- Email: [email protected]
Quantifying Inter and Intra-Fraction Tumor Motion using Respiration-Correlated Cone Beam CT in Lung Stereotactic Body Radiotherapy (SBRT)
Proceedings of the 49th Annual ASTRO Meeting
Author Disclosure: C. Dehing-Oberije, None; G. Fung, None; D. De Ruysscher, None; H. van der Weide, None; S. Krishnan, None; R.B. Rao, None; P. Lambin, None.
2519
Quantifying Inter and Intra-Fraction Tumor Motion using Respiration-Correlated Cone Beam CT in Lung Stereotactic Body Radiotherapy (SBRT)
K. N. Franks1, T. G. Purdie1,2, A. Bezjak1,2, D. Moseley1,2, S. Pearson1, D. A. Jaffray1,2, J. Bissonnette1 1 Radiation Medicine Program, Princess Margaret Hospital, Toronto, ON, Canada, 2Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): Lung SBRT is an effective treatment for medically inoperable stage I non-small cell lung cancer (NSCLC) resulting in high rates of local control. 4DCT planning allows tumor motion to be incorporated into a patient-specific ITV. Changes in breathing patterns during a SBRT course may cause a geographic miss or unnecessarily over-treat normal tissues. We evaluate inter and intra-fraction tumor motion over a SBRT course. Methods/Materials: Ten patients with inoperable stage I NSCLC received image-guided SBRT. Tumor motion was assessed fluoroscopically and abdominal compression applied if motion .10 mm. 4DCT images were acquired and binned into 10 datasets, each corresponding to a phase of breathing. The GTV (GTV = CTV) was contoured on the max exhale (ME) and max inhale (MI) datasets and fused to form an ITV. A uniform 5 mm margin was added to create the PTV. Cone beam CT (CBCT) was used for tumor localisation (3 mm tolerance) and repeated to verify any corrections to patient position. Two additional CBCT were acquired at mid and at end of each SBRT fraction, for 3 fractions. Respiration-correlated CBCT (rcCBCT) reconstruction was performed off-line, creating 10 respiratory-sorted datasets to allow comparison with 4DCT planning. Tumor motion was retrospectively determined by measuring the magnitude of the target displacement between the ME and MI phases on both imaging modalities. Motion was measured in the lateral (X), sup/inf (Z) and ant/post (Z) directions and expressed as a 3D vector. Results: The mean tumor size was 25 mm (SD ± 12). Tumor location was upper lobe 6 pts, lower lobe 4 pts. Abdominal compression was required for 2 pts. Mean treatment time was 35 minutes. 112 rcCBCTs were analysed. At planning (n = 10 4DCTs), the mean tumor vector motion was 4.2 ± 3.8 mm which corresponded to a mean motion of: X = 0.7 ± 0.6 mm; Y = 3.4 ± 4.1 mm; Z = 1.3 ± 1.4 mm. On treatment (n = 112 rcCBCTs) the mean vector motion was 3.3 ± 2.5 mm; mean motion of: X = 0.9 ± 0.8 mm; Y = 2.7 ± 2.9 mm; Z = 1.3 ± 1.1 mm. Compared to 4DCT, the difference in either X, Y or Z motion observed with rcCBCT scans was 5 mm in 3% (11). In a minority of pts, more motion was observed on treatment, by 2–5 mm in 6% and by .5 mm in 1% of the X, Y and Z measurements. The 2 patients treated with abdominal compression accounted for 37 of 60 (62%) differences .2 mm, of which more motion (.2 mm) was observed in 14 (38%) measurements.
S489
I. J. Radiation Oncology d Biology d Physics
S490
Volume 69, Number 3, Supplement, 2007
Conclusions: In the majority of cases, tumor motion determined on 4DCT corresponds well to tumor motion at time of SBRT treatment. In this analysis, the greatest differences in inter and intra-fraction tumor motion occurred in patients with abdominal compression, probably due to variations in daily compression setup. These changes in breathing amplitude, seen in a minority of cases, could potentially compromise local control and/or increase normal tissue toxicity. Author Disclosure: K.N. Franks, Elekta Inc, B. Research Grant; CIHR Grant, B. Research Grant; The Addie MacNaugton Chair in Thoracic Radiation Oncology, C. Other Research Support; T.G. Purdie, None; A. Bezjak, Elekta Inc, B. Research Grant; The Addie MacNaughton Chair in Thoracic Radiation Oncology, C. Other Research Support; D. Moseley, None; S. Pearson, None; D.A. Jaffray, Elekta Inc, B. Research Grant; J. Bissonnette, None.
2520
Concurrent Pemetrexed/Cisplatin/Radiation for Unresectable Stage IIIA/B Non-Small Cell Lung Cancer: A Phase I/II Study
A. M. Brade1, A. Bezjak1, R. MacRae2, S. Laurie3, G. R. Pond4, A. Afinec5, N. Iscoe6,7, F. Shepherd5 1 Dept. of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada, 2Dept. of Radiation Oncology, Ottawa Regional Cancer Centre, Ottawa, ON, Canada, 3Dept. of Medical Oncology, Ottawa Regional Cancer Centre, Ottawa, ON, Canada, 4Dept. of Biostatistics, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada, 5Dept. of Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada, 6Dept. of Medical Oncology, Sunnybrook Hospital, University of Toronto, Toronto, ON, Canada, 7Eli Lilly (Canada), Toronto, ON, Canada
Purpose/Objective(s): Concurrent chemoradiation is the accepted standard of care for most patients with unresectable stage III A/B non-small cell lung cancer (NSCLC) but no standard chemotherapy regimen or schedule has yet been established. Cisplatin, combined with a third generation agent, provides the greatest activity in advanced NSCLC but, to date, no third generation agent has been shown to be tolerable at full dose in combination with radiotherapy (RT) and cisplatin. Pemetrexed/cisplatin (PemC) has shown promising activity in the advanced disease setting and full dose pemetrexed combined with RT or RT/carboplatin appears tolerable. Materials/Methods: From Dec 15, 2005 to Decmber 19, 2006, 10 patients with unresectable stage IIIA/B NSCLC were entered on three dose levels of a phase I trial evaluating PemC combined with 61–66 Gy RT (date of last follow up February 1, 2007). Eligible patients had\5% weight loss, ECOG PS 0/1, no malignant effusions, FEV1 . 1.3 l and adequate organ function. Patients received two q21 day cycles of PemC (Pem 300, 400 or 500 mg/m2 day 1, C 25 mg/m2 days 1–3) concurrent with RT (61–66 Gy over 6 to 6.5 weeks) followed by two consolidation q21 day cycles (Pem 500 mg/m2 day 1, C 75 mg/m2 day 1). All patients received dexamethasone premedication and B12/folate vitamin supplementation. Results: Ten patients were accrued (3 at dose levels 1 and 2, 4 at dose level 3). Demographics: median age–63 years [range 46–69]; stage IIIA/B–4/6; PS 0/1–2/8; median radiation dose–65 Gy [range 60.5–66]. One patient had dose reduction of cisplatin for cycles 3 and 4 due to elevated creatinine levels, two patients received only cycles one and two (one due to patient refusal despite only grade 2 toxicity having been observed; one in a patient with pre-existing metal allergies who developed progressive cisplatin allergy). Neutropenia: gr 3–0 patients, gr 4–2 patients; with fever–0 patients. One patient on dose level 3 required hospital admission for grade 3 esophagitis but was able to complete all planned concurrent chemoradiotherapy and start consolidation chemotherapy at full dose. Other gr 3 toxicities were uncommon: hypertension (2); diarrhea (1); anemia (1); hyperglycemia (1); hypophosphatemia (1); thrombocytopenia (1). Seven of 8 evaluable patients achieved partial response by RECIST (88%) after independent review with no local progression to date (median f/u 5.3 months). All patients remain alive, with one patient having distant relapse (.12 months after commencing treatment). One patient on dose level two was subsequently deemed to have become resectable and was resected in PR with no evidence of tumour progression 5.5 months after starting study therapy. The specimen contained some viable tumour tissue in the primary and two N2 lymph nodes with negative resection margins. Two previously involved N2 lymph nodes were free of tumour. Conclusions: Full dose PemC and full dose concurrent RT is well tolerated and preliminary efficacy appears promising. The study is ongoing and has been amended to add a fourth dose level increasing the dose intensity of cisplatin during RT to 20 mg/m2 daily 5 (Pem remains at 500 mg/m2). A phase II study is planned. Author Disclosure: A.M. Brade, None; A. Bezjak, None; R. MacRae, None; S. Laurie, None; G.R. Pond, None; A. Afinec, None; N. Iscoe, Eli Lilly, Canada, A. Employment; Stock (Lilly), E. Ownership Interest; F. Shepherd, None.
2521
Time Trends in Nodal CT Volume and Nodal Motion During Radiotherapy for Patients With Stage III Non-Small Cell Lung Cancer
G. Bosmans, L. Boersma, A. van Baardwijk, A. Dekker, M. Oellers, S. Wanders, P. Lambin, D. De Ruysscher Department of Radiation Oncology (MAASTRO), GROW, University Hospital, Maastricht, The Netherlands Purpose/Objective(s): Knowledge of changes in volume and motion of either tumor or involved lymph nodes during a course of radiotherapy is necessary to improve the treatment (adaptive radiotherapy). These changes for the primary tumor were already reported (Bosmans et al, Int J Radiat Oncol Biol Phys, 2006). The purpose of this study is describing the time trends in nodal CT volume and nodal motion, for patients with locally advanced non-small cell lung cancer. Materials/Methods: Eleven patients, with a total of 21 nodes, from a prospective clinical trial underwent CT-PET scans prior to treatment, which was repeated in the first and second week following the start of radiotherapy. For 20 nodes, the motion could be measured based on a respiration correlated CT (RCCT) scan. Moreover, repeated RCCT scans were available for 11 nodes to evaluate the change in motion. Patients were treated with an accelerated fractionation schedule, 1.8 Gy BID, with a total tumor dose depending on pre-set dose constraints for the lungs and the spinal cord. Results: A heterogeneity of nodal volume changes was observed at all time points similar to the tumor volume changes. In some patients the nodal volume increased .50% (4/21) in others the volume decreased .50% (1/21) but for the majority of nodal areas
Author Disclosure: C. Dehing-Oberije, None; G. Fung, None; D. De Ruysscher, None; H. van der Weide, None; S. Krishnan, None; R.B. Rao, None; P. Lambin, None.
2519
Quantifying Inter and Intra-Fraction Tumor Motion using Respiration-Correlated Cone Beam CT in Lung Stereotactic Body Radiotherapy (SBRT)
K. N. Franks1, T. G. Purdie1,2, A. Bezjak1,2, D. Moseley1,2, S. Pearson1, D. A. Jaffray1,2, J. Bissonnette1 1 Radiation Medicine Program, Princess Margaret Hospital, Toronto, ON, Canada, 2Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): Lung SBRT is an effective treatment for medically inoperable stage I non-small cell lung cancer (NSCLC) resulting in high rates of local control. 4DCT planning allows tumor motion to be incorporated into a patient-specific ITV. Changes in breathing patterns during a SBRT course may cause a geographic miss or unnecessarily over-treat normal tissues. We evaluate inter and intra-fraction tumor motion over a SBRT course. Methods/Materials: Ten patients with inoperable stage I NSCLC received image-guided SBRT. Tumor motion was assessed fluoroscopically and abdominal compression applied if motion .10 mm. 4DCT images were acquired and binned into 10 datasets, each corresponding to a phase of breathing. The GTV (GTV = CTV) was contoured on the max exhale (ME) and max inhale (MI) datasets and fused to form an ITV. A uniform 5 mm margin was added to create the PTV. Cone beam CT (CBCT) was used for tumor localisation (3 mm tolerance) and repeated to verify any corrections to patient position. Two additional CBCT were acquired at mid and at end of each SBRT fraction, for 3 fractions. Respiration-correlated CBCT (rcCBCT) reconstruction was performed off-line, creating 10 respiratory-sorted datasets to allow comparison with 4DCT planning. Tumor motion was retrospectively determined by measuring the magnitude of the target displacement between the ME and MI phases on both imaging modalities. Motion was measured in the lateral (X), sup/inf (Z) and ant/post (Z) directions and expressed as a 3D vector. Results: The mean tumor size was 25 mm (SD ± 12). Tumor location was upper lobe 6 pts, lower lobe 4 pts. Abdominal compression was required for 2 pts. Mean treatment time was 35 minutes. 112 rcCBCTs were analysed. At planning (n = 10 4DCTs), the mean tumor vector motion was 4.2 ± 3.8 mm which corresponded to a mean motion of: X = 0.7 ± 0.6 mm; Y = 3.4 ± 4.1 mm; Z = 1.3 ± 1.4 mm. On treatment (n = 112 rcCBCTs) the mean vector motion was 3.3 ± 2.5 mm; mean motion of: X = 0.9 ± 0.8 mm; Y = 2.7 ± 2.9 mm; Z = 1.3 ± 1.1 mm. Compared to 4DCT, the difference in either X, Y or Z motion observed with rcCBCT scans was 5 mm in 3% (11). In a minority of pts, more motion was observed on treatment, by 2–5 mm in 6% and by .5 mm in 1% of the X, Y and Z measurements. The 2 patients treated with abdominal compression accounted for 37 of 60 (62%) differences .2 mm, of which more motion (.2 mm) was observed in 14 (38%) measurements.
S489
I. J. Radiation Oncology d Biology d Physics
S490
Volume 69, Number 3, Supplement, 2007
Conclusions: In the majority of cases, tumor motion determined on 4DCT corresponds well to tumor motion at time of SBRT treatment. In this analysis, the greatest differences in inter and intra-fraction tumor motion occurred in patients with abdominal compression, probably due to variations in daily compression setup. These changes in breathing amplitude, seen in a minority of cases, could potentially compromise local control and/or increase normal tissue toxicity. Author Disclosure: K.N. Franks, Elekta Inc, B. Research Grant; CIHR Grant, B. Research Grant; The Addie MacNaugton Chair in Thoracic Radiation Oncology, C. Other Research Support; T.G. Purdie, None; A. Bezjak, Elekta Inc, B. Research Grant; The Addie MacNaughton Chair in Thoracic Radiation Oncology, C. Other Research Support; D. Moseley, None; S. Pearson, None; D.A. Jaffray, Elekta Inc, B. Research Grant; J. Bissonnette, None.
2520
Concurrent Pemetrexed/Cisplatin/Radiation for Unresectable Stage IIIA/B Non-Small Cell Lung Cancer: A Phase I/II Study
A. M. Brade1, A. Bezjak1, R. MacRae2, S. Laurie3, G. R. Pond4, A. Afinec5, N. Iscoe6,7, F. Shepherd5 1 Dept. of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada, 2Dept. of Radiation Oncology, Ottawa Regional Cancer Centre, Ottawa, ON, Canada, 3Dept. of Medical Oncology, Ottawa Regional Cancer Centre, Ottawa, ON, Canada, 4Dept. of Biostatistics, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada, 5Dept. of Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada, 6Dept. of Medical Oncology, Sunnybrook Hospital, University of Toronto, Toronto, ON, Canada, 7Eli Lilly (Canada), Toronto, ON, Canada
Purpose/Objective(s): Concurrent chemoradiation is the accepted standard of care for most patients with unresectable stage III A/B non-small cell lung cancer (NSCLC) but no standard chemotherapy regimen or schedule has yet been established. Cisplatin, combined with a third generation agent, provides the greatest activity in advanced NSCLC but, to date, no third generation agent has been shown to be tolerable at full dose in combination with radiotherapy (RT) and cisplatin. Pemetrexed/cisplatin (PemC) has shown promising activity in the advanced disease setting and full dose pemetrexed combined with RT or RT/carboplatin appears tolerable. Materials/Methods: From Dec 15, 2005 to Decmber 19, 2006, 10 patients with unresectable stage IIIA/B NSCLC were entered on three dose levels of a phase I trial evaluating PemC combined with 61–66 Gy RT (date of last follow up February 1, 2007). Eligible patients had\5% weight loss, ECOG PS 0/1, no malignant effusions, FEV1 . 1.3 l and adequate organ function. Patients received two q21 day cycles of PemC (Pem 300, 400 or 500 mg/m2 day 1, C 25 mg/m2 days 1–3) concurrent with RT (61–66 Gy over 6 to 6.5 weeks) followed by two consolidation q21 day cycles (Pem 500 mg/m2 day 1, C 75 mg/m2 day 1). All patients received dexamethasone premedication and B12/folate vitamin supplementation. Results: Ten patients were accrued (3 at dose levels 1 and 2, 4 at dose level 3). Demographics: median age–63 years [range 46–69]; stage IIIA/B–4/6; PS 0/1–2/8; median radiation dose–65 Gy [range 60.5–66]. One patient had dose reduction of cisplatin for cycles 3 and 4 due to elevated creatinine levels, two patients received only cycles one and two (one due to patient refusal despite only grade 2 toxicity having been observed; one in a patient with pre-existing metal allergies who developed progressive cisplatin allergy). Neutropenia: gr 3–0 patients, gr 4–2 patients; with fever–0 patients. One patient on dose level 3 required hospital admission for grade 3 esophagitis but was able to complete all planned concurrent chemoradiotherapy and start consolidation chemotherapy at full dose. Other gr 3 toxicities were uncommon: hypertension (2); diarrhea (1); anemia (1); hyperglycemia (1); hypophosphatemia (1); thrombocytopenia (1). Seven of 8 evaluable patients achieved partial response by RECIST (88%) after independent review with no local progression to date (median f/u 5.3 months). All patients remain alive, with one patient having distant relapse (.12 months after commencing treatment). One patient on dose level two was subsequently deemed to have become resectable and was resected in PR with no evidence of tumour progression 5.5 months after starting study therapy. The specimen contained some viable tumour tissue in the primary and two N2 lymph nodes with negative resection margins. Two previously involved N2 lymph nodes were free of tumour. Conclusions: Full dose PemC and full dose concurrent RT is well tolerated and preliminary efficacy appears promising. The study is ongoing and has been amended to add a fourth dose level increasing the dose intensity of cisplatin during RT to 20 mg/m2 daily 5 (Pem remains at 500 mg/m2). A phase II study is planned. Author Disclosure: A.M. Brade, None; A. Bezjak, None; R. MacRae, None; S. Laurie, None; G.R. Pond, None; A. Afinec, None; N. Iscoe, Eli Lilly, Canada, A. Employment; Stock (Lilly), E. Ownership Interest; F. Shepherd, None.
2521
Time Trends in Nodal CT Volume and Nodal Motion During Radiotherapy for Patients With Stage III Non-Small Cell Lung Cancer
G. Bosmans, L. Boersma, A. van Baardwijk, A. Dekker, M. Oellers, S. Wanders, P. Lambin, D. De Ruysscher Department of Radiation Oncology (MAASTRO), GROW, University Hospital, Maastricht, The Netherlands Purpose/Objective(s): Knowledge of changes in volume and motion of either tumor or involved lymph nodes during a course of radiotherapy is necessary to improve the treatment (adaptive radiotherapy). These changes for the primary tumor were already reported (Bosmans et al, Int J Radiat Oncol Biol Phys, 2006). The purpose of this study is describing the time trends in nodal CT volume and nodal motion, for patients with locally advanced non-small cell lung cancer. Materials/Methods: Eleven patients, with a total of 21 nodes, from a prospective clinical trial underwent CT-PET scans prior to treatment, which was repeated in the first and second week following the start of radiotherapy. For 20 nodes, the motion could be measured based on a respiration correlated CT (RCCT) scan. Moreover, repeated RCCT scans were available for 11 nodes to evaluate the change in motion. Patients were treated with an accelerated fractionation schedule, 1.8 Gy BID, with a total tumor dose depending on pre-set dose constraints for the lungs and the spinal cord. Results: A heterogeneity of nodal volume changes was observed at all time points similar to the tumor volume changes. In some patients the nodal volume increased .50% (4/21) in others the volume decreased .50% (1/21) but for the majority of nodal areas