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PV-0320: Stereotactic body radiotherapy for liver metastases based on functional treatment planning
S166 ESTRO 36 _______________________________________________________________________________________________ V30, and V40) were obtained. Receiver operating characteristic (ROC) curve identified DVH thresholds that predicted for grade≥ II HT toxicity with highest specificity. All data was dichotomized across these cut-offs. Univariate and multivariate analysis was performed with SPSS, version 20. Results Of the 94 patients randomized to IMRT arm, 74 received concurrent cisplatin (median cycles=4). Grades I-V HT was seen in 55.5%, 32.5%, 5%, 0% and 0% patients, respectively demonstrating low incidence of HT during bowel sparing IMRT. Leukopenia, neutropenia, anemia, and thrombocytopenia ≥ grade II was observed in 24.3%, 5.3%, 17.6%, and 0%, respectively. None of the HT resulted in treatment break. On comparing BM delineation techniques the FH sub volumes were 25%-47% of WB sub-volumes. The mean V5, V10, V20, V30, and V40 for WP FH and WB were 99%, 93%, 77%, 60%, and 36%; and 99%, 94%, 80%, 60%, and 36%, respectively suggesting unintended desirable BM sparing. On univariate analysis WPL FH V30 > 55% (p=0.04) predicted for overall grade ≥ II HT, WP V10 >95% (p= 0.04) for grade ≥ II leucopenia and ilium V20 > 90% (p=0.04) for hemoglobin toxicity. On multivariate analysis, only WP FH V10 >95% (p value 0.04, OR 3.3 (1-11.5) was statistically significant for grade ≥ II leucopenia. Conclusion The IMRT arm of NCT01279135 (PARCER study) that employed strict bowel constraints also had unintentional dosimetrically desirable BM sparing. This was associated with low absolute rates of HT. Within the setting of bowel sparing IMRT WP FH V10 should be restricted to ≤95% for simultaneous bowel and BM sparing. However as none of the other dosimetric variables predicted for HT, WB marrow contours could serve as a resource sparing strategy while planning pelvic IMRT.
mean pathologic node volume at diagnosis was 3.4±5.8 cm3. The mean EBRT and nodal boost doses were 44.3±0.9 Gy and 10.0±2.9 Gy respectively. The mean IGABT contribution to pelvic nodes was 4.2±2.6 Gy. Finally the mean total dose to lymphadenopathies was 55.3±5.6 Gy. Concomitant chemotherapy was administrated in 96.5% of the patients. After a median follow-up of 33.5 months, 20 patients (17.4%) experienced relapses in nodes initially considered pathologic at diagnosis (local relapse). Among them recurrences were observed in a total of 44 nodes (15.3%). The mean time from treatment completion to relapse was 9.0±11.8 months. There was no significant relationship between the dose delivered to pathologic nodes and local control probability (p=0.38). Univariate analyses tested various factors: subtypes (SCC versus others, p=0.35), concomitant chemotherapy (p=0.39), use of SIB (p=0.07), volume at diagnosis (threshold: 3 cm3, p<0.0001) and dose (≥ 57.5 Gy, p=0.039). The last three factors were entered in a multivariate analysis. Volume (HR=8.2, 4.0-16.6, p<0.0001) and dose (HR=2, 1.05-3.9, P=0.034) remained independent, whereas SIB was not (p=0.99). Subsequent Probit analysis combining dose and volume showed significant relationships with the probability of local control (Figure).
OC-0319 Cervix cancer: dose-volume effects in pathologic lymph nodes W. Bacorro1, R. Mazeron2, I. Dumas3, A. Escande2, A. Huertas2, R. Sun2, P. Castelnau-Marchand2, C. HaieMeder2, C. Chargari2 1 Benavides Cancer Institute- UST Hospital, Radiation Oncology, Manila, Philippines 2 Gustave Roussy, Radiation Oncology, Villejuif, France 3 Gustave Roussy, Medical Physics, Villejuif, France Purpose or Objective Whereas clear dose-volume relationships have been demonstrated for the tumor and organs at risk in locally advanced cervix cancer, the optimal threshold to reach for pathologic lymph nodes remains uncertain. The objective was to identify planning aim for pathologic nodes. Material and Methods Patients treated with curative intent for a cervical cancer with nodal involvement were identified. Their treatment combined external beam radiotherapy (EBRT) and imageguided brachytherapy (IGABT). Nodal boosts were performed sequentially or using the simultaneous integrated boost (SIB) technique depending on the EBRT technique used. The contributions of EBRT, IGABT (D98) and nodal boosts were converted in 2-Gy equivalent (α/β=10 Gy) and summed. Each node was considered individually, and followed from diagnosis to relapse. Resected nodes during para-aortic node surgical staging were not considered. Statistical analyses comprised logrank tests (univariate analyses), Cox proportional model (factors with p ≤0.1 in univariate) and probit analyses. Results One hundred and fifteen patients were included, with a total number of nodes of 288 (2.5 per patient). PET-CT was performed in 90.6% of the patients; para-aortic dissection in 53.8%. Histologic subtypes comprised squamous cell carcinomas (SCC) in 88.9%, adenocarcinomas in 8.5% and adenosquamous in 2.6%. The
Conclusion The initial volume was the main prognostic factor of control in pathologic lymph nodes. A dose superior to 57.5 Gy was also associated with a better local control probability. Further studies are required to refine these findings. Poster Viewing : Session 7: Upper and lower GI PV-0320 Stereotactic body radiotherapy for liver metastases based on functional treatment planning M.M. Fode1, J. Petersen2, E. Worm2, M. Sørensen3, K. Bak-Fredslund3, S. Keiding3, M. Høyer4 1 Aarhus University Hospital, Department of Oncology, Aarhus C, Denmark 2 Aarhus University Hospital, Department of Medical Physics, Aarhus C, Denmark
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Aarhus University Hospital, Department of Nuclear Medicine & PET Centre and Department of Hepatology and Gastroenterology, Aarhus C, Denmark 4 Aarhus University Hospital, Danish Centre for Particle Therapy, Aarhus C, Denmark Purpose or Objective 2[18F]fluoro-2-deoxy-D-galactose (FDGal) is a hepatocytespecific positron emission tomography (PET) tracer. It was used as a marker for hepatocyte function for applying functional treatment planning (FTP) to minimize the radiation dose to the normal liver tissue. We report the results of a cohort of patients treated with FTPstereotactic body radiotherapy (SBRT) for liver metastases. Material and Methods Fourteen patients referred for SBRT for liver metastases from colorectal cancer were included in the study between December 2013 and August 2016. Nine patients were irradiated for a solitary metastasis and five patients for two (n=4) or three (n=1) metastases. The mean cumulated CTV was 70.3 cc (range 2.0 - 189.7 cc). FDGal PET/CT was performed at baseline and one month posttreatment. The liver was divided into nine iso-functioning volumes based on radioactivity concentration SUV of FDGal on the baseline FDGal PET/CT and transferred to the planning CT using deformable co-registration. The prescribed mean dose to the CTV was 45-60 Gy in 3-6 fractions. The post-treatment FDGal PET/CT was used for evaluation of radiation dose-response for the normal liver tissue. Results FTPs were created and applied for all patients and all plans met the predefined dose-volume constraints with the exception of a soft constraint of mean dose to the liver-CTV that was not met in three patients. Eight patients (57%) were treated with local therapy for liver metastases before inclusion in the present study (surgery n=1; SBRT n=1; combined local therapy n=6. No severe (CTCAE 4.0 grade 3-5) acute morbidity was registered. Teen grade 1 gastrointestinal and six grade 1-2 nongastrointestinal acute morbidities were registered. No patients had liver-related morbidity. Analysis of the posttreatment FDGal PET/CT revealed a dose-dependent depression in hepatocyte function measured in SUV of FDGal uptake in the irradiated normal liver tissue. Conclusion The study shows feasibility for FTP in patients with colorectal liver metastases referred for SBRT using FDGal PET/CT as a marker for hepatocyte function and the radiation dose to the normal liver tissue was minimized without compromising the organs at risk. The acute morbidity was minimal. PV-0321 MRI guided stereotactic radiotherapy for locally advanced pancreatic cancer H.D. Heerkens1, M. Van Vulpen1, B. Erickson2, O. Reerink3, M. Intven1, C.A.T. Van den Berg1, I.Q. Molenaar4, F.P. Vleggaar5, G.J. Meijer1 1 UMC Utrecht, Radiation Oncology Department, Utrecht, The Netherlands 2 Medical College of Wisconsin, Radiation Oncology Department, Milwaukee, USA 3 Isala Clinic, Radiation Oncology Department, Zwolle, The Netherlands 4 UMC Utrecht, Surgery Department, Utrecht, The Netherlands 5 UMC Utrecht, Gastroenterology Department, Utrecht, The Netherlands Purpose or Objective Patients with locally advanced pancreatic cancer (LAPC) show a poor survival due to limited effective therapeutic options. Stereotactic radiotherapy (SBRT) may delay the development of metastasis and physical discomfort, and it
may lead to better palliation and possibly increase survival with the advantage of a short overall treatment time. The superior soft tissue contrast of MRI might improve tumour contouring and MRI is capable of tumour motion quantification. We want to investigate the technical feasibility and safety of MRI-guided SBRT for LAPC. Material and Methods From July 2013 to January 2016, 20 patients with LAPC or medically unresectable pancreatic cancer without distant metastasis were included in this study (Table). A custom made abdominal corset was manufactured to reduce breathing induced tumour motion. Contouring of the gross tumour volume (GTV) and organs at risk (OARs) was performed on 4D treatment planning CT and multiparametric MRI. A GTV-to-PTV margin of 3 mm was applied. We quantified tumour motion with cine MRI. After treatment planning, the static dose distribution was convolved with the cine MRI based motion trajectory to simulate and evaluate the delivered dose to the GTV, PTV, and OARs. SBRT was carried out up to a dose of 24 Gray in 3 fractions in one week. Online position verification was performed with 4D CBCTs, with 4D matching based on gold fiducial markers at the midventilation position. Results All patients underwent uncomplicated endoscopic fiducial marker placement. Tumours and OARS were clearly visible with contrast enhanced CT and multiparametric MRI (Figure). On the 4D planning CT and on the 4D CBCT scans, the fiducial markers were clearly visible. The corset decreased peak-to-peak tumour motion in craniocaudal direction on average from 11.3 to 7.2 mm. With incorporation of the tumour motion trajectory, the dose distribution was blurred and, in this way, the actual delivered dose was simulated. In all patients, an adequate dose distribution was achieved with acceptable dose in the OARs (Table). Position verification based on 4D marker matching was feasible. No grade 3 or higher treatment related toxicity was observed in these patients to date.
mean pathologic node volume at diagnosis was 3.4±5.8 cm3. The mean EBRT and nodal boost doses were 44.3±0.9 Gy and 10.0±2.9 Gy respectively. The mean IGABT contribution to pelvic nodes was 4.2±2.6 Gy. Finally the mean total dose to lymphadenopathies was 55.3±5.6 Gy. Concomitant chemotherapy was administrated in 96.5% of the patients. After a median follow-up of 33.5 months, 20 patients (17.4%) experienced relapses in nodes initially considered pathologic at diagnosis (local relapse). Among them recurrences were observed in a total of 44 nodes (15.3%). The mean time from treatment completion to relapse was 9.0±11.8 months. There was no significant relationship between the dose delivered to pathologic nodes and local control probability (p=0.38). Univariate analyses tested various factors: subtypes (SCC versus others, p=0.35), concomitant chemotherapy (p=0.39), use of SIB (p=0.07), volume at diagnosis (threshold: 3 cm3, p<0.0001) and dose (≥ 57.5 Gy, p=0.039). The last three factors were entered in a multivariate analysis. Volume (HR=8.2, 4.0-16.6, p<0.0001) and dose (HR=2, 1.05-3.9, P=0.034) remained independent, whereas SIB was not (p=0.99). Subsequent Probit analysis combining dose and volume showed significant relationships with the probability of local control (Figure).
OC-0319 Cervix cancer: dose-volume effects in pathologic lymph nodes W. Bacorro1, R. Mazeron2, I. Dumas3, A. Escande2, A. Huertas2, R. Sun2, P. Castelnau-Marchand2, C. HaieMeder2, C. Chargari2 1 Benavides Cancer Institute- UST Hospital, Radiation Oncology, Manila, Philippines 2 Gustave Roussy, Radiation Oncology, Villejuif, France 3 Gustave Roussy, Medical Physics, Villejuif, France Purpose or Objective Whereas clear dose-volume relationships have been demonstrated for the tumor and organs at risk in locally advanced cervix cancer, the optimal threshold to reach for pathologic lymph nodes remains uncertain. The objective was to identify planning aim for pathologic nodes. Material and Methods Patients treated with curative intent for a cervical cancer with nodal involvement were identified. Their treatment combined external beam radiotherapy (EBRT) and imageguided brachytherapy (IGABT). Nodal boosts were performed sequentially or using the simultaneous integrated boost (SIB) technique depending on the EBRT technique used. The contributions of EBRT, IGABT (D98) and nodal boosts were converted in 2-Gy equivalent (α/β=10 Gy) and summed. Each node was considered individually, and followed from diagnosis to relapse. Resected nodes during para-aortic node surgical staging were not considered. Statistical analyses comprised logrank tests (univariate analyses), Cox proportional model (factors with p ≤0.1 in univariate) and probit analyses. Results One hundred and fifteen patients were included, with a total number of nodes of 288 (2.5 per patient). PET-CT was performed in 90.6% of the patients; para-aortic dissection in 53.8%. Histologic subtypes comprised squamous cell carcinomas (SCC) in 88.9%, adenocarcinomas in 8.5% and adenosquamous in 2.6%. The
Conclusion The initial volume was the main prognostic factor of control in pathologic lymph nodes. A dose superior to 57.5 Gy was also associated with a better local control probability. Further studies are required to refine these findings. Poster Viewing : Session 7: Upper and lower GI PV-0320 Stereotactic body radiotherapy for liver metastases based on functional treatment planning M.M. Fode1, J. Petersen2, E. Worm2, M. Sørensen3, K. Bak-Fredslund3, S. Keiding3, M. Høyer4 1 Aarhus University Hospital, Department of Oncology, Aarhus C, Denmark 2 Aarhus University Hospital, Department of Medical Physics, Aarhus C, Denmark
S167 ESTRO 36 _______________________________________________________________________________________________ 3
Aarhus University Hospital, Department of Nuclear Medicine & PET Centre and Department of Hepatology and Gastroenterology, Aarhus C, Denmark 4 Aarhus University Hospital, Danish Centre for Particle Therapy, Aarhus C, Denmark Purpose or Objective 2[18F]fluoro-2-deoxy-D-galactose (FDGal) is a hepatocytespecific positron emission tomography (PET) tracer. It was used as a marker for hepatocyte function for applying functional treatment planning (FTP) to minimize the radiation dose to the normal liver tissue. We report the results of a cohort of patients treated with FTPstereotactic body radiotherapy (SBRT) for liver metastases. Material and Methods Fourteen patients referred for SBRT for liver metastases from colorectal cancer were included in the study between December 2013 and August 2016. Nine patients were irradiated for a solitary metastasis and five patients for two (n=4) or three (n=1) metastases. The mean cumulated CTV was 70.3 cc (range 2.0 - 189.7 cc). FDGal PET/CT was performed at baseline and one month posttreatment. The liver was divided into nine iso-functioning volumes based on radioactivity concentration SUV of FDGal on the baseline FDGal PET/CT and transferred to the planning CT using deformable co-registration. The prescribed mean dose to the CTV was 45-60 Gy in 3-6 fractions. The post-treatment FDGal PET/CT was used for evaluation of radiation dose-response for the normal liver tissue. Results FTPs were created and applied for all patients and all plans met the predefined dose-volume constraints with the exception of a soft constraint of mean dose to the liver-CTV that was not met in three patients. Eight patients (57%) were treated with local therapy for liver metastases before inclusion in the present study (surgery n=1; SBRT n=1; combined local therapy n=6. No severe (CTCAE 4.0 grade 3-5) acute morbidity was registered. Teen grade 1 gastrointestinal and six grade 1-2 nongastrointestinal acute morbidities were registered. No patients had liver-related morbidity. Analysis of the posttreatment FDGal PET/CT revealed a dose-dependent depression in hepatocyte function measured in SUV of FDGal uptake in the irradiated normal liver tissue. Conclusion The study shows feasibility for FTP in patients with colorectal liver metastases referred for SBRT using FDGal PET/CT as a marker for hepatocyte function and the radiation dose to the normal liver tissue was minimized without compromising the organs at risk. The acute morbidity was minimal. PV-0321 MRI guided stereotactic radiotherapy for locally advanced pancreatic cancer H.D. Heerkens1, M. Van Vulpen1, B. Erickson2, O. Reerink3, M. Intven1, C.A.T. Van den Berg1, I.Q. Molenaar4, F.P. Vleggaar5, G.J. Meijer1 1 UMC Utrecht, Radiation Oncology Department, Utrecht, The Netherlands 2 Medical College of Wisconsin, Radiation Oncology Department, Milwaukee, USA 3 Isala Clinic, Radiation Oncology Department, Zwolle, The Netherlands 4 UMC Utrecht, Surgery Department, Utrecht, The Netherlands 5 UMC Utrecht, Gastroenterology Department, Utrecht, The Netherlands Purpose or Objective Patients with locally advanced pancreatic cancer (LAPC) show a poor survival due to limited effective therapeutic options. Stereotactic radiotherapy (SBRT) may delay the development of metastasis and physical discomfort, and it
may lead to better palliation and possibly increase survival with the advantage of a short overall treatment time. The superior soft tissue contrast of MRI might improve tumour contouring and MRI is capable of tumour motion quantification. We want to investigate the technical feasibility and safety of MRI-guided SBRT for LAPC. Material and Methods From July 2013 to January 2016, 20 patients with LAPC or medically unresectable pancreatic cancer without distant metastasis were included in this study (Table). A custom made abdominal corset was manufactured to reduce breathing induced tumour motion. Contouring of the gross tumour volume (GTV) and organs at risk (OARs) was performed on 4D treatment planning CT and multiparametric MRI. A GTV-to-PTV margin of 3 mm was applied. We quantified tumour motion with cine MRI. After treatment planning, the static dose distribution was convolved with the cine MRI based motion trajectory to simulate and evaluate the delivered dose to the GTV, PTV, and OARs. SBRT was carried out up to a dose of 24 Gray in 3 fractions in one week. Online position verification was performed with 4D CBCTs, with 4D matching based on gold fiducial markers at the midventilation position. Results All patients underwent uncomplicated endoscopic fiducial marker placement. Tumours and OARS were clearly visible with contrast enhanced CT and multiparametric MRI (Figure). On the 4D planning CT and on the 4D CBCT scans, the fiducial markers were clearly visible. The corset decreased peak-to-peak tumour motion in craniocaudal direction on average from 11.3 to 7.2 mm. With incorporation of the tumour motion trajectory, the dose distribution was blurred and, in this way, the actual delivered dose was simulated. In all patients, an adequate dose distribution was achieved with acceptable dose in the OARs (Table). Position verification based on 4D marker matching was feasible. No grade 3 or higher treatment related toxicity was observed in these patients to date.