 1H magnetic resonance spectroscopy in monitoring response to therapy. Thirteen cases of brain cancer treated by radiation therapy were examined by 1H magnetic resonance spectroscopy and gadolinium-enhanced T1-weighted magnetic resonance imaging and reexamined at 2-month intervals. Follow-up after radiation therapy showed changes in post-gadolinium magnetic resonance imaging contrast that are inversely correlated with the changes in choline level (r = -0.69, P < 0.00001) and in tumor volume (r = -0.35, P < 0.05). The choline loss in tumors gaining post-gadolinium magnetic resonance imaging contrast after therapy is unexpected in view of previously reported correlation between the two in untreated metastatic brain tumors. Indicated is the use of 1H magnetic resonance spectroscopy to discriminate enhancing brain tumors with a high content of vital tumor cells (high choline) from tumors, combining decreased cell density with increased interstitial space (low choline).
International Journal of Radiation Oncology Biology Physics, Oct 1, 2005
The median volumes of respectively. The treatment plans showed that the D95 and V95 of GTV were 6... more The median volumes of respectively. The treatment plans showed that the D95 and V95 of GTV were 66.9Gy and 98.3%, respectively. The minimum, maximum and mean dose to GTV was 54.8Gy, 77.1Gy and 69.8Gy. The mean fractional dose was 2.32Gy (1.99 -2.91Gy). The average doses of the surrounding critical structures were much lower than the tolerance thresholds. Median follow-up was 12 months (range, 2-47 months). The 1-, 2-and 3-year local progression-free and overall survival rates were 96.4%, 88.4%, 85.3%, and 65.9%, 49.6%, 41.6%, respectively. Eleven patients (8.3%) developed distant metastases. On univariate analysis, T stage (pϭ0.009), maximum reirradiation dose to GTV (pϭ0.006), fractional dose to GTV (pϭ0.02), the volume of GTV and CTV (pϭ0.003 & 0.004), were significant prognostic factors for overall survival. On multivariate analysis by Cox proportional hazard model, only fractional dose (pϭ 0.029) and the volume of GTV and CTV (pϭ0.000) remained significant for overall survival. Conclusions: Reirradiation using IMRT may improve the local control of the local recurrence and prolong survival of these patients. The fractional dose was delivered to GTV and the volume of GTV and CTV were independent prognostic factors for overall survival.
We investigated the influence of tensile stress on plaque growth after balloon angioplasty with a... more We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy.
Aims We sought to compare the effect of intracoronary -radiation on the vessel dimensions in de n... more Aims We sought to compare the effect of intracoronary -radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting.
Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used ... more Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used for measurement of the volume through which the stents traversed during the cardiac cycle. This volume, less than 0.8% of the whole heart volume in all patients, represents a target volume for high-precision radiotherapy to treat coronary artery in-stent restenosis. q
This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response... more This study is the contribution by the Thoraxcenter, Rotterdam, to the European 32 P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease.
After treatment with intracoronary brachytherapy, enlargement of lumen (negative late loss) at fo... more After treatment with intracoronary brachytherapy, enlargement of lumen (negative late loss) at follow-up has been demonstrated. The aim of the study is to analyze the sensitivity and specificity of quantitative coronary angiography (QCA) parameters to detect a positive vessel remodeling after intracoronary -radiation as compared to intravascular ultrasound (IVUS). Twenty-seven patients (27 vessels) treated with balloon angioplasty followed by catheter-based intracoronary -radiation with a (90)Strontium/(90)Yttrium source were assessed by both QCA and three-dimensional IVUS with electrocardiogram-gated pullback. Irradiated segments were analyzed over the total treatment length and in subsegment lengths of 5 mm. Change in minimum luminal diameter (MLD) was not a predictor for the positive remodeling in either total irradiated segments or 5 mm subsegments, with a 54.3% ROC curve area [95% confidence interval (CI), 30-79%], sensitivity of 39% and specificity of 44% (p = not significant) in the total irradiated segments and a 55.9% ROC curve area (95% CI, 46-66%), sensitivity of 55% and specificity of 54% (p = not significant) in the 5 mm subsegments. Changes in mean and maximal lumen diameter were not significant parameters to detect positive vessel remodeling. When only central subsegments were analyzed, change in MLD was a significant predictor, with a 63.3% ROC curve area (95% CI, 52-75%), sensitivity of 55% and specificity of 64% (p = 0.029). Lumen enlargement detected by QCA does not reliably indicate a positive vessel remodeling after intracoronary radiation. IVUS analysis may be necessary to investigate the mechanism of restenosis after balloon angioplasty followed by catheter-based radiation.
Advances in image guidance and dose delivery techniques, and increased use of hypofractionation, ... more Advances in image guidance and dose delivery techniques, and increased use of hypofractionation, have led to prolonged radiotherapy fraction duration. This is also the case with robotic radiosurgery, as extensive on-line image guidance procedures, many beams, and usually high fraction doses are used for tumor irradiation. At this institution, early stage non-small-cell lung cancer patients are treated with image guided tumor tracking for respiratory motion compensation. Approximately 130 circular beams and up to approximately 39 000 monitor units (MUs) are used for delivery of a total treatment dose of 60 Gy. The large number of MUs leads to long treatment times and the radiation leakage increases with the number of MUs. Generally, per patient, a single (small) cone is used. To substantially reduce the number of MUs, the authors have developed a new planning strategy for combined use of a small and a large cone. The large cone aims at dose delivery around the PTV center, while the small cone shapes the dose around the (irregular) PTV edges. The authors systematically investigated relationships between the number of MUs, the plan quality, the selected cone diameters, and the beam-direction setup. Plan quality was assessed with the conformity index, mean lung dose (MLD), V20 of the lungs, and by visual inspection. The reduction in MUs was determined by comparing two-cone plans with corresponding one-cone plans that yielded equal MLD, i.e., equal predicted lung toxicity. With the proposed two-cone approach, the required number of MUs reduced by on average 31% (range 4%-56%). The beam-on time per treatment fraction reduced by on average 8 min (range 1-15.2 min). All plans obeyed the clinically applied constraints and were considered clinically acceptable by an involved physician.
Http Dx Doi Org 10 1089 Ten 2006 12 3395, Dec 18, 2006
Oral mucositis is a major side effect of radiation therapy. Development of strategies for reducti... more Oral mucositis is a major side effect of radiation therapy. Development of strategies for reduction of this problem calls for quantitative models. The goal of the present study was to test the feasibility of detecting double-strand breaks (DSBs) and DSB repair proteins upon radiation of mucosa in a 3-dimensional culture system using morphology and immunohistochemistry. Human oral keratinocytes and fibroblasts were seeded onto and into an acellular dermal carrier to produce a cultured mucosal substitute (CMS). CMSs were gamma-irradiated with 0, 2, and 12 Gy. One group received 4 Gy through 2 Gy fractions with a 24-h interval. Radiation-induced damage was quantified using hematoxylin and eosin (H&E). DSBs and DSB repair proteins were visualized and quantified using antibodies against P53 binding protein 1 (53BP1), MRE11, and RAD51. As in cell culture, CMSs showed intranuclear loci of damage and repair, mostly in the proliferative basal cell layers. Maximum percentages of damaged basal layer keratinocytes were 54.8% using H&E (12 Gy) up to 78.9% (12 Gy) for 53BP1. This study shows the feasibility of DNA repair markers to quantify radiation damage. This is an important step forward in the study of mucositis and the development of treatment and prevention strategies, proving once more the power and clinical importance of tissue engineering.
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Papers by Peter Levendag